gebhart/patrepeval huggingface dataset:
An increased ratio of dietary tryptophan to lysine improves feed efficiency and elevates plasma tryptophan and kynurenine in the absence of antimicrobials and regardless of infection with enterotoxigenic Escherichia coli in weaned pigs (2012)

This experiment examined if a higher ratio of dietary Trp:Lys in the absence of antimicrobials improves production indices and modulates diarrhea in weaned pigs infected with enterotoxigenic Escherichia coli (ETEC). Effects of the Trp:Lys ratio on plasma levels of Trp and its metabolite kynurenine (Kyn) were also examined. Individually housed mixed-sex pigs (n = 72) weaned at 21 d of age (Landrace × Large White; initial BW of 6.3 ± 0.32 kg) were stratified into 1 of 6 treatments (n = 12) according to a 2 × 3 factorial arrangement of (i) infection or without infection with ETEC and (ii) 3 dietary standardized ileal digestible (SID) Trp:Lys ratios of 0.17, 0.21, or 0.26 in a randomized complete block design. Pigs were fed diets (10.4 MJ NE; 1.24% SID Lys; 19.5% CP) ad libitum for 3 wk after weaning. Pigs were infected with ETEC (O149:K98:K88) at 72, 96, and 120 h after weaning and then bled on day 11. A Trp:Lys ratio of 0.26 improved (P = 0.021) G:F over the study period compared to other ratios, without an infection effect (P > 0.05). Treatments did not affect ADG or ADFI (P > 0.05). Infection increased (P = 0.039) the diarrhea index and increased fecal consistency scores (P = 0.010). Plasma Trp and Kyn were lower (P < 0.001) in pigs fed 0.17 Trp:Lys than those fed ratios of 0.21 and 0.26 and were not affected (P > 0.05) by infection. In conclusion, in the absence of antimicrobials, increasing the dietary Trp:Lys ratio to 0.26 improved G:F after weaning and increased plasma levels of Trp and Kyn.
Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition (2020)

Abstract Migraine is the third most prevalent disease worldwide but the mechanisms that underlie migraine chronicity are poorly understood. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on dynamic microtubules. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated models of migraine to show that HDAC6-inhibition is a promising migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in headache-processing regions, which were reversed by HDAC6 inhibition. Cortical spreading depression (CSD), a physiological correlate of migraine aura, also decreased cortical neurite growth, while HDAC6-inhibitor restored neuronal complexity and decreased CSD. Importantly, a calcitonin gene-related peptide receptor antagonist also restored blunted neuronal complexity induced by nitroglycerin. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and effective migraine therapies might include agents that restore microtubule/neuronal plasticity.
Seeing in Extra Darkness Using a Deep-Red Flash (2021)

We propose a new flash technique for low-light imaging, using deep-red light as an illuminating source. Our main observation is that in a dim environment, the human eye mainly uses rods for the perception of light, which are not sensitive to wavelengths longer than 620nm, yet the camera sensor still has a spectral response. We propose a novel modulation strategy when training a modern CNN model for guided image filtering, fusing a noisy RGB frame and a flash frame. This fusion network is further extended for video reconstruction. We have built a prototype with minor hardware adjustments and tested the new flash technique on a variety of static and dynamic scenes. The experimental results demonstrate that our method produces compelling reconstructions, even in extra dim conditions.
Towards Practical Reactive Security Audit Using Extended Static Checkers (2013)

This paper describes our experience of performing reactive security audit of known security vulnerabilities in core operating system and browser COM components, using an extended static checker HAVOCLITE. We describe the extensions made to the tool to be applicable on such large C++ components, along with our experience of using an extended static checker in the large. We argue that the use of such checkers as a configurable static analysis in the hands of security auditors can be an effective tool for finding variations of known vulnerabilities. The effort has led to finding and fixing around 70 previously unknown security vulnerabilities in over 10 millions lines operating system and browser code.
Predictors for permanent pacing after transcatheter aortic valve implantation (2010)

CoreValve insertion was associated with an increase in PR interval and QRS duration. PR interval continued to rise during admission, peaking on Day 4 post procedure, making a prolonged period of monitoring highly desirable. There was a significant requirement for permanent pacing, which was predicted by pre-procedural QRS morphology, annulus measurement, and the learning curve. © 2010 Wiley-Liss, Inc.
Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1 (2009)

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.
In Vitro–In Vivo Correlation: A Regulatory Perspective with Case Studies (2007)

