gebhart/patrepeval huggingface dataset:
Identification and Characterization of a Linear-Plasmid-Encoded Factor H-Binding Protein (FhbA) of the Relapsing Fever Spirochete Borrelia hermsii (2004)

In North America, tick-borne relapsing fever (TBRF) is caused by the spirochete species Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae. We previously demonstrated that some isolates of B. hermsii and B. parkeri are capable of binding factor H and that cell-bound factor H can participate in the factor I-mediated cleavage of C3b. Isolates that bound factor H expressed a factor H-binding protein (FHBP) that we estimated to be approximately 19 to 20 kDa in size and thus, pending further characterization, temporarily designated FHBP19. Until this report, none of the FHBPs of the TBRF spirochetes had been characterized. Here we have recovered the gene encoding the FHBP of B. hermsii YOR from a lambda ZAP II library and determined its sequence. The gene encodes a full-length protein of 22.7 kDa, which after processing is predicted to be 20.5 kDa. This protein, which we redesignate factor H-binding protein A (FhbA), is unique to B. hermsii. Two-dimensional pulsed-field gel electrophoresis and hybridization analyses revealed that the B. hermsii gene encoding FhbA is a single genetic locus that maps to a linear plasmid of approximately 220 kb. The general properties of FhbA were also assessed. The protein was found to be surface exposed and lipidated. Analysis of the antibody response to FhbA in infected mice revealed that it is antigenic during infection, indicating expression during infection. The identification and characterization of FhbA provides further insight into the molecular mechanisms of pathogenesis of the relapsing fever spirochetes.
Involvement of the PTEN–AKT–FOXO3a Pathway in Neuronal Apoptosis in Developing Rat Brain after Hypoxia–Ischemia (2009)

The proapoptotic function of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphatase has been linked to its capacity to antagonize the phosphatidylinositol-3-kinase-Akt signaling pathway. Previous studies have shown that the Forkhead transcriptional factor (FOXO3a) is a critical effector of the PTEN-mediated tumor suppressor. However, whether the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in developing rat brain after hypoxia-ischemia (HI) is unclear. In this study, we generated an HI model using postnatal day 10 rats. Immunohistochemistry and western blot were used to detect the expression of total and phosphorylated PTEN, Akt, and FOXO3a, as well as its target gene Bim. We found that dephosphorylation of PTEN was accompanied by dephosphorylation of Akt and FOXO3a, which induced FOXO3a translocation into the nucleus and upregulated the expression of Bim. Furthermore, we found that PTEN inhibition by bisperoxovanadium significantly increased the phosphorylation of Akt and FOXO3a, decreased the nuclear translocation of FOXO3a, and inhibited Bim expression after HI. Moreover, the downregulation of Bim caused by PTEN inhibition attenuated cellular apoptosis in developing rat brain. Our findings suggest that the PTEN-Akt-FOXO3a pathway is involved in neuronal apoptosis in neonatal rat brain after HI. Agents targeting PTEN may offer a promise to rescue neurons from HI brain damage.
Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. (1990)

The process of metastasis is not random. Rather, it consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, as a whole, metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems. Moreover, we have found tumor growth that is specific to a particular site within one organ. Whether the same conclusions can be reached for human cancers remained unanswered until very recently. Studies from our laboratory and from others have shown that the implantation of human cancer cells derived from surgical specimens into correct anatomical sites of nude mice can provide a suitable model of metastasis of human tumors. Clonal analysis of a human renal carcinoma, colon carcinomas, and melanomas has revealed that these tumors are indeed heterogeneous for metastatic properties, an observation made only after orthotopic implantation. Thus, growth in the environment of specific organs can be selective and the environment per se influences this process. While it is clear that vascularity and local immunity can facilitate or retard tumor growth, we have concentrated on understanding how damage to an organ and the subsequent repair process can facilitate tumor cell proliferation. Accelerated growth of human colon cancer cells was found in hepatectomized nude mice, whereas accelerated growth of human renal cancer cells was found in nephrectomized nude mice. These data suggest that systemic physiological signals can be recognized by neoplastic cells presumably by mechanisms similar to those shared by their normal cell counterparts. In summary, the critical factors that regulate metastasis are the intrinsic properties of metastatic cells and host factors involved in homeostasis. The recent increase in our understanding of metastasis should provide important leads for developing more effective approaches to the treatment of disseminated cancer.
Transforming growth factor β in bovine milk: concentration, stability and molecular mass forms (1996)

