gebhart/patrepeval huggingface dataset:
PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1 (2010)

The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete for PD-1 binding. PD-L1 and PD-L2 bound PD-1 with comparable affinities, but striking differences were observed at the level of the association and dissociation characteristics. PD-L1, but not PD-L2, had a delayed interaction reminiscent of a phenomenon of conformational transition. These mechanisms were confirmed by using PD-L1 mAbs that delayed the dissociation of PD-L1 from PD-1. This mechanism was not restricted to PD-1 binding since PD-L1 behaved in a similar manner with its second ligand, CD80. Finally, we could demonstrate that PD-L1 and PD-L2 competed for PD-1 binding and conversely, an antagonist PD-1 mAb blocked both PD-L1 and PD-L2 binding to PD-1 and strongly enhanced T-cell proliferation. These data further emphasize the differential molecular mechanisms of interaction of PD-L1 and PD-L2 with PD-1, and suggest possible new approach for the therapy of chronic infection, cancer and transplantation.
Hepatitis C virus RNA tests: performance attributes and their impact on clinical utility (2003)

The diagnostic market is driven by the burden of disease in the population and the ease or difficulty of disease diagnosis. The efficacy of available therapeutics determines the need for monitoring. Hepatitis C virus currently affects approximately 3% of the world's population, although the overall response rate to the best available therapies is 56%. Research regarding hepatitis C virus remains elusive due to lack of an efficient cell culture system. Diagnosis and monitoring of active hepatitis C virus infection therefore rely on sophisticated molecular tests. This review will focus on current molecular tests for hepatitis C virus RNA and the performance attributes that these tests require for accurate diagnosis and monitoring of infection.
Prediction-based dynamic load-sharing heuristics (1993)

Presents dynamic load-sharing heuristics that use predicted resource requirements of processes to manage workloads in a distributed system. A previously developed statistical pattern-recognition method is employed for resource prediction. While nonprediction-based heuristics depend on a rapidly changing system status, the new heuristics depend on slowly changing program resource usage patterns. Furthermore, prediction-based heuristics can be more effective since they use future requirements rather than just the current system state. Four prediction-based heuristics, two centralized and two distributed, are presented. Using trace driven simulations, they are compared against random scheduling and two effective nonprediction based heuristics. Results show that the prediction-based centralized heuristics achieve up to 30% better response times than the nonprediction centralized heuristic, and that the prediction-based distributed heuristics achieve up to 50% improvements relative to their nonpredictive counterpart.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Rheological Properties of Rennet Gels Containing Milk Protein Concentrates (2008)

Different milk protein concentrates (MPC), with protein concentrations of 56, 70, and 90%, were dispersed in water under different treatments (hydration, shear, heat, and overnight storage at 4 degrees C), as well as in a combination of all the treatments in a factorial design. The particle size distribution of the dispersions was then measured to determine the optimal conditions for the dispersion. Heating at 60 degrees C for 30 min with 5 min of shear was chosen as the best condition to dissolve MPC powders. The samples were also characterized for composition, presence of protein aggregates, and ratio of calcium to protein. The total calcium present in MPC increased with increasing concentration of protein; however, the total calcium-to-protein ratio was lower in MPC90 than in MPC56 and MPC70. The level of whey protein denaturation, the presence of kappa-casein-whey protein aggregates in the supernatant after centrifugation, and the amount of caseins dissociated from the micelle increased as the protein concentration in the powder increased. The total amount of casein macropeptide released was lower in samples from powders with a higher protein concentration than for MPC56 or the skim milk control. The gelation behavior of reconstituted MPC was tested in systems dispersed in water (5% protein) as well as in systems dispersed in skim milk (6% protein). The gelation time of MPC dispersions was considerably lower and the gel modulus was higher than those of reconstituted skim milk with the same protein concentration. When MPC dispersions were dialyzed against skim milk, a significant decrease in the gelation time and modulus were shown, with a complete loss of gelling functionality in MPC90 dispersed in water. This demonstrated that the ionic equilibrium was key to the functionality of MPC.
A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population (2000)

The survival of SLE in our southern Chinese patients is similar to that of the Caucasian series reported in the 1990s. Although nephritis contributes to organ damage, it is not a major determinant for survival. Infection remains the commonest cause of death. High-dose steroid treatment and thrombocytopenia are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of SLE.
Control of ion flux and selectivity by negatively charged residues in the outer mouth of rat sodium channels. (1996)

