gebhart/patrepeval huggingface dataset:
Catalytic Reactions of the Homogentisate Prenyl Transferase Involved in Plastoquinone-9 Biosynthesis (2010)

Homogentisate solanesyl transferase (HST) catalyzes the prenylation and decarboxylation of homogentisate to form 2-methyl-6-solanesyl-1,4-benzoquinol, the first intermediate in plastoquinone-9 biosynthesis. In vitro, HST from Spinacia oleracea L., Arabidopsis thaliana, and Chlamydomonas reinhardtii were all found to use not only solanesyl diphosphate but also short chain prenyl diphosphates of 10-20 carbon atoms as prenyl donors. Surprisingly, with these donors, prenyl transfer was largely decoupled from decarboxylation, and thus the major products were 6-prenyl-1,4-benzoquinol-2-methylcarboxylates rather than the expected 2-methyl-6-prenyl-1,4-benzoquinols. The 6-prenyl-1,4-benzoquinol-2-methylcarboxylates were not substrates for HST-catalyzed decarboxylation, and the enzyme kinetics associated with forming these products appeared quite distinct from those for 2-methyl-6-prenyl-1,4-benzoquinol formation in respect of catalytic rate, substrate K(m) value, and the pattern of inhibition by haloxydine, a molecule that appeared to act as a dead end mimic of homogentisate. These observations were reconciled into a simple model for the HST mechanism. Here, prenyl diphosphate binds to HST to form at least two alternative complexes that go on to react differently with homogentisate and prenylate it either with or without it first being decarboxylated. It is supposed that solanesyl diphosphate binds tightly and preferentially in the mode that compels prenylation with decarboxylation.
Structural determinants of the conformations of medium‐sized loops in proteins (1989)

Loops are integral components of protein structures, providing links between elements of secondary structure, and in many cases contributing to catalytic and binding sites. The conformations of short loops are now understood to depend primarily on their amino acid sequences. In contrast, the structural determinants of longer loops involve hydrogen-bonding and packing interactions within the loop and with other parts of the protein. By searching solved protein structures for regions similar in main chain conformation to the antigen-binding loops in immunoglobulins, we identified medium-sized loops of similar structure in unrelated proteins, and compared the determinants of their conformations. For loops that form compact substructures the major determinant of the conformation is the formation of hydrogen bonds to inward-pointing main chain atoms. For loops that have more extended conformations, the major determinant of their structure is the packing of a particular residue or residues against the rest of the protein. The following picture emerges: Medium-sized loops of similar conformation are stabilized by similar interactions. The groups that interact with the loop have very similar spatial dispositions with respect to the loop. However, the residues that provide these interactions may arise from dissimilar parts of the protein: The conformation of the loop requires certain interactions that the protein may provide in a variety of ways.
High-performance planar native-oxide buried-mesa index-guided AlGaAs-GaAs quantum well heterostructure lasers (1992)

High-performance planar ‘‘buried-mesa’’ index-guided AlGaAs-GaAs quantum well heterostructure (QWH) lasers have been fabricated by oxidation (H2O vapor+N2 carrier gas, 425–525 °C) of a significant thickness of the high composition AlxGa1−xAs upper confining layer (outside the active stripe). The oxide provides excellent current confinement for low-threshold laser operation and a low refractive index (n∼1.6) for transverse optical confinement and index guiding. Laser diodes with ∼4 μm-wide active regions exhibit 300 K continuous (cw) laser thresholds of 8 mA, with single longitudinal mode operation to 23 mW/facet, and maximum output powers of 45 mW/facet (uncoated). Devices fabricated on a lower confinement AlxGa1−xAs-GaAs QWH crystal (x≲0.6 instead of x≳0.8) with ∼4 μm-wide active stripes exhibit 300 K cw thresholds of 9 mA and total external differential quantum efficiencies of 66%. Peak output powers ≳80 mW/facet (uncoated) with linear L-I characteristics over the entire operating range are observed. In limited ‘‘lifetest’’ these laser diodes have been operated ≳500 h without significant degradation.
Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences (2001)

