gebhart/patrepeval huggingface dataset:
Blood coagulation dynamics in haemostasis (2009)

Summary Our studies involve computational simulations, a reconstructed plasma/platelet proteome, whole blood in vitro and blood exuding from microvascular wounds. All studies indicate that in normal haemostasis, the binding of tissue factor (TF) with plasma factor (F) VIIa (extrinsic FXase complex) results in the initiation phase of the procoagulant response. This phase is negatively regulated by tissue factor pathway inhibitor (TFPI) in combination with antithrombin (AT) and the protein C (PC) pathway. The synergy between these inhibitors provides a threshold-limited reaction in which a stimulus of sufficient magnitude must be provided for continuation of the reaction. With sufficient stimulus, the FXa produced activates some prothrombin. This initial thrombin activates the procofactors and platelets required for presentation of the intrinsic FXase (FVIIIa- FIXa) and prothrombinase (FVa-FXa) complexes which drive the subsequent propagation phase; continuous downregulation of which is provided by AT and the thrombinthrombomodulin- PC complex. FXa generation during the propagation phase is largely (>90%) provided by the intrinsic FXase complex. TF is required for the initiation phase of the reaction but becomes non-essential once the propagation phase has been achieved. The propagation phase catalysts (FVIIIa-FIXa and FVa-FXa) continue to drive the reaction as blood is resupplied to the wound site by flow. Ultimately, the control of the reaction is governed by the pro- and anticoagulant dynamics and the supply of blood reactants to the site of a perforating injury. Our systems have been utilized to examine the qualities of hypothetical and novel antihaemorrhagic and anticoagulation agents and in epidemiologic studies of venous and arterial thrombosis and haemorrhagic pathology.
Operation of harmonic side-drive micromotors studied through gear ratio measurements (2002)

The detailed operation of variable capacitance harmonic (or wobble) side-drive micromotors was studied through gear ratio measurements. The gear ratio of the wobble micromotor is affected by wear in the bearing and by rotor slip. Rotor slip is a function of motive torque magnitude, excitation angle, and friction torques. The gear ratio of a wobble micromotor can be expressed as a constant term plus a term that accounts for rotor slip. The constant term is the nominal gear ratio which is equal to the bearing radius divided by the bearing clearance. The rotor slip term is directly proportional to the bushing friction torque and inversely proportional to the square of the excitation voltage. Micromotor operation in air as opposed to nitrogen demonstrates a significantly larger bushing friction torque.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A Pattern-recognition Protein for β-1,3-Glucan (2000)

The beta-1,3-glucan recognition protein (betaGRP) has strong specific affinity for beta-1,3-glucan, a component of the fungal cell wall. Its interaction with beta-1,3-glucan initiates the activation of the prophenoloxidase cascade, which is an important defense system in invertebrates of many species. We cloned the cDNA of the betaGRP of the silkworm Bombyx mori. The betaGRP mRNA transcript was constitutively expressed in the hemocytes, fat body, and epithelial cells of the naive silkworm. At the same time, a bacterial or yeast challenge was indicated to intensify the transcription. Comparison of the deduced amino acid sequence with known sequences revealed that the betaGRP contained a region (Thr(264) to Pro(386)) displaying significant similarity to the catalytic regions of bacterial beta-1,3-glucanases and much higher similarity to the glucanase-like regions of Gram-negative bacteria-binding proteins found in the silkworm B. mori and the mosquito Anopheles gambiae. The region (Thr(264) to Pro(386)) of the betaGRP, however, was demonstrated not to have appreciable affinity for beta-1,3-glucan. A recombinant peptide corresponding to an N-terminal region (Tyr(1) to Ala(102)) of the betaGRP bound strongly to beta-1,3-glucan. These results indicate that the binding domain of the betaGRP for beta-1,3-glucan is located in the N-terminal region. Glucanases and the current pattern-recognition proteins that contain a glucanase-like region seem to have a common origin in their molecular evolution.
Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson’s disease models (2009)

alpha-Synuclein (alpha-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because alpha-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson's disease (PD). We previously created a yeast model of alpha-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to alpha-syn expression. We also uncovered a core group of proteins with diverse activities related to alpha-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of alpha-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress alpha-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of alpha-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced alpha-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of alpha-syn foci, re-established ER-to-Golgi trafficking and ameliorated alpha-syn-mediated damage to mitochondria. They also corrected the toxicity of alpha-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of alpha-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD.
Importance of Matching Physical Friction, Hardness, and Texture in Creating Realistic Haptic Virtual Surfaces (2016)