1. The sodium channel has a ring of negatively charged amino acids on its external face. This common structural feature of cation-selective channels has been proposed to optimize conduction by electrostatic attraction of permeant cations into the channel mouth. We tested this idea by mutagenesis of mu1 rat skeletal sodium channels expressed in Xenopus oocytes. 2. Replacement of the external glutamate residue in domain II by cysteine reduces sodium current by decreasing single-channel conductance. While this effect can be reversed by the negatively charged sulfhydryl modifying reagent methanethiosulphonate ethylsulphonate (MTSES), the flux saturation behaviour cannot be rationalized simply by changes in the surface charge. 3. The analogous mutations in domains I, III and IV affect not only conductance but also selectivity. These changes in selectivity are only partially reversed by exposure to MTSES. 4. Our findings necessitate revision of prevailing concepts regarding the role of superficial negatively charged residues in the process of ion permeation. These residues do not act solely by electrostatic attraction of permeant ions, but instead may help to form ion-specific binding sites within the pore.
Production of Hydroxy Unsaturated Fatty Acids Using Crude Lipoxygenase Obtained from Infected Rice Plants (1996)

Abstract In order to explore the oxidation mode of lipoxygenase (LOX) obtained from infected rice plants, typical unsaturated fatty acids (3—8) were treated with LOX and oxygen. It was observed that ω-10 and ω-6 positions of unsaturated fatty acids were oxidized predominantly in the cases of exotic ω-6 (4 and 5) and ω-3 (7 and 8) series, respectively. In the case of endogenous fatty acids (3 and 6), oxidation at ω-6 position predominated. All the allylic alcohols obtained by reduction of the oxidation products with NaBH4 possess S-configuration.
Resection and Liver Transplantation for Hepatocellular Carcinoma (2005)

Surveillance programs in cirrhotic patients enable the detection of hepatocellular carcinoma (HCC) at early stages, when the tumor is amenable to curative treatments (60% of cases in Japan; 25 to 40% in Europe and the United States). Resection is the mainstay of treatment in noncirrhotic patients and in cirrhotics with well-preserved liver function. In modern series, a perioperative mortality < or = 3% and 5-year survival rates above 50% are expected. Tumor recurrence complicates half of the cases at 3 years, but there is no unquestionable preventive treatment. Liver transplantation provides excellent outcomes applying the Milan criteria (single nodule < or = 5 cm or two or three nodules < or = 3 cm), with 5-year survival rates of 70% and low recurrence rates. Although expansion of selection criteria is appealing, it should be assessed in the setting of prospective well-designed studies. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Living donor liver transplantation is having a minor impact in HCC management. Molecular markers are needed to better select the candidates for surgery.
Rivastigmine for Alzheimer's Disease (2000)

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in later life. It is manifested by gradual and progressive decline in cognitive function and ability to perform activities of daily living (ADL) and the development of behavioral disturbances. Progressive reduction in functional ability reduces independence and quality of life and adversely affects caregivers and society. Therefore, benefit from any AD therapy may be obtained not only from improved function but also from stabilization or reduced worsening of function. METHOD: This retrospective study of pooled data from 3 randomized, placebo-controlled trials (N = 2126) compared the incidence of different levels of worsening between 2 rivastigmine treatment groups and a placebo group at week 26 for cognition, using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog); global functioning, using the Clinicians' Interview-Based Impression of Change-Plus (CIBIC-Plus); and ADL, using the Progressive Deterioration Scale (PDS). Categories of worsening analyzed for each scale were as follows: ADAS-Cog: any decline, >/= 4-point decline, >/= 7-point decline; CIBIC-Plus: stabilized/worsened (rating = 4, 5, 6, or 7), any worsening (rating = 5, 6, or 7); PDS: any worsening, >/= 10% worsening. RESULTS: Patients treated with rivastigmine, 6-12 mg/day, showed significantly less decline in cognition, global functioning, and ADL for all categories of worsening examined compared with patients who received placebo. The reduction in decline compared with placebo was greater in the group receiving 6-12 mg/day of rivastigmine compared with the treatment group receiving 1-4 mg/day of rivastigmine. CONCLUSION: Rivastigmine reduces the amount of worsening observed in cognition, global functioning, and ADL in a 6-month trial period.
Efinaconazole and Tavaborole (2016)

This article will review efinaconazole and tavaborole, 2 new topical antifungal agents released in 2014.
Effects of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) alone and in combination with methotrexate in adjuvant arthritic rats. (1999)

Combination therapy with PEG sTNF-RI and methotrexate results in additive benefit, with the final result being excellent inhibition of all arthritis parameters. Data from these studies supports the clinical investigation of the use of combination therapy of PEG sTNF-RI and methotrexate in rheumatoid arthritis patients.
Dietary incorporation of jojoba extract eliminates oxidative damage in livers of rats fed fumonisin-contaminated diet (2015)

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.
The central Z-disk region of titin is assembled from a novel repeat in variable copy numbers (1996)

The giant sarcomeric protein titin (also described as connectin) is composed mainly of immunoglobulin (Ig)-like and fibronectin type III (fn3)-like domains arranged consecutively. At both ends of the molecule, these domains are interrupted by sequence insertions. The amino terminus of titin is localized in the Z-disk, a structure of great variability in different muscle types. We have determined the ultrastructural position of sequences in this region of the molecule in skeletal and cardiac muscle by immunoelectron microscopy using antibodies directed against unique epitopes. Titin molecules entering the Z-disk from two half sarcomeres do not significantly overlap, showing that the amino terminus is at the centre of the Z-disk. A serine/proline rich site, which can be phosphorylated by kinases in developing muscle tissues, was identified near the amino terminus of titin. Sequence analysis revealed the presence of a novel 45 residue repeat ('Z-repeats') in this region of the molecule. The number of titin Z-repeats varies due to differential splicing. We propose that this mechanism is a means of assembling Z-disks of variable thickness and mechanical strength.
Adaptive nonlinear cancellation for high-speed fiber-optic systems (1992)

The authors propose techniques for adaptive nonlinear cancellation of intersymbol interference (ISI) in the electrical signal at the receiver in Gb/s lightwave systems and describe several demonstrations of these techniques. Techniques for adjustable nonlinear cancellations are discussed and demonstrations of these techniques using commercially available integrated circuits (ICs) at data rates as high as 1.7 Gb/s are described. Techniques for automatic adjustment are discussed, and a demonstration of adaptive nonlinear cancellation at 450 Mb/s is described. The authors discuss how these techniques can be integrated onto the detector IC for operations at 2.5 Gb/s and higher data rates. These techniques allow a single IC detector with adaptive nonlinear cancellation to be used in long-haul and undersea lightwave systems to optimize the detector threshold and compensate for the ISI.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning (2009)

Natural rewards and drugs of abuse can alter dopamine signaling, and ventral tegmental area (VTA) dopaminergic neurons are known to fire action potentials tonically or phasically under different behavioral conditions. However, without technology to control specific neurons with appropriate temporal precision in freely behaving mammals, the causal role of these action potential patterns in driving behavioral changes has been unclear. We used optogenetic tools to selectively stimulate VTA dopaminergic neuron action potential firing in freely behaving mammals. We found that phasic activation of these neurons was sufficient to drive behavioral conditioning and elicited dopamine transients with magnitudes not achieved by longer, lower-frequency spiking. These results demonstrate that phasic dopaminergic activity is sufficient to mediate mammalian behavioral conditioning.
Shape Descriptors for Maximally Stable Extremal Regions (2007)

This paper introduces an affine invariant shape descriptor for maximally stable extremal regions (MSER). Affine invariant feature descriptors are normally computed by sampling the original grey-scale image in an invariant frame defined from each detected feature, but we instead use only the shape of the detected MSER itself. This has the advantage that features can be reliably matched regardless of the appearance of the surroundings of the actual region. The descriptor is computed using the scale invariant feature transform (SIFT), with the resampled MSER binary mask as input. We also show that the original MSER detector can be modified to achieve better scale invariance by detecting MSERs in a scale pyramid. We make extensive comparisons of the proposed feature against a SIFT descriptor computed on grey-scale patches, and also explore the possibility of grouping the shape descriptors into pairs to incorporate more context. While the descriptor does not perform as well on planar scenes, we demonstrate various categories of full 3D scenes where it outperforms the SIFT descriptor computed on grey-scale patches. The shape descriptor is also shown to be more robust to changes in illumination. We show that a system can achieve the best performance under a range of imaging conditions by matching both the texture and shape descriptors.
Isolation and Expression of Lactate Dehydrogenase Genes fromRhizopus oryzae (2000)

Rhizopus oryzae is used for industrial production of lactic acid, yet little is known about the genetics of this fungus. In this study I cloned two genes, ldhA and ldhB, which code for NAD(+)-dependent L-lactate dehydrogenases (LDH) (EC 1.1.1.27), from a lactic acid-producing strain of R. oryzae. These genes are similar to each other and exhibit more than 90% nucleotide sequence identity and they contain no introns. This is the first description of ldh genes in a fungus, and sequence comparisons revealed that these genes are distinct from previously isolated prokaryotic and eukaryotic ldh genes. Protein sequencing of the LDH isolated from R. oryzae during lactic acid production confirmed that ldhA codes for a 36-kDa protein that converts pyruvate to lactate. Production of LdhA was greatest when glucose was the carbon source, followed by xylose and trehalose; all of these sugars could be fermented to lactic acid. Transcripts from ldhB were not detected when R. oryzae was grown on any of these sugars but were present when R. oryzae was grown on glycerol, ethanol, and lactate. I hypothesize that ldhB encodes a second NAD(+)-dependent LDH that is capable of converting L-lactate to pyruvate and is produced by cultures grown on these nonfermentable substrates. Both ldhA and ldhB restored fermentative growth to Escherichia coli (ldhA pfl) mutants so that they grew anaerobically and produced lactic acid.
5,10-Dideazatetrahydrofolic acid (DDATHF) transport in CCRF-CEM and MA104 cell lines. (1993)

5,10-Dideazatetrahydrolic acid (DDATHF) is representative of a new class of antifolates acting through inhibition of de novo purine synthesis. We report here the transport characteristics of the diastereomers of DDATHF, which differ in configuration at C6, and comparison studies with other folate and antifolate analogs. (6R)-DDATHF showed high affinity for the influx system of CCRF-CEM cells with a Km of 1.07 microM and an influx Vmax of 4.04 pmol/min/10(7) cells. Comparative studies with methotrexate yielded an influx Km of 4.98 microM and a Vmax of 6.64 pmol/min/10(7) cells, and with 5-formyltetrahydrofolate an influx Km of 2.18 microM and a Vmax of 6.84 pmol/min/10(7) cells. Uptake of (6R)-DDATHF was competitively inhibited by (6S)-DDATHF, methotrexate (MTX), and 5-formyltetrahydrofolate, all with Ki values similar to their influx Km. The (6S)-DDATHF diastereomer had an influx Km of 1.04 microM, similar to that of (6R)-DDATHF; however, the Vmax of 1.72 pmol/min/10(7) cells was 2.3-fold lower than for (6R)-DDATHF. The transport properties of DDATHF were also studied in a mutant cell line (CEM/MTX), resistant to MTX based on impaired drug transport. In this system (6R)-DDATHF showed an influx Km of 1.49 microM and a decreased influx Vmax of 0.60 pmol/min/10(7) cells. A similar effect was shown for MTX (Km of 7.48 microM, Vmax of 1.02 pmol/min/10(7) cells). The number of binding sites in CCRF-CEM cells was similar for (6R)-DDATHF, (6S)-DDATHF, and MTX, 0.74, 0.71, and 0.76 pmol/10(7) cells, respectively. These values were slightly higher in the CEM/MTX cell line (1.07 and 1.09 pmol/10(7) cells for (6R)-DDATHF and MTX, respectively). Treatment of CCRF-CEM cells with either the N-hydroxysuccinimide ester of MTX or the corresponding N-hydroxysuccinimide ester of (6R)-DDATHF caused substantial inhibition (> 90%) of the influx of (6R)-[3H]DDATHF and [3H]MTX, respectively. These results suggest strongly that DDATHF and MTX share a common influx mechanism through the reduced folate transport system. The internalization of DDATHF by monkey kidney epithelial MA104 cells, which express a high affinity folate receptor, was also studied. Competitive binding studies using purified folate receptor and radiolabeled 5-methyltetrahydrofolate showed that (6S)- and (6R)-DDATHF both had I50 values lower than 5-methyltetrahydrofolate (12 nM). Further studies indicate that both DDATHF isomers are actively intracellularly concentrated through this route and are also rapidly converted to high chain length polyglutamates. Transport via this system was inhibited in folate-depleted cells by 10 nM folic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
Ubiquitin E3 ligase MARCH7 promotes ovarian tumor growth (2015)

Ubiquitin E3 ligase MARCH7 is involved in T cell proliferation and neuronal development. We found that expression of MARCH7 was higher in ovarian cancer tissues than normal ovarian tissues. Silencing MARCH7 decreased cell proliferation, migration, and invasion. Ectopic expression of MARCH7 increased cell proliferation, migration and invasion. Silencing MARCH7 prevented ovarian cancer growth in mice. Silencing MARCH7 inhibited NFkB and Wnt/β-catenin pathway. In agreement, ectopically expressed MARCH7 activated NFkB and Wnt/β-catenin pathways. Finally, MARCH7 was regulated by miR-101. Thus, MARCH7 is oncogenic and a potential target (oncotarget) for ovarian cancer therapy.
Decoder-side block motion estimation for H.264 / MPEG-4 AVC based video coding (2009)

In video coding standards like H.264 / MPEG-4 AVC, the encoder performs motion estimation in order to utilise temporal dependencies within a sequence. In addition to the rate of the residue, the encoder has to allocate bits for motion vectors required to compensate the motion at the decoder. This bit rate increases for smaller block sizes, since more motion vectors need to be transmitted. Therefore, motion compensation using dense motion vector field is not feasible for such an architecture. This paper proposes to estimate motion for coding of B frames at the decoder. Using this decoder-side motion estimation, the transmission of the motion vectors is not necessary and the bit rate is reduced. Furthermore, prediction quality is higher in many cases resulting in a coding gain of up to 1.7 dB at low bit rates and 0.2 dB at higher bit rates.