gebhart/patrepeval huggingface dataset:
Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines (2020)

The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.
Aspergilli as Ochratoxin Producers (1972)

SUMMARYTo determine whether ochratoxin is produced by species of Aspergillus other than A. ochraceus, 44 strains representative of the nine species composing the A. ochraceus group were grown on both pearled wheat and cracked corn in duplicate shaken flasks at 28 C for 5 days. Rice was a poor substrate for production of ochratoxin. Molded substrates were extracted with acetonitrile-water; partially purified extracts were assayed for ochratoxins by thin-layer chromatography. All positive samples were confirmed by solubility in sodium bicarbonate and the preparation of methyl esters. Ochratoxins A and B were found in some strains of A. sulphureus, A. sclerotiorum, A. alliaceus, A. melleus, A. ochraceus, A. ostianus, and A. petrakii. No ochratoxin was produced by the one strain of A. elegans or any of six strains of A. auricomus. Five of nine strains of A. sclerotiorum and five of 11 strains of A. ochraceus were negative. All seven strains of A. alliaceus were positive, but one was at a very low level. Generally, yields of ochratoxin were higher in wheat than in corn. Occasionally, as much ochratoxin B was produced as A. Highest yields of ochratoxins A and B were obtained from respective strains of A. ochraceus NRRL 3174 and NRRL 3519. Some strains of most species of the A. ochraceus group produce this mycotoxin as a secondary metabolite.
GINS and Sld3 Compete with One Another for Mcm2-7 and Cdc45 Binding (2011)

Sld3 is essential for the initiation of DNA replication, but Sld3 does not travel with a replication fork. GINS binds to Cdc45 and Mcm2-7 to form the replication fork helicase in eukaryotes. We purified Sld3, Cdc45, GINS, and Mcm2-7 and studied their interaction and assembly into complexes. Sld3 binds tightly to Cdc45 in the presence or absence of cyclin-dependent kinase activity. Furthermore, Sld3 binds tightly to the Mcm2-7 complex, and a ternary complex forms among Cdc45, Mcm2-7, and Sld3, with a 1:1:1 stoichiometry (CMS complex). GINS binds directly to Mcm2-7, and GINS competes with Sld3 for Mcm2-7 binding. GINS also binds directly to Cdc45, and GINS competes with Sld3 for Cdc45 binding. Cdc45, Mcm2-7, and GINS form a ternary complex with a stoichiometry of 1:1:1 (CMG complex). Size exclusion data reveal that when Sld3, Cdc45, Mcm2-7, and GINS are added together, the result is a mixture of CMS and CMG complexes. The data suggest that GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding. Our results are consistent with a model wherein GINS trades places with Sld3 at a replication origin, contributing to the activation of the replication fork helicase.
Efficient support for irregular applications on distributed-memory machines (1995)

Irregular computation problems underlie many important scientific applications. Although these problems are computationally expensive, and so would seem appropriate for parallel machines, their irregular and unpredictable run-time behavior makes this type of parallel program difficult to write and adversely affects run-time performance. This paper explores three issues—partitioning, mutual exclusion, and data transfer—crucial to the efficient execution of irregular problems on distributed-memory machines. Unlike previous work, we studied the same programs running in three alternative systems on the same hardware base (a Thinking Machines CM-5): the CHAOS irregular application library, Transparent Shared Memory (TSM), and eXtensible Shared Memory (XSM). CHAOS and XSM performed equivalently for all three applications. Both systems were somewhat (13%) to significantly faster (991%) than TSM.
A discriminative framework for clustering via similarity functions (2008)

Problems of clustering data from pairwise similarity information are ubiquitous in Computer Science. Theoretical treatments typically view the similarity information as ground-truth and then design algorithms to (approximately) optimize various graph-based objective functions. However, in most applications, this similarity information is merely based on some heuristic; the ground truth is really the unknown correct clustering of the data points and the real goal is to achieve low error on the data. In this work, we develop a theoretical approach to clustering from this perspective. In particular, motivated by recent work in learning theory that asks "what natural properties of a similarity (or kernel) function are sufficient to be able to learn well?" we ask "what natural properties of a similarity function are sufficient to be able to cluster well?"
Hardware-aware training for large-scale and diverse deep learning inference workloads using in-memory computing-based accelerators (2023)

