gebhart/patrepeval huggingface dataset:
Genetics of lipopolysaccharide biosynthesis in enteric bacteria (1993)

From a historical perspective, the study of both the biochemistry and the genetics of lipopolysaccharide (LPS) synthesis began with the enteric bacteria. These organisms have again come to the forefront as the blocks of genes involved in LPS synthesis have been sequenced and analyzed. A number of new and unanticipated genes were found in these clusters, indicating a complexity of the biochemical pathways which was not predicted from the older studies. One of the most dramatic areas of LPS research has been the elucidation of the lipid A biosynthetic pathway. Four of the genes in this pathway have now been identified and sequenced, and three of them are located in a complex operon which also contains genes involved in DNA and phospholipid synthesis. The rfa gene cluster, which contains many of the genes for LPS core synthesis, includes at least 17 genes. One of the remarkable findings in this cluster is a group of several genes which appear to be involved in the synthesis of alternate rough core species which are modified so that they cannot be acceptors for O-specific polysaccharides. The rfb gene clusters which encode O-antigen synthesis have been sequenced from a number of serotypes and exhibit the genetic polymorphism anticipated on the basis of the chemical complexity of the O antigens. These clusters appear to have originated by the exchange of blocks of genes among ancestral organisms. Among the large number of LPS genes which have now been sequenced from these rfa and rfb clusters, there are none which encode proteins that appear to be secreted across the cytoplasmic membrane and surprisingly few which encode integral membrane proteins or proteins with extensive hydrophobic domains. These data, together with sequence comparison and complementation experiments across strain and species lines, suggest that the LPS biosynthetic enzymes may be organized into clusters on the inner surface of the cytoplasmic membrane which are organized around a few key membrane proteins.
An Ultralow Phase Noise Coupled Optoelectronic Oscillator (2007)

Ultralow jitter optical pulse sources are much needed in optical communications, optical sampling, and metrology applications. We report a coupled optoelectronic oscillator employing nonpolarization-maintaining components and an erbium-doped fiber amplifier that generates 9.4-GHz microwave signals with -150-dBc/Hz phase noise at 10- to 100-kHz offset, and 2-fs jitter (integrated in 100-Hz to 100-kHz range) optical pulses. To our knowledge, this is the lowest phase noise and time jitter reported in the same frequency range for such mode-locked laser-based systems
Challenges of rural development in India (2001)

The author attempts to assess the level and nature of development in rural India, which presently comprises about three-fourths of the total population, during the last five decades of country's Independence. It has been argued that the progress made so far is not up to scratch. The tasks ahead for rural development with an eye to ameliorating the standard of living of the rural people are quite gigantic and arduous in the face of the country's resource crunch, slow-growing economy and politics of under-development. Furthermore, the tasks loom larger with the lapse of time, ensuing from rapid rise in population and bad governance.
Early inflammation and dementia: A 25‐year follow‐up of the Honolulu‐Asia aging study (2002)

Inflammatory responses are associated with cardiovascular disease and may be associated with dementing disease. We evaluated the long-term prospective association between dementia and high-sensitivity C-reactive protein, a nonspecific marker of inflammation. Data are from the cohort of Japanese American men who were seen in the second examination of the Honolulu Heart Program (1968-1970) and subsequently were reexamined 25 years later for dementia in the Honolulu-Asia Aging Study (1991-1996). In a random subsample of 1,050 Honolulu-Asia Aging Study cases and noncases, high-sensitivity C-reactive protein concentrations were measured from serum taken at the second examination; dementia was assessed in a clinical examination that included neuroimaging and neuropsychological testing and was evaluated using international criteria. Compared with men in the lowest quartile (<0.34mg/L) of high-sensitivity C-reactive protein, men in the upper three quartiles had a 3-fold significantly increased risk for all dementias combined, Alzheimer's disease, and vascular dementia. For vascular dementia, the risk increased with increasing quartile. These relations were independent of cardiovascular risk factors and disease. These data support the view that inflammatory markers may reflect not only peripheral disease, but also cerebral disease mechanisms related to dementia, and that these processes are measurable long before clinical symptoms appear.
In Vitro Stability of Growth Hormone Releasing Factor (GRF) Analogs in Porcine Plasma (1991)

