gebhart/patrepeval huggingface dataset:
Dual mode transmitter with adaptively controlled slew rate and impedance supporting wide range data rates (2002)

A novel dual mode transmitter that can be configured either in rail-to-rail voltage mode supporting 1.5 Mb/s and 12 Mb/s data rate or in a 400 mV low-swing current mode supporting 480 Mb/s data rate is presented. In addition, adaptive control schemes for the output impedance and the slew rate are also integrated. The test circuit is implemented using a 0.25 /spl mu/m standard CMOS process technology. It occupies an area of about 800 /spl mu/m/spl times/200 /spl mu/m and consumes less than 70 mW power. A better than 10/sup -9/ BER was measured at 480 Mb/s data rate over a USB cable with a 2/sup 15/-1 pseudo-random data stream.
Chimeric Antigen Receptor-Modified T Cells for Solid Tumors: Challenges and Prospects (2016)

Recent studies have highlighted the successes of chimeric antigen receptor-modified T- (CART-) cell-based therapy for B-cell malignancies, and early phase clinical trials have been launched in recent years. The few published clinical studies of CART cells in solid tumors have addressed safety and feasibility, but the clinical outcome data are limited. Although antitumor effects were confirmed in vitro and in animal models, CART-cell-based therapy still faces several challenges when directed towards solid tumors, and it has been difficult to achieve the desired outcomes in clinical practice. Many studies have struggled to improve the clinical responses to and benefits of CART-cell treatment of solid tumors. In this review, the status quo of CART cells and their clinical applications for solid tumors will be summarized first. Importantly, we will suggest improvements that could increase the therapeutic effectiveness of CART cells for solid tumors and their future clinical applications. These interventions will make treatment with CART cells an effective and routine therapy for solid tumors.
The role of a repetitive DNA motif (5′‐CAAT‐3′) in the variable expression of the Haemophilus influenzae lipopolysaccharide epitope αGal(1–4)βGal (1993)

Haemophilus influenzae lipopolysaccharide (LPS) contains structures, defined by monoclonal antibodies, which undergo phase variation. This investigation reports the nucleotide sequence of lic2A, which is required for the expression of at least three phase-variable LPS epitopes, one of which has the structure alpha Gal(1-4)beta Gal. lic2A contains multiple tandem repeats of the tetramer 5'-CAAT-3'. Previous studies have correlated changes in the number of 5'-CAAT-3' repeats with the phase-variable expression of the alpha Gal(1-4)beta Gal epitope. To obtain direct evidence for this, the 5'-CAAT-3' repeat region from lic2A was amplified directly from immunostained colonies and sequenced. This demonstrated that the variable expression of LPS epitopes, including alpha Gal(1-4)beta Gal, is in part directly dependent upon the number of copies of 5'-CAAT-3' within lic2A.
Initiation and adaptation: a paradigm for understanding psychotropic drug action (1996)

Biological investigation in psychiatry has often focused too narrowly on synaptic pharmacology, especially on neurotransmitter turnover and neurotransmitter receptors. This review focuses on molecular and cellular changes in neural function that are produced as adaptations to chronic administration of addictive drugs such as psychostimulants and therapeutic drugs such as antidepressants. To understand normal brain function, psychopathology, and the actions of psychiatric treatments, and to exploit the eventual findings of psychiatric genetics, psychiatric research must now extend its efforts beyond the synapse, to an understanding of cellular and molecular neurobiology (in particular, postreceptor signal transduction) as well as to a better understanding of the architecture and function of neural systems. A paradigm is presented to help understand the long-term effects of psychotropic drugs, including the latency in onset of their therapeutic actions.
Reaching Agreement in the Presence of Faults (1980)

The problem addressed here concerns a set of isolated processors, some unknown subset of which may be faulty, that communicate only by means of two-party messages. Each nonfaulty processor has a private value of information that must be communicated to each other nonfaulty processor. Nonfaulty processors always communicate honestly, whereas faulty processors may lie. The problem is to devise an algorithm in which processors communicate their own values and relay values received from others that allows each nonfaulty processor to infer a value for each other processor. The value inferred for a nonfaulty processor must be that processor's private value, and the value inferred for a faulty one must be consistent with the corresponding value inferred by each other nonfaulty processor. It is shown that the problem is solvable for, and only for, n ≥ 3 m + 1, where m is the number of faulty processors and n is the total number. It is also shown that if faulty processors can refuse to pass on information but cannot falsely relay information, the problem is solvable for arbitrary n ≥ m ≥ 0. This weaker assumption can be approximated in practice using cryptographic methods.
Protein‐Resistant Surfaces through Mild Dopamine Surface Functionalization (2008)

The synthesis and evaluation of new dopamine-based catechol anchors coupled to poly(ethylene glycol) (PEG) for surface modification of TiO(2) are reported. Dopamine is modified by dimethylamine-methylene (7) or trimethylammonium-methylene (8) groups, and the preparation of mPEG-Glu didopamine polymer 11 is presented. All these PEG polymers allow stable adlayers on TiO(2) to be generated through mild dip-and-rinse procedures, as evaluated both by variable angle spectroscopic ellipsometry and X-ray photoelectron spectroscopy. The resulting surfaces substantially reduced protein adsorption upon exposure to full human serum.
Changes in the 2-5A synthetase/RNase L antiviral pathway in a controlled clinical trial with poly(I)-poly(C12U) in chronic fatigue syndrome. (1995)

Latent 2', 5'-oligoadenylate (2-5A) synthetase activity, bioactive 2-5A and RNase L activity were measured in extracts of peripheral blood mononuclear cells (PMBC) before and during a randomized, multicenter, placebo-controlled, double-blind study of poly(I)-poly(C12U) in individuals with chronic fatigue syndrome (CFS) as defined by the Centers for Disease Control and Prevention. The mean values for bioactive 2-5A and RNase L activity were significantly elevated at baseline compared to controls (p < .0001 and p = .001, respectively). In individuals that presented with elevated RNase L activity at baseline, therapy with poly(I)-poly(C12U) resulted in a significant decrease in both bioactive 2-5A and RNase L activity (p = .09 and p = .005, respectively). Decrease in RNase L activity in individuals treated with poly(I)-poly(C12U) correlated with cognitive improvement (p = .007). Poly(I)-poly(C12U) therapy resulted in a significant decrease in bioactive 2-5A and RNase L activity in agreement with clinical and neuropsychological improvements (Strayer DR, et al., Clin. Infectious Dis. 18:588-595, 1994). The results described show that poly(I)-poly(C12U) is a biologically active drug in CFS.
Diagnosis of Chlamydia trachomatis genital infections by cell culture and two enzyme immunoassays detecting different chlamydial antigens (1989)

The enzyme-amplified immunoassay IDEIA (CellTech Diagnostics), which measures lipopolysaccharide antigen, and Chlamydiazyme (Abbott Laboratories, North Chicago, Ill.), which measures several antigenic components of Chlamydia trachomatis, were compared for specimens from urethral swabs from 235 men attending a clinic for sexually transmitted diseases (culture prevalence of 14.9%) and 458 endocervical swabs from women attending planned parenthood and obstetrics-gynecology clinics (culture prevalences of 5.9 and 7.7%, respectively). Compared with cell culture, the percent sensitivites, specificities, and positive and negative predictive values for IDEIA were 62.5, 99.5, 95.2, and 94.3%, respectively, for specimens from men and 96.3, 97.9, 74.3, and 99.8%, respectively, for specimens from women; results for Chlamydiazyme for specimens from men were 81.8, 99.5, 96.4, and 97.1%, respectively, and for specimens from women, results were 85.2, 99.3, 88.5, and 99.1%, respectively. Although the specificities of IDEIA and Chlamydiazyme were comparable, the sensitivity of IDEIA appeared higher for women (96.3%) than for men (67.5%), while the sensitivities of Chlamydiazyme were similar for men (81.8%) and women (85.2%). Western blot (immunoblot) analysis of the detector reagents from the two immunoassays indicated that the differences in performance observed for the two immunoassays may be due to measurement of different antigens.
Toll-Like Receptor 3 Mediates a More Potent Antiviral Response Than Toll-Like Receptor 4 (2003)

