gebhart/patrepeval huggingface dataset:
The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study (2007)

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.
Sensitive homologous recombination strand-transfer assay: partial purification of a Drosophila melanogaster enzyme and detection of sequence effects on the strand-transfer activity of RecA protein. (1988)

A sensitive homologous recombination strand-transfer assay is described that employs short radiolabeled double-stranded DNA fragments from the lac/polylinker region of plasmid pUC18 and (+)viral M13mp18 single-stranded DNA as substrates. Substitution of a short radiolabeled double-stranded fragment for full-length linear M13 double-stranded DNA results in an assay whose sensitivity is improved greater than 8-fold. In addition, it is less sensitive to interference from nucleases or ligases than previous assays. The assay was used to partially purify an ATP-independent strand-transfer activity from a crude nuclear extract of Drosophila melanogaster embryos. We have also tested the efficiency with which various short double-stranded DNA segments are assembled into plectonemic joints by RecA protein with this assay and found 5- to 10-fold differences. These results are interpreted as evidence for DNA sequence-specific effects in RecA-mediated homologous pairing in vitro.
Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. (1990)

We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.
Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase cDNA. (1990)

We have previously isolated a murine UDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase (alpha(1,3)-GT) cDNA (Larsen, R. D., Rajan, V. P., Ruff, M. M., Kukowska-Latallo, J., Cummings, R. D., and Lowe, J. B. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 8227-8231). This enzyme constructs the terminal alpha(1,3)-galactosyl linkage within the epitope Gal alpha 1----3Gal. This epitope is expressed by New World monkeys and many nonprimate mammals but generally not by Old World primates, anthropoid apes, or man. To investigate the molecular basis for the apparent species-specific absence of this enzyme and its oligosaccharide product, we have sequenced a human genomic DNA fragment homologous to the murine alpha(1,3)-GT cDNA. This fragment contains a 703-nucleotide region that shares 82% identity with a region of the murine cDNA encoding part of the enzyme's catalytic domain. The human sequence, however, has suffered deletion of single nucleotides at two separate positions, relative to the murine sequence. These frameshift mutations disrupt the translational reading frame that would otherwise maintain a 76% amino acid sequence identity between the human sequence and the murine alpha(1,3)-GT. Moreover, nonsense mutations exist within this disrupted reading frame that would truncate the human polypeptide, relative to the murine enzyme. We therefore propose that this human sequence represents a pseudogene and cannot determine expression of Gal alpha 1----3Gal epitopes on human cells.
A Lamellar Unit of Aortic Medial Structure and Function in Mammals (1967)

The close association of elastin, collagen, and smooth muscle in the mammalian aortic media results in viscoelastic properties that account for many of its static and dynamic mechanical features. The structural components of the media are precisely oriented in concentric layers, or lamellar units, of fairly uniform composition. A comparative study of the adult thoracic aorta in 10 mammalian species, including 15 canine breeds, showed that the number of lamellar units in the media of adult mammalian aortas is very nearly proportional to aortic radius regardless of species or variations in measured wall thickness. Estimated wall tensions ranged from 7,820 dynes/cm in a 28-g mouse to 203,000 dynes/cm in a 200,000-g sow, but the average tension per lamellar unit of an aortic media was remarkably constant regardless of species, ranging from 1,090 to 3,010 dynes/cm. The findings suggest that the elastin lamella and the contents of its adjacent interlamellar zone represent the unit of structure and function of the mammalian aortic wall.
Formation of sarcomeres in developing myotubes: role of mechanical stretch and contractile activation (2000)

In a series of experiments, cultured myotubes were exposed to passive stretch or pharmacological agents that block contractile activation. Under these experimental conditions, the formation of Z lines and A bands (morphological structures, resulting from the specific structural alignment of sarcomeric proteins, necessary for contraction) was assessed by immunofluorescence. The addition of an antagonist of the voltage-gated Na(+) channels [tetrodotoxin (TTX)] for 2 days in developing rat myotube cultures led to a nearly total absence of Z lines and A bands. When contractile activation was allowed to resume for 2 days, the Z lines and A bands reappeared in a significant way. The appearance of Z lines or A bands could not be inhibited nor facilitated by the application of a uniaxial passive stretch. Electrical stimulation of the cultures increased sarcomere assembly significantly. Antagonists of L-type Ca(2+) channels (verapamil, nifedipine) combined with electrical stimulation led to the absence of Z lines and A bands to the same degree as the TTX treatment. Western blot analysis did not show a major change in the amount of sarcomeric alpha-actinin nor a shift in myosin heavy chain phenotype as a result of a 2-day passive stretch or TTX treatment. Results of experiments suggest that temporal Ca(2+) transients play an important factor in the assembly and maintenance of sarcomeric structures during muscle fiber development.
Identification of the fibronectin sequences required for assembly of a fibrillar matrix. (1991)

During extracellular matrix assembly, fibronectin (FN) binds to cell surface receptors and initiates fibrillogenesis. As described in this report, matrix assembly has been dissected using recombinant FN polypeptides (recFNs) expressed in mammalian cells via retroviral vectors. RecFNs were assayed for incorporation into the detergent-insoluble cell matrix fraction and for formation of fibrils at the cell surface as detected by indirect immunofluorescence. Biochemical and immunocytochemical data are presented defining the minimum domain requirements for FN fibrillogenesis. The smallest functional recFN is half the size of native FN and contains intact amino- and carboxy-terminal regions with a large internal deletion spanning the collagen binding domain and the first seven type III repeats. Five type I repeats at the amino terminus are required for assembly and have FN binding activity. The dimer structure mediated by the carboxy-terminal interchain disulfide bonds is also essential. Surprisingly, recFNs lacking the RGDS cell binding site formed a significant fibrillar matrix. Therefore, FN-FN interactions and dimeric structure appear to be the major determinants of fibrillogenesis.
Ionