gebhart/patrepeval huggingface dataset:
Concise Review: Therapeutic Strategies for Parkinson Disease Based on the Modulation of Adult Neurogenesis (2006)

Parkinson disease (PD) is a progressive neurodegenerative disorder affecting millions of people worldwide. To date, treatment strategies are mainly symptomatic and aimed at increasing dopamine levels in the degenerating nigrostriatal system. Hope rests upon the development of effective neurorestorative or neuroregenerative therapies based on gene and stem cell therapy or a combination of both. The results of experimental therapies based on transplanting exogenous dopamine-rich fetal cells or glial cell line-derived neurotrophic factor overexpression into the brain of Parkinson disease patients encourage future cell- and gene-based strategies. The endogenous neural stem cells of the adult brain provide an alternative and attractive cell source for neuroregeneration. Prior to designing endogenous stem cell therapies, the possible impact of PD on adult neuronal stem cell pools and their neurogenic potential must be investigated. We review the experimental data obtained in animal models or based on analysis of patients' brains prior to describing different treatment strategies. Strategies aimed at enhancing neuronal stem cell proliferation and/or differentiation in the striatum or the substantia nigra will have to be compared in animal models and selected prior to clinical studies.
Active feedback receiver with integrated tunable RF channel selectivity, distortion cancelling, 48dB stopband rejection and &#x003E;&#x002B;12dBm wideband IIP3, occupying &#x003C;0.06mm<sup>2</sup> in 65nm CMOS (2012)

The impedance transformation property of passive mixers enables integrated high-Q channel selection at RF with a programmable center frequency through a clock [1,2]. As such, this technique is suitable for addressing both linearity and flexibility requirements in wideband and cognitive radio applications. However, given the typically low resistance level at the RF side of the receiver chain, the RC product necessary for filtering results in large capacitors, and, consequently, large die area that does not scale with technology. In addition, filter rejection at the RF side is limited by the resistance of the switches of the passive mixer. Thus, large switches are typically needed for moderate rejection values (5Ω switches for 16dB rejection [2]), which translates to higher power consumption in the LO buffers. Furthermore, filtering prior to the LNA [1] or eliminating it altogether [3] improves linearity at the expense of noise and switching harmonics being injected directly at the antenna node. Conversely, an LNA first architecture offers an opposite trade-off. This work demonstrates a highly compact design of a direct-conversion receiver with an active feedback frequency translation loop to perform channel selection at the LNA output while simultaneously cancelling its distortion.
Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements. (1991)

We report 31 point mutations in the factor IX gene and explore the relationship between the level of evolutionary conservation of an amino acid and the probability of a mutation causing hemophilia B. From our total sample of 125 hemophiliacs and from those reported by others, we identify 95 independent missense mutations, 94 of which occur at amino acids that are evolutionarily conserved in the available mammalian factor IX sequences. The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease. In contrast, missense mutations in factor IX-specific residues (i.e., those conserved in human, cow, dog, and mouse factor IX but not in the related proteases) are sixfold less likely to cause disease. Missense mutations at nonconserved residues are 33-fold less likely to cause disease. At least three models are compatible with these observations. A comparison of sequence alignments from four and nine species of factor IX and an examination of the missense mutations occurring at CpG residues suggest a model in which most residues fall on opposite ends of a spectrum. In about 40% of residues, virtually any missense mutation in a minority of the residues will cause disease, while virtually no missense mutations will cause disease in most of the remaining residues. Thus, many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant.
Characterization of the Anti–PD-1 Antibody REGN2810 and Its Antitumor Activity in Human PD-1 Knock-In Mice (2017)

Abstract The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of T-cell effector function and tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 and PD-L1 restore the cytotoxic function of tumor antigen-specific T cells, yielding durable objective responses in multiple cancers. This report describes the preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4(S228P) high-affinity anti–PD-1 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2. REGN2810 was characterized in a series of binding, blocking, and functional cell-based assays, and preclinical in vivo studies in mice and monkeys. In cell-based assays, REGN2810 reverses PD-1–dependent attenuation of T-cell receptor signaling in engineered T cells and enhances responses of human primary T cells. To test the in vivo activity of REGN2810, which does not cross-react with murine PD-1, knock-in mice were generated to express a hybrid protein containing the extracellular domain of human PD-1, and transmembrane and intracellular domains of mouse PD-1. In these mice, REGN2810 binds the humanized PD-1 receptor and inhibits growth of MC38 murine tumors. As REGN2810 binds to cynomolgus monkey PD-1 with high affinity, pharmacokinetic and toxicologic assessment of REGN2810 was performed in cynomolgus monkeys. High doses of REGN2810 were well tolerated, without adverse immune-related effects. These preclinical studies validate REGN2810 as a potent and promising candidate for cancer immunotherapy. Mol Cancer Ther; 16(5); 861–70. ©2017 AACR.
Toward securing untrusted storage without public-key operations (2005)

Adding security capabilities to shared, remote and untrusted storage file systems leads to performance degradation that limits their use. Public-key cryptographic primitives, widely used in such file systems, are known to have worse performance than their symmetric key counterparts. In this paper we examine design alternatives that avoid public-key cryptography operations to achieve better performance. We present the trade-offs and limitations that are introduced by these substitutions.
Migraine. (2004)

Extract: Migraine is a very common primary episodic headache disorder characterized by combinations of neurologic, gastrointestinal, and autonomic changes. Diagnosis is based on the headache's characteristics and associated symptoms. The International Headache Society (IHS) diagnostic criteria for headache disorders provide definitions for seven subtypes of migraine. Approximately 28 million Americans have severe, disabling migraine headaches, and 17.6% of American women and 6% of American men had one migraine attack in the previous year. The WHO ranks migraine among the world's most disabling medical illnesses.
Cloning of a Chinese Hamster Ovary (CHO) cDNA Encoding Phosphatidylserine Synthase (PSS) II, Overexpression of Which Suppresses the Phosphatidylserine Biosynthetic Defect of a PSS I-lacking Mutant of CHO-K1 Cells (1997)

Phosphatidylserine (PtdSer) in mammalian cells is synthesized through the exchange of free L-serine for the polar head group (base) of preexisting phospholipid. We previously showed the presence of two different enzymes catalyzing the serine base exchange in Chinese hamster ovary (CHO) cells and isolated the cDNA of one of the enzymes, PtdSer synthase (PSS) I, which also catalyzes the exchange of the base moiety of phospholipid(s) for ethanolamine and choline. In this study, we cloned a CHO cDNA, designated as pssB, which encodes a protein exhibiting 32% amino acid sequence identity with CHO PSS I. Introduction of the pssB cDNA into CHO-K1 cells resulted in striking increases in both the serine and ethanolamine base exchange activities. In contrast to the PSS I cDNA, the pssB cDNA was incapable of increasing the choline base exchange activity. The expression of the pssB gene in Sf9 insect cells also results in striking increases in both serine and ethanolamine base exchange activities. The pssB cDNA was found to transform a PtdSer-auxotrophic PSS I-lacking mutant of CHO-K1 cells to PtdSer prototrophy. The PtdSer content of the resultant transformant grown without exogenous PtdSer for 2 days was 4-fold that of the mutant and similar to that of CHO-K1 cells, indicating that the pssB cDNA complemented the PtdSer biosynthetic defect of the PSS I-lacking mutant. These results suggested that the pssB cDNA encoded the second PtdSer synthase PSS II, which catalyzed the serine and ethanolamine base exchange, but not the choline base exchange.
Utilization of Photon Orbital Angular Momentum in the Low-Frequency Radio Domain (2007)

We show numerically that vector antenna arrays can generate radio beams that exhibit spin and orbital angular momentum characteristics similar to those of helical Laguerre-Gauss laser beams in paraxial optics. For low frequencies (< or = 1 GHz), digital techniques can be used to coherently measure the instantaneous, local field vectors and to manipulate them in software. This enables new types of experiments that go beyond what is possible in optics. It allows information-rich radio astronomy and paves the way for novel wireless communication concepts.
Coevolution Learning: Synergistic Evolution of Learning Agents and Problem Representations (1996)

