gebhart/patrepeval huggingface dataset:
Parathyroid Hormone Added to Established Hormone Therapy: Effects on Vertebral Fracture and Maintenance of Bone Mass After Parathyroid Hormone Withdrawal (2001)

Our best pharmacologic agents for osteoporosis treatment prevent no more than 40-60% of osteoporotic fractures in patients at highest risk. Thus, there is a need for agents that can further augment bone mass and reduce fracture risk more substantially. To this end, we investigated the utility of parathyroid hormone (PTH) in combination with established hormone-replacement therapy (HRT) in women with osteoporosis. Fifty-two women who had been on HRT for at least 2 years were enrolled in this trial in which 25 were assigned randomly to remain on HRT alone and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH(1-34) 400 U (25 microg) per day for 3 years. Bone mineral density (BMD) measurements at the spine, hip, and total body as well as biochemical determinations of bone turnover and calcium homeostasis were obtained every 6 months. Lateral thoracic and lumbar spine X-rays were obtained at baseline and annually. Subjects also had measurements of bone density and biochemical indices of bone turnover 1 year after discontinuation of PTH, while HRT was continued. In the group receiving HRT alone, bone density and biochemical variables of bone turnover remained stable throughout the 3-year treatment trial and 1-year follow-up. In the PTH + HRT group, biochemical variables of bone formation and resorption peaked at 6 months and subsequently remained elevated until 30 months at which time levels were indistinguishable from baseline. Subjects in the PTH + HRT group increased bone mass by 13.4+/-1.4% in the spine, 4.4+/-1.0% in the total hip, and 3.7+/-1.4% in the total body. Bone density measurements remained stable 1 year after discontinuation of PTH without any significant loss while women continued HRT. Biochemical variables did not change significantly after cessation of PTH through the 1-year follow-up period. PTH + HRT reduced the percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15% height reduction criterion) and from 25% to 0% (using a 20% height reduction criterion) compared with women receiving HRT alone (p < 0.02 for both). We conclude that ongoing HRT maintains almost all of the PTH-induced bone mass increment for 1 year after discontinuation of PTH. Furthermore, PTH in combination with hormone therapy is an effective means of increasing bone mass throughout the skeleton and specifically reducing vertebral fracture occurrence by 75-100%, compared with HRT alone.
U.S. Department of Energy Summary of 2012 Occupational Radiation Exposure (Poster) (2012)

This poster provides graphic data for 2010-2012 of collective total effective dose (TED) by site, and graphical data for 2008-2012 of components of TED, average measurable TED, percentage of collective TED above dose, collective dose and average measurable dose (1974-2012), and numbers of individuals in the DOE workforce, total number of records of monitored individuals, and number of individuals with a measurable dose. Also, there is a table of the number of individuals receiving >2 rems administrative control level and >5 rems annual limit for 2008-2012.
Fine mapping of a mouse metallothionein gene metal response element. (1989)

Metal-regulated transcription of metallothionein (MT) genes in higher eucaryotes involves multiple copies of a highly conserved 17-base-pair metal-regulatory element (MRE). We have assayed by transient transfection the ability of mouse MT-I element d (MREd) to confer metal responsivity to constructs containing the mouse MT-I TATA box and the bacterial chloramphenicol acetyltransferase indicator gene. A single copy of MREd works bidirectionally to afford a three- to fourfold induction, and dual copies act cooperatively to yield a 10- to 20-fold response. Element d responds to the same spectrum of heavy metals as doses the complete MT gene promoter. The sequences involved in induction by metals were delineated by analyzing point mutations in MREd. While nucleotides of the highly conserved core sequence TGCPuCXC are critical, substitutions in the less conserved regions affect the induction response only marginally. These sequences include residues of a potential Sp1-binding site, suggesting that if Sp1 binds to MREd, it has little if any role in induction by metals.
Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1 (2001)

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiology in isolated myocytes and electrocardiography in vivo. HERG increased the rapid component, I(Kr), of the delayed rectifier current, thereby accelerating repolarization, increasing refractoriness, and diminishing beat-to-beat action potential variability. Conversely, HERG-G628S suppressed I(Kr) without significantly delaying repolarization. Nevertheless, HERG-G628S abbreviated refractoriness and increased beat-to-beat variability, leading to early afterdepolarizations (EADs). KCNE1 increased the slow component of the delayed rectifier, I(Ks), without clear phenotypic sequelae. In contrast, KCNE1-D76N suppressed I(Ks) and markedly slowed repolarization, leading to frequent EADs and electrocardiographic QT prolongation. Thus, the two genes predispose to sudden death by distinct mechanisms: the KCNE1 mutant flagrantly undermines cardiac repolarization, and HERG-G628S subtly facilitates the genesis and propagation of premature beats. Our ability to produce electrocardiographic long QT in vivo with a clinical KCNE1 mutation demonstrates the utility of somatic gene transfer in creating genotype-specific disease models.
Chemopreventive Agent Resveratrol, a Natural Product Derived From Grapes, Triggers CD95 Signaling-Dependent Apoptosis in Human Tumor Cells (1998)

Resveratrol, a constituent of grapes and other food products, has been shown to prevent carcinogenesis in murine models. We report here that resveratrol induces apoptotic cell death in HL60 human leukemia cell line. Resveratrol-treated tumor cells exhibit a dose-dependent increase in externalization of inner membrane phosphatidylserine and in cellular content of subdiploid DNA, indicating loss of membrane phospholipid asymmetry and DNA fragmentation. Resveratrol-induced cell death is mediated by intracellular caspases as observed by the dose-dependent increase in proteolytic cleavage of caspase substrate poly (ADP-ribose) polymerase (PARP) and the ability of caspase inhibitors to block resveratrol cytotoxicity. We also show that resveratrol treatment enhances CD95L expression on HL60 cells, as well as T47D breast carcinoma cells, and that resveratrol-mediated cell death is specifically CD95-signaling dependent. On the contrary, resveratrol treatment of normal human peripheral blood lymphocytes (PBLs) does not affect cell survival for up to 72 hours, which correlates with the absence of a significant change in either CD95 or CD95L expression on treated PBLs. These data show specific involvement of the CD95-CD95L system in the anti-cancer activity of resveratrol and highlight the chemotherapeutic potential of this natural product, in addition to its recently reported chemopreventive activity.
Human DNA Polymerase ι Promiscuous Mismatch Extension (2001)

Human DNA polymerase iota is a low-fidelity template copier that preferentially catalyzes the incorporation of the wobble base G, rather than the Watson-Crick base A, opposite template T (Tissier, A., McDonald, J. P., Frank, E. G., and Woodgate, R. (2000) Genes Dev. 14, 1642-1650; Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., and Prakash, L. (2000) Nature 406, 1015-1019; Zhang, Y., Yuan, F., Wu, X., and Wang, Z. (2000) Mol. Cell. Biol. 20, 7099-7108). Here, we report on its ability to extend all 12 possible mispairs and 4 correct pairs in different sequence contexts. Extension from both matched and mismatched primer termini is generally most efficient and accurate when A is the next template base. In contrast, extension occurs less efficiently and accurately when T is the target template base. A striking exception occurs during extension of a G:T mispair, where the enzyme switches specificity, "preferring" to make a correct A:T base pair immediately downstream from an originally favored G:T mispair. Polymerase iota generates a variety of single and tandem mispairs with high frequency, implying that it may act as a strong mutator when copying undamaged DNA templates in vivo. Even so, its limited ability to catalyze extension from a relatively stable primer/template containing a "buried" mismatch suggests that polymerase iota-catalyzed errors are confined to short template regions.
Role of Complement Activation in Obliterative Bronchiolitis Post–Lung Transplantation (2013)

Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17-regulated autoimmunity to type V collagen and alloimmunity, which could be enhanced by complement activation. However, the specific role of complement activation in lung allograft pathology, IL-17 production, and OB is unknown. The current study examines the role of complement activation in OB. Complement-regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of complement activation, was upregulated locally. IL-17 differentially suppressed complement receptor 1-related protein y expression in airway epithelial cells in vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and decreased local C3a production. Exogenous C3a enhanced IL-17 production from alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically neutralizing C5 abrogated the development of OB, reduced acute rejection severity, lowered systemic and local levels of C3a and C5a, recovered CRP expression, and diminished systemic IL-17 and IL-6 levels. These data indicated that OB induction is in part complement dependent due to IL-17-mediated downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed-forward loop that may enhance CRP downregulation, suggesting that complement blockade could be a therapeutic strategy for OB.
Amplification of 100-fs Pulses in Alexandrite Using Chirped Pulse Techniques (1989)

Chirped pulse amplification is used to generate 2 mJ pulses of 106 fs duration in an alexandrite amplifier. Compression of the optical pulse is achieved by using a sequence of intracavity prisms in conjunction with diffraction gratings. This allows for the compensation of both linear and quadratic contributions to the dispersion from the amplifier.
Cytochrome P450 2J2 Promotes the Neoplastic Phenotype of Carcinoma Cells and Is Up-regulated in Human Tumors (2005)

Cytochrome P450 (CYP) arachidonic acid epoxygenase 2J2 converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids, which exert diverse biological activities in cardiovascular system and endothelial cells. However, it is unknown whether this enzyme highly expresses and plays any role in cancer. In this study, we found that very strong and selective CYP2J2 expression was detected in human carcinoma tissues in 101 of 130 patients (77%) as well as eight human carcinoma cell lines but undetectable in adjacent normal tissues and nontumoric human cell lines by Western, reverse transcription-PCR, and immunohistochemical staining. In addition, forced overexpression of CYP2J2, and CYP BM3F87V or addition of epoxyeicosatrienoic acids (EET) in cultured carcinoma cell lines in vitro markedly accelerated proliferation by analyses of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell accounts, and cell cycle analysis, and protected carcinoma cells from apoptosis induced by tumor necrosis factor alpha (TNF-alpha) in cultures. In contrast, antisense 2J2 transfection or addition of epoxygenase inhibitors 17-ODYA inhibited proliferation and accelerated cell apoptosis induced by TNF-alpha. Examination of signaling pathways on the effects of CYP2J2 and EETs revealed activation of mitogen-activated protein kinases and PI3 kinase-AKT systems and elevation of epithelial growth factor receptor phosphorylation level. These results strongly suggest that CYP epoxygenase 2J2 plays a previously unknown role in promotion of the neoplastic cellular phenotype and in the pathogenesis of a variety of human cancers.
FGF-2 binding to fibrin(ogen) is required for augmented angiogenesis (2005)

We have shown previously that fibrin(ogen) binds fibroblast growth factor 2 (FGF-2) and potentiates stimulation of endothelial-cell (EC) proliferation. We have now used 2 FGF-2 mutants differing only in the 5 residues constituting the binding site to characterize the importance of this interaction in angiogenesis. The nonbinding (2212) and binding (221*2) mutants stimulated EC proliferation by 2.2 +/- 0.4-fold and 2.9 +/- 0.3-fold over control, respectively, and both were similar to wild-type (wt) FGF-2 (2.5 +/- 0.3-fold). Proliferation was augmented by fibrinogen to 5.3 +/- 1.2-fold and 4.8 +/- 0.8-fold with wtFGF-2 and 221*2, whereas no augmentation occurred with 2212 and fibrinogen. Using a placental explant model in a fibrin matrix, wtFGF-2 resulted in 2.6 +/- 0.9-fold more growth over control, and 221*2 increased growth 3.3 plus or minus 0.9-fold. Vessel outgrowth with 2212 was minimal and comparable to control. Similarly, fibrinogen potentiated wtFGF-2 or 221*2-mediated angiogenesis in the chicken chorioallantoic membrane model. In a mouse Matrigel implant model, fibrinogen significantly increased angiogenesis with either wtFGF-2 or 221*2, whereas there was no augmentation with 2212. These results demonstrate that binding of FGF-2 to fibrin(ogen) mediated by the 5-residue FGF-2-fibrin(ogen) interactive site is required for augmented angiogenesis.
A Novel Cytoplasmic Dual Specificity Protein Tyrosine Phosphatase Implicated in Muscle and Neuronal Differentiation (1996)

Dual specificity protein tyrosine phosphatases (dsPTPs) are a subfamily of protein tyrosine phosphatases implicated in the regulation of mitogen-activated protein kinase (MAPK). In addition to hydrolyzing phosphotyrosine, dsPTPs can hydrolyze phosphoserine/threonine-containing substrates and have been shown to dephosphorylate activated MAPK. We have identified a novel dsPTP, rVH6, from rat hippocampus. rVH6 contains the conserved dsPTP active site sequence, VXVHCX2GX2RSX5AY(L/I)M, and exhibits phosphatase activity against activated MAPK. In PC12 cells, rVH6 mRNA is induced during nerve growth factor-mediated differentiation but not during insulin or epidermal growth factor mitogenic stimulation. In MM14 muscle cells, rVH6 mRNA is highly expressed in proliferating cells and declines rapidly during differentiation. rVH6 expression correlates with the inability of fibroblast growth factor to stimulate MAPK activity in proliferating but not in differentiating MM14 cells. rVH6 protein localizes to the cytoplasm and is the first dsPTP to be localized outside the nucleus. This novel subcellular localization may expose rVH6 to potential substrates that differ from nuclear dsPTPs substrates.
<title>Novel frequency-agile interrogating system for fiber Bragg grating sensors</title> (1993)

We have demonstrated a new frequency-agile system for the interrogation of in-fiber Bragg grating sensors. The scheme involves frequency shift keying (FSK) of the rf drive to an acousto-optic tunable filter (AOTF) to track the wavelength shifts of a Bragg grating. Theoretical studies to derive the optimum frequency deviation for achieving maximum sensitivity are given, and experimental results are presented for temperature measurement. This technique is capable of rapid, random access and very wide tuning range, showing the potential for interrogating multiplexed arrays of Bragg-grating-based sensors.
The molecular mechanisms of dicarboxylic acid transport in Escherichia coli K12. The role and orientation of the two membrane-bound dicarboxylate binding proteins (1978)

