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Background:
Minimally invasive pedicle screw fixation has less approach-related morbidity than open screw placement and is allegedly less traumatizing on paravertebral muscles, as there is no requirement to mobilize and retract the adjacent muscle portion. The approach-related long-term effects to the morphology of the paravertebral muscles are unknown. The purpose of this study was to compare the long-term amount of fatty degeneration of the multifidus muscle in patients treated with a classical open or a minimally invasive approach.
Methods:
Fourteen Patients meeting inclusion criteria were selected. In all patients a singular fracture of the thoracolumbar spine with a two-level posterior instrumentation was treated, either using an open approach or a minimally invasive approach. All patients underwent quantitative MRI spectroscopy for quantification of the fatty degeneration in the multifidus muscle as a long-term proof for muscle loss after minimum 4-year follow-up. Clinical outcome was assessed using Oswestry Low Back Pain Disability Questionnaire, SF-36 and VA-scale for pain.
Results:
The minimally invasive approach group failed to show less muscle degeneration in comparison to the open group. Total amount of fatty degeneration was 14.22% in the MIS group and 12.60% in the open group (p = 0.64). In accordance to MRI quantitative results there was no difference in the clinical outcome after a mean follow up of 5.9 years (±1.8).
Conclusion:
As short-term advantages of minimal invasive screw placement have been widely demonstrated, no advantage of the MIS, displaying a significant difference in the amount of fatty degeneration and resulting in a better clinical outcome could be found. Besides the well-known short-term advantage of minimally invasive pedicle screw placement, a long-term advantage, such as less muscle degeneration and thus superior clinical results, compared to the open approach could not be shown.
The presented thesis summarizes the results from four and a half years of intense lithography development on (Cd,Hg)Te/HgTe/(Cd,Hg)Te quantum well structures. The effort was motivated by the unique properties of this topological insulator. Previous work from Molenkamp at al.\ has proven that the transport through such a 2D TI is carried by electrons with opposite spin, counter-propagating in 1D channels along the sample edge. However, up to this thesis, the length of quantized spin Hall channels has never been reported to exceed 4 µm. Therefore, the main focus was put on a reproducible and easy-to-handle fabrication process that reveals the intrinsic material parameters.
Every single lithography step in macro as well as microscopic sample fabrication has been re-evaluated. In the Development, the process changes have been presented along SEM pictures, microgaphs and, whenever possible, measurement responses.
We have proven the conventional ion milling etch method to damage the remaining mesa and result in drastically lower electron mobilities in samples of microscopic size.
The novel KI:I2:HBr wet etch method for macro and microstructure mesa fabrication has been shown to leave the crystalline structure intact and result in unprecedented mobilities, as high as in macroscopic characterization Hall bars. Difficulties, such as an irregular etch start and slower etching of the conductive QW have been overcome by concentration, design and etch flow adaptations. In consideration of the diffusive regime, a frame around the EBL write field electrically decouples the structure mesa from the outside wafer. As the smallest structure, the frame is etched first and guarantees a non-different etching of the conductive layer during the redox reaction. A tube-pump method assures reproducible etch results with mesa heights below 300 nm. The PMMA etch mask is easy to strip and leaves a clean mesa with no redeposition. From the very first attempts, to the final etch process, the reader has been provided with the characteristics and design requirements necessary to enable the fabrication of nearly any mesa shape within an EBL write field of 200 µm.
Magneto resistance measurement of feed-back samples have been presented along the development chronology of wet etch method and subsequent lithography steps. With increasing feature quality, more and more physics has been revealed enabling detailed evaluation of smallest disturbances. The following lithography improvements have been implemented. They represent a tool-box for high quality macro and microstructure fabrication on (CdHg)Te/HgTe of almost any kind.
The optical positive resist ECI 3027 can be used as wet and as dry etch mask for structure sizes larger than 1 µm. It serves to etch mesa structures larger than the EBL write field.
The double layer PMMA is used for ohmic contact fabrication within the EBL write field. Its thickness allows to first dry etch the (Cd,Hg)Te cap layer and then evaporate the AuGe contact, in situ and self-aligned. Because of an undercut, up to 300 nm can be metalized without any sidewalls after the lift-off. An edge channel mismatch within the contact leads can be avoided, if the ohmic contacts are designed to reach close to the sample and beneath the later gate electrode.
The MIBK cleaning step prior to the gate application removes PMMA residuals and thereby improves gate and potential homogeneity.
The novel low HfO2-ALD process enables insulator growth into optical and EBL lift-off masks of any resolvable shape. Directly metalized after the insulator growth, the self-aligned method results in thin and homogeneous gate electrode reproducibly withholding gate voltages to +-10 V.
The optical negative resist ARN 4340 exhibits an undercut when developed. Usable as dry etch mask and lift-off resist, it enables an in-situ application of ohmic contacts first etching close to the QW, then metalizing AuGe. Up to 500 nm thickness, the undercut guarantees an a clean lift-off with no sidewalls.
The undertaken efforts have led to micro Hall bar measurements with Hall plateaus and SdH-oszillations in up to now unseen levels of detail.
The gap resistance of several micro Hall bars with a clear QSH signal have been presented in Quantum Spin Hall. The first to exhibit longitudinal resistances close to the expected h/2e2 since years, they reveal unprecedented details in features and characteristics. It has been shown that their protection against backscattering through time reversal symmetry is not as rigid as previously claimed. Values below and above 12.9 kΩ been explained, introducing backscattering within the Landauer-Büttiker formalism of edge channel transport. Possible reasons have been discussed. Kondo, interaction and Rashba-backscattering arising from density inhomogeneities close to the edge are most plausible to explain features on and deviations from a quantized value. Interaction, tunneling and dephasing mechanisms as well as puddle size, density of states and Rashba Fields are gate voltage dependent. Therefore, features in the QSH signal are fingerprints of the characteristic potential landscape.
Stable up to 11 K, two distinct but clear power laws have been found in the higher temperature dependence of the QSH in two samples. However, with ΔR = Tα, α = ¼ in one (QC0285) and α = 2 in the other (Q2745), none of the predicted dependencies could be confirmed. Whereas, the gap resistances of QC0285 remains QSH channel dominated up to 3.9 T and thereby confirmed the calculated lifting of the band inversion in magnetic field. The gate-dependent oscillating features in the QSH signal of Q2745 immediately increase in magnetic field. The distinct field dependencies allowed the assumption of two different dominant backscattering mechanisms.
Resulting in undisturbed magneto transport and unprecedented QSH measurements The Novel Micro Hall Bar Process has proven to enable the fabrication of a new generation of microstructures.
In the context of quantum mechanical calculations, the properties of non-adiabatic coupling in a small system, the Shin-Metiu model, is investigated.
The transition from adiabatic to non-adiabatic dynamics is elucidated in modifying the electron-nuclear interaction. This allows the comparison of weakly correlated electron-nuclear motion with the case where the strong correlations determine the dynamics.
The studies of the model are extended to include spectroscopical transitions being present in two-dimensional and degenerate four-wave mixing spectroscopy.
Furthermore, the quantum and classical time-evolution of the coupled motion in the complete electron-nuclear phase space is compared for the two coupling cases.
Additionally, the numerically exact electron flux within the weak coupling case is compared to the Born-Oppenheimer treatment.
In the last part of the thesis, the model is extended to two dimensions.
The system then possesses potential energy surfaces which exhibit a typical 'Mexican hat'-like structure and a conical intersection in the adiabatic representation.
Thus, it is possible to map properties of the system onto a vibronic coupling (Jahn-Teller) hamiltonian. Exact wave-packet propagations as well as nuclear wave-packet dynamics in the adiabatic and diabatic representation are performed.
Two-level emitters are the main building blocks of photonic quantum technologies and are model systems for the exploration of quantum optics in the solid state. Most interesting is the strict resonant excitation of such emitters to control their occupation coherently and to generate close to ideal quantum light, which is of utmost importance for applications in photonic quantum technology. To date, the approaches and experiments in this field have been performed exclusively using bulky lasers, which hinders the application of resonantly driven two-level emitters in compact photonic quantum systems. Here we address this issue and present a concept for a compact resonantly driven single-photon source by performing quantum-optical spectroscopy of a two-level system using a compact high-β microlaser as the excitation source. The two-level system is based on a semiconductor quantum dot (QD), which is excited resonantly by a fiber-coupled electrically driven micropillar laser. We dress the excitonic state of the QD under continuous wave excitation, and trigger the emission of single photons with strong multi-photon suppression (g\(^{(2)}\)(0)=0.02) and high photon indistinguishability (V = 57±9%) via pulsed resonant excitation at 156 MHz. These results clearly demonstrate the high potential of our resonant excitation scheme, which can pave the way for compact electrically driven quantum light sources with excellent quantum properties to enable the implementation of advanced quantum communication protocols.
Although questionable research practices (QRPs) and p-hacking have received attention in recent years, little research has focused on their prevalence and acceptance in students. Students are the researchers of the future and will represent the field in the future. Therefore, they should not be learning to use and accept QRPs, which would reduce their ability to produce and evaluate meaningful research. 207 psychology students and fresh graduates provided self-report data on the prevalence and predictors of QRPs. Attitudes towards QRPs, belief that significant results constitute better science or lead to better grades, motivation, and stress levels were predictors. Furthermore, we assessed perceived supervisor attitudes towards QRPs as an important predictive factor. The results were in line with estimates of QRP prevalence from academia. The best predictor of QRP use was students’ QRP attitudes. Perceived supervisor attitudes exerted both a direct and indirect effect via student attitudes. Motivation to write a good thesis was a protective factor, whereas stress had no effect. Students in this sample did not subscribe to beliefs that significant results were better for science or their grades. Such beliefs further did not impact QRP attitudes or use in this sample. Finally, students engaged in more QRPs pertaining to reporting and analysis than those pertaining to study design. We conclude that supervisors have an important function in shaping students’ attitudes towards QRPs and can improve their research practices by motivating them well. Furthermore, this research provides some impetus towards identifying predictors of QRP use in academia.
Background
Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC.
Methods
This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery.
Results
Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms.
Conclusions
Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.
Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression.
The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc&acc=GSE37015.
Background: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA (R) trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk.
Methods: CARMELINA (R) is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, >= 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA (R) was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided a-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure.
Results: Between July 2013 and August 2016, 6980 patients were randomized and took >= 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean +/- SD age was 65.8 +/- 9.1 years, HbA1c 7.9 +/- 1.0%, BMI 31.3 +/- 5.3 kg/m(2), and eGFR 55 +/- 25 mL/min/1.73 m(2). A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m(2) or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common.
Conclusions: CARMELINA (R) will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk.
The sequencing of several ant genomes within the last six years open new research avenues for understanding not only the genetic basis of social species but also the complex systems such as immune responses in general. Similar to other social insects, ants live in cooperative colonies, often in high densities and with genetically identical or closely related individuals. The contact behaviours and crowd living conditions allow the disease to spread rapidly through colonies. Nevertheless, ants can efficiently combat infections by using diverse and effective immune mechanisms. However, the components of the immune system of carpenter ant Camponotus floridanus and also the factors in bacteria that facilitate infection are not well understood.
To form a better view of the immune repository and study the C. floridanus immune responses against the bacteria, experimental data from Illumina sequencing and mass-spectrometry (MS) data of haemolymph in normal and infectious conditions were analysed and integrated with the several bioinformatics approaches. Briefly, the tasks were accomplished in three levels. First, the C. floridanus genome was re-annotated for the improvement of the existing annotation using the computational methods and transcriptomics data. Using the homology based methods, the extensive survey of literature, and mRNA expression profiles, the immune repository of C. floridanus were established. Second, large-scale protein-protein interactions (PPIs) and signalling network of C. floridanus were reconstructed and analysed and further the infection induced functional modules in the networks were detected by mapping of the expression data over the networks. In addition, the interactions of the immune components with the bacteria were identified by reconstructing inter-species PPIs networks and the interactions were validated by literature. Third, the stage-specific MS data of larvae and worker ants were analysed and the differences in the immune response were reported.
