gebhart/patrepeval huggingface dataset:
A NOTCH2 Single Nucleotide Polymorphism is Associated with Colorectal Adenoma Location in a Multi-ethnic Screening Group (2011)

Purpose: A single nucleotide polymorphism (SNP) in the NOTCH2 gene (rs10923931 G>T) has an association with BMI and type II diabetes mellitus, both known risk factors for colorectal cancer (CRC). Given the known link of CRC with obesity, a modifiable risk factor, the aim of this study was to evaluate the NOTCH2 SNP as a potential non-modifiable risk factor of CRC in a multi-ethnic cohort. Methods: Consecutive patients presenting for screening colonoscopy were prospectively enrolled. A detailed history and blood sample were obtained from each subject. During colonoscopy, the number, size, and location of any polyps were noted. Nested PCR was used to amplify a specific fragment on chromosome 1 containing the NOTCH2 gene, which was then digested with FatI restriction endonuclease. PAGE and subsequent ethidium bromide staining followed by ultraviolet photography were utilized to determine the SNP genotype of each patient. Binary logistic regression, Pearson's chi-square test, and Fisher's exact test were performed using SPSS software PASW Statistics 18 for Windows (SPSS Inc., Chicago, IL), and a two-tailed p value of <0.05 was considered statistically significant. Results: A total of 256 patients were enrolled (55.1% female; mean age 55.6 ± 9.5). Overall, 35.7% of Blacks, 29.2% of Caucasians, 20.7% of Hispanics, and 12.5% of Asians had at least one variant T allele. The prevalence of abnormal BMI (BMI≥25) was higher in individuals with the T allele compared to those without the T allele (75.0% vs. 64.3%). Patients with at least one T allele had a significantly higher percentage of diabetes when compared to those with no T allele (32.1% vs. 16.0%; p=0.007). Prevalence of adenomas did not differ significantly between patients with and those without at least one T allele (14.3% vs. 15.7%; p=0.802). Among patients with adenomas, those with at least one T allele were more likely to have only proximal adenomas, defined as any adenoma proximal to the splenic flexure or greater than 60cm from the anal sphincter, compared to those without the T allele (87.5% vs. 35.5%; p=0.015). This association remained significant after correction for age, gender, race, and BMI (OR = 13.90; 95% CI 1.08 to 178.90; p=0.044). Conclusion: In this multi-ethnic cohort, NOTCH2 genotype was not associated with the presence but rather the location of adenomas. This finding has potential implications for choosing screening modalities that evaluate the colon partially or completely.
Techniques and Patterns for Safe and Efficient Real-Time Middleware (2004)

Over 90 percent of all microprocessors are now used for real-time and embedded applications. The behavior of these applications is often constrained by the physical world. It is therefore important to devise higher-level languages and middleware that meet conventional functional requirements, as well as dependably and productively enforce real-time constraints. Real-Time Java is emerging as a safe, real-time environment. In this thesis we use it as our experimentation platform; however, our ﬁndings are easily adapted to other similar platforms. This thesis provides the following contributions to the study of safe and efﬁcient real-time middleware. First, it identiﬁes potential bottlenecks and problem with respect to guaranteeing real-time performance in middleware. Second, it presents a series of techniques and patterns that allow the design and implementation of safe, predictable, and highly efﬁcient real-time middleware. Third, it provides a set of architectural and design patterns that application developers can use when designing real-time systems. Finally, it provides a methodology for evaluating the merits and beneﬁts of real-time middleware. Empirical results are presented using that methodology for the techniques presented in this thesis. The methodology helps compare the performance and predictability of general, real-time middleware platforms.
Oncolysis of Prostate Cancers Induced by Vesicular Stomatitis Virus in PTEN Knockout Mice (2010)

Abstract Vesicular stomatitis virus (VSV) is an oncolytic virus which selectively infects and kills cancer cells. The goal of the present study was to determine the safety and efficacy of VSV treatment of prostate tumors that arise in situ in immunocompetent, transgenic prostate-specific PTEN-null (PTEN−/−) mice. Interferon-sensitive VSV(AV3 strain), which expresses luciferase, was injected intraprostatically into tumor-bearing PTEN−/− and control mice and then monitored for tissue bioluminescence over 96 hours. Virus readily dispersed throughout the bodies of mice after only 3 hours; however, it persisted at high levels for &amp;gt;72 hours in PTEN−/− mice, but at relatively low levels and for only ∼48 hours in controls. Plaque assays provided a similar pattern, with much higher concentrations of replicating virus in prostates of PTEN−/− mice than in controls. Transient, low levels of virus were detected in the spleens of both groups. Apoptotic analyses by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining revealed that VSV(AV3) is able to selectively infect and kill prostate cells in PTEN−/− mice, while sparing normal cells in control mice. The primary mechanism for cell kill is apparently apoptotic oncolysis as opposed to neutrophil invasion as has been reported using xenograft models. These results suggest that control of locally advanced human prostate cancer may be achievable through intraprostatic injection and amplification of a safe oncolytic virus, such as VSV(AV3). Cancer Res; 70(4); 1367–76
Influence of temperature on the molecular composition of ions and charged clusters during pure biogenic nucleation (2017)

Abstract. It was recently shown by the CERN CLOUD experiment that biogenic highly oxygenated molecules (HOMs) form particles under atmospheric conditions in the absence of sulfuric acid where ions enhance the nucleation rate by one to two orders of magnitude. The biogenic HOMs were produced from ozonolysis of α-pinene at 5 °C. Here we extend this study to compare the molecular composition of positive and negative HOM clusters measured with atmospheric pressure interface time-of-flight mass spectrometers (APi-TOFs), at three different temperatures (25 °C, 5 °C and −25 °C). Most negative HOM clusters include a nitrate (NO3−) ion and the spectra are similar to those seen in the nighttime boreal forest. On the other hand, most positive HOM clusters include an ammonium (NH4+) ion and the spectra are characterized by mass bands that differ in their molecular weight by ~ 20 C atoms, corresponding to HOM dimers. At lower temperatures the average oxygen to carbon (O : C) ratio of the HOM clusters decreases for both polarities, reflecting an overall reduction of HOM formation with decreasing temperature. This indicates a decrease in the rate of autoxidation with temperature due to a rather high activation energy as has previously been determined by quantum chemical calculations. Furthermore, at the lowest temperature (−25 °C) the presence of C30 clusters show that HOM monomers start to contribute to the nucleation of positive clusters. These experimental findings are supported by quantum chemical calculations of the binding energies of representative neutral and charged clusters.
P2X receptor-mediated visceral hyperalgesia in a rat model of chronic visceral hypersensitivity (2008)

These data suggest that the large enhancement of P2XR expression and function may contribute to the maintenance of visceral hypersensitivity, thus identifying a specific neurobiological target for the treatment of chronic visceral hyperalgesia.
An Efficient Catalytic Asymmetric Synthesis of a β2-Amino Acid on Multikilogram Scale (2013)

We describe herein a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a β2-amino acid. A short and efficient synthesis of the starting unsaturated N-Boc-protected β2-enamide was developed followed by extensive catalysis screening and optimization studies that identified a simple Ru-BINAP catalyst system to directly afford the (S) product in high enantiomeric excess and yield. The final process enabled the multikilogram production in >99% ee, to be used as a key component for one of our clinical candidates.
Modular multi-level converter based HVDC system for grid connection of offshore wind power plant (2010)

This paper explores the application of modular multi-level converters (MMC) as a means for harnessing the power from off-shore wind power plants. The MMC consists of a large number of simple voltage sourced converter (VSC) submodules that can be easily assembled into a converter for high-voltage and high power. The paper shows that the MMC converter has a fast response and low harmonic content in comparison with a two-level VSC option. The paper discusses the modeling approach used, including a solution to the modeling challenge imposed by the very large number of switching devices in the MMC. (5 pages)
Targeting the A3 adenosine receptor to prevent and reverse chemotherapy-induced neurotoxicities in mice (2022)

Cisplatin is used to combat solid tumors. However, patients treated with cisplatin often develop cognitive impairments, sensorimotor deficits, and peripheral neuropathy. There is no FDA-approved treatment for these neurotoxicities. We investigated the capacity of a highly selective A<sub>3</sub> adenosine receptor (AR) subtype (A<sub>3</sub>AR) agonist, MRS5980, to prevent and reverse cisplatin-induced neurotoxicities. MRS5980 prevented cisplatin-induced cognitive impairment (decreased executive function and impaired spatial and working memory), sensorimotor deficits, and neuropathic pain (mechanical allodynia and spontaneous pain) in both sexes. At the structural level, MRS5980 prevented the cisplatin-induced reduction in markers of synaptic integrity. In-situ hybridization detected Adora3 mRNA in neurons, microglia, astrocytes and oligodendrocytes. RNAseq analysis identified 164 genes, including genes related to mitochondrial function, of which expression was changed by cisplatin and normalized by MRS5980. Consistently, MRS5980 prevented cisplatin-induced mitochondrial dysfunction and decreased signs of oxidative stress. Transcriptomic analysis showed that the A<sub>3</sub>AR agonist upregulates genes related to repair pathways including NOTCH1 signaling and chromatin modification in the cortex of cisplatin-treated mice. Importantly, A<sub>3</sub>AR agonist administration after completion of cisplatin treatment resolved cognitive impairment, neuropathy and sensorimotor deficits. Our results highlight the efficacy of a selective A<sub>3</sub>AR agonist to prevent and reverse cisplatin-induced neurotoxicities via preventing brain mitochondrial damage and activating repair pathways. An A<sub>3</sub>AR agonist is already in cancer, clinical trials and our results demonstrate management of neurotoxic side effects of chemotherapy as an additional therapeutic benefit.
Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination (2010)

Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals, including large and small ruminants and swine. Current vaccine strategies are all directed toward the induction of neutralizing antibody responses. However, the role of cytotoxic T lymphocytes (CTLs) has not received a great deal of attention, in part because of the technical difficulties associated with establishing a reliable assay of cell killing for this highly cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation and effectively increasing the class I major histocompatibility complex (MHC)/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell-targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8(+) CTL killing of MHC-matched target cells in an antigen-specific manner. Further, we confirm these results by MHC tetramer staining. This work presents the first demonstration of FMDV-specific CTL killing and confirmation by MHC tetramer staining in response to vaccination against FMDV.
Anti-Endotoxin Agents. 2. Pilot High-Throughput Screening for Novel Lipopolysaccharide-Recognizing Motifs in Small Molecules (2004)

Lipopolysaccharides (LPS), otherwise termed 'endotoxins', are an integral part of the outer leaflet of the outer-membrane of Gram-negative bacteria. Lipopolysaccharides play a pivotal role in the pathogenesis of 'Septic Shock', a major cause of mortality in the critically ill patient, worldwide. The sequestration of circulatory endotoxin may be a viable therapeutic strategy for the prophylaxis and treatment of Gram-negative sepsis. We have earlier shown that the pharmacophore necessary for small molecules to bind LPS is simple, comprising of two protonatable cationic functions separated by about 15 A, permitting the simultaneous interaction with the negatively charged phosphates on lipid A, the toxically active center of endotoxin. In this report, we employ high-throughput screening methods, using a novel fluorescent probe displacement method. Searches in three-dimensional structure databases yielded about approximately 4000 commercially available small molecules, each possessing two cationic functions spaced approximately 15 A apart. Approximately 400 such compounds have been screened in an effort to validate the method by which high-affinity endotoxin binders can be identified. We show that the IC50 values that are obtained from the fluorescence-based primary screen are correlated both to the enthalpy of binding, as measured by isothermal titration calorimetry, as well as to biological potency in vitro assays. By performing rapid toxicity screens in tandem with the bioassays, lead compounds of interest can be easily identified for further systematic structural modifications and SAR studies.
Modified Discontinuous PWM for Size Reduction of the Circulating Current Filter in Parallel Interleaved Converters (2014)

Parallel voltage-source converters (VSCs) require an inductive filter to suppress the circulating current. The size of this filter can be minimized by reducing either the maximum value of the flux linkage or the core losses. This paper presents a modified discontinuous pulsewidth modulation (DPWM) scheme to reduce the maximum value of the flux linkage and the core losses in the circulating current filter. In the proposed PWM scheme, the dwell time of an active vector is divided within a half-carrier cycle to ensure simultaneous occurrence of the same zero vectors in both VSCs. A function to decide the ratio of the dwell time of the divided active vector is also presented. The effect of the proposed PWM scheme on the maximum value of the flux linkage and the core losses is analyzed and compared with that of the space vector modulation and 60$^\circ$ clamped DPWM schemes. The analytical expressions for the maximum value of the flux linkage are derived for each of these PWM schemes. In addition, the effect of the proposed PWM scheme on the line current ripple and the switching losses is also analyzed and compared. To verify the analysis, experimental results are presented, which prove the effectiveness of the proposed PWM scheme.
How does a drug-coated balloon work? Overview about coating technologies and their impact. (2015)

For the time being paclitaxel remains the drug of choice, the dose varies between 2 and 3.5 μg/mm² balloon surface. Neither in animal experiments nor in clinical trials problems have been detected in vessel segments treated with overlapping balloons. Future developments are expected improving efficacy in additional disease conditions (e.g., calcified vessels) and vessel territories.
Session Initiation Protocol (SIP) Recording Metadata (2016)

Session recording is a critical requirement in many communications environments, such as call centers and financial trading organizations. In some of these environments, all calls must be recorded for regulatory, compliance, and consumer protection reasons. The recording of a session is typically performed by sending a copy of a media stream to a recording device. This document describes the metadata model as viewed by the Session Recording Server (SRS) and the recording metadata format.
ChemInform Abstract: Lewis Acid Promoted Deoxygenative Di[β,β‐bis(ethylthio)]vinylation of Aldehydes with Trimethylsilylketene Bis(ethylthio)acetal. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Nanoscale Encapsulation of Hybrid Perovskites Using Hybrid Atomic Layer Deposition (2022)

Organic-inorganic hybrid perovskites have shown tremendous potential for optoelectronic applications. Ion migration within the crystal and across heterointerfaces, however, imposed severe problems with material degradation and performance loss in devices. Encapsulating hybrid perovskite with a thin physical barrier can be essential for suppressing the undesirable interfacial reactions without inhibiting the desirable transport of charge carriers. Here, we demonstrated that nanoscale, pinhole-free Al<sub>2</sub>O<sub>3</sub> layer can be coated directly on the perovskite CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub> using atomic layer deposition (ALD). The success can be attributed to a multitude of strategies including surface molecular modification and hybrid ALD processing combining the thermal and plasma-enhanced modes. The Al<sub>2</sub>O<sub>3</sub> films provided remarkable protection to the underlying perovskite films, surviving by hours in solvents without noticeable decays in either structural or optical properties. The results advanced the understanding of applying ALD directly on hybrid perovskite and provided new opportunities to implement stable and high-performance devices based on the perovskites.
Evaluation of innate and adaptive immunity contributing to the antitumor effects of PD1 blockade in an orthotopic murine model of pancreatic cancer (2016)

Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice. This protective effect appeared to be mostly mediated by T cells, as adoptive transfer of purified natural killer (NK) cells and/or granulocyte receptor 1 (Gr1)(+) cells or splenocytes depleted of Gr1(+) cells and NK cells did not exhibit transferrable antitumor activity following short-term PD1 blockade. Nevertheless, splenic and tumor-derived CD11b(+)Gr1(+) cells and NK cells showed significant persistence of α-PD1 bound to these cells in the treated primary recipient mice. We observed that short-term inhibition of PD1 signaling modulated the profiles of multifunctional cytokines in the tumor immune-infiltrate, including downregulation of vascular endothelial growth factor A (VEGF-A). Altogether, the data suggest that systemic blockade of PD1 results in rapid modulation of antitumor immunity that differs in the tumor microenvironment (TME) when compared to the spleen. These results demonstrate a key role for early immune-mediated events in controlling tumor progression in response to α-PD1 treatment and warrant further investigation into the mechanisms governing responses to the therapy at the innate-adaptive immune interface.
ELECTROCHEMICAL PROPERIES OF HYDROTHERMALLY SYNTHESIZED LiCoPO<sub>4</sub> AS A HIGH VOLTAGE CATHODE MATERIAL FOR LITHIUM SECONDARY BATTERY (2010)

Carbon-coated LiCoPO4 which is a high voltage cathode material for lithium secondary battery was prepared under hydrothermal condition and its electrochemical property was compared with carbon-coated LiFePO4 and carbon-coated LiMnPO4 prepared under same condition. Highly crystallized particles of LiCoPO4 without impurity phase were obtained successfully. Particle size were almost same (250 – 500 nm) among the samples. Raman spectra indicated that carbon layer on the LiCoPO4 would be thinner than that on the LiFePO4 and the LiMnPO4. Discharge capacities of the LiFePO4 and the LiMnPO4 were 155 and 109 mA h g-1, respectively, and LiCoPO4 was 45 mA h g-1, 27% of theoretical capacity. Such low capacity of the LiCoPO4 would be attributed to the thin carbon layer which could not provide enough electronic conductivity. To prepare high performance LiCoPO4, optimization of hydrothermal condition to form thick carbon layer is required.
Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity (2021)

COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whilst commonly characterised as a respiratory disease, is reported to have extrapulmonary manifestations in multiple organs. Extrapulmonary involvement in COVID-19 includes autoimmune-like diseases such as Guillain-Barré syndrome and Kawasaki disease, as well as the presence of various autoantibodies including those associated with autoimmune diseases such a systemic lupus erythematosus (e.g. ANA, anti-La). Multiple strains of SARS-CoV-2 have emerged globally, some of which are found to be associated with increased transmissibility and severe disease. We performed an unbiased comprehensive mapping of the potential for cross-reactivity with self-antigens across multiple SARS-CoV-2 proteins and compared identified immunogenic regions across multiples strains. Using the Immune Epitope Database (IEDB) B cell epitope prediction tool, regions predicted as antibody epitopes with high prediction scores were selected. Epitope sequences were then blasted to eight other global strains to identify mutations within these regions. Of the 15 sequences compared, eight had a mutation in at least one other global strain. Predicted epitopes were then compared to human proteins using the NCBI blast tool. In contrast to studies focusing on short sequences of peptide identity, we have taken an immunological approach to selection criteria for further analysis and have identified 136 alignments of 6-23 amino acids (aa) in 129 human proteins that are immunologically likely to be cross-reactive with SARS-CoV-2. Additionally, to identify regions with significant potential to interfere with host cell function-or promote immunopathology, we identified epitope regions more likely to be accessible to pathogenic autoantibodies in the host, selected using a novel combination of sequence similarity, and modelling protein and alignment localization with a focus on extracellular regions. Our analysis identified 11 new predicted B-cell epitopes in host proteins, potentially capable of explaining key aspects of COVID-19 extrapulmonary pathology, and which were missed in other <i>in silico</i> studies which used direct identity rather than immunologically related functional criteria.