The recent advances in dissolution methodologies coupled with the availability of sophisticated modeling software enabled dissolution testing to be used more and more both by the industry and regulatory agencies, as a predictor of differences in bioavailability. This chapter gives an overview for the various requirements from a regulatory perspective for establishing, validating, and applying an in vitro–in vivo correlation (IVIVC). It presents case studies on how a predictive IVIVC could be used from both a regulatory and industrial perspective to obtain in vivo bioavailability waivers, as well as setting meaningful dissolution specifications. The chapter encompasses case studies on both conventional modified release (MR) dosage forms and specialized dosage forms such as implantables and vaginal rings. It discusses issues relating to the elution of drug-eluting stents (DES). Once an IVIVC has been established, a crucial determination of its applicability is its ability to predict the plasma concentration time profile accurately and consistently.
Fluorescence of tryptophan dipeptides: correlations with the rotamer model (1991)

The multiexponential decay of tryptophan derivatives has previously been explained by the presence of rotamers having different fluorescence lifetimes, but it has been difficult to correlate rotamer structure and physical properties. New time-resolved and static data on dipeptides of the type Trp-X and X-Trp, where X is another aminoacyl residue, are consistent with the rotamer model and allow some correlations. That a dominant rotamer of Trp-X zwitterion has the -NH3+ group near the indole ring was inferred from absorption and fluorescence spectra, titrimetric determination of pKa values, photochemical hydrogen-deuterium-exchange experiments, decay-associated spectra, quantum yields, and decay kinetics. Analysis of the lifetime and quantum yield data for Trp dipeptides, especially X-Trp, suggests that static self-quenching is not uncommon. Highly quenched and weak components of the fluorescence do not contribute to the calculated mean lifetime, thus resulting in apparent static quenching. We propose the term quasi-static self-quenching (QSSQ) to distinguish this phenomenon from quenching due to ground-state formation of a dark complex. Mechanisms of quenching and the structure of statically quenched rotamers are discussed. The occurrence of QSSQ supports the idea that rotamers interconvert slowly. A major perceived deficiency of the rotamer model, namely, the apparent inability to predict reasonable rotamer populations from fluorescence decay data, may result from the presence of statically quenched species, which do not contribute to the fluorescence.
Ultracompact visible R-G-B lasers for defense applications (2009)

Compact, efficient visible lasers are important for heads up displays, pointing and illumination, undersea communications, and less than lethal threat detection. We report on high power red, green, and blue lasers with output powers above 3 watts and efficiencies greater than 20%, 15%, and 5% respectively.
Solvent vapor annealing on perylene-based organic solar cells (2015)

Solvent vapor annealing on crystalline DIP and amorphous DBP induces morphological changes, which can improve organic solar cell efficiency.
Oestrogen-induced pro-cathepsin D in breast cancer: from biology to clinical applications (1989)

Synopsis In addition to secreted growth factors, acting as autocrine or paracrine mitogens, breast cancer cells secrete other proteins whose function and significance in mammary carcinogenesis may be important. Among them, proteases are particularly interesting since it has been suggested that they play a role in metastatic process, and since at least two of them, the tissue type plasminogen activator and pro-cathepsin D, the precursor of a lysosomal protease, are induced by oestrogens and secreted in excess in some mammary cancer cells. In oestrogen-receptor-positive human breast cancer cell lines (MCF7, ZR75–1), oestrogens stimulate cell proliferation and specifically increase the secretion into the culture medium of a 52,000-dalton (52-kDa) glycoprotein identified as the secreted precursor of a cathepsin D bearing mannose-6-phosphate signals, which is routed to lysosomes via mannose-6-phosphate-IGF-II receptors. We have determined the structure of this procathepsin D by sequencing its complete cDNA sequence, its chromosomal localisation and its transcriptional regulation by oestrogens and other mitogens. In breast cancer cells, pro-cathepsin D production and secretion is much higher and its processing is altered compared to normal mammary epithelial cells in culture. In vitro , pro-cathepsin D acts as an autocrine mitogen on breast cancer cells and can be activated at acidic pH to degrade extracellular matrix, suggesting a role in mediating the effect of oestrogens on tumour growth and invasion. Retrospective clinical studies indicate a significant correlation between high 52-kDa cathepsin D concentrations in the cytosol of primary breast cancer and poor prognosis (Danish Breast Cancer Group, S. Thorpe, Copenhagen). We propose that among the proteases secreted by cancer cells, 52-kDa cathepsin D is important both as a tissue marker in breast cancer and as a potential factor involved in carcinogenesis.
An S1 subunit vaccine and combination adjuvant (COVAC-1) elicits robust protection against SARS-CoV-2 challenge in African green monkeys (2022)

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent responsible for the ongoing global pandemic. With over 500 million cases and more than 6 million deaths reported globally, the need for access to effective vaccines is clear. An ideal SARS-CoV-2 vaccine will prevent pathology in the lungs and prevent virus replication in the upper respiratory tract, thus reducing transmission. Here, we assessed the efficacy of an adjuvanted SARS-CoV-2 S1 subunit vaccine, called COVAC-1, in an African green monkey (AGM) model. AGMs immunized and boosted with COVAC-1 were protected from SARS-CoV-2 challenge compared to unvaccinated controls based on reduced pathology and reduced viral RNA levels and infectious virus in the respiratory tract. Both neutralizing antibodies and antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC) were observed in vaccinated animals prior to the challenge. COVAC-1 induced effective protection, including in the upper respiratory tract, thus supporting further development and utility for determining the mechanism that confers this protection. AUTHOR SUMMARY Vaccines that can prevent the onward transmission of SARS-CoV-2 and prevent disease are highly desirable. Whether this can be accomplished without mucosal immunization by a parenterally administered subunit vaccine is not well established. Here we demonstrate that following two vaccinations, a protein subunit vaccine containing the S1 portion of the SARS-CoV-2 spike glycoprotein and the novel adjuvant TriAdj significantly reduces the amount of virus in the lungs and also mediates rapid clearance of the virus from the upper respiratory tract. Further support of the effectiveness of COVAC-1 was the observation of reduced pathology in the lungs and viral RNA being largely absent from tissues, blood, and rectal swabs. Thus COVAC-1 appears promising at mediating protection in both the upper and lower respiratory tract and may be capable of reducing subsequent transmission of SARS-CoV-2. Further investigation into the mechanism of protection in the upper respiratory tract and the initial immune response that supports this would be warranted.
Three-Dimensional Urban Path Planning for Aerial Vehicles Regarding Many Objectives (2023)

Planning flight paths for unmanned aerial vehicles in urban areas requires consideration of safety, legal, and economic aspects as well as attention to social factors for gaining public acceptance. To solve this many-objective path planning problem in the three-dimensional space, we propose a hybrid framework combining an exact Dijkstra search and a metaheuristic evolutionary optimization. Given a start and an endpoint, we optimize a path regarding the risk in case of a system failure, the radio signal disturbance between the aerial vehicle and a ground station, the energy consumption, and the noise immission on city residents. The optimization includes constraints for static obstacle collision avoidance and compliance with the minimum flight altitude. The result is a set of smooth and three-dimensional paths that realize different trade-offs between the defined objectives. As an example, we consider an urban transportation application for aerial vehicles in San Francisco. For all tests, we use real-world data from OpenStreetMap. In a statistical evaluation, we test the efficiency of our framework against different state-of-the-art optimizers. Moreover, we extend the framework with two features that allow the user to integrate arbitrary objectives and unknown scenarios into the path planning framework.
Kinematic and dynamic models of hybrid robot manipulator for propeller grinding (1999)

In this article, we develop a hybrid robot manipulator for propeller grinding and derive its kinematic and dynamic models. The manipulator is constructed by combining a parallel mechanism and a serial one to increase high stiffness as well as workspace. Based on geometric constraints, inverse–direct kinematics and Jacobian are derived to be implemented in real time control. The velocity control is used to measure the surface of a propeller blade and the position control is conducted to grind the removal depth. The dynamic model, which is developed by a motor algebra, can compute the forces and moments acting at a passive joint and an active one. ©1999 John Wiley & Sons, Inc.
ChemInform Abstract: Substrate‐Directed Synthesis: The Rapid Assembly of Novel Macropolycyclic Structures via Stereoregular Diels‐Alder Oligomerizations. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The X-ray structure ofL-threonine dehydrogenase from the common hospital pathogenClostridium difficile (2021)

In many prokaryotes, the first step of threonine metabolism is catalysed by the enzyme threonine dehydrogenase (TDH), which uses NAD<sup>+</sup> to oxidize its substrate to 2-amino-3-ketobutyrate. The absence of a functional TDH gene in humans suggests that inhibitors of this enzyme may have therapeutic potential against pathogens which are reliant on this enzyme. Here, TDH from Clostridium difficile has been cloned and overexpressed, and the X-ray structure of the apoenzyme form has been determined at 2.6 Å resolution.
Evidence for spatial frequency and orientation labelled detectors in second-order visual processing (2004)