Transforming growth factor beta (TGF-beta) is one of the predominant growth factors present in milk. The concentration, molecular mass forms and stability of TGF-beta in bovine milk were investigated using a standard bioassay measuring the growth inhibition of a milk lung epithelial cell line. Most of the TGF-beta bioactivity in milk was found to be in a latent form, which was also retained in the whey fraction. After acid activation, the total TGF-beta concentration was 4.3 +/- 0.8 ng and 3.7 +/- 0.7 ng TGF-beta per ml of milk and cheese whey respectively. Cation-exchange chromatography at pH 6.5 was used to concentrate latent whey-derived TGF-beta, which could be activated by transient exposure to extremes of pH, urea or heat. Heparin did not significantly activate milk-derived TGF-beta. Neutral gel filtration of the cationic whey fraction revealed a major peak of latent TGF-beta with a molecular mass of 80 kDa and a smaller peak at 600 kDa. Transient acidification of the cationic whey fraction prior to neutral gel filtration, or gel filtration under acidic conditions, released low molecular mass TGF-beta from both high molecular mass peaks. Whey-derived TGF-beta was purified using a five-step chromatographic procedure. An N-terminal sequence was obtained for TGF-beta 2, which accounted for over 85% of the TGF-beta bioactivity in whey. All TGF-beta activity in whey could be neutralised by a monoclonal antibody directed against TGF-beta 1, -beta 2 and -beta 3. The results suggest that the majority of TGF-beta in bovine milk is present in a small latent complex.
Flocculant and Chemical Properties of a Polysaccharide from Pullularia pullulans (1973)

An extracellular polysaccharide, PP-floc, was synthesized from glucose by Pullularia pullulans (or Aureobasidium pullulans) in a pilot plant batch fermentor containing 175 liters of culture medium. At 58 h of fermentation, the concentration of PP-floc was 1.03 g/100 ml, giving a 25.8% conversion of initial glucose to polysaccharide. The flocculant activity of the culture medium increased during the fermentation process and reached its maximum at 50 h of culture age. Less PP-floc (0.33 lb/ton of slimes [approximately 149.7 g/0.907 t]) was required to give the same flocculant activity as a synthetic polymer of acrylamide, Separan NP-10 (0.5 lb/ton of slimes [approximately 226.8 g/0.907 t]), at all temperatures from 25 to 100 C. The degree of inactivation of PP-floc and Separan NP-10 at elevated temperatures was almost identical, and they were completely inactivated at about the same temperature (80 C). PP-floc also gave better compaction of slimes than Separan NP-10 at all temperatures tested. PP-floc was soluble in water and its specific optical rotation was [alpha](D) (25) + 194 degrees in water (c, 0.4). PP-floc contained 83.3% carbohydrate, 3.2% protein, and 8.1% water. Glucose was found to be the principal sugar monomer with traces (>5%) of galactose and mannose present. Structural studies on the fractions of purified polysaccharide by methylation and by periodate oxidation techniques prove that PP-floc is linear and composed of alpha-(1 --> 4) and alpha-(1 --> 6) glucopyranosyl units in the approximate ratio of 2:1. The action of pullulanase on crude PP-floc suggested the ordered arrangement of two consecutive alpha-(1 --> 4)-linked glucopyranosyl units flanked by alpha-(1 --> 6)-linked glucopyranose residues.
Effect of Direct-to-Consumer Genomewide Profiling to Assess Disease Risk (2011)