The stability of growth-hormone releasing factor (growth regulating factor; GRF) analogs in porcine plasma was examined. GRF analogs were incubated in porcine plasma at 37 degrees C, extracted and subsequently analyzed using high performance liquid chromatography (HPLC). GRF(1-29)-NH2 was rapidly broken down in the plasma with a degradation rate of t1/2 = 13 min. The primary degradation product was identified as GRF(3-29)-NH2. Substitution of Gly15 by Ala15 slightly prolonged the plasma half-life (t1/2 = 17 min) and the major degradative fragment was found to be [Ala15]GRF(3-29)-NH2. The cleavage between the 2 and 3 position of the peptide was not inhibited by trasylol at a concentration of 1,000 KIU/ml but was dramatically reduced by the combined use of diprotin A and trasylol. Absence of the free amino group at the N-terminus and/or substitution of a D-amino acid residue at the penultimate position completely prevented cleavage between the 2 and 3 position in the structural linear GRF analogs. Side-chain to side-chain cyclization between Asp8 and Lys12 amino acid residues significantly improved the stability of GRF in plasma with t1/2 greater than 2 hr. An additional stability was provided by substitution of D-Ala2 for Ala2 in the structural cyclic analog. Cyclization between Lys21 and Asp25 also improved the stability of the GRF peptide in the plasma. Stability was further enhanced by the presence of D-Ala2 or by forming a dicyclic analog through an additional linkage between Asp8 and Lys12.
Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2:  Synthesis, X-ray Crystallographic Analysis, and Biological Activities (2002)

High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC(50) values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.
Prostaglandin E1Accelerates Subcutaneous Insulin Absorption in Insulin‐dependent Diabetic Patients (1984)

The powerful vasodilator, prostaglandin E1 (PGE1), was added to Actrapid insulin to try to accelerate the early phase of subcutaneous insulin absorption through increasing injection site blood flow. Actrapid insulin alone (6U) and insulin containing PGE1 (7.5 X 10(-6) M) were injected on different days into 13 fasting insulin-dependent diabetics. With the insulin/PGE1 mixture, increases in both free and total plasma insulin concentrations were greater at all times up to 120 minutes after injection than with insulin alone, with significant differences in the first 40 minutes. With insulin/PGE1 the area under the total plasma insulin curve increased significantly more rapidly between 80 and 120 minutes. Plasma glucose concentrations fell consistently more rapidly with insulin/PGE1 than with insulin alone although the differences were small (mean fall +/- S.E.M. at 120 minutes: 4.9 +/- 0.5 mmol/l vs 4.0 +/- 0.6; p = 0.02). Addition of local hyperaemic agents to short-acting insulin preparations could be therapeutically useful in hastening insulin entry to the circulation at mealtimes.
Targeting of CD22‐positive B‐cell lymphoma cells by synthetic divalent sialic acid analogues (2012)

CD22 is an inhibitory co-receptor of the B-cell receptor (BCR) on B cells. Since CD22 is ubiquitously expressed in the B-cell lineage and CD22 endocytosis can be triggered efficiently, antibodies and antibody-based immunotoxins against CD22 are used to target B cells both in B-cell lymphomas and leukemias, as well as in autoimmune diseases. CD22 recognizes α2,6-linked sialic acids as endogenous ligands. We have developed new synthetic sialosides as ligands for human CD22. These sialosides bind CD22 on human B cells with high affinity and can efficiently enhance IgM-triggered Ca(2+) signaling. We coupled these sialosides to Pseudomonas exotoxin A to generate a novel CD22 ligand-based immunotoxin. This sialoside-exotoxin-A construct can specifically kill CD22-positive B-cell lymphoma cells. It binds specifically to CD22-positive B-cell lymphoma cells and is dominant over endogenous cis-ligands on the B-cell surface. The sialoside-exotoxin-A construct is efficiently internalized by endocytosis into B-cell lymphoma cell lines. Thus we show the development of a new therapeutic compound for targeting CD22 on human B cells, both for B-cell lymphoma, as well as for B-cell-mediated autoimmune diseases.
Hyperbaric oxygen: does it promote growth or recurrence of malignancy? (2003)