The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.
NMR and Molecular Dynamics Studies of the Conformational Epitope of the Type III Group BStreptococcusCapsular Polysaccharide and Derivatives (1997)

The conformational epitope of the type III group B Streptococcus capsular polysaccharide (GBSP III) exhibits unique properties which can be ascribed to the presence of sialic acid in its structure and the requirement for an extended binding site. By means of NMR and molecular dynamics studies on GBSP III and its fragments, the extended epitope of GBSP III was further defined. The influence of sialic acid on the conformational properties of GBSP III was examined by performing conformational analysis on desialylated GBSP III, which is identical to the polysaccharide of Streptococcus pneumoniae type 14, and also on oxidized and reduced GBSP III. Conformational changes were gauged by 1H and 13C chemical shift analysis, NOE, 1D selective TOCSY-NOESY experiments, J(HH) and J(CH) variations, and NOE of OH resonances. Changes in mobility were examined by 13C T1 and T2 measurements. Unrestrained molecular dynamics simulations with explicit water using the AMBER force field and the GLYCAM parameter set were used to assess static and dynamic conformational models, simulate the observable NMR parameters and calculate helical parameters. GBSP III was found to be capable of forming extended helices. Hence, the length dependence of the conformational epitope could be explained by its location on extended helices within the random coil structure of GBSP III. The interaction of sialic acid with the backbone of the PS was also found to be important in defining the conformational epitope of GBSP III.
Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2synthase in human lung fibroblasts: implications for lung inflammation and cancer (2004)

Cigarette smoking can lead to many human pathologies including cardiovascular and respiratory disease. Recent studies have defined a role for fibroblasts in the development of colon cancer. Moreover, fibroblasts are now thought of as key "sentinel" cells that initiate inflammation by releasing proinflammatory mediators including prostaglandins (PGs). Pathological overexpression of cyclooxygenase-2 (COX-2) and excess eicosanoid production are found in the early stages of carcinogenesis. By promoting chronic inflammation, COX-2 and eicosanoid production may actually cause a predisposition to malignancy. Furthermore, the associated inflammation induced by production of these mediators is central to the pathogenesis of chronic obstructive pulmonary disease. Little is known of the responses of normal lung fibroblasts to cigarette smoke, despite their abundance. We report herein that normal human lung fibroblasts, when exposed to cigarette smoke extract, induce COX-2 with concurrent synthesis of prostaglandin E2 (PGE2). The mechanisms by which cigarette-derived toxicants lead to increased COX-2 levels and PGE2 synthesis include increases in steady-state COX-2 mRNA levels (approximately four- to fivefold), phosphorylation of ERK1/2, and nuclear translocation of the p50 and p65 subunits of the transcription factor NF-kappaB, which are important elements in COX-2 expression. Furthermore, there was a dramatic 25-fold increase in microsomal prostaglandin E synthase, the key enzyme involved in the production of PGE2. We propose that normal human lung fibroblasts, when exposed to cigarette smoke constituents, elicit COX-2 expression with consequent prostaglandin synthesis, thus creating a proinflammatory environment. This chronic inflammatory state may act as one of the first steps towards epithelial transformation.
An Internalizing Antibody Specific for the Human Asialoglycoprotein Receptor (2009)

The liver possesses a variety of characteristics that make this organ a very attractive target for gene and drug delivery. The asialoglycoprotein receptor (ASGPR) is a heterodimeric liver-specific C-type lectin that mediates endocytosis and degradation of desialylated glycoproteins and is considered a preferable target for liver-specific drug delivery. Asialoglycoprotein-coupled, galactosylated, or anti-ASGPR antibody-targeted molecules may be used to deliver pharmaceutical agents to the liver. Here we present a new anti-ASGPR single-chain antibody (scFv) that was isolated from the synthetic human "Ronit-1" antibody phage display library. This scFv (B11) was shown to bind the recombinant and native forms of the ASGPR and could also facilitate ASGPR specific internalization of a B11-PE38KDEL immunotoxin and cause cell death. Thus, this newly isolated antibody can serve as a targeting moiety for ASGPR-directed drug delivery.
Investigation of the Optical Properties in InGaN/GaN Quantum Well Structure (1999)

The paper investigates the optical properties of InGaN/GaN single quantum well and multiple quantum well structures. For the multiple quantum well structure, we investigated the thickness dependence of the optical properties. Based on these studies, this paper presents 1. for the single quantum well structure with 2.5 nm well thickness, there exists a strong piezoelectric field, which induces the quantum confined Stark effect; 2. for the ten period multiple quantum well structure, if the well thickness is 2.5 nm, there is no apparent piezoelectric field to be observed. If the well thickness is above 2.5 nm, the optical behavior can be explained by a model based on the formation of self-organized small In-rich regions, rather than by the piezoelectric field-induced quantum confined Stark effect.
Structural Basis for Tumor Pyruvate Kinase M2 Allosteric Regulation and Catalysis, (2005)

Four isozymes of pyruvate kinase are differentially expressed in human tissue. Human pyruvate kinase isozyme M2 (hPKM2) is expressed in early fetal tissues and is progressively replaced by the other three isozymes, M1, R, and L, immediately after birth. In most cancer cells, hPKM2 is once again expressed to promote tumor cell proliferation. Because of its almost ubiquitous presence in cancer cells, hPKM2 has been designated as tumor specific PK-M2, and its presence in human plasma is currently being used as a molecular marker for the diagnosis of various cancers. The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate (FBP) has been determined to a resolution of 2.82 A. The active site of hPKM2 is in a partially closed conformation most likely resulting from a ligand-induced domain closure promoted by the binding of FBP. In all four subunits of the enzyme tetramer, a conserved water molecule is observed on the 2-si face of the prospective enolate and supports the hypothesis that a proton-relay system is acting as the proton donor of the reaction (1). Significant structural differences among the human M2, rabbit muscle M1, and the human R isozymes are observed, especially in the orientation of the FBP-activating loop, which is in a closed conformation when FBP is bound. The structural differences observed between the PK isozymes could potentially be exploited as unique structural templates for the design of allosteric drugs against the disease states associated with the various PK isozymes, especially cancer and nonspherocytic hemolytic anemia.
The World-Wide Web Gateway to Hyper-G: Using a Connectionless Protocol to Access Session-Oriented Services (1995)

In this thesis, possibilities are studied how session-oriented services on the Internet can be made accessible to users of client programs that use a connectionless application-level protocol. The concepts and properties of two Hypermedia Information Systems, the World-Wide Web (WWW) and Hyper-G, are described and a comparison between these two systems is given. A gateway program was developed which is used as a protocol converter between the sessionoriented Hyper-G client-server protocol and the connectionless Hypertext Transfer Protocol (HTTP). A mechanism was implemented that allows to differentiate HTTP requests and to assign them to Hyper-G sessions. The gateway provides users of World-Wide Web clients with session-oriented access to information residing on Hyper-G servers.
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity (2000)

By integrating an agonist satiety signal, provided by alpha-melanocyte-stimulating hormone (alpha-MSH), and an antagonist signal, provided by agouti-related protein (AGRP), the melanocortin-4 receptor (MC4-R) is a key element in the hypothalamic control of food intake. Inactivation of the gene encoding this G protein-coupled receptor causes obesity in mice. In humans, frameshift mutations in MC4-R cause an early-onset dominant form of obesity in two families. In this study we find a high frequency (4%) of rare heterozygous MC4-R mutations in a large population of morbidly obese patients. No such mutations were found in controls. By analyzing the phenotypes of the probands carrying these mutations, we demonstrate that these patients display a common, nonsyndromic form of obesity. Interestingly, functional analysis of the mutant receptors indicates that obesity-associated defects in MC4-R range from loss of function to constitutive activation. Transmission of these mutations in the families of the carriers indicates a variable expressivity that is not related to the functional severity of the mutations. This variable expressivity of MC4-R-associated obesity is not due to variations in genes for alpha-MSH or AGRP. Taken together, these results demonstrate that MC4-R mutations are a frequent but heterogeneous genetic cause of morbid obesity.
Treatment of B-Cell Lymphoma with Monoclonal Anti-Idiotype Antibody (1982)

HUMAN B-cell malignant tumors result from the proliferation of single clones of cells that express surface markers characteristic of normal B lymphocytes.1 , 2 In particular, the surface immunoglobulin expressed by these cells is monoclonal — i.e., restricted to a single light-chain type and to a particular variable region unique to each case. The unique immunoglobulin variable region (idiotype) of each lymphoma clone may be considered a tumor-specific marker, distinguishing tumor cells from normal cells in the patient. We and others have shown that anti-idiotype antibodies can be used to monitor B-cell tumors and to investigate the biology of these tumors.3 4 5 Because . . .
Reverse sequestration in a case of sickle crisis (1996)

A patient with homozygous sickle cell disease presented with sickle crisis complicated by hepatic and pulmonary sequestration and required intensive therapy. During the recovery phrase she developed a rapid rise of haemoglobin concentration, unrelated to blood transfusion, followed by hypertension, congestive cardiac failure and catastrophic intracerebral haemorrhage. This serious haemodynamic disturbance was considered to be caused by a reversal of the sequestration process. Careful monitoring of a sickle cell patient's blood pressure, blood counts, haematocrits, haemoglobin S level and plasma viscosity, even after the end of a sequestration crisis, is recommended.
Remotely powered distributed microfluidic pumps and mixers based on miniature diodes (2007)

We demonstrate new principles of microfluidic pumping and mixing by electronic components integrated into a microfluidic chip. The miniature diodes embedded into the microchannel walls rectify the voltage induced between their electrodes from an external alternating electric field. The resulting electroosmotic flows, developed in the vicinity of the diode surfaces, were utilized for pumping or mixing of the fluid in the microfluidic channel. The flow velocity of liquid pumped by the diodes facing in the same direction linearly increased with the magnitude of the applied voltage and the pumping direction could be controlled by the pH of the solutions. The transverse flow driven by the localized electroosmotic flux between diodes oriented oppositely on the microchannel was used in microfluidic mixers. The experimental results were interpreted by numerical simulations of the electrohydrodynamic flows. The techniques may be used in novel actively controlled microfluidic-electronic chips.
Tantalkatalysatoren auf Kieselgel für die asymmetrische Epoxidierung von Allylalkoholen (1999)

Tantal erfolgversprechend – Titan erfolglos: Dies scheint für auf Kieselgel als Trägermaterial fixierte Katalysatoren zu gelten, die für die asymmetrische Epoxidierung von Allylalkoholen entwickelt wurden. Komplexe wie [SiO−Ta(OEt)4] wurden aus Kieselgel und [Ta(=CHCMe3)(CH2CMe3)3] synthetisiert. In Gegenwart eines Tartrats und eines Alkylhydroperoxids bilden diese Materialien, an deren Oberfläche sich Tantalzentren befinden, effiziente und leicht handhabbare Katalysatoren für die asymmetrische Epoxidierung von 2-Propen-1-ol (R=H) und trans-2-Hexen-1-ol (R=nPr; siehe Reaktionsgleichung).
Update on diabetic neuropathy (2002)

An increasing understanding of the pathogenetic mechanisms holds out promise for the effective treatment of diabetic neuropathy. The early detection of abnormal glucose metabolism is particularly important, as treatments will probably be most effective if administered early in the course of the neuropathy, when abnormalities of peripheral nerves are more likely to be reversible.
Evidence for secretory pathway localization of a voltage-dependent anion channel isoform (2000)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
High-Efficiency Multiplex Genome Editing of Streptomyces Species Using an Engineered CRISPR/Cas System (2014)

Actinobacteria, particularly those of genus Streptomyces, remain invaluable hosts for the discovery and engineering of natural products and their cognate biosynthetic pathways. However, genetic manipulation of these bacteria is often labor and time intensive. Here, we present an engineered CRISPR/Cas system for rapid multiplex genome editing of Streptomyces strains, demonstrating targeted chromosomal deletions in three different Streptomyces species and of various sizes (ranging from 20 bp to 30 kb) with efficiency ranging from 70 to 100%. The designed pCRISPomyces plasmids are amenable to assembly of spacers and editing templates via Golden Gate assembly and isothermal assembly (or traditional digestion/ligation), respectively, allowing rapid plasmid construction to target any genomic locus of interest. As such, the pCRISPomyces system represents a powerful new tool for genome editing in Streptomyces.
Analysis of Tat transactivation of human immunodeficiency virus transcription in vitro. (1992)

The HIV Tat protein is a potent transactivator of HIV transcription, increasing both RNA initiation and elongation. We now demonstrate that purified, full-length 86 amino acid Tat protein specifically transactivates the HIV LTR in vitro to a high level (25- to 60-fold). Tat transactivation was specifically blocked by anti-Tat serum, but not preimmune serum. Tat did not transactivate transcription from the control adenovirus major late promoter (AdMLP). HIV transcription was blocked at various functional steps during initiation and elongation complex formation. Similar to the control AdMLP, HIV basal initiation complex assembly was sensitive to the addition of 0.015% sarkosyl prior to the addition of nucleoside triphosphates. Resistance to 0.05% sarkosyl required the addition of G, C, and U, which constitute the first 13 bases of the HIV RNA transcript. The addition of Tat to the in vitro transcription relieved the 0.015% sarkosyl block. These Tat-induced complexes were sensitive to 0.05% sarkosyl, suggesting that transcriptional initiation had not occurred. Consistent with this hypothesis, the addition of G, C, and U to the Tat-induced transcription complexes allowed the rapid conversion to transcription initiation complexes. Tat also facilitated the formation of 0.015% sarkosyl-resistant complexes in a reconstituted transcription system containing partially purified transcription factors and polymerase II. Following the formation of stable initiation complexes, Tat increased the rate and efficiency of transcription elongation on the HIV but not the AdML template. Kinetic analysis of Tat transactivation suggests that approximately 30% of the Tat initiation complexes are converted to elongation complexes. We conclude that Tat, in addition to its demonstrated role in RNA elongation, facilitates transcription initiation in vitro.
A tool for the culturally competent assessment of suicide: The Cultural Assessment of Risk for Suicide (CARS) Measure. (2013)

Despite important differences in suicide presentation and risk among ethnic and sexual minority groups, cultural variations have typically been left out of systematic risk assessment paradigms. A new self-report instrument for the culturally competent assessment of suicide, the Cultural Assessment of Risk for Suicide (CARS) measure, was administered to a diverse sample of 950 adults from the general population. Exploratory factor analysis yielded a 39-item, 8-factor structure subsumed under and consistent with the Cultural Theory and Model of Suicide (Chu, Goldblum, Floyd, & Bongar, 2010), which characterizes the vast majority of cultural variation in suicide risk among ethnic and sexual minority groups. Psychometric properties showed that the CARS total and subscale scores demonstrated good internal consistency, convergent validity with scores on other suicide-related measures (the Suicide Ideation Scale, the Beck Depression Inventory suicide item, and the Beck Hopelessness Scale), and an ability to discriminate between participants with versus without history of suicide attempts. Regression analyses indicated that the CARS measure can be used with a general population, providing information predictive of suicidal behavior beyond that of minority status alone. Minorities, however, reported experiencing the CARS cultural risk factors to a greater extent than nonminorities, though effect sizes were small. Overall, results show that the CARS items are reliable, and the instrument identifies cultural suicide risk factors not previously attended to in suicide assessment. The CARS is the first to operationalize a systematic model that accounts for cultural competency across multiple cultural identities in suicide risk assessment efforts.