Concisely, all the three omics levels resulted to multiple findings, for instance, re-annotation and transcriptome profiling resulted in the overall improvement of structural and functional annotation and detection of alternative splicing events, network analysis revealed the differentially expressed topologically important proteins and the active functional modules, MS data analysis revealed the stage specific differences in C. floridanus immune responses against bacterial pathogens.
Taken together, starting from re-annotation of C. floridanus genome, this thesis provides a transcriptome and proteome level characterization of ant C. floridanus, particularly focusing on the immune system responses to pathogenic bacteria from a biological and a bioinformatics point of view. This work can serve as a model for the integration of omics data focusing on the immuno-transcriptome of insects.
Although it is becoming increasingly popular to monitor parameters related to training, recovery, and health with wearable sensor technology (wearables), scientific evaluation of the reliability, sensitivity, and validity of such data is limited and, where available, has involved a wide variety of approaches. To improve the trustworthiness of data collected by wearables and facilitate comparisons, we have outlined recommendations for standardized evaluation. We discuss the wearable devices themselves, as well as experimental and statistical considerations. Adherence to these recommendations should be beneficial not only for the individual, but also for regulatory organizations and insurance companies.
This work considered the frequency-modulated balanced steady-state free precession (fm-bSSFP) sequence as a tool to provide banding free bSSFP MR images. The sequence was implemented and successfully applied to suppress bandings in various in vitro and in vivo examples. In combination with a radial trajectory it is a promising alternative for standard bSSFP applications. First, two specialized applications were shown to establish the benefits of the acquisition strategy in itself. In real time cardiac imaging, it was shown that the continuous shift in frequency causes a movement of the bandings across the FOV. Thus, no anatomical region is constantly impaired, and a suitable timeframe can be found to examine all important structures. Furthermore, a combination of images with different artifact positions, similar to phase-cycled acquisitions is possible. In this way, fast, banding-free imaging of the moving heart was realized. Second, acquisitions with long TR were shown. While standard bSSFP suffers from increasing incidence of bandings with higher TR values, the frequency-modulated approach provided banding free images, regardless of the TR.
A huge disadvantage of fm-bSSFP, in combination with the radial trajectory, is the decrease in signal intensity. In this work a specialized reconstruction method, the multifrequency reconstruction for frequency-modulated bSSFP (Muffm), was established, which successfully compensated that phenomena. The application of Muffm to several anatomical sites, such as inner ear, legs and cardiac acquisitions, proofed the advantageous SNR of the reconstruction.
Furthermore, fm-bSSFP was applied to the clinically highly relevant task of water-fat separation. Former approaches of a phase-sensitive separation procedure in combination with standard bSSFP showed promising results but failed in cases of high inhomogeneity or high field strengths where banding artifacts become a major issue. The novel approach of using the fm-bSSFP acquisition strategy with the separation approach provided robust, reliable images of high quality. Again, losses in signal intensity could be regained by Muffm, as both approaches are completely compatible.
Opposed to conventional banding suppression techniques, like frequency-scouts or phase-cycling, all reconstruction methods established in this work rely on a single radial acquisition, with scan times similar to standard bSSFP scans. No prolonged measurement times occur and patient time in the scanner is kept as short as possible, improving patient comfort, susceptibility to motion or physiological noise and cost of one scan.
All in all, the frequency-modulated acquisition in combination with specializes reconstruction methods, leads to a completely new quality of images with short acquisition times.
Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors.
Ill-posed optimization problems appear in a wide range of mathematical applications, and their numerical solution requires the use of appropriate regularization techniques. In order to understand these techniques, a thorough analysis is inevitable.
The main subject of this book are quadratic optimal control problems subject to elliptic linear or semi-linear partial differential equations. Depending on the structure of the differential equation, different regularization techniques are employed, and their analysis leads to novel results such as rate of convergence estimates.
Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters
(2018)
Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with efficiency of T cell activation by cytokine secretion, although direct evidence of a functional role was not obtained by knockdown experiments. Our findings indicate a link between members of the ABC protein superfamily and the BTN3A-dependent activation of γδ T cells by endogenous and exogenous pAg.
Regulatory focus (RF) theory (Higgins, 1997) states that individuals follow different strategic concerns when focusing on gains (promotion) rather than losses (prevention). Applying the Reflective-Impulsive Model (RIM, Strack & Deutsch, 2004), this dissertation investigates RF’s influence on basic information processing, specifically semantic processing (Study 1), semantic (Study 2) and affective (Study 3) associative priming, and basic reflective operations (Studies 4-7). Study 1 showed no effect of RF on pre-activation of RF-related semantic concepts in a lexical decision task (LDT). Study 2 indicated that primes fitting a promotion focus improve performance in a LDT for chronically promotion-focused individuals, but not chronically prevention-focused individuals. However, the latter performed better when targets fit their focus. Stronger affect and arousal after processing valent words fitting an RF may explain this pattern. Study 3 showed some evidence for stronger priming effects for negative primes in a bona-fide pipeline task (Fazio et al., 1995) for chronically prevention-focused participants, while also providing evidence that situational prevention focus insulates individuals from misattributing the valence of simple primes. Studies 4-7 showed that a strong chronic prevention focus leads to greater negation effects for valent primes in an Affect Misattribution Procedure (Payne et al., 2005), especially when it fits the situation. Furthermore, Study 6 showed that these effects result from stronger weighting of negated valence rather than greater ease in negation. Study 7 showed that the increased negation effect is independent of time pressure. Broad implications are discussed, including how RF effects on basic processing may explain higher-order RF effects.
PURPOSE. To investigate the effect of selective retina therapy (SRT) on the release of AMD-relevant cell mediators, such as matrix metalloproteinases (MMPs), VEGF, and pigment epithelium derived factor (PEDF) using different laser spot sizes and densities.
METHODS. Porcine RPE-choroid explants were treated with a pulsed 532 nm Nd:YAG laser using (1) large spot sizes, (2) small spot sizes with a high-density (hd) treatment, and (3) small spot sizes with a low-density (1d) treatment. Explains were cultivated in modified Ussing chambers. RPE regeneration and RPE cell death were investigated by calcein-AM staining and immunofluorescence. The MMP release was examined via zymography and immunofluorescence. VEGF and PEDF secretion was analyzed by ELISA.
