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The aim of the study was to evaluate the reliability and validity of cardiorespiratory and metabolic variables, that is, peak oxygen uptake (V'O\(_{2peak}\)) and heart rate (HR\(_{peak}\)), obtained from an agility‐like incremental exercise test for team sport athletes. To investigate the test–retest reliability, 25 team sport athletes (age: 22 ± 3 years, body mass: 75 ± 7 kg, height: 182 ± 6 cm) performed an agility‐like incremental exercise test on the SpeedCourt (SC) system incorporating multidirectional change‐of‐direction (COD) movements twice. For each step of the incremental SC test, the athletes covered a 40‐m distance interspersed with a 10‐sec rest period. Each 40 m distance was split into short sprints (2.25–6.36 m) separated by multidirectional COD movements (0°–180°), which were performed in response to an external visual stimulus. All performance and physiological data were validated with variables obtained from a ramp‐like treadmill and Yo‐Yo intermittent recovery level 2 test (Yo‐Yo IR2). The incremental SC test revealed high test–retest reliability for the time to exhaustion (ICC = 0.85, typical error [TE] = 0.44, and CV% = 3.88), V'O\(_{2peak}\), HR\(_{peak}\), ventilation, and breathing frequency (ICC = 0.84, 0.72, 0.89, 0.77, respectively). The time to exhaustion (r = 0.50, 0.74) of the incremental SC test as well as the peak values for V'O\(_{2}\) (r = 0.59, 0.52), HR (r = 0.75, 0.78), ventilation (r = 0.57, 0.57), and breathing frequency (r = 0.68, 0.68) were significantly correlated (P ≤ 0.01) with the ramp‐like treadmill test and the Yo‐Yo IR2, respectively. The incremental SC test represents a reliable and valid method to assess peak values for V'O\(_{2}\) and HR with respect to the specific demand of team sport match play by incorporating multidirectional COD movements, decision making, and cognitive components.
Purpose:
The aim of the study was to evaluate the mucosal immune function and circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate and mood during a period of high-intensity interval training (HIIT) compared to long-slow distance training (LSD).
Methods:
Recreational male runners (n = 28) completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4 × 4 min of running at 90–95% of maximum heart rate interspersed with 3 min of active recovery while the LSD comprised of continuous running at 70–75% of maximum heart rate for 60–80 min. The psycho-immunological stress-response was investigated with a full daily profile of salivary cortisol and immunoglobin-A (sIgA) secretion rate along with the mood state on a baseline day, the first and last day of training and at follow-up 4 days after the last day of training. Before and after the training period, each athlete's running performance and peak oxygen uptake (V·O\(_{2peak}\)) was determined with an incremental exercise test.
Results:
The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and increased V·O\(_{2peak}\) compared to LSD (P = 0.01). The circadian variation of sIgA secretion rate showed highest values in the morning immediately after waking up followed by a decrease throughout the day in both groups (P < 0.05). With HIIT, the wake-up response of sIgA secretion rate was higher on the last day of training (P < 0.01) as well as the area under the curve (AUC\(_{G}\)) higher on the first and last day of training and follow-up compared to the LSD (P = 0.01). Also the AUC\(_{G}\) for the sIgA secretion rate correlated with the increase in V·O\(_{2peak}\) and running performance. The AUC\(_{G}\) for cortisol remained unaffected on the first and last day of training but increased on the follow-up day with both, HIIT and LSD (P < 0.01).
Conclusion:
The increased sIgA secretion rate with the HIIT indicates no compromised mucosal immune function compared to LSD and shows the functional adaptation of the mucosal immune system in response to the increased stress and training load of nine sessions of HIIT.
This paper discusses complementation strategies in Spanish, focusing on a specific construction most speakers are not aware of: the complementation clause preceded by the verb conocer. Not being a typical complement-taking verb, conocer surprises with a stable and persistent presence throughout the centuries, from Old Spanish to Modern Spanish. After giving an introduction into the field of complementation clauses and one of its main focus of study, grammatical mood, this study uses empirical data from the corpus programs CORDE, CREA and CORPES XXI to show the usage and prevalence of the construction in question. In doing so, this analysis gives a quantitative insight, exemplifying the results with several examples from all ages.
Background:
Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver.
Methods:
The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks. RNA sequencing performed on the Illumina platform was employed to evaluate the expression profiles of more than 14,000 genes, utilizing the RNA of the cell line cells and liver metastases as well as from corresponding tumour-free liver.
Results:
A total of 3329 differentially expressed genes (DEGs) were identified when cultured CMT-93 cells propagated as metastases in the liver. Hierarchical clustering on heat maps demonstrated the clear changes in gene expression of CMT-93 cells on propagation in the liver. Gene ontology analysis determined inflammation, angiogenesis, and signal transduction as the top three relevant biological processes involved. Using a selection list, matrix metallopeptidases 2, 7, and 9, wnt inhibitory factor, and chemokine receptor 4 were the top five significantly dysregulated genes.
Conclusion:
Bioinformatics assists in elucidating the factors and processes involved in CRC liver metastasis. Our results support the notion of an invasion-metastasis cascade involving CRC cells forming metastases on successful invasion and expansion within the liver. Furthermore, we identified a gene expression signature correlating strongly with invasiveness and migration. Our findings may guide future research on novel therapeutic targets in the treatment of CRC liver metastasis.
Chromium dioxide CrO\(_2\) belongs to a class of materials called ferromagnetic half-metals, whose peculiar aspect is that they act as a metal in one spin orientation and as a semiconductor or insulator in the opposite one. Despite numerous experimental and theoretical studies motivated by technologically important applications of this material in spintronics, its fundamental properties such as momentumresolved electron dispersions and the Fermi surface have so far remained experimentally inaccessible because of metastability of its surface, which instantly reduces to amorphous Cr\(_2\)O\(_3\). In this work, we demonstrate that direct access to the native electronic structure of CrO\(_2\) can be achieved with soft-x-ray angle-resolved photoemission spectroscopy whose large probing depth penetrates through the Cr\(_2\)O\(_3\) layer. For the first time, the electronic dispersions and Fermi surface of CrO\(_2\) are measured, which are fundamental prerequisites to solve the long debate on the nature of electronic correlations in this material. Since density functional theory augmented by a relatively weak local Coulomb repulsion gives an exhaustive description of our spectroscopic data, we rule out strong-coupling theories of CrO\(_2\). Crucial for the correct interpretation of our experimental data in terms of the valence-band dispersions is the understanding of a nontrivial spectral response of CrO\(_2\) caused by interference effects in the photoemission process originating from the nonsymmorphic space group of the rutile crystal structure of CrO\(_2\).
