gebhart/patrepeval huggingface dataset:
Do common <i>in silico</i> tools predict the clinical consequences of amino‐acid substitutions in the CFTR gene? (2010)

Computational methods are used to predict the molecular consequences of amino-acid substitutions on the basis of evolutionary conservation or protein structure, but their utility in clinical diagnosis or prediction of disease outcome has not been well validated. We evaluated three popular computer programs, namely, PANTHER, SIFT and PolyPhen, by comparing the predicted clinical outcomes for a group of known CFTR missense mutations against the diagnosis of cystic fibrosis (CF) and clinical manifestations in cohorts of subjects with CF-disease and CFTR-related disorders carrying these mutations. Owing to poor specificity, none of tools reliably distinguished between individual mutations that confer CF disease from mutations found in subjects with a CFTR-related disorder or no disease. Prediction scores for CFTR mutations derived from PANTHER showed a significant overall statistical correlation with the spectrum of disease severity associated with mutations in the CFTR gene. In contrast, PolyPhen- and SIFT-derived scores only showed significant differences between CF-causing and non-CF variants. Current computational methods are not recommended for establishing or excluding a CF diagnosis, notably as a newborn screening strategy or in patients with equivocal test results.
Hepatocyte Growth Factor (HGF) Induces Interleukin-11 Secretion From Osteoblasts: A Possible Role for HGF in Myeloma-Associated Osteolytic Bone Disease (1999)

Multiple myeloma is associated with unbalanced bone remodeling causing lytic bone lesions. Interleukin-11 (IL-11) promotes osteoclast formation and inhibits osteoblast activity and may, thus, be one factor involved in cancer-induced bone destruction. We have previously shown that myeloma cells produce hepatocyte growth factor (HGF). We now report that HGF induces IL-11 secretion from human osteoblast-like cells and from the osteosarcoma cell lines Saos-2 and HOS. In coculture experiments, both the myeloma cell line JJN-3 and primary myeloma cells from 3 patients induced IL-11 secretion from osteoblasts, whereas no induction was observed with the non-HGF producing myeloma cell line OH-2. Enhanced IL-11 induction was observed with physical contact between osteoblasts and myeloma cells as compared with experiments in which contact was prohibited by tissue inserts. Anti-HGF serum strongly reduced the myeloma cell-induced IL-11 secretion. Furthermore, we show that JJN-3 cells express HGF on the cell-surface. Removal of surface-bound HGF on JJN-3 cells reduced IL-11 production induced in cocultures. Transforming growth factor β1 and IL-1 potentiated the effect of HGF on IL-11 secretion, whereas an additive effect was observed with tumor necrosis factor. Thus, myeloma-derived HGF can influence the bone marrow environment both as a soluble and a surface-bound factor. Furthermore, HGF emerges as a possible factor involved in myeloma bone disease by its ability to induce IL-11.
Uniform Scale-Independent Gene Transfer to Striated Muscle After Transvenular Extravasation of Vector (2005)

Uniform scale- and vector-independent skeletal and cardiac myofiber transduction is facilitated by pressurized venous infusion in anatomic domains isolated from the central circulation without pharmacological interference with cardiovascular homeostasis. We provide the first demonstration of uniform gene transfer to muscle fibers of an entire extremity in the dog, providing a firm foundation for further translational studies of efficacy in canine models for human diseases.
Spectral Dynamics of Spatially Incoherent Modulation Instability (2012)

To date, all experiments in nonlinear statistical optics have relied on beams whose transverse spatial statistics were Gaussian. Here, we present a new technique to generalize these studies by using a spatial light modulator to create spatially incoherent beams with arbitrary spectral distributions. As a specific example of the new dynamics possible, we consider the spatial modulation instability of a partially coherent beam. We show that, for statistical beams of uniform intensity and equal correlation length, the underlying spectral shape determines the threshold and visibility of intensity modulations as well as the spectral profile of the growing sidebands. We demonstrate the behavior using statistical light, but the results will hold for any wave-kinetic system, such as plasma, ultracold gases, and turbulent acoustic waves.
A Review of Hydrogen Direct Injection for Internal Combustion Engines: Towards Carbon-Free Combustion (2019)

A paradigm shift towards the utilization of carbon-neutral and low emission fuels is necessary in the internal combustion engine industry to fulfil the carbon emission goals and future legislation requirements in many countries. Hydrogen as an energy carrier and main fuel is a promising option due to its carbon-free content, wide flammability limits and fast flame speeds. For spark-ignited internal combustion engines, utilizing hydrogen direct injection has been proven to achieve high engine power output and efficiency with low emissions. This review provides an overview of the current development and understanding of hydrogen use in internal combustion engines that are usually spark ignited, under various engine operation modes and strategies. This paper then proceeds to outline the gaps in current knowledge, along with better potential strategies and technologies that could be adopted for hydrogen direct injection in the context of compression-ignition engine applications—topics that have not yet been extensively explored to date with hydrogen but have shown advantages with compressed natural gas.
A linear algorithm for generating random numbers with a given distribution (1991)