RESULTS. During pigment epithelium regeneration (PER), mitosis and RPE cell migration were observed. Four days after SRT (large spot size) the content of active MMP2 increased significantly (P < 0.01). Hd treatment with small spot sizes resulted also in an increase of active MMP2 (P < 0.05). In immunofluorescence explants showed a localized expression of MMP2 within the healing lesions after irradiation. The PEDF level increased significantly (P = 0.01) after SRT with large spot sizes. VEGF secretion decreased significantly (P < 0.05) following SRT with large spot sizes and with hd treatment of small spot sizes.
CONCLUSIONS. SRT induces a cytokine profile, which may improve the flux across Brach's membrane, slows down progression of early AMD by RPE regeneration, and inhibits the formation of choroidal neovascularization. The cytokine release depends on the size and density of applied laser spots.
Forest biodiversity conservation requires precise, area-wide information on the abundance and distribution of key habitat structures at multiple spatial scales. We combined airborne laser scanning (ALS) data with color-infrared (CIR) aerial imagery for identifying individual tree characteristics and quantifying multi-scale habitat requirements using the example of the three-toed woodpecker (Picoides tridactylus) (TTW) in the Bavarian Forest National Park (Germany). This bird, a keystone species of boreal and mountainous forests, is highly reliant on bark beetles dwelling in dead or dying trees. While previous studies showed a positive relationship between the TTW presence and the amount of deadwood as a limiting resource, we hypothesized a unimodal response with a negative effect of very high deadwood amounts and tested for effects of substrate quality. Based on 104 woodpecker presence or absence locations, habitat selection was modelled at four spatial scales reflecting different woodpecker home range sizes. The abundance of standing dead trees was the most important predictor, with an increase in the probability of TTW occurrence up to a threshold of 44–50 dead trees per hectare, followed by a decrease in the probability of occurrence. A positive relationship with the deadwood crown size indicated the importance of fresh deadwood. Remote sensing data allowed both an area-wide prediction of species occurrence and the derivation of ecological threshold values for deadwood quality and quantity for more informed conservation management.
Highly invasive animal based test procedures for risk assessment such as the Draize eye test are under increasing criticism due to poor transferability for the human organism and animal-welfare concerns. However, besides all efforts, the Draize eye test is still not completely replaced by alternative animal-free methods. To develop an in vitro test to identify all categories of eye irritation, we combined organotypic cornea models based on primary human cells with an electrical readout system that measures the impedance of the test models. First, we showed that employing a primary human cornea epithelial cell based model is advantageous in native marker expression to the primary human epidermal keratinocytes derived models. Secondly, by employing a non-destructive measuring system based on impedance spectroscopy, we could increase the sensitivity of the test system. Thereby, all globally harmonized systems categories of eye irritation could be identified by repeated measurements over a period of 7 days. Based on a novel prediction model we achieved an accuracy of 78% with a reproducibility of 88.9% to determine all three categories of eye irritation in one single test. This could pave the way according to the 3R principle to replace the Draize eye test.
Despite their popularity as enzyme engineering targets structural information about Sucrose Phosphorylases remains scarce. We recently clarified that the Q345F variant of Bifidobacterium adolescentis Sucrose Phosphorylase is able to accept large polyphenolic substrates like resveratrol via a domain shift. Here we present a crystal structure of this variant in a conformation suitable for the accommodation of the donor substrate sucrose in excellent agreement with the wild type structure. Remarkably, this conformation does not feature the previously observed domain shift which is therefore reversible and part of a dynamic process rather than a static phenomenon. This crystallographic snapshot completes our understanding of the catalytic cycle of this useful variant and will allow for a more rational design of further generations of Sucrose Phosphorylase variants.
The quantum mechanical screening of a spin via conduction electrons depends sensitively on the environment seen by the magnetic impurity. A high degree of responsiveness can be obtained with metal complexes, as the embedding of a metal ion into an organic molecule prevents intercalation or alloying and allows for a good control by an appropriate choice of the ligands. There are therefore hopes to reach an “on demand” control of the spin state of single molecules adsorbed on substrates. Hitherto one route was to rely on “switchable” molecules with intrinsic bistabilities triggered by external stimuli, such as temperature or light, or on the controlled dosing of chemicals to form reversible bonds. However, these methods constrain the functionality to switchable molecules or depend on access to atoms or molecules. Here, we present a way to induce bistability also in a planar molecule by making use of the environment. We found that the particular “habitat” offered by an antiphase boundary of the Rashba system BiAg2 stabilizes a second structure for manganese phthalocyanine molecules, in which the central Mn ion moves out of the molecular plane. This corresponds to the formation of a large magnetic moment and a concomitant change of the ground state with respect to the conventional adsorption site. The reversible spin switch found here shows how we can not only rearrange electronic levels or lift orbital degeneracies via the substrate, but even sway the effects of many-body interactions in single molecules by acting on their surrounding.
Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain
(2018)
The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsinguanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio > 1000. After light excitation the putative signaling state forms with tau = 31 ms and decays with tau = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 angstrom) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.
Bacteria adapt to changing environmental conditions by rapid changes in their transcriptome. This is achieved not only by adjusting rates of transcription but also by processing and degradation of RNAs. We applied TIER-Seq (transiently inactivating an endoribonuclease followed by RNA-Seq) for the transcriptome-wide identification of RNase E cleavage sites and of 5′ RNA ends, which are enriched when RNase E activity is reduced in Rhodobacter sphaeroides. These results reveal the importance of RNase E for the maturation and turnover of mRNAs, rRNAs, and sRNAs in this guanine-cytosine-rich α-proteobacterium, some of the latter have well-described functions in the oxidative stress response. In agreement with this, a role of RNase E in the oxidative stress response is demonstrated. A remarkably strong phenotype of a mutant with reduced RNase E activity was observed regarding the formation of photosynthetic complexes and phototrophic growth, whereas there was no effect on chemotrophic growth.