Complete NLO corrections to W\(^{+}\)W\(^{+}\) scattering and its irreducible background at the LHC
(2017)
The process pp → μ\(^{+}\)ν\(_{μ}\)e\(^{+}\)ν\(_{e}\)jj receives several contributions of different orders in the strong and electroweak coupling constants. Using appropriate event selections, this process is dominated by vector-boson scattering (VBS) and has recently been measured at the LHC. It is thus of prime importance to estimate precisely each contribution. In this article we compute for the first time the full NLO QCD and electroweak corrections to VBS and its irreducible background processes with realistic experimental cuts. We do not rely on approximations but use complete amplitudes involving two different orders at tree level and three different orders at one-loop level. Since we take into account all interferences, at NLO level the corrections to the VBS process and to the QCD-induced irreducible background process contribute at the same orders. Hence the two processes cannot be unambiguously distinguished, and all contributions to the μ\(^{+}\)ν\(_{μ}\)e\(^{+}\)ν\(_{e}\)jj final state should be preferably measured together.
The production of a neutral and a charged vector boson with subsequent decays into three charged leptons and a neutrino is a very important process for precision tests of the Standard Model of elementary particles and in searches for anomalous triple-gauge-boson couplings. In this article, the first computation of next-to-leading-order electroweak corrections to the production of the four-lepton final states μ\(^{+}\)μ\(^{−}\)e\(^{+}\)ν\(_{e}\), μ\(^{+}\)μ\(^{−}\)e\(^{−}\)ν\(_{e}\), μ\(^{+}\)μ\(^{−}\)μ\(^{+}\)ν\(_{μ}\), and μ\(^{+}\)μ\(^{−}\)μ\(^{−}\)ν\(_{μ}\) at the Large Hadron Collider is presented. We use the complete matrix elements at leading and next-to-leading order, including all off-shell effects of intermediate massive vector bosons and virtual photons. The relative electroweak corrections to the fiducial cross sections from quark-induced partonic processes vary between −3% and −6%, depending significantly on the event selection. At the level of differential distributions, we observe large negative corrections of up to −30% in the high-energy tails of distributions originating from electroweak Sudakov logarithms. Photon-induced contributions at next-to-leading order raise the leading-order fiducial cross section by +2%. Interference effects in final states with equal-flavour leptons are at the permille level for the fiducial cross section, but can lead to sizeable effects in off-shell sensitive phase-space regions.
Next-to-leading-order electroweak corrections to the production of four charged leptons at the LHC
(2017)
We present a state-of-the-art calculation of the next-to leading-order electroweak corrections to ZZ production, including the leptonic decays of the Z bosons into μ\(^+\)μ\(^ −\)e\(^+\)e\(^−\) or μ\(^+\)μ\(^−\)μ\(^+\)μ\(^−\) final states. We use complete leading-order and next-to-leading-order matrix elements for four-lepton production, including contributions of virtual photons and all off-shell effects of Z bosons, where the finite Z-boson width is taken into account using the complex-mass scheme. The matrix elements are implemented into Monte Carlo programs allowing for the evaluation of arbitrary differential distributions. We present integrated and differential cross sections for the LHC at 13 TeV both for an inclusive setup where only lepton identification cuts are applied, and for a setup motivated by Higgs-boson analyses in the four-lepton decay channel. The electroweak corrections are divided into photonic and purely weak contributions. The former show the well-known pronounced tails near kinematical thresholds and resonances; the latter are generically at the level of ∼ −5% and reach several −10% in the high-energy tails of distributions. Comparing the results for μ\(^+\)μ\(^−\)e\(^+\)e\(^−\) and μ\(^+\)μ\(^−\)μ\(^+\)μ\(^−\) final states, we find significant differences mainly in distributions that are sensitive to the μ\(^+\)μ\(^−\) pairing in the μ\(^+\)μ\(^−\)μ\(^+\)μ\(^−\) final state. Differences between μ\(^+\)μ\(^−\)e\(^+\)e\(^−\) and μ\(^+\)μ\(^−\)μ\(^+\)μ\(^−\) channels due to interferences of equal-flavour leptons in the final state can reach up to 10% in off-shell-sensitive regions. Contributions induced by incoming photons, i.e. photon-photon and quark-photon channels, are included, but turn out to be phenomenologically unimportant.
This publication presents the combination of the one-loop matrix-element generator Recola with the multipurpose Monte Carlo program Sherpa. Since both programs are highly automated, the resulting Sherpa +Recola framework allows for the computation of – in principle – any Standard Model process at both NLO QCD and EW accuracy. To illustrate this, three representative LHC processes have been computed at NLO QCD and EW: vector-boson production in association with jets, off-shell Z-boson pair production, and the production of a top-quark pair in association with a Higgs boson. In addition to fixed-order computations, when considering QCD corrections, all functionalities of Sherpa, i.e. particle decays, QCD parton showers, hadronisation, underlying events, etc. can be used in combination with Recola. This is demonstrated by the merging and matching of one-loop QCD matrix elements for Drell–Yan production in association with jets to the parton shower. The implementation is fully automatised, thus making it a perfect tool for both experimentalists and theorists who want to use state-of-the-art predictions at NLO accuracy.
Antimicrobial resistance is a growing global concern in human and veterinary medicine, with an ever-increasing void in the arsenal of clinicians. Novel classes of compounds including carbon monoxoide-releasing molecules (CORMs), for example the light-activated metal complex [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br, could be used as alternatives/to supplement traditional antibacterials. Avian pathogenic \(Escherichia\) \(coli\) (APEC) represent a large reservoir of antibiotic resistance and can cause serious clinical disease in poultry, with potential as zoonotic pathogens, due to shared serotypes and virulence factors with human pathogenic \(E.\) \(coli\). The \(in\) \(vitro\) activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br against multidrug-resistant APECs was assessed via broth microtitre dilution assays and synergy testing with colistin performed using checkerboard and time-kill assays. \(In\) \(vivo\) antibacterial activity of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br alone and in combination with colistin was determined using the \(Galleria\) \(mellonella\) wax moth larvae model. Animals were monitored for life/death, melanisation and bacterial numbers enumerated from larval haemolymph. \(In\) \(vitro\) testing produced relatively high [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br minimum inhibitory concentrations (MICs) of 1024 mg/L. However, its activity was significantly increased with the addition of colistin, bringing MICs down to \(\geq\)32 mg/L. This synergy was confirmed in time-kill assays. \(In\) \(vivo\) assays showed that the combination of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br with colistin produced superior bacterial killing and significantly increased larval survival. In both \(in\) \(vitro\) and \(in\) \(vivo\) assays light activation was not required for antibacterial activity. This data supports further evaluation of [Mn(CO)\(_3\)(tpa-\(\kappa^{3}N\))]Br as a potential agent for treatment of systemic infections in humans and animals, when used with permeabilising agents such as colistin.
Automatic orienting to unexpected changes in the environment is a pre-requisite for adaptive behavior. One prominent mechanism of automatic attentional control is the Orienting Response (OR). Despite the fundamental significance of the OR in everyday life, only little is known about how the OR is affected by healthy aging. We tested this question in two age groups (19–38 and 55–72 years) and measured skin-conductance responses (SCRs) and event-related brain potentials (ERPs) to novels (i.e., short environmental sounds presented only once in the experiment; 10% of the trials) compared to standard sounds (600 Hz sinusoidal tones with 200 ms duration; 90% of the trials). Novel and standard stimuli were presented in four conditions differing in the inter-stimulus interval (ISI) with a mean ISI of either 10, 3, 1, or 0.5 s (blocked presentation). In both age groups, pronounced SCRs were elicited by novels in the 10 s ISI condition, suggesting the elicitation of stable ORs. These effects were accompanied by pronounced N1 and frontal P3 amplitudes in the ERP, suggesting that automatic novelty processing and orientation of attention are effective in both age groups. Furthermore, the SCR and ERP effects declined with decreasing ISI length. In addition, differences between the two groups were observable with the fastest presentation rates (i.e., 1 and 0.5 s ISI length). The most prominent difference was a shift of the peak of the frontal positivity from around 300 to 200 ms in the 19–38 years group while in the 55–72 years group the amplitude of the frontal P3 decreased linearly with decreasing ISI length. Taken together, this pattern of results does not suggest a general decline in processing efficacy with healthy aging. At least with very rare changes (here, the novels in the 10 s ISI condition) the OR is as effective in healthy older adults as in younger adults. With faster presentation rates, however, the efficacy of the OR decreases. This seems to result in a switch from novelty to deviant processing in younger adults, but less so in the group of older adults.
This article seeks to analyse urban representation in José Cardoso Pires’s Lisboa – Livro de Bordo (1997), a book dedicated to the author’s home city Lisbon, by focusing on its prevailing nautical and maritime imagery. This imagery as well as its tendency to design Lisbon as a city-ship shall be examined with regard to spatial construction in the Livro de Bordo. Urban sailing as well as the recurrent representations of the Portuguese capital’s spaces as heterotopias will be interpreted as approaches to subvert institutional and homogenic discourses on Lisbon.
Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn\(^{2+}\) ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn\(^{2+}\). In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays.
Background:
There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT.
Methods:
Sixty-eight patients (mean age 76 ± 6 years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted.
Results:
Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23–27 mm vs. 23 mm; IQR 21–25; p = 0.009).
Conclusions:
Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings.
The CCHC-type zinc finger nucleic acid-binding protein (CNBP/ZNF9) is conserved in eukaryotes and is essential for embryonic development in mammals. It has been implicated in transcriptional, as well as post-transcriptional, gene regulation; however, its nucleic acid ligands and molecular function remain elusive. Here, we use multiple systems-wide approaches to identify CNBP targets and function. We used photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) to identify 8,420 CNBP binding sites on 4,178 mRNAs. CNBP preferentially bound G-rich elements in the target mRNA coding sequences, most of which were previously found to form G-quadruplex and other stable structures in vitro. Functional analyses, including RNA sequencing, ribosome profiling, and quantitative mass spectrometry, revealed that CNBP binding did not influence target mRNA abundance but rather increased their translational efficiency. Considering that CNBP binding prevented G-quadruplex structure formation in vitro, we hypothesize that CNBP is supporting translation by resolving stable structures on mRNAs.
Nearly a quarter of the Alpine area is covered by a dense network of large protected areas (LPAs) of the four categories national park(NP), biosphere reserve (BR), nature park and world natural heritage site (WNHS). From the time of early industrialization, the Alpine area has undergone a mixed and increasingly polarized demographic development between the poles of immigration and emigration. This article investigates the possible mutual impact of population development and the existence of LPAs. The research design includes a quantitative survey of all Alpine LPAs in terms of their population development and the structure of immigration in the first decade of the 21st century. This will be linked with qualitative expert interviews in four selected NPs. The overall results allow an interpretation of the statistical
correlations between type of LPA and migration.
Objective: Perception of time as well as rhythm in musical structures rely on complex brain mechanisms and require an extended network of multiple neural sources. They are therefore sensitive to impairment. Several psychophysical studies have shown that patients with Parkinson's disease (PD) have deficits in perceiving time and rhythms due to a malfunction of the basal ganglia (BG) network.
Method: In this study we investigated the time perception of PD patients during music perception by assessing their just noticeable difference (JND) in the time perception of a complex musical Gestalt. We applied a temporal discrimination task using a short melody with a clear beat-based rhythm. Among the subjects, 26 patients under L-Dopa administration and 21 age-matched controls had to detect an artificially delayed time interval in the range between 80 and 300 ms in the middle of the musical period. We analyzed the data by (a) calculating the detection threshold directly, (b) by extrapolating the JNDs, (c) relating it to musical expertise.
Results: Patients differed from controls in the detection of time-intervals between 220 and 300 ms (*p = 0.0200, n = 47). Furthermore, this deficit depended on the severity of the disease (*p = 0.0452; n = 47). Surprisingly, PD patients did not show any deficit of their JND compared to healthy controls, although the results showed a trend (*p = 0.0565, n = 40). Furthermore, no significant difference of the JND was found according to the severity of the disease. Additionally, musically trained persons seemed to have lower thresholds in detecting deviations in time and syntactic structures of music (*p = 0.0343, n = 39).
Conclusion: As an explanation of these results, we would like to propose the hypothesis of a time-syntax-congruency in music perception suggesting that processing of time and rhythm is a Gestalt process and that cortical areas involved in processing of musical syntax may compensate for impaired BG circuits that are responsible for time processing and rhythm perception. This mechanism may emerge more strongly as the deficits in time processing and rhythm perception progress. Furthermore, we presume that top-down-bottom-up-processes interfere additionally and interact in this context of compensation.
Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results.
Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.
Background:
Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients.
Methods:
A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated.
Results:
A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7%). The rate of lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected.
Conclusions:
The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.
Background:
Metastatic Adrenocortical Carcinoma (ACC) is a rare malignancy with a poor 5-year-survival rate (<15%). A surgical approach is recommended in selected patients if complete resection of distant metastasis can be achieved. To date there are only limited data on the outcome after surgical resection of hepatic metastases of ACC.
Methods:
A retrospective analysis of the German Adrenocortical Carcinoma Registry was conducted. Patients with liver metastases of ACC but without extrahepatic metastases or incomplete tumour resection were included.
Results:
Seventy-seven patients fulfilled these criteria. Forty-three patients underwent resection of liver metastases of ACC. Complete tumour resection (R0) could be achieved in 30 (69.8%). Median overall survival after liver resection was 76.1 months in comparison to 10.1 months in the 34 remaining patients with unresected liver metastases (p < 0.001). However, disease free survival after liver resection was only 9.1 months. Neither resection status (R0/R1) nor extent of liver resection were significant predictive factors for overall survival. Patients with a time interval to the first metastasis/recurrence (TTFR) of greater than 12 months or solitary liver metastases showed significantly prolonged survival.
Conclusions:
Liver resection in the case of ACC liver metastases can achieve long term survival with a median overall survival of more than 5 years, but disease free survival is short despite metastasectomy. Time to recurrence and single versus multiple metastases are predictive factors for the outcome.
Detailed information on the land cover types present and the horizontal position of the land–water interface is needed for sensitive coastal ecosystems throughout the Arctic, both to establish baselines against which the impacts of climate change can be assessed and to inform response operations in the event of environmental emergencies such as oil spills. Previous work has demonstrated potential for accurate classification via fusion of optical and SAR data, though what contribution either makes to model accuracy is not well established, nor is it clear what shorelines can be classified using optical or SAR data alone. In this research, we evaluate the relative value of quad pol RADARSAT-2 and Landsat 5 data for shoreline mapping by individually excluding both datasets from Random Forest models used to classify images acquired over Nunavut, Canada. In anticipation of the RADARSAT Constellation Mission (RCM), we also simulate and evaluate dual and compact polarimetric imagery for shoreline mapping. Results show that SAR data is needed for accurate discrimination of substrates as user’s and producer’s accuracies were 5–24% higher for models constructed with quad pol RADARSAT-2 and DEM data than models constructed with Landsat 5 and DEM data. Models based on simulated RCM and DEM data achieved significantly lower overall accuracies (71–77%) than models based on quad pol RADARSAT-2 and DEM data (80%), with Wetland and Tundra being most adversely affected. When classified together with Landsat 5 and DEM data, however, model accuracy was less affected by the SAR data type, with multiple polarizations and modes achieving independent overall accuracies within a range acceptable for operational mapping, at 89–91%. RCM is expected to contribute positively to ongoing efforts to monitor change and improve emergency preparedness throughout the Arctic.
Marine sponge-derived Streptomyces sp SBT343 extract inhibits staphylococcal biofilm formation
(2017)
Staphylococcus epidermidis and Staphylococcus aureus are opportunistic pathogens that cause nosocomial and chronic biofilm-associated infections. Indwelling medical devices and contact lenses are ideal ecological niches for formation of staphylococcal biofilms. Bacteria within biofilms are known to display reduced susceptibilities to antimicrobials and are protected from the host immune system. High rates of acquired antibiotic resistances in staphylococci and other biofilm-forming bacteria further hamper treatment options and highlight the need for new anti-biofilm strategies. Here, we aimed to evaluate the potential of marine sponge-derived actinomycetes in inhibiting biofilm formation of several strains of S. epidermidis, S. aureus, and Pseudomonas aeruginosa. Results from in vitro biofilm-formation assays, as well as scanning electron and confocal microscopy, revealed that an organic extract derived from the marine sponge-associated bacterium Streptomyces sp. SBT343 significantly inhibited staphylococcal biofilm formation on polystyrene, glass and contact lens surfaces, without affecting bacterial growth. The extract also displayed similar antagonistic effects towards the biofilm formation of other S. epidermidis and S. aureus strains tested but had no inhibitory effects towards Pseudomonas biofilms. Interestingly the extract, at lower effective concentrations, did not exhibit cytotoxic effects on mouse fibroblast, macrophage and human corneal epithelial cell lines. Chemical analysis by High Resolution Fourier Transform Mass Spectrometry (HRMS) of the Streptomyces sp. SBT343 extract proportion revealed its chemical richness and complexity. Preliminary physico-chemical characterization of the extract highlighted the heat-stable and non-proteinaceous nature of the active component(s). The combined data suggest that the Streptomyces sp. SBT343 extract selectively inhibits staphylococcal biofilm formation without interfering with bacterial cell viability. Due to absence of cell toxicity, the extract might represent a good starting material to develop a future remedy to block staphylococcal biofilm formation on contact lenses and thereby to prevent intractable contact lens-mediated ocular infections.
Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.
(2017)
Background:
MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).
Methods:
MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.
Results:
FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.
Conclusions:
The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.
