gebhart/patrepeval huggingface dataset:
FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system (2009)

FTY720 (fingolimod) is a first-in-class sphingosine 1-phosphate (S1P) receptor modulator that was highly effective in Phase II clinical trials for Multiple Sclerosis (MS). FTY720 is phosphorylated in vivo by sphingosine kinase-2 to form the active moiety FTY720-phosphate that binds to four of the five G protein-coupled S1P receptor subtypes. Studies using conditional S1P1 receptor-deficient and sphingosine kinase-deficient mice showed that the egress of lymphocytes from lymph nodes requires signalling of lymphocytic S1P1 receptors by the endogenous ligand S1P. The S1P mimetic FTY720-phosphate causes internalization and degradation of cell membrane-expressed S1P1, thereby antagonizing S1P action at the receptor. In models of human MS and demyelinating polyneuropathies, functional antagonism of lymphocytic S1P1 slows S1P-driven egress of lymphocytes from lymph nodes, thereby reducing the numbers of autoaggressive TH17 cells that recirculate via lymph and blood to the central nervous system and the sciatic/ischiatic nerves. Based on its lipophilic nature, FTY720 crosses the blood-brain barrier, and ongoing experiments suggest that the drug also down-modulates S1P1 in neural cells/astrocytes to reduce astrogliosis, a phenomenon associated with neurodegeneration in MS. This may help restore gap-junctional communication of astrocytes with neurons and cells of the blood-brain barrier. Additional effects may result from (down-) modulation of S1P3 in astrocytes and of S1P1 and S1P5 in oligodendrocytes. In conclusion, FTY720 may act through immune-based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma. Beyond the autoimmune indications, very recent studies suggest that short-term, low-dose administration of FTY720 could help treat chronic (viral) infections. Differential effects of the drug on the trafficking of naïve, central memory and effector memory T cell subsets are discussed.
Multilevel (Hierarchical) Modeling: What It Can and Cannot Do (2006)

Multilevel (hierarchical) modeling is a generalization of linear and generalized linear modeling in which regression coefficients are themselves given a model, whose parameters are also estimated from data. We illustrate the strengths and limitations of multilevel modeling through an example of the prediction of home radon levels in U.S. counties. The multilevel model is highly effective for predictions at both levels of the model, but could easily be misinterpreted for causal inference.
Flash memory cells-an overview (1997)

The aim of this paper is to give a thorough overview of flash memory cells. Basic operations and charge-injection mechanisms that are most commonly used in actual flash memory cells are reviewed to provide an understanding of the underlying physics and principles in order to appreciate the large number of device structures, processing technologies, and circuit designs presented in the literature. New cell structures and architectural solutions have been surveyed to highlight the evolution of the flash memory technology, oriented to both reducing cell size and upgrading product functions. The subject is of extreme interest: new concepts involving new materials, structures, principles, or applications are being continuously introduced. The worldwide semiconductor memory market seems ready to accept many new applications in fields that are not specific to traditional nonvolatile memories.
Automobile Accidents, Tort Law, Externalities, and Insurance: An Economist's Critique (1968)

Preface – By Todd Litman This is a seminal article concerning traffic accident cost analysis and vehicle insurance pricing reform by Professor William Vickrey, winner of the 1996 Nobel Prize for economics. It describes how to determine the marginal accident costs of vehicle travel, identifies several problems associated with current insurance pricing and compensation practices, and proposes innovative solutions. It recommends distance-based pricing, that is, basing premiums directly on annual vehicle mileage. In recent years there has been increasing interest in this idea, including pilot projects and legislation intended to promote implementation of distance-based insurance pricing.
Studies on Sulfur-containing Chelating Agents. X. Mercapto-acid Amides and their Metal Chelates (1962)

Amides of β-mercaptohydrocinnamic acid were prepared by the addition of hydrogen sulfide to amides of cinnamic acid. Amides of thiosalicylic acid were also prepared. Some of these mercapto-amides formed stable chelates with copper and nickel. Cobalt chelate was not stable enough to be separated in pure state. The ratio of the ligand to the metal was 1:1 in copper chelate and 2:1 in nickel chelate. It was found that these chelate compounds were S-O chelating compounds from the infrared spectra.
The use of fiber optics in cable communications networks (1993)

