gebhart/patrepeval huggingface dataset:
Use of a human ribonuclease variant, QBI-139, for the treatment of cancer. (2010)

TPS162 Background: A phase I trial has been initiated for QBI-139, a variant of the human pancreatic ribonuclease 1, which shares 95% sequence identity with the native protein. Unlike the native protein, the drug QBI-139 is able to evade the ribonuclease inhibitor protein found in the cytosol, allowing the ribonuclease to be active when the enzyme enters cancer cells. Treatment of cancer cells with QBI-139 results in apoptosis. QBI- 139 has shown efficacy in models of a variety of cancers, including colorectal, non-small cell lung, ovarian, pancreatic, and prostate cancers. A critical next step for QBI-139 is to identify indications for the next stage of clinical development given the agent's broad efficacy in model systems. Methods: Due to the range of activity, the phase I trial was designed for patients with advanced solid tumors. Patients receive QBI- 139 by intravenous infusion once weekly for three weeks with treatment repeating every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of three to six patients receive escalating doses of QBI-139 until the maximum tolerated dose (MTD) is determined. The trial is expected to enroll approximately 30 patients, with about half of the patients currently enrolled (January 2010). The primary outcomes of the trial are to evaluate the toxicity and tolerability of and the maximum tolerated dose for QBI-139 in patients with advanced refractory solid tumors. In addition, patient response to QBI- 139 will be measured using the RECIST criteria and the pharmacokinetics of QBI-139 will be evaluated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Quintessence Biosciences, Inc. Quintessence Biosciences, Inc. Quintessence Biosciences, Inc.
The impact of telomere shortening on human hippocampal neurogenesis: Implications for cognitive function and psychiatric disorder risk (2020)

Abstract Telomere shortening is one hallmark of cell ageing that can limit the proliferative capacity of cell populations and increase risk for age-related disease. It has been hypothesized that short telomeres, and subsequently a limited proliferative capacity of hippocampal progenitor cells, could contribute to smaller hippocampal volumes and impaired cognition, amongst psychiatric disorder patients. The current study employed a systematic, multidisciplinary approach which aimed to model the effects of telomere shortening on human hippocampal neurogenesis, and to explore its relationship with cognition and psychiatric disorder risk. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. Aged progenitors demonstrated shorter telomeres (p&lt;0.05), and reduced rates of cell proliferation, as marked by bromodeoxyuridine staining (p&lt;0.001), with no changes in the ability of cells to differentiate into neurons or glia. RNA-sequencing and gene set enrichment analysis revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Downregulated transcripts showed a significant overlap with genes regulating cognitive function and risk for schizophrenia and bipolar disorder. Collectively, our results suggest that reductions in adult hippocampal neurogenesis, caused by telomere shortening, could represent a cellular mechanism contributing to age-related cognitive impairment and psychiatric disorder risk.
Algal biomass pretreatment in Seawater Reverse Osmosis. (2017)

Harmful algal blooms (HABs) can result in a substantial increase in the organic and solids load in the seawater feed to be treated at a desalination plant. In this chapter, the removal of this material is addressed in the context of the multi-barrier treatment process for seawater reverse osmosis (SWRO) as presented in Chapter 8 on risk management for HAB events. While this chapter covers removal of non-toxic material, Chapter 10 builds upon these principles and discusses the mechanisms and effectiveness for each barrier with respect to toxin removal. This chapter covers only the main barriers used in the SWRO desalination plants for HAB bloom risk mitigation, though the authors acknowledge that other niche treatment barriers exist in SWRO systems. The treatment processes discussed here are chlorination and dechlorination, dissolved air flotation (DAF), granular media filtration (GMF), microscreens for microfiltration/ultrafiltration (MF/UF), MF/UF itself, cartridge filtration and SWRO. Coagulation is discussed in general terms and then more specifically for DAF, GMF, and MF/UF pretreatments. Each treatment process is broken down into a discussion of how the process works and then how HAB cells affect the process operation. Importantly, the chapter deals with how upstream actions can detrimentally affect downstream treatment processes with respect to algal blooms. In particular, this chapter discusses removal mechanisms for algal organic matter (AOM) and how operational actions can prevent detrimental effects of AOM. As discussed in Chapter 2, the chemical composition of AOM usually includes proteins, polysaccharides, nucleic acids, lipids, and other dissolved organic substances. AOM compounds typically cover a wide size spectrum, ranging from less than 1 nm to more than 1 mm. Based on their size cut-off, GMF and MF/UF are expected to remove only part of high molecular weight AOM (as shown in Chapter 2, Figure 2.2). SWRO is expected to achieve complete removal of AOM, but will suffer from fouling issues if AOM is not removed upstream
Cyclic AMP-dependent phosphorylation of the actin-binding protein filamin. (1978)

