gebhart/patrepeval huggingface dataset:
Acidosis and Deafness in Patients with Recessive Mutations in FOXI1 (2017)

Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in <i>FOXI1</i> (p.L146F and p.R213P) predicted to affect the highly conserved DNA binding domain. Patients presented with early-onset sensorineural deafness and distal renal tubular acidosis. In cultured cells, the mutations reduced the DNA binding affinity of FOXI1, which hence, failed to adequately activate genes crucial for normal inner ear function and acid-base regulation in the kidney. A substantial proportion of patients with a clinical diagnosis of inherited distal renal tubular acidosis has no identified causative mutations in currently known disease genes. Our data suggest that recessive mutations in FOXI1 can explain the disease in a subset of these patients.
Protective effects of Phlomis umbrosa extract on a monosodium iodoacetate–induced osteoarthritis model and prediction of molecular mechanisms using transcriptomics (2020)

Abstract Background Phlomis umbrosa Turczaninow root has been traditionally used to treat fractures, rheumatoid arthritis, and arthralgia. However, the effects and mechanisms of P. umbrosa on osteoarthritis (OA) remain poorly understood and a functional genomic approach has not been investigated. Aim The purpose of this study was to investigate the effects and mechanisms of P. umbrosa extract (PUE) on OA using transcriptomic analysis. Methods We performed joint diameter measurements, micro computed tomography, and histopathological analysis of monosodium iodoacetate (MIA)-induced OA rats treated with PUE (200 mg/kg) for 3 weeks. Gene expression profiling in articular cartilage tissue was then performed using RNA sequencing (RNA-seq) followed by signaling pathway analysis of regulatory genes. Results PUE treatment improved OA based on decreased joint diameter, increased joint morphological parameters, and histopathological features. Many genes involved in multiple signal transduction pathway and collagen activation in OA were differentially regulated by PUE. These included genes related to Wnt/β-catenin, OA pathway, and sonic hedgehog signaling activity. Furthermore, PUE treatment downregulated cartilage damage factors (MMP-9, MMP-13, ADAMTs4, and ADMATs5) and upregulated chondrogenesis (COL2A1 and SOX-9) by regulating the transcription factors SOX-9, Ctnnb1, and Epas1. Conclusion Based on the results of gene expression profiling, this study highlighted the molecular mechanisms underlying the effects of PUE in MIA-induced OA rats. The findings provide novel insight into the mechanisms by which PUE treatment-induced gene expression changes may influence OA disease progression. Taken together, the results suggest that PUE may be used as a source of therapeutic agents for OA.
Evaluating Emergency Evacuation Events Using Building WiFi Data (2020)

Building operators are required to conduct periodic drills to ensure smooth evacuations in the event of emergencies. However, quantitative evaluation of the drill for adherence to building codes is largely manual and error-prone. Further, unplanned evacuations are seldom documented, let alone evaluated. This paper explores the use of building WiFi data for quantitative evaluations of both planned and unplanned evacuation events. We collect and analyze WiFi connectivity logs spanning a period of 180 days from 14 buildings in a large University campus. For our first contribution, we isolate WiFi data for known planned evacuation drills, conduct floor-level analysis to eliminate noise associated with transient WiFi connections or persistently connected devices, and highlight the anatomy of evacuations across multiple representative buildings each with differing number of levels, exit layouts, and occupant types. Armed with a detailed understanding of the anatomy of a planned evacuation, our second contribution develops a novel method to automatically identify evacuation events from WiFi data; we use it to detect 29 unplanned evacuations, and corroborate them against documented records where available. Our third contribution deduces quantitative measures to compare planned and unplanned evacuations, in terms of evacuation speed and occupancy levels, and further quantifies the man-days of productivity loss arising from unplanned evacuation events across campus. We believe our work is the first to show that building evacuations can be evaluated systematically and accurately at scale using WiFi data, both to corroborate current manual records and to gain new insights.
Abstract 3264: Sotorasib, a selective G12C K-RAS inhibitor, modulates the tumor microenvironment to promote TNFα and IFNγ signaling and augment immunotherapy response (2023)

Abstract KRAS-G12C mutation represents a highly prevalent mutation in lung and colon carcinoma with unfavorable clinical outcome. Recently, new compounds were developed that selectively bind to K-RAS with G12C mutation. While recent clinical results demonstrate activity of these compounds, their underlying mechanisms of action and impact on the antitumor immune response are not well understood. Here, we tested G12C-Kras inhibitor (Sotorasib/AMG-510) using multiple approaches. We found that Sotorasib significantly promoted the tumor regression and the expansion of tumor infiltrating lymphocytes (TILs) in both CT26-G12C heterotopic colon cancer, and KP-G12C autochthonous GEMM lung cancer mouse models, with more profound impact when combined with anti-PD1 ICB immunotherapy. In addition, it generated a “hot” tumor microenvironment with strikingly augmented T cell effector phenotype, endorsed by enrichment of MHC-II high macrophage and reduction of suppressive myeloid cells. Interestingly, Single cell RNA sequencing of CT26-G12C tumors shows an enrichment of tumor clusters with TNFα and IFNγ as top upregulated pathways in Sotorasib-treated tumors, generating a more immune active TME. These immune active tumor clusters were conserved or further expanded upon cotreatment with anti-PD1 ICI. Conversely, immune-deficient, or Sotorasib-resistant tumors exhibited a remarkable contraction of the immune active clusters, substantiating that the immune-modulatory impact of Sotorasib relies on tumor cells adaptation and their cross talk with the tumor infiltrated lymphocytes. In vitro, Single cell RNA sequencing of CT26-G12C cells also revealed that Sotorasib and TNFα/IFNγ cytokines are affecting different tumor clusters. Moreover, further in vitro testing demonstrated that Sotorasib dramatically enhances KRAS-G12C mutant cancer cell killing by PSCA-specific CART cells. These findings provide insight into the molecular basis of G12C-Kras inhibitor-mediated immune modulation in the TME and provide insight for combinatorial regimens with checkpoint inhibitor and adoptive T cell immunotherapy to achieve optimum anti-tumor activity. Citation Format: Mohammed L. Ibrahim, Dana Foresman, Hong Zheng, Eric B. Haura, Daniel Abate-Daga, Xiaoqing Yu, Amer A. Beg. Sotorasib, a selective G12C K-RAS inhibitor, modulates the tumor microenvironment to promote TNFα and IFNγ signaling and augment immunotherapy response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3264.
Predictors of job satisfaction among academic faculty members: do instructional and clinical staff differ? (2010)

Greater emphasis must be placed on faculty members' well-being at both the institutional level and the level of departmental leadership. Efforts to enhance job satisfaction and improve retention are more likely to succeed if they are directed by locally designed assessments involving department chairs and are specifically aimed at fostering more effective mentoring relationships and increasing the opportunities available for career advancement activities such as research work. Our findings show that these strategies can have significant impacts on job satisfaction and the retention of clinical track faculty members.
Human papillomaviruses in normal oral mucosa: a comparison of methods for sample collection (1992)

The prevalence of six genital genotypes of HPV was assessed in the clinically normal oral mucosa of an adult Caucasian population, and three methods of sample collection compared. HPV DNA was detected in the mouth of 60% of 60 subjects. HPV 16 was the most prevalent genotype, and positive samples were found most frequently in men over 50. A 3% sucrose mouthwash produced more positive results (51%) than mucosal scrapes of three separate sites (45%) or buccal mucosal biopsies (12%). There was no association of a positive result for HPV DNA with any particular mucosal site. A mouthwash was the preferred single screening method for epidemiologic studies of HPV DNA in the mouth, but the greatest yield of positive samples was obtained if multiple sampling techniques were employed.
Sugar Containing Compounds and Biological Activities of Lagochilus setulosus (2021)

Phytochemical investigation of the methanolic extract obtained from the aerial parts of <i>Lagochilus setulosus</i> (Lamiaceae) afforded the new compound 1-methoxy-3-<i>O</i>-<i>β</i>-glucopyranosyl-α-l-oliose (<b>1</b>) together with five known glycosides, namely sitosterol-3-<i>O</i>-<i>β</i>-glucoside (<b>2</b>), stigmasterol-3-<i>O</i>-<i>β</i>-glucoside (<b>3</b>), pinitol (<b>4</b>), 6<i>β</i>-hydroxyl-7-<i>epi</i>-loganin (<b>5</b>), and chlorotuberoside (<b>6</b>). The structures of these compounds were elucidated by extensive spectroscopic analyses, especially HR-MS, 1D and 2D NMR spectroscopy. The in vitro cytotoxic activity of the methanolic extract and the isolated compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and crystal violet (CV) staining assays. In addition, the antifungal activities of the components were evaluated against <i>Botrytis cinerea, Septoria tritici,</i> and <i>Phytophthora infestans.</i> The anthelmintic potential was determined against <i>Caenorhabditis elegans</i> nematodes. Neither the extract nor the isolated compounds showed promising activity in all the bioassays.
Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms (2018)

Site-specific eukaryotic genome editing with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems has quickly become a commonplace amongst researchers pursuing a wide variety of biological questions. Users most often employ the Cas9 protein derived from Streptococcus pyogenes in a complex with an easily reprogrammed guide RNA (gRNA). These components are introduced into cells, and through a base pairing with a complementary region of the double-stranded DNA (dsDNA) genome, the enzyme cleaves both strands to generate a double-strand break (DSB). Subsequent repair leads to either random insertion or deletion events (indels) or the incorporation of experimenter-provided DNA at the site of the break. The use of a purified single-guide RNA and Cas9 protein, preassembled to form an RNP and delivered directly to cells, is a potent approach for achieving highly efficient gene editing. RNP editing particularly enhances the rate of gene insertion, an outcome that is often challenging to achieve. Compared to the delivery via a plasmid, the shorter persistence of the Cas9 RNP within the cell leads to fewer off-target events. Despite its advantages, many casual users of CRISPR gene editing are less familiar with this technique. To lower the barrier to entry, we outline detailed protocols for implementing the RNP strategy in a range of contexts, highlighting its distinct benefits and diverse applications. We cover editing in two types of primary human cells, T cells and hematopoietic stem/progenitor cells (HSPCs). We also show how Cas9 RNP editing enables the facile genetic manipulation of entire organisms, including the classic model roundworm Caenorhabditis elegans and the more recently introduced model crustacean, Parhyale hawaiensis.
Reimagining Secret Sharing: Creating a Safer and More Versatile Primitive by Adding Authenticity, Correcting Errors, and Reducing Randomness Requirements (2020)

Aiming to strengthen classical secret-sharing to make it a more directly useful primitive for human endusers, we develop definitions, theorems, and efficient constructions for what we call adept secret-sharing. Our primary concerns are the properties we call privacy, authenticity, and error correction. Privacy strengthens the classical requirement by ensuring maximal confidentiality even if the dealer does not employ fresh, uniformly random coins with each sharing. That might happen either intentionally—to enable reproducible secretsharing— or unintentionally, when an entropy source fails. Authenticity is a shareholder’s guarantee that a secret recovered using his or her share will coincide with the value the dealer committed to at the time the secret was shared. Error correction is the guarantee that recovery of a secret will succeed, also identifying the valid shares, exactly when there is a unique explanation as to which shares implicate what secret. These concerns arise organically from a desire to create general-purpose libraries and apps for secret sharing that can withstand both strong adversaries and routine operational errors.
The Epidemiology of Respiratory Syncytial Virus Lower Respiratory Tract Infection on Young Children (2012)

To the Editors: Respiratory syncytial virus (RSV) is a cause of substantial morbidity in infants <6 months of age. Thus, we read with interest the study by Simões et al1 reporting on the epidemiology of RSV among children in 2 Indonesian communities. They identify a striking lack of RSV lower respiratory infection (LRI) cases in infants <2 months of age, which may be due to differences in epidemiology in the developing world or higher neutralizing antibody titers passively transferred from the infants’ mothers. As the authors indicate, most other studies identified a significant burden of severe RSV LRI in infants <6 weeks of age.2 In the Simões study, potential cases of RSV infection were identified by kaders, paraprofessional health care workers who visited the homes of the infants each week. Possibly, the application of the World Health Organization LRI definition by the kaders was insufficient to identify RSV-infected newborns. We agree with the authors that more studies of RSV epidemiology in the developing world are warranted. In the accompanying invited commentary, Bont and Houben3 characterize the burden of RSV illness in infants <6 months of age in Indonesia as low but also make the misleading conclusion that RSV LRI during the first 3–6 months of life is generally rare. In fact, the rate of RSV LRI in infants 3–5 months of age in the Simões study was 50/1000 child years, not an insubstantial burden. The commentary also cites a study by Hall et al4 in which rates of proven RSV infection among US children 0–5 months of age in a pediatric practice ranged from 108 to 132/1000. These studies indicate that RSV causes substantial morbidity in young infants. Brian W. Cooper, MD Philip R. Dormitzer, MD, PhD Max Ciarlet, PhD Novartis Vaccines and Diagnostics Cambridge, MA
Humidity‐Induced Switching between Two Magnetic and Structural Phases in a Co<sup>II</sup>‐[W<sup>V</sup>(CN)<sub>8</sub>] Molecular Magnet (2019)

The self-assembly of cobalt(II) with purine and octacyanidotungstate(V) results in the formation of the three-dimensional Co<sub>3</sub> [W(CN)<sub>8</sub> ]<sub>2</sub> (purine)<sub>2</sub> ⋅8.5H<sub>2</sub> O (1) coordination polymer. This compound exhibits humidity-induced variation of the number of water molecules of crystallisation leading to a reversible structural phase transition and the alternation of the long-range ferromagnetic ordering temperature from T<sub>C</sub> =29 K for the pristine assembly (1) to T<sub>C</sub> =49 K for the sample stored in a low-humidity atmosphere (1-deh). This phenomenon can be attributed to a reversible change in the hydrogen-bonding network resulting in the modification of the local geometries of cobalt(II) as well as the cyanido bridges.
Low-Frequency Quantum Sensing (2022)

Quantum sensing of low-frequency fields is important for nuclear magnetic resonance (NMR) due to its rich structure and narrow line widths, both at low fields focusing on $J$ couplings and at high fields for down-converted frequencies from conventional NMR. However, the most sensitive and coherent quantum sensing methods work at dc and high-frequency fields only. This study utilizes a quantum oscilloscope approach to bridge this gap. The resulting algorithm has a frequency-independent sensitivity and is able to work in the zero-field region. This approach would have an impact on designing low-frequency measurements where the high sensitivities of quantum sensors are an indispensable treat.
Opaque WDM optical-crossconnect networks (2003)

In response to the recent lurch in data-networking demand, we are speedily moving from core long-haul telecommunications networks whose fibers transport tens of 45-Mb/s signals to systems whose fibers transport tens of wavelengths. This sudden leap places a massive burden on current mechanisms for restoring the network in the event of failures, and will rapidly come to overtax available mechanisms for provisioning new connections. Thus, as WDM transmission technology is deployed, it becomes increasingly important to find ways of extracting value from it in the form of enhanced provisioning and restoration functionality.
Streptococcus pneumoniae genomic datasets from an Indian population describing pre-vaccine evolutionary epidemiology using a whole genome sequencing approach (2021)

Globally, India has a high burden of pneumococcal disease, and pneumococcal conjugate vaccine (PCV) has been rolled out in different phases across the country since May 2017 in the national infant immunization programme (NIP). To provide a baseline for assessing the impact of the vaccine on circulating pneumococci in India, genetic characterization of pneumococcal isolates detected prior to introduction of PCV would be helpful. Here we present a population genomic study of 480 <i>Streptococcus pneumoniae</i> isolates collected across India and from all age groups before vaccine introduction (2009-2017), including 294 isolates from pneumococcal disease and 186 collected through nasopharyngeal surveys. Population genetic structure, serotype and antimicrobial susceptibility profile were characterized and predicted from whole-genome sequencing data. Our findings revealed high levels of genetic diversity represented by 110 Global Pneumococcal Sequence Clusters (GPSCs) and 54 serotypes. Serotype 19F and GPSC1 (CC320) was the most common serotype and pneumococcal lineage, respectively. Coverage of PCV13 (Pfizer) and 10-valent Pneumosil (Serum Institute of India) serotypes in age groups of ≤2 and 3-5 years were 63-75 % and 60-69 %, respectively. Coverage of PPV23 (Merck) serotypes in age groups of ≥50 years was 62 % (98/158). Among the top five lineages causing disease, GPSC10 (CC230), which ranked second, is the only lineage that expressed both PCV13 (serotypes 3, 6A, 14, 19A and 19F) and non-PCV13 (7B, 13, 10A, 11A, 13, 15B/C, 22F, 24F) serotypes. It exhibited multidrug resistance and was the largest contributor (17 %, 18/103) of NVTs in the disease-causing population. Overall, 42 % (202/480) of isolates were penicillin-resistant (minimum inhibitory concentration ≥0.12 µg ml<sup>-1</sup>) and 45 % (217/480) were multidrug-resistant. Nine GPSCs (GPSC1, 6, 9, 10, 13, 16, 43, 91, 376) were penicillin-resistant and among them six were multidrug-resistant. Pneumococci expressing PCV13 serotypes had a higher prevalence of antibiotic resistance. Sequencing of pneumococcal genomes has significantly improved our understanding of the biology of these bacteria. This study, describing the pneumococcal disease and carriage epidemiology pre-PCV introduction, demonstrates that 60-75 % of pneumococcal serotypes in children ≤5 years are covered by PCV13 and Pneumosil. Vaccination against pneumococci is very likely to reduce antibiotic resistance. A multidrug-resistant pneumococcal lineage, GPSC10 (CC230), is a high-risk clone that could mediate serotype replacement.
Komplexchemie reaktiver organischer Verbindungen. XLV. Metallorganische Methandiazo – Komplexe: Protonierung und Cycloaddition (1984)

Abstract Stark ausgeprägte Solvens‐Effekte beeinflussen die Säure‐Reaktionen des Methandiazo–Wolfram‐Komplexes (η 5 ‐C 5 H 5 )W(CO) 2 (N 2 CH 3 ) ( 1 ): Während Trifluormethansulfonsäure in Diethylether die glatte Protonierung zum salzartigen Derivat [(η 5 ‐C 5 H 5 )W(CO) 2 (HN 2 CH 3 )]+CF 3 SO 3 − ( 3 ) bewirkt, bildet sich im koordinationsfähigen Lösungsmittel Acetonitril die Verbindung 4 , die durch eine neuartige Cycloaddition eines Solvens‐Moleküls an die protonierte Spezies [(η 5 ‐C 5 H 5 )‐W(CO)(CH 3 CN)(HN 2 CH 3 )]+CF 3 SO 3 − zustandekommt. Mit Bromwasserstoff erfolgt vollständige Abspaltung des stickstoffhaltigen Ligandensembles zum Halogeno‐Komplex (η 5 ‐C 5 H 5 )W(CO) 2 Br 3 ( 5 ).
[Standardization of measurement of catalytic activity concentration of enzymes--current situation regarding the external quality assessment program provided by the Japan Medical Association]. (2010)

Measurement of the catalytic activity concentration of enzymes has been standardized using a traceability chain, consisting a reference measurement system for enzyme catalytic activity and reference standard-JSCC enzyme. The Japan Medical Association (JMA) has provided an external quality assessment (EQA) survey program for clinical laboratory testing. More than 3,100 clinical laboratories participated in 2008. The EQA program indicated that standardization of the measurement of the catalytic activity concentration of enzymes has been completed for AST, ALT, LD, ALP, gammaGT, and CK in more than 90% laboratories, and for Amy and ChE in nearly 80% of laboratories. Because such a large survey program must use artificial specimens, a matrix effect cannot be avoided, especially in dry chemistry. However, the bias produced by a matrix effect usually has a predictable tendency: it can be corrected. Next, after standardization of the measurement of the catalytic activity concentration of enzymes, we should develop and use common reference intervals. On completing the standardization, we can make standard medical decisions using reference measurement systems and rules.
Novel phenylamine‐based oxime ester photoinitiators for <scp>LED</scp>‐induced free radical, cationic, and hybrid polymerization (2021)

Abstract Four new photoinitiators (PI's) containing various phenylamine‐based groups as chromophores and oxime ester (OXE) as initiating groups are proposed for the free radical polymerization, the cationic polymerization, and interpenetrated polymer networks upon visible light exposure using a light emitting diodes at 405 nm. These compounds showed outstanding polymerization photoinitiation ability, that is, high‐polymerization rates and good final reactive function conversions were obtained. The chemical mechanisms by which these OXE's generate reactive species were investigated through different techniques including real‐time Fourier transform infrared spectroscopy, UV–visible spectroscopy, fluorescence (time‐resolved or steady state) as well as cyclic voltammetry. Markedly, the proposed structures can be used as thermal initiators indicating all of them can be polymerized under suitable reaction temperature. In addition, due to their high efficiency, these optimized PI's were found to be useful @405 nm for both direct laser write and 3D printing applications.