gebhart/patrepeval huggingface dataset:
An operon encoding three glycolytic enzymes in Lactobacillus delbrueckii subsp. bulgaricus: glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and triosephosphate isomerase (1998)

The structural genes gap, pgk and tpi encoding three glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK) and triosephosphate isomerase (TPI), respectively, have been cloned and sequenced from Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus). The genes were isolated after screening genomic sublibraries with specific gap and pgk probes obtained by PCR amplification of chromosomal DNA with degenerate primers corresponding to amino acid sequences highly conserved in GAPDHs and PGKs. Nucleotide sequencing revealed that the three genes were organized in the order gap-pgk-tpi. The translation start codons of the three genes were identified by alignment of the N-terminal sequences. These genes predicted polypeptide chains of 338, 403 and 252 amino acids for GAPDH, PGK and TPI, respectively, and they were separated by 96 bp between gap and pgk, and by only 18 bp between pgk and tpi. The codon usage in gap, pgk, tpi and three other glycolytic genes from L. bulgaricus differed, noticeably from that in other chromosomal genes. The site of transcriptional initiation was located by primer extension, and a probable promoter was identified for the gap-pgk-tpi operon. Northern hybridization of total RNA with specific probes showed two transcripts, an mRNA of 1.4 kb corresponding to the gap gene, and a less abundant mRNA of 3.4 kb corresponding to the gap-pgk-tpi cluster. The absence of a visible terminator in the 3'-end of the shorter transcript and the location of this 3'-end inside the pgk gene indicated that this shorter transcript was produced by degradation of the longer one, rather than by an early termination of transcription after the gap gene.
The pH independence of mammalian retrovirus infection (1990)

The pH dependence of early steps in the infection of human and other cells by mammalian retroviruses and retroviral pseudotype particles of vesicular stomatitis virus (VSV) was investigated for 10 strains of retrovirus, including C-type and D-type oncoviruses and human lentiviruses. When cells were treated with weak bases (NH4Cl and amantadine) to raise the pH of endocytic vesicles, only ecotropic murine leukaemia virus (MLV-E) and VSV showed pH-dependent entry. Pretreatment of retrovirus stocks in media below pH 5.0 did not reduce their titres but inactivated VSV to less than 10(-8) of the initial titre. VSV (MLV-E) pseudotype infection in five out of six mouse and rat cell lines was inhibited by NH4Cl, indicating that infection proceeds via receptor-mediated endocytosis. In contrast, NH4Cl treatment has no effect on the infection of XC cells in which MLV-E induces syncytia. It is postulated that the pH-independent entry and cell fusion of XC cells by MLV-E may result from the activity of a cell surface proteinase that cleaves viral gp70 at neutral pH.
Interpreting the BOLD Signal (2004)

The development of functional magnetic resonance imaging (fMRI) has brought together a broad community of scientists interested in measuring the neural basis of the human mind. Because fMRI signals are an indirect measure of neural activity, interpreting these signals to make deductions about the nervous system requires some understanding of the signaling mechanisms. We describe our current understanding of the causal relationships between neural activity and the blood-oxygen-level-dependent (BOLD) signal, and we review how these analyses have challenged some basic assumptions that have guided neuroscience. We conclude with a discussion of how to use the BOLD signal to make inferences about the neural signal.
Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice (2010)

Although adenovirus (Ad) has been regarded as an excellent vaccine vector, there are 2 major drawbacks to using this platform: (a) Ad-based vaccines induce a relatively weak humoral response against encoded transgenes, and (b) preexisting immunity to Ad is highly prevalent among the general population. To overcome these obstacles, we constructed an Ad-based malaria vaccine by inserting a B cell epitope derived from a Plasmodium yoelii circumsporozoite (CS) protein (referred to as the PyCS-B epitope) into the capsid proteins of WT/CS-GFP, a recombinant Ad expressing P. yoelii CS protein and GFP as its transgene. Multiple vaccinations with the capsid-modified Ad induced a substantially increased level of protection against subsequent malaria challenge in mice when compared with that of unmodified WT/CS-GFP. Increased protection correlated with augmented antibody responses against the PyCS-B epitope expressed in the capsid. Furthermore, replacement of hypervariable region 1 (HVR1) of the Ad capsid proteins with the PyCS-B epitope circumvented neutralization of the modified Ad by preexisting Ad-specific antibody, both in vivo and in vitro. Importantly, the immunogenicity of the Ad-containing PyCS-B epitope in the HVR1 and a P. yoelii CS transgene was maintained. Overall, this study demonstrates that the HVR1-modifed Ad vastly improves upon Ad as a promising malaria vaccine platform candidate.
Flavan derivatives. XXV. Mass spectra of 3-hydroxyflavanones, flavan-3-ols, and flavan-3,4-diols (1968)

Mass spectral data are reported for eight 3-hydroxyflavanones, ten flavan-3-ols, and twelve flavan-3,4-diol derivatives. The principal fragmentation of each of these three classes of compound yields ions derived by retro Diels-Alder fission of the heterocyclic nucleus, accompanied in the case of 3-hydroxyflavanones and flavan-3-ols by hydrogen transfer from the 3-hydroxyl group to the A ring fragment. Deuteration experiments with flavan-3-ols confirmed the origin of the hydrogen atom transferred. Flavan-3,4-diols show two characteristic fragmentation patterns depending on the insertion technique. Mass spectra obtained by indirect insertion of flavan-3,4-diols showed a very marked enhancement of the intensities of the M-18 and M-18-28 peaks, and of their fragmentation ions, compared with spectra obtained by direct insertion.
Investigation of surface treatment schemes on n-type GaN and Al0.20Ga0.80N (2005)

The effects of SiCl4 reactive-ion-etching (RIE) plasma treatment on n-GaN and n-Al0.20Ga0.80N surfaces, and the subsequent cleaning of the surfaces using ammonium hydroxide (NH4OH), hydrochloric acid (HCl), and buffered oxide etch (BOE) solutions, have been investigated using x-ray photoelectron spectroscopy and Auger electron spectroscopy measurements. Of these cleaning schemes, BOE was found to be the most effective treatment to remove oxides from the surfaces of the SiCl4 plasma treated samples. The SiCl4 plasma treatment of GaN and AlGaN resulted in the blueshift of Ga–N (Ga3d) peaks to higher binding energies corresponding to a shift of the Fermi level (EF) toward the conduction band edge at the surface. It has been reported that this type of shift is caused by the creation of N vacancies, which act as n-type dopant [D. W. Jenkins and J. D. Dow, Phys. Rev. B. 39, 3317 (1989); M. E. Lin, Z. F. Fan, Z. Ma, L. H. Allen, and H. Morkoç, Appl. Phys. Lett. 64, 887 (1994); A. T. Ping, Q. Chen, J. W. Yang, M. A. Khan, and I. Adesida, J. Electron. Mater. 27, 261 (1998)] on the surface due to SiCl4 plasma treatment. This corresponds to an increase in n-type dopant density on the surface. Thus, SiCl4 plasma treatment in a RIE system thins the Schottky barrier heights of n-GaN and n-AlGaN and aids in the formation of ohmic contacts on such surfaces.
Multi-planar image formation using NMR spin echoes (1977)

A new method of two- or three-dimensional spin density imaging by nuclear magnetic resonance (NMR) is proposed, which exploits the properties of spin echoes in time-dependent magnetic field gradients. An analysis shows that simultaneous observation and differentiation of signals, arising from all spins distributed in a plane or set of planes within the specimen, is possible. The method is thus capable of producing visual pictures faster than previously described planar imaging methods.
Atherosclerosis: imaging techniques and the evolving role of nuclear medicine. (1997)

Magnetic resonance angiography, being noninvasive, may replace conventional angiography for anatomical imaging of the vasculature. Ultrafast electron beam CT measures the calcium content in the atherosclerotic lesions. Intravascular ultrasound is the only technique that appears to be clinically useful in imaging the unstable, vulnerable plaques in coronary arteries. Magnetic resonance imaging techniques may be able to image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus associated with the plaques. In regard to the nuclear scientigraphic imaging techniques, radiolabeled lipoproteins, platelets and immunoglobulins have shown some clinical potential as imaging agents, but due to poor target-to-background and target-to-blood ratios these agents are not ideal for imaging coronary or even carotid lesions. Technetium-99m-labeled peptides and monoclonal antibody fragments that clear from circulation rapidly and bind specifically to different components of the atherosclerotic lesion showed significant potential in animal models and in limited clinical studies. FRE Peptides capable of binding to GPIIb/IIIA receptors on activated platelets appear to offer significant diagnostic potential for imaging intra-arterial thrombus. Positron emission tomography with metabolic tracers like [18F]-fluorodeoxyglucose (FDG) also appears to offer new opportunities for noninvasive imaging of atherosclerosis and atherothrombosis.
Update on therapeutic neovascularization (2004)

Therapeutic neovascularization for cardiovascular ischemia is a promising avenue in spite of disappointing early clinical trial results. The concept of three different mechanisms of neovascularization has served to define potential therapeutic targets such as vascular remodeling and stem cell recruitment, but it is anticipated that this will lose significance as the pleiotropic nature of angiogenic cytokines becomes fully understood. With the rapidly growing body of data on growth factors and pro-angiogenic strategies, approaches will emerge that are more effective than the ones that have been tested clinically thus far. Combinations of growth factors, for instance to stabilize vessels, or growth factors combined with cell transplants deserve more attention but will make the design of preclinical and clinical studies increasingly complex. Recent developments suggest that when using the appropriate dose and treatment regimens, even single growth factor therapy can result in stable and functional vessels. Whether gene therapy or protein therapy will be optimal for this purpose depends mainly on technical developments in vector design and production and on progress in the engineering of slow release matrix formulations for proteins. With the increasing complexity of therapeutic strategies, it remains imperative that these approaches are rationally based on fundamental and preclinical data.
Cellular stress response and apoptosis in cancer therapy (2001)

Anticancer treatment using cytotoxic drugs is considered to mediate cell death by activating key elements of the apoptosis program and the cellular stress response. While proteolytic enzymes (caspases) serve as main effectors of apoptosis, the mechanisms involved in activation of the caspase system are less clear. Two distinct pathways upstream of the caspase cascade have been identified. Death receptors, eg, CD95 (APO-1/Fas), trigger caspase-8, and mitochondria release apoptogenic factors (cytochrome c, Apaf-1, AIF), leading to the activation of caspase-9. The stressed endoplasmic reticulum (ER) contributes to apoptosis by the unfolded protein response pathway, which induces ER chaperones, and by the ER overload response pathway, which produces cytokines via nuclear factor-kappaB. Multiple other stress-inducible molecules, such as p53, JNK, AP-1, NF-kappaB, PKC/MAPK/ERK, and members of the sphingomyelin pathway have a profound influence on apoptosis. Understanding the complex interaction between different cellular programs provides insights into sensitivity or resistance of tumor cells and identifies molecular targets for rational therapeutic intervention strategies.
Modifying the Substrate Specificity of Staphylococcal Lipases (1999)

The lipase from Staphylococcus hyicus (SHL) displays a high phospholipase activity whereas the homologous S. aureus lipase (SAL) is not active or hardly active on phospholipid substrates. Previously, it has been shown that elements within the region comprising residues 254-358 are essential for the recognition of phospholipids by SHL. To specifically identify the important residues, nine small clusters of SHL were individually replaced by the corresponding SAL sequence within region 254-358. For cloning convenience, a synthetic gene fragment of SHL was assembled, thereby introducing restriction sites into the SHL gene and optimizing the codon usage. All nine chimeras were well-expressed as active enzymes. Eight chimeras showed lipase and phospholipase activities within a factor of 2 comparable to WT-SHL in standard activity assays. Exchange of the polar SHL region 293-300 by the more hydrophobic SAL region resulted in a 32-fold increased k(cat)/K(m) value for lipase activity and a concomitant 68-fold decrease in k(cat)/K(m) for phospholipase activity. Both changes are due to effects on catalytic turnover as well as on substrate affinity. Subsequently, six point mutants were generated; G293N, E295F, T297P, K298F, I299V, and L300I. Residue E295 appeared to play a minor role whereas K298 was the major determinant for phospholipase activity. The mutation K298F caused a 60-fold decrease in k(cat)/K(m) on the phospholipid substrate due to changes in both k(cat) and K(m). Substitution of F298 by a lysine in SAL resulted in a 4-fold increase in phospholipase activity. Two additional hydrophobic to polar substitutions further increased the phospholipase activity 23-fold compared to WT-SAL.
β57-Asp Plays an Essential Role in the Unique SDS Stability of HLA-DQA1*0102/DQB1*0602 αβ Protein Dimer, the Class II MHC Allele Associated with Protection from Insulin-Dependent Diabetes Mellitus (2000)

Studies of the stability of HLA-DQ have revealed a correlation between SDS stability of MHC class II alphabeta dimers and insulin-dependent diabetes mellitus (IDDM) susceptibility. The MHC class II alphabeta dimer encoded by HLA-DQA1*0102/DQB1*0602 (DQ0602), which is a dominant protective allele in IDDM, exhibits the greatest SDS stability among HLA-DQ molecules in EBV-transformed B-lymphoblastoid cells and PBLs. DQ0602 is also uniquely SDS stable in the HLA-DM-deficient cell line, BLS-1. We addressed the molecular mechanism of the stability of DQ0602 in BLS-1. A panel of mutants based on the polymorphic differences between HLA-DQA1*0102/DQB1*0602 and HLA-DQA1*0102/DQB1*0604 were generated and expressed in BLS-1. An Asp at beta57 was found to be critical for SDS stability, whereas Tyr at beta30, Gly at beta70, and Ala at beta86 played secondary roles. Furthermore, the level of class II-associated invariant chain peptide bound to HLA-DQ did not correlate with SDS stability, suggesting that class II-associated invariant chain peptide does not play a direct role in the unique SDS stability of DQ0602. These results support a role for DQB1 codon 57 in HLA-DQ alphabeta dimer stability and IDDM susceptibility.
Multi-Level, Multi-Dimensional Coding for High-Speed and High-Spectral-Efficiency Optical Transmission (2009)

We review and study several single carrier based multi-level and multi-dimensional coding (ML-MDC) technologies recently demonstrated for spectrally-efficient 100-Gb/s transmission. These include 16-ary PDM-QPSK, 64-ary PDM-8PSK, 64-ary PDM-8QAM as well as 256-ary PDM-16 QAM. We show that high-speed QPSK, 8PSK, 8QAM, and 16QAM can all be generated using commercially available optical modulators using only binary electrical drive signals through novel synthesis methods, and that all of these modulation formats can be detected using a universal receiver front-end and digital coherent detection. We show that the constant modulus algorithm (CMA), which is highly effective for blind polarization recovery of PDM-QPSK and PDM-8PSK signals, is much less effective for PDM-8QAM and PDM-16 QAM. We then present a recently proposed, cascaded multi-modulus algorithm for these cases. In addition to the DSP algorithms used for constellation recovery, we also describe a DSP algorithm to improve the performance of a coherent receiver using single-ended photo-detection. The system impact of ASE noise, laser phase noise, narrowband optical filtering and fiber nonlinear effects has been investigated. For high-level modulation formats using full receiver-side digital compensation, it is shown that the requirement on LO phase noise is more stringent than the signal laser. We also show that RZ pulse shaping significantly improves filter- and fiber-nonlinear tolerance. Finally we present three high-spectral-efficiency and high-speed DWDM transmission experiments implementing these ML-MDC technologies.
Rho GTPase regulation of exocytosis in yeast is independent of GTP hydrolysis and polarization of the exocyst complex (2005)

Rho GTPases are important regulators of polarity in eukaryotic cells. In yeast they are involved in regulating the docking and fusion of secretory vesicles with the cell surface. Our analysis of a Rho3 mutant that is unable to interact with the Exo70 subunit of the exocyst reveals a normal polarization of the exocyst complex as well as other polarity markers. We also find that there is no redundancy between the Rho3-Exo70 and Rho1-Sec3 pathways in the localization of the exocyst. This suggests that Rho3 and Cdc42 act to polarize exocytosis by activating the exocytic machinery at the membrane without the need to first recruit it to sites of polarized growth. Consistent with this model, we find that the ability of Rho3 and Cdc42 to hydrolyze GTP is not required for their role in secretion. Moreover, our analysis of the Sec3 subunit of the exocyst suggests that polarization of the exocyst may be a consequence rather than a cause of polarized exocytosis.
Effects of various histamine H2-receptor antagonists on gastrointestinal motility and gastric emptying. (1993)

Effects of various histamine H2-receptor antagonists (H2-RA) on gastrointestinal motility and gastric emptying were investigated. Ranitidine, nizatidine and cimetidine dose dependently induced contractions over the entire gastrointestinal tract, and the order of their effects was ranitidine > nizatidine > cimetidine. Roxatidine or famotidine had no effects on motility of the gastrointestinal tract. Ranitidine and nizatidine also induced contractions during the postprandial period and facilitated gastric emptying, while cimetidine, roxatidine or famotidine did not influence gastric emptying. Since acid reduction is thought to be the most important element of the treatment of peptic ulcer and reflux esophagitis, it was inferred that administration of a H2-RA selected with consideration of its property of facilitating gastrointestinal motility is effective in the treatment of patients with abnormal gastrointestinal motility.
Effective clearance of a persistent viral infection requires cooperation between virus-specific Lyt2+ T cells and nonspecific bone marrow-derived cells (1987)

The lifelong chronic lymphocytic choriomeningitis virus (LCMV) infection established in neonatally or congenitally infected mice can be eliminated by adoptive transfer of lymphoid cells from LCMV-immune mice. In this study, we have identified the effector cells mediating the clearance of persistent and disseminated LCMV infection. Using mice that are recombinant in the H-2 region and by selective depletion of lymphocyte subpopulations, we show that viral clearance was mediated by LCMV-specific Lyt2+ L3T4- T cells that are restricted to the class I genes of the major histocompatibility complex. In addition, our results show a requirement for host-derived bone marrow cells for the effective elimination of virus from the liver. These studies emphasize the importance of virus-specific T cells and an intact bone marrow function in viral clearance.
The HMG Box Transcription Factor Sox4 Contributes to the Development of the Endocrine Pancreas (2005)

To investigate the role of the Sry/hydroxymethylglutaryl box (Sox) transcription factors in the development of the pancreas, we determined the expression pattern of Sox factors in the developing mouse pancreas. By RT-PCR, we detected the presence of multiple Sox family members in both the developing pancreas and mature islets and then focused on two factors, Sox2 and Sox4. The expression field of Sox2, which plays a role in the maintenance of some stem cell populations, included the developing duodenum, but Sox2 was specifically excluded from the pancreatic buds. In contrast, Sox4 was detected broadly in the early pancreatic buds and eventually became restricted to the nuclei of all islet cells in the adult mouse. Mice homozygous for a null mutation of the sox4 gene showed normal pancreatic bud formation and endocrine cell differentiation up to embryonic day 12.5. Beyond that date, cultured pancreatic explants lacking sox4 failed to form normal islets. Instead, a markedly reduced number of endocrine cells were found scattered through the explant. We show here that several Sox transcription factors are expressed in the developing pancreas and in the islet, and that one of these factors, Sox4, is required for the normal development of pancreatic islets.
Idiotype-like molecules on cells of a human T cell leukemia. (1983)

Two monoclonal antibodies were obtained that showed unique specificities for the leukemic T cells used for immunization. One antibody, S160, was totally specific for the antigen. The other antibody, S511, also reacted with a small population of normal T cells. This was made especially evident by concentrating these normal T cells with the antibody. Considerable evidence was obtained that both antibodies reacted with the same membrane molecules. In the unreduced state a major component of approximately 80 kdaltons was observed; after reduction this split into two components of approximately 43 and approximately 38 kdaltons. The reaction of the two antibodies with different antigenic sites on the same molecule, one representing a private site and the other a more cross-reactive site, strongly suggests an antibodylike molecule, but composed of polypeptide chains differing from immunoglobulins.
Passage of Heme-Iron Across the Envelope of Staphylococcus aureus (2003)

The cell wall envelope of Gram-positive pathogens functions as a scaffold for the attachment of virulence factors and as a sieve that prevents diffusion of molecules. Here the isd genes (iron-regulated surface determinant) of Staphylococcus aureus were found to encode factors responsible for hemoglobin binding and passage of heme-iron to the cytoplasm, where it acts as an essential nutrient. Heme-iron passage required two sortases that tether Isd proteins to unique locations within the cell wall. Thus, Isd appears to act as an import apparatus that uses cell wall-anchored proteins to relay heme-iron across the bacterial envelope.
Recessive truncating titin gene, TTN , mutations presenting as centronuclear myopathy (2013)

Our study identifies truncating TTN mutations as a cause of congenital myopathy that is reported as CNM. Unlike the classic CNM genes that are all involved in excitation-contraction coupling at the triad, TTN encodes the giant sarcomeric protein titin, which forms a myofibrillar backbone for the components of the contractile machinery. This study expands the phenotypic spectrum associated with TTN mutations and indicates that TTN mutation analysis should be considered in cases of possible CNM without mutations in the classic CNM genes.