This paper discuss past, present, and future use of fiber optics and optoelectronics, in conjunction with coaxial communications networks, to provide enhanced communications and networking capabilities. The role of network architectures and various options regarding wavelengths and modulation techniques are discussed and compared, as are several scenarios of fiber to the neighborhood, service area, curb, and home.
Regulatory regions that control expression of two chloramphenicol-inducible cat genes cloned in Bacillus subtilis (1984)

Plasmid pPL603 is a promoter cloning vector for Bacillus subtilis and consists of a 1.1-kilobase fragment of Bacillus pumilus DNA inserted between the EcoRI and BamHI sites of pUB110. The gene cat-86, specifying chloramphenicol-inducible chloramphenicol acetyltransferase, is located on the 1.1-kilobase cloned DNA. When pPL603 is present in B. subtilis, cat-86 is unexpressed during vegetative growth but expressed during sporulation. The regulation of cat-86 in pPL603 is due to sequences within two restriction fragments, designated P1 and R1, that precede the main coding portion of the gene. The P1 fragment promotes transcription of cat-86 only during sporulation, whereas the adjacent R1 fragment lacks promoter function but contains sequences essential to chloramphenicol inducibility. A second B. pumilus gene, cat-66, was cloned in B. subtilis and is expressed throughout the vegetative growth and sporulation cycle. The cat-66 coding region is preceded by two adjacent restriction fragments designated as P2 and R2. P1 and P2 are identical in size and share 95% conservation of base sequence. R1 and R2 are also identical in size and share 91% conservation of base sequence. Fragment substitution experiments demonstrate that R2 can functionally replace R1. The substitution of P2 for P1 promotes cat-86 expression throughout vegetative growth and sporulation. Analysis of a derivative of pPL603 in which P2 has replaced P1 demonstrates that P2 promotes transcription of cat-86 during vegetative growth and that P2 contains the start site for transcription of cat-86. Thus, P1 and P2 differ strikingly in vegetative promoter function, yet they differ by single-base substitutions at only 11 positions of 203.
Use of a Monoclonal Antibody Directed against the Platelet Glycoprotein IIb/IIIa Receptor in High-Risk Coronary Angioplasty (1994)

Ischemic complications of coronary angioplasty and atherectomy were reduced with a monoclonal antibody directed against the platelet IIb/IIIa glycoprotein receptor, although the risk of bleeding was increased.
Nucleotide sequence of the Serratia marcescens threonine operon and analysis of the threonine operon mutations which alter feedback inhibition of both aspartokinase I and homoserine dehydrogenase I (1993)

The nucleotide sequence of the Serratia marcescens threonine operon (thrA1A2BC) was determined. Three long open reading frames were identified; these open reading frames code for aspartokinase I (AKI)-homoserine dehydrogenase I (HDI), homoserine kinase, and threonine synthase, in that order. The predicted amino acid sequences of these enzymes were similar to the amino acid sequences of the corresponding enzymes in Escherichia coli. The AKI-HDI protein is apparently a tetramer composed of monomer polypeptides that are 819 amino acids long. A deletion analysis revealed that the central and C-terminal region was responsible for threonine-resistant HDI activity, a monomeric fragment extending from the N terminus to residue 306 was responsible for threonine-resistant AKI activity, and an N-terminal portion containing 468 residues was responsible for threonine-sensitive AKI activity. The thrA(1)1A(2)1 and thrA(1)5A(2)5 mutations of threonine-excreting strains HNr21 and TLr156, which result in the loss of threonine-mediated feedback inhibition of both AKI activity and HDI activity, cause single amino acid substitutions (Gly to Asp at position 330 and Ser to Phe at position 352, respectively) in the central region of the AKI-HDI protein. The thrA1+A(2)2 mutation of strain HNr59, which results in a threonine-sensitive AKI and a threonine-resistant HDI, also causes a single amino acid substitution (Ala to Thr at position 479).
Confidence-based active learning (2006)