Interacting with physical objects through a tool elicits tactile and kinesthetic sensations that comprise your haptic impression of the object. These cues, however, are largely missing from interactions with virtual objects, yielding an unrealistic user experience. This article evaluates the realism of virtual surfaces rendered using haptic models constructed from data recorded during interactions with real surfaces. The models include three components: surface friction, tapping transients, and texture vibrations. We render the virtual surfaces on a SensAble Phantom Omni haptic interface augmented with a Tactile Labs Haptuator for vibration output. We conducted a human-subject study to assess the realism of these virtual surfaces and the importance of the three model components. Following a perceptual discrepancy paradigm, subjects compared each of 15 real surfaces to a full rendering of the same surface plus versions missing each model component. The realism improvement achieved by including friction, tapping, or texture in the rendering was found to directly relate to the intensity of the surface's property in that domain (slipperiness, hardness, or roughness). A subsequent analysis of forces and vibrations measured during interactions with virtual surfaces indicated that the Omni's inherent mechanical properties corrupted the user's haptic experience, decreasing realism of the virtual surface.
Cholesterol lowering in the older population: time for reassessment? (2001)

Hypercholesterolaemia is an established major risk factor for coronary heart disease (CHD) in the general population. In the vast majority of studies that focused on this particular age group and carefully eliminated other confounding factors such as co-morbid conditions, hypercholesterolaemia was a risk factor for CHD in the older population. Because the prevalence of CHD increases with advancing age, studies that consider not only the relative risk attributed to cholesterol but also the absolute numbers of people affected, show hypercholesterolaemia to be an even stronger risk factor in the elderly. Large primary and secondary prevention studies of HMG-CoA reductase inhibitors (statins) in the elderly have shown a reduction in major coronary events similar to that observed in the younger age group. The role of hypercholesterolaemia as a risk factor for stroke is less clear, and a major limitation is the heterogeneous nature of the disease. Nevertheless, most studies that evaluated non-haemorrhagic strokes separately showed a positive association with cholesterol levels, and statin therapy is effective in preventing stroke. These data provide a rationale for treating older hypercholesterolaemic people with statins, not only to prevent CHD, but also to prevent stroke.
Bridge-Plug Millout With Coiled Tubing—Case Histories (2000)

Abstract Downhole plugs are now commonly used for isolating multistage stimulation jobs. These plugs allow for more timely completion, yet they must also be removed in a timely fashion. This paper discusses how coiled tubing (CT) can efficiently mill out these plugs. The three case histories in this paper demonstrate the successful use of coiled tubing to mill out bridge plugs set in multistage stimulation jobs. Specifically, each case history provides a brief history of the well, a description of the equipment used to meet downhole and surface needs, and the operating procedure used for the job. The paper concludes with procedures to improve CT millout efficiency.
Relationship between carbohydrate sweeteners and oral diseases. (1988)

Dental caries and periodontal disease are wide-spread oral illnesses whose etiology is intimately associated with the consumption of carbohydrate sweeteners. Since dental caries is multifactorial in nature, it is reasonable to assume that there is no single method, usable in the foreseeable future, which would lead to its eradication. Consequently, any new caries preventive measures must function coherently with those currently in use, so that the concerted action of all methods would lead to the best cariostatic effect. Strict restriction of sucrose intake without suggestion of alternatives is not realistic. This fact has given rise to attempts to replace sucrose, especially in products consumed between meals, with sweeteners that are less cariogenic. Human clinical trials and several animal experiments have shown promising clinical results obtained by replacing sucrose with certain sugar alcohols (polyols). Among the sugar alcohols, the best results so far have been obtained with xylitol, which is chemically a pentitol containing five carbon atoms. Chewing gums containing xylitol have been shown to be strong instruments against caries in caries-active age-groups and in high-risk subjects. More research is needed to assess the ability of mixtures of xylitol with sorbitol, palatinit, maltitol, other sugar alcohols, and intense sweeteners to prevent oral plaque diseases. Although thorough clinical trials on the relationship between carbohydrate sweeteners and periodontal diseases have not been performed, the available data indicate that dietary polyols may have a restricted dampening effect on periodontal and gingival inflammations.
A novel bandwidth estimation algorithm for IEEE 802.11 TCP data transmissions (2012)