In a selected sample of subjects who completed follow-up after undergoing consumer genomewide testing, such testing did not result in any measurable short-term changes in psychological health, diet or exercise behavior, or use of screening tests. Potential effects of this type of genetic testing on the population at large are not known. (Funded by the National Institutes of Health and Scripps Health.).
Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires (2012)

Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage-sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-dependent PeT should be amenable to much further optimization, but the existing probes are already valuable indicators of neuronal activity.
Identification of depot-specific human fat cell progenitors through distinct expression profiles and developmental gene patterns (2006)

Anatomically separate fat depots differ in size, function, and contribution to pathological states, such as the metabolic syndrome. We isolated preadipocytes from different human fat depots to determine whether the basis for this variation is partly attributable to differences in inherent properties of fat cell progenitors. We found that genome-wide expression profiles of primary preadipocytes cultured in parallel from abdominal subcutaneous, mesenteric, and omental fat depots were distinct. Interestingly, visceral fat was not homogeneous. Preadipocytes from one of the two main visceral depots, mesenteric fat, had an expression profile closer to that of subcutaneous than omental preadipocytes, the other main visceral depot. Expression of genes that regulate early development, including homeotic genes, differed extensively among undifferentiated preadipocytes isolated from different fat depots. These profiles were confirmed by real-time PCR analysis of preadipocytes from additional lean and obese male and female subjects. We made preadipocyte strains from single abdominal subcutaneous and omental preadipocytes by expressing telomerase. Depot-specific developmental gene expression profiles persisted for 40 population doublings in these strains. Thus, human fat cell progenitors from different regions are effectively distinct, consistent with different fat depots being separate mini-organs.
Erythrocyte entrapment of daunomycin by amphotericin B without hemolysis. (1980)

Amphotericin B is a polyene that binds to sterols and perforates cell membranes. An antileukemic drug such as daunomycin added exogenously is impermeable to the red cell membrane. However, when the cells are incubated with a low concentration of amphotericin B, daunomycin is entrapped in the red cells without hemolysis or alteration in the chemical parameter of the erythrocytes. The erythrocyte has been used as a carrier vehicle to enhance the cytotoxic activity of daunomycin against L1210 leukemic cells. In comparison to control preparations, the greatest increase in survival was obtained in vivo when the erythrocytes with entrapped daunomycin were given to C57BL X DBA/2 F1 mice bearing L1210 cells.
Defining a Novel cis-Element in the 3′-Untranslated Region of Mammalian Ribonucleotide Reductase Component R2 mRNA (1996)

Mammalian ribonucleotide reductase is a highly regulated activity essential for DNA synthesis and repair. The 3'-untranslated region (3'-UTR) of mammalian ribonucleotide reductase R2 mRNA has been implicated in the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate-mediated stabilization of mouse BALB/c 3T3 R2 message. We investigated the possibility that the 3'-UTR contains regulatory information for R2 mRNA turnover. Using 3'-end-labeled RNA in gel shift and UV cross-linking analyses, we detected in the 3'-UTR a novel 9-nucleotide cis-element, 5'-UCGUGUGCU-3', which interacted with a widely distributed cellular cytosolic protease-sensitive factor(s) in a sequence-specific manner to form a 45-kDa R2 binding protein complex. The binding activity was redox-sensitive and down-regulated by 12-O-tetradecanoylphorbol-13-acetate and okadaic acid in a dose-dependent manner. Insertion of a 154-base pair fragment containing the cis-element led to markedly reduced accumulation of chloramphenicol acetyltransferase hybrid mRNA relative to the same insert carrying a series of G --> A mutations within this element that eliminated binding. We suggest that the 9-nucleotide region functions as a destabilizing element. These results provide a model for ribonucleotide reductase gene expression through a novel and specific mRNA cis-trans-interaction involving a phosphorylation signal pathway that leads to changes in the stability of R2 message.
The effects of local hypothermia on odontogenesis. (1979)