This paper describes exploratory work inspired by a recent mathematical model of genetic and cultural coevolution. In this work, a simulator implements two independent evolutionary competitions which act simultaneously on a diverse population of learning agents: one competition searches the space of free parameters of the learning agents, and the other searches the space of input representations used to characterize the training data. The simulations interact with each other indirectly, both effecting the fitness (and hence reproductive success) of agents in the population. This framework simultaneously addresses several open problems in machine learning: selection of representation, integration of multiple heterogeneous learning methods into a single system, and the automated selection of learning bias appropriate for a particular problem. Introduction One clear lesson of machine learning research is that problem representation is crucial to the success of all inference methods (see, ...
Wound Healing Properties of Cimetidine in Vitro (1986)

Cimetidine was one of a variety of drugs frequently given to surgical patients perioperatively tested for their effect on gap closure of wounded monolayers of human fascia cells in vitro. Cimetidine-treated cultures closed faster and had greater cell proliferation than controls. Closure of cimetidine-treated cultures occurred at six hours compared to ten hours in controls. Cimetidine concentrations of 1000 micrograms/ml resulted in 13.5 +/- 0.67 (SEM) X 10(4) cells/cm2 at six hours compared to 7.9 +/- 0.48 X 10(4) cells/cm2 in controls (p less than 0.05); the area covered by cells was 6.5 +/- 0.02 mm2 in treated cultures compared to 3.0 +/- 0.01 mm2 in controls (p less than 0.05). It is concluded that cimetidine stimulates fibroblast proliferation in vitro.
Peptide Labeling with Isobaric Tags Yields Higher Identification Rates Using iTRAQ 4-Plex Compared to TMT 6-Plex and iTRAQ 8-Plex on LTQ Orbitrap (2010)

Peptide labeling with isobaric tags has become a popular technique in quantitative shotgun proteomics. Using two different samples viz. a protein mixture and HeLa extracts, we show that three commercially available isobaric tags differ with regard to peptide identification rates: The number of identified proteins and peptides was largest with iTRAQ 4-plex, followed by TMT 6-plex, and smallest with iTRAQ 8-plex. In all experiments, we employed a previously described method where two scans were acquired for each precursor on an LTQ Orbitrap: A CID scan under standard settings for identification, and a HCD scan for quantification. The observed differences in identification rates were similar when data was searched with either Mascot or Sequest. We consider these findings to be the result of a combination of several factors, most notably prominent ions in CID spectra as a consequence of loss of fragments of the label tag from precursor ions. These fragment ions cannot be explained by current search engines and were observed to have a negative impact on peptide scores.
In Planta Mutagenesis Determines the Functional Regions of the Wheat Puroindoline Proteins (2009)

In planta analysis of protein function in a crop plant could lead to improvements in understanding protein structure/function relationships as well as selective agronomic or end product quality improvements. The requirements for successful in planta analysis are a high mutation rate, an efficient screening method, and a trait with high heritability. Two ideal targets for functional analysis are the Puroindoline a and Puroindoline b (Pina and Pinb, respectively) genes, which together compose the wheat (Triticum aestivum L.) Ha locus that controls grain texture and many wheat end-use properties. Puroindolines (PINs) together impart soft texture, and mutations in either PIN result in hard seed texture. Studies of the PINs' mode of action are limited by low allelic variation. To create new Pin alleles and identify critical function-determining regions, Pin point mutations were created in planta via EMS treatment of a soft wheat. Grain hardness of 46 unique PIN missense alleles was then measured using segregating F(2):F(3) populations. The impact of individual missense alleles upon PIN function, as measured by grain hardness, ranged from neutral (74%) to intermediate to function abolishing. The percentage of function-abolishing mutations among mutations occurring in both PINA and PINB was higher for PINB, indicating that PINB is more critical to overall Ha function. This is contrary to expectations in that PINB is not as well conserved as PINA. All function-abolishing mutations resulted from structure-disrupting mutations or from missense mutations occurring near the Tryptophan-rich region. This study demonstrates the feasibility of in planta functional analysis of wheat proteins and that the Tryptophan-rich region is the most important region of both PINA and PINB.
A 0.5-μm CMOS 4.0-Gbit/s serial link transceiver with data recovery using oversampling (1998)

