A Measurement of the Differential Drell-Yan Cross Section as a Function of Invariant Mass in Proton–Proton Collisions at √ S = 13 Tev

The Drell-Yan process, a crucial mechanism for producing lepton pairs in highenergy hadron collisions, serves as an essential probe for testing the Standard Model of particle physics. This dissertation presents a comprehensive measurement of the differential cross section with respect to the invariant mass of the lepton pairs, utilizing data collected by the CMS experiment at CERN from 2016 to 2018. Cross sections are essential for refining our understanding of parton distribution functions and the underlying quantum chromodynamics processes, thereby providing constraints on theoretical predictions. In this analysis, the cross sections are compared to theoretical models and simulations, offering new insights into precision tests of the Standard Model. These measurements are expected to aid theorists in improving parton distribution functions. The cross section results presented in this dissertation are consistent with earlier Drell-Yan measurements and the Standard Model, with improved uncertainties over previous measurements. This reinforces the robustness of the Standard Model and contributes to the precision of future theoretical predictions. Advisor: Ilya Kravchenk

An Environmental Conversation

Federal environmental law and policy ambitiously purports to provide clean air and water, protect endangered and threatened species, clean-up hazardous and toxic waste sites, and infuse environmental considerations into the decision-making process of all federal agencies with respect to major proposals impacting the environment. Despite such lofty goals and an expansion of the regulatory state, certain types of activities and associated risks have eluded statutory coverage. Additionally, these uncoordinated federal environmental statutes typically embody a singular and sometimes myopic focus, leading to unpredictable or undesirable regulatory gaps, constraints, and inefficiencies. Further, limitations on standing and judicial review may significantly limit the ability of private litigants to enforce compliance with substantive and procedural duties of federal agencies and other private actors. This article illuminates these complexities through the lens of a hypothetical but plausible scenario presenting controversial environmental issues associated with hydraulic fracturing operations. The various issues presented are discussed and analyzed by a fictional Supreme Court, drawing upon both recent and historically significant judicial decisions of the real U.S. Supreme Court and others. This conceit highlights the problematic interplay of the federal statutes and standards of judicial review. It also provides insight into potential methods to navigate the substantive and procedural challenges faced by private litigants, federal agencies, and the courts in applying these complex statutes to address modern environmental threats, such as those presented in hydraulic fracturing activities

Alcohol beverage control, privatization and the geographic distribution of alcohol outlets

BACKGROUND: With Pennsylvania currently considering a move away from an Alcohol Beverage Control state to a privatized alcohol distribution system, this study uses a spatial analytical approach to examine potential impacts of privatization on the number and spatial distribution of alcohol outlets in the city of Philadelphia over a long time horizon. METHODS: A suite of geospatial data were acquired for Philadelphia, including 1,964 alcohol outlet locations, 569,928 land parcels, and school, church, hospital, park and playground locations. These data were used as inputs for exploratory spatial analysis to estimate the expected number of outlets that would eventually operate in Philadelphia. Constraints included proximity restrictions (based on current ordinances regulating outlet distribution) of at least 200 feet between alcohol outlets and at least 300 feet between outlets and schools, churches, hospitals, parks and playgrounds. RESULTS: Findings suggest that current state policies on alcohol outlet distributions in Philadelphia are loosely enforced, with many areas exhibiting extremely high spatial densities of outlets that violate existing proximity restrictions. The spatial model indicates that an additional 1,115 outlets could open in Philadelphia if privatization was to occur and current proximity ordinances were maintained. CONCLUSIONS: The study reveals that spatial analytical approaches can function as an excellent tool for contingency-based “what-if” analysis, providing an objective snapshot of potential policy outcomes prior to implementation. In this case, the likely outcome is a tremendous increase in alcohol outlets in Philadelphia, with concomitant negative health, crime and quality of life outcomes that accompany such an increase

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We found that certain highly chlorinated PCBs are potent activators of rodent PXR but antagonize its human ortholog, the steroid and xenobiotic receptor (SXR), inhibiting target gene induction. Thus, exposure to PCBs may blunt the human xenobiotic response, inhibiting the detoxification of steroids, bioactive dietary compounds, and xenobiotics normally mediated by SXR. The antagonistic PCBs are among the most stable and abundant in human tissues. These findings have important implications for understanding the biologic effects of PCB exposure and the use of animal models to predict the attendant risk