Filamin is a high molecular weight protein that binds to actin filaments in cells. It is found in large amounts in several different cells and tissues, including smooth muscle, fibroblasts, platelets, and macrophages. It is immunologically related to the previously described macrophage high molecular weight actin-binding protein but clearly different from erythrocyte spectrin. Filamin is a phosphoprotein; it is phosphorylated in vivo in intact tissues and cells. It can be phosphorylated in vitro with endogenous kinases; cyclic AMP stimulates this phosohorylation. Furthermore, the purified protein can be phosphorylated by purified cyclic AMP-dependent protein kinase. In smooth muscle homogenates, the stimulation of filamin phosphorylation by cyclic AMP is specific. Cyclic GMP and Ca2+ do not increase its phosphorylation, although they do stimulate phosphorylation of other proteins.
ChemInform Abstract: α,α‐Difluoro Ketone Inhibitors of HMG CoA Reductase. (1989)

Abstract Starting with the (o‐bromomethyl)phenyl ether (IV), the difluoro ketone (VIII) is prepared.
Cardiac Autonomic Modulation by Estrogen in Female Mice Undergoing Ambulatory Monitoring and In Vivo Electrophysiologic Testing (2004)

Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.
Performance improvement of joint THP/pre-FDE with lattice reduction using LLL-algorithm (2008)

Average bit error rate (BER) performance of single-carrier (SC) transmission significantly degrades due to the strong inter-symbol interference (ISI) in a severe frequency-selective fading channel. Recently, we proposed a joint Tomlinson-Harashima precoding (THP)/frequency-domain pre-equalization (pre-FDE) using LQ-decomposition to improve the BER performance of SC transmission. However, since the dummy symbols insertion is necessary, the data rate reduces. In this paper, we apply LLL-algorithm to joint THP/pre-FDE to avoid the dummy symbol insertion and evaluate the BER performance by computer simulation.
Therapeutic Drug Monitoring in Patients with Chronic Renal Failure: Evaluation of the Abbott TDx<sup>TM</sup> Drug Assay System (1986)

Immunoassay techniques have been widely used for therapeutic drug monitoring, but lack of antibody specificity can lead to measurement of erroneous drug concentrations due to cross-reactivity with other drugs, metabolites, or endogenous substances, particularly in patients with excretory organ compromise such as renal dysfunction. The Abbott TDx system, a popular automated immunoassay method for therapeutic drug monitoring, was used to measure apparent serum concentrations of carbamazepine, digoxin, gentamicin, lidocaine, phenobarbital, phenytoin, quinidine, valproic acid, and vancomycin in patients with renal failure who were not receiving these drugs. Endogenous substances and other concomitantly administered drugs did not lead to spuriously elevated drug levels, and a previous report of cross-reactive digoxin-like substances was not confirmed. Pooled plasma samples from the patients were spiked with digoxin or phenytoin, each at two concentrations, and the samples were assayed for the drug concentration using the TDx system. No falsely elevated values were found. This work suggests that the TDx system may be better suited for the measurement of these drugs in patients with renal failure than some other immunoassay methods.
Fluorescence-based single-strand conformation polymorphism analysis of mutations by capillary electrophoresis (2000)

Capillary electrophoresis in combination with fluorescence-based single-strand conformation polymorphism (SSCP) analysis was used to screen for known mutations as well as for unknown mutations. The mutations causing hemochromatosis and thrombogenetic diseases (factor V Leiden mutation and prothrombin mutation) are well defined. Familial hypercholesterolemia is caused by mutations in the low density lipoprotein (LDL) receptor gene. Because the mutations are heterogeneously localized in all 18 exons of the LDL receptor gene, effective screening procedures are necessary. The three well known mutations and 59 of 61 previously characterized mutations in the LDL receptor gene were detected by a distinct abnormal fragment pattern in capillary electrophoresis. The remaining two mutations in the LDL receptor gene showed only slight abnormalities under standard electrophoresis conditions (13 kV, 30°C, 30 min). However, the abnormal pattern could be amplified by increasing the electrophoresis temperature. In all cases, heterozygous and homozygous mutations could clearly be differentiated from wild-type alleles. Because of the high efficiency of mutation detection, capillary electrophoresis in combination with fluorescence-based SSCP analysis would be attractive for the detection of well-defined mutations as well as for the screening of unknown mutations. The accuracy and the degree of automation make this technique well suited for routine genetic diagnosis.
AIM1 promoter hypermethylation as a predictor of decreased risk of recurrence following radical prostatectomy (2011)