In this thesis stability and robustness properties of systems of functional differential equations which dynamics depends on the maximum of a solution over a prehistory time interval is studied. Max-operator is analyzed and it is proved that due to its presence such kind of systems are particular case of state dependent delay differential equations with piecewise continuous delay function. They are nonlinear, infinite-dimensional and may reduce to one-dimensional along its solution. Stability analysis with respect to input is accomplished by trajectory estimate and via averaging method. Numerical method is proposed.
Platelets, small anucleated blood cells responsible for hemostasis, interact at sights of injury with several exposed extracellular matrix (ECM) proteins through specific receptors. Ligand binding leads to activation, adhesion and aggregation of platelets. Already megakaryocytes (MKs), the immediate precursor cells in bone marrow (BM), are in constant contact to these ECM proteins (ECMP). The interaction of ECMP with MKs is, in contrast to platelets, less well understood. It is therefore important to study how MKs interact with sinusoids via the underlying ECMP. This thesis addresses three major topics to elucidate these interactions and their role in platelet biogenesis.
First, we studied the topology of ECMP within BM and their impact on proplatelet formation (PPF) in vitro. By establishing a four-color immunofluorescence microscopy we localized collagens and other ECMP and determined their degree of contact towards vessels and megakaryocytes (MKs). In in vitro assays we could demonstrate that Col I mediates increased MK adhesion, but inhibits PPF by collagen receptor GPVI. By immunoblot analyses we identified that the signaling events underyling this inhibition are different from those in platelet activation at the Src family kinase level.
Second, we determined the degree of MK-ECM interaction in situ using confocal laser scanning microscopy of four-color IF-stained femora and spleen sections. In transgenic mouse models lacking either of the two major collagen receptors we could show that these mice have an impaired association of MKs to collagens in the BM, while the MK count in spleen increased threefold. This might contribute to the overall unaltered platelet counts in collagen receptor-deficient mice.
In a third approach, we studied how the equilibrium of ECMP within BM is altered after irradiation. Collagen type IV and laminin-α5 subunits were selectively degraded at the sinusoids, while the matrix degrading protease MMP9 was upregulated in MKs. Platelet numbers decreased and platelets became hyporesponsive towards agonists, especially those for GPVI activation.
Taken together, the results indicate that MK-ECM interaction differs substantially from the well-known platelet-ECM signaling. Future work should further elucidate how ECMP can be targeted to ameliorate the platelet production and function defects, especially in patients after BM irradiation.
Milk-derived antibacterial peptides (ABPs) are protein fragments with a positive influence on the functions and conditions of a living organism. Milk-derived ABPs have several useful properties important for human health, comprising a significant antibacterial effect against various pathogens, but contain toxic side-effects. These compounds are mainly produced from milk proteins via fermentation and protein hydrolysis. However, they can also be produced using recombinant DNA techniques or organic synthesis. This review describes the role of milk-derived ABPs in modern food biotechnology with an emphasis on their synthesis and applications. Additionally, we also discuss the mechanisms of action and the main bioproperties of ABPs. Finally, we explore future perspectives for improving ABP physicochemical properties and diminishing their toxic side-effects.
We review the role of oscillations in the brain and in the auditory system showing that the ability of humans to distinguish changes in pitch can be explained as a precise analysis of temporal information in auditory signals by neural oscillations. The connections between auditory brain stem chopper neurons construct neural oscillators, which discharge spikes at various constant intervals that are integer multiples of 0.4 ms, contributing to the temporal processing of auditory cochlear output. This is subsequently spatially mapped in the inferior colliculus. Electrophysiological measurements of auditory chopper neurons in different species show oscillations with periods which are integer multiples of 0.4 ms. The constant intervals of 0.4 ms can be attributed to the smallest synaptic delay between interconnected simulated chopper neurons. We also note the patterns of similarities between microcircuits in the brain stem and other parts of the brain (e.g., the pallidum, reticular formation, locus coeruleus, oculomotor nuclei, limbic system, amygdala, hippocampus, basal ganglia and substantia nigra), dedicated to the processing of temporal information. Similarities in microcircuits across the brain reflect the importance of one of the key mechanisms in the information processing in the brain, namely the temporal coupling of different neural events via coincidence detection.
The production of human induced pluripotent stem cells (hiPSCs) in quantities that are relevant for cell-based therapies and cell-loaded implants through standard adherent culture is hardly achievable and lacks process scalability. A promising approach to overcoming these hurdles is the culture of hiPSCs in suspension. In this study, stirred suspension culture vessels were investigated for their suitability in the expansion of two hiPSC lines inoculated as a single cell suspension, with a free scalability between volumes of 50 and 2400 ml. The simple and robust two-step process reported here first generates hiPSC aggregates of 324 ± 71 μm diameter in 7 days in 125 ml spinner flasks (100 ml volume). These are subsequently dissociated into a single cell suspension for inoculation in 3000 ml bioreactors (1000 ml volume), finally yielding hiPSC aggregates of 198 ± 58 μm after 7 additional days. In both spinner flasks and bioreactors, hiPSCs can be cultured as aggregates for more than 40 days in suspension, maintain an undifferentiated state as confirmed by the expression of pluripotency markers TRA-1-60, TRA-1-81, SSEA-4, OCT4, and SOX2, can differentiate into cells of all three germ layers, and can be directed to differentiate into specific lineages such as cardiomyocytes. Up to a 16-fold increase in hiPSC quantity at the 100 ml volume was achieved, corresponding to a fold increase per day of 2.28; at the 1000 ml scale, an additional 10-fold increase was achieved. Taken together, 16 × 106 hiPSCs were expanded into 2 × 109 hiPSCs in 14 days for a fold increase per day of 8.93. This quantity of hiPSCs readily meets the requirements of cell-based therapies and brings their clinical potential closer to fruition.
A search is presented for the direct pair production of the stop, the supersymmetric partner of the top quark, that decays through an R-parity-violating coupling to a final state with two leptons and two jets, at least one of which is identified as a b-jet. The data set corresponds to an integrated luminosity of 36.1 fb(-1) of proton-proton collisions at a center-of-mass energy of root s = 13 TeV, collected in 2015 and 2016 by the ATLAS detector at the LHC. No significant excess is observed over the Standard Model background, and exclusion limits are set on stop pair production at a 95% confidence level. Lower limits on the stop mass are set between 600 GeV and 1.5 TeV for branching ratios above 10% for decays to an electron or muon and a b-quark.
A search is conducted for new resonances decaying into a WW or WZ boson pair, where one W boson decays leptonically and the other W or Z boson decays hadronically. It is based on proton-proton collision data with an integrated luminosity of 36.1 fb(-1) collected with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of root s = 13 TeV in 2015 and 2016. The search is sensitive to diboson resonance production via vector-boson fusion as well as quark-antiquark annihilation and gluon-gluon fusion mechanisms. No significant excess of events is observed with respect to the Standard Model backgrounds. Several benchmark models are used to interpret the results. Limits on the production cross section are set for a new narrow scalar resonance, a new heavy vector-boson and a spin-2 Kaluza-Klein graviton.
A search for a heavy neutral Higgs boson, A, decaying into a Z boson and another heavy Higgs boson, H, is performed using a data sample corresponding to an integrated luminosity of 36.1 fb(-1) from proton-proton collisions at root s = 13 TeV recorded in 2015 and 2016 by the ATLAS detector at the Large Hadron Collider. The search considers the Z boson decaying to electrons or muons and the H boson into a pair of b-quarks. No evidence for the production of an A boson is found. Considering each production process separately, the 95% confidence-level upper limits on the pp -> A -> ZH production cross-section times the branching ratio H -> bb are in the range of 14-830 fb for the gluon-gluon fusion process and 26-570 fb for the b-associated process for the mass ranges 130-700 GeV of the H boson and 230-800 GeV of the A boson. The results are interpreted in the context of two-Higgs-doublet models. (C) 2018 Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP(3).
The results of a search for new heavy W' bosons decaying to an electron or muon and a neutrino using proton-proton collision data at a centre-of-mass energy of root s = 13 TeV are presented. The dataset was collected in 2015 and 2016 by the ATLAS experiment at the Large Hadron Collider and corresponds to an integrated luminosity of 36.1 fb(-1). As no excess of events above the Standard Model prediction is observed, the results are used to set upper limits on the W' boson cross-section times branching ratio to an electron or muon and a neutrino as a function of the W' mass. Assuming a W' boson with the same couplings as the Standard Model W boson, W' masses below 5.1 TeV are excluded at the 95% confidence level.
Search for a Structure in the B-s(0) π\(^{±}\) Invariant Mass Spectrum with the ATLAS Experiment
(2018)
A search for the narrow structure, X(5568), reported by the DO Collaboration in the decay sequence X -> B-s(0) pi +/-, B-s(0) -> J/psi phi, is presented. The analysis is based on a data sample recorded with the ATLAS detector at the LHC corresponding to 4.9 fb(-1) of pp collisions at 7 TeV and 19.5 fb(-1)at 8 TeV. No significant signal was found. Upper limits on the number of signal events, with properties corresponding to those reported by DO, and on the A production rate relative to B-s(0) mesons, rho x, were determined at 95% confidence level. The results are N(X) < 382 and rho x <0.015 for B-s(0) mesons with transverse momenta above 10 GeV and N(X) < 356 and rho(x) < 0.016 for transverse momenta above 15 GeV. Limits are also set for potential B-s(0) pi(+) resonances in the mass range 5550 to 5700 MeV.
A search for an invisibly decaying Higgs boson or dark matter candidates produced in association with a leptonically decaying Z boson in proton-proton collisions at root s = 13 TeV is presented. This search uses 36.1 fb(-1) of data collected by the ATLAS experiment at the Large Hadron Collider. No significant deviation from the expectation of the Standard Model backgrounds is observed. Assuming the Standard Model ZH production cross-section, an observed (expected) upper limit of 67% (39%) at the 95% confidence level is set on the branching ratio of invisible decays of the Higgs boson with mass m(H) = 125 GeV. The corresponding limits on the production cross-section of the ZH process with the invisible Higgs boson decays are also presented. Furthermore, exclusion limits on the dark matter candidate and mediator masses are reported in the framework of simplified dark matter models. (c) 2017 The Author(s). Published by Elsevier B.V.
A search for weakly interacting massive dark matter particles produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and missing transverse momentum are considered. The analysis uses 36.1 fb(-1) of proton proton collision data recorded by the ATLAS experiment at root s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are interpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour-neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross-section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour-charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements.
Narrow resonances decaying into WW, WZ or ZZ boson pairs are searched for in 36.7 fb(-1) of proton-proton collision data at a centre-of-mass energy of root s = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015 and 2016. The diboson system is reconstructed using pairs of large-radius jets with high transverse momentum and tagged as compatible with the hadronic decay of high-momentum Wor Zbosons, using jet mass and substructure properties. The search is sensitive to diboson resonances with masses in the range 1.2-5.0 TeV. No significant excess is observed in any signal region. Exclusion limits are set at the 95% confidence level on the production cross section times branching ratio to dibosons for a range of theories beyond the Standard Model. Model-dependent lower limits on the mass of new gauge bosons are set, with the highest limit set at 3.5 TeV in the context of mass-degenerate resonances that couple predominantly to bosons. (c) 2017 The Author(s). Published by Elsevier B.V.
A search for doubly charged Higgs bosons with pairs of prompt, isolated, highly energetic leptons with the same electric charge is presented. The search uses a proton-proton collision data sample at a centre-of-mass energy of 13 TeV corresponding to 36.1 fb(-1) of integrated luminosity recorded in 2015 and 2016 by the ATLAS detector at the LHC. This analysis focuses on the decays H-+/-+/- -> e(+/-)e(+/-), H-+/-+/- -> e(+/-)mu(+/-) and H-+/-+/- -> mu(+/-)mu(+/-), fitting the dilepton mass spectra in several exclusive signal regions. No significant evidence of a signal is observed and corresponding limits on the production cross-section and consequently a lower limit on m(H-+/-+/-) are derived at 95% confidence level. With l(+/-)l(+/-) = e(+/-)e(+/-)/mu(+/-)mu(+/-)/e(+/-)mu(+/-), the observed lower limit on the mass of a doubly charged Higgs boson only coupling to left-handed leptons varies from 770 to 870GeV (850GeV expected) for B(H-+/-+/- -> l(+/-)l(+/-)) = 100% and both the expected and observed mass limits are above 450GeV for B(H-+/-+/- -> l(+/-)l(+/-)) = 10% and any combination of partial branching ratios.
A search for electroweak production of supersymmetric particles in scenarios with compressed mass spectra in final states with two low-momentum leptons and missing transverse momentum is presented. This search uses proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015-2016, corresponding to 36.1 tb(-1) of integrated luminosity at root s = 13 TeV. Events with same flavor pairs of electrons or muons with opposite electric charge are selected. The data are found to be consistent with the Standard Model prediction. Results are interpreted using simplified models of R-parity conserving supersymmetry in which there is a small mass difference between the masses of the produced supersymmetric particles and the lightest neutralino. Exclusion limits at 95% confidence level are set on next-to-lightest neutralino masses of up to 145 GeV for Higgsino production and 175 GeV for wino production, and slepton masses of up to 190 GeV for pair production of sleptons. In the compressed mass regime, the exclusion limits extend down to mass splittings of 2.5 GeV for Higgsino production, 2 GeV for wino production, and 1 GeV for slepton production. The results are also interpreted in the context of a radiatively-driven natural supersymmetry model with nonuniversal Higgs boson masses.
Search for exclusive Higgs and Z boson decays to phi gamma and rho gamma with the ATLAS detector
(2018)
A search for the exclusive decays of the Higgs and Z bosons to a phi or rho meson and a photon is performed with a pp collision data sample corresponding to an integrated luminosity of up to 35.6 fb(-1) collected at root s = 13 TeV with the ATLAS detector at the CERN Large Hadron Collider. These decays have been suggested as a probe of the Higgs boson couplings to light quarks. No significant excess of events is observed above the background, as expected from the Standard Model. Upper limits at 95% confidence level were obtained on the branching fractions of the Higgs boson decays to phi gamma and rho gamma of 4.8 x 10(-4) and 8.8 x 10(-4), respectively. The corresponding 95% confidence level upper limits for the Z boson decays are 0.9 x 10(-6) and 25 x 10(-6) for phi gamma and rho gamma, respectively.
A search for flavour-changing neutral-current processes in top-quark decays is presented. Data collected with the ATLAS detector from proton-proton collisions at the Large Hadron Collider at a centre-of-mass energy of root s = 13TeV, corresponding to an integrated luminosity of 36.1 fb(-1), are analysed. The search is performed using top-quark pair events, with one top quark decaying through the t -> qZ (q = u, c) flavour-changing neutral-current channel, and the other through the dominant Standard Model mode t -> bW. Only Z boson decays into charged leptons and leptonic W boson decays are considered as signal. Consequently, the final-state topology is characterized by the presence of three isolated charged leptons (electrons or muons), at least two jets, one of the jets originating from a b-quark, and missing transverse momentum from the undetected neutrino. The data are consistent with Standard Model background contributions, and at 95% confidence level the search sets observed (expected) upper limits of 1.7 x 10(-4) (2.4 x 10(-4)) on the t -> uZ branching ratio and 2.4 x 10(-4) (3.2 x 10(-4)) on the t -> cZ branching ratio, constituting the most stringent limits to date.
A search for heavy resonances decaying into a pair of Z bosons leading to l(+) l(-) l(+) l(-) and l(+) l(-) nu(nu) over bar final states, where l stands for either an electron or a muon, is presented. The search uses proton-proton collision data at a centre-of-mass energy of 13 TeV corresponding to an integrated luminosity of 36.1 fb(-1) collected with the ATLAS detector during 2015 and 2016 at the Large Hadron Collider. Different mass ranges for the hypothetical resonances are considered, depending on the final state and model. The different ranges span between 200 and 2000 GeV. The results are interpreted as upper limits on the production cross section of a spin-0 or spin-2 resonance. The upper limits for the spin-0 resonance are translated to exclusion contours in the context of Type-I and Type-II two-Higgs-doublet models, while those for the spin-2 resonance are used to constrain the Randall-Sundrum model with an extra dimension giving rise to spin-2 graviton excitations.
A search for neutral heavy resonances is performed in the WW -> e nu mu nu decay channel using pp collision data corresponding to an integrated luminosity of 36.1 fb(-1), collected at a centre-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. No evidence of such heavy resonances is found. In the search for production via the quark-antiquark annihilation or gluon-gluon fusion process, upper limits on sigma(X) x B(X -> WW) as a function of the resonance mass are obtained in the mass range between 200 GeV and up to 5 TeV for various benchmark models: a Higgs-like scalar in different width scenarios, a two-Higgs-doublet model, a heavy vector triplet model, and a warped extra dimensions model. In the vector-boson fusion process, constraints are also obtained on these resonances, as well as on a Higgs boson in the Georgi-Machacek model and a heavy tensor particle coupling only to gauge bosons.
A search is conducted for new resonances decaying into a W or Z boson and a 125 GeV Higgs boson in the nu(nu) over barb (b) over bar, l(+/-)nu b (b) over bar, and l(+)l(-)b (b) over bar final states, where l(+/-) = e(+/-) or mu(+/-), in pp collisions at root s = 13 TeV. The data used correspond to a total integrated luminosity of 36.1 fb(-1) collected with the ATLAS detector at the Large Hadron Collider during the 2015 and 2016 data-taking periods. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Wh and Zh candidates for evidence of a localised excess in the mass range of 220 GeV up to 5 TeV. No significant excess is observed and the results are interpreted in terms of constraints on the production cross-section times branching fraction of heavy W' and Z' resonances in heavy-vector-triplet models and the CP-odd scalar boson A in two-Higgs-doublet models. Upper limits are placed at the 95% confidence level and range between 9.0 x 10(-4) pb and 7.3 x 10(-1) pb depending on the model and mass of the resonance.
Many extensions of the Standard Model predict new resonances decaying to a Z, W, or Higgs boson and a photon. This paper presents a search for such resonances produced in pp collisions at root s = 13 TeV using a data set with an integrated luminosity of 36.1 fb(-1) collected by the ATLAS detector at the LHC. The Z/W/H bosons are identified through their decays to hadrons. The data are found to be consistent with the Standard Model expectation in the entire investigated mass range. Upper limits are set on the production cross section times branching fraction for resonance decays to Z.W + gamma in the mass range from 1.0 to 6.8 TeV and for the first time into H + gamma in the mass range from 1.0 to 3.0 TeV.
This Letter presents a search for exotic decays of the Higgs boson to a pair of new (pseudo) scalar particles, H -> aa, where the a particle has a mass in the range 20-60 GeV, and where one of the a bosons decays into a pair of photons and the other to a pair of gluons. The search is performed in event samples enhanced in vector-boson fusion Higgs boson production by requiring two jets with large invariant mass in addition to the Higgs boson candidate decay products. The analysis is based on the full dataset of pp collisions at root s = 13 TeV recorded in 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider, corresponding to an integrated luminosity of 36.7 fb(-1). The data are in agreement with the Standard Model predictions and an upper limit at the 95% confidence level is placed on the production cross section times the branching ratio for the decay H -> aa -> gamma gamma gg. This limit ranges from 3.1 pb to 9.0 pb depending on the mass of the a boson. (C) 2018 The Author. Published by Elsevier B.V.
A search is conducted for a beyond-the-Standard-Model boson using events where a Higgs boson with mass 125 GeV decays to four leptons (l = e or mu). This decay is presumed to occur via an intermediate state which contains one or two on-shell, promptly decaying bosons: H -> ZX/XX -> 4l , where X is a new vector boson Z(d) or pseudoscalar a with mass between 1 and 60 GeV. The search uses pp collision data collected with the ATLAS detector at the LHC with an integrated luminosity of 36.1 fb(-1) at a centre-of-mass energy root s = 13TeV. No significant excess of events above Standard Model background predictions is observed; therefore, upper limits at 95% confidence level are set on model-independent fiducial cross-sections, and on the Higgs boson decay branching ratios to vector and pseudoscalar bosons in two benchmark models.
A search for high-mass resonances decaying to tau nu using proton-proton collisions at root s = 13 TeV produced by the Large Hadron Collider is presented. Only tau-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb(-1). No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible tau nu production cross section. Heavy W' bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2-3.8 TeV depending on the coupling in the nonuniversal Go(221) model are excluded at the 95% credibility level.
This paper presents a search for direct electroweak gaugino or gluino pair production with a chargino nearly mass-degenerate with a stable neutralino. It is based on an integrated luminosity of 36.1 fb(-1) of pp collisions at root s = 13 TeV collected by the ATLAS experiment at the LHC. The final state of interest is a disappearing track accompanied by at least one jet with high transverse momentum from initial-state radiation or by four jets from the gluino decay chain. The use of short track segments reconstructed from the innermost tracking layers significantly improves the sensitivity to short chargino lifetimes. The results are found to be consistent with Standard Model predictions. Exclusion limits are set at 95% confidence level on the mass of charginos and gluinos for different chargino lifetimes. For a pure wino with a lifetime of about 0.2 ns, chargino masses up to 460 GeV are excluded. For the strong production channel, gluino masses up to 1.65 TeV are excluded assuming a chargino mass of 460 GeV and lifetime of 0.2 ns.
A search for long-lived, massive particles predicted by many theories beyond the Standard Model is presented. The search targets final states with large missing transverse momentum and at least one highmass displaced vertex with five or more tracks, and uses 32.8 fb(-1) of root s = 13 TeV pp collision data collected by the ATLAS detector at the LHC. The observed yield is consistent with the expected background. The results are used to extract 95% C.L. exclusion limits on the production of long-lived gluinos with masses up to 2.37 TeV and lifetimes of O(10(-2)) - O(10) ns in a simplified model inspired by split supersymmetry.
Searches for dijet resonances with sub-TeV masses using the ATLAS detector at the Large Hadron Collider can be statistically limited by the bandwidth available to inclusive single-jet triggers, whose data-collection rates at low transverse momentum are much lower than the rate from standard model multijet production. This Letter describes a new search for dijet resonances where this limitation is overcome by recording only the event information calculated by the jet trigger algorithms, thereby allowing much higher event rates with reduced storage needs. The search targets low-mass dijet resonances in the range 450-1800 GeV. The analyzed data set has an integrated luminosity of up to 29.3 fb(-1) and was recorded at a center-of-mass energy of 13 TeV. No excesses are found; limits are set on Gaussian-shaped contributions to the dijet mass distribution from new particles and on a model of dark-matter particles with axial-vector couplings to quarks.
A search for new phenomena in events with two same- charge leptons or three leptons and jets identi fi ed as originating from b - quarks in a data sample of 36.1 fb of pp collisions at ps = 13TeV recorded by the ATLAS detector at the Large Hadron Collider is reported. No signi fi cant excess is found and limits are set on vector- like quark, fourtop- quark, and same- sign top- quark pair production. The observed ( expected) 95% CL mass limits for a vector- like T - and B - quark singlet are mT > 0 : 98 ( 0 : 99) TeV and mB > 1 : 00 ( 1 : 01) TeV respectively. Limits on the production of the vector- like T5=3 - quark are also derived considering both pair and single production; in the former case the lower limit on the mass of the T5=3 - quark is ( expected to be) 1.19 ( 1.21) TeV. The Standard Model fourtop- quark production cross- section upper limit is ( expected to be) 69 ( 29) fb. Constraints are also set on exotic four- top- quark production models. Finally, limits are set on samesign top- quark pair production. The upper limit on uu ! tt production is ( expected to be) 89 ( 59) fb for a mediator mass of 1TeV, and a dark- matter interpretation is also derived, excluding a mediator of 3TeV with a dark- sector coupling of 1.0 and a coupling to ordinary matter above 0.31.