Efficient bandwidth estimation is significant for Quality of Service (QoS) of multimedia services in IEEE 802.11 WLANs. Many bandwidth estimation solutions have been developed such as probing-based technique and cross-layer scheme. However, these solutions either introduce additional traffic or require modification to the standard protocols. This paper develops a model based bandwidth estimation algorithm at application layer when TCP traffic is delivered in the IEEE 802.11 networks. The proposed model firstly considers both TCP congestion control mechanism and IEEE 802.11 contention-based channel access mechanism. The bandwidth estimation process at the server estimates the achievable bandwidth using two types of parameters: data size to be sent and the feedback information from receivers, i.e. packet loss rate and the number of clients. The two tailed T-test analysis demonstrates that there is a 95% confidence level that there is no statistical difference between the results from the proposed bandwidth estimation algorithm and the results from the real test. Additionally, the proposed algorithm achieves higher accuracy and lower standard deviation of bandwidth, in comparison with other state-of-the art bandwidth estimation schemes.
United States Trends in Lumbar Fusion Surgery for Degenerative Conditions (2005)

Lumbar fusion rates rose even more rapidly in the 90s than in the 80s. The most rapid increases followed the approval of new surgical implants and were much greater than increases in other major orthopedic procedures. The most rapid increases in fusion rates were among adults aged 60 and above. These increases were not associated with reports of clarified indications or improved efficacy, suggesting a need for better data on the efficacy of various fusion techniques for various indications.
Catches of the grape leafhopper, Arboridia apicalis Nawa (Homoptera:Cicadellidae), on yellow cylindrical sticky trap. (1986)

フタテンヒメヨコバイについて,黄色粘着トラップの成虫に対する誘引性を明らかにし,透明フィルムを利用した調査の簡便法を示した。さらに,黄色粘着トラップを用いてブドウ栽培の露地とガラス室で誘殺消長をみたところ,少なくとも露地での誘殺消長は,発生消長に関するこれまでの知見と矛盾しなかった。
Thia fatty acids with the sulfur atom in even or odd positions have opposite effects on fatty acid catabolism (2006)

As tools for mechanistic studies on lipid metabolism, with the long-term goal of developing a drug for the treatment of lipid disorders, thia FA with the sulfur atom inserted at positions 3-9 from the carboxyl group were fed to male Wistar rats for 1 wk to determine their impact on key parameters in lipid metabolism and hepatic levels of thia FA metabolites. Thia FA with the sulfur atom in even positions decreased hepatic and cardiac mitochondrial beta-oxidation and profoundly increased hepatic and cardiac TAG levels. The plasma TAG level was unchanged and the hepatic acyl-CoA oxidase activity increased. In contrast, thia FA with the sulfur atom in odd positions, especially 3-thia FA, tended to increase hepatic and cardiac FA oxidation and acyl-CoA oxidase and carnitine palmitoyltransferase-II activities, and decreased the plasma TAG levels. The effects seem to be related to differences in the catabolic rate of the thia FA. Differences between the two groups of acids were also observed with respect to the regulation of genes involved in FA transport and catabolism. Feeding experiments with 3- and 4-thia FA in combination indicated that the 4-thia FA partly attenuated the effects of the 3-thia FA on mitochondrial FA oxidation and the hepatic TAG level. In summary, the position of the sulfur atom in the alkyl chain, especially whether it is placed in the even or odd position, is crucial for the biological effect of the thia FA.
When can government subsidize research joint ventures? Politics, economics, and limits to (1994)

Research joint ventures (RJV's) between private firms and government bureaus play a central position in the Clinton Administration's R&D strategy to promote productivity and of American firms. The government's role in the programs varies from subsidizing private projects to providing the expertise and facilities of the federal research laboratories. A substantial literature now exists that investigates the economic efficiency of private RJV's. The purpose of this paper is to expand the debate to consider the conditions under which the government will choose to subsidize RJV's and whether these conditions are likely to yield desirable economic results. It is useful to characterize the government as a consortium member who differs from the private venturers in several critical ways. First, these programs are based on the presumption that private firms are far better than government at choosing projects with commercial merit. Even in those programs where the government contributes scientists and facilities, industry partners usually have primary responsibility for initiating projects. Second, the objective function of the government differs from industry members. Indeed, it is in part because government actors have goals other than competitiveness that these programs are intended to keep government bureaucrats at arm's length from technical choices. Finally, the financial contribution of the government is usually a set share of the total bill. Introducing this form of subsidy changes the research investment strategies employed by a joint venture, and the incentives facing firms either to participate in a consortium or to oppose its establishment. The basic premise of this analysis is that a subsidized joint venture will persist only when all members, including the government, are satisfied. A viable policy depends on economic consequences to member firms, and to the extent that they have access to policy-making, to nonmember firms and consumers. Furthermore, some of the relevant consequences follow predictably from market and technology characteristics.
Software Framework for Topic Modelling with Large Corpora (2010)