Diabetes mellitus (DM) is one of the major current health problems due to lifestyle changes. Before diagnosis and in the early years of disease, insulin blood levels are elevated. However, insulin generates low levels of reactive oxygen species (ROS) which are integral to the regulation of a variety of intracellular signaling pathways, but excess levels of insulin may also lead to DNA oxidation and DNA damage. Three pharmaceutical compounds, resveratrol, lovastatin and the mTOR-inhibitor RAD-001, were investigated due to their known beneficial effects. They showed protective properties against genotoxic damage and significantly reduced ROS after in vitro treatment of cultured cells with insulin. Therefore, the selected pharmaceuticals may be attractive candidates to be considered for support of DM therapy.
The reaction of [(cAAC\(^{Me}\))BH\(_{3}\)] (cAAC\(^{Me}\) = 1-(2,6-iPr\(_{2}\)C\(_{6}\)H\(_{3}\))-3,3,5,5-tetramethylpyrrolidin-2-ylidene) with a range of organolithium compounds led to the exclusive formation of the corresponding (dihydro)organoborates, Li\(^{+}\)[(cAAC\(^{Me}\)H)BH\(_{2}\)R]− (R = sp\(^{3}\)-, sp\(^{2}\)-, or sp-hybridised organic substituent), by migration of one boron-bound hydrogen atom to the adjacent carbene carbon of the cAAC ligand. A subsequent deprotonation/salt metathesis reaction with Me3SiCl or spontaneous LiH elimination yielded the neutral cAAC-supported mono(organo)boranes, [(cAAC\(^{Me}\)H)BH\(_{2}\)R]− (R]. Similarly the reaction of [cAAC\(^{Me}\))BH\(_{3}\)] with a neutral donor base L resulted in adduct formation by shuttling one boron-bound hydrogen to the cAAC ligand, to generate [(cAAC\(^{Me}\)H)BH\(_{2}\)L], either irreversibly (L = cAAC\(^{Me}\)) or reversibly (L = pyridine). Variable-temperature NMR data and DFT calculations on [(cAAC\(^{Me}\)H)BH\(_{2}\)(cAAC\(^{Me}\))] show that the hydrogen on the former carbene carbon atom exchanges rapidly with the boron-bound hydrides.
\(Enterococcus\) species cause increasing numbers of infections in hospitals. They contribute to the increasing mortality rates, mostly in patients with comorbidities, who suffer from severe diseases. \(Enterococcus\) resistances against most antibiotics have been described, including novel antibiotics. Therefore, there is an ongoing demand for novel types of antibiotics that may overcome bacterial resistances. We discovered a novel class of antibiotics resulting from a simple one-pot reaction of indole and \(o\)-phthaldialdehyde. Differently substituted indolyl benzocarbazoles were yielded. Both the indole substitution and the positioning at the molecular scaffold influence the antibacterial activity towards the various strains of \(Enterococcus\) species with the highest relevance to nosocomial infections. Structure-activity relationships are discussed, and the first lead compounds were identified as also being effective in the case of a vancomycin resistance.
Background:
To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems.
Methods:
In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months.
Results:
The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases.
Conclusion:
In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort."
Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β.
Materials and Methods: We generated different recombinant FVVs encoding enhanced green fluorescent protein (EGFP) or IL1RA and examined their transduction efficiencies and transgene expression profiles using different cell lines and human primary MSCs derived from bone marrow-aspirates. Transgene expression was evaluated by fluorescence microscopy (EGFP), flow cytometry (EGFP), and ELISA (IL1RA). For evaluation of the functionality of the IL1RA transgene to block the inhibitory effects of IL1β on chondrogenesis of primary MSCs and an immortalized MSC cell line (TERT4 cells), the cells were maintained following transduction as aggregate cultures in standard chondrogenic media in the presence or absence of IL1β. After 3 weeks of culture, pellets were harvested and analyzed by histology and immunohistochemistry for chondrogenic phenotypes.
Results: The different FVV efficiently transduced cell lines as well as primary MSCs, thereby reaching high transgene expression levels in 6-well plates with levels of around 100 ng/ml IL1RA. MSC aggregate cultures which were maintained in chondrogenic media without IL1β supplementation revealed a chondrogenic phenotype by means of strong positive staining for collagen type II and matrix proteoglycan (Alcian blue). Addition of IL1β was inhibitory to chondrogenesis in untreated control pellets. In contrast, foamyviral mediated IL1RA expression rescued the chondrogenesis in pellets cultured in the presence of IL1β. Transduced MSC pellets reached thereby very high IL1RA transgene expression levels with a peak of 1087 ng/ml after day 7, followed by a decrease to 194 ng/ml after day 21, while IL1RA concentrations of controls were permanently below 200 pg/ml.
Conclusion: Our results indicate that FVV are capable of efficient gene transfer to MSCs, while reaching IL1RA transgene expression levels, that were able to efficiently block the impacts of IL1β in vitro. FVV merit further investigation as a means to study the potential as a gene transfer tool for MSC based therapies for cartilage repair.
Plants initially accepted by foraging leaf-cutting ants are later avoided if they prove unsuitable for their symbiotic fungus. Plant avoidance is mediated by the waste produced in the fungus garden soon after the incorporation of the unsuitable leaves, as foragers can learn plant odors and cues from the damaged fungus that are both present in the recently produced waste particles. We asked whether avoidance learning of plants unsuitable for the symbiotic fungus can take place entirely at the colony dump. In order to investigate whether cues available in the waste chamber induce plant avoidance in naïve subcolonies, we exchanged the waste produced by subcolonies fed either fungicide-treated privet leaves or untreated leaves and measured the acceptance of untreated privet leaves before and after the exchange of waste. Second, we evaluated whether foragers could perceive the avoidance cues directly at the dump by quantifying the visits of labeled foragers to the waste chamber. Finally, we asked whether foragers learn to specifically avoid untreated leaves of a plant after a confinement over 3 hours in the dump of subcolonies that were previously fed fungicide-treated leaves of that species. After the exchange of the waste chambers, workers from subcolonies that had access to waste from fungicide-treated privet leaves learned to avoid that plant. One-third of the labeled foragers visited the dump. Furthermore, naïve foragers learned to avoid a specific, previously unsuitable plant if exposed solely to cues of the dump during confinement. We suggest that cues at the dump enable foragers to predict the unsuitable effects of plants even if they had never been experienced in the fungus garden.
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.
Background:
In recent years, there has been an increasing interest in psychosocial workplace risk assessments in Germany. One of the questionnaires commonly employed for this purpose is the Short Questionnaire for Workplace Analysis (KFZA). Originally, the KFZA was developed and validated for office workers. The aim of the present study was to examine the factorial validity of the KFZA when applied to hospital settings. Therefore, we examined the factorial structure of a questionnaire that contained all the original items plus an extension adding 11 questions specific to hospital workplaces and analyzed both, the original version and the extended version.
Methods:
We analyzed questionnaire data of a total of 1731 physicians and nurses obtained over a 10-year period. Listwise exclusion of data sets was applied to account for variations in questionnaire versions and yielded 1163 questionnaires (1095 for the extended version) remaining for factor analysis. To examine the factor structure, we conducted a principal component factor analysis. The number of factors was determined using the Kaiser criterion and scree-plot methods. Factor interpretation was based on orthogonal Varimax rotation as well as oblique rotation.
Results:
The Kaiser criterion revealed a 7-factor solution for the 26 items of the KFZA, accounting for 62.0% of variance. The seven factors were named: “Social Relationships”, “Job Control”, “Opportunities for Participation and Professional Development”, “Quantitative Work Demands”, “Workplace Environment”, “Variability” and “Qualitative Work Demands”. The factor analysis of the 37 items of the extended version yielded a 9-factor solution. The two additional factors were named “Consequences of Strain” and “Emotional Demands”. Cronbach’s α ranged from 0.63 to 0.87 for these scales.
Conclusions:
Overall, the KFZA turned out to be applicable to hospital workers, and its content-related structure was replicated well with some limitations. However, instead of the 11 factors originally proposed for office workers, a 7-factor solution appeared to be more suitable when employed in hospitals. In particular, the items of the KFZA factor “Completeness of Task” might need adaptation for the use in hospitals. Our study contributes to the assessment of the validity of this popular instrument and should stimulate further psychometric testing.
The two articles of «Langage» and «Langue», published in 1765 in the 9th volume of the great French Encyclopédie by Diderot and D’Alembert, treat some essential philosophical questions on the human ability of communication with linguistic signs. Nevertheless, as the two authors Jaucourt and Beauzée did not share completely identic points of view, the comparative lecture of both articles reveals a complementary perspective, particularly relating to the origin of language as a divine gift or humans’ creation for communicative needs. A further aspect of divergence concerns the textual composition of the article « Langage » as a structured informative text, and the article « Langue » as a long and freely composed writing including personal remarks by the author. The following article deals with the potential of approaches to the Encyclopédie in modern linguistics, concretely demonstrated in the comparative analysis of these two articles.
Background:
Commensal bacteria like Neisseria meningitidis sometimes cause serious disease. However, genomic comparison of hyperinvasive and apathogenic lineages did not reveal unambiguous hints towards indispensable virulence factors. Here, in a systems biological approach we compared gene expression of the invasive strain MC58 and the carriage strain α522 under different ex vivo conditions mimicking commensal and virulence compartments to assess the strain-specific impact of gene regulation on meningococcal virulence.
Results:
Despite indistinguishable ex vivo phenotypes, both strains differed in the expression of over 500 genes under infection mimicking conditions. These differences comprised in particular metabolic and information processing genes as well as genes known to be involved in host-damage such as the nitrite reductase and numerous LOS biosynthesis genes. A model based analysis of the transcriptomic differences in human blood suggested ensuing metabolic flux differences in energy, glutamine and cysteine metabolic pathways along with differences in the activation of the stringent response in both strains. In support of the computational findings, experimental analyses revealed differences in cysteine and glutamine auxotrophy in both strains as well as a strain and condition dependent essentiality of the (p)ppGpp synthetase gene relA and of a short non-coding AT-rich repeat element in its promoter region.
Conclusions:
Our data suggest that meningococcal virulence is linked to transcriptional buffering of cryptic genetic variation in metabolic genes including global stress responses. They further highlight the role of regulatory elements for bacterial virulence and the limitations of model strain approaches when studying such genetically diverse species as N. meningitidis.
We analyze the concomitant spontaneous breaking of translation and conformal symmetries by introducing in a CFT a complex scalar operator that acquires a spatially dependent expectation value. The model, inspired by the holographic Q-lattice, provides a privileged setup to study the emergence of phonons from a spontaneous translational symmetry breaking in a conformal field theory and offers valuable hints for the treatment of phonons in QFT at large. We first analyze the Ward identity structure by means of standard QFT techniques, considering both spontaneous and explicit symmetry breaking. Next, by implementing holographic renormalization, we show that the same set of Ward identities holds in the holographic Q-lattice. Eventually, relying on the holographic and QFT results, we study the correlators realizing the symmetry breaking pattern and how they encode information about the low-energy spectrum.
Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.
The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.
Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.
In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
Past and the projected future climate change in Afghanistan has been analyzed systematically and differentiated with respect to its different climate regions to gain some first quantitative insights into Afghanistan’s vulnerability to ongoing and future climate changes. For this purpose, temperature, precipitation and five additional climate indices for extremes and agriculture assessments (heavy precipitation; spring precipitation; growing season length (GSL), the Heat Wave Magnitude Index (HWMI); and the Standardized Precipitation Evapotranspiration Index (SPEI)) from the reanalysis data were examined for their consistency to identify changes in the past (data since 1950). For future changes (up to the year 2100), the same parameters were extracted from an ensemble of 12 downscaled regional climate models (RCM) of the Coordinated Regional Climate Downscaling Experiment (CORDEX)-South Asia simulations for low and high emission scenarios (Representative Concentration Pathways 4.5 and 8.5). In the past, the climatic changes were mainly characterized by a mean temperature increase above global level of 1.8 °C from 1950 to 2010; uncertainty with regard to reanalyzed rainfall data limited a thorough analysis of past changes. Climate models projected the temperature trend to accelerate in the future, depending strongly on the global carbon emissions (2006–2050 Representative Concentration Pathways 4.5/8.5: 1.7/2.3 °C; 2006–2099: 2.7/6.4 °C, respectively). Despite the high uncertainty with regard to precipitation projections, it became apparent that the increasing evapotranspiration is likely to exacerbate Afghanistan’s already existing water stress, including a very strong increase of frequency and magnitude of heat waves. Overall, the results show that in addition to the already extensive deficiency in adaptation to current climate conditions, the situation will be aggravated in the future, particularly in regard to water management and agriculture. Thus, the results of this study underline the importance of adequate adaptation to climate change in Afghanistan. This is even truer taking into account that GSL is projected to increase substantially by around 20 days on average until 2050, which might open the opportunity for extended agricultural husbandry or even additional harvests when water resources are properly managed.