We have recently described an IFN regulatory factor 3-mediated antiviral gene program that is induced by both Toll-like receptor (TLR)3 and TLR4 ligands. In our current study, we show that activation of IFN/viral response gene expression in primary macrophage cells is stronger and prolonged with TLR3 stimulation compared with that of TLR4. Our data also reveal that the cytoplasmic tails of both TLR3 and TLR4 can directly interact with myeloid differentiation factor 88 (MyD88). However, although Toll/IL-1 receptor homology domain-containing adaptor protein/MyD88 adaptor-like is able to associate with TLR4, we were unable to detect any interaction between Toll/IL-1 receptor homology domain-containing adaptor protein/MyD88 adaptor-like and TLR3. By using quantitative real-time PCR assays, we found that TLR3 expression is inducible by both TLR3 and TLR4 ligands, while TLR4 expression is not inducible by these same stimuli. Furthermore, using cells derived from mice deficient in the IFN-alphabetaR, we show that both TLR3 and TLR4 require IFN-beta autocrine/paracrine feedback to induce TLR3 expression and activate/enhance genes required for antiviral activity. More specifically, a subset of antiviral genes is initially induced independent of IFN-beta, yet the cytokine further enhances expression at later time points. This was in contrast to a second set of genes (including TLR3) that is induced only after IFN-beta production. Taken together, our data argue that, despite both TLR3 and TLR4 being able to use IFN-beta to activate/enhance antiviral gene expression, TLR3 uses multiple mechanisms to enhance and sustain the antiviral response more strongly than TLR4.
Nonoxidative Fungicidal Mechanisms of Mammalian Granulocytes: Demonstration of Components with Candidacidal Activity in Human, Rabbit, and Guinea Pig Leukocytes (1975)

Granulocytes from the peripheral blood of normal subjects and a patient with hereditary myeloperoxidase deficiency were homogenized in 0.34 M sucrose. A granule-rich fraction, prepared by sedimentation at 27,000 × g for 20 min, contained components that killed C. parapsilosis in vitro. These were extractable with 0.01 M citric acid and were shown by micropreparative polyacrylamide electrophoresis to be multiple. The candidacidal activity of these neutrophil components was heat stable and they were somewhat more active at pH 5.0 than at pH 7.0. When rabbit or guinea pig heterophils were obtained from sterile peritoneal exudates and similarly fractionated, they also were found to contain components that killed C. parapsilosis in vitro. These were primarily associated with a group of lysosomal cationic proteins lacking direct counterpart in human neutrophils. Among the candidacidal components of the human neutrophil was a protein, more cationic than lysozyme, that exhibited naphthol-ASD acetate esterase activity.
Scalability and biasing strategy for CMOS with active well bias (2002)

We analyze the scalability of the two well bias strategies: reverse bias to reduce standby power, and forward bias to improve the speed or to reduce active power. We then present the device design space that includes well bias as an integral part of the design variables following the SIA Roadmap specifications. We show that proper well biases are needed for bulk CMOS just to continue to meet the SIA Roadmap requirements for performance and standby current. The scalabilities for forward bias and reverse bias are different. The advantage of reverse bias is diminishing with scaling due to low initial V/sub t/ values, short-channel effects, and band-to-band tunneling. The advantage of the forward body bias is preserved better with scaling due to high initial V/sub t/ values as well as smaller depletion width, and increases with V/sub t/ nonscaling. The forward bias approach is not effective in speed improvement for ultra-high performance applications with high V/sub dd/ overdrive and low V/sub t/ to start with, but is effective in active power reduction at a fixed speed target.
The influence of different combinations of γ-linolenic acid, stearidonic acid and EPA on immune function in healthy young male subjects (2004)

