gebhart/patrepeval huggingface dataset:
A Clinicopathologic Study of Malignancy in VCP-Associated Multisystem Proteinopathy (2021)

Abstract Background Valosin containing protein (VCP) is an important protein with many vital functions mostly related to the ubiquitin-proteasome system that provides protein quality control. VCP-associated inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD), also termed VCP disease and multisystem proteinopathy (MSP 1), is an autosomal dominant disorder caused by variants in the VCP gene on human chromosome 9. VCP has also been strongly involved in cancer, with over-activity of VCP found in several cancers such as prostate, pancreatic, endometrial, esophageal cancers and osteosarcoma. Since MSP1 is caused by gain of function variants in the VCP gene, our hypothesis is that we would find an increased tendency of developing malignancies amongst our patients. Results Upon surveying 106 families with confirmed VCP variants, we found increased incidence of unusual tumors including malignant peripheral nerve sheath tumor, anaplastic pleomorphic xanthoastrocytoma and thymoma. Some of these cases developed cancer before displaying other classic VCP disease manifestations. We also present cases of common cancers; however, we did not find an increased incidence compared to the general population. This could be related to the early mortality associated with this disease. Conclusion This is the first study that expands the phenotype of VCP disease to potentially include unusual cancers and highlights the importance of further investigation of the role of VCP in cancer development. The results of this study in VCP disease patients suggests that patients may be at an increased risk for unusual tumors.
NaOH Treatment to Neutralize Inhibitors of Taq Polymerase (1999)

The introduction of polymerase chain reaction (PCR) into the forensic field has greatly extended the ability to analyze DNA from small or degraded samples. However, one significant problem with PCR analysis is the sensitivity of Taq Polymerase to inhibitors found in many substrates commonly encountered with evidentiary materials. We hypothesize that the most problematic of these compounds intercalate into double stranded DNA (dsDNA) and have significantly less affinity for single stranded DNA (ssDNA). This study presents a comprehensive analysis of a novel method for the neutralization of Taq inhibitors by denaturation and washing with NaOH in Microcon-100 filtration units. The data show that DNA recovered following NaOH repurification routinely amplifies when other inhibitor neutralization techniques are unsuccessful. Genetic profiles have been obtained with both AmpliType PM + DQA1 and D1S80 systems. However, the NaOH protocol is not advised when the quantity of DNA is limited since the treatment results in significant loss of DNA.
ChemInform Abstract: An Efficient Synthesis of 1,2,6,7‐Tetrahydro‐8H‐indeno[5,4‐b]furan‐8‐one. (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.
Nonlinear absorption of terahertz radiation due to light impact ionization. (2005)

A nonlinear increase in free carrier absorption in InSb bulk samples with rising intensity of terahertz radiation has been observed. It is shown that the effect is caused by a generation of electron-hole pairs at intense excitation with photon energies several factors of ten smaller than the energy gap. The experimental results give strong evidence that the increase of carrier density is caused by light impact ionization in the radiation field. In contrast to well known impact ionization in static or low frequency fields, when the frequency of the electric field is less than the reciprocal relaxation time of free carriers and ionization is due to the acceleration of electrons in one half period, at terahertz frequencies the opposite limit is achieved and carriers acquire high energies entirely because of collisions. Nonlinear transmission and photoconductive response has been observed in n- and p-type InSb with carrier density in the range of 10$^{13}$ cm$^{-3 }$to 10$^{16}$ cm$^{-3}$ applying 40 ns pulses at wavelengths 90.5 $\\mu $m, 152 $\\mu $m and 250 $\\mu $m with a maximum radiation intensity of 3 MW/cm$^{2}$.
Blebbistain, a Myosin II Inhibitor, as a Novel Strategy to Regulate Detrusor Contractility in a Rat Model of Partial Bladder Outlet Obstruction (2011)

