Protestors Have Fourth Amendment Rights, Too: In \u3ci\u3eGraves v. City of Coeur D\u27Alene\u3c/i\u3e, the Ninth Circuit Clouds Clearly Established Law Governing Searches

In Graves v. City of Coeur d\u27Alene, the United States Court of Appeals for the Ninth Circuit concluded that a police officer should not have arrested a protestor at an Aryan Nations parade when the protestor refused to allow the officer to search his backpack. The court held that the arrest was illegal because the officer had no probable cause to believe the protestor was carrying a weapon. However, the court also held that the arresting officer was entitled to qualified immunity and thus not liable for his violation of the protestor\u27s rights. Qualified immunity is a privilege that shields a public official from liability in situations where the underlying substantive law is not clearly established. In Graves, the court held that under the circumstances surrounding the Aryan Nations parade, the standard for probable cause to search the protestor\u27s backpack was not clearly established. This Note argues that the police officer in Graves searched the protestor without sufficient individualized suspicion. Instead, as a basis for the search the officer relied on a broad profile of otherwise ordinary conduct that would include a number of innocent individuals. Because the law was clearly established at the time of the search that police officers must have some individualized suspicion of a person to perform a search, and that individualized suspicion cannot be based on ordinary conduct that would include a number of innocent people, the defendant police officer was not entitled to qualified immunity

Searching for Heavy Photons With Detached Vertices in the Heavy Photon Search Experiment

The Jefferson Lab Heavy Photon Search (HPS) experiment is searching for a hypothetical massive particle called the heavy photon which could mediate a dark electromagnetic-type force. If heavy photons kinetically mix with Standard Model photons, they may be radiated by electrons scattering from a heavy nucleus and then decay to e+e- pairs. HPS uniquely searches for heavy photons that either decay at the target or a measurable distance after. The experiment utilizes a silicon vertex tracker (SVT) for momentum and vertex reconstruction, together with an electromagnetic calorimeter for measuring particle energies and triggering events. The HPS experiment took its first data during the spring 2015 engineering run using a 1 GeV electron beam incident on a tungsten target and its second data in the spring of 2016 at a beam energy of 2.3 GeV. The 2015 run obtained two days of production data that was used for the first physics results. The analysis of the data was conducted as a blinded analysis by tuning cuts on 10% of the data. This dissertation discusses the displaced vertex search for heavy photons in the 2015 engineering run. It describes the theoretical motivation for looking for heavy photons and provides an overview of the HPS experimental design and performance. The performance details of the experiment are primarily derived from the 2015 engineering run with some discussion from the higher energy running in 2016. This dissertation further discusses the cuts used to optimize the displaced vertex search and the results of the search. The displaced vertex search did not set a limit on the heavy photon but did validate the methodology for conducting the search. Finally, we used the full data set to make projections and guide future analyses

Searching for an Enhanced Signal of the Onset of Color Transparency in Baryons with D(e,e′p)n Scattering

Observation of the onset of color transparency in baryons would provide a new means of studying the nuclear strong force and would be the first clear evidence of baryons transforming into a color-neutral point-like size in the nucleus as predicted by quantum chromodynamics. Recent C (e, e′p) results from electron-scattering did not observe the onset of color transparency (CT) in protons up to spacelike four-momentum transfers squared, Q2 = 14.2 GeV 2 . The traditional methods of searching for CT in (e, e′p) scattering use heavy targets favoring kinematics with already initially reduced final state interactions (FSIs) such that any CT effect that further reduces FSIs will be small. The reasoning behind this choice is the difficulty in accounting for all FSIs. D (e, e′p)η , on the other hand, has well-understood FSI contributions from double scattering with a known dependence on the kinematics and can show an increased sensitivity to hadrons in point-like configurations. Double scattering is the square of the re-scattering amplitude in which the knocked-out nucleon interacts with the spectator nucleon, a process that is suppressed in the presence of point-like configurations and is particularly well-studied for the deuteron. This suppression yields a quadratic sensitivity to CT effects and is strongly dependent on the choice of kinematics. Here, we describe a possible Jefferson National Accelerator Facility (JLab) electron-scattering experiment that utilizes these kinematics and explores the potential signal for the onset of CT with enhanced sensitivity as compared to recent experiments

Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy)

Purpose: There is currently no true macrophage cell line and in vitro experiments requiring these cells currently require mitogenic stimulation of a macrophage precursor cell line (THP-1) or ex vivo maturation of circulating primary monocytes. In this study, we characterise a human macrophage cell line, derived from THP-1 cells, and compare its phenotype to the THP-1 cells. Methods: THP-1 cells with and without mitogenic stimulation were compared to the newly derived macrophage-like cell line (Daisy) using microscopy, flow cytometry, phagocytosis assays, antigen binding assays and gene microarrays. Results: We show that the cell line grows predominantly in an adherent monolayer. A panel of antibodies were chosen to investigate the cell surface phenotype of these cells using flow cytometry. Daisy cells expressed more CD11c, CD80, CD163, CD169 and CD206, but less CD14 and CD11b compared with mitogen-stimulated THP-1 cells. Unlike stimulated THP-1 cells which were barely able to bind immune complexes, Daisy cells showed large amounts of immune complex binding. Finally, although not statistically significant, the phagocytic ability of Daisy cells was greater than mitogen-stimulated THP-1 cells, suggesting that the cell line is more similar to mature macrophages. Conclusions: The observed phenotype suggests that Daisy cells are a good model of human macrophages with a phenotype similar to human alveolar macrophages

ABCA7 frameshift deletion associated with Alzheimer disease in African Americans

Objective: To identify a causative variant(s) that may contribute to Alzheimer disease (AD) in African Americans (AA) in the ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene, a known risk factor for late-onset AD. Methods: Custom capture sequencing was performed on ∼150 kb encompassing ABCA7 in 40 AA cases and 37 AA controls carrying the AA risk allele (rs115550680). Association testing was performed for an ABCA7 deletion identified in large AA data sets (discovery n = 1,068; replication n = 1,749) and whole exome sequencing of Caribbean Hispanic (CH) AD families. Results: A 44-base pair deletion (rs142076058) was identified in all 77 risk genotype carriers, which shows that the deletion is in high linkage disequilibrium with the risk allele. The deletion was assessed in a large data set (531 cases and 527 controls) and, after adjustments for age, sex, and APOE status, was significantly associated with disease (p = 0.0002, odds ratio [OR] = 2.13 [95% confidence interval (CI): 1.42–3.20]). An independent data set replicated the association (447 cases and 880 controls, p = 0.0117, OR = 1.65 [95% CI: 1.12–2.44]), and joint analysis increased the significance (p = 1.414 × 10−5, OR = 1.81 [95% CI: 1.38–2.37]). The deletion is common in AA cases (15.2%) and AA controls (9.74%), but in only 0.12% of our non-Hispanic white cohort. Whole exome sequencing of multiplex, CH families identified the deletion cosegregating with disease in a large sibship. The deleted allele produces a stable, detectable RNA strand and is predicted to result in a frameshift mutation (p.Arg578Alafs) that could interfere with protein function. Conclusions: This common ABCA7 deletion could represent an ethnic-specific pathogenic alteration in AD

Copy Number Variants in Extended Autism Spectrum Disorder Families Reveal Candidates Potentially Involved in Autism Risk

Copy number variations (CNVs) are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs). In the multifaceted etiology of autism spectrum disorders (ASDs), CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology

Evidence of novel finescale structural variation at autism spectrum disorder candidate loci

Background: Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism. Methods: As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members. Results: Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions. Conclusions: These results provide additional support for the role of rare structural variation in ASD

SORL1 mutations in early- and late-onset Alzheimer disease.

OBJECTIVE: To characterize the clinical and molecular effect of mutations in the sortilin-related receptor (SORL1) gene. METHODS: We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants. The phenotypic consequences associated with SORL1 mutations were characterized based on clinical reviews of medical records. Functional studies were completed to evaluate β-amyloid (Aβ) production and amyloid precursor protein (APP) trafficking associated with SORL1 mutations. RESULTS: SORL1 alterations were present in 2 EOAD families. In one, a SORL1 T588I change was identified in 4 individuals with AD, 2 of whom had parkinsonian features. In the second, an SORL1 T2134 alteration was found in 3 of 4 AD cases, one of whom had postmortem Lewy bodies. Among LOAD cases, 4 individuals with either SORL1 A528T or T947M alterations had parkinsonian features. Functionally, the variants weaken the interaction of the SORL1 protein with full-length APP, altering levels of Aβ and interfering with APP trafficking. CONCLUSIONS: The findings from this study support an important role for SORL1 mutations in AD pathogenesis by way of altering Aβ levels and interfering with APP trafficking. In addition, the presence of parkinsonian features among select individuals with AD and SORL1 mutations merits further investigation

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Ice core chemistry database: an Antarctic compilation of sodium and sulfate records spanning the past 2000 years

Changes in sea ice conditions and atmospheric circulation over the Southern Ocean play an important role in modulating Antarctic climate. However, observations of both sea ice and wind conditions are limited in Antarctica and the Southern Ocean, both temporally and spatially, prior to the satellite era (1970 onwards). Ice core chemistry data can be used to reconstruct changes over annual, decadal, and millennial timescales. To facilitate sea ice and wind reconstructions, the CLIVASH2k (CLimate Variability in Antarctica and the Southern Hemisphere over the past 2000 years) working group has compiled a database of two species, sodium [Na+] and sulfate [SO2− 4 ], commonly measured ionic species. The database (https://doi.org/10.5285/9E0ED16E-F2AB4372-8DF3-FDE7E388C9A7; Thomas et al., 2022) comprises records from 105 Antarctic ice cores, containing records with a maximum age duration of 2000 years. An initial filter has been applied, based on evaluation against sea ice concentration, geopotential height (500 hPa), and surface wind fields to identify sites suitable for reconstructing past sea ice conditions, wind strength, or atmospheric circulation