Theodore Roosevelt acknowledges an editorial from The Kansas City Star sent to him by the newspaper's founder, Colonel Nelson.
Hybrid silicon–organic nanoparticle memory device (2003)

We demonstrate a nonvolatile electrically erasable programmable read-only memory device using gold nanoparticles as charge storage elements deposited at room temperature by chemical processing. The nanoparticles are deposited over a thermal silicon dioxide layer that insulates them from the device silicon channel. An organic insulator deposited by the Langmuir–Blodget technique at room temperature separates the aluminum gate electrode from the nanoparticles. The device exhibits significant threshold voltage shifts after application of low-voltage pulses (⩽±6 V) to the gate and has nonvolatile retention time characteristics.
Identification and Characterization of the Genes for Mitochondrial Ribosomal Proteins of Saccharomyces Cerevisiae (1997)

We have purified 13 large subunit proteins of the mitochondrial ribosome of the yeast Saccharomyces cerevisiae and determined their partial amino acid sequences. To elucidate the structure and function of these proteins, we searched for their genes by comparing our sequence data with those deduced from the genomic nucleotide sequence data of S. cerevisiae and analyzed them. In addition, we searched for the genes encoding proteins whose N-terminal amino acid sequences we have reported previously [Grohmann, L., Graack, H.-R., Kruft, V., Choli, T., Goldschmidt-Reisin, S. & Kitakawa, M. (1991) FEBS Lett. 284, 51-56]. Thus, we were able to identify and characterize 12 new genes for large subunit proteins of the yeast mitochondrial ribosome. Furthermore, we determined the N-terminal amino acid sequences of seven small subunit proteins and subsequently identified the genes for five of them, three of which were found to be new.
Chemistry and Mechanism of Urease Inhibition (2002)

Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs useful in a variety of physiological conditions. The enzyme inhibitors can interact with enzymes and block their activity towards natural substrates. Urease inhibitors have recently attracted much attention as potential new anti-ulcer drugs. Ironically, urease was the first enzyme crystallized but its mechanism of action is still largely misunderstood. This chapter therefore reviews comprehensive developments in the field of urease inhibitors. Inhibitors of urease can be broadly classified into two categories: (1) active site directed (substrate-like), (2) mechanism-based directed. We present here the examples of selected inhibitors along with their mechanisms of action to characterize their mode of urease inhibition. The observations that urease due to its high substrate (urea) specificity can only bind to a few inhibitors with a similar binding mode as urea is also discussed. Several non-covalent interactions including hydrogen bonds and hydrophobic contacts stabilize the enzyme-inhibitor complex. Regardless of the class of compound, it is reported that only a few functional groups with electronegative atoms such as oxygen, nitrogen and sulfur act either as bidentate (mostly), tridentate (rarely), or as ligand-chelator to form octahedral complexes with two slightly distorted octahedral Ni ions of the enzyme. Bulky groups attached to the pharmacophore were found to decrease the activity of inhibitors, since the lack of a bulky attachment makes it easier for urease inhibitors to enter the substrate-binding pocket as well as avoid unfavorable steric interactions with amino acid residues in its vicinity. This review is intended to provide highlights of the inhibition of urease by hydroxamic acids (HXAs), phosphorodiamidates (PPDs), imidazoles, phosphazene and related compounds. These compounds are compared to previously reported urease inhibitors for the catalytic models proposed for urease activity. The differences in inhibition of urease activities from plants and of bacterial origin by various inhibitors and physiological implications of urease inhibition are discussed.
Hypoxia‐induced pathways in breast cancer (2002)

Hypoxia, a common consequence of solid tumor growth in breast cancer and other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and alterations in microenvironmental pH. Hypoxia-inducible factors, heterodimeric DNA binding complexes composed of two subunits, provide critical regulation of this response. This review presents a synopsis of the genes induced by hypoxia in the context of breast cancer and discusses how upregulation of HIF-1 activity, and the homologous factor HIF-2, are not only fundamental for the adaptation to hypoxia but also may be critical for tumor progression.
Interactive control of diverse complex characters with neural networks (2015)

