gebhart/patrepeval huggingface dataset:
Semen parameters in a fertile versus subfertile population: a need for change in the interpretation of semen testing (1997)

This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non-bacterial cultures turned out to be of little prognostic value.
IRAK-4 Inhibitors for Inflammation (2009)

Interleukin-1 receptor-associated kinases (IRAKs) are key components in the signal transduction pathways utilized by interleukin-1 receptor (IL-1R), interleukin-18 receptor (IL-18R), and Toll-like receptors (TLRs). Out of four members in the mammalian IRAK family, IRAK-4 is considered to be the "master IRAK", the only family member indispensable for IL-1R/TLR signaling. In humans, mutations resulting in IRAK-4 deficiency have been linked to susceptibility to bacterial infections, especially recurrent pyogenic bacterial infections. Furthermore, knock-in experiments by several groups have clearly demonstrated that IRAK-4 requires its kinase activity for its function. Given the critical role of IRAK-4 in inflammatory processes, modulation of IRAK-4 kinase activity presents an attractive therapeutic approach for the treatment of immune and inflammatory diseases. The recent success in the determination of the 3-dimensional structure of the IRAK-4 kinase domain in complex with inhibitors has facilitated the understanding of the mechanistic role of IRAK-4 in immunity and inflammation as well as the development of specific IRAK-4 kinase inhibitors. In this article, we review the biological function of IRAK-4, the structural characteristics of the kinase domain, and the development of small molecule inhibitors targeting the kinase activity. We also review the key pharmacophores required for several classes of inhibitors as well as important features for optimal protein/inhibitor interactions. Lastly, we summarize how these insights can be translated into strategies to develop potent IRAK-4 inhibitors with desired properties as new anti-inflammatory therapeutic agents.
Fast Failure Isolation of Thermal Defects, Generally Shorts (2013)

Abstract The shrinking geometries in today’s 3-D integrated circuit (IC) designs generate an urgent need for a variety of tools to isolate failures on advanced semiconductor devices. There has been no single technique that adequately addresses all types of failures with the required fast cycle time. Complex failures that are not resolved by the faster global approaches are best addressed by probing technologies, where waveforms or voltages are measured from node to node. These approaches are time-consuming and usually require detailed understanding of the circuit operation. Global techniques that map the secondary effects of defects have been widely used for as many failures as possible. These secondary effects include thermal emission, photon emission, and circuit operation dependencies on localized heating or carrier generation at a defect site. Each technique addresses some segment of the failure mechanisms, but none is universally effective in itself. The use of thermal emission techniques has waned due to the issues of lower power supply voltages, which result in poor sensitivity for older techniques and decrease in minimum resolved feature sizes.
An Evaluation of Six Disposable Heat and Moisture Exchangers (1987)

Six disposable heat and moisture exchangers were tested on patients undergoing anaesthesia requiring mechanical ventilation. Inspiratory humidity and temperature were monitored to find the steady-state values reached with each device together with the times taken for these to be achieved. The exchangers were tested in a non-rebreathing T-piece circuit and in a conventional circle system with a fresh gas flow of 6 l/min: the Siemens 150 provided 28 and 32 mg of water/litre of inspired gas (at about 30 degrees C) in 10 and 5 min respectively, but is rather heavy and bulky. The Portex Humidvent provided 25 and 30 mg/l, and although taking longer to reach steady state (27 and 15 min respectively) is small, light and cheap. The Siemens 151 provided 25 and 27 mg/l in 18 and 10 min respectively, but is heavier than the Portex exchanger. The performances of these three devices were not significantly different from each other in either study (P less than 0.05). For the T-piece system the Pall and Engstrom exchangers were the next most efficient. The Pall device provided 18 and 23 mg/l (in 18 and 8 min respectively) and the Engstrom provided 20 and 23 mg/l (in 19 and 10 min respectively). In the circle system, there were no significant differences between the performances of the Portex, Siemens 151, Pall and Engstrom exchangers. The Pall is also a very effective bacterial filter and has been found to be satisfactory in the intensive care setting. The Terumo appeared to perform no better than a circle system with catheter mount (13 mg/l at 27 degrees C). It would seem that more complex humidification equipment is not necessary during anaesthesia if an efficient heat and moisture exchanger is used.
A Time-Triggered Network-on-Chip (2007)

In this paper we propose a time-triggered network-on-chip (NoC) for on-chip real-time systems. The NoC provides time predictable on-and off-chip communication, a mandatory feature for dependable real-time systems. A regular structured NoC with a pseudo-static communication schedule allows for a high bandwidth. In this paper we argue for a simple, time-triggered NoC structure to achieve maximum bandwidth. We have implemented the proposed TT-NoC in a low-cost FPGA. The base bandwidth is 29 Gbit/s and the peak bandwidth 230 Gbit/s for eight nodes. The idea is in line with current on-chip multiprocessor designs, such as the Cell processor. The simple design of the network and the network interface easies certification of the proposed NoC for safety critical applications.
High-Resolution Magnetic Resonance Imaging of Articular Cartilage (1998)

Summary Current explanations of the link between magnetic resonance (MR) images and cartilage histology are reviewed. The influence of the three-dimensional cartilage matrix structure on T2 decay is emphasi/ed and illustrated through the use of MR microimaging. T2 mapping, and correlative scanning electron microscopy (SEM). Special emphasis is given to the topics of T2 heterogeniety and orientation anisotropy. Common degenerative changes in the structure and biochemistry of cartilage are discussed and illustrated with examples of MR microimaging and T2 quantification with correlative SEM and light microscopy.
Role of Neutrophils in Myocardial Ischemia and Reperfusion (1995)

In the intact organism, ischemic myocardial injury initiates an acute inflammatory response in which polymorphonuclear leukocytes (PMNs) are major participants. Evidence indicates that the interplaying inflammatory reactions are augmented by reperfusion and that accumulating PMNs can contribute to myocardial damage, eg, by release of oxygen-derived free radicals, proteases, and leukotrienes. In experimental models, interventions aimed at PMN inhibition can exert cardioprotective effects, and some of these strategies raise hope for future clinical applications. A greater understanding of the mechanisms involved in PMN-mediated myocardial damage is necessary for designing a rational approach to reduce the putative detrimental effects of PMNs without antagonizing their favorable consequences in tissue healing.
Effect on Body Weight and Safety of RC-1291, a Novel, Orally Available Ghrelin Mimetic and Growth Hormone Secretagogue: Results of a Phase I, Randomized, Placebo-Controlled, Multiple-Dose Study in Healthy Volunteers (2007)

Results indicate that RC-1291 produces dose-related increases in body weight with no dose-limiting adverse effects, and may be an effective treatment for anorexia/cachexia.
Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice (2002)

Glucose homeostasis was examined in male transgenic (Tg) mice that overexpressed the human insulin-like growth factor (IGF)-binding protein (IGFBP)-3 cDNA, driven by either the cytomegalovirus (CMV) or the phosphoglycerate kinase (PGK) promoter. The Tg mice of both lineages demonstrated increased serum levels of human (h) IGFBP-3 and total IGF-I compared with wild-type (Wt) mice. Fasting blood glucose levels were significantly elevated in 8-wk-old CMV-binding protein (CMVBP)-3- and PGK binding protein (PGKBP)-3-Tg mice compared with Wt mice: 6.35 +/- 0.22 and 5.22 +/- 0.39 vs. 3.99 +/- 0.26 mmol/l, respectively. Plasma insulin was significantly elevated only in CMVBP-3-Tg mice. The responses to a glucose challenge were significantly increased in both Tg strains: area under the glucose curve = 1,824 +/- 65 and 1,910 +/- 115 vs. 1,590 +/- 67 mmol. l(-1). min for CMVBP-3, PGKBP-3, and Wt mice, respectively. The hypoglycemic effects of insulin and IGF-I were significantly attenuated in Tg mice compared with Wt mice. There were no differences in adipose tissue resistin, retinoid X receptor-alpha, or peroxisome proliferator-activated receptor-gamma mRNA levels between Tg and Wt mice. Uptake of 2-deoxyglucose was reduced in muscle and adipose tissue from Tg mice compared with Wt mice. These data demonstrate that overexpression of hIGFBP-3 results in fasting hyperglycemia, impaired glucose tolerance, and insulin resistance.
Automatic verification of requirements implementation (1994)

Requirements of event-based systems can be automatically analyzed to determine if certain safety properties hold. However, we lack comparable methods to verify that implementations maintain the properties guaranteed by the requirements. We have built a tool that compares implementations written in C with their requirements. Requirements describe events which cause state transitions. Implementations are annotated to describe changes in the values of their requirement's variables, and dataflow analysis techniques are used to determine the set of events which cause particular state changes. To show that an implementation is consistent with its requirements, we show that each event causing a change of state in the implementation appears in the requirements, and that all the events specified to cause state changes in the requirements appear in the implementation. The annotation language encourages programmers to describe local program behaviors. These behaviors are collected into system-level behaviors, which are compared to those in the requirements. Since our analysis is not based on program code, annotations can describe behaviors at any level of granularity. We illustrate the use of our tool with several different annotations of a temperature-control system.
Myositis ossificans traumatica. (1992)

Myositis ossificans is a benign condition of heterotopic bone formation. It is a generalized term for four separate clinical entities. Although not a rare disease process, diagnosis often remains difficult. This article reviews the various forms of myositis ossificans, as well as the pathology, diagnostic tests, and treatment options.
Nutrition Modulation of Cachexia/Proteolysis (2006)

Cachexia represents progressive wasting of muscle and adipose tissue and is associated with increased morbidity and mortality. Although anorexia usually accompanies cachexia, cachexia rarely responds to increased food intake alone. Our knowledge of the underlying mechanisms responsible for cachexia remains incomplete. However, most states of cachexia are associated with underlying inflammatory processes and/or cancer. These processes activate protein degradation and lipolytic pathways, resulting in tissue loss. In this article, we briefly review the pathophysiology of cachexia and discuss the role of specific nutrient supplements for the treatment of cachexia. The branched chain amino acid leucine, the leucine metabolite beta-hydroxy-beta-methylbutyrate, arginine, glutamine, omega-3 long chain fatty acids, conjugated linoleic acid, and polyphenols have demonstrated some efficacy in animal and/or human studies. Optimal treatment for cachexia is likely aimed at maximizing muscle and adipose synthesis while minimizing degradation.
Immune reconstitution after allogeneic transplantation and expanding options for immunomodulation: an update (2010)

Allogeneic hematopoietic stem cell transplantation (HSCT) has advanced to a common procedure for treating also older patients with malignancies and immunodeficiency disorders by redirecting the immune system. Unfortunately, cure is often hampered by relapse of the underlying disease, graft-versus-host disease, or severe opportunistic infections, which account for the majority of deaths after HSCT. Enhancing immune reconstitution is therefore an area of intensive research. An increasing variety of approaches has been explored preclinically and clinically: the application of cytokines, keratinocyte growth factor, growth hormone, cytotoxic lymphocytes, and mesenchymal stem cells or the blockade of sex hormones. New developments of allogeneic HSCT, for example, umbilical cord blood or haploidentical graft preparations leading to prolonged immunodeficiency, have further increased the need to improve immune reconstitution. Although a slow T-cell reconstitution is regarded as primarily responsible for deleterious infections with viruses and fungi, graft-versus-host disease, and relapse, the importance of innate immune cells for disease and infection control is currently being reevaluated. The groundwork has been prepared for the creation of individualized therapy partially based on genetic features of the underlying disease. We provide an update on selected issues of development in this fast evolving field; however, we do not claim completeness.
Coherent addition of AlGaAs lasers using microlenses and diffractive coupling (1988)

A near single-lobed far-field pattern was obtained from coherent operation of a nonevanescently coupled AlGaAs laser diode array. A diffractive microlens array collimated the individual beams to approximate a plane wave, and diffractive coupling from an external cavity mirror provided mutual coherence. A diffraction-limited far-field pattern was observed with 82% of the power contained in the central lobe. The method is directly applicable to two-dimensional laser arrays and can be implemented as a single thin optical element.
Clinical Islet Transplantation: A Review (1999)

For decades, the inability of insulin therapy to physiologically control glycemia in type I diabetic patients has motivated the search for insulin-delivering grafts. Islet autotransplantation is such a therapeutic approach to prevent diabetes mellitus following a major pancreatectomy, whereas allotransplantation is generally prescribed for type I diabetic patients with a functional solid organ graft, or for patients awaiting one. As of today, over 150 patients have been autotransplanted world-wide, following total or subtotal pancreatectomy, permitting an insulin-independence in nearly 40% of patients. Furthermore, more than 350 islet allotransplantations have been performed. Recent results show improved metabolic control in over 50% of cases and insulin-independence in approximately 20%. This chapter presents a literature review including preliminary human islet transplantation data from the University of Geneva.
5' CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. (2001)

Allele loss and loss of expression of fragile histidine triad (FHIT), a putative tumor suppressor gene located in chromosome region 3p14.2, are frequent in several types of cancers. Tumor-acquired methylation of promoter region CpG islands is one method for silencing tumor suppressor genes. We investigated 5' CpG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissues, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cancer cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer. FHIT methylation was detected in 37% of primary NSCLCs, 31% of primary breast cancers, and 65% of lung and 86% of breast cancer cell lines. The frequency of methylation in small cell and NSCLC cell lines were identical. Methylation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation was significantly correlated with loss of FHIT mRNA expression by Northern blot analysis in lung cancer cell lines and with loss of Fhit expression in NSCLC and breast tumors by immunostaining. We conclude that methylation of FHIT is a frequent event in NSCLC and breast cancers and is an important mechanism for loss of expression of this gene. Methylation of FHIT commences during lung cancer pathogenesis and may represent a marker for risk assessment.
Micro-Blog (2008)

Recent years have witnessed the impacts of distributed content sharing (Wikipedia, Blogger), social networks (Facebook, MySpace), sensor networks, and pervasive computing. We believe that significant more impact is latent in the convergence of these ideas on the mobile phone platform. Phones can be envisioned as people-centric sensors capable of aggregating participatory as well as sensory inputs from local surroundings. The inputs can be visualized in different dimensions, such as space and time. When plugged into the Internet, the collaborative inputs from phones may enable a high resolution view of the world. This paper presents the architecture and implementation of one such system, called Micro-Blog. New kinds of application-driven challenges are identified and addressed in the context of this system. Implemented on Nokia N95 mobile phones, Micro-Blog was distributed to volunteers for real life use. Promising feedback suggests that Micro-Blog can be a deployable tool for sharing, browsing, and querying global information.
A VHH That Neutralizes the Zinc Metalloproteinase Activity of Botulinum Neurotoxin Type A (2010)

The current treatment of botulism is to administer animal-derived antitoxin, which frequently causes severe adverse reactions in the recipients. In this study, a heavy chain antibody fragment (VH/V(H)H) phage display library was constructed by amplification of the immunoglobulin genes of a nonimmune camel, Camelus dromedarius, using primers specific to human VH gene segments. A recombinant light chain of type A botulinum toxin, BoTxA/LC, with zinc endoprotease activity was used in phage bio-panning to select phage clones displaying BoTxA/LC-bound VH/V(H)H. Soluble VH/V(H)H were produced and purified from 10 VH/V(H)H phagemid-transformed E. coli clones. Complementary determining regions (CDRs) and immunoglobulin frameworks (FRs) of the 10 camel VH/V(H)H-deduced amino acid sequences were determined. FR2 sequences of two clones showed a hallmark of camel V(H)H, i.e. (F/Y)(42)E(49)R(50)(G/F)(52). The remaining eight clones had an FR2 amino acid tetrad of conventional VH, i.e. V(42)G(49)L(50)W(52). V(H)H of one clone (V(H)H17) neutralized the SNAP25 hydrolytic activity of BoTxA/LC, whereas mouse polyclonal anti-BoTxA/LC did not have such activity. Mimotope sequences of V(H)H17 matched with the 194-206 amino acid residues of BoTxA/LC, which are located near the S'1 subsite of the catalytic cleft of the enzyme. Molecular docking revealed that CDR3 of the V(H)H17 bound to epitope in the toxin enzymatic cleft. Therefore, the BoTxA/LC neutralization by the V(H)H17 should be due to the V(H)H insertion into the enzymatic cleft of the toxin, which is usually inaccessible to a conventional antibody molecule. This antibody fragment warrants further development as a therapeutic agent for botulism.
Tolerosome‐induced oral tolerance is MHC dependent (2005)

Oral administration of a protein antigen generates a serum factor that induces tolerance when transferred into naïve recipients. This serum factor has been described in rats as consisting of exosome-like structures or tolerosomes, which express major histocompatibility complex class II molecules (MHCII) and mediate antigen-specific tolerance. In this study, we investigated the functions of serum-derived tolerosomes both in vivo and in vitro. Tolerosomes were purified from the 100,000 g pellet fraction of serum from ovalbumin (OVA)-fed mice. When transferred into naïve recipient mice, the tolerosomes mediated OVA-specific tolerance. We also found that tolerosomes from OVA-fed mice induced the activation of OVA-specific T cells both in vivo and in vitro. The inoculation of severe combined immunodeficiency (SCID) mice with an interferon-gamma-producing cell line normalized the expression of MHCII in the intestinal epithelial cells and restored their ability to generate tolerosomes. Syngeneic but not allogeneic transfer of tolerosomes from OVA-fed donors induced tolerance in the recipients. Our results show that tolerosomes can be isolated from mouse serum, that tolerosome-induced oral tolerance requires MHCII expression in intestinal epithelial cells, and that tolerosomes are functional only in syngeneic recipients.
NAS-FPN: Learning Scalable Feature Pyramid Architecture for Object Detection (2019)

Current state-of-the-art convolutional architectures for object detection are manually designed. Here we aim to learn a better architecture of feature pyramid network for object detection. We adopt Neural Architecture Search and discover a new feature pyramid architecture in a novel scalable search space covering all cross-scale connections. The discovered architecture, named NAS-FPN, consists of a combination of top-down and bottom-up connections to fuse features across scales. NAS-FPN, combined with various backbone models in the RetinaNet framework, achieves better accuracy and latency tradeoff compared to state-of-the-art object detection models. NAS-FPN improves mobile detection accuracy by 2 AP compared to state-of-the-art SSDLite with MobileNetV2 model in [32] and achieves 48.3 AP which surpasses Mask R-CNN [10] detection accuracy with less computation time.