To determine the effects of EPA, stearidonic acid (STA) or gamma-linolenic acid (GLA) on immune outcomes, healthy male subjects consumed one of seven oil blends for 12 weeks. EPA consumption increased the EPA content of peripheral blood mononuclear cells (PBMC). Consumption of GLA (2.0 g/d) in the absence of STA or EPA increased di-homo-GLA content in PBMC. Neither STA nor its derivative 20 : 4n-3 appeared in PBMC when STA (<1.0 g/d) was consumed. However, STA (1.0 g/d), in combination with GLA (0.9 g/d), increased the proportion of EPA in PBMC. None of the treatments altered neutrophil or monocyte phagocytosis or respiratory burst, production of inflammatory cytokines by monocytes, T lymphocyte proliferation or the delayed-type hypersensitivity response. Production of cytokines by T lymphocytes increased in all groups, with no differences among them. The proportion of lymphocytes that were natural killer cells decreased significantly in subjects receiving 2.0 g EPA or GLA/d. There were no other effects on lymphocyte sub-populations. Plasma IgE concentration decreased in most groups, but not in the control group. Plasma IgG2 concentration increased in the EPA group. Thus, EPA or GLA at a dose of 2.0 g/d have little effect on key functions of neutrophils, monocytes and T lymphocytes, although at this dose these fatty acids decrease the number of natural killer cells. At this dose EPA increases IgG2 concentrations. STA can increase immune cell EPA status, but at 1.0 g/d does not affect human immune function.
Gating of Transient Receptor Potential Melastatin 8 (TRPM8) Channels Activated by Cold and Chemical Agonists in Planar Lipid Bilayers (2010)

The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental cold temperatures. It is activated by cold and chemical agonists, such as menthol and icilin. The activation of these channels both by cold and cooling agents requires the presence of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)]. The mechanism of TRPM8 activation by physical and chemical factors is unknown, and the involvement of cellular signaling pathways has been considered. Here we have characterized the gating mechanism of the rat TRPM8 reconstituted in planar lipid bilayers and its activation by different stimuli. In this system, the influence of cellular signaling pathways can be excluded. We found that TRPM8 activated by cold exhibits steep temperature dependence [temperature coefficient (Q(10)) of ∼40], and the channel openings are accompanied by large changes in entropy and enthalpy, suggesting a substantial conformation change. TRPM8 channel behavior upon menthol and icilin activation was distinguishable, and the effect of icilin depended on the presence of calcium on the intracellular side of the protein. Here we also demonstrate that PI(4,5)P(2) is the prime factor that impacts the gating of TRPM8 and that other phosphoinositides are less efficient in supporting channel activity. Menthol increases the potency of PI(4,5)P(2) to activate the channels and increases binding of phosphoinositides to the full-length channel protein. Our data demonstrate conclusively that TRPM8 is gated by cold and its chemical agonists directly, and that dependence of its gating on PI(4,5)P(2) is a result of direct specific interactions with the lipid.
CD18-dependent and -independent mechanisms of neutrophil emigration in the pulmonary and systemic microcirculation of rabbits. (1990)

Neutrophil (PMN) migration in the systemic and pulmonary circulation of rabbits was compared by using different inflammatory stimuli to determine the role of the leukocyte adhesion complex, CD11/CD18, in each of these vascular beds. The adhesion complex was blocked by administering the anti-CD18 mAb 60.3. The data show that mAb 60.3 blocks PMN emigration into inflammatory foci in the abdominal wall produced by implanting sponges containing either hydrochloric acid, Streptococcus pneumoniae, Escherichia coli endotoxin, or PMA. mAb 60.3 also inhibited PMN emigration in response to peritoneal instillation of S. pneumoniae. The effect of mAb 60.3 on PMN emigration in the lungs varied depending upon the stimulus. PMN failed to migrate into the PMA-induced pneumonia; however, mAb 60.3 pretreatment only partially inhibited endotoxin-induced pneumonia and did not inhibit S. pneumoniae or hydrochloric acid-induced pneumonias. PMN lavaged from the alveolar spaces in the Streptococcal pneumonia had similar quantities of mAb 60.3 bound to their surfaces as the circulating PMN. We conclude that the CD11/CD18 complex mediates PMN adherence in the systemic circulation. However, PMN adherence in the pulmonary circulation may occur by either CD18-dependent or -independent mechanisms that are specific to the inciting stimulus.
Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing (2009)

Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing-related human diseases.
Primary structure of human proacrosin deduced from its cDNA sequence (1989)

cDNA clones encoding proacrosin, the zymogen of acrosin, were isolated from a human testis cDNA library by using a fragment of boar acrosin cDNA as a probe. Nucleotide sequencing of the longest cDNA clone has predicted that human proacrosin is synthesized with a 19-amino-acid signal peptide at the N-terminus. The cleavable signal sequence is followed by a 23-residue segment corresponding to the light chain and then by a 379-residue stretch that constitutes the heavy chain containing the catalytic site of the mature protease. The C-terminal portion of the deduced sequence for the heavy chain is very rich in proline residues, most of which are encoded by a unique repeat of CCCCCA. The active-site residues including histidine, aspartic acid, and serine are also predicted to be located at residues 69, 123, and 221, respectively.
Phenylboronic Acid−Salicylhydroxamic Acid Bioconjugates. 1. A Novel Boronic Acid Complex for Protein Immobilization (2001)