Partial bladder outlet obstruction (PBOO), a common urologic pathology mostly caused by benign prostatic hyperplasia, can coexist in 40-45% of patients with overactive bladder (OAB) and is associated with detrusor overactivity (DO). PBOO that induces DO results in alteration in bladder myosin II type and isoform composition. Blebbistatin (BLEB) is a myosin II inhibitor we recently demonstrated potently relaxed normal detrusor smooth muscle (SM) and reports suggest varied BLEB efficacy for different SM myosin (SMM) isoforms and/or SMM vs nonmuscle myosin (NMM). We hypothesize BLEB inhibition of myosin II as a novel contraction protein targeted strategy to regulate DO. Using a surgically-induced male rat PBOO model, organ bath contractility, competitive and Real-Time-RT-PCR were performed. It was found that obstructed-bladder weight significantly increased 2.74-fold while in vitro contractility of detrusor to various stimuli was impaired ∼50% along with decreased shortening velocity. Obstruction also altered detrusor spontaneous activities with significantly increased amplitude but depressed frequency. PBOO switched bladder from a phasic-type to a more tonic-type SM. Expression of 5' myosin heavy chain (MHC) alternatively spliced isoform SM-A (associated with tonic-type SM) increased 3-fold while 3' MHC SM1 and essential light chain isoform MLC(17b) also exhibited increased relative expression. Total SMMHC expression was decreased by 25% while the expression of NMM IIB (SMemb) was greatly increased by 4.5-fold. BLEB was found to completely relax detrusor strips from both sham-operated and PBOO rats pre-contracted with KCl, carbachol or electrical field stimulation although sensitivity was slightly decreased (20%) only at lower doses for PBOO. Thus we provide the first thorough characterization of the response of rat bladder myosin to PBOO and demonstrate complete BLEB-induced PBOO bladder SM relaxation. Furthermore, the present study provides valuable evidence that BLEB may be a novel type of potential therapeutic agent for regulation of myogenic and nerve-evoked DO in OAB.
Lupus Anticoagulant Activity Is Frequently Dependent on the Presence of β2-Glycoprotein I (1992)

Summary Antiphospholipid antibodies (aPL) are defined by anticardioli-pin antibody (aCL) ELISA and prolongation of phospholipid dependent coagulation assays (lupus anticoagulant; LAC). For the binding of aCL to cardiolipin a cofactor, β2-glycoprotein I (β2-GPI), is necessary. We have investigated whether the same cofactor is essential for LAC activity. Plasma from 6 LAC positive patients and 3 controls was depleted from β2-GPI by means of affinity chromatography. From the 6 LAC positive plasmas, 4 became LAC negative (tested with dRWT) when β2-GPI was depleted and became positive again when purified β2-GPI (200 μg/ml) was added. A dose response curve showed that addition of 50 μg/ml β2-GPI to β2-GPI deficient patient plasma, led to a positive dRWT. Depletion of, and addition of β2-GPI to plasma from controls had no effect on the dRWT. Measurement of β2-GPI plasma levels in 19 LAC positive patients, 40 LAC negative patients and 15 controls showed no difference in β2-GPI levels. These results show that a combination of aPL and β2-GPI is essential not only for binding to cardiolipin, but also for LAC activity and imply that low β2-GPI levels (&lt;50 μg/ml) can lead to false negative LAC tests. These observations may lead to new insights in the pathophysiological complications associated with aPL.
Nonracemic α-Allenyl Carbinols from Asymmetric Propargylation with the 10-Trimethylsilyl-9-borabicyclo[3.3.2]decanes (2005)

[reaction: see text] The asymmetric propargylboration of aldehydes at -78 degrees C in <3 h with 1 provides silylated alpha-allenyl carbinols 6 (60-87%) in high ee (94% to >98% ee). The reagents 1 are easily prepared in both enantiomeric forms with a simple Grignard procedure and air-stable borinate complexes 2. The ozonolysis of 6 proceeds smoothly through an acylsilane intermediate to give a TMS ester, which is hydrolyzed to the alpha-hydroxy acid quantitatively with water.
Variation Among Processors Under Turbo Boost in HPC Systems (2016)