We compared the number of spatial frequency and orientation mechanisms (or labelled detectors) (Watson & Robson, 1981, VR, 21) underlying first- versus second-order processing. We measured discrimination at detection threshold for first- and second-order gratings in order to determine the smallest difference in spatial frequency (Exp. 1) and orientation (Exp. 2) that permits accurate discrimination. When the psychometric functions for detection and discrimination are statistically equivalent, the underlying mechanisms are considered to be different. In a 2 × 2 AFC paradigm, observers indicated whether the grating was presented in the first or second interval, and identified the spatial frequency or orientation of the grating. One of the authors and two inexperienced observers participated in the study. In agreement with previous findings, for first-order gratings between 0.1 and 22 cpd, we found evidence for seven labelled channels for spatial frequency discrimination at detection threshold. For second-order gratings, the number of channels is the same as for first-order gratings for spatial frequencies up to about 2cpd; however, there are fewer second-order channels at higher spatial frequencies. In contrast, the number of labelled channels for orientation is the same for first- and second-order gratings. In conclusion, our findings provide evidence for distinct spatial frequency and orientation labelled detectors in second-order visual processing. Second, relative to first-order, there are fewer second-order channels processing higher spatial frequencies. This is consistent with a filter-rectify-filter scheme for second-order in which the second stage of filtering is at lower spatial frequencies.
Decoding order recovery for multi flow transmission of scalable video coding (SVC) over mobile IP channels (2009)

Recent standardization activities for the transport of Scalable Video Coding over multimedia networking channels have introduced means to differentiate layers of a scalable media in transport. Therefore in RTP, those layers are transported in different RTP flows respectively RTP sessions. To decode
Biodegradable Wound Dressing for Skin Regeneration (2020)

Using the delayed healing model of diabetic (db/db) mice, we evaluated the ability of a novel silk based dressing to facilitate healing of full-thickness excisional wounds. Silk protein from Bombyx mori was used to create wound dressings via a proprietary electrospinning technique. The resulting dressing is vapor and air transmissible. Eight millimeter diameter full-thickness wounds were created on the backs of diabetic mice and covered with either a standard (n=12) telfa-gauze or the silk (n=12) dressing. At 2 day intervals, the telfa dressings were removed, the wounds photographed, measured and fresh dressings placed. For mice receiving the silk dressing, it was allowed to remain in place unless it became dislodged. In that case, a fresh dressing was placed into the wound bed. Wound healing was followed for 21 days at which time the mice were sacrificed, the wound areas excised and subjected to H & E and Trichrome staining. Wounds covered with the silk dressings developed an eschar encompassing the silk whereas wounds dressed with gauze remained moist and without eschar throughout the study period. Upon histologic examination, 1 of the gauze dressed wounds developed a complete epithelial layer across the wound. The remaining 11 wounds had large areas remaining without an epithelial cover. In contrast, 5 of 12 mice receiving the silk dressing developed complete epithelial layers, 2 additional mice had very small areas remaining without a complete epithelium. The remaining 5 had modest areas without an epithelial covering. The ability of silk dressings to permit the formation of an eschar versus gauze in which the wounds remained wet may contribute significantly to the healing response observed. These results suggest that the breathable, vapor transmissible nature of the silk dressing may be an effective dressing for difficult to heal wounds such as diabetic foot ulcers.
Complement Receptor 1 availability on red blood cell surface modulates Plasmodium vivax invasion of human reticulocytes (2019)

Plasmodium vivax parasites preferentially invade reticulocyte cells in a multistep process that is still poorly understood. In this study, we used ex vivo invasion assays and population genetic analyses to investigate the involvement of complement receptor 1 (CR1) in P. vivax invasion. First, we observed that P. vivax invasion of reticulocytes was consistently reduced when CR1 surface expression was reduced through enzymatic cleavage, in the presence of naturally low-CR1-expressing cells compared with high-CR1-expressing cells, and with the addition of soluble CR1, a known inhibitor of P. falciparum invasion. Immuno-precipitation experiments with P. vivax Reticulocyte Binding Proteins showed no evidence of complex formation. In addition, analysis of CR1 genetic data for worldwide human populations with different exposure to malaria parasites show significantly higher frequency of CR1 alleles associated with low receptor expression on the surface of RBCs and higher linkage disequilibrium in human populations exposed to P. vivax malaria compared with unexposed populations. These results are consistent with a positive selection of low-CR1-expressing alleles in vivax-endemic areas. Collectively, our findings demonstrate that CR1 availability on the surface of RBCs modulates P. vivax invasion. The identification of new molecular interactions is crucial to guiding the rational development of new therapeutic interventions against vivax malaria.