A chemical affinity system exhibiting antibody-like properties is described. The system exploits bioconjugates with appended phenylboronic acid (PBA) moieties and a support-bound phenylboronic acid complexing reagent derived from salicylhydroxamic acid (SHA) for protein immobilization on a chromatographic support. The structure of the PBA.SHA complex was characterized by 11B NMR and mass spectrometry and compared with complexes derived from model compounds. Protein modification reagents were synthesized from 3-aminophenylboronic acid and utilized to prepare bioconjugates from alkaline phosphatase (AP) and horseradish peroxidase (HRP). AP obtained from one source afforded PBA bioconjugates exhibiting significant loss of enzymatic activity, whereas AP obtained from a second source afforded PBA bioconjugates exhibiting only a modest loss of enzymatic activity. Conversely, HRP afforded PBA bioconjugates exhibiting no loss of enzymatic activity. SHA-modified Sepharose was prepared by reaction of methyl 4-[(6-aminohexanoylamino)methyl]salicylate with CNBr-activated Sepharose 4B, followed by treatment with aqueous alkaline hydroxylamine. PBA-AP and PBA-HRP conjugates were efficiently immobilized on SHA-Sepharose at pH 8.3. PBA-AP conjugates were retained after washing with acidic buffers at pH 6.7, 4.2, and 2.5, whereas PBA-HRP conjugates were retained after washing with buffer at pH 6.7, but were eluted to some extent at and below pH 4.2. The results are interpreted in terms of multivalent interactions involving boronic acid complex formation between the enzyme bioconjugates and immobilized complexing reagent.
Methyl‐CpG binding column‐based identification of nine genes hypermethylated in colorectal cancer (2011)

DNA methylation is an epigenetic event that plays a role in gene expression regulation. Alterations in DNA methylation contribute to cancer development and progression. The aim of this study was to identify gene promoters aberrantly methylated in colorectal tumor tissue in comparison to normal colonic mucosa. Analyses were performed on two pooled DNA samples: from normal and cancerous tissue obtained from CRC patients. DNA was fractionated according to methylation degree with the use of affinity column containing methyl-CpG binding domain. To identify novel hypermethylated gene promoters, methylated DNA from normal and from cancerous tissues were analyzed with the use of promoter microarrays. We identified nine novel genes hypermethylated in colorectal cancer. The frequency of their promoter methylation was assessed in the larger group of patients (n = 77): KCNK12 (methylated in 41% of CRC patients), GPR101 (40%), CDH2 (45%), BARX1 (56%), CNTFR (22%), SYT6 (64%), SMO (21%), EPHA5 (43%), and GSPT2 (21%). The results of gene expression level analysis suggest the role of promoter methylation in downregulation of six out of nine genes examined. We did not find correlation between gene methylation and age, gender, tumor grade or stage. Importantly, in stage IV CRC methylation of GPR101 correlated with longer time to progression (P = 0.0042; HR = 2.5468; 95% CI 1.5391-10.0708).
MyoD is required for myogenic stem cell function in adult skeletal muscle. (1996)

To investigate the function of MyoD in adult skeletal muscle, we interbred MyoD mutant mice with mdx mice, a model for Duchenne and Becker muscular dystrophy. Mice lacking both MyoD and dystrophin displayed a marked increase in severity of myopathy leading to premature death, suggesting a role for MyoD in muscle regeneration. Examination of MyoD mutant muscle revealed elevated numbers of myogenic cells; however, myoblasts derived from these cells displayed normal differentiation potential in vitro. Following injury, MyoD mutant muscle was severely deficient in regenerative ability, and we observed a striking reduction in the in vivo proliferation of myogenic cells during regeneration. Therefore, we propose that the failure of MyoD-deficient muscle to regenerate efficiently is not caused by a reduction in numbers of satellite cells, the stem cells of adult skeletal muscle, but results from an increased propensity for stem-cell self-renewal rather than progression through the myogenic program.