Analog in-memory computing (AIMC) -- a promising approach for energy-efficient acceleration of deep learning workloads -- computes matrix-vector multiplications (MVMs) but only approximately, due to nonidealities that often are non-deterministic or nonlinear. This can adversely impact the achievable deep neural network (DNN) inference accuracy as compared to a conventional floating point (FP) implementation. While retraining has previously been suggested to improve robustness, prior work has explored only a few DNN topologies, using disparate and overly simplified AIMC hardware models. Here, we use hardware-aware (HWA) training to systematically examine the accuracy of AIMC for multiple common artificial intelligence (AI) workloads across multiple DNN topologies, and investigate sensitivity and robustness to a broad set of nonidealities. By introducing a new and highly realistic AIMC crossbar-model, we improve significantly on earlier retraining approaches. We show that many large-scale DNNs of various topologies, including convolutional neural networks (CNNs), recurrent neural networks (RNNs), and transformers, can in fact be successfully retrained to show iso-accuracy on AIMC. Our results further suggest that AIMC nonidealities that add noise to the inputs or outputs, not the weights, have the largest impact on DNN accuracy, and that RNNs are particularly robust to all nonidealities.
Influence of melatonin and its precursor L-tryptophan on Th1 dependent contact hypersensitivity. (2007)

There is strong evidence that melatonin possesses immunomodulatory activity. It has been shown that it enhances the immune response, acting as a pro-inflammatory agent. It is suggested that melatonin promotes Th1-mediated immune responses by upregulating IL-12 production by antigen presenting cells. In contrast, it has also been shown that melatonin can inhibit Th1 immunity and instead promote a Th2 response. This discrepancy between different observations of the regulatory activity of melatonin on Th1 immunity encouraged us to further investigate the influence of melatonin and its precursor L-tryptophan on Th1 mediated contact hypersensitivity (CHS). Our results show that both melatonin and L-tryptophan inhibit the inflammatory response associated with CHS. Melatonin inhibited the Th1-dependent immune response by suppressing the production of IFN-gamma and IL-12 by cells in the lymph node. On the other hand treatment with L-tryptophan inhibits CHS without affecting INF-gamma production by Th1 effector cells. Observed suppression of CHS after L-tryptophan treatment is at least partly through the production of the anti-inflammatory cytokine IL-10.
Functional verification of the superscalar SH-4 microprocessor (2002)

Functional verification of modern complex processors is a formidable and time consuming task. In spite of substantial manual effort, it is extremely difficult to systematically cover the corner cases of the control logic design, within a short processor design cycle. The SH4 processor is a dual issue superscalar RISC architecture with extensive hardware support for 3D graphics. We present the development of a semi automated methodology for functional verification. In particular, we elaborate a scheme to automatically generate test programs to verify the superscalar issue logic, bypass/multi bypass logic and stall logic, starting from the microarchitectural specification. Finally, we present the Random Test Generation methodology and the specific Random Test Generators.
Efficacy and safety of ERCP in patients with gastroesophageal varices (2020)

Addressing pancreaticobiliary disorders concomitant with gastroesophageal varices remains challenging. The goal of this study was to evaluate and compare the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in cirrhotic and noncirrhotic patients with gastroesophageal varices.We retrospectively analyzed the data of consecutive patients with gastroesophageal varices who underwent ERCP.Two hundred seventy ERCP procedures were performed on 208 patients. The overall technical success rate was 98.5%, and no difference was found between cirrhotic and noncirrhotic patients (98.7% vs 97.7%, P = .511); of these, endoscopic retrograde biliary drainage, endoscopic metal biliary endoprosthesis placement, endoscopic retrograde pancreatic drainage, and stone extraction were conducted in 173/270 (64.1%), 27/270 (10.0%), 26/270 (9.6%), and 116/270 (43.0%) cases, respectively. Endoscopic retrograde biliary drainage and stone extraction were more frequently performed in cirrhotic cases (67.7% versus 45.5%, P = .005; 46.5% versus 25.0%, P = .009, respectively), while the noncirrhotic group had significantly higher rates of endoscopic metal biliary endoprosthesis placement (31.8% versus 5.8%, P = .000) and endoscopic retrograde pancreatic drainage (18.2% versus 8.0%, P = .036) than the cirrhotic group. The overall rate of adverse events was 21.1%, including fever (6.7%), post-ERCP pancreatitis ( 3.0%), hyperamylasemia (6.3%), duodenal papilla bleeding (3.3%), cardiac mucosal laceration (1.1%), and perforation (0.4%). No differences in any of the adverse events were found between the 2 groups. Additionally, gastroesophageal variceal bleeding occurred in 1 patient with grade III varices 7 days after ERCP.ERCP may be effective and safe for patients with gastroesophageal varices, irrespective of the etiologies caused by liver cirrhosis.
Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification (2017)

