gebhart/patrepeval huggingface dataset:
Reduction of common-mode currents in PWM inverter motor drives (1999)

Modern pulsewidth modulation (PWM) inverter motor drives are affected by dangerous common-mode currents due to the high rate of variation of the modulated voltage. An inexpensive alternative to low-pass filters, which are normally used to limit common-mode currents, consists in reducing such currents by using suitable modulation strategies. In this paper, a new approach for designing PWM strategies is presented, which is able to reduce common-mode currents by limiting the amount of variations of the common-mode voltage. The main characteristics of the proposed approach are experimentally evaluated on a standard PWM induction motor drive.
232 ASSESSMENT OF IN VITRO PARAOXONASE 2 ENZYMATIC ACTIVITY: APPLICATIONS TO CARDIOVASCULAR DISEASE. (2006)

<h3></h3> Oxidation of low-density lipoprotein (LDL) plays an integral role in the initiation and progression of atherosclerosis, an underlying cause for cardiovascular diseases. High-density lipoprotein (HDL) is antiatherogenic; HDL-associated proteins, including the paraoxonases (PON), contribute to the protective effects of HDL. The PON gene family consists of three members—<i>PON 1, PON 2</i> and <i>PON3</i>—located on human chromosome 7q21.3-22.1. Biochemical studies have shown that all three PON proteins possess antioxidant properties against LDL in vitro. Although the physiological function and enzymatic substrates for the PON gene products remain unknown, the proteins possess a common enzyme activity: lactonase activity. In contrast to PON1 and PON3, PON2 is not associated with HDL in the circulation but instead remains intracellular. PON2 is ideal to study the mechanism of action of paraoxonases in vitro because it is associated with the plasma membrane fraction of cells. In the present study, we utilized cell culture models to determine whether the enzymatic activities of PON2 and two of its polymorphisms, A148M and C311S, correspond to their predicted roles in cardiovascular disease. Wild-type PON2, PON2 (A148M), and PON2 (C311S) were overexpressed in COS-7 cells using an adenoviral system. The activity of each enzyme was measured in a lactonase assay using 5-HETE lactone as the substrate. The results showed no significant difference in lactonase activity between the wild-type and variant enzymes. Based on these preliminary studies, we conclude that PON2 lactonase activity may not be associated with the predicted epidemiological link between PON2 polymorphisms and cardiovascular disease.
Clinical Validation of Model-based RSA for a Total Knee Prosthesis (2007)

Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
Targeting T Cell Immunometabolism for Cancer Immunotherapy; Understanding the Impact of the Tumor Microenvironment (2014)

The immune system has a key role to play in controlling cancer initiation and progression. T cell activation, which is central to anti-tumor immune responses, coincides with changes in cellular metabolism. Naïve T cells predominantly require an ATP generating metabolic profile, whereas proliferating effector T cells require anabolic metabolic profiles that promote rapid growth and proliferation. Furthermore, specific T cell subsets require distinct energetic and biosynthetic pathways to match their functional requirements. The often hostile tumor microenvironment can affect T cell immune responses by altering the resulting cellular metabolism. Tailoring immune responses by manipulating cellular metabolic pathways may provide an exciting new option for cancer immunotherapy. T cell responses might also be skewed via metabolic manipulation to treat the complications of obesity-associated inflammation, which is a rapidly growing global health problem and a major risk factor for many malignancies. In this review, the diverse metabolic requirements of T cells in anti-tumor immunity are discussed, as well as the profound influence of the tumor microenvironment and the possible avenues for manipulation to enhance anti-tumor immunity.
P.064 FIREFISH Part 1: 1-year results on motor function in infants with Type 1 spinal muscular atrophy (SMA) receiving risdiplam (RG7916) (2019)

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2 , produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.
Overview of Companion Diagnostics (CDx) for Precision Medicine (2019)

Improvement in technical, regulatory, and clinical areas is likely to significantly increase the number of new oncology drugs requiring CDx tests over the next few decades. Immunohistochemistry (IHC) is one of the most frequently used CDx assay formats with Polymerase Chain Reaction (PCR) and ISH-based methods. Because IHC is simple to perform and well established in most hospitals, its simplicity and popularity are the biggest strength for its use as a CDx assay. However, several weaknesses of Sanger sequencing prevent it from being widely used as a CDx assay. Sanger sequencing was the gold standard for most genetic analyses until Next-Generation Sequencing (NGS) became available in 2004. For a multivariate analysis, multiple independent experiments should be done when using Sanger sequencing, whereas only one test is enough for NGS. ISH methods can detect both known and novel fusion types, whereas PCR or targeted NGS methods are likely to miss a novel type of fusion not covered by primers or probes.
Sensors, Controls, and Man-Machine Interface for Advanced Teleoperation (1980)

Some advances have been made in teleoperator technology through the introduction of various sensors, computers, automation, and new man-machine interface devices and techniques for remote manipulator control. The development of dexterous articulated mechanisms, smart sensors, flexible computer controls, intelligent man-machine interfaces, and innovative system designs for advanced teleoperation is, however, far from complete, and poses many interdisciplinary challenges. This article summarizes the state of the art, gives a brief outline of the basic problems, and presents the results of teleoperator research and development at the Jet Propulsion Laboratory.
A model to study local effects of thermal trauma on muscle metabolism. (1983)

To study local effects of burn on muscle in the absence of direct tissue damage, a rat's foot was insulated and one hindlimb was scalded by immersion in 85 degrees C water for 3 sec. Upon recovery, rats exhibited normal locomotion with both hindlimbs in spite of a full-thickness burn from ankle to knee. Thus the effects of the burn were not complicated by disuse atrophy. As in human burns, histological examination of soleus from the burned leg showed it to be morphologically indistinguishable from normal tissue. After 2 or 4 days postburn, the rat was sacrificed and the soleus muscles from the burned and unburned leg were incubated in vitro to measure protein turnover. Muscle from the burned leg demonstrated a maximal increase in protein breakdown 2 days postburn with no change in protein synthesis. At 4 days postburn, protein breakdown remained elevated and synthesis remained unchanged. Since metabolism of contralateral (unburned) muscle was identical to muscle from unburned animals, burn-induced changes must be ascribed to local and not to systemic mediators. Therefore, these experiments demonstrate that local mediators of burn-induced muscle catabolism primarily augment protein breakdown.
Biosynthesis of peptide precursors and protease inhibitors using new constitutive and inducible eukaryotic expression vectors (1990)

A series of expression vectors has been constructed as based on the pML derivative of pBR322. The eukaryotic transcription units employ various promoters followed by polycloning sites for 3-9 commonly used restriction enzymes and are completed by the SV40 polyadenylation sequence. In 4 of the vectors, designed for co-transfection or transient expression studies, only a single transcription unit containing either a constitutive or an inducible promoter was incorporated. The human ubiquitin (UbC) promoter was used as a strong constitutive promoter, while the mouse metallothionein promoter and the promoter of the long terminal repeats of the mouse mammary tumor virus were used as inducible promoters. Another vector contained an additional transcription unit encoding a eukaryotic selection marker, the neomycin resistance encoding gene. The vectors were used in CHO cells and in neuroendocrine CA77 cells to synthesize peptide precursors, protease inhibitors and a protease. It is shown that these vectors are very efficient for the constitutive and inducible expression of nucleotide sequences in both transient and stable transfections of eukaryotic cells.
Fabrication of in-plane aligned a-axis oriented YBa2Cu3O7−x trilayer Josephson junctions (1996)

We have fabricated vertical YBa 2Cu3O7−x/PrBa 2Cu3O7−x/YBa 2Cu3O7−x (YBCO/PBCO/YBCO) Josephson junctions using in-plane aligned a-axis oriented YBCO multilayers on (100) LaSrGaO4(LSGO). The Tc’s of the device electrodes are typically greater than 80 K. Josephson coupling is observed for barrier thickness up to 800 Å. Strong nonlinear I–V characteristics arising from the properties of PBCO are observed for thicker barrier devices. Chip to chip spread in the device characteristics may be intrinsically due to the PBCO barrier.
Interaction of TLR4 and TLR8 in the Innate Immune Response against Mycobacterium Tuberculosis (2021)

The interaction and crosstalk of Toll-like receptors (TLRs) is an established pathway in which the innate immune system recognises and fights pathogens. In a single nucleotide polymorphisms (SNP) analysis of an Indian cohort, we found evidence for both TLR4-399T and TRL8-1A conveying increased susceptibility towards tuberculosis (TB) in an interdependent manner, even though there is no established TLR4 ligand present in <i>Mycobacterium tuberculosis</i> (Mtb), which is the causative pathogen of TB. Docking studies revealed that TLR4 and TLR8 can build a heterodimer, allowing interaction with TLR8 ligands. The conformational change of TLR4-399T might impair this interaction. With immunoprecipitation and mass spectrometry, we precipitated TLR4 with TLR8-targeted antibodies, indicating heterodimerisation. Confocal microscopy confirmed a high co-localisation frequency of TLR4 and TLR8 that further increased upon TLR8 stimulation. The heterodimerisation of TLR4 and TLR8 led to an induction of IL12p40, NF-κB, and IRF3. TLR4-399T in interaction with TLR8 induced an increased NF-κB response as compared to TLR4-399C, which was potentially caused by an alteration of subsequent immunological pathways involving type I IFNs. In summary, we present evidence that the heterodimerisation of TLR4 and TLR8 at the endosome is involved in Mtb recognition via TLR8 ligands, such as microbial RNA, which induces a Th1 response. These findings may lead to novel targets for therapeutic interventions and vaccine development regarding TB.
A rigorous method of moments solution for curved waveguide bends and its applications (2003)

An accurate and computationally efficient method of moments solution, together with a mode-matching technique, for the analysis of curved planar waveguide bends is described. The method is applied to single and cascaded curved bends in rectangular waveguides, quantum waveguides and microstrips. The effect of the orientation of cascaded bends on the transmission properties is examined. The computed results for the scattering parameters converge very rapidly with increasing number of expansion functions and modes used in the method of moments, and mode-matching analysis, respectively. As a rule, only a few expansion terms and modes need to be considered for accurate solutions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
15-micro-m 128 x 128 GaAs/Al(x)Ga(1-x) As Quantum Well Infrared Photodetector Focal Plane Array Camera (1997)

FT-IR and FT-Raman spectra of 1, 3-Bis (hydroxymethyl) benzimidazolin-2-one were recorded and analyzed in the solid phase. The optimized molecular geometry and vibrational wavenumbers have also been calculated in optimized structure by using DFT method. Scaled quantum mechanical force fields have also been used to calculate potential energy distributions in order to make conspicuous vibrational assignments. The red shifting of the O-H stretching wavenumber is due to the formation of O-H···O intermolecular hydrogen bonding. The lowering and splitting of the carbonyl stretching vibrational modes is assigned to the intermolecular association based on C=O···H type hydrogen bonding in the molecule. Chemical interpretation of hyperconjugative interactions was done by natural bond orbital analysis.
Bone Morphogenetic Protein 3 Controls Insulin Gene Expression and Is Down-regulated in INS-1 Cells Inducibly Expressing a Hepatocyte Nuclear Factor 1A–Maturity-onset Diabetes of the Young Mutation (2011)

Inactivating mutations in the transcription factor hepatocyte nuclear factor (HNF) 1A cause HNF1A-maturity-onset diabetes of the young (HNF1A-MODY), the most common monogenic form of diabetes. To examine HNF1A-MODY-induced defects in gene expression, we performed a microarray analysis of the transcriptome of rat INS-1 cells inducibly expressing the common hot spot HNF1A frameshift mutation, Pro291fsinsC-HNF1A. Real-time quantitative PCR (qPCR), Western blotting, immunohistochemistry, reporter assays, and chromatin immunoprecipitation (ChIP) were used to validate alterations in gene expression and to explore biological activities of target genes. Twenty-four hours after induction of the mutant HNF1A protein, we identified a prominent down-regulation of the bone morphogenetic protein 3 gene (Bmp-3) mRNA expression. Reporter assays, qPCR, and Western blot analysis validated these results. In contrast, inducible expression of wild-type HNF1A led to a time-dependent increase in Bmp-3 mRNA and protein levels. Moreover, reduced protein levels of BMP-3 and insulin were detected in islets of transgenic HNF1A-MODY mice. Interestingly, treatment of naïve INS-1 cells or murine organotypic islet cultures with recombinant human BMP-3 potently increased their insulin levels and restored the decrease in SMAD2 phosphorylation and insulin gene expression induced by the HNF1A frameshift mutation. Our study suggests a critical link between HNF1A-MODY-induced alterations in Bmp-3 expression and insulin gene levels in INS-1 cells and indicates that the reduced expression of growth factors involved in tissue differentiation may play an important role in the pathophysiology of HNF1A-MODY.
Progesterone supplementation to lactating dairy cows without a corpus luteum at initiation of the Ovsynch protocol (2015)

The objectives were to determine the effect of progesterone supplementation on fertility responses in lactating dairy cows without corpora lutea (CL) at initiation of the timed artificial insemination (AI) program. Holstein cows from 5 commercial dairy farms were subjected to the Ovsynch-56 protocol (d -10 GnRH, d -3 PGF2α, d -0.7 GnRH, d 0 AI). Ovaries were scanned by ultrasonography on d -10. Within farm, cows without CL were blocked by pen and assigned randomly to remain as nonsupplemented controls (CON; n = 652) or to receive 2 controlled internal drug-release (CIDR) inserts containing 1.38 g of progesterone each from d -10 to -3 (2CIDR; n = 642). Cows with CL were randomly selected within pen and used as positive controls as cows in diestrus at the initiation of the Ovsynch protocol (DIEST; n = 640). Signs of estrus were detected beginning on d -9 based on removal of tail chalk, and cows in estrus received AI on the same day. Blood samples from subsets of cows on d -10, -9, -7, -5, -3, and 0 (n = 109) and on d 6, 13, and 19 (n = 156) were analyzed for progesterone concentrations. Pregnancy was diagnosed on d 32 and 60 after AI. The average progesterone concentration during the timed AI program was lowest for CON, intermediate for 2CIDR, and highest for DIEST (0.92, 2.77, and 4.93 ng/mL, respectively). The proportions of cows that ovulated in response to the first GnRH (63.6, 61.1, and 47.2%, respectively) and that had a new CL on d -3 at PGF2α injection (72.4, 67.9, and 47.4%, respectively) were greater for CON and 2CIDR compared with DIEST, respectively. The diameter of the ovulatory follicle and the proportion of cows that ovulated in response to the second GnRH did not differ among treatments. A greater proportion of CON and 2CIDR cows were detected in estrus at AI compared with DIEST cows (35.8, 39.6, and 30.6%, respectively). Pregnancy per AI was less for CON compared with 2CIDR and DIEST on d 32 (31.3, 42.2, and 38.4%, respectively) and d 60 after AI (28.9, 37.2, and 33.9%, respectively), indicating that progesterone supplementation reestablished fertility in cows lacking a CL similar to that of cows in diestrus at the initiation of the timed AI program. Treatment did not affect pregnancy loss between d 32 and 60 of gestation. Pregnancy from a subset of cows with plasma progesterone concentrations indicated that a minimum concentration of 2.0 ng/mL was needed to optimize fertility. A single ultrasound examination effectively identified a low-fertility cohort of cows based on the absence of CL at the first GnRH injection of the Ovsynch protocol. Supplementation with 2 CIDR inserts increased progesterone in plasma by an additional 1.85 ng/mL compared with CON, resulting in concentrations of 2.77 ng/mL during development of the ovulatory follicle, which restored fertility in dairy cows lacking CL to a level similar to that of cows in diestrus.
High-Impedance Transformer Parameter Determination Method for Limiting Short-Circuit Current of Power System (2019)

High-impedance transformers can reduce short-circuit currents, but they can also cause system stability problem. This paper establishes a BPA simulation model to study the influence of transformer short-circuit impedance on system stability. Through the simulation of three-phase sudden short circuit fault of the system, the influence of different short circuit impedances of high resistance transformer on the dynamic process of the system is studied. It is concluded that the high-impedance transformer has a great influence on the short-circuit current, bus voltage and power angle of the system, revealing the law of short-circuit current, bus voltage and power angle with short-circuit impedance. Through these three criteria, the general method for selecting the short-circuit impedance parameters of the transformer is obtained. In the model established in this paper, when the short-circuit impedance of the transformer is 24%, the short-circuit current can be effectively reduced without seriously degrading the stability of the system. The results of the research in this paper provide important theoretical support for the power system to limit short-circuit current.
Reconstruction of the medial patellofemoral ligament for the treatment of habitual or recurrent dislocation of the patella in children (2003)

We investigated the clinical outcome of a reconstructive procedure of the medial patellofemoral ligament for the treatment of habitual or recurrent dislocation of the patella in four children (6 knees), with a minimum follow-up of four years. The technique involves transfer of the tendon of semitendinosus to the patella using the posterior one-third of the femoral insertion of the medial collateral ligament as a pulley. There was no recurrence of dislocation after surgery. The mean Kujala score at follow-up was 96.3 points. Radiological assessment showed that the congruence angle, the tilt angle and the lateral shift radio were restored to normal. The lateral and medial stress shift ratios and the Insall-Salvati ratio remained abnormal. We conclude that this technique can be recommended for the treatment of habitual or recurrent patellar dislocation in children, although hypermobility and patella alta are not fully corrected.
Solid-Phase Synthesis and Chemical Properties of 2-(2-Amino/hydroxyethyl)-1-aryl-3,4-dihydropyrazino[1, 2-b]indazol-2-iums (2009)

Amino alcohols, diamines, benzenesulfonyl chlorides, and bromoketones were used to prepare polymer-supported 2-(2-(2-(amino/hydroxyl)ethylamino)ethyl)-3-benzoyl-2H-indazoles. Acid-mediated release yielded 2-((amino/hydroxyl)ethyl)-1-aryl-3,4-dihydropyrazino[1,2-b]indazole-2-iums. In neutral pH, iminiums spontaneously cyclized to complex fused heterocycles 3,6,9,10-tetraazatetracyclo[7.7.0.0(2,6).0(11,16)]hexadeca-11,13,15-trienes, 3-oxa-6,9,10-triazatetracyclo[7.7.0.0(2,6).0(11,16)]hexadeca-11,13,15-trienes, and 3,7,10,11-tetraazatetracyclo[8.7.0.0(2,7).0(12,17)]heptadeca-12,14,16-trienes. Transformations were carried out under mild conditions and tolerated diverse substitution patterns.
NMR dynamics investigation of ligand induced changes of main and side chain arginine N‐H's in human phosphomevalonate kinase (2009)

Human phosphomevalonate kinase (PMK) is involved in phosphoryl transfer from mevalonate 5‐phosphate (M5P) to mevalonate 5‐diphosphate. There are 17 arginines in PMK with the most important being R18, which is part of the "Walker A" domain, a highly conserved motif for binding ATP. Other important arginines are R42, R73, R110, and R142, as these are in the binding pocket and are potentially used to stabilize charge of interacting ligands. In order to characterize the effect/importance of these arginines in ligand binding, PMK was overexpressed with selectively labeled 15N‐arginines and monitored by 2D‐NMR. This is the first report of monitoring ligand induced side chain mobility and dynamics by modelfree analysis. Apo‐PMK side chains are relatively mobile (S2= 0.44 ± 0.04) and binding of M5P causes nearly all of the labeled side chains to get more ordered (S2= 0.71 ± 0.05), indicating ligand‐side chain interaction. It's curious that more side chains, than are in the binding site, get less mobile and to assess this we are attempting to assign the side chains to main chain residues that are assigned. We are also investigating arginine dynamics in ATP binding as well as the ternary complex (PMK/ATP/M5P). (AHA 05303072 to D.S.S.)
Early experiences with scientific applications on the IBM Blue Gene/Q supercomputer (2013)

We report early experiences with porting highly complex scientific applications to the IBM Blue Gene®/Q platform. In addition, we report our progress in porting performance analysis tools that are deemed to be key in helping users understand massively parallel, massively threaded applications. Porting proved to be quite a smooth process. Although in this early study we did not use the full array of the novel architectural features, we nevertheless obtained quite satisfactory, though preliminary, performance results. Thus, we can safely anticipate impressive further improvements in overall performance once the full capability of the Blue Gene/Q architecture is exploited.