gebhart/patrepeval huggingface dataset:
Investigation of the Binding Geometry of a Peripheral Membrane Protein (2005)

A growing number of modules including FYVE domains target key signaling proteins to membranes through specific recognition of lipid headgroups and hydrophobic insertion into bilayers. Despite the critical role of membrane insertion in the function of these modules, the structural mechanism of membrane docking and penetration remains unclear. In particular, the three-dimensional orientation of the inserted proteins with respect to the membrane surface is difficult to define quantitatively. Here, we determined the geometry of the micelle penetration of the early endosome antigen 1 (EEA1) FYVE domain by obtaining NMR-derived restraints that correlate with the distances between protein backbone amides and spin-labeled probes. The 5- and 14-doxyl-phosphatidylcholine spin-labels were incorporated into dodecylphosphocholine (DPC) micelles, and the reduction of amide signal intensities of the FYVE domain due to paramagnetic relaxation enhancement was measured. The vector of the FYVE domain insertion was estimated relative to the molecular axis by minimizing the paramagnetic restraints obtained in phosphatidylinositol 3-phosphate (PI3P)-enriched micelles containing only DPC or mixed with phosphatidylserine (PS). Additional distance restraints were obtained using a novel spin-label mimetic of PI(3)P that contains a nitroxyl radical near the threitol group of the lipid. Conformational changes indicative of elongation of the membrane insertion loop (MIL) were detected upon micelle interaction, in which the hydrophobic residues of the loop tend to move deeper into the nonpolar core of micelles. The micelle insertion mechanism of the FYVE domain defined in this study is consistent with mutagenesis data and chemical shift perturbations and demonstrates the advantage of using the spin-label NMR approach for investigating the binding geometry by peripheral membrane proteins.
Butyrate and propionate inhibit antigen-specific CD8+ T cell activation by suppressing IL-12 production by antigen-presenting cells (2017)

Short chain fatty acids (SCFAs), such as acetate, butyrate and propionate, are products of microbial macronutrients fermentation that distribute systemically and are believed to modulate host immune responses. Recent data have indicated that certain SCFAs, such as butyrate and propionate, directly modulate human dendritic cell (DC) function. Given the role of DCs in initiating and shaping the adaptive immune response, we now explore how SCFAs affect the activation of antigen-specific CD8<sup>+</sup> T cells stimulated with autologous, MART1 peptide-pulsed DC. We show that butyrate reduces the frequency of peptide-specific CD8<sup>+</sup> T cells and, together with propionate, inhibit the activity of those cells. On the contrary, acetate does not affect them. Importantly, butyrate and propionate inhibit the production of IL-12 and IL-23 in the DCs and exogenous IL-12 fully restores the activation of the MART-1-specific CD8<sup>+</sup> T cells, whereas IL-23 has no effect. In conclusion, these results point to a pivotal role of butyrate and propionate in modulating CD8<sup>+</sup> T cell activation via the inhibition of IL-12 secretion from DCs. These findings reveal a novel mechanism whereby bacterial fermentation products may modulate CD8<sup>+</sup> T cell function with possible implications in anti-cancer immunotherapy.
Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies (2011)

Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk.
The pseudophosphatase MK-STYX interacts with G3BP and decreases stress granule formation (2010)

MK-STYX [MAPK (mitogen-activated protein kinase) phospho-serine/threonine/tyrosine-binding protein] is a pseudophosphatase member of the dual-specificity phosphatase subfamily of the PTPs (protein tyrosine phosphatases). MK-STYX is catalytically inactive due to the absence of two amino acids from the signature motif that are essential for phosphatase activity. The nucleophilic cysteine residue and the adjacent histidine residue, which are conserved in all active dual-specificity phosphatases, are replaced by serine and phenylalanine residues respectively in MK-STYX. Mutations to introduce histidine and cysteine residues into the active site of MK-STYX generated an active phosphatase. Using MS, we identified G3BP1 [Ras-GAP (GTPase-activating protein) SH3 (Src homology 3) domain-binding protein-1], a regulator of Ras signalling, as a binding partner of MK-STYX. We observed that G3BP1 bound to native MK-STYX; however, binding to the mutant catalytically active form of MK-STYX was dramatically reduced. G3BP1 is also an RNA-binding protein with endoribonuclease activity that is recruited to 'stress granules' after stress stimuli. Stress granules are large subcellular structures that serve as sites of mRNA sorting, in which untranslated mRNAs accumulate. We have shown that expression of MK-STYX inhibited stress granule formation induced either by aresenite or expression of G3BP itself; however, the catalytically active mutant MK-STYX was impaired in its ability to inhibit G3BP-induced stress granule assembly. These results reveal a novel facet of the function of a member of the PTP family, illustrating a role for MK-STYX in regulating the ability of G3BP1 to integrate changes in growth-factor stimulation and environmental stress with the regulation of protein synthesis.
A Novel Mutation in<i>ELOVL4</i>Leading to Spinocerebellar Ataxia (SCA) With the Hot Cross Bun Sign but Lacking Erythrokeratodermia (2015)

Combined with the results of the family with SCA34 reported previously, this report confirms that mutations in ELOVL4 can cause dominantly inherited neurodegeneration severely affecting the cerebellum and brainstem. We should be aware that the presence of multiple system atrophy-like features on magnetic resonance imaging scans, together with cerebellar and brainstem atrophy, suggests SCA34, even when erythrokeratodermia variabilis is absent. The present study further broadened the spectrum of the clinical presentations of SCA34 associated with mutations in ELOVL4, which is involved in the biosynthesis of very long-chain fatty acids.
Use of a stochastic simulation model to estimate the cost per case of digital dermatitis, sole ulcer, and white line disease by parity group and incidence timing (2018)

A farm-level stochastic simulation model was modified to estimate the cost per case of 3 foot disorders (digital dermatitis, sole ulcer, and white line disease) by parity group and incidence timing. Disorder expenditures considered within the model included therapeutics, outside labor, and on-farm labor. Disorder losses considered within the model included discarded milk, reduced milk production, extended days open, an increased risk of culling, an increased risk of death (natural or euthanized), and disease recurrence. All estimates of expenditures and losses were defined using data from previously published research in stochastic distributions. Stochastic simulation was used to account for variation within the farm model; 1,000 iterations were run. Sensitivity of foot disorder costs to selected market prices (milk price, feed price, replacement heifer price, and slaughter price) and herd-specific performance variables (pregnancy rate) were analyzed. Using our model assumptions, the cost per disorder case over all combinations of parity group and incidence timing, regardless of incidence likelihood, was lowest for digital dermatitis ($64 ± 24; mean ± standard deviation), followed by white line disease ($152 ± 26) and sole ulcer ($178 ± 29). Disorder costs were greater in multiparous versus primiparous cows and were always highest at the beginning of lactation. The greatest contributing cost categories were decreased milk production, an increased risk of culling, and disease recurrence. The contribution of cost categories to the total cost of disorder varied by disorder type, parity group, and incidence timing. For all disorders, the cost per case increased as milk price or replacement heifer price increased and decreased as feed price, pregnancy rate, or slaughter price increased. Understanding how foot disorder costs change according to cow-specific conditions (i.e., disorder type, parity group, and days in milk at incidence) and herd-specific conditions (i.e., market prices and performance variables) can help improve on-farm decisions about treatment and prevention of foot disorders.
Water Quality Investigation and Assessment for Guzhenkou Port Sea Area (2003)

Based on the monitoring results of Guzhenkou Port sea area from 1998 to 2002, a preliminary discussion on the variabilities of environmental factors and the nutrient level of the sea area was made. It is shown from the monitoring results that the water quality except oils and COD Mn of the sea area was comparatively good, the water quality in 1998 achieved the standards for seawater quality of first category (GB 3097 1977), that in 1999 was in excess of the standards for that of fourth category, those in 2000 and 2001 achieved the standards for that of third category, and that in 2002 achieved the standards of second category. Among them, the contents of dissolved inorganic nitrogen and reactive phosphate increased slightly in recent years and the mean ratio of N to P was 26.8; the mean eutrophication index was 37.2 and the index decreased drastically from 137 in 1999 to 0.733 in 2002. However, the sea area was seriously contaminated by oils and COD Mn , the contents of COD Mn were in excess of the standards for seawater quality of fourth category from 1999 to 2001, and that in 2002 was reduced obviously to achieve the standards for that of first category; the contents of oils achieved the standards for that of third category from 1998 to 2002. In summary, the seawater quality in the sea area is comparatively good at present.
1187. Retrospective and Prospective Analysis of Acinetobacter Modern-Day Clinical Isolates in a Large Mid-West Hospital System (2018)

Abstract Background The epidemiology of contemporary Acinetobacter calcoaceticus-baumannii complex (AcbC) strains in the United States is understudied. In addition to increasing multidrug resistance, there is concern that the rates of AcbC infections acquired outside of hospitals and the anatomic distribution of these infections may differ from what is previously reported. Furthermore, the epidemiology of non-AcbC clinical isolates is poorly characterized. Methods We retrospectively identified all cases associated with Acinetobacter clinical isolates in the Barnes-Jewish/Children’s Hospital system (St. Louis, MO) from 2007 to 2017. First isolates were classified as AcbC or non-AcbC. Tissue of origin, hospital-day of isolation, and antibiotic resistance profiles were determined. Results were compared with an ongoing prospective analysis of Acinetobacter isolates in the same system, started in July 2017. Results We identified 2,959 and 1,243 cases associated with AcbC and non-AcbC isolates, respectively. In both groups, isolates were most commonly obtained from respiratory (34% and 30% of total isolates) and connective tissue (34% and 27% of total isolates) sites. Urinary tract specimens were more likely to occur among AcbC isolates compared with non-AcBC isolates (664/2,959 [22%] vs. 147/1,243 [12%], P &amp;lt; 0.001). The percentage of isolates obtained prior to hospital-day-2 are 62% and 78% for AcbC and non-AcbC isolates, respectively. AcbC isolates were markedly more resistant to all classes of antibiotics. Analysis of 77 AcbC and 58 non-AcbC prospectively collected isolates revealed similar clinical findings. Conclusion Our study confirms the protean nature of Acinetobacter clinical isolates, and begins to describe relevant differences between AcbC and non-AcbC strains. These distinctions support the practice of identifying clinical isolates using AcbC and non-AcbC labels. Ongoing studies will further describe the patient characteristics and clinical outcomes associated with Acinetobacter disease in our system. Disclosures All authors: No reported disclosures.
Correction Annotation for Non-Native Arabic Texts: Guidelines and Corpus (2015)

We present our correction annotation guidelines to create a manually corrected nonnative (L2) Arabic corpus. We develop our approach by extending an L1 large-scale Arabic corpus and its manual corrections, to include manually corrected non-native Arabic learner essays. Our overarching goal is to use the annotated corpus to develop components for automatic detection and correction of language errors that can be used to help Standard Arabic learners (native and non-native) improve the quality of the Arabic text they produce. The created corpus of L2 text manual corrections is the largest to date. We evaluate our guidelines using inter-annotator agreement and show a high degree of consistency.
Chronic Inflammation Under the Microscope (2016)

Widefield microscopy is characterized by the illumination of the complete specimen and differs from confocal microscopy where only a small spot is illuminated. Its variants, especially widefield fluorescence microscopy, are among the most applied techniques in life sciences. For example, the detection of various fluorescence markers in a specimen—fixed or alive—can deliver insight into many biological processes such as the human immune system. The human body exhibits both innate and adaptive immune responses upon microbial invasion. Whereas the adaptive response develops a highly specific reaction over time, the innate response immediately reacts on special structures that are found on pathogens. They are called pathogen-associated molecular patterns (PAMPs). Lipopolysaccharides (LPS), which are specific to the cell walls of gram-negative bacteria, are a typical example of such a pattern. LPS binds to a special receptor on the surface of human cells—the toll-like receptor 4 (TLR4). Once bound, it can trigger an intracellular process ending up with the production of pro-inflammatory proteins called cytokines (Figure 1). One step during this intracellular process is the translocation of the protein NF-κB from the cytoplasm into the cell nucleus. In its role as a transcription factor, NF-κB supports the transcription of the relevant cytokine genes. The produced cytokines afterward prompt white blood cells (leukocytes) to release reactive oxygen species (ROS) and reactive nitrogen species (RNS) that can kill bacteria and viruses. Unfortunately, ROS/RNS also cause collateral damage and can have negative effects on the cells themselves. Injured by ROS/RNS, tissue cells release so-called damage-associated molecular patterns (DAMPs), which themselves can trigger TLRs, starting the whole process again and leading to chronic inflammation. This auto-amplifying toll-like receptor radical cycle (TLR radical cycle) can be associated with a number of diseases such as Parkinson’s disease, stroke, depression, (auto)immune disorders, or chronic obstructive pulmonary disease (COPD), to name but a few [1,2].
Progress on lamellarins (2011)

The latest developments towards the synthesis of lamellarins, their structure–activity relationship and advances in the mechanism of action are described.
Suppl. Figure S4 from Amplification of Wild-type &lt;i&gt;KRAS&lt;/i&gt; Imparts Resistance to Crizotinib in &lt;i&gt;MET&lt;/i&gt; Exon 14 Mutant Non–Small Cell Lung Cancer (2023)

&lt;p&gt;Combination therapies fail to inhibit MAPK/ERK pathway; overexpression of KRAS in Hs746T&lt;/p&gt;
Commutation Method for a Three-Phase Current-Sourced High-Frequency AC-link Inverter (2020)

This paper presents the results of recent work on developing a three-phase current-sourced high-frequency (HF) ac-link inverter. Two significant contributions are presented: first, the basic operation principles of the topology are analyzed, and second, a new commutation method for a three-phase current-sourced HF link is introduced. The HF ac-link inverter includes neither a large size line frequency transformer nor dc-link capacitors, so the size of the inverter can be reduced, and the reliability of the inverter can be improved. However, modulation methods for a voltage-sourced HF ac-link inverter are not suitable for a three-phase current-sourced HF ac-link inverter. Therefore, based on the analysis of the operations of a three-phase current-sourced HF ac-link inverter and the specific requirements for current commutations, this paper develops a new commutation method for a three-phase current-sourced HF ac-link inverter. MATLAB/Simulink simulations verify the new commutation method.
Thermal Deactivation of a Three-Way Catalyst: Changes of Structural and Performance Properties (1990)

&lt;div class="htmlview paragraph"&gt;A standard commercial three-way catalyst was aged at 950°C for 24 hours in dry N&lt;sub&gt;2&lt;/sub&gt; with 2% O&lt;sub&gt;2&lt;/sub&gt;. The performance of the aged and a fresh samples were characterized using a synthetic exhaust flow system.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The light-off temperature for all three pollutants on the aged sample was more than 70°C higher than for the fresh one. The effect of aging on steady-state performance at higher temperatures (&amp;gt;400°C) was more moderate.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;In order to explain the decrease in activity the samples were analysed for their bulk and surface composition using electron microscopy (TEM/STEM/EDS), photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). In addition the precious metal dispersion were determined by CO chemisorption and the total area by standard BET measurement.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;TEM micrographs showed that the metal particles containing platinum had an average diameter between 3-4 nm in the fresh sample but grow considerably in size upon aging. Very large sintered platinum particles (&amp;gt;1μm) were occasionally observed in the aged sample. The Pt/Rh ratio in these particles measured by STEM/EDS was twice as high on the aged catalyst compared to the fresh one, presumably due to a higher surface mobility for platinum. XPS measurements showed a higher degree of rhodium oxidation in the aged sample.&lt;/div&gt;
New vistas in zeolite and molecular sieve catalysis (1993)

