gebhart/patrepeval huggingface dataset:
Differential interaction of the tyrosine phosphatases PTP-SL, STEP and HePTP with the mitogen-activated protein kinases ERK1/2 and p38alpha is determined by a kinase specificity sequence and influenced by reducing agents (2003)

The protein tyrosine phosphatases (PTPs) PTP-SL, STEP and HePTP are mitogen-activated protein kinase (MAPK) substrates and regulators that bind to MAPKs through a kinase-interaction motif (KIM) located in their non-catalytic regulatory domains. We have found that the binding of these PTPs to the MAPKs extracellular-signal-regulated kinase 1 and 2 (ERK1/2), and p38α is differentially determined by the KIM-adjacent C-terminal regions of the PTPs, which have been termed kinase-specificity sequences, and is influenced by reducing agents. Under control conditions, PTP-SL bound preferentially to ERK1/2, whereas STEP and HePTP bound preferentially to p38α. Under reducing conditions, the association of p38α with STEP or HePTP was impaired, whereas the association with PTP-SL was unaffected. On the other hand, the association of ERK1/2 with HePTP was increased under reducing conditions, whereas the association with STEP or PTP-SL was unaffected. In intact cells, PTP-SL and STEP distinctively regulated the kinase activity and the nuclear translocation of ERK1/2 and p38α. Our results suggest that intracellular redox conditions could modulate the activity and subcellular location of ERK1/2 and p38α by controlling their association with their regulatory PTPs.
Algorithm Design (2005)

Algorithm Design introduces algorithms by looking at the real-world problems that motivate them. The book teaches students a range of design and analysis techniques for problems that arise in computing applications. The text encourages an understanding of the algorithm design process and an appreciation of the role of algorithms in the broader field of computer science.
Characterization of A U‐937 subline which can be induced to differentiate in serum‐free medium (1992)

We report the selection and characterization of a U-937 subline which is capable of long-term growth in serum-free medium and can be induced to differentiate. The subline (U-937-1SF) can be maintained in standard RPMI-1640 medium supplemented by antibiotics only. As compared to the serum-dependent U-937 parental cell line, U-937-1SF produced lower amounts of lysozyme and elastase and had a decreased surface expression of complement receptor 1 (CD35) and myeloid antigens CDw17 and CD38. Apart from these alterations, the U-937-1SF cells appear to be morphologically, cytogenetically and phenotypically similar to the parental U-937 clone-1 cells. The capacity of U-937 clone-1 cells to undergo phorbol myristic acid (PMA)-, vitamin D3 (VitD3)- and retinoic-acid (RA)-induced differentiation was retained in the U-937-1SF cells as evidenced by the induced growth arrest, development of a monocyte/macrophage morphology and increased expression of differentiation-associated antigens, e.g. CD11b, CD11c, CD14 and CD18. The growth-inhibitory response to cytokines involved in the activation and differentiation of monocytes, IFN-gamma, TNF-alpha, IL-1 beta, IL-6 and GM-CSF, was normal. Our results suggest that the U-937-1SF subline can be used as a serum-free model system for studies on various aspects of monocyte differentiation.
Monoclonal antibody neutralization escape mutants of respiratory syncytial virus with unique alterations in the attachment (G) protein. (1998)

Five monoclonal antibody (MAb) neutralization escape mutants of respiratory syncytial virus (RSV) were produced by growing the Long strain RSV (group A virus) in the presence of a neutralizing, group cross-reactive MAb specific for the attachment protein (G). Four viruses (RSV-2, -6, -14 and -15) had amino acid replacements clustered within a highly conserved centrally located 13 amino acid region (position 164-176). Reactivity with group A-specific MAbs and with polyclonal anti-G serum was maintained and growth kinetics were unaffected. An additional virus (RSV-3) had four amino acid substitutions in the cytoplasmic tail and transmembrane region of G, and had restricted growth and formed small syncytia. Immunofluorescent and Western blot analysis indicated that G protein was not membrane associated and had reduced incorporation into the virion, thereby escaping neutralization by L9 and polyclonal anti-G serum. The predominant form of G produced by RSV-3 was found in infected cell supernatants, consistent with the size of secreted G.
Physiologic and biochemical effects of electroacupuncture combined with intramuscular administration of dexmedetomidine to provide analgesia in goats (2016)

Abstract OBJECTIVE To investigate physiologic and biochemical effects of electroacupuncture and dexmedetomidine administration to goats. ANIMALS 30 healthy adult goats. PROCEDURES Goats were allotted to 5 groups (6 goats/group) and received electroacupuncture, dexmedetomidine (5 or 20 μg/kg, IM), electroacupuncture plus dexmedetomidine (5 μg/kg, IM), or saline (0.9% NaCl) solution (IM [control treatment]). Pain threshold, cardiorespiratory effects, rectal temperature, and hematologic and biochemical variables were assessed. RESULTS Dexmedetomidine (20 μg/kg) increased pain threshold and decreased heart rate, respiratory rate, and rectal temperature. Pain threshold of goats receiving electroacupuncture plus dexmedetomidine (5 μg/kg) was higher than that of goats receiving electroacupuncture or of goats receiving dexmedetomidine at 5 μg/kg at 30 minutes, but did not differ from that of goats receiving dexmedetomidine at 20 μg/kg. Compared with goats administered dexmedetomidine at 20 μg/kg, goats receiving electroacupuncture plus dexmedetomidine at 5 μg/kg had a higher heart rate from 30 to 60 minutes and a higher respiratory rate from 5 to 60 minutes. Electroacupuncture plus dexmedetomidine (5 μg/kg) did not affect rectal temperature. Serum glucose concentrations of goats receiving electroacupuncture plus dexmedetomidine (5 μg/kg) were higher than for goats receiving dexmedetomidine at 5 μg/kg at 30 minutes but not for goats receiving dexmedetomidine at 20 μg/kg. Creatinine and BUN concentrations, alanine or aspartate aminotransferase activities, and hematologic variables of treated goats did not change. CONCLUSIONS AND CLINICAL RELEVANCE Electroacupuncture in combination with a low dose of dexmedetomidine (5 μg/kg, IM) administered to goats provided antinociception.
N-Benzyloxycarbonyl-Valyl-Prolinal, a Potent Inhibitor of Post-Proline Cleaving Enzyme1 (1984)

A peptide aldehyde inhibitor possessing prolinal at the carboxyl terminus was designed as an inhibitor of post-proline cleaving enzyme by analogy with peptide aldehyde inhibitors of serine and thiol proteases. N-Benzyloxycarbonyl-valyl-prolinal was found to be a potent inhibitor of post-proline cleaving enzyme from ascidian sperm with a K1 value of 2.4 nM. The presence of the aldehyde portion of the inhibitor, as well as its prolonged incubation with the enzyme, is indispensable for the potent inhibitory activity of the inhibitor. These results indicate that N-benzyloxycarbonyl-valyl-prolinal functions as a transition-state aldehyde inhibitor of post-proline cleaving enzyme.
Phases of Aβ-deposition in the human brain and its relevance for the development of AD (2002)

Abeta-deposition in the entire brain follows a distinct sequence in which the regions are hierarchically involved. Abeta-deposition, thereby, expands anterogradely into regions that receive neuronal projections from regions already exhibiting Abeta. There are also indications that clinically proven AD cases with full-blown beta-amyloidosis may be preceded in early stages by nondemented cases exhibiting AD-related Abeta pathology.
Discrimination of von Willebrands Disease (VWD) Subtypes: Direct Comparison of von Willebrand Factor:Collagen Binding Assay (VWF:CBA) with Monoclonal Antibody (MAB) Based VWF-capture Systems (2000)

Discrimination of von Willebrand's Disease (VWD) subtypes is important since it influences management. Qualitative [ie Type 2A, 2B, 2M] defects exhibit von Willebrand factor (VWF) discordance and give high VWF:Ag to VWF:'activity' ratios. Classically, VWF:'activity' is assessed using the VWF:RCof assay. The VWF:CBA is an ELISA-based VWF-functional adhesive assay which has consistently proved to be superior to VWF:RCof. A commercially available monoclonal antibody (MAB) based ELISA assay system claimed to mimic a VWF:RCof-like activity has also been recently described ('SE'), as has the production and characterisation of a large number [n = 10] of locally generated anti-VWF MAB. In the current study, we have adapted these MAB to in-house ELISA assays to assess their utility for VWD diagnosis and subtype discrimination, and to compare them with other assay systems. Thus, the VWF:CBA, VWF:RCof by agglutination, the SE assay, and in-house MAB based assays have been directly compared for their ability to discriminate Type 1 [n = 9] from Type 2 VWD samples [phenotypes 2A and 2B; n = 11]. In summary, MAB-based systems can be used to measure VWF and confirm a diagnosis of VWD, as well as exhibiting some VWD-subtype-discriminatory capabilities. However, better evidence of VWF-discordance was usually achieved using the VWF:RCof (agglutination) assay, while the greatest degree of VWF-discordance was consistently observed using the VWF:CBA assay. In conclusion, the VWF:CBA assay proved to offer the best diagnostic predictive tool for a Type 2 VWD defect, while MAB-based systems appear to be less effective in this regard.
Antibody production of a human EBV-transformed B cell line and its heterohybridoma and trioma cell line descendants in different culture systems. (1994)

Cells of an EBV-transformed human lymphoblastoid B cell line, producing antibodies directed against tetanus toxin, were fused with mouse myeloma cells (SP2/0) and with mouse-human heteromyeloma cells (SPAM-8) resulting in the formation of heterohybridoma and trioma cells, respectively. Antibody production of the three cell lines were studied under different culture conditions. All three cell lines produced antibodies in concentrations ranging from 2.6 to 6.4 micrograms ml-1 in spent medium from stationary flask cultures. Dialysis cultures of trioma and heterohybridoma cells resulted in concentrations of 36 and 20 micrograms ml-1, respectively, whereas no significant increase was obtained with the EBV-transformed cells. Trioma cells, cultured in a hollow fiber cartridge bioreactor produced antibodies in concentrations of average of 303 micrograms ml-1, whereas the EBV-transformed cells did not adapt to this system. Furthermore, trioma and heterohybridoma cells injected into the intraperitoneal cavity of SCID-mice, produced antibodies in ascites fluid in concentrations of 500 and 640 micrograms ml-1 respectively.
The Molecular Architecture of Galactose Mutarotase/UDP-Galactose 4-Epimerase from Saccharomyces cerevisiae (2005)

The metabolic pathway by which beta-D-galactose is converted to glucose 1-phosphate is known as the Leloir pathway and consists of four enzymes. In most organisms, these enzymes appear to exist as soluble entities in the cytoplasm. In yeast such as Saccharomyces cerevisiae, however, the first and last enzymes of the pathway, galactose mutarotase and UDP-galactose 4-epimerase, are contained within a single polypeptide chain referred to as Gal10p. Here we report the three-dimensional structure of Gal10p in complex with NAD(+), UDP-glucose, and beta-D-galactose determined to 1.85-A resolution. The enzyme is dimeric with dimensions of approximately 91 A x 135 A x 108 A and assumes an almost V-shaped appearance. The overall architecture of the individual subunits can be described in terms of two separate N- and C-terminal domains connected by a Type II turn formed by Leu-357 to Val-360. The first 356 residues of Gal10p fold into the classical bilobal topology observed for all other UDP-galactose 4-epimerases studied thus far. This N-terminal domain contains the binding sites for NAD(+) and UDP-glucose. The polypeptide chain extending from Glu-361 to Ser-699 adopts a beta-sandwich motif and harbors the binding site for beta-D-galactose. The two active sites of Gal10p are separated by over 50 A. This investigation represents the first structural analysis of a dual function enzyme in the Leloir pathway.
Induction of CD4+ and CD8+ anti‐tumor effector T cell responses by bacteria mediated tumor therapy (2015)

