gebhart/patrepeval huggingface dataset:
Data from Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; We undertook this study to determine the prevalence of estrogen receptor (ER) α (&lt;i&gt;ESR1&lt;/i&gt;) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER&lt;sup&gt;+&lt;/sup&gt;/HER2&lt;sup&gt;−&lt;/sup&gt;) and, as controls, 115 ER-negative (ER&lt;sup&gt;−&lt;/sup&gt;) tumors. The ER&lt;sup&gt;+&lt;/sup&gt; samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER&lt;sup&gt;+&lt;/sup&gt; metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95% confidence interval (CI), 6%–21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95% CI, 7%–41%). These mutations were not detected in primary or treatment-naïve ER&lt;sup&gt;+&lt;/sup&gt; cancer or in any stage of ER&lt;sup&gt;−&lt;/sup&gt; disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; In this study, we show evidence for the temporal selection of functional &lt;i&gt;ESR1&lt;/i&gt; mutations as potential drivers of endocrine resistance during the progression of ER&lt;sup&gt;+&lt;/sup&gt; breast cancer. &lt;i&gt;Clin Cancer Res; 20(7); 1757–67. ©2014 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Minimum Bayes risk discriminative language models for Arabic speech recognition (2011)

In this paper we explore discriminative language modeling (DLM) on highly optimized state-of-the-art large vocabulary Arabic broadcast speech recognition systems used for the Phase 5 DARPA GALE Evaluation. In particular, we study in detail a minimum Bayes risk (MBR) criterion for DLM. MBR training outperforms perceptron training. Interestingly, we found that our DLMs generalized to mismatched conditions, such as using a different acoustic model during testing. We also examine the interesting problem of unsupervised DLM training using a Bayes risk metric as a surrogate for word error rate (WER). In some experiments, we were able to obtain about half of the gain of the supervised DLM.
Constellation: a Multi-User Interface for Remote Drone Tours (2021)

Remotely controlled camera drones can support live, dynamic, and interactive virtual tours for travelers to overcome distance, expense, and health barriers. Yet, assigning one drone to one traveler may incur unnecessary waste of resources, and an abundance of concurrent drones raises safety concerns. While sharing the input and output of a single drone among multiple concurrent users can alleviate these limitations, standard control sharing protocols, such as turn-taking, are often inefficient. We present Constellation, a multi-user drone control system that synthesizes diverse user goals and generates efficient flight paths for the group. It supports point-of-interest specification on both static 3D environmental maps and live camera views. The generated paths minimize all users’ total extra waiting time. A web-based study with 16 participants show that Constellation could help groups navigate to their points-of-interest faster in comparison to the turn-taking baseline.
Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells (2022)

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and is characterized by poor clinical outcomes, with the majority of patients not being eligible for curative therapy and treatments only being applicable for early-stage tumors. CD44 is a receptor for hyaluronic acid (HA) and is involved in HCC progression. The aim of this work is to propose HA- and PEGylated-liposomes as promising approaches for the treatment of HCC. It has been found, in this work, that CD44 transcripts are up-regulated in HCC patients, as well as in a murine model of NAFLD/NASH-related hepatocarcinogenesis. Cell culture experiments indicate that HA-liposomes are more rapidly and significantly internalized by Huh7 cells that over-express CD44, compared with HepG2 cells that express low levels of the receptor, in which the uptake seems due to endocytic events. By contrast, human and murine macrophage cell lines (THP-1, RAW264.7) show improved and rapid uptake of PEG-modified liposomes without the involvement of the CD44. Moreover, the internalization of PEG-modified liposomes seems to induce polarization of THP1 towards the M1 phenotype. In conclusion, data reported in this study indicate that this strategy can be proposed as an alternative for drug delivery and one that dually and specifically targets liver cancer cells and infiltrating tumor macrophages in order to counteract two crucial aspect of HCC progression.
A Novel Dual-Layered Electrolytic Resistance Memory with Enhanced Retention (2008)

A novel dual-layered electrolytic resistance memory is proposed and its high retention ability at room and elevated temperature is successfully demonstrated. This dual-layered memory cell was fabricated as cross-point structure with active material, Cu containing Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.3</sub> Se <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.7</sub> based solid electrolyte and a thin insulator layer stack, sandwiched between an inert Pt bottom electrode and an oxidizable Cu top electrode. The reduction of the cell programming current up to few nA achieved with this dual- layered memory cell is promising for low power consumption applications.
PET/CT targeted tissue sampling reveals virus specific dIgA can alter the distribution and localization of HIV after rectal exposure (2021)

Human immunodeficiency virus (HIV) vaccines have not been successful in clinical trials. Dimeric IgA (dIgA) in the form of secretory IgA is the most abundant antibody class in mucosal tissues, making dIgA a prime candidate for potential HIV vaccines. We coupled Positron Emission Tomography (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP HIV (PA-GFP-BaL) and fluorescently labeled dIgA to determine how dIgA antibodies influence virus interaction with mucosal barriers and viral penetration in colorectal tissue. Our results show that HIV virions rapidly disseminate throughout the colon two hours after exposure. The presence of dIgA resulted in an increase in virions and penetration depth in the transverse colon. Moreover, virions were found in the mesenteric lymph nodes two hours after viral exposure, and the presence of dIgA led to an increase in virions in mesenteric lymph nodes. Taken together, these technologies enable in vivo and in situ visualization of antibody-virus interactions and detailed investigations of early events in HIV infection.
State assignment algorithm for incompletely specified finite state machines (1990)

This paper presents an algorithm for state assignment in incompletely specified finite state machines, based on a set of heuristic rules. These rules are used to build a desired adjacency graph in which a weight is associated to each possible adjacency. A new method of assigning codes to each state is presented with the goal of choosing adjacencies with large weights.
Effects of Intra-aortic Balloon Pumping on Coronary Flow and Metabolism in Man (1971)

Coronary blood flow (CBF) and myocardial oxygen consumption (MVO 2 ), myocardial lactate extraction, blood gases, and hemodynamics were measured on and off intra-aortic balloon pumping (IABP) 14 times in 10 patients during treatment of cardiovascular collapse following myocardial infarction. At the time of study an average of 14 hours of IABP had elapsed and all but one patient had stabilized out of cardiogenic shock. With IABP, CBF fell in 7 instances, was unaffected in 3, and rose in 4. Changes in MVO 2 correlated closely with the observed effects on CBF. Lactate extraction and blood gases were not significantly affected. Systolic arterial pressure fell an average of 11 mm Hg with IABP, while mean diastolic pressure rose 8 mm Hg. These results suggest that the net result of IABP on coronary flow and metabolism depends on the interplay between increased blood flow to ischemic areas provided by increased diastolic perfusion pressure and diminution of blood flow to normal myocardium in which the oxygen requirements are reduced by diminished afterload.
A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells (2008)

The specific features of the plasticity of adult stem cells are largely unknown. Recently, we demonstrated the hepatic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs). To identify the genes responsible for hepatic differentiation, we examined the gene expression profiles of AT-MSC-derived hepatocytes (AT-MSC-Hepa) using several microarray methods. The resulting sets of differentially expressed genes (1639 clones) were comprehensively analyzed to identify the pathways expressed in AT-MSC-Hepa. Clustering analysis revealed a striking similarity of gene clusters between AT-MSC-Hepa and the whole liver, indicating that AT-MSC-Hepa were similar to liver with regard to gene expression. Further analysis showed that enriched categories of genes and signaling pathways such as complementary activation and the blood clotting cascade in the AT-MSC-Hepa were relevant to liver-specific functions. Notably, decreases in Twist and Snail expression indicated that mesenchymal-to-epithelial transition occurred in the differentiation of AT-MSCs into hepatocytes. Our data show a similarity between AT-MSC-Hepa and the liver, suggesting that AT-MSCs are modulated by their environmental conditions, and that AT-MSC-Hepa may be useful in basic studies of liver function as well as in the development of stem cell-based therapy.
Serum albumin disrupts Cryptococcus neoformans and Bacillus anthracis extracellular vesicles (2012)

For both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. However, there are many unresolved issues regarding vesicle synthesis and stability, including the fact that vesicular packaging for extracellular factors involved in virulence must also have a mechanism for vesicle unloading. Consequently, we studied the kinetics of vesicle production and stability using [1-(14) C] palmitic acid metabolic labelling and dynamic light scattering techniques. Cryptococcus neoformans vesicles were produced throughout all stages of fungal culture growth and they were stable once isolated. Density gradient analysis revealed that only a portion of the vesicle population carried cryptococcal polysaccharide, implying heterogeneity in vesicular cargo. Vesicle incubation with macrophages resulted in rapid vesicle instability, a phenomenon that was ultimately associated with serum albumin. Additionally, albumin, along with mouse serum and murine immunoglobulin destabilized Bacillus anthracis vesicles, but the effect was not observed with ovalbumin or keyhole limpet haemocyanin, demonstrating that this phenomenon is neither host-, microbe- nor protein-specific. Our findings strongly suggest that cryptococcal vesicles are short-lived in vivo and vesicle destabilization is mediated by albumin. The ability of albumin to promote vesicular offload through destabilization indicates a new activity for this abundant serum protein.
ChemInform Abstract: Discovery of Potent and Practical Antiangiogenic Agents Inspired by Cortistatin A. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.
ChemInform Abstract: Enantioselective Synthesis of Diisopropyl α‐, β‐, and . gamma.‐Hydroxyarylalkylphosphonates from Ketophosphonates: A Study on the Effect of the Phosphonyl Group. (1996)

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.
Lamivudine for Patients with Chronic Hepatitis B and Advanced Liver Disease (2004)

Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.
Glucose Variability and Flash Glucose Monitoring in the Real World (2018)

High glucose variability is associated with increased hypoglycemia. Previous analyses of real-world data have shown that increased testing using flash glucose monitoring (FreeStyle LibreTM system) is associated with lower hypoglycemia and hyperglycemia. Here we studied: 1) The relationship between glucose variability and hypoglycemia/hyperglycemia during flash glucose monitoring 2) The relationship between increased glucose testing and glucose variability. De-identified glucose data is collected from individuals using the system when they upload data from their readers to the desktop software. Data from 237,747 individuals was analyzed. To understand the relationship between variability and hypoglycemia/hyperglycemia, individuals were divided into groups of high and low glucose variability using CV=36% as the threshold. Hypoglycemia (time below 70mg/dL) and hyperglycemia (time above 180mg/dL) metrics were then analyzed in the two groups. To understand the impact of testing frequency on glycemic variability, individuals were divided into 20 equal sized groups spanning the full range of daily testing frequency. Average CV was then calculated for each group. It was observed that individuals with high variability showed 35% more hyperglycemia (10.1±5.9 hours/day) compared to individuals with low variability (7.5±7.0 hours/day). Similarly, individuals with high variability showed 167% more hypoglycemia (144±281 minutes/day) compared to those with low variability (54±185 minutes/day). It was observed that increased testing with the system was associated with lower glucose variability. CV decreased from 40.6% to 34.5% from the lowest to highest testing frequency groups. High variability is associated with both increased hyperglycemia and hypoglycemia in a large sample population from the real world. Increased testing is associated with decreased glucose variability. Disclosure S. Jangam: Employee; Self; Abbott. Y. Xu: Employee; Self; Abbott. G. Hayter: Employee; Self; Abbott. T. Dunn: Employee; Self; Abbott.
ChemInform Abstract: Enantio‐ and Regioselective CuH‐Catalyzed Hydroamination of Alkenes. (2014)

Abstract A mild method for the synthesis of chiral tertiary amines using an asymmetric copper‐catalyzed hydroamination is reported.
Diminished frequency of interleukin‐10‐secreting, T‐cell receptor peptide‐reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene (2001)