Zeolites and zeolite-like molecular sieves are able to&#13;\nrecognize, discriminate, and organize molecules with&#13;\nprecisions that can be less than 1 Å. Because these structures (Figure 1) contain uniformly sized pores in the range of 4-13 Å, they have been exploited by the petrochemical industries to perform many large-scale,&#13;\nshape-selective hydrocarbon reactions. Further information&#13;\non the materials listed in Figure 1 is provided in Table I. The pore sizes listed are the crystallographic free diameters from each structure. Additionally, the dimensionality of the pore systems is provided. (A simple way to think about the dimensionality of the pore system is to place an organic molecule into the void space and observe in how many different directions it can move. For example, an n-hexane molecule can move in one direction in the channels of VPI-5 whereas it can travel in all three directions in NaX.) For more details on the structures of zeolites and molecular sieves, see ref 3.
Towards the Direct Detection of Viral Materials at the Surface of Protective Face Masks via Infrared Spectroscopy (2021)

Abstract The ongoing COVID-19 pandemic represents a considerable risk for the general public and especially for health care workers. To avoid an overloading of the health care system and to control transmission chains, the development of rapid and cost-effective techniques allowing for the reliable diagnosis of individuals with acute respiratory infections are crucial. Uniquely, the present study focuses on a direct face mask sampling approach, as worn (i.e., used) disposable face masks contain exogenous environmental constituents, as well as endogenously exhaled breath aerosols. Optical techniques – and specifically infrared (IR) molecular spectroscopic techniques - are promising tools for direct virus detection at the surface of such masks. In the present study, a rapid and non-destructive approach for monitoring exposure scenarios via medical face masks using attenuated total reflection infrared spectroscopy is presented. Complementarily, IR external reflection spectroscopy was evaluated in comparison for rapid mask analysis. The utility of a face mask-based sampling approach was demonstrated by differentiating water, proteins, and virus-like particles sampled onto the mask. Data analysis using multivariate statistical algorithms enabled unambiguously classifying spectral signatures of individual components and biospecies. This approach readily extends towards the rapid detection of SARS-CoV-2 – as shown herein for the example of virus-like particles which are morphologically equivalent to authentic virus - without any additional sample preparation or elaborate testing equipment at laboratory facilities. Therefore, this strategy may be implemented as a routine large-scale monitoring routine, e.g., at health care institutions, nursing homes, etc. ensuring the health and safety of medical personnel.
Advances in conversational case-based reasoning (2005)

A considerable amount of research in case-based reasoning (CBR) has recently focused on conversational CBR as a means of providing more effective support for interactive problem solving. We review progress made to date and identify challenges that remain to be addressed.
Aqueous microdroplets containing only ketones or aldehydes undergo Dakin and Baeyer–Villiger reactions (2019)

The Dakin and Baeyer-Villiger (BV) oxidation reactions require addition of peroxides as oxidants and an acid or a base as a catalyst. Reaction times range from hours to days to obtain target products. Previously, we reported that hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is spontaneously generated in water microdroplets without any added chemicals or applied electrical potential. Here, we report that the Dakin and BV reactions occur in modest yields within milliseconds in aqueous microdroplets at room-temperature without the addition of external peroxides and catalysts. H<sub>2</sub>O<sub>2</sub> generation is the result of the special environment of the microdroplet surface, which promotes water autoionization. We find that increasing the content of water and decreasing the droplet size improve the product yield of the Dakin and BV reactions, supporting the contention that the amount of H<sub>2</sub>O<sub>2</sub> generated in aqueous microdroplets could induce the two reactions and the reactions occur at or near the air-water interface of the microdroplet surface.
Low and high body mass index and lower numbers of screws in the articular segment are risk factors for non-union of distal humeral fractures in the elderly: A multi-center retrospective study (TRON study) (2022)

Low and high body mass index and three or fewer screws in the articular segment might be risk factors for non-union of distal humerus fracture in the elderly. Non-union is associated with poor clinical outcomes.
Disentangling Social Networks inferred from Call Logs (2010)

Analysis of an unusually detailed telephone call data set — a month of nearly all mobile and landline phone calls placed during August 2005 the United Kingdom — allows us to identify several different types of social networks that are formed, and relate them to different activities that generate them. We distinguish, among others, work-related and personal or leisure-focused activities and show that the networks they form have very different characteristics. Our principal tool for the analysis, k-core decomposition, shows that distinct distributions of connectivity are present in the two spheres, and that this differentiation affects dramatically the dynamics of information diffusion. Both differ from the simpler and more globally connected structure evident in communications data such as the Internet AS graph.