gebhart/patrepeval huggingface dataset:
Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease (2012)

This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.
Efficacy of combined octreotide and cabergoline treatment in patients with acromegaly: a retrospective clinical study and review of the literature (2013)

Although somatostatin analogues are effective medical therapy for acromegaly, the serum insulin-like growth factor-I (IGF-I) levels remain uncontrolled in 35% of patients. Combined therapy with octreotide LAR and cabergoline has been reported to normalize IGF-I levels in 42-56% of Caucasian patients with acromegaly. However, it remains to be clarified whether combination therapy is effective in Japanese patients and on tumor shrinkage. We conducted a retrospective study on combined therapy in patients with octreotide-resistant acromegaly. Ten patients with acromegaly who showed octreotide-resistance were enrolled in this study. Cabergoline was added in doses of 0.25-2.0mg/week. Serum GH and IGF-I levels and tumor volume were assessed before and after treatment, and factors correlated with effect of the combined therapy were analyzed. Although serum GH levels did not decrease, serum IGF-I levels significantly decreased by 20% after 6 months of combined therapy compared with baseline (p < 0.05). As a result, serum IGF-I levels normalized in 30% of the patients. Tumor volume after combined therapy also significantly decreased (p < 0.01). There were no correlations between the decrease of serum IGF-I levels during combined therapy and the response of GH in a bromocriptine test, random GH, IGF-I, and PRL levels, the tumor volume, and the expression of PRL and dopamine D2 receptor in the tumor. In conclusion, we demonstrated that the addition of cabergoline to octreotide LAR is a beneficial option in Japanese patients with octreotide-resistant acromegaly, irrespective of serum PRL levels and the response of GH levels in a bromocriptine test.
Fundamentals of Solid State Electronics (1991)

Electrons, bonds, bands and holes homogeneous semiconductor at equilibrium drift, diffusion, generation, recombination, trapping and tunneling metal-oxide-semiconductor capacitor P/N and other junction diodes metal-oxide-semiconductor and other field-effect transistors bipolar junction transistor and other bipolar transistor devices.
A Reconfigurable Fabric for Accelerating Large-Scale Datacenter Services (2015)

To advance datacenter capabilities beyond what commodity server designs can provide, the authors designed and built a composable, reconfigurable fabric to accelerate large-scale software services. Each instantiation of the fabric consists of a 6 x 8 2D torus of high-end field-programmable gate arrays (FPGAs) embedded into a half-rack of 48 servers. The authors deployed the reconfigurable fabric in a bed of 1,632 servers and FPGAs in a production datacenter and successfully used it to accelerate the ranking portion of the Bing Web search engine by nearly a factor of two.
Lotus Notes 4 Administrator's Survival Guide (1996)

Specific to system administrators, this book describes in detail the procedures and techniques necessary to run an efficient Lotus Notes environment. It specifies installation, configuration, system administration, and day-to-day maintenance techniques crucial to any Notes administrator.Provides unparalleled coverage of the physical components of the environmentDetails tuning, optimization, and troubleshooting tipsCD-ROM contains source code from the book and various demos from Notes-related software companies
Human Pericytes for Ischemic Heart Repair (2012)

Human microvascular pericytes (CD146(+)/34(-)/45(-)/56(-)) contain multipotent precursors and repair/regenerate defective tissues, notably skeletal muscle. However, their ability to repair the ischemic heart remains unknown. We investigated the therapeutic potential of human pericytes, purified from skeletal muscle, for treating ischemic heart disease and mediating associated repair mechanisms in mice. Echocardiography revealed that pericyte transplantation attenuated left ventricular dilatation and significantly improved cardiac contractility, superior to CD56+ myogenic progenitor transplantation, in acutely infarcted mouse hearts. Pericyte treatment substantially reduced myocardial fibrosis and significantly diminished infiltration of host inflammatory cells at the infarct site. Hypoxic pericyte-conditioned medium suppressed murine fibroblast proliferation and inhibited macrophage proliferation in vitro. High expression by pericytes of immunoregulatory molecules, including interleukin-6, leukemia inhibitory factor, cyclooxygenase-2, and heme oxygenase-1, was sustained under hypoxia, except for monocyte chemotactic protein-1. Host angiogenesis was significantly increased. Pericytes supported microvascular structures in vivo and formed capillary-like networks with/without endothelial cells in three-dimensional cocultures. Under hypoxia, pericytes dramatically increased expression of vascular endothelial growth factor-A, platelet-derived growth factor-β, transforming growth factor-β1 and corresponding receptors while expression of basic fibroblast growth factor, hepatocyte growth factor, epidermal growth factor, and angiopoietin-1 was repressed. The capacity of pericytes to differentiate into and/or fuse with cardiac cells was revealed by green fluorescence protein labeling, although to a minor extent. In conclusion, intramyocardial transplantation of purified human pericytes promotes functional and structural recovery, attributable to multiple mechanisms involving paracrine effects and cellular interactions.
Fungicidal action of aureobasidin A, a cyclic depsipeptide antifungal antibiotic, against Saccharomyces cerevisiae (1997)