A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

<p>Abstract</p> <p>Background</p> <p>High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate <it>de novo </it>sequencing for identification of post-translational modifications and amino acid polymorphisms.</p> <p>Results</p> <p>In this study, a new <it>de novo </it>sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of <it>Rhodopseudomonas palustris</it>. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of <it>de novo </it>sequenced spectra and the sequencing accuracy.</p> <p>Conclusions</p> <p>Here, we improved <it>de novo </it>sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at <url>http://compbio.ornl.gov/Vonode</url>.</p

Targeted next-generation sequencing identifies novel variants in candidate genes for Parkinson’s disease in Black South African and Nigerian patients

Background: The prevalence of Parkinson’s disease (PD) is increasing in sub-Saharan Africa, but little is known about the genetics of PD in these populations. Due to their unique ancestry and diversity, sub-Saharan African populations have the potential to reveal novel insights into the pathobiology of PD. In this study, we aimed to characterise the genetic variation in known and novel PD genes in a group of Black South African and Nigerian patients. Methods: We recruited 33 Black South African and 14 Nigerian PD patients, and screened them for sequence variants in 751 genes using an Ion AmpliSeq™ Neurological Research panel. We used bcftools to filter variants and annovar software for the annotation. Rare variants were prioritised using MetaLR and MetaSVM prediction scores. The effect of a variant on ATP13A2’s protein structure was investigated by molecular modelling. Results: We identified 14,655 rare variants with a minor allele frequency ≤ 0.01, which included 2448 missense variants. Notably, no common pathogenic mutations were identified in these patients. Also, none of the known PD-associated mutations were found highlighting the need for more studies in African populations. Altogether, 54 rare variants in 42 genes were considered deleterious and were prioritized, based on MetaLR and MetaSVM scores, for follow-up studies. Protein modelling showed that the S1004R variant in ATP13A2 possibly alters the conformation of the protein. Conclusions: We identified several rare variants predicted to be deleterious in sub-Saharan Africa PD patients; however, further studies are required to determine the biological effects of these variants and their possible role in PD. Studies such as these are important to elucidate the genetic aetiology of this disorder in patients of African ancestry

Opportunities for improving animal welfare in rodent models of epilepsy and seizures

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

The Inhibition of Polo Kinase by Matrimony Maintains G2 Arrest in the Meiotic Cell Cycle

Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase

Myosin5a tail associates directly with Rab3A-containing compartments in neurons

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of American Society for Biochemistry and Molecular Biology. The definitive version was published in Journal of Biological Chemistry, 286 (2011): 14352-14361, doi:10.1074/jbc.M110.187286.Myosin-Va (Myo5a) is a motor protein associated with synaptic vesicles (SVs) but the mechanism by which it interacts has not yet been identified. A potential class of binding partners are Rab GTPases and Rab3A is known to associate with SVs and is involved in SV trafficking. We performed experiments to determine whether Rab3A interacts with Myo5a and whether it is required for transport of neuronal vesicles. In vitro motility assays performed with axoplasm from the squid giant axon showed a requirement for a Rab GTPase in Myo5a-dependent vesicle transport. Furthermore, mouse recombinant Myo5a tail revealed that it associated with Rab3A in rat brain synaptosomal preparations in vitro and the association was confirmed by immunofluorescence imaging of primary neurons isolated from the frontal cortex of mouse brains. Synaptosomal Rab3A was retained on recombinant GST-tagged Myo5a tail affinity columns in a GTP-dependent manner. Finally, the direct interaction of Myo5a and Rab3A was determined by sedimentation v e l o c i t y analytical ultracentrifugation using recombinant mouse Myo5a tail and human Rab3A. When both proteins were incubated in the presence of 1 mM GTPγS, Myo5a tail and Rab3A formed a complex and a direct interaction was observed. Further analysis revealed that GTP-bound Rab3A interacts with both the monomeric and dimeric species of the Myo5a tail. However, the interaction between Myo5a tail and nucleotidefree Rab3A did not occur. Thus, our results show that Myo5a and Rab3A are direct binding partners and interact on SVs and that the Myo5a/Rab3A complex is involved in transport of neuronal vesicles