gebhart/patrepeval huggingface dataset:
Modeling of Open, Closed, and Open-Inactivated States of the hERG1 Channel: Structural Mechanisms of the State-Dependent Drug Binding (2012)

The human ether-a-go-go related gene 1 (hERG1) K ion channel is a key element for the rapid component of the delayed rectified potassium current in cardiac myocytes. Since there are no crystal structures for hERG channels, creation and validation of its reliable atomistic models have been key targets in molecular cardiology for the past decade. In this study, we developed and vigorously validated models for open, closed, and open-inactivated states of hERG1 using a multistep protocol. The conserved elements were derived using multiple-template homology modeling utilizing available structures for Kv1.2, Kv1.2/2.1 chimera, and KcsA channels. Then missing elements were modeled with the ROSETTA De Novo protein-designing suite and further refined with all-atom molecular dynamics simulations. The final ensemble of models was evaluated for consistency to the reported experimental data from biochemical, biophysical, and electrophysiological studies. The closed state models were cross-validated against available experimental data on toxin footprinting with protein-protein docking using hERG state-selective toxin BeKm-1. Poisson-Boltzmann calculations were performed to determine gating charge and compare it to electrophysiological measurements. The validated structures offered us a unique chance to assess molecular mechanisms of state-dependent drug binding in three different states of the channel.
The Optimal Design of Heat Sinks: A Review (2020)

Heat sinks are used in industrial equipment to dissipate the excess heat from their heat-generating parts to the ambient. In the last few years, efforts on manufacturing electronic or mechanical devices with less weight, space, and lower cost were spent. Heat dissipation from the heat sink is stalling a big problem which many researchers are trying to solve. The aim of this study is to brief the previous investigation attempted enhancing the heat sinks thermal performance and to provide help to understand the cooling ability of their specific geometries. The various enhancement techniques used for optimizing the hydrothermal design of a pin fin, flat fin, micro-channel, and topology optimized heat sinks were summarized. The way in which the heat sinks’ thermal performance is affected by orientation, shapes, perforation, slot, interruption, and space between fins and their arrangement under free and forced convection condition also reviewed.
Comparison of the efficacy and safety of two preseasonal regimens of glutaraldehyde modified, tyrosine-adsorbed parietaria pollen extract over a period of three years in monosensitive patients. (1999)

The purpose of this study was to evaluate the clinical efficacy over a period of three years (1988-90) of two preseasonal dosage regimens of a Parietaria allergoid (Bencard Tyrosine Parietaria) in patients who were only sensitive to this pollen. Fifty patients were included (14 men and 36 women, age: mean, 28 years; range, 14-47 years). Twenty five patients (group A) were treated each january with the basic course of Bencard Tyrosine Parietaria. This consisted of injecting subcutaneously 0.5 ml from each of three vials, with one week between each injection. A further injection using the vial with the highest dose was given one week later. Each january and february, twenty five patients (group B) were treated with the basic course of Bencard Tyrosine Parietaria, repeating the last dose five times, with one week between each injection. Immunotherapy with a tyrosine-adsorbed Parietaria judaica allergoid is an effective method for mitigating nasal (p < 0.0001), bronchial (p < 0.005), conjunctival (p < 0.001) and palatal itching symptoms (p < 0.0001) in patients who are sensitive to this pollen. Sensitivity to Parietaria pollen, as verified by skin test and nasal challenge, decreased during immunotherapy (p < 0.001). Histamine release by peripheral blood basophils decreased during the course of the study, falling from 43.5 ng/ml to 12.3 ng/ml in group A and from 42.9 ng/ml to 10.0 ng/ml in group B; during the second and third years, IgG levels were increased one and four months after starting treatment with the extract, while this was not the case after ten months; IgE levels were also increased. Finally, overall tolerance to this immunotherapy product was good in almost all patients.
Analysis of domestic column internals industry (2011)