Previous communications from this laboratory have indicated that dicarboxylic acid transport in Escherichia coli is an active process, and that at least three genes are responsible for this transport system. In attempts to identify the transport components, one periplasmic binding protein and two membrane integral proteins (SBP 1 and SBP 2) were implicated to participate in the transport system in vivo. In the present communication, we demonstrate, through biochemical analysis of the transport mutants, that the two membrane transport genes, dctA and dctB, are responsible for the two membrane-bound dicarboxylate binding proteins, SBP 2 and SBP 1, respectively. We also find that the substrate recognition sites of SBP 1 and SBP 2 are exposed to the inner and outer surfaces of the membrane, respectively. This may have important implications for the role of SBP 1 and SBP 2 in the translocation process.
Stem Cell Recruitment of Newly Formed Host Cells via a Successful Seduction? Filling the Gap between Neurogenic Niche and Injured Brain Site (2013)

Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.
Fetal and adult bovine interferon production during bovine viral diarrhea virus infection (1976)

Levels of interferon in adult bovine serum and in fetal bovine serum and tissues were examined during the course of transplacental bovine viral diarrhea virus infection. The cows produced circulating interferon between 2 and 9 days after viral inoculation, with mean peak levels in the serum on day 4. Interferon could be routinely detected in fetal tissues (e.g., thymus, spleen, and kidney) between days 4 and 21 after viral inoculation of the cows at 149 to 150 days of gestation (mid-second trimester) and in fetal serum from day 13 through day 21. Interferon was also detectable in the serum and tissues of fetuses from dams infected at day 95 of gestation (the beginning of the second trimester). In general, no differences were found between the ability of the adult and fetus to produce interferon. Fetal lamb kidney cells were more sensitive to the antiviral effects of bovine interferon than were fetal bovine kidney cells. The antiviral substance from the fetal and adult animals was characterized as interferon by standard criteria.
Medical image interpretation: a generic approach using deformable templates (1994)

We describe a generic approach to image interpretation, based on combining a general method of building flexible template models with genetic algorithm (GA) search. The method can be applied to a given image interpretation problem simply by training a statistical shape model, using a set of examples of the image structure to be located. A local optimization technique has been incorporated into the GA search and shown to improve the speed of convergence and optimality of solution. We present results from three medical applications, demonstrating that the new method offers significant improvements when compared with previously reported approaches to flexible template matching, particularly the ability to deal with different domains of application using a standard method and the possibility of employing complex multipart models. We also describe how the method can be simply extended to track structures in image sequences and segment three dimensional objects in volume images.
Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro. (1989)

To investigate the possibility that the host fever response in malaria may affect parasite development, we studied the effect of temperature on Plasmodium falciparum in erythrocytic culture in vitro. Growth was markedly suppressed at 40 degrees C compared with 37 degrees C, due to disruption of the second half of the 48-h erythrocytic cycle. However, young intraerythrocytic parasites, which are highly exposed to fever during natural infection, appeared to develop normally at 40 degrees C. Because of the differential temperature sensitivity within the erythrocytic cycle, asynchronous cultures could be synchronized by transient elevations of temperature. Pronounced synchronization was observed when cultures were exposed to periodic elevations of temperature that simulated the 48-h fever cycle of tertian malaria. These findings indicate that malaria fever might act to promote parasite synchronization in vivo.
Bacterial effect of hydrogen peroxide on urinary tract pathogens (1980)

Bacterial contamination of urinary drainage bags is a frequent source of bladder bacteriuria in patients with indwelling catheters. Previous work demonstrated that the addition of 30 ml of 3% H2O2 prevented bacterial contamination of urinary drainage bags for up to 8 h in patients with urinary infections (greater than 10(5) colony-forming units per ml). Survival curves of a variety of organisms in filter-sterilized urine with various concentrations of H2O2 (0.6 to 0.01%) were constructed. Organisms with high cellular catalase activity (Staphylococcus aureus, Serratia marcescens, and Proteus mirabilis) required 30 to 60 min of exposure to 0.6% H2O2 for a reduction of 10(8) to less than 1 colony-forming unit per ml, whereas Escherichia coli, Streptococcus sp., and Pseudomonas sp. required only 15 min of exposure. The efficacy of H2O2 in urine was maintained despite exposure to room temperature for 5 days and reinoculation with bacterial suspensions. H2O2 is inexpensive and relatively nontoxic, and these data suggest that periodic instillation of H2O2 into urinary drainage bags may eliminate a source of bladder bacteriuria and environmental contamination.