The design and manufacture of present-day CPUs causes inherent variation in supercomputer architectures such as variation in power and temperature of the chips. The variation also manifests itself as frequency differences among processors under Turbo Boost dynamic overclocking. This variation can lead to unpredictable and suboptimal performance in tightly coupled HPC applications. In this study, we use compute-intensive kernels and applications to analyze the variation among processors in four top supercomputers: Edison, Cab, Stampede, and Blue Waters. We observe that there is an execution time difference of up to 16% among processors on the Turbo Boost-enabled supercomputers: Edison, Cab, Stampede. There is less than 1% variation on Blue Waters, which does not have a dynamic overclocking feature. We analyze measurements from temperature and power instrumentation and find that intrinsic differences in the chips' power efficiency is the culprit behind the frequency variation. Moreover, we analyze potential solutions such as disabling Turbo Boost, leaving idle cores and replacing slow chips to mitigate the variation. We also propose a speed-aware dynamic task redistribution (load balancing) algorithm to reduce the negative effects of performance variation. Our speed-aware load balancing algorithm improves the performance up to 18% compared to no load balancing performance and 6% better than the non-speed aware counterpart.
Isolated PFC Pre-Regulator for LED Lamps (2008)

The efficiency and lifetime of light-emitting-diode (LED) lamps are approaching and exceeding that of fluorescent lamps. LED light sources are finding more applications than conventional light bulbs due to their compactness, lower heat dissipation, real-time color changing capability and most importantly, long life which is much longer life than that of conventional offline power converters. Conventional power converters normally use high voltage electrolytic capacitors as energy storage element which could have the shortest lifetime when compared to other components of the LED lighting system. In this paper, a new isolated PFC power pre-regulator is proposed. The pre-regulator allows the charge storage capacitor to be positioned on the secondary side of the isolation transformer. Longer lifetime low voltage and high capacitance value capacitors can therefore be used to extend the overall lifetime of the LED lighting system. Steady-state state-space averaging analysis is preformed for designing the converter. A prototype converter is built to verify performance of the proposed PFC LED preregulator.
H+ Transport by K+ EXCHANGE ANTIPORTER3 Promotes Photosynthesis and Growth in Chloroplast ATP Synthase Mutants (2020)

The composition of the thylakoid proton motive force (pmf) is regulated by thylakoid ion transport. Passive ion channels in the thylakoid membrane dissipate the membrane potential (Δψ) component to allow for a higher fraction of pmf stored as a proton concentration gradient (ΔpH). K<sup>+</sup>/H<sup>+</sup> antiport across the thylakoid membrane via K+ EXCHANGE ANTIPORTER3 (KEA3) instead reduces the ΔpH fraction of the pmf. Thereby, KEA3 decreases nonphotochemical quenching (NPQ), thus allowing for higher light use efficiency, which is particularly important during transitions from high to low light. Here, we show that in the background of the Arabidopsis (<i>Arabidopsis thaliana</i>) chloroplast (cp)ATP synthase assembly mutant <i>cgl160</i>, with decreased cpATP synthase activity and increased pmf amplitude, KEA3 plays an important role for photosynthesis and plant growth under steady-state conditions. By comparing <i>cgl160</i> single with <i>cgl160 kea3</i> double mutants, we demonstrate that in the <i>cgl160</i> background loss of KEA3 causes a strong growth penalty. This is due to a reduced photosynthetic capacity of <i>cgl160 kea3</i> mutants, as these plants have a lower lumenal pH than <i>cgl160</i> mutants, and thus show substantially increased pH-dependent NPQ and decreased electron transport through the cytochrome <i>b</i> <sub><i>6</i></sub> <i>f</i> complex. Overexpression of <i>KEA3</i> in the <i>cgl160</i> background reduces pH-dependent NPQ and increases photosystem II efficiency. Taken together, our data provide evidence that under conditions where cpATP synthase activity is low, a KEA3-dependent reduction of ΔpH benefits photosynthesis and growth.
Supplementary figure legend from Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats (2023)