Column internals industry is an auxiliary part of process industries and also affects the product quality,energy consumption,operation safety and wastes control.In the last 20 years,domestic column internals industry has got great development with higher design level and greater technology power.Meanwhile it also has experienced some difficulties and frustration.Step by step,China will become the center of global column internals industry in the future.The current situation of domestic column internals industry is analyzed in terms of both market and technology so that a proper strategy could be found for its long-term development.
Decreased Intestinal Microbiome Diversity in Pediatric Sepsis: A Conceptual Framework for Intestinal Dysbiosis to Influence Immunometabolic Function (2021)

Intestinal dysbiosis was associated with altered short-chain fatty acid metabolites in children with sepsis, but these findings were not linked directly to mitochondrial or immunologic changes. More detailed mechanistic studies are needed to test the role of microbial-derived short-chain fatty acids in the progression of sepsis.
Quantification of Arterial, Venous, and Cerebrospinal Fluid Flow Dynamics by Magnetic Resonance Imaging Under Simulated Micro-Gravity Conditions: A Prospective Cohort Study (2020)

Abstract Background: Astronauts undergoing long-duration spaceflight are exposed to numerous health risks, including Spaceflight-Associated Neuro-Ocular Syndrome (SANS), a spectrum of ophthalmic changes that can result in permanent loss of visual acuity. The etiology of SANS is not well understood but is thought to involve changes in cerebrovascular flow dynamics in response to microgravity. There is a paucity of knowledge in this area; in particular, cerebrospinal fluid (CSF) flow dynamics have not been well characterized under microgravity conditions. Our study was designed to determine the effect of simulated microgravity (head-down tilt [HDT]) on cerebrovascular flow dynamics. We hypothesized that microgravity conditions simulated by HDT would result in increased intracranial pressure (ICP) reflected by increases in CSF pulsatile flow. Methods: In a prospective cohort study, we measured flow in major cerebral arteries, veins, and CSF spaces in fifteen healthy volunteers using phase contrast magnetic resonance (PCMR) before and during 15° HDT. Results: We found a decrease in all CSF flow variables [systolic peak flow (p=0.009), and peak-to-peak pulse amplitude (p=0.001)]. Cerebral arterial average flow (p=0.04), systolic peak flow (p=0.04), and peak-to-peak pulse amplitude (p=0.02) all also significantly decreased. We additionally found a decrease in average cerebral arterial flow (p=0.040). Finally, a significant increase in cerebral venous cross-sectional area with HDT (p=0.005) was also observed. Conclusions: These results collectively demonstrate that acute application of 15° HDT caused a reduction in CSF flow variables (systolic peak flow and peak-to-peak pulse amplitude) which, when coupled with a decrease in average cerebral arterial flow, systolic peak flow, and peak-to-peak pulse amplitude, is consistent with a decrease in cardiac-related pulsatile CSF flow. These results suggest that decreases in cerebral arterial inflow were the principal drivers of decreases in CSF pulsatile flow.
Novel Estimator for the Location Parameter of the Generalized Gaussian Distribution (2012)

The estimation of the location parameter of the generalized Gaussian distribution with shape parameter p ≥ 2 is studied and a novel estimator, based on an approximation to the maximum likelihood estimator, is proposed. The new estimator is simple with low complexity and is proved to be unbiased. Numerical results show that the mean square error of the new estimator is much lower than that of the widely used mean estimator. The new estimator has almost identical mean square error as the maximum likelihood estimator.
STEM-10. SUPER-ENHANCER SCREEN IDENTIFIES LIPID METABOLISM AS A CANCER STEM CELL DEPENDENCY IN GLIOBLASTOMA (2017)