Methylation status of AIM1 in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort.
General Approach for the Total Synthesis of the Sarpagine Related Indole Alkaloids (+)‐Na‐Methyl‐16‐epipericyclivine, (‐)‐Alkaloid Q3 and (‐)‐Panarine via the Asymmetric Pictet—Spengler Reaction (2003)

ChemInformVolume 34, Issue 16 Natural Products General Approach for the Total Synthesis of the Sarpagine Related Indole Alkaloids (+)-Na-Methyl-16-epipericyclivine, (-)-Alkaloid Q3 and (-)-Panarine via the Asymmetric Pictet—Spengler Reaction Jianming Yu, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this authorXiangyu Z. Wearing, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this authorJames M. Cook, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this author Jianming Yu, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this authorXiangyu Z. Wearing, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this authorJames M. Cook, Dep. Chem., Univ. Wis., Milwaukee, WI 53201, USASearch for more papers by this author First published: 02 April 2003 https://doi.org/10.1002/chin.200316206Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume34, Issue16April 22, 2003 RelatedInformation
CCDC 285635: Experimental Crystal Structure Determination (2006)

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
ChemInform Abstract: NEWER ASPECTS OF LONGIFOLENE. II. UNIQUE OXIDATIVE DECARBOXYLATION BY LEAD TETRAACETATE TO CYCLOPROPANE‐ FORMATION OF NORLONGICYCLENE FROM LONGIFOLIC ACIDS (1977)

Abstract Bleitetraacetat reagiert mit Longifolsäure und ihrem Epimeren (Ia) und (Ib) über ein Kation zum Norlongicyclen (II).
Tetronic Acid Insecticides and Acaricides Inhibiting Acetyl‐CoA Carboxylase (2012)

This chapter contains sections titled: Introduction History Synthesis Mode of Action Biological Activity Structure-Activity Relationship References
A Verifiable Imputation Analysis for Univariate Time Series and Enabling Package (2020)

This paper proposes a verifiable imputation process and an enabling tool for univariate time series. Common ad-hoc and case-specific imputation are not enough to ensure high quality and effective imputation. We adopt the similar verification logic of supervised learning. We use artificial missing sampling as the test set to estimate a set of imputers' performances and use the estimated performances to select the best imputer. To ensure the correctness of selection, we analyze the impact of various factors on estimation accuracy. Those factors are missing rate, size of artificial missing data and patterns, selected imputers, and noise level. We propose a two-step verifiable imputation process to integrate all of the steps. With this process, we can always leverage the most suitable imputer to achieve a high quality of imputation without tedious and error-prone data cleaning efforts. We implement the tool as a Python package, with many imputers with their unique capabilities and a API. We automate the imputation through a standard process, which returns imputed results and detailed rationales of selection along with quality metrics.
P‐115: Novel PSV‐FLCDs with High Response Speed, High Optical Throughput, and High Contrast Ratio with Small Voltage Shift by Temperature: Application to Field Sequential Full Color LCDs (2007)

Abstract By doping newly synthesized photo‐curable monomers into FLC media and performing an appropriate photo‐curing, we succeeded in fabricating novel Polymer‐stabilized FLCDs exhibiting V shaped switching (PSV‐FLCDs) with τ=100 μs to 200 μs and with a free from the temperature dependence of operating voltage within 3mV/°C in the range from −5°C to 50°C. We also demonstrate a field sequential full color LCD with 4 inch diagonal and 254ppi that is capable of displaying moving images without blurring and break.
Evolution of the Hemagglutinin Protein of the New Pandemic H1N1 Influenza Virus: Maintaining Optimal Receptor Binding by Compensatory Substitutions (2013)

Pandemic influenza A H1N1 (pH1N1) virus emerged in 2009. In the subsequent 4 years, it acquired several genetic changes in its hemagglutinin (HA). Mutations may be expected while virus is adapting to the human host or upon evasion from adaptive immune responses. However, pH1N1 has not displayed any major antigenic changes so far. We examined the effect of the amino acid substitutions found to be most frequently occurring in the pH1N1 HA protein before 1 April 2012 on the receptor-binding properties of the virus by using recombinant soluble HA trimers. Two changes (S186P and S188T) were shown to increase the receptor-binding avidity of HA, whereas two others (A137T and A200T) decreased binding avidity. Construction of an HA protein tree revealed the worldwide emergence of several HA variants during the past few influenza seasons. Strikingly, two major variants harbor combinations of substitutions (S186P/A137T and S188T/A200T, respectively) with opposite individual effects on binding. Stepwise reconstruction of the HA proteins of these variants demonstrated that the mutations that increase receptor-binding avidity are compensated for by the acquisition of subsequent mutations. The combination of these substitutions restored the receptor-binding properties (avidity and specificity) of these HA variants to those of the parental virus. The results strongly suggest that the HA of pH1N1 was already optimally adapted to the human host upon its emergence in April 2009. Moreover, these results are in agreement with a recent model for antigenic drift, in which influenza A virus mutants with high and low receptor-binding avidity alternate.
Enhanced Platelet Force Development Despite Drug-Induced Inhibition of Platelet Aggregation in Patients with Thromboanglitis Obliterans (2002)