T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes.
Data from High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;This study analyzes the potential of stromal platelet-derived growth factor receptor-beta (PDGFRb) expression as biomarker for radiotherapy (RT) benefit on ipsilateral breast events (IBE) in ductal carcinoma &lt;i&gt;in situ&lt;/i&gt; (DCIS). Improved identification of DCIS patients refractory to adjuvant whole-breast RT is needed. Predictive biomarker studies in DCIS have focused on tumor cell features rather than the tumor-associated stroma, despite growing evidence of its influence on therapy efficiency.&lt;/p&gt;Experimental Design:&lt;p&gt;Samples from the Swedish randomized radiotherapy DCIS trial (SweDCIS) were subjected to IHC analysis for stromal PDGFRb expression. IBE incidence at 10 years after breast-conserving surgery was the primary endpoint. Interactions between marker and treatment were analyzed.&lt;/p&gt;Results:&lt;p&gt;PDGFRb score was predictive for RT benefit with regard to IBE (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;interaction&lt;/sub&gt; = 0.002 and &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;interaction&lt;/sub&gt; = 0.008 adjusted multivariably). Patients of the PDGFRb&lt;sup&gt;low&lt;/sup&gt; group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12–0.45; &lt;i&gt;P&lt;/i&gt; &lt; 0.001] with an absolute risk reduction of 21% (cumulative risk 7% vs. 28%) at 10 years. No significant risk reduction by RT was observed for patients of the PDGFRb&lt;sup&gt;high&lt;/sup&gt; group (HR, 0.83; 0.51–1.34; &lt;i&gt;P&lt;/i&gt; = 0.444; cumulative risk 22% vs. 25%). The RT response–predictive effect of stromal PDGFRb was equally strong in analyses for &lt;i&gt;in situ&lt;/i&gt; and invasive IBE when analyzed separately (&lt;i&gt;in situ&lt;/i&gt; IBE: &lt;i&gt;P&lt;/i&gt; = 0.029; invasive IBE: &lt;i&gt;P&lt;/i&gt; = 0.044).&lt;/p&gt;Conclusions:&lt;p&gt;Results suggest high stromal PDGFRb expression as a novel biomarker identifying DCIS patients who are refractory to standard whole-breast adjuvant RT. The data imply previously unrecognized fibroblast-mediated modulation of radiosensitivity of DCIS, which should be further explored from mechanistic and targeting perspectives.&lt;/p&gt;&lt;/div&gt;
A computational model of the inhibition of Mycobacterium tuberculosis ATPase by a new drug candidate R207910 (2007)

Diarylquinolines (DARQs) are a new class of potent inhibitors of the ATPase of Mycobacterium tuberculosis. We have created a homology model of a binding site for this class of compounds located on the contact area of the a-subunit (gene atpB) and c-subunits (gene atpE) of Mycobacterium tuberculosis ATPase. The binding pocket that was identified from the analysis of the homology model is formed by 4 helices of three c-subunits and 2 helices of the a-subunit. The lead compound of the DARQ series, R207910, was docked into the pocket using a simulated annealing, multiple conformer, docking algorithm. Different stereoisomers were treated separately. The best docking pose for each stereoisomer was optimized by molecular dynamics simulation on the 5300 atoms of the binding region and ligand. The interaction energies in the computed complexes enable us to rank the different stereoisomers in order of interaction strength with the ATPase binding pockets. We propose that the activity of R207910 against Mycobacterium tuberculosis is based on interference of the compound with the escapement geometry of the proton transfer chain. Upon binding the compound mimics the conserved Arg-186 residue of the a-subunit and interacts in its place with the conserved acidic residue Glu-61 of the c-subunit. This mode of action is corroborated by the good agreement between the computed interaction energies and the observed pattern of stereo-specificity in the model of the binding region.
The complex genetics of gait speed: genome-wide meta-analysis approach (2016)

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.
Applying statistical multiplexing and traffic grooming in optical networks jointly (2006)

Multilayer optical core networks are able to provide huge bandwidth. With traffic grooming we can utilize more efficiently the available resources. The principle of grooming: if the routes of two different traffic flows (or demands) have common links, their traffic can be joined in to the same wavelength channel. Another well-known solution for increased efficiency of resource usage is multiplexing the traffic. The statistical multiplexing does not allocate the maximal bandwidth for each traffic demand, but less than the maximal and more than the average. The aim of this article is to investigate the effects of applying both solutions.
Optimization of Quadralayer Structures for Various Magneto-Optical Recording Materials (1991)

Computer simulation of magneto-optical responses as a function of wavelength (300 - 800 nm), thicknesses, and material were made, based on the scattering matrix formulation for the calculation of optical and magneto-optical response of multilayer systems. 1 Results from the following MO materials systems are presented: bismuth substituted garnets, TbFeCo, PtMnSb, and NiMnSb. Silicon nitride and silicon carbide were the dielectrics used in the simulations, and aluminum was assumed for the reflector. The optimum structure for each of these materials systems has been found. The Kerr rotation, ellipticity, reflectance, and figures of merit for recording were calculated.