Large corpora are ubiquitous in today’s world and memory quickly becomes the limiting factor in practical applications of the Vector Space Model (VSM). In this paper, we identify a gap in existing implementations of many of the popular algorithms, which is their scalability and ease of use. We describe a Natural Language Processing software framework which is based on the idea of document streaming, i.e. processing corpora document after document, in a memory independent fashion. Within this framework, we implement several popular algorithms for topical inference, including Latent Semantic Analysis and Latent Dirichlet Allocation, in a way that makes them completely independent of the training corpus size. Particular emphasis is placed on straightforward and intuitive framework design, so that modifications and extensions of the methods and/or their application by interested practitioners are effortless. We demonstrate the usefulness of our approach on a real-world scenario of computing document similarities within an existing digital library DML-CZ. 1.
LuxS influences<i>Escherichia coli</i>biofilm formation through autoinducer-2-dependent and autoinducer-2-independent modalities (2012)

Escherichia coli produces biofilms in response to the small molecule autoinducer-2 (AI-2), a product of the LuxS enzyme. LuxS is part of the activated methyl cycle and could also affect biofilm development by AI-2-independent effects on metabolism. A luxS deletion mutant of E. coli W3110 and an inducible plasmid-luxS-complemented strain were used to identify AI-2-independent phenotypes. Differential interference contrast microscopy revealed distinct surface colonization patterns. Confocal microscopy followed by quantitative image analysis determined differences in biofilm topography correlating with luxS expression; deletion mutant biofilms had a 'spreading' phenotype, whereas the complement had a 'climbing' phenotype. Addition of exogenous 4,5-dihydroxy-2,3-pentanedione (DPD), an AI-2 precursor, to the deletion mutant increased biofilm height and biomass, whereas addition of the methyl donor S-adenosyl methionine or aspartate prevented the luxS-complemented strain from producing a thick biofilm. The luxS-complemented strain autoaggregated, indicating that fimbriae production was inhibited, which was confirmed by transmission electron microscopy. DPD could not induce autoaggregation in the deletion mutant, demonstrating that fimbriation was an AI-2-independent phenotype. Carbon utilization was affected by LuxS, potentially contributing to the observed phenotypic differences. Overall, the work demonstrated that LuxS affected E. coli biofilm formation independently of AI-2 and could assist in adapting to diverse conditions.
Structural Insights into the Interaction of Clinically Relevant Phosphorothioate mRNA Cap Analogs with Translation Initiation Factor 4E Reveal Stabilization via Electrostatic Thio-Effect (2021)

mRNA-based therapies and vaccines constitute a disruptive technology with the potential to revolutionize modern medicine. Chemically modified 5' cap structures have provided access to mRNAs with superior translational properties that could benefit the currently flourishing mRNA field. Prime examples of compounds that enhance mRNA properties are antireverse cap analog diastereomers that contain an O-to-S substitution within the β-phosphate (β-S-ARCA D1 and D2), where D1 is used in clinically investigated mRNA vaccines. The compounds were previously found to have high affinity for eukaryotic translation initiation factor 4E (eIF4E) and augment translation <i>in vitro</i> and <i>in vivo</i>. However, the molecular basis for the beneficial "thio-effect" remains unclear. Here, we employed multiple biophysical techniques and captured 11 cap analog-eIF4E crystallographic structures to investigate the consequences of the β-O-to-S or -Se substitution on the interaction with eIF4E. We determined the <i>S</i><sub>P</sub>/<i>R</i><sub>P</sub> configurations of β-S-ARCA and related compounds and obtained structural insights into the binding. Unexpectedly, in both stereoisomers, the β-S/Se atom occupies the same binding cavity between Lys162 and Arg157, indicating that the key driving force for complex stabilization is the interaction of negatively charged S/Se with positively charged amino acids. This was observed for all structural variants of the cap and required significantly different conformations of the triphosphate for each diastereomer. This finding explains why both β-S-ARCA diastereomers have higher affinity for eIF4E than unmodified caps. Binding affinities determined for di-, tri-, and oligonucleotide cap analogs suggested that the "thio-effect" was preserved in longer RNAs. Our observations broaden the understanding of thiophosphate biochemistry and enable the rational design of translationally active mRNAs and eIF4E-targeting drugs.