Facultative anaerobic bacteria like E. coli can colonize solid tumors often resulting in tumor growth retardation or even clearance. Little mechanistic knowledge is available for this phenomenon which is however crucial for optimization and further implementation in the clinic. Here, we show that intravenous injections with E. coli TOP10 can induce clearance of CT26 tumors in BALB/c mice. Importantly, re-challenging mice which had cleared tumors showed that clearance was due to a specific immune reaction. Accordingly, lymphopenic mice never showed tumor clearance after infection. Depletion experiments revealed that during induction phase, CD8(+) T cells are the sole effectors responsible for tumor clearance while in the memory phase CD8(+) and CD4(+) T cells were involved. This was confirmed by adoptive transfer. CD4(+) and CD8(+) T cells could reject newly set tumors while CD8(+) T cells could even reject established tumors. Detailed analysis of adoptively transferred CD4(+) T cells during tumor challenge revealed expression of granzyme B, FasL, TNF-α and IFN-γ in such T cells that might be involved in the anti-tumor activity. Our findings should pave the way for further optimization steps of this promising therapy.
Workload design: selecting representative program-input pairs (2002)

Having a representative workload of the target domain of a microprocessor is extremely important throughout its design. The composition of a workload involves two issues: (i) which benchmarks to select and (ii) which input data sets to select per benchmark. Unfortunately, it is impossible to select a huge number of benchmarks and respective input sets due to the large instruction counts per benchmark and due to limitations on the available simulation time. In this paper, we use statistical data analysis techniques such as principal components analysis (PCA) and cluster analysis to efficiently explore the workload space. Within this workload space, different input data sets for a given benchmark can be displayed, a distance can be measured between program-input pairs that gives us an idea about their mutual behavioral differences and representative input data sets can be selected for the given benchmark. This methodology is validated by showing that program-input pairs that are close to each other in this workload space indeed exhibit similar behavior. The final goal is to select a limited set of representative benchmark-input pairs that span the complete workload space. Next to workload composition, there are a number of other possible applications, namely getting insight in the impact of input data sets on program behavior and profile-guided compiler optimizations.
Characterization and functional expression in Escherichia coli of the sodium/proton/glutamate symport proteins of Bacillus stearothermophilus and Bacillus caldotenax (1992)

The genes encoding the Na+/H+/L-glutamate symport proteins of the thermophilic organisms Bacillus stearothermophilus (gltTBs) and Bacillus caldotenax (gltTBc) were cloned by complementation of Escherichia coli JC5412 for growth on glutamate as sole source of carbon, energy and nitrogen. The nucleotide sequences of the gltTBs and gltTBc genes were determined. In both cases the translated sequences corresponded with proteins of 421 amino acid residues (96.7% amino acid identity between GltTBs and GltTBc). Putative promoter, terminator and ribosome-binding-site sequences were found in the flanking regions. These expression signals were functional in E. coli. The hydropathy profiles indicate that the proteins are hydrophobic and could form 12 membrane-spanning regions. The Na+/H+ coupled L-glutamate symport proteins GltTBs and GltTBc are homologous to the strictly H+ coupled L-glutamate transport protein of E. coli K-12 (overall 57.2% identity). Functional expression of glutamate transport activity was demonstrated by uptake of glutamate in whole cells and membrane vesicles. In accordance with previous observations (de Vrij et al., 1989; Heyne et al., 1991), glutamate uptake was driven by the electrochemical gradients of sodium ions and protons.
Film surface morphology and field‐emission characteristics of a carbon‐nanotube array pattern fabricated under a magnetic field (2008)

Abstract— This study focuses on the influence of sodium metasilicate binder on CNT paste and the arrangment of Mg‐Ni alloy multi‐walled carbon nanotubes on the surface of CNT film under the influence of a magnetic field. The CNT paste was prepared by mixing CNTs with silver epoxy resin and sodium metasilicate solution and coating them onto the surface of indium tin oxide (ITO) glass. The impact of sodium metasilicate solution and magnetic strength on the morphology of the paste film's surface and on the field‐emission (FE) characterics of the cathode was examined. The experimental results showed that the CNT paste provided good adhesion between the CNT array and silver epoxy resin when sodium metasilicate solution was presented. CNT paste containing sodium metasilicate showed a better dispersion with silver epoxy resin and a better CNT‐array pattern, and better vertical alignment of the CNT was obtained when the magnetic field and grid were both appied. An optimal condition for a better CNT‐array pattern for both the morphology and FE characteristics had a magnetic strength of 1 89 mT, magnetization time of 30 min, and a grid above the cathode.
High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen (2005)

Surgical resection remains a definitive treatment for prostate cancer. Yet, prostate cancer surgery is performed without image guidance for tumor margin, extension beyond the capsule and lymph node positivity, and without verification of other occult metastases in the surgical field. Recently, several imaging systems have been described that exploit near-infrared (NIR) fluorescent light for sensitive, real-time detection of disease pathology intraoperatively. In this study, we describe a high-affinity (9 nM), single nucleophile-containing, small molecule specific for the active site of the enzyme PSMA. We demonstrate production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent derivative of this molecule using a high-yield LC/MS purification strategy. Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we provide mechanistic insight into this observation. We describe the preparative production of enzymatically active PSMA using a baculovirus expression system and an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and specific in vitro imaging of endogenous and ectopically expressed PSMA in human cells and in vivo imaging of xenograft tumors. We also discuss chemical strategies for improving performance even further. Taken together, this study describes nearly complete preclinical development of an optically based small-molecule contrast agent for image-guided surgery.
Basic fibroblast growth factor stimulates articular cartilage enlargement in young rats in vivo (1996)

Basic fibroblast growth factor is a potent mitogen for chondrocytes and influences the protein synthesis of their extracellular matrix in vitro. To investigate its effect on normal developing articular cartilage in vivo, we injected basic fibroblast growth factor once into the knee joints of 4-week-old rats. Phosphate buffered saline was similarly injected into the contralateral knee joints as controls. A histological analysis showed that an injection of basic fibroblast growth factor induced enlargement of the articular cartilage area, especially in the condylar ridge region on day 7 after the injection. The extent of the enlargement was dose-dependent. The localization and amount of proliferating cells in the articular cartilage were analyzed immunohistochemically by the detection of proliferating cell nuclear antigen. On day 1 after the injection, the number of cells positive for proliferating cell nuclear antigen increased significantly in the joints that were injected compared with the controls, and Northern blot analysis showed that the level of messenger RNA for alpha 1(II) procollagen was lower in these joints than in the controls. The message in the joints that had been injected increased on day 7, and it was greater than that in the controls. This suggests that proliferating chondrocytes in developing articular cartilage respond to basic fibroblast growth factor with a resulting proliferation of chondrocytes followed by enlargement of cartilage.
Pharmacological Rescue of Human K + Channel Long-QT2 Mutations (2002)

Pharmacological rescue can occur without channel block. This could represent a new antiarrhythmic paradigm in the treatment of some trafficking-defective LQT2 mutations.
Fast estimation of the parameters of alpha-stable impulsive interference (1996)

We address the problem of estimation of the parameters of the recently proposed symmetric, alpha-stable model for impulsive interference. We propose new estimators based on asymptotic extreme value theory, order statistics, and fractional lower order moments, which can be computed fast and are, therefore, suitable for the design of real-time signal processing algorithms. The performance of the new estimators is theoretically evaluated, verified via Monte Carlo simulation, and compared with the performance of maximum-likelihood estimators.
IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection (1992)

Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF.
Analysis of utility interactive photovoltaic generation system using a single power static inverter (2002)

This paper presents the analysis of a static conversion system for treatment of the solar energy from photovoltaic panels. This system is interconnected with the mains power supply, contributing to the generation of the electrical energy. The power structure is composed of a current-fed push-pull converter, a buck converter, and a current inverter. The main features of the system are: simple control strategy, robustness, lower harmonic distortion of the current and natural isolation. The principle of operation, design procedure and experimental results are presented.