Super-enhancer screen identifies lipid metabolism as a cancer stem cell dependency in glioblastoma Ryan C. Gimple, Stephen C. Mack, Jeremy N. Rich Glioblastoma is the most prevalent and aggressive primary intrinsic brain tumor in adults and is among the most lethal of all human cancers with poor responses to all therapeutic modalities. Functionally defined glioma stem cells (GSCs) are proposed to contribute to this poor prognosis by mediating therapy resistance, self-renewal, and maintenance of cellular heterogeneity. To understand the cell-type-specific molecular processes that underlie GSC maintenance and tumorigenicity, we profiled super-enhancers through analysis of active enhancer histone modification data (H3K27ac) in matched GSC and differentiated glioma cell (DGC) samples. Super-enhancers, defined as clusters of typical enhancers, function as master epigenetic regulators that define cell state, orchestrate cell-type dependent transcriptional networks, and drive key oncogenes in a variety of cancers. This approach revealed lipid biosynthesis as a potential epigenetically regulated GSC dependency pathway. Knockdown of a key lipid metabolism gene in patient-derived GSCs resulted in decreased cell proliferation, diminished self-renewal, and induction of apoptosis in vitro, as well as impaired tumor formation in vivo. In a validation cohort, patient derived GSC tumor models containing the identified super-enhancer exhibited high expression of the lipid metabolism gene, suggesting that the expression of this gene is epigenetically driven. Next, we analyzed the upstream transcription factor control circuits that underlie a critical super-enhancer in this pathway. Expression of two neurodevelopmental transcription factors, OLIG2 and SOX2, were found to be significantly positively correlated with that of a lipid metabolism gene in clinical samples, suggesting that occupancy of these factors may drive the persistence of this super-enhancer. This discovery implicates aberrant lipid metabolism networks in glioma pathogenesis and suggests that targeting of fatty acid synthesis may provide a specific way to more effectively treat patients with glioblastoma.
A sensitive scoring system for the longitudinal clinical evaluation and prediction of lethal disease outcomes in newborn mice (2019)

Neonatal animal models are increasingly employed in order to unravel age-specific disease mechanisms. Appropriate tools objectifying the clinical condition of murine neonates are lacking. In this study, we tested a scoring system specifically designed for newborn mice that relies on clinical observation and examination. Both, in a neonatal sepsis model and an endotoxic shock model, the scoring results strongly correlated with disease-induced death rates. Full as well as observation-restricted scoring, reliably predicted fatality and the remaining time until death. Clinical scores even proved as more sensitive biomarker than 6 traditionally used plasma cytokine levels in detecting sepsis at an early disease stage. In conclusion, we propose a simple scoring system that detects health impairments of newborn mice in a non-invasive longitudinal and highly sensitive manner. Its usage will help to meet animal welfare requirements and might improve the understanding of neonatal disease mechanisms.
Maximum A Posteriori Estimation Of Radar Cross Section In Sar Images Using The Heavy-Tailed Rayleigh Model (2005)

Publication in the conference proceedings of EUSIPCO, Antalya, Turkey, 2005
The Information Revolution--Culture and Sovereignty--A Canadian Perspective (1998)

This session is unusual in at least two respects: it is a rematch from 1997, and it is your entertainment for today.We are going to do it in a debate/drama style.You have heard of the "Thrilla from Manila," and there was the "Rumble in the Jungle."Well, this is the "Clash in Cleveland on Culture."Belligerence in the United States on this subject seems to be rather popular these days.I noticed in the newspaper a couple of days ago that Dick Cunningham's former partner, Charlene Barshefsky, the United States Trade Representative (USTR), has gotten on the belligerency bandwagon.She characterized the United States as a seven trillion-pound gorilla in terms of some current trade negotiations.The idea was that, if someone wanted to negotiate with the United States, they are like a seven-trillion-pound gorilla.I do not think a gorilla that big could run very fast in the hundred-yard dash.Anyway, I hope Charlene will back off from that sort of posture, but it did get quite a bit of coverage in the Canadian press.I am both a free trader and a cultural protectionist, and that dichotomy is very hard for our American colleagues to understand.Kim Campbell, the Consul General of Canada, is similarly bifurcated.She is a former Prime Minister of Canada.In an address to the U.S. film industry out at a university in southern California, she made that apology (or boast, depending on your point of view) and said she used to try to apologize to Bill Clinton.He did not understand her
RNAse A‐like enzymes in serum inhibit the anti‐neoplastic activity of siRNA targeting polo‐like kinase 1 (2007)

Down-modulation of target molecules in tumor cells by small interfering (si) RNAs is a promising anti-cancer strategy. A major challenge of this approach is the loss of silencing activity of the siRNAs in vivo. Our study aimed at investigating the influence of the serum compartment on the anti-tumor activity of siRNA directed against Polo-like kinase 1 (Plk1), a mitosis-associated serine/threonine kinase. The data showed that siRNA-induced suppression of Plk1 expression effectively reduced the viable cell mass and increased apoptosis in several cancer cell lines. Preincubation of the siRNA in human serum led to shortening of the siRNA as well as loss of its Plk1 silencing and anti-tumor activity. This loss of activity was prevented by inhibition of RNAse A-like enzymes. These data indicate that the anti-neoplastic effect of siRNAs declines upon incubation in human serum. This loss of anti-neoplastic activity can be prevented by inhibition of their degradation by RNAse A-like enzymes. This may have important implications for the development of a human therapeutic application of siRNAs.
Cascade attitude observer for the SLAM filtering problem (2017)

This article presents an attitude observer that exploits both bearing and range measurements from landmarks, in addition to reference vectors such as magnetometer and accelerometer. It is a gyro bias observer in cascade with a simplified complementary filter, driven by a gyro measurement, in which the gyro bias is estimated by comparing the bearing dynamics with the gyro measurements. The observer is compared to a full complimentary filter, and it is shown that it is more robust to initial gyro bias estimation error compared to the complimentary filter. The article also reveals how this new observer handles magnetometer failure and can use landmarks as reference vectors.
Satellite communication protocols-a performance comparison considering on-board processing (2003)

A comparison is made of error control techniques for digital satellite communication by both analytical methods and simulations. Throughput and delays are studied as functions of the satellite channel bit error rate. Advantages of onboard processing (OBP) offered by future satellite systems are taken into consideration. It is shown that performance of link layer protocols on satellite links can be improved significantly applying OBP. Furthermore, the flexibility of OBP satellites allows protocols, transmission rates, and transmission power to be chosen separately on uplink and downlink, so that the specific conditions can be taken into account.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Darzens Reactions with Quinonoid Systems. Spiro Oxirane‐2,2′‐Chrysenes from Chrysenequinone, and Chryso‐oxazoles from Chrysenequinone Imine or Chrysenequinone Monoxime (1978)

Darzensreaktion mit chinoiden Systemen. Darstellung von Spirooxiran‐2,2′‐chrysenen aus Chrysenchinonen und Chrysooxazolen aus Chrysenchinoniminen oder Chrysenchinon‐monoximen Chrysenchinone reagieren mit substituierten Benzol‐ und Phenacylhalogeniden in Gegenwart von Basen zu Derivaten des Spiro‐oxiran‐2,2′‐chrysens oder einer Methylendioxyverbindung, Chrysenchinonimin und ‐monoxim geben unter analogen Bedingungen Chrysooxazole.
Glucose- and lipid-metabolism of long-term risperidone mono therapy in patients with schizophrenia: RISMO study (2005)

Murashita, Mari; Inoue, Takeshi; Kusumi, Ichiro; Nakagawa, Shin; Itoh, Kouichi; Tanaka, Teruaki; Izumi, Tuyoshi; Hosoda, Hiroshi; Kangawa, Kenji; Koyamam, Tsukasa Author Information
Adult-Onset Ligneous Conjunctivitis with Detection of a Novel Plasminogen Gene Mutation and Anti-Plasminogen IgA Antibody: A Clinicopathologic Study and Review of Literature (2015)

A novel plasminogen gene mutation, deficiency of plasminogen antigen and activity, and anti-plasminogen IgG and IgA antibodies were identified in a patient with adult-onset ligneous conjunctivitis. Sixty percent FFP maintained this patient disease-free for over five years.
STATAWAARS: a promoter motif associated with spatial expression in the major effector-producing tissues of the plant-parasitic nematode Bursaphelenchus xylophilus (2018)

Following publication of the original article [1], the authors reported that one of the authors' names was erroneously changed during proofing and published incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.
Generating Timelines by Modeling Semantic Change (2019)

Though languages can evolve slowly, they can also react strongly to dramatic world events. By studying the connection between words and events, it is possible to identify which events change our vocabulary and in what way. In this work, we tackle the task of creating timelines-records of historical 'turning points', represented by either words or events, to understand the dynamics of a target word. Our approach identifies these points by leveraging both static and time-varying word embeddings to measure the influence of words and events. In addition to quantifying changes, we show how our technique can help isolate semantic changes. Our qualitative and quantitative evaluations show that we are able to capture this semantic change and event influence.
Anionic Conjugated Polyelectrolytes for FRET‐based Imaging of Cellular Membrane Potential (2020)

We report a Förster resonance energy transfer (FRET)-based imaging ensemble for the visualization of membrane potential in living cells. A water-soluble poly(fluorene-cophenylene) conjugated polyelectrolyte (FsPFc10) serves as a FRET donor to a voltage-sensitive dye acceptor (FluoVolt<sup>™</sup> ). We observe FRET between FsPFc10 and FluoVolt<sup>™</sup> , where the enhancement in FRET-sensitized emission from FluoVolt<sup>™</sup> is measured at various donor/acceptor ratios. At a donor/acceptor ratio of 1, the excitation of FluoVolt<sup>™</sup> in a FRET configuration results in a three-fold enhancement in its fluorescence emission (compared to when it is excited directly). FsPFc10 efficiently labels the plasma membrane of HEK 293T/17 cells and remains resident with minimal cellular internalization for ~ 1.5 h. The successful plasma membrane-associated colabeling of the cells with the FsPFc10-FluoVolt<sup>™</sup> donor-acceptor pair is confirmed by dual-channel confocal imaging. Importantly, cells labeled with FsPFc10 show excellent cellular viability with no adverse effect on cell membrane depolarization. During depolarization of membrane potential, HEK 293T/17 cells labeled with the donor-acceptor FRET pair exhibit a greater fluorescence response in FluoVolt<sup>™</sup> emission relative to when FluoVolt<sup>™</sup> is used as the sole imaging probe. These results demonstrate the conjugated polyelectrolyte to be a new class of membrane labeling fluorophore for use in voltage sensing schemes.
CHML suppresses cell growth and induces apoptosis in multiple human tumor lines. (2000)

In the present study, we have investigated the effect of cytotropic heterogeneous molecular lipid (CHML), a new anticancer agent, on growth suppression in a variety of human tumor cell lines. At a non-toxic concentration (a range from 25 micrograms/ml to 100 micrograms/ml), CHML has shown to strongly inhibit tumor cell growth by using a typical colony survival assay. At a treatment of concentration of 50 micrograms/ml for 6 hours, CHML is able to suppress 50% of the tumor cell colony formation. At a concentration of 100 micrograms/ml (the therapeutic dosage in the clinical trial), more than 90% of the cells were killed in human breast carcinoma MCF-7, colorectal carcinoma RKO, kidney carcinoma G410, lung carcinoma and human myeloid leukemia ML-1 lines. In contrast, growth suppression of non-cancerous human skin fibroblasts by CHML was observed much less than that seen in tumor lines. These results indicate that CHML is an efficient inhibiting agent in tumor cell growth and is able to generate greater suppression in tumor cells than in noncancerous cells. With the use of DNA fragmentation assay, CHML was found to induce apoptosis in MCF-7, ML-1, H1299 and RKO lines after treatment at a concentration of 75 micrograms/ml for 8 hours. Following the CHML treatment, the tumor suppressor p53 protein elevated in RKO cells at 2 h posttreatment. The induction of p53 reached a peak at 4 hr and returned to normal level 16 hr later. Consistent with this result, Bax, which is regulated by p53 and is able to promote apoptosis, was also found to increase in a same kinetic manner as p53. These results suggest that the p53-pathway is activated by CHML and the activation of p53 may contribute to CHML-induced apoptosis in some tumor cells, such as MCF-7, RKO and ML-1. Considering that CHML is able to induce apoptosis in H1299 cells, which are of p53-negative status, it is speculated that CHML induces programmed cell death through both the p53-dependent and- independent pathways.