Let xi be a random variable over a finite set with an arbitrary probability distribution. Improvements to a fast method of generating sample values for xi in constant time are suggested. The proposed modification reduces the time required for initialization to O(n). For a simple genetic algorithm, this improvement changes an O(g n 1n n) algorithm into an O(g n) algorithm (where g is the number of generations, and n is the population size).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Named Entity Recognition with stack residual LSTM and trainable bias\n decoding (2017)

Recurrent Neural Network models are the state-of-the-art for Named Entity\nRecognition (NER). We present two innovations to improve the performance of\nthese models. The first innovation is the introduction of residual connections\nbetween the Stacked Recurrent Neural Network model to address the degradation\nproblem of deep neural networks. The second innovation is a bias decoding\nmechanism that allows the trained system to adapt to non-differentiable and\nexternally computed objectives, such as the entity-based F-measure. Our work\nimproves the state-of-the-art results for both Spanish and English languages on\nthe standard train/development/test split of the CoNLL 2003 Shared Task NER\ndataset.\n
Measurement of lipase activity by a differential pH technique. (1985)

This is a new electrochemical method for determination of lipase activity in biological fluids, including serum, plasma, and duodenal juice. Advantages of turbidimetric methods--short reaction time, and small sample and reagent volumes--are combined with those of titrimetric methods: measurement of absolute activity (i.e., no standardization required), saturated substrate conditions, and direct measurement of reaction products. The proposed method is easy, inexpensive, and takes only 3 min. Precision is good: CV = 3.74% within day and 7.3% between days at the clinical-decision concentration, CV = 1.86% within day and 4.65% between days for above-normal lipase activities. The standard curve is linear up to 4500 U/L. Results (y) correlate well with those by turbidimetry (x): y = 0.9287x - 65.3 (r = 0.9719). Reference values are between 0 and 130 U/L.
Tolerogenic dendritic cells impede priming of naïve <scp>CD</scp>8<sup>+</sup><scp>T</scp> cells and deplete memory <scp>CD</scp>8<sup>+</sup><scp>T</scp> cells (2012)

Type 1 diabetes is a T-cell-mediated autoimmune disease in which autoreactive CD8(+) T cells destroy the insulin-producing pancreatic beta cells. Vitamin D3 and dexamethasone-modulated dendritic cells (Combi-DCs) loaded with islet antigens inducing islet-specific regulatory CD4(+) T cells may offer a tissue-specific intervention therapy. The effect of Combi-DCs on CD8(+) T cells, however, remains unknown. To investigate the interaction of CD8(+) T cells with Combi-DCs presenting epitopes on HLA class I, naive, and memory CD8(+) T cells were co-cultured with DCs and proliferation and function of peptide-specific T cells were analyzed. Antigen-loaded Combi-DCs were unable to prime naïve CD8(+) T cells to proliferate, although a proportion of T cells converted to a memory phenotype. Moreover, expansion of CD8(+) T cells that had been primed by mature monocyte-derived DCs (moDCs) was curtailed by Combi-DCs in co-cultures. Combi-DCs expanded memory T cells once, but CD8(+) T-cell numbers collapsed by subsequent re-stimulation with Combi-DCs. Our data point that (re)activation of CD8(+) T cells by antigen-pulsed Combi-DCs does not promote, but rather deteriorates, CD8(+) T-cell immunity. Yet, Combi-DCs pulsed with CD8(+) T-cell epitopes also act as targets of cytotoxicity, which is undesirable for survival of Combi-DCs infused into patients in therapeutic immune intervention strategies.
Subacute Hemodynamic Effects of Nebivolol in Man at Rest and During Exercise (1987)

In a subacute experiment 7 apparently healthy volunteers received a daily oral dose of 5 mg nebivolol for seven days, followed by a seven-day washout period with placebo. From the first day during treatment with nebivolol, peak exercise heart rate and systolic blood pressure, as measured during a standardized submaximal treadmill exercise, significantly decreased by 15% and 19% respectively. A prolonged treatment for one week did not further increase the response of exercise heart rate and systolic blood pressure to nebivolol. However, the ratio of preejection period (PEPc) to left ventricular ejection time (LVETc), an indirect and valuable measure of left ventricular performance, progressively and significantly decreased during the seven-day treatment period with nebivolol from a mean value of 0.37 +/- 0.012 to 0.31 +/- 0.009. The improvement of systolic time intervals resulted from a shortening of the PEPc and a lengthening of the LVETc. At rest, heart rate did not change significantly with nebivolol, whereas both systolic and diastolic blood pressure gradually and significantly lowered. The postexercise LVETc significantly shortened during treatment with nebivolol, and this shortening was more pronounced after seven days of treatment. After discontinuation of treatment with nebivolol, all these effects persisted for more than thirty hours after the last intake and gradually returned to pretreatment values thereafter. From these data it appears that nebivolol effectively reduces blood pressure at rest and during exercise in healthy volunteers, beneficially influencing preload and afterload, as measured by systolic time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Cathodes for lithium ion batteries: the benefits of using nanostructured materials (2006)

Commercially available lithium ion cells, which are the most advanced among rechargeable batteries available so far, employ microcrystalline transition metal oxides as cathodes, which function as Li insertion hosts. In search for better electrochemical performance the use of nanomaterials in place of these conventional ones has emerged as excellent alternative. In this review we present a brief introduction about the motivations to use nanostructured materials as cathodes in lithium ion batteries. To illustrate such advantages we present some examples of research directed toward preparations and electrochemical data of the most used cathodes in nanoscale, such as LiCoO2, LiMn2O4, LiMnO2, LiV2O5 e LiFePO4.
Methanisierung kohlenmonoxidreicher Gase beim Energie‐Transport (1980)

Abstract Methanization of carbon monoxide‐rich gases for energy‐transport . The partners of the NFE project (Nukleare Fernenergie, Remote nuclear energy) – Kernforschungsanlage Jülich GmbH (Germany) and Rheinische Braunkohlenwerke AG, Köln (Germany) – in collaboration with Haldor Topsøe A/S, Copenhagen (Denmark), have investigated various problems of the methanization of synthesis gases rich in carbon monoxide. Preliminary results obtained from trial operations with the pilot‐scale methanization plant ADAM I at KFR Jülich and from the catalyst‐development project at Haldor Topsøe A/S are reported. A detailed account is given of the catalyst investigations carried out on the Haldor Topsøe pilot plant for the further development of the TREMP process for SNG manufacture and of the complementary catalyst investigation in the NFE project at the Union Rheinische Braunkohlen Kraftstoff AG and the Kernforschungsanlage Jülich GmbH for the optimization of the methanization process in the remote energy system EVA‐ADAM. In the pilot plant ADAM I, a three‐stage methanization process with product gas recycling and maximum temperature of 600 °C utilizing synthesis gas from methane vapour reforming (EVA) has been demonstrated for the first time. In further experiments to be carried out with ADAM I the influence of operating irregularities on the behaviour of the methanization plant and the dynamics of the remote energy system will be investigated, data for the preparation of mathematical models collected, new components tested, and the process of methanization optimized.
Fracture compliance estimation using borehole tube waves (2013)

ABSTRACT We tested two models, one for tube-wave generation and the other for tube-wave attenuation at a fracture intersecting a borehole that can be used to estimate fracture compliance, fracture aperture, and lateral extent. In the tube-wave generation model, we consider tube-wave excitation in the borehole when a P-wave is incident on the fracture. The amplitude ratio of the pressure due to the tube wave to that of the incident P-wave is a function of fracture compliance, aperture, and length. Similarly, the attenuation of a tube wave in the borehole as it crosses a fracture intersecting the borehole is also a function of fracture properties. Numerically solving the dispersion relation in the fracture, we study tube-wave generation and the attenuation coefficient as a function of frequency. We observed that measuring amplitude ratios or attenuation near a transition frequency can help constrain the fracture properties. The transition frequency corresponds to the regime in which the viscous skin depth in the fracture is comparable to its aperture. Measurements in the high-frequency limit can place a lower bound on fracture compliance and lateral extent. We evaluated the applicability of the tube-wave generation model to a previously published VSP data set and found that compliance values of the order 10−10–10−9 m/Pa are likely in the field. These observations support scaling of fracture compliance with fracture size.
Mixed‐linkage (1→3),(1→4)‐β <scp>‐d‐</scp> glucan is not unique to the Poales and is an abundant component of <i>Equisetum arvense</i> cell walls (2008)