Aureobasidin A, an antifungal antibiotic inhibiting a wide range of pathogenic fungi, is lethal for growing cells of susceptible fungi. We did cytological studies on the mechanism of its fungicidal action against Saccharomyces cerevisiae. When cultures were treated with 5.0 micrograms of aureobasidin A per ml, the numbers of viable cells started to decrease after 2 to 3 h of incubation, and most cells had lost viability after 5 to 6 h. When cell death in the treated cultures began, amino acids released by the cells could be detected, indicating disruption of the cell membrane. The proportion of cells with a single small bud or two or more buds increased as the population of viable cells decreased. Most such cells had the DNA content of cells in the G2 phase of the cell cycle, suggesting that the drug inhibited some cellular process involved in normal bud growth but did not affect DNA replication. Disruption of actin assembly was found in many cells treated for 2 to 3 h, as was chitin delocalization. The results suggest that aureobasidin A has a previously unknown mechanism of fungicidal action toward S. cerevisiae. It causes aberrant actin assembly, inhibiting the normal budding process and leading to cell death, probably through destruction of membrane integrity.
X-ray Structures of Human Neutrophil Collagenase Complexed with Peptide Hydroxamate and Peptide Thiol Inhibitors. Implications for Substrate Binding and Rational Drug Design (1995)

Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases involved in tissue remodeling. They have also been implicated in various disease processes including tumour invasion and joint destruction and are therefore attractive targets for inhibitor design. For rational drug design, information of inhibitor binding at the atomic level is essential. Recently, we have published the refined high-resolution crystal structure of the catalytic domain of human neutrophil collagenase (HNC) complexed with the inhibitor Pro-Leu-Gly-NHOH, which is a mimic for the unprimed (P3-P1) residues of a bound peptide substrate. We have now determined two additional HNC complexes formed with the thiol inhibitor HSCH2CH(CH2Ph)CO-L-Ala-Gly-NH2 and another hydroxamate inhibitor, HONHCOCH(iBu)CO-L-Ala-Gly-NH2, which were both refined to R -values of 0.183/0.198 at 0.240/0.225-nm resolution. The inhibitor thiol and hydroxamate groups ligand the catalytic zinc, giving rise to a slightly distorted tetrahedral and trigonal-bipyramidal coordination sphere, respectively. The thiol inhibitor diastereomer with 5-configura-tion at the PI′ residue (corresponding to an L-amino acid analog) binds to HNC. Its peptidyl moiety mimics binding of primed (PI′–P3′) residues of the substrate. In combination with our first structure a continuous hexapeptide corresponding to a peptide substrate productively bound to HNC was constructed and energy-minimized. Proteolytic cleavage of this Michaelis complex is probably general base-catalyzed as proposed for thermolysin, i.e. a glutamate assists nucleophilic attack of a water molecule. Although there are many structural and mechanistic similarities to thermolysin, substrate binding to MMPs differs due to the interactions beyond S1′-P1′. While thermolysin binds substrates with a kink at PI′, substrates are bound in an extended conformation in the collagenases. This property explains the tolerance of theimolysin for D-amino acid residues at the PI′ position, in contrast to the collagenases. The third inhibitor, HONHCOCH(iBu)CO-L-Ala-Gly-NH2, unexpectedly binds in a different manner than anticipated from its design and binding mode in thermolysin. Its hydroxamate group obviously interacts with the catalytic zinc in a favourable bidentate manner, but in contrast its isobutyl (iBu) side chain remains outside of the SI′ pocket, presumably due to severe constraints imposed by the adjacent planar hydroxamate group. Instead, the C-terminal Ala-Gly-NH2 tail adopts a bent conformation and inserts into this SI′ pocket, presumably in a non-optimized manner. Both the isobutyl side chain and the C-terminal peptide tail could be replaced by other, better fitting groups. Thus this inhibitor seems to represent a new lead structure suitable for designing better drugs.
A Bioorthogonal Quadricyclane Ligation (2011)

New additions to the bioorthogonal chemistry compendium can advance biological research by enabling multiplexed analysis of biomolecules in complex systems. Here we introduce the quadricyclane ligation, a new bioorthogonal reaction between the highly strained hydrocarbon quadricyclane and Ni bis(dithiolene) reagents. This reaction has a second-order rate constant of 0.25 M(-1) s(-1), on par with fast bioorthogonal reactions of azides, and proceeds readily in aqueous environments. Ni bis(dithiolene) probes selectively labeled quadricyclane-modified bovine serum albumin, even in the presence of cell lysate. We have demonstrated that the quadricyclane ligation is compatible with, and orthogonal to, strain-promoted azide-alkyne cycloaddition and oxime ligation chemistries by performing all three reactions in one pot on differentially functionalized protein substrates. The quadricyclane ligation joins a small but growing list of tools for the selective covalent modification of biomolecules.
The functional capacity of the natural amino acids for molecular recognition (2010)

We tested the functional capacity of the natural amino acids for molecular recognition in a minimalist background of binary Tyr/Ser diversity. In phage-displayed synthetic antibody libraries, we replaced either Tyr or Ser with other residues. We find that Tyr is optimal for mediating contacts that contribute favourably to both affinity and specificity, but it can be replaced by Trp, which contributes favourably to affinity but is detrimental to specificity. Arg exhibited a limited capacity for mediating molecular recognition but was less effective than either Tyr or Trp, and moreover, was the major contributor to non-specific interactions. Nine other residue types (Phe, Leu, Ile, Asn, Thr, Pro, Cys, Ala, and Gly) were found to be ineffective as replacements for Tyr. By replacing Ser with Gly or Ala, we found that Gly is as effective as Ser for providing conformational flexibility that allows bulky Tyr residues to achieve optimal binding contacts, while Ala is less effective but still functional in this capacity. For some antigens, high affinity antibodies could be derived using only Tyr/Ser/Gly diversity, but for others, additional chemical diversity was required to achieve high affinity. Our results establish a minimal benchmark for the generation of synthetic antigen-binding sites with affinities comparable to those of natural antibodies. Moreover, our findings illuminate the fundamental principles underlying protein-protein interactions and provide valuable guidelines for engineering synthetic binding proteins with functions beyond the scope of natural proteins.
Involvement of cyclic AMP and its receptor protein in filamentation of an Escherichia coli fic mutant (1982)

Cyclic AMP (cAMP) inhibited septum formation in Escherichia coli PA3092 and induced cell filamentation at elevated temperatures. This phenomenon was first observed in E. coli PA3092 and is due to a temperature-sensitive mutation. We tentatively named this mutation fic (filamentation induced by cAMP). The fic gene was located near rpsL (formerly strA) on the E. coli K-12 map. the inhibitory effect of cAMP on cell division and filamentation in a fic mutant was not observed in a crp mutant. When cAMP was removed from the culture medium, filaments were divided into rods as the intracellular cAMP level decreased. These results suggest that the cAMP-cAMP receptor protein complex causes filamentation in the fic mutant, E. coli PA3092.
The PGE2 EP2 receptor and its selective activation are beneficial against ischemic stroke (2010)

Together, our results reveal that pharmacologic stimulation of the EP2 receptor has an important beneficial role in cerebral ischemia and might be considered as an adjunct therapy for ischemic stroke.
Migraine Treatment With Rizatriptan and Almotriptan: A Crossover Study (2009)

Times to achieve PR and PF were significantly shorter for patients using rizatriptan, as compared with those using almotriptan.
N -Acetylglucosaminyltransferase V (Mgat5)-Mediated N -Glycosylation Negatively Regulates Th1 Cytokine Production by T Cells (2004)

The differentiation of naive CD4(+) T cells into either proinflammatory Th1 or proallergic Th2 cells strongly influences autoimmunity, allergy, and tumor immune surveillance. We previously demonstrated that beta1,6GlcNAc-branched complex-type (N-acetylglucosaminyltransferase V (Mgat5)) N-glycans on TCR are bound to galectins, an interaction that reduces TCR signaling by opposing agonist-induced TCR clustering at the immune synapse. Mgat5(-/-) mice display late-onset spontaneous autoimmune disease and enhanced resistance to tumor progression and metastasis. In this study we examined the role of beta1,6GlcNAc N-glycan expression in Th1/Th2 cytokine production and differentiation. beta1,6GlcNAc N-glycan expression is enhanced by TCR stimulation independent of cell division and declines at the end of the stimulation cycle. Anti-CD3-activated splenocytes and naive T cells from Mgat5(-/-) mice produce more IFN-gamma and less IL-4 compared with wild-type cells, the latter resulting in the loss of IL-4-dependent down-regulation of IL-4Ralpha. Swainsonine, an inhibitor of Golgi alpha-mannosidase II, blocked beta1,6GlcNAc N-glycan expression and caused a similar increase in IFN-gamma production by T cells from humans and mice, but no additional enhancement in Mgat5(-/-) T cells. Mgat5 deficiency did not alter IFN-gamma/IL-4 production by polarized Th1 cells, but caused an approximately 10-fold increase in IFN-gamma production by polarized Th2 cells. These data indicate that negative regulation of TCR signaling by beta1,6GlcNAc N-glycans promotes development of Th2 over Th1 responses, enhances polarization of Th2 cells, and suggests a mechanism for the increased autoimmune disease susceptibility observed in Mgat5(-/-) mice.
Optical Flow Switching Networks (2012)