It has been a concern that a therapeutic modality recommended as an adjunct to healing and administered to promote proliferation of fibroblasts, epithelial cells and blood vessels in a wound could also lead to proliferation of malignant cells and angiogenesis in a malignant tumor. The first reported concern that hyperbaric oxygen (HBO2) might have cancer growth enhancing effects appeared in a paper by Johnson and Lauchlan in 1966. In a series of patients treated with HBO2 radiosensitization, they reported a more frequent than expected incidence of metastases and an unusual pattern of metastases. The published literature from clinical reports, animal studies and cell culture studies are reviewed. Putative mechanisms whereby HBO2 could have carcinogenic effects are discussed. The processes of angiogenesis in wound healing and in cancer growth are compared and contrasted. In vitro, in vivo and clinical studies strongly suggest no more than a neutral effect of HBO2 on tumor growth. In fact some studies suggest a negative impact of HBO2 on malignant progression or formation. For angiogenesis, similarities in wound healing and cancer are striking but significant differences are found including the relative importance of angiogenic factors and the process of cessation of angiogenesis. Tumors that grow in hypoxic environments are more prone to metastases and more lethal to the patient. They are also more likely to mutate toward resistant genotypes. Discussion of postulated mechanisms of carcinogenesis including free radical and immunosuppressive effects points out why they are not likely to enhance or cause cancer growth or initiation. In conclusion, the published literature on tumor angiogenesis mechanisms and other possible mechanisms of cancer causation or accelerated growth provides little basis for HBO2 to enhance malignant growth or metastases. A history of malignancy should not be considered a contraindication for HBO2 therapy.
The "Other" Circadian System: Food as a Zeitgeber (2002)

It is not surprising that limiting food access to a particular time of day has profound effects on the behavior and physiology of animals. It has been clear for some time that pre-meal behavioral activation, a rise in core temperature, elevated serum corticosterone, and an increase in duodenal disaccharidases are under circadian control and that the observed circadian properties are not abolished by lesions of the suprachiasmatic nucleus (SCN), but the search for the locus of a separate food-entrainable oscillator (FEO) has not been successful. The cloning of circadian clock genes and the discovery that these genes are expressed in many central nervous system structures outside the SCN and in peripheral tissues have led to new strategies for investigating potential loci of an FEO. Recent findings concerning the entrainment of clock gene expression in the central nervous system and in peripheral tissues by periodic food access are presented, and the implications of these findings for a better understanding of a circadian system that entrains to meals, rather than to light, are discussed.
Identification and concerted function of two receptor binding surfaces on basic fibroblast growth factor required for mitogenesis. (1994)

Members of the fibroblast growth factor (FGF) family promote angiogenesis and wound repair, modulate early developmental events and survival of neurons, and have been associated with the pathogenesis of various diseases. FGFs interact with specific FGF receptors (FGFRs) and heparan sulfate proteoglycans on cell surfaces to mediate mitogenesis. Using protein structure-based site-directed mutagenesis of basic FGF (bFGF), we have identified two FGFR binding sites on bFGF which act in concert to initiate signal transduction. Both FGFR binding surfaces are distinct from the heparan sulfate proteoglycan binding domain. The primary, higher affinity, binding interaction comprises a cluster of solvent exposed hydrophobic amino acids (Tyr-24, Tyr-103, Leu-140, and Met-142), and two polar residues (Arg-44 and Asn-101). The hydrophobic contacts dominate the primary binding interaction and provide approximately 75% of the binding affinity. The secondary FGFR binding site on bFGF has an approximately 250-fold lower affinity and is composed of amino acids Lys-110, Tyr-111, and Trp-114 in a surface-exposed type I beta-turn (formerly known as the putative receptor binding loop). Binding of FGFR to both bFGF surfaces in a stoichiometry of 2FGFR:1bFGF is required for growth factor mediated cell proliferation. This represents a mechanism for the fibroblast growth factor/receptor family in which FGF facilitates FGFR dimerization and subsequent signal transduction events as a monomeric ligand.
High-Dose Samarium-153 Ethylene Diamine Tetramethylene Phosphonate: Low Toxicity of Skeletal Irradiation in Patients With Osteosarcoma and Bone Metastases (2002)

PURPOSE: Samarium-153 ethylene diamine tetramethylene phosphonate ( 153 Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic bone metastases. Because the dose-limiting toxicity of 153 Sm-EDTMP is thrombocytopenia, a dose-escalation trial using peripheral-blood progenitor cells (PBPCs) or marrow support was conducted to treat metastatic bone cancer. PATIENTS AND METHODS: Patients with locally recurrent or metastatic osteosarcoma or skeletal metastases avid on bone scan were treated with 1, 3, 4.5, 6, 12, 19, or 30 mCi/kg of 153 Sm-EDTMP. RESULTS: Thirty patients were treated with 153 Sm-EDTMP. Transient symptoms of hypocalcemia were seen at 30 mCi/kg. Estimates of radioisotope bound to bone surfaces and marrow radiation dose were linear with injected amount of 153 Sm-EDTMP. Cytopenias also occurred in all subjects and were dose-related. At day +13 after 153 Sm-EDTMP, residual whole-body radioactivity was 1% to 65% of whole-body radioactivity considered safe for PBPC infusion, 3.6 mCi. After PBPC or marrow infusion on day +14 after 153 Sm-EDTMP, recovery of hematopoiesis was problematic in two patients at the 30 mCi/kg dose infused with less than 2 × 10 6 CD34 + /kg on day +14, but not in other patients. Reduction or elimination of opiates for pain was seen in all patients. Patients had no adverse changes in appetite or performance status. CONCLUSION: 153 Sm-EDTMP with PBPC support can provide bone-specific therapeutic irradiation (estimates of 39 to 241 Gy). Hematologic toxicity at 30 mCi 153 Sm-EDTMP/kg requires PBPC grafts with more than 2 × 10 6 CD34 + /kg to overcome myeloablative effects of skeletal irradiation. Nonhematologic side effects are minimal.
Pichia stipitis Genes for Alcohol Dehydrogenase with Fermentative and Respiratory Functions (1998)

Two genes coding for isozymes of alcohol dehydrogenase (ADH); designated PsADH1 and PsADH2, have been identified and isolated from Pichia stipitis CBS 6054 genomic DNA by Southern hybridization to Saccharomyces cerevisiae ADH genes, and their physiological roles have been characterized through disruption. The amino acid sequences of the PsADH1 and PsADH2 isozymes are 80.5% identical to one another and are 71.9 and 74.7% identical to the S. cerevisiae ADH1 protein. They also show a high level identity with the group I ADH proteins from Kluyveromyces lactis. The PsADH isozymes are presumably localized in the cytoplasm, as they do not possess the amino-terminal extension of mitochondrion-targeted ADHs. Gene disruption studies suggest that PsADH1 plays a major role in xylose fermentation because PsADH1 disruption results in a lower growth rate and profoundly greater accumulation of xylitol. Disruption of PsADH2 does not significantly affect ethanol production or aerobic growth on ethanol as long as PsADH1 is present. The PsADH1 and PsADH2 isozymes appear to be equivalent in the ability to convert ethanol to acetaldehyde, and either is sufficient to allow cell growth on ethanol. However, disruption of both genes blocks growth on ethanol. P. stipitis strains disrupted in either PsADH1 or PsADH2 still accumulate ethanol, although in different amounts, when grown on xylose under oxygen-limited conditions. The PsADH double disruptant, which is unable to grow on ethanol, still produces ethanol from xylose at about 13% of the rate seen in the parental strain. Thus, deletion of both PsADH1 and PsADH2 blocks ethanol respiration but not production, implying a separate path for fermentation.
ADP-Ribosylation of Elongation Factor 2 by Diphtheria Toxin (1980)

NMR spectral analysis of the novel amino acid, diphthamide, in elongation factor 2 which is ADP-ribosylated by diphtheria toxin suggests that it is 2-[3carboxyamido-3-(trimethylammonio)propyl]histidine. Ribosyl-diphthamide was prepared by enzymatic hydrolysis of ADP-ribosyl-elongation factor 2 and three compounds were produced by its chemical hydrolysis (Van Ness, B. G., Howard, J. B., and Bodley, J. W. (1980) J. BioL Chem 266,10717-10720). Proton NMR spectroscopy in ‘HzO of diphthine demonstrated the elements of histidine minus the carbon 2 proton plus 14 additional nonexchangeable protons. These protons were attributed to an extensive modification at carbon 2 of the imidazole ring. Proton NMR spectroscopy in ‘HzO of ribosyl-diphthamide showed only those protons seen in diphthine plus those expected of a ribofuranosylmoiety. Chemical shift dependence on pH was demonstrated for the histidine-derived protons as well as several protons of the modifying side chain. Natural abundance carbon 13 NMR spectroscopy of ribosyldiphthamide also showed the elements of histidine and ribose plus 7 additional carbon atoms attributed to the modification of the imidazole ring. Based on the NMR spectral properties of the anomeric proton of ribosyldiphthamide we propose that the ribose is linked to one of the nitrogens of the histidine imidazole ring.
Polymorphisms, but lack of mutations or instability, in the promotor region of the mitochondrial genome in human colonic tumors. (1994)

The region of the human mitochondrial D-loop has been sequenced from DNA of colonic tumors and paired normal colonic tissue to determine if mutations in the promotors for the heavy or light strands are responsible for the decrease in mitochondrial gene expression present in colonic tumors. No mutations were detected in the colonic tumors, but new polymorphisms, including a sequence analogous to CA microsatellites in genomic DNA, were revealed. These polymorphisms are restricted to positions within the D-loop which are not essential for accurate and efficient in vitro mitochondrial transcription. Thus, these data confirm the boundaries of the functional heavy and light strand promotors determined by in vitro assays. Further, although some of the tumors investigated show genomic microsatellite instability similar to that recently reported for colonic tumors, the CA polymorphic region in the mitochondrial D-loop does not show coincident instability in the tumors. Therefore, as in yeast, there may be both a mitochondrial and a nuclear enzyme responsible for mismatch repair, with only the latter involved in generation of instability in some human colon cancers. In summary, our data do not find any structural alterations in the D-loop region of the human mitochondrial genome encompassing the heavy and light strand promotors which can account for the decreased expression of the mitochondrial genome in colonic tumors.
An incremental XSLT transformation processor for XML document manipulation (2002)

In this paper, we present an incremental transformation framework called incXSLT. This framework has been experimented for the XSLT language defined at the World Wide Web Consortium. For the currently available tools, designing the XML content and the transformation sheets is an inefficient, a tedious and an error prone experience. Incremental transformation processors such as incXSLT represent a better alternative to help in the design of both the content and the transformation sheets. We believe that such frameworks are a first step toward fully interactive transformation-based authoring environments.