&lt;p&gt;Supplementary figure legend&lt;/p&gt;
Flow Enhancement and Cavitation Suppression in Nozzle Flow by Viscoelastic Additives (2018)

Numerical simulations of turbulent cavitating nozzle flow of Phan-Thien-Tanner and Newtonian fluids are compared to study the effect of viscoelastic additives on cavitation dynamics. The results show that viscoelasticity can stabilize the flow-field and reduce turbulence and vorticity inside the nozzle. Subsequently small scale vortices are suppressed and larger eddies become dominant in the flowfield. Vapor formation in the core of Kelvin-Helmholtz vortices in the shear layer is delayed and overall vapor volume fraction inside the nozzle is reduced by viscoelasticity. Therefore, the density of the two-phase flow passing through the nozzle is higher and the pressure drop across the nozzle is reduced. Hence flow resistance due to turbulence and cavitation inside the nozzle is reduced and the mass flow rate is enhanced.
Supplementary material from "Stress hormones predict a host superspreader phenotype in the West Nile virus system" (2017)

Glucocorticoid stress hormones, such as corticosterone (CORT), have profound effects on the behaviour and physiology of organisms and thus have the potential to alter host competence and the contributions of individuals to population and community-level pathogen dynamics. For example, CORT could alter the rate of contacts among hosts, pathogens and vectors through its widespread effects on host metabolism and activity levels. CORT could also affect the intensity and duration of pathogen shedding and risk of host mortality during infection. We experimentally manipulated songbird CORT, asking how CORT affected behavioural and physiological responses to a standardized West Nile virus (WNV) challenge. Although all birds became infected after exposure to the virus, only birds with elevated CORT had viral loads at or above the infectious threshold. Moreover, though the rate of mortality was faster in birds with elevated CORT compared to controls, most hosts with elevated CORT survived past the day of peak infectiousness. CORT concentrations just prior to inoculation with WNV and anti-inflammatory cytokine concentrations following viral exposure were predictive of individual duration of infectiousness and the ability to maintain physical performance during infection (i.e. tolerance), revealing putative biomarkers of competence. Collectively, our results suggest that glucocorticoid stress hormones could directly and indirectly mediate the spread of pathogens.
858. Mechanism of adsorption of cationic dyes by alumina, and a note on heat changes in solution adsorption (1964)

C. H. Giles, I. A. Easton and R. B. McKay, J. Chem. Soc., 1964, 4495 DOI: 10.1039/JR9640004495
Design and evaluation of small peptides mapping the exposed surface of IL‐8 (1996)

In an effort to determine which regions of IL-8 are involved in interactions with its receptors, eight peptides were designed to correspond to distinct exposed regions of the IL-8 monomer, using the proton NMR-derived structure of the dimer as a basis. The peptides were evaluated singularly, and as equimolar mixtures of two to six peptides, in an IL-8 receptor binding assay and found to have no binding interaction with either alpha or beta IL-8 receptor as single peptides or mixtures of two peptides. In contrast, one of these peptides having the sequence AVLPRSAKEL, which corresponds to the N-terminal 10 amino acid residues of the 77 amino acid form of IL-8, exhibited potent chemotactic activity in human neutrophils. These results indicate that there is no contiguous ligand that can be designed based on the NMR and X-ray determined structure of IL-8 and that there may be multiple receptors responsible for neutrophil activation and chemotaxis.
Effect of age on human neutrophil function (2000)

Neutrophil phagocytosis, reactive oxygen intermediate production (intra- and extracellular), neutrophil bactericidal activity, and chemotaxis/chemokinesis were assessed in three age groups: 21-36, 38-56, and 62-83 years. A significant age-dependent reduction in the number of phagocytized Escherichia coli per neutrophil (measured by acridine orange staining) and Staphylococcus aureus phagocytosis (measured by flow cytometry) was seen (r = 0.669 and r = 0.684, P<0.001 for both). These findings correlated with an age-dependent increase in intracellular calcium concentrations in resting neutrophils (r = 0.698, P<0.001) and a reduced hexose uptake (r = 0.591, P<0.01). In addition, a significant reduction in the intracellular reactive oxygen production was seen after stimulation with S. aureus (P<0.001) with increasing age. In contrast, no differences between the groups in reactive oxygen production was seen after stimulation with E. coli. The neutrophil bactericidal activity was impaired with increasing age (64+/-4% of the phagocytized bacteria were killed in group 1; 66+/-2 in group 2, and 59+/-6 in group 3; P<0.01). In addition, a trend toward a reduced neutrophil chemotaxis was seen with increasing age (P = 0.022). The findings suggest that increased intracellular calcium concentrations in resting neutrophils and/or a reduced hexose uptake result in reduced phagocytic ability and decreased bactericidal activity of neutrophils in the elderly.
Degarelix versus LHRH agonists: Differential skeletal and urinary tract outcomes from an analysis of six comparative randomized clinical trials. (2013)

68 Background: The use of ADT in men with prostate cancer is well established. GnRH antagonists have a mode of action distinct to that of LHRH agonists and comparative trials have shown differences in efficacy and safety between these agents. Adverse events (AE) from the musculoskeletal and renal and urinary systems have now been analysed. Methods: Results were pooled from 6 prospective, comparative randomised trials (n=2328). Most patients (pts) received 1 year of degarelix or LHRH agonist treatment (n=1686); the remaining men had 3–7 months’ treatment (n=642). AEs were analysed using Kaplan Meier plots and a log-rank test for homogeneity on relevant groups of MedDRA terms. Results: Treatment groups (degarelix, n=1491; LHRH agonist, n=837) were balanced for baseline characteristics such as age, testosterone, PSA and disease stage. In men with metastatic disease alkaline phosphatase (ALP) was reduced to a greater extent with degarelix (p=0.0373) throughout the year. Overall probability of fracture (&lt;1% vs. 2%, p=0.0411) and incidence of joint related AEs (4% vs. 6%, p=0.0116) were significantly lower for degarelix-treated men. Incidence of muscle or bone pain was lower for degarelix (9% vs. 12%, p=0.0822). Incidence of urinary infections (UI) was reduced (5% vs. 8% with agonists) and time to first UI was significantly increased (p=0.0010) with degarelix. Overall probability of any renal or urinary tract AEs, including lower urinary tract symptoms (LUTS), was significantly lower in pts receiving degarelix (p&lt;0.0001). Consistent with fewer skeletal and urinary tract AEs indicating better disease control, men with baseline PSA &gt;50 ng/mL had significantly higher PSA PFS compared to agonist treated pts. OS during 1 year of treatment was significantly higher for degarelix pts (98.3% vs. 96.7%, p=0.0329). Conclusions: This analysis of 2,328 men shows degarelix-treated men had lower ALP, significantly fewer fractures, a lower incidence of urinary tract symptoms and higher overall survival than pts receiving an LHRH agonist over one year. Control of such disease symptoms is consistent with previous data on a significantly lower risk of PSA PFS during the first year of treatment.
Phosphorylation of Aminoheterocycles and Phosphorotropic Tautomerism (1990)

Abstract The reaction of phosphorylation of aminoheterocycles [aminodihydro(iminotetrahydro)-1,3-thiazines, amino(imino)-thiasoli (di)nes, amino (imino)pirroli (di) nes, isoindol (en)- ines] has been studied by means of NMR 1H, 13C, 31P spectroscopy. The processes of intra- and intermolecular migrations of the phosphoryl groups PIV between endo- and exo-cyclic nitrogens have been detected and examined.
Neutral Polymeric Micelles for RNA Delivery (2013)

RNA interference (RNAi) drugs have significant therapeutic potential, but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-(pyridin-2-yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions and a second ampholytic block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization with an overall molecular weight of 22 000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL, respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90% mRNA knockdown and 65% protein knockdown at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates demonstrate the potential utility of this carrier design for delivering therapeutic siRNA drugs.