This paper proposes a new active learning approach, confidence-based active learning, for training a wide range of classifiers. This approach is based on identifying and annotating uncertain samples. The uncertainty value of each sample is measured by its conditional error. The approach takes advantage of current classifiers' probability preserving and ordering properties. It calibrates the output scores of classifiers to conditional error. Thus, it can estimate the uncertainty value for each input sample according to its output score from a classifier and select only samples with uncertainty value above a user-defined threshold. Even though we cannot guarantee the optimality of the proposed approach, we find it to provide good performance. Compared with existing methods, this approach is robust without additional computational effort. A new active learning method for support vector machines (SVMs) is implemented following this approach. A dynamic bin width allocation method is proposed to accurately estimate sample conditional error and this method adapts to the underlying probabilities. The effectiveness of the proposed approach is demonstrated using synthetic and real data sets and its performance is compared with the widely used least certain active learning method.
Seroepidemiology of Chlamydia pneumoniae TWAR Infection in Seattle Families, 1966-1979 (1992)

Incidence rates of Chlamydia pneumoniae infection and information on reinfection and transmission within families were obtained by serologic study of serum samples from prospective family studies conducted 1966-1979. Specimens (n = 3671) from 343 subjects in 68 families were tested for TWAR antibody using the microimmunofluorescence assay. Acute infection was defined as a fourfold rise in antibody titer between consecutive specimens. Sixty-four episodes of infection were identified in 58 persons; 4 had 2 infections and 1 had 3. From late 1975 until early 1979, when 3 serum specimens were collected yearly, rates of infection by age groups 0-4, 5-9, 10-14, 15-19, and greater than or equal to 20 years were 0, 9.2, 6.2, 2.2, and 1.5/100 person-years, respectively. Reinfections, defined as infections in persons with previous antibody, constituted most acute infections among adults. Acute infections more often affected a single family member than multiple members, but 2 or 3 family members were infected during the same period 12 times.
Influence of C4-dicarboxylic acid transporters on succinate production (2011)

Current climate issues and the ongoing depletion of oil reserves have led to increased attention for biobased production processes. Not only has the production of bio-energy gained interest, but also the production of biochemicals. Succinate is one of those biochemicals. In the presented work, the dicarboxylic acid transport system of Escherichia coli was modified to enhance production of succinate, a highly attractive chemical building block. The engineering comprised the elimination of succinate uptake and the overexpression of succinate export. However, succinate export in Escherichia coli is normally only active under anaerobic conditions and import only under aerobic conditions. Therefore, the gene responsible for succinate import, dctA, was knocked out and the gene coding for succinate export, dcuC, was overexpressed with a constitutive artificial promoter. In the applied batch cultivations, these modifications increased succinate yield and specific production rate more than 50% in a ΔsdhAΔsdhB background (0.16 C-mole/C-mole glucose and 0.17 C-mole/C-mole biomass/h, respectively), but also revealed alternative succinate import proteins, YdjN and YbhI. Mutations in the genes coding for these proteins led to increased growth rates and specific production rates, however, they did not increase succinate yield (e.g. the deletion of ybhI resulted in a growth rate of 0.54 h−1 and a specific production rate of 0.23 C-mole/C-mole biomass/h).
Flow-dependent re-endothelialization of tissue-engineered heart valves. (2006)

Moderate pulsatile flow with small increments stimulates EC proliferation on the ovine decellularized valve scaffold. A rapid increase in bioreactor flow to physiological levels leads to significant damage of the reseeded endothelium and complete loss of cusp cellularity. This effect may be responsible for the in-vivo failure of static reseeded tissue-engineered valves exposed to physiological hemodynamic forces.
A new edge detector for obstacle detection with a linear stereo vision system (2002)