Mixed-linkage (1-->3),(1-->4)-beta-D-glucan (MLG) is widely considered to be a defining feature of the cell walls of plants in the Poales order. However, we conducted an extensive survey of cell-wall composition in diverse land plants and discovered that MLG is also abundant in the walls of the horsetail Equisetum arvense. MALDI-TOF MS and monosaccharide linkage analysis revealed that MLG in E. arvense is an unbranched homopolymer that consists of short blocks of contiguous 1,4-beta-linked glucose residues joined by 1,3-beta linkages. However, in contrast to Poaceae species, MLG in E. arvense consists mostly of cellotetraose rather than cellotetriose, and lacks long 1,4-beta-linked glucan blocks. Monosaccharide linkage analyses and immunochemical profiling indicated that, in E. arvense, MLG is a component of cell walls that have a novel architecture that differs significantly from that of the generally recognized type I and II cell walls. Unlike in type II walls, MLG in E. arvense does not appear to be co-extensive with glucuroarabinoxylans but occurs in walls that are rich in pectin. Immunofluorescence and immunogold localization showed that MLG occurs in both young and old regions of E. arvense stems, and is present in most cell types apart from cells in the vascular tissues. These findings have important implications for our understanding of cell-wall evolution, and also demonstrate that plant cell walls can be constructed in a way not previously envisaged.
The Global Burden of Cancer (2017)

The worldwide burden of cancer is expected to double in the next 20 years, largely due to the aging and growth of the population. Other contributing factors include the adoption of unhealthy behaviors such as smoking and high-calorie food in economically developing countries and the obesity epidemic in all countries. Incidence rates for female breast, prostate, and colorectal cancers are increasing in most parts of the world. Breast cancer in women and prostate cancer in men are the most commonly diagnosed cancers in most countries, including several economically developing countries, overtaking infection-related cancers.
Implantable medical devices as agents and part of multiagent systems (2006)

The consideration of medical implants as an increasingly important population of isolated agents is a valuable perspective that should not be ignored by the agent community. Implanted Medical Device (IMD) applications are complex, naturally distributed, and could benefit from such attention. This paper explores implantable medical devices and their attributes in an agent context and terminology. It submits that an increasing body of IMDs should be considered agents and that there are opportunities for incorporating these implantable agents into multiagent systems (MAS). This will include: (i) Discussion of several IMDs in traditional agent terms. (ii) Discussion of trends and issues in IMDs related to their potential role in MAS. (iii) Experimental exploration of some potential MAS applications in the problem of medical monitoring. (iv) Broader discussion of the value of framing IMDs and applications involving them in the agent paradigm.
Enhancing biological therapy through conditional regulation of protein stability (2010)

The ability to externally regulate the expression or function of a gene product has proven to be a powerful tool in the study of proteins and disease in vitro, and more recently in transgenic animal models. The transfer of these technologies to regulate a therapeutic, adoptively transferred gene product in a clinical setting may provide a means to exert additional control over a large variety of therapies for many diseases, leading to increased safety and effectiveness. This could be applied to any biological therapy, including gene therapy, viral therapies, cellular therapies (such as immune cell therapies, stem cell therapies and bone marrow transplant), some vaccines and even organ transplant. A variety of systems have been used in a basic research setting to conditionally regulate the function of a protein, including control of transcription and mRNA stability, and the use of protein inhibitors. However, most of these have disadvantages for medical use, where a simple, specific, tunable, reversible and broadly applicable means to regulate protein function is needed. Recent advances in controlling the stability or function of proteins through the interaction of small-molecule effectors and fusion domains on the protein have raised the possibility that direct and highly specific external control of therapeutic protein function in humans will be feasible.
Asymmetric hexagonal QAM based OFDM system (2003)

OFDM (orthogonal frequency division multiplexing) has been widely used in wire and wireless communications, because of its efficient use of the frequency spectrum and good multi-path tolerance. However, the OFDM system is very sensitive to frequency offset and phase noise. In order to overcome this disadvantage, asymmetric hexagonal QAM is presented in this paper as a new modulation method to solve this problem. Without weakening the resistance to noise, an asymmetric hexagonal QAM based OFDM system is easy to get the sub-carrier frequency and it is more convenient for its synchronization. In this paper, the asymmetric hexagonal QAM based OFDM system is designed and simulated by SystemView. Then the simulation results are presented and analyzed; the properties of asymmetric hexagonal QAM and rectangular QAM are compared.
Diabetic corneal neuropathy: clinical perspectives (2018)

Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy.
Deciphering the RAS/ERK pathway <i>in vivo</i> (2017)

The RAS/ERK pathway has been intensely studied for about three decades, not least because of its role in human pathologies. ERK activation is observed in the majority of human cancers; in about one-third of them, it is driven by mutational activation of pathway components. The pathway is arguably one of the best targets for molecule-based pharmacological intervention, and several small-molecule inhibitors are in clinical use. Genetically engineered mouse models have greatly contributed to our understanding of signaling pathways in development, tissue homeostasis, and disease. In the specific case of the RAS/ERK pathway, they have revealed unique biological roles of structurally and functionally similar proteins, new kinase-independent effectors, and unsuspected relationships with other cascades. This short review summarizes the contribution of mouse models to our current understanding of the pathway.