We describe optimized fragmentation schemes and data analysis strategies substantially enhancing the depth and accuracy in identifying protein cross-links using non-restricted whole proteome databases. These include a novel hybrid data acquisition strategy to sequence cross-links at both MS2 and MS3 level and a new algorithmic design XlinkX v2.0 for data analysis. As proof-of-concept we investigated proteome-wide protein interactions in E. coli and HeLa cell lysates, respectively, identifying 1,158 and 3,301 unique cross-links at ∼1% false discovery rate. These protein interaction repositories provide meaningful structural information on many endogenous macromolecular assemblies, as we showcase on several protein complexes involved in translation, protein folding and carbohydrate metabolism.
SARS-CoV-2 nsp14 Exoribonuclease Removes the Natural Antiviral 3′-Deoxy-3′,4′-didehydro-cytidine Nucleotide from RNA (2022)

The on-going global pandemic of COVID-19 is caused by SARS-CoV-2, which features a proofreading mechanism to facilitate the replication of its large RNA genome. The 3'-to-5' exoribonuclease (ExoN) activity of SARS-CoV-2 non-structural protein 14 (nsp14) removes nucleotides misincorporated during RNA synthesis by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and thereby compromises the efficacy of antiviral nucleoside/nucleotide analogues. Here we show biochemically that SARS-CoV-2 nsp14 can excise the natural antiviral chain-terminating nucleotide, 3'-deoxy-3',4'-didehydro-cytidine 5'-monophosphate (ddhCMP), incorporated by RdRp at the 3' end of an RNA strand. Nsp14 ExoN processes an RNA strand terminated with ddhCMP more efficiently than that with a non-physiological chain terminator 3'-deoxy-cytidine monophosphate (3'-dCMP), whereas RdRp is more susceptible to chain termination by 3'-dCTP than ddhCTP. These results suggest that nsp14 ExoN could play a role in protecting SARS-CoV-2 from ddhCTP, which is produced as part of the innate immune response against viral infections, and that the SARS-CoV-2 enzymes may have adapted to minimize the antiviral effect of ddhCTP.
Simultaneous Data Transmission Using Multilevel LED in Hybrid OCC/LiFi System: Concept and Demonstration (2019)

In this letter, a hybrid-encoding scheme is developed for an integrated optical camera communication (OCC)/light-fidelity (LiFi) system. A single multilevel light-emitting diode (LED) is used for transmitting both OCC and LiFi data. Two data streams are transmitted, where each stream is intended for LiFi and OCC. The first stream is transmitted at a very high frequency using the LED. The LED flickers in two different power levels creating consecutive sequences. A smartphone camera receives the sequences as binary successions, wherein the second data stream is modulated. The modulation is referred to as intensity-shift keying. A testbed prototype is implemented to demonstrate the proof-of-concept, which is also used to show the bit-error-rate performance of the proposed scheme.
949-P: Dulaglutide Improves Kidney Fibrosis Biomarker Levels in Patients with Type 2 Diabetes and Moderate-to-Severe Chronic Kidney Disease (2020)

The AWARD-7 clinical trial demonstrated that once-weekly dulaglutide slowed the decline in estimated glomerular filtration rate (eGFR) and decreased urine albumin/creatinine ratio compared to insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD). Lower levels of urinary C3M, a marker for type III collagen degradation, and increased level of plasma PRO-C6, a marker for type VI collagen formation, have been reported to correlate with CKD progression and lower eGFR. This exploratory analysis evaluated changes in urinary C3M and plasma PRO-C6 in response to treatment with dulaglutide 1.5 mg compared to insulin glargine in AWARD-7. At baseline, urinary C3M and serum PRO-C6 levels were comparable between the dulaglutide 1.5 mg and insulin glargine groups. At week 26 and 52 of treatment, urinary C3M levels were significantly higher and serum PRO-C6 levels were significantly lower in the dulaglutide 1.5 mg group compared with insulin glargine group, respectively (Table). In conclusion, dulaglutide was associated with decreased levels of biomarkers for type VI collagen formation and increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. These anti-fibrotic effects could be a potential mechanism for the beneficial effects observed with dulaglutide treatment on CKD in type 2 diabetes. Disclosure K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc. J.M. Wilson: Employee; Self; Lilly Diabetes. Y. Lin: None. H. Qian: Employee; Self; Eli Lilly and Company. K. Kelly-Boruff: Employee; Self; Eli Lilly and Company. F. Genovese: None. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. K.L. Duffin: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Pfizer Inc. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Funding Eli Lilly and Company
Low Levels of Natural Anti-α-N-Acetylgalactosamine (Tn) Antibodies Are Associated With COVID-19 (2021)

Human serum contains large amounts of anti-carbohydrate antibodies, some of which may recognize epitopes on viral glycans. Here, we tested the hypothesis that such antibodies may confer protection against COVID-19 so that patients would be preferentially found among people with low amounts of specific anti-carbohydrate antibodies since individual repertoires vary considerably. After selecting glycan epitopes commonly represented in the human anti-carbohydrate antibody repertoire that may also be expressed on viral glycans, plasma levels of the corresponding antibodies were determined by ELISA in 88 SARS-CoV-2 infected individuals, including 13 asymptomatic, and in 82 non-infected controls. We observed that anti-Tn antibodies levels were significantly lower in patients as compared to non-infected individuals. This was not observed for any of the other tested carbohydrate epitopes, including anti-αGal antibodies used as a negative control since the epitope cannot be synthesized by humans. Owing to structural homologies with blood groups A and B antigens, we also observed that anti-Tn and anti-αGal antibodies levels were lower in blood group A and B, respectively. Analyses of correlations between anti-Tn and the other anti-carbohydrates tested revealed divergent patterns of correlations between patients and controls, suggesting qualitative differences in addition to the quantitative difference. Furthermore, anti-Tn levels correlated with anti-S protein levels in the patients' group, suggesting that anti-Tn might contribute to the development of the specific antiviral response. Overall, this first analysis allows to hypothesize that natural anti-Tn antibodies might be protective against COVID-19.
Rapid Evaluation of Integral Quality and Safety of Surface and Waste Waters by a Multisensor System (Electronic Tongue) (2019)

The paper describes a wide-range practical application of the potentiometric multisensor system (MS) (1) for integral safety evaluation of a variety of natural waters at multiple locations, under various climatic conditions and anthropogenic stress and (2) for close to real consistency evaluation of waste water purification processes at urban water treatment plants. In total, 25 natural surface water samples were collected around St. Petersburg (Russia), analyzed as is, and after ultrasonic treatment. Toxicity of the samples was evaluated using bioassay and MS. Relative errors of toxicity assessment with MS in these samples were below 20%. The system was also applied for fast determination of integral water quality using chemical oxygen demand (COD) values in 20 samples of water from river and ponds in Kolkata (India) and performed with an acceptable precision of 20% to 22% in this task. Furthermore, the MS was applied for fast simultaneous evaluation of COD, biochemical oxygen demand, inorganic phosphorous, ammonia, and nitrate nitrogen at two waste water treatment plants (over 320 samples). Reasonable precision (within 25%) of such analysis is acceptable for rapid water safety evaluation and enables fast control of the purification process. MS proved to be a practicable analytical instrument for various real-world tasks related to water safety monitoring.
Brief Report: Immune Response in Mice with Plasma-Cell Tumor (X5563) Assayed by Agar Plaque Technique (1968)

Abstract The immune response to sheep erythrocytes in mice with the gamma-type plasma-cell tumor (X5563) was measured on a cellular level by agar plaque technique of Jerne et al. It was demonstrated that there was a reduction in the number of plaque-forming cells involved in the primary response but not in the secondary response in the mice which were immunized shortly before the inoculation of the tumor. These findings indicate that the lowered antibody response in mice with the tumor is due to a diminished number of antibody-forming cells.
Deficiency in the Wiskott-Aldrich protein induces premature proplatelet formation and platelet production in the bone marrow compartment (2006)

The pathophysiology of microthrombocytopenia in the Wiskott-Aldrich syndrome (WAS) and its milder form, X-linked thrombocytopenia (XLT), is unclear. Although quantitative defects are correctable by splenectomy, residual platelet abnormalities are suggestive of intrinsic disturbances of production. In contrast to human patients, murine models of WASp deficiency exhibit only mild thrombocytopenia, and platelets are of normal size. Here, we have identified a critical role for WASp during murine platelet biogenesis. By electron microscopy, WASp-deficient MKs appeared to have shed platelets ectopically within the bone marrow space. WASp-deficient megakaryocytes (MKs) also displayed defects in response to fibrillar collagen I (CI) in vitro, the major matrix component of bone. These included a loss of normal CI receptor (alpha2beta1 integrin)-mediated inhibition of proplatelet formation, a marked abrogation of SDF-1-induced chemotactic migration of CD41+ MKs adherent to CI, and an almost complete lack of actin-rich podosomes, normally induced by interaction between CI and its receptors GPVI or alpha2beta1 integrin. These findings highlight the central and highly specialized role of WASp in MKs during platelet biogenesis, and may provide a mechanism for the mild thrombocytopenia observed in WASp-deficient mice. In addition, they suggest a novel explanation for some of the platelet abnormalities characteristic of patients with WAS.