The problem addressed is obstacle detection in front of a moving vehicle. One of the main difficulties encountered when scanning stereo pairs of linear images is the extraction of significant features from the left and right images. The better the features, the more reliable is the matching procedure for 3-D reconstruction of the car environment. In this paper we present a new edge detector which has been developed for this application. Its performances, in terms of detection, localization and multiple responses, are determined according to Canny's criteria. The system has been evaluated in real traffic conditions. It operates in real-time, due to the highly efficient recursive implementation of the filters proposed in this paper.
Atomic Decomposition by Basis Pursuit (2001)

The time-frequency and time-scale communities have recently developed a large number of overcomplete waveform dictionaries---stationary wavelets, wavelet packets, cosine packets, chirplets, and warplets, to name a few. Decomposition into overcomplete systems is not unique, and several methods for decomposition have been proposed, including the method of frames (MOF), matching pursuit (MP), and, for special dictionaries, the best orthogonal basis (BOB). Basis pursuit (BP) is a principle for decomposing a signal into an "optimal"' superposition of dictionary elements, where optimal means having the smallest l1 norm of coefficients among all such decompositions. We give examples exhibiting several advantages over MOF, MP, and BOB, including better sparsity and superresolution. BP has interesting relations to ideas in areas as diverse as ill-posed problems, abstract harmonic analysis, total variation denoising, and multiscale edge denoising. BP in highly overcomplete dictionaries leads to large-scale optimization problems. With signals of length 8192 and a wavelet packet dictionary, one gets an equivalent linear program of size 8192 by 212,992. Such problems can be attacked successfully only because of recent advances in linear and quadratic programming by interior-point methods. We obtain reasonable success with a primal-dual logarithmic barrier method and conjugate-gradient solver.
Inactivation of maize transposon Mu suppresses a mutant phenotype by activating an outward-reading promoter near the end of Mu1. (1991)

We described previously a mutation in maize, hcf106, caused by the insertion of a Mu1 transposon. When the Mu transposon system is in an active phase, hcf106 conditions a nonphotosynthetic, pale green phenotype. However, when the Mu system is inactive (a state correlated with hypermethylation of Mu elements), the plant adopts a normal phenotype despite the continued presence of the transposon within the gene. The molecular mechanisms that mediate this suppression of the mutant phenotype have now been investigated. We show here that the Mu element responsible for the hcf106 lesion lies within sequences encoding the 5'-untranslated leader of the Hcf106 mRNA. When the Mu transposon system is active, this insertion interferes with the accumulation of mRNA from the hcf106 allele. However, when Mu is inactive, mRNA similar in size and abundance to that transcribed from the normal allele accumulates. These transcripts initiate at many sites throughout a 70-base-pair region, within and immediately downstream of the Mu1 insertion. Thus, an unusual promoter spanning the downstream junction between Mu1 and Hcf106 substitutes for the normal Hcf106 promoter but only when Mu is inactive. The pattern of mRNA accumulation in different organs and in response to light suggests that the activity of this promoter is conditional not only upon the phase of Mu activity, but also upon signals that regulate the normal Hcf106 promoter.
Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. (1987)

Human immunodeficiency virus encodes a gene product termed tat that is able to activate viral gene expression when present in trans. The mechanism of action of the tat gene product appears to be bimodal, resulting in both an increase in the steady-state level of viral mRNA and the enhanced translation of that RNA. In this report we have examined the mechanism by which tat elevates viral mRNA levels. Data are presented demonstrating that tat acts by increasing the rate of viral transcription, rather than by modulating the stability of viral mRNA. Indirect immunofluorescence was used to show that tat is predominantly localized in the nucleus of expressing cells, a location consistent with a role in the regulation of viral transcription. These results suggest that tat could play a role in human immunodeficiency virus replication essentially similar to that proposed for the trans-acting nuclear gene products described for several other virus species.
Parkin is recruited into aggresomes in a stress-specific manner: over-expression of parkin reduces aggresome formation but can be dissociated from parkin's effect on neuronal survival (2003)

Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra and the presence of cytoplasmic inclusions known as Lewy bodies (LBs). Mutations in parkin cause autosomal recessive juvenile parkinsonism (AR-JP) that is distinct from sporadic PD by the general absence of LBs. Several studies have reported that parkin is present in LBs of sporadic PD but the role of parkin in LB formation is unclear. Aggresomes are perinuclear aggregates representing intracellular deposition of misfolded protein. LBs and aggresomes have been reported to share a common biogenesis. We have investigated the role of parkin in aggresome formation. In human SH-SY5Y neuroblastoma cells we observe that endogenous parkin is present in aggresomes induced by a variety of stresses including dopamine, proteosome inhibition and a pro-apoptopic stimulus. We show that vimentin is invariably collapsed around the aggresome but that the detection of ubiquitin is variable depending on the stress. We show that cells that stably over-express human wild-type parkin form fewer aggresomes upon stress compared to cells that express vector alone whereas over-expression of AR-JP causing mutants of parkin have no effect on stress-induced aggresome formation. Finally, we show that the prevention of aggresome formation by over-expression of wild-type parkin is not always associated with a beneficial effect on neuronal survival. Our findings suggest that parkin is important for aggresome formation in human neuronal cells and may lead to a better understanding of the biogenesis of LBs in sporadic PD.
Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral Sclerosis (1996)

A subset of individuals with familial amyotrophic lateral sclerosis (FALS) possesses dominantly inherited mutations in the gene that encodes copper-zinc superoxide dismutase (CuZnSOD). A4V and G93A, two of the mutant enzymes associated with FALS, were shown to catalyze the oxidation of a model substrate (spin trap 5,5'-dimethyl-1-pyrroline N-oxide) by hydrogen peroxide at a higher rate than that seen with the wild-type enzyme. Catalysis of this reaction by A4V and G93A was more sensitive to inhibition by the copper chelators diethyldithiocarbamate and penicillamine than was catalysis by wild-type CuZnSOD. The same two chelators reversed the apoptosis-inducing effect of mutant enzymes expressed in a neural cell line. These results suggest that oxidative reactions catalyzed by mutant CuZnSOD enzymes initiate the neuropathologic changes in FALS.
Characterization of cDNA clones for the 2-methyl branched-chain enoyl-CoA reductase. An enzyme involved in branched-chain fatty acid synthesis in anaerobic mitochondria of the parasitic nematode Ascaris suum. (1993)

The 2-methyl branched-chain enoyl-CoA reductase plays a pivotal role in the reversal of beta-oxidation operating in anaerobic mitochondria of the parasitic nematode Ascaris suum. An affinity-purified polyclonal anti-serum against the reductase was used to screen a cDNA library constructed in lambda gt11 with poly(A)+ RNA from adult A. suum muscle. A 1.2-kilobase partial cDNA clone was isolated, subcloned, and sequenced in both directions. Additional sequence at the 5' end of the mRNA was determined by the RACE (rapid amplification of cDNA ends) procedure. Nucleotide sequence analysis of the cDNAs revealed the 22-nucleotide trans-spliced leader sequence characteristic of many nematode mRNAs, an open reading frame of 1236 nucleotides and a 3'-untranslated sequence of 109 nucleotides including a short poly(A) tail 14 nucleotides from a polyadenylation signal (AATAAA). The open reading frame encoded a 396-amino acid sequence (M(r) 43,046) including a 16-amino acid leader peptide. Two-dimensional gel electrophoresis of the purified reductase yielded multiple spots with two distinct but overlapping amino-terminal amino acid sequences. Both sequences overlapped with the sequence predicted from the mRNA, and one of the sequences was identical to the predicted sequence. Comparison of the ascarid sequence with that of mammalian acyl-CoA dehydrogenases revealed a high degree of sequence identity, suggesting that these enzymes may have evolved from a common ancestral gene even though the ascarid enzyme functions as a reductase, not as a dehydrogenase. Immunoblotting of A. suum larval stages and adult tissues with antisera that cross-reacted with each of the spots separated on two-dimensional gels suggested that the reductase was only found in adult muscle. Northern blotting using the partial cDNA revealed a hybridization band of about 1.5 kilobases and also suggested that the enzyme was tissue-specific and developmentally regulated in agreement with the results of the immunoblotting.