In the present report, well-defined WO3 nanorods (NRs) and a rGO–WO\(_3\) composite were successfully synthesized using a one-pot hydrothermal method. The crystal phase, structural morphology, shape, and size of the as-synthesized samples were studied using X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements. The optical properties of the synthesized samples were investigated by Raman, ultraviolet-visible (UV-Vis) and photoluminescence (PL) spectroscopy. Raman spectroscopy and TEM results validate the formation of WO\(_3\) (NRs) on the rGO sheet. The value of the dielectric constant (ε′) of WO3 NRs and rGO–WO\(_3\) composite is decreased with an increase in frequency. At low frequency (2.5 to 3.5 Hz), the value of ε′ for the rGO–WO3 composite is greater than that of pure WO\(_3\) NRs. This could be due to the fact that the induced charges follow the ac signal. However, at higher frequency (3.4 to 6.0), the value of ε′ for the rGO–WO\(_3\) composite is less compared to that of the pure WO3 NRs. The overall decrease in the value of ε′ could be due to the occurrence of a polarization process at the interface of the rGO sheet and WO3 NRs. Enhanced interfacial polarization in the rGO–WO\(_3\) composite is observed, which may be attributed to the presence of polar functional groups on the rGO sheet. These functional groups trap charge carriers at the interface, resulting in an enhancement of the interfacial polarization. The value of the dielectric modulus is also calculated to further confirm this enhancement. The values of the ac conductivity of the WO\(_3\) NRs and rGO–WO\(_3\) composite were calculated as a function of the frequency. The greater value of the ac conductivity in the rGO–WO\(_3\) composite compared to that of the WO\(_3\) NRs confirms the restoration of the sp:\(^{++}\) network during the in situ synthesis of the rGO–WO\(_3\) composite, which is well supported by the results obtained by Raman spectroscopy.
Radiationless energy transfer is at the core of diverse phenomena, such as light harvesting in photosynthesis\(^1\), energy-transfer-based microspectroscopies\(^2\), nanoscale quantum entanglement\(^3\) and photonic-mode hybridization\(^4\). Typically, the transfer is efficient only for separations that are much shorter than the diffraction limit. This hampers its application in optical communication and quantum information processing, which require spatially selective addressing. Here, we demonstrate highly efficient radiationless coherent energy transfer over a distance of twice the excitation wavelength by combining localized and delocalized\(^5\) plasmonic modes. Analogous to the Tavis-Cummings model, two whispering-gallery-mode antennas\(^6\) placed in the foci of an elliptical plasmonic cavity\(^7\) fabricated from single-crystal gold plates act as a pair of oscillators coupled to a common cavity mode. Time-resolved two-photon photoemission electron microscopy (TR 2P-PEEM) reveals an ultrafast long-range periodic energy transfer in accordance with the simulations. Our observations open perspectives for the optimization and tailoring of mesoscopic energy transfer and long-range quantum emitter coupling.
A search for high-energy neutrino emission correlated with gamma-ray bursts outside the electromagnetic prompt-emission time window is presented. Using a stacking approach of the time delays between reported gamma-ray burst alerts and spatially coincident muon-neutrino signatures, data from the Antares neutrino telescope recorded between 2007 and 2012 are analysed. One year of public data from the IceCube detector between 2008 and 2009 have been also investigated. The respective timing profiles are scanned for statistically significant accumulations within 40 days of the Gamma Ray Burst, as expected from Lorentz Invariance Violation effects and some astrophysical models. No significant excess over the expected accidental coincidence rate could be found in either of the two data sets. The average strength of the neutrino signal is found to be fainter than one detectable neutrino signal per hundred gamma-ray bursts in the Antares data at 90% confidence level.
MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.
A measurement of the \(t\)-channel single-top-quark and single-top-antiquark production cross-sections in the lepton+jets channel is presented, using 3.2 fb\(^{−1}\) of proton-proton collision data at a centre-of-mass energy of 13 TeV, recorded with the ATLAS detector at the LHC in 2015. Events are selected by requiring one charged lepton (electron or muon), missing transverse momentum, and two jets with high transverse momentum, exactly one of which is required to be \(b\)-tagged. Using a binned maximum-likelihood fit to the discriminant distribution of a neural network, the cross-sections are determined to be \({σ(tq)}\) = 156 ± 5 (stat.) ± 27 (syst.) ± 3 (lumi.) pb for single top-quark production and \(σ(\overline{t}q)\) = 91 ± 4 (stat.) ± 18 (syst.) ± 2 (lumi.) pb for single top-antiquark production, assuming a top-quark mass of 172.5 GeV. The cross-section ratio is measured to be \(R_{t}\) = \(σ(tq)/σ(\overline{t}q)\) = 1.72 ± 0.09 (stat.) ± 0.18 (syst.). All results are in agreement with Standard Model predictions.
We present charged-particle distributions sensitive to the underlying event, measured by the ATLAS detector in proton-proton collisions at a centre-of-mass energy of 13 TeV, in low-luminosity Large Hadron Collider fills corresponding to an integrated luminosity of 1.6 nb\(^{−1}\). The distributions were constructed using charged particles with absolute pseudorapidity less than 2.5 and with transverse momentum greater than 500 MeV, in events with at least one such charged particle with transverse momentum above 1 GeV. These distributions characterise the angular distribution of energy and particle flows with respect to the charged particle with highest transverse momentum, as a function of both that momentum and of charged-particle multiplicity. The results have been corrected for detector effects and are compared to the predictions of various Monte Carlo event generators, experimentally establishing the level of underlying-event activity at LHC Run 2 energies and providing inputs for the development of event generator modelling. The current models in use for UE modelling typically describe this data to 5% accuracy, compared with data uncertainties of less than 1%.
This article presents searches for the \({Zγ}\) decay of the Higgs boson and for narrow high-mass resonances decaying to \(Z\)γ, exploiting \(Z\) boson decays to pairs of electrons or muons. The data analysis uses 36.1 fb\(^{−1}\) of \({pp}\) collisions at \(\sqrt{s}=13\) recorded by the ATLAS detector at the CERN Large Hadron Collider. The data are found to be consistent with the expected Standard Model background. The observed (expected — assuming Standard Model \({pp} → H → {Z}γ\) production and decay) upper limit on the production cross section times the branching ratio for \({pp} → H → {Z}γ\) is 6.6. (5.2) times the Standard Model prediction at the 95% confidence level for a Higgs boson mass of 125.09 GeV. In addition, upper limits are set on the production cross section times the branching ratio as a function of the mass of a narrow resonance between 250 GeV and 2.4 TeV, assuming spin-0 resonances produced via gluon-gluon fusion, and spin-2 resonances produced via gluon-gluon or quark-antiquark initial states. For high-mass spin-0 resonances, the observed (expected) limits vary between 88 fb (61 fb) and 2.8 fb (2.7 fb) for the mass range from 250 GeV to 2.4 TeV at the 95% confidence level.
A search for strongly produced supersymmetric particles using signatures involving multiple energetic jets and either two isolated same-sign leptons (\(e\) or \(µ\)), or at least three isolated leptons, is presented. The analysis relies on the identification of \(b\)-jets and high missing transverse momentum to achieve good sensitivity. A data sample of proton-proton collisions at \(\sqrt{s} = 13\) TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 and 2016, corresponding to a total integrated luminosity of 36.1 fb\(^{−1}\), is used for the search. No significant excess over the Standard Model prediction is observed. The results are interpreted in several simplified supersymmetric models featuring \(R\)-parity conservation or \(R\)-parity violation, extending the exclusion limits from previous searches. In models considering gluino pair production, gluino masses are excluded up to 1.87 TeV at 95% confidence level. When bottom squarks are pair-produced and decay to a chargino and a top quark, models with bottom squark masses below 700 GeV and light neutralinos are excluded at 95% confidence level. In addition, model-independent limits are set on a possible contribution of new phenomena to the signal region yields.
Measurements of differential cross-sections of top-quark pair production in fiducial phase-spaces are presented as a function of top-quark and \(t\overline{t}\) system kinematic observables in proton-proton collisions at a centre-of-mass energy of \(\sqrt{s}\) = 13 TeV. The data set corresponds to an integrated luminosity of 3.2 fb\(^{−1}\), recorded in 2015 with the ATLAS detector at the CERN Large Hadron Collider. Events with exactly one electron or muon and at least two jets in the final state are used for the measurement. Two separate selections are applied that each focus on different top-quark momentum regions, referred to as resolved and boosted topologies of the \(t\overline{t}\) final state. The measured spectra are corrected for detector effects and are compared to several Monte Carlo simulations by means of calculated \(χ^2\) and \(p\)-values.
A measurement of the calorimeter response to isolated charged hadrons in the ATLAS detector at the LHC is presented. This measurement is performed with 3.2 nb\(^{−1}\) of proton–proton collision data at \(\sqrt{s}\) = 7 TeV from 2010 and 0.1 nb\(^{−1}\) of data at \(\sqrt{s}\) = 8 TeV from 2012. A number of aspects of the calorimeter response to isolated hadrons are explored. After accounting for energy deposited by neutral particles, there is a 5% discrepancy in the modelling, using various sets of GEANT4 hadronic physics models, of the calorimeter response to isolated charged hadrons in the central calorimeter region. The description of the response to anti-protons at low momenta is found to be improved with respect to previous analyses. The electromagnetic and hadronic calorimeters are also examined separately, and the detector simulation is found to describe the response in the hadronic calorimeter well. The jet energy scale uncertainty and correlations in scale between jets of different momenta and pseudorapidity are derived based on these studies. The uncertainty is 2–5% for jets with transverse momenta above 2 TeV, where this method provides the jet energy scale uncertainty for ATLAS.
This paper reports a search for triboson \({W^\pm}{W^\pm}{W^\mp}\) production in two decay channels (\({W^\pm}{W^\pm}{W^\mp}\) → \({ℓ^\pm}{νℓ^\pm}{νℓ^\mp}{ν}\) and \({W^\pm}{W^\pm}{W^\mp}\) → \({ℓ^\pm}{νℓ^\pm}{νjj}\) with \(ℓ=e,μ\)) in proton-proton collision data corresponding to an integrated luminosity of 20.3 fb\(^{−1}\) at a centre-of-mass energy of 8 TeV with the ATLAS detector at the Large Hadron Collider. Events with exactly three charged leptons, or two leptons with the same electric charge in association with two jets, are selected. The total number of events observed in data is consistent with the Standard Model (SM) predictions. The observed 95% confidence level upper limit on the SM \({W^\pm}{W^\pm}{W^\mp}\) production cross section is found to be 730 fb with an expected limit of 560 fb in the absence of SM \({W^\pm}{W^\pm}{W^\mp}\) production. Limits are also set on \(WWWW\) anomalous quartic gauge couplings.
A search is presented for particles that decay producing a large jet multiplicity and invisible particles. The event selection applies a veto on the presence of isolated electrons or muons and additional requirements on the number of \(b\)-tagged jets and the scalar sum of masses of large-radius jets. Having explored the full ATLAS 2015-2016 dataset of LHC proton-proton collisions at \(\sqrt{s}\) = 13 TeV, which corresponds to 36.1 fb\(^{−1}\) of integrated luminosity, no evidence is found for physics beyond the Standard Model. The results are interpreted in the context of simplified models inspired by R-parity-conserving and R-parity-violating supersymmetry, where gluinos are pair-produced. More generic models within the phenomenological minimal supersymmetric Standard Model are also considered.