Thromboangiitis obliterans (TAO) is a nonatherosclerotic, nonnecrotizing, nonspecific, segmental inflammatory obliterative vasculitis, characterized by decreased flow to the distal extremities and increased risk of amputation. While smoking cessation is viewed as critical to successful treatment, various therapeutic options have been employed. While many treatment regimens seek to diminish platelet function, there are relatively few studies of platelet function in this disease entity and even fewer that have offered evidence of increased platelet activity. The authors report here 2 cases of TAO in which evaluations for hypercoagulable states and of platelet function were performed. Platelet contractile force (PCF) was found to be 82% higher than a normal control in 1 TAO patient and 340% higher than normal in the second patient. This was true despite the fact that platelet aggregations confirmed suppression of aggregation by antiplatelet medications. Elevated PCF has been seen in a variety of conditions, such as coronary artery disease and diabetes mellitus, in which endothelial function is abnormal. Whether high PCF values play a role in the pathogenesis of these diseases or simply serve as markers of enhanced platelet function and/or endothelial dysfunction awaits additional evaluations.
Structural basis for antibody recognition of vulnerable epitopes on Nipah virus F protein (2023)

Nipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G/RBP) and fusion protein (F), facilitate entry into host cells. Due to its vital role, NiV F presents an attractive target for developing vaccines and therapeutics. Several neutralization-sensitive epitopes on the NiV F apex have been described, however the antigenicity of most of the F protein's surface remains uncharacterized. Here, we immunize mice with prefusion-stabilized NiV F and isolate ten monoclonal antibodies that neutralize pseudotyped virus. Cryo-electron microscopy reveals eight neutralization-sensitive epitopes on NiV F, four of which have not previously been described. Novel sites span the lateral and basal faces of NiV F, expanding the known library of vulnerable epitopes. Seven of ten antibodies bind the Hendra virus (HeV) F protein. Multiple sequence alignment suggests that some of these newly identified neutralizing antibodies may also bind F proteins across the Henipavirus genus. This work identifies new epitopes as targets for therapeutics, provides a molecular basis for NiV neutralization, and lays a foundation for development of new cross-reactive antibodies targeting Henipavirus F proteins.
Matlab extensions for the development, testing and verification of real-time DSP software (2005)

The purpose of this paper is to present the required tools for the development, testing and verification of DSP software in Matlab. The paper motivates a DSP Simulator concept that can be combined with the MATLAB executable interface to develop, evaluate and test DSP software within a single environment. Programming guidelines and optimization results are also provided to demonstrate the effectiveness of the intrinsics software development approach.
Thermal Treatment of a Novel Saponin-Cholesterol Nanoparticle Vaccine Adjuvant Named NanoQuil F70 Secures a Uniform Morphology and Size Distribution (2022)

Quil-A and cholesterol can, under certain conditions, form nanoparticles, but the conditions for the formation of a homogeneous population of a particular kind of particles with the same morphology and size have remained elusive. However, a well-defined uniformity, as well as a high degree of batch-to-batch consistency, are prerequisites for adjuvant formulations to be used for practical vaccines. To accomplish the above stated tasks in the present study, we demonstrated that Quil-A and cholesterol form well-defined worm-like stable particles with a mean diameter of around 40 nm by dynamic light scattering (DLS) under carefully controlled thermodynamical conditions with little or no Quil-A degradation. The nanoparticles thus prepared possessed a significantly reduced hemolytic effect in comparison to unformulated free Quil-A. However, when the same conditions were applied to QS-21/cholesterol nanoparticle formation the morphology achieved was coil spring-like particles with a mean diameter of around 70 nm. This discrepancy in particle morphology and size was attributed to the differences in hydrophobicity of the Quil-A, being a heterogenic fraction of acylated as well as deacylated saponins, and the QS-21. With the process optimizations leading to a standardized particle size distribution and nanoparticle morphology presented here, NanoQuil F70 holds the potential as a well-tolerated vaccine adjuvant for veterinary use raising a Th1/Th2 balanced immune response.