We present a method for training recurrent neural networks to act as near-optimal feedback controllers. It is able to generate stable and realistic behaviors for a range of dynamical systems and tasks - swimming, flying, biped and quadruped walking with different body morphologies. It does not require motion capture or task-specific features or state machines. The controller is a neural network, having a large number of feed-forward units that learn elaborate state-action mappings, and a small number of recurrent units that implement memory states beyond the physical system state. The action generated by the network is defined as velocity. Thus the network is not learning a control policy, but rather the dynamics under an implicit policy. Essential features of the method include interleaving supervised learning with trajectory optimization, injecting noise during training, training for unexpected changes in the task specification, and using the trajectory optimizer to obtain optimal feedback gains in addition to optimal actions.
Quantitative studies on the bactericidal actions of serum and complement. III. Observations on sera obtained after T.A.B. vaccination or during typhoid fever. (1956)

Summary Measurements of the bactericidal activity toward Salmonella typhosa of a variety of human and rabbit antisera have been made with the photometric growth assay technique. The strains employed were the 0901, Vi I and Ty 2, which differ in their content of the O- and Vi-antigens. Increases in bactericidal activity of human sera have been demonstrated following immunization with T.A.B. vaccine, or during the course of typhoid fever. The presence of Vi-antibody has been shown to increase the slope of the response curve. It has been discussed whether this may be related to the relative efficiencies of O- and Vi-antibodies in animal infections with S. typhosa .
CD40-CD40 ligand (2000)

CD40 is a cell surface receptor that belongs to the tumor necrosis factor-R (TNF-R) family, and that was first identified and functionally characterized on B lymphocytes. Its critical role in T cell-dependent humoral immune responses was demonstrated by patients with the hyper-IgM syndrome, as well as by gene targeting in mice. However, in recent years it has become clear that CD40 is expressed much more broadly, including expression on monocytes, dendritic cells, endothelial cells, and epithelial cells. In addition, the CD40-ligand (CD40-L/CD154), a member of the TNF family, is also expressed more widely than activated CD4+ T cells only. Therefore it is now thought that CD40-CD40-L interactions play a more general role in immune regulation. Collectively these studies have culminated in pre-clinical and clinical studies that are in progress. This article reviews recent developments in this field of research, with main emphasis on (1) structure and expression of CD40 and its ligand; (2) CD40 signal transduction; (3) in vitro function of CD40 on different cell types; and (4) in vivo functions of CD40/CD40-L interactions.
Misguided Axonal Projections, Neural Cell Adhesion Molecule 180 mRNA Upregulation, and Altered Behavior in Mice Deficient for the Close Homolog of L1 (2002)

Cell recognition molecules are involved in nervous system development and participate in synaptic plasticity in the adult brain. The close homolog of L1 (CHL1), a recently identified member of the L1 family of cell adhesion molecules, is expressed by neurons and glia in the central nervous system and by Schwann cells in the peripheral nervous system in a pattern overlapping, but distinct from, the other members of the L1 family. In humans, CHL1 (also referred to as CALL) is a candidate gene for 3p- syndrome-associated mental impairment. In the present study, we generated and analyzed CHL1-deficient mice. At the morphological level, these mice showed alterations of hippocampal mossy fiber organization and of olfactory axon projections. Expression of the mRNA of the synapse-specific neural cell adhesion molecule 180 isoform was upregulated in adult CHL1-deficient mice, but the mRNA levels of several other recognition molecules were not changed. The behavior of CHL1-deficient mice in the open field, the elevated plus maze, and the Morris water maze indicated that the mutant animals reacted differently to their environment. Our data show that the permanent absence of CHL1 results in misguided axonal projections and aberrant axonal connectivity and alters the exploratory behavior in novel environments, suggesting deficits in information processing in CHL1-deficient mice.