A 4-Gbit/s serial link transceiver is fabricated in a MOSIS 0.5-/spl mu/m HPCMOS process. To achieve the high data rate without speed critical logic on chip, the data are multiplexed when transmitted and immediately demultiplexed when received. This parallelism is achieved by using multiple phases tapped from a PLL using the phase spacing to determine the bit time. Using an 8:1 multiplexer yields 4 Gbits/s, with an on-chip VCO running at 500 MHz. The internal logic runs at 250 MHz. For robust data recovery, the input is sampled at 3/spl times/ the bit rate and uses a digital phase-picking logic to recover the data. The digital phase picking can adjust the sample at the clock rate to allow high tracking bandwidth. With a 3.3-V supply, the chip has a measured bit error rate (BER) of <10/sup -14/.
Role of endogenous interleukin-12 (IL-12) in induced and spontaneous relapses of experimental autoimmune encephalomyelitis in mice. (1999)

Actively induced, chronic relapsing experimental autoimmune encephalomyelitis (CREAE) was studied in SJL/J and in Biozzi ABH mice. In Biozzi ABH mice, relapses occurred spontaneously with high frequency. In SJL/J mice, spontaneous relapses occurred infrequently; however they could be induced reproducibly by reimmunization. In both models, moderately increased levels of serum IL-12(p40) were consistently found shortly before primary attacks, but irregularly at later times. Injections of anti-IL-12 antibody inhibited disease development in both SJL/J and in Biozzi ABH mice. The time window during which treatment needed to be initiated in order to be effective, ranged from before induction until shortly before the symptoms of primary attacks emerged. Such treatment inhibited not only the first attack but also the spontaneous or induced relapses. Most significantly, anti-IL-12 antibody given during remission of primary disease inhibited actively re-induced relapses in SJL/J, but not spontaneous relapses in Biozzi ABH mice. These results indicate that endogenous IL-12 favours EAE development by crucially affecting the active induction process, but that a second burst of IL-12 production may not be necessary for triggering spontaneous relapses.
Teaching tape for the motor section of the toronto western spasmodic torticollis scale (1997)

The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) assesses the character and severity of cervical dystonia (CD). We developed a teaching tape of the TWSTRS scoring for the motor symptoms of CD. The tape provides investigators with visual representations of each component of the motor section of the TWSTRS as agreed upon by three independently scoring raters. The rate of agreement for the nondichotomous components was always significant, with a Kendall's coefficient of concordance W ranging between 0.98 and 0.76 (p < 0.01 for all measures). For the two dichotomous components, a weighted kappa coefficient was also significant at 0.86 for lateral shift and 0.89 for sagittal shift (p < 0.01 for both measures). Scale deficiencies identified by the raters were an explicit definition of midline for assessment of range of motion, the absence of a separate scoring category assessing dystonic tremor, and the specification of duration for the effect of sensory tricks. These observations should be taken into account in future revisions of the TWSTRS and in refinements of other rating scales for CD.
Perspectives on the RNA polymerase II core promoter (2006)

The RNA polymerase II core promoter is a critical yet often overlooked component in the transcription process. The core promoter is defined as the stretch of DNA, which encompasses the RNA start site and is typically approx. 40-50 nt in length, that directs the initiation of gene transcription. In the past, it has been generally presumed that core promoters are general in function and that transcription initiation occurs via a common shared mechanism. Recent studies have revealed, however, that there is considerable diversity in core promoter structure and function. There are a number of DNA elements that contribute to core promoter activity, and the specific properties of a given core promoter are dictated by the presence or absence of these core promoter motifs. The known core promoter elements include the TATA box, Inr (initiator), BRE(u) {BRE [TFIIB (transcription factor for RNA polymerase IIB) recognition element] upstream of the TATA box} and BRE(d) (BRE downstream of the TATA box), MTE (motif ten element), DCE (downstream core element) and DPE (downstream core promoter element). In this paper, we will provide some perspectives on current and future issues that pertain to the RNA polymerase II core promoter.
Antithrombotic Effects of Orally Active Synthetic Antagonist of Activated Factor X in Nonhuman Primates (1995)

An oral synthetic antagonist of FXa, APAP, inhibits the formation of venous-type fibrin-rich thrombus by inactivating bound and soluble FXa without impairing platelet hemostatic function.
PD-L1 Monoclonal Antibody Treats Ischemic Stroke by Controlling Central Nervous System Inflammation (2015)

This study demonstrates for the first time the beneficial therapeutic effects of PD-L1 checkpoint blockade on MCAO, thus validating proposed mechanisms obtained in our previous studies using PD-1- and PD-L-deficient mice. These results provide strong support for the use of available humanized anti-PD-L1 antibodies for treatment of human stroke subjects.
Stable blue second-harmonic generation in a KTP waveguide with a diode laser in an external cavity (1993)

Stable second-harmonic generation from a diode laser, using a quasi-phasematching KTP waveguide and a grating in an external cavity is described. 1.35 mW of blue light was generated and the power fluctuation was less than 0.3%.
Staphylococcal enterotoxin B gene is associated with a discrete genetic element (1988)

The chromosomal location of the enterotoxin B gene in Staphylococcus aureus is unknown. Southern hybridization analysis of the chromosomal DNA from several enterotoxin B (SEB)-producing strains has shown that at least 26.8 kilobases (kb) of DNA is associated with the enterotoxin B gene (entB). We have found that one end of the entB element is located approximately 1.5 kb downstream of the entB gene. The chromosomal region adjacent to this end of the entB element was found to be homologous in several SEB-producing (SEB+) and SEB-nonproducing (SEB-) S. aureus strains. The chromosomes of all the SEB+ strains studied were homologous for at least 24 kb upstream of the entB gene. Some naturally occurring SEB- strains lacked the entire entB element, while others showed variable homology to the region upstream of the entB gene. These data suggest that the entB gene is part of a discrete genetic element that is at least 26.8 kb in size.
Oxidative Cleavage of Ketoximes with Iodosobenzene Diacetate (1986)

Abstract Hypervalent iodine oxidation of ketoximes (1) using iodosobenzene diacetate leads to cleavage of 1 with the formation of corresponding ketones (2) under neutral conditions in good yields. The scope and limitations of the reaction are discussed as well as the mechanism.
Cartilage Restoration, Part 1 (2005)

Surgical procedures designed to treat focal chondral lesions are evolving and are supported by basic science principles of cartilage physiology and known responses to injury. Selecting the proper treatment algorithm for a particular patient depends on careful patient evaluation, including the recognition of comorbidities such as ligamentous instability, deficient menisci, or malalignment of the mechanical limb axis or extensor mechanism. These comorbidities may need to be treated in conjunction with symptomatic chondral injuries to provide a mutually beneficial effect. A central tenet of cartilage restoration is to leave future treatment options available should they become necessary. In this article (part 1), the authors review the basic science of chondral injuries, the historical perspective of the available surgical options, and present guidelines for patient evaluation and treatment.
Generation of Electric Potentials by Bone in Response to Mechanical Stress (1962)

The amplitude of electrical potentials generated in stressed bone is dependent upon the rate and magnitude of bony deformation, while polarity is determined by the direction of bending. Areas under compression develop negative potentials with respect to other areas. Similar results were obtained both in living and dead bone. Removal of the inorganic fraction from bone abolishes its ability to generate stress potentials. It is probable that these potentials influence the activity of osseous cells directly. Furthermore, it is conceivable that they may direct, in some manner, the aggregation pattern of the macromolecules of the extracellular matrix.