gebhart/patrepeval huggingface dataset:
Reduction kinetics of Fe(III), Co(III), U(VI), Cr(VI), and Tc(VII) in cultures of dissimilatory metal‐reducing bacteria (2002)

The reduction kinetics of Fe(III)citrate, Fe(III)NTA, Co(III)EDTA-, U(VI)O(2) (2+), Cr(VI)O(4) (2-), and Tc(VII)O(4) (-) were studied in cultures of dissimilatory metal reducing bacteria (DMRB): Shewanella alga strain BrY, Shewanella putrefaciens strain CN32, Shewanella oneidensis strain MR-1, and Geobacter metallireducens strain GS-15. Reduction rates were metal specific with the following rate trend: Fe(III)citrate > or = Fe(III)NTA > Co(III)EDTA- >> UO(2)(2+) > CrO(4)(2-) > TcO(4)(-), except for CrO(4) (2-) when H(2) was used as electron donor. The metal reduction rates were also electron donor dependent with faster rates observed for H(2) than lactate- for all Shewanella species despite higher initial lactate (10 mM) than H2 (0.48 mM). The bioreduction of CrO(4) (2-) was anomalously slower compared to the other metals with H(2) as an electron donor relative to lactate and reduction ceased before all the CrO(4)(2-) had been reduced. Transmission electron microscopic (TEM) and energy-dispersive spectroscopic (EDS) analyses performed on selected solids at experiment termination found precipitates of reduced U and Tc in association with the outer cell membrane and in the periplasm of the bacteria. The kinetic rates of metal reduction were correlated with the precipitation of reduced metal phases and their causal relationship discussed. The experimental rate data were well described by a Monod kinetic expression with respect to the electron acceptor for all metals except CrO(4)(2-), for which the Monod model had to be modified to account for incomplete reduction. However, the Monod models became statistically over-parameterized, resulting in large uncertainties of their parameters. A first-order approximation to the Monod model also effectively described the experimental results, but the rate coefficients exhibited far less uncertainty. The more precise rate coefficients of the first-order model provided a better means than the Monod parameters, to quantitatively compare the reduction rates between metals, electron donors, and DMRB species.
Isolation and properties of recombinant DNA produced variants of human alpha 1-proteinase inhibitor. (1985)

Using the glyceraldehyde-3-phosphate dehydrogenase promoter, nonglycosylated human alpha 1-proteinase inhibitor, representing 10% of the soluble cell protein, has been synthesized in yeast. Two forms of this protein were isolated with one being analogous to the human plasma protein and the other having the amino acid valine replacing methionine at position 358 (the P1 position). Both proteins were more sensitive to heat inactivation than the plasma form, and both had shorter half-lives in rabbits. These differences were presumably due to the absence of carbohydrate. Each protein could bind neutrophil elastase at a rate only slightly slower than that of human plasma alpha 1-proteinase inhibitor. However, the valine variant was stable to oxidation, while the P1 methionine-containing protein was readily inactivated. The specificity of alpha 1-proteinase inhibitor (methionine) was identical to that of the plasma form; however, the valine form could only effectively bind to neutrophil or pancreatic elastase, "trypsin-like" serine proteinases not being inactivated at all. These data indicate the potential importance of mutant forms of proteinase inhibitors, produced by recombinant DNA technology, as therapeutic agents for the inactivation of excess proteinases of a specific type in tissues.
A novel serotonin antagonist 2,2′‐bis[3‐(2‐N,N‐dimethylaminoethyl)indolyl]sulfide (BDIS) (1984)

Abstract A novel serotonin antagonist, 2,2′‐bis[3‐(2‐ N,N ‐dimethylaminoethyl)indolyl]sulfide (BDIS) was synthesized in one step from the reaction of N,N ‐dimethyltryptamine with thionyl chloride.
Reactive radio frequency sputter deposition of higher nitrides of titanium, zirconium, and hafnium (1986)

Higher nitrides of Ti, Zr, and Hf have been prepared by reactive rf sputtering of Ti, Zr, and Hf metals in a pure nitrogen atmosphere. The electrical and optical properties of these films are highly dependent on two deposition parameters, namely, the substrate temperature and the target voltage. We find that at each particular target voltage, there exists a critical temperature below which the higher nitride phase can be deposited and above which the phase cannot form. This suggests that the higher nitride phase (which is speculated to be an ordered defect structure) is metastable and is not energetically favored at high processing temperature or at high input power. At 2000 V target voltage, this critical temperature is determined to be approximately 200 °C for Hf–N, 25 °C for Zr–N, and is unknown for Ti–N system. The optical band gap of the ZrNx films decreases from 5.31 to 1.66 eV as the substrate temperature varies from −196 to 750 °C. Thermal analyses, using modulated beam mass spectrometry for monitoring the desorption rate of N2 gas, show that the principal decomposition reaction for TiNx, ZrNx, and HfNx films peak at 753, 773, and 788 °C, respectively.
Aggresomes Resemble Sites Specialized for Virus Assembly (2001)

The large cytoplasmic DNA viruses such as poxviruses, iridoviruses, and African swine fever virus (ASFV) assemble in discrete perinuclear foci called viral factories. Factories exclude host proteins, suggesting that they are novel subcellular structures induced by viruses. Novel perinuclear structures, called aggresomes are also formed by cells in response to misfolded protein (Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. J. Cell Biol. 143:1883--1898; García-Mata, R., Z. Bebök, E.J. Sorscher, and E.S. Sztul. 1999. J. Cell Biol. 146:1239--1254). In this study, we have investigated whether aggresomes and viral factories are related structures. Aggresomes were compared with viral factories produced by ASFV. Aggresomes and viral factories were located close to the microtubule organizing center and required an intact microtubular network for assembly. Both structures caused rearrangement of intermediate filaments and the collapse of vimentin into characteristic cages, and both recruited mitochondria and cellular chaperones. Given that ASFV factories resemble aggresomes, it is possible that a cellular response originally designed to reduce the toxicity of misfolded proteins is exploited by cytoplasmic DNA viruses to concentrate structural proteins at virus assembly sites.
Functional Flexibility of Intestinal IgA – Broadening the Fine Line (2012)

Intestinal bacteria outnumber our own human cells in conditions of both health and disease. It has long been recognized that secretory antibody, particularly IgA, is produced in response to these microbes and hypothesized that this must play an important role in defining the relationship between a host and its intestinal microbes. However, the exact role of IgA and the mechanisms by which IgA can act are only beginning to be understood. In this review we attempt to unravel the complex interaction between so-called "natural," "primitive" (T-cell-independent), and "classical" IgA responses, the nature of the intestinal microbiota/intestinal pathogens and the highly flexible dynamic homeostasis of the mucosal immune system. Such an analysis reveals that low-affinity IgA is sufficient to protect the host from excess mucosal immune activation induced by harmless commensal microbes. However, affinity-maturation of "classical" IgA is essential to provide protection from more invasive commensal species such as segmented filamentous bacteria and from true pathogens such as Salmonellatyphimurium. Thus a correlation is revealed between "sophistication" of the IgA response and aggressiveness of the challenge. A second emerging theme is that more-invasive species take advantage of host inflammatory mechanisms to more successfully compete with the resident microbiota. In many cases, the function of IgA may be to limit such inflammatory responses, either directly by coagulating or inhibiting virulence of bacteria before they can interact with the host or by modulating immune signaling induced by host recognition. Therefore IgA appears to provide an added layer of robustness in the intestinal ecosystem, promoting "commensal-like" behavior of its residents.
Immune RNA therapy as an effective adjuvant immunotherapy after surgery: An animal model (1983)

Transfer of tumor immunity as adjuvant cancer therapy has been a topic of intense interest. We have examined the efficacy of various combinations of surgery, xenogeneic immune RNA, xenogeneic normal RNA, tumor vaccine, and nonspecific splenocytes as adjuvant therapy for B16 melanoma in the C57BL/6J mouse system. B16 melanoma was transplanted by trocar into the right hind limb of 6-week-old mice. The tumors were readily palpable on the ninth day posttransplantation. The tumors were amputated at that time under mild anesthesia. Immune RNA was prepared by hot phenol extraction from immune sheep spleens. Various combinations of immune RNA, normal RNA, and tumor antigen, with or without normal mouse spleen cells, were administered every other day for a total of 10 injections. The survival and mode of death was followed up to 120 days. All mice without any treatment died within 30 days. Immunotherapy had no effect on the survival of mice that did not have surgical therapy. Individual group comparisons between mice that underwent surgery only and mice that had surgery plus immune RNA immunotherapy revealed a striking statistical improvement (P less than 0.01). Comparing all groups that received amputation plus various combinations of adjuvant immunotherapy showed no statistical difference in survival. However, immune RNA appears somewhat superior to normal RNA or antigen only. It appears that adjuvant immune RNA immunotherapy following surgical excision in the B16 melanoma model significantly improves survival and retards the spread of metastases.
Articles : Characterization of Protein Disulfide Isomerase during Lactoferrin Polypeptide Structural Maturation in the Endoplasmic Reticulum (2001)

A time-dependent folding process was used to determine whether or not protein disulfide isomerase (PDI) plays an important role in the maturation of nascent lactoferrin polypeptides. Interaction between lactoferrin and PDI was analyzed according to the co-immunoprecipitation of the two proteins. The results indicate that lactoferrin folding requires a significant interaction with PDI and its binding is relatively brief compared to other nascent polypeptides. The amount of lactoferrin interacting with PDI increases up to half a minute and sharply decreases beyond this time point. During the refolding process that follows reduction by DTT, lactoferrin polypeptides heavily interact with PDI and the interaction period was extended compared to the normal folding process. In terms of the temperature effect on PDI-lactoferrin interaction, PDI binds to lactoferrin polypeptides longer at a lower temperature (here, 25℃) than 37℃. The lactoferrin-PDI interaction was also studied in vitro. According to the in vitro experiment data, PDI was still functional in cell lysates assisting lactoferrin folding into the mature form. PDI interacts with lactoferrin polypeptides for an extended period during the folding in vitro. During the refolding process in vitro, intermolecular aggregates and refolding oligomers matured into a functional form after PDI binds to the lactoferrin. These results suggest that PDI provides a prolonged chaperoning activity in the refolding processes and that there appears to be a greater requirement for PDI chaperone activity in the refolding of lactoferrin polypeptides.
Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319 (2013)

Fibroblast growth factor 21 is a novel hormonal regulator with the potential to treat a broad variety of metabolic abnormalities, such as type 2 diabetes, obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild type FGF21 (FGF21) has been shown to ameliorate metabolic disorders in rodents and non-human primates. However, development of FGF21 as a drug is challenging and requires re-engineering of its amino acid sequence to improve protein expression and formulation stability. Here we report the design and characterization of a novel FGF21 variant, LY2405319. To enable the development of a potential drug product with a once-daily dosing profile, in a preserved, multi-use formulation, an additional disulfide bond was introduced in FGF21 through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP), which was subject to proteolytic cleavage. In addition, to eliminate an O-linked glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing large-scale, homogenous protein production in Pichia pastoris. Altogether re-engineering of FGF21 led to significant improvements in its biopharmaceutical properties. The impact of these changes was assessed in a panel of in vitro and in vivo assays, which confirmed that biological properties of LY2405319 were essentially identical to FGF21. Specifically, subcutaneous administration of LY2405319 in ob/ob and diet-induced obese (DIO) mice over 7-14 days resulted in a 25-50% lowering of plasma glucose coupled with a 10-30% reduction in body weight. Thus, LY2405319 exhibited all the biopharmaceutical and biological properties required for initiation of a clinical program designed to test the hypothesis that administration of exogenous FGF21 would result in effects on disease-related metabolic parameters in humans.
Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. (1995)

We investigated the role of hepatocyte apoptosis in four different murine models of acute inflammatory liver failure. Liver damage induced in D-galactosamine-sensitized mice by endotoxin infection was initiated by processes typical of apoptosis, ie, chromatin condensation, DNA fragmentation, and formation of intracellular apoptotic bodies. DNA was cleaved into oligonucleosomal fragments in the liver before a significant rise of alanine aminotransferase in plasma occurred. Passive immunization against tumor necrosis factor (TNF) completely inhibited the injury caused by endotoxin. Direct injection of recombinant TNF-alpha also caused DNA fragmentation followed by alanine aminotransferase release into the plasma. Pretreatment of mice with interleukin-1 beta, which is known to suppress TNF-induced lethality, completely prevented apoptosis and liver failure in this model. These results demonstrate the causal role of TNF in endotoxin-induced hepatic apoptosis. TNF-inducible hepatocyte apoptosis in vivo was not only observed in D-galactosamine-sensitized mice, but also when the alternative transcriptional inhibitor actinomycin D was used. In mice injected with the TNF-inducing T cell mitogen concanavalin A, hepatic apoptosis was even noticed without requirement of additional sensitizers. We conclude that TNF-induced hepatocyte apoptosis is an early, general, and possibly causal event during experimental liver failure triggered by inflammatory stimuli.
A Two-Stage Cross Correlation Approach to Template Matching (1984)

Two-stage template matching with sum of absolute differences as the similarity measure has been developed by Vanderburg and Rosenfeld [1], [2]. This correspondence shows the development of two-stage template matching with cross correlation as the similarity measure. The threshold value of the first-stage is derived analytically and its validity is verified experimentally. Considerable speed-up over the one-stage process can be obtained by introducing only a small false dismissal probability.
Antimetastatic effect of CpG DNA mediated by type I IFN. (2001)

The mechanisms involved in the antimetastatic effect of CpG-containing DNA were investigated in a mouse model of experimental metastasis. Tumor cell colony formation in lungs or livers of mice after i.v. inoculation with syngeneic fibrosarcoma or thymoma cells was determined. The i.v. injection of plasmid DNA or synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs before tumor cell application strongly inhibited metastasis. Because synthetic CpG-ODN was not directly tumor cytotoxic, the target cells for this CpG-ODN effect were determined. The cytotoxic activity on standard natural killer (NK) targets as well as on fibrosarcoma cells of splenic NK cells and NKT cell-containing liver mononuclear cells derived from CpG-ODN-treated mice was strongly enhanced. Participation of NK/NKT cells in the CpG-induced antimetastatic effect was demonstrated by reduction of the antimetastatic effect in mice depleted of NK/NKT cells and beta2-microglobulin-deficient mice. Neutralization of interleukin 12, interleukin 18, or IFN-gamma did not interfere with the CpG-induced antimetastatic effect. However, in sera of CpG-ODN-treated mice, high levels of IFN-alpha were detected, and in IFN-alpha/beta receptor-deficient mice, the CpG-ODN-induced antimetastatic effect was strongly reduced. These data indicate that CpG-ODNs activate NK/NKT cells for antimetastatic activity indirectly via IFN-alpha/beta receptor activation. The exploitation of the stimulatory activity of CpG-ODN for the innate immune system might be a useful strategy for antimetastatic therapy.
A Biotin-Regulated Locus, bioS, in a Possible Survival Operon of Rhizobium meliloti (1997)

A novel biotin-inducible DNA locus, bioS, was found in Rhizobium meliloti 1021 by mutation with a transposable promoter probe. The promoterless nptII reporter responded to 40 nM biotin with a sixfold increase in NPTII protein. Stationary-phase mutant cells accumulated 50% more 14C-biotin than corresponding wild-type cells. The prototrophic mutant competed equally with the wild type in biotin-free medium but poorly when 40 nM biotin was present. The 588-bp bioS is located among three genes showing homology to survival operons of other bacteria, and it may be part of a system that R. meliloti uses to respond to plant biotin signals.
Expression and clinical significance of Nectin-4 in hepatocellular carcinoma (2016)

Nectin-4 is upregulated in HCC and may be a novel prognostic biomarker for the patients after surgical resection.
Impact of early cART in the gut during acute HIV infection (2016)

Early after HIV infection there is substantial depletion of CD4<sup>+</sup> T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I-V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4<sup>+</sup> T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4<sup>+</sup> T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4<sup>+</sup> T cells after 96 weeks of cART.
Structure−Cytoprotective Activity Relationship of Simple Molecules Containing an α,β-Unsaturated Carbonyl System (1997)

In previous reports we attributed the cytoprotective activity of several sesquiterpene lactones to the presence of a nonhindered electrophilic acceptor in their structure. We suggested that the mechanism of protection would be, at least in part, mediated through a reaction between the electrophilic acceptor and the sulfhydryl-containing groups of the mucosa. We report here the gastric cytoprotective effect of simple molecules containing an alpha, beta-unsaturated carbonyl group. In the present paper, we undertake the study of molecular accessibility and molecular shape, in addition to conformational, electronic, and steric factors. Our results helped to establish two important facts connecting chemical structure with cytoprotective effect. Firstly, an adequate molecular accessibility appears to be necessary to produce the biological response, and secondly, the alpha,beta-unsaturated carbonyl system has to be included in a cyclic structure or, at least, in the proximity of a cyclic system.
Investigation of carrier to envelope phase and repetition rate: fingerprints of mode-locked laser cavities (2009)

We use mode locked lasers in a non-conventional way, as a sensor to perform intracavity measurements. To understand this new technique of intracavity phase interferometry (IPI), one should take a detailed look at the characteristics of the frequency comb and its sensitivity to its parent cavity. The laser cavity provides a means to perform phase interferometry while outside the cavity one can only observe amplitude intereference. Many physical quantities such as nonlinear index, Earth rotation, magnetic field, Fresnel drag, etc are converted to phase. IPI is performed by designing laser cavities in which two pulses circulate independently, generating two pulse trains that can have a phase difference that will be converted to frequency. We also explore repetition rate spectroscopy in Rb87 by tailoring a laser wavelength, power and bandwidth. Coherent population trapping is observed when the laser repetition rate matches submultiples of hyperfine splitting.
USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma (2014)

In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target.