Present-day networks are being challenged by dramatic increases in data rate demands of emerging applications. A new network architecture, incorporating “optical flow switching,” will enable significant rate growth, power efficiency, and cost-effective scalability of next-generation networks. We will explore architecture concepts germinated 22 years ago, technology and testbed demonstrations performed in the last 17 years, and the architecture construct from the physical layer to the transport layer of an implementable optical flow switching network that is scalable and manageable.
Acid Phosphatase from Rat Liver (1968)

Rat liver acid phosphatase (EC 3.1.3.2) was separated into two highly purified fractions, differing in isoelectric point and Km. One fraction was crystallized and proved homogeneous by ultracentrifugation and polyacrylamide gel electrophoresis. The molecular weights (100,000), substrate specificities, and pH optima of both enzymes were similar. Oxalate was a mixed type inhibitor to both enzymes. In the presence of dioxane, both enzymes exhibited sigmoidal inhibition curves by oxalate and by trypan blue.
Structure of the Protease Domain of Memapsin 2 (β-Secretase) Complexed with Inhibitor (2000)

Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.
Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation (2007)

Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array-based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR, prompting us to search for such genomic imbalances in autism. Here we describe a 1.5-Mb duplication on chromosome 16p13.1 that was found by high-resolution array CGH in four severe autistic male patients from three unrelated families. The same duplication was identified in several variably affected and unaffected relatives. A deletion of the same interval was detected in three unrelated patients with MR and other clinical abnormalities. In one patient we revealed a further rearrangement of the 16p13 imbalance that was not present in his unaffected mother. Duplications and deletions of this 1.5-Mb interval have not been described as copy number variants in the Database of Genomic Variants and have not been identified in >600 individuals from other cohorts examined by high-resolution array CGH in our laboratory. Thus we conclude that these aberrations represent recurrent genomic imbalances which predispose to autism and/or MR.
Light-Induced Conversion of Nicotinamide Adenine Dinucleotide to Nicotinamide Adenine Dinucleotide Phosphate in Higher Plant Leaves (1981)

Light-induced conversion of NAD to NADP was investigated in higher plants. Upon illumination, conversion of NAD to NADP was observed in intact leaves of wheat and pea following incubation in the dark. This conversion was also observed in mesophyll protoplasts of wheat leaves when they were isolated in the dark or isolated in light and then preincubated in the dark. Chloroplasts isolated from wheat protoplasts prepared in the dark carried out the conversion. The conversion in the mechanically isolated spinach chloroplasts was observed only when they were isolated in the dark from leaves preincubated in darkness.Sucrose density gradient centrifugation of wheat protoplast extracts and differential centrifugation of protoplast extracts from various plants showed that most of the NAD kinase was localized in the chloroplasts. Therefore, the conversion of NAD to NADP is considered to occur in the chloroplasts. However, with extracts of maize mesophyll protoplasts, the enzyme was localized in the extrachloroplast fraction. The NAD kinase was activated some 30% by illumination of leaves or protoplasts of pea and wheat after preincubation in the dark.These results suggest that, in general, the light-induced conversion of NAD to NADP occurs in the chloroplast and is catalyzed by photoactivated NAD kinase using photochemically produced ATP.
Biochemical Interactions Integrating Itk with the T Cell Receptor-initiated Signaling Cascade (2000)

Itk, a Tec family tyrosine kinase, acts downstream of Lck and phosphatidylinositol 3'-kinase to facilitate T cell receptor (TCR)-dependent calcium influxes and increases in extracellular-regulated kinase activity. Here we demonstrate interactions between Itk and crucial components of TCR-dependent signaling pathways. First, the inositide-binding pocket of the Itk pleckstrin homology domain directs the constitutive association of Itk with buoyant membranes that are the primary site of TCR activation and are enriched in both Lck and LAT. This association is required for the transphosphorylation of Itk. Second, the Itk proline-rich region binds to Grb2 and LAT. Third, the Itk Src homology (SH3) 3 and SH2 domains interact cooperatively with Syk-phosphorylated SLP-76. Notably, SLP-76 contains a predicted binding motif for the Itk SH2 domain and binds to full-length Itk in vitro. Finally, we show that kinase-inactive Itk can antagonize the SLP-76-dependent activation of NF-AT. The inhibition of NF-AT activation depends on the Itk pleckstrin homology domain, proline-rich region, and SH2 domain. Together, these observations suggest that multivalent interactions recruit Itk to LAT-nucleated signaling complexes and facilitate the activation of LAT-associated phospholipase Cgamma1 by Itk.
Adipocyte iron regulates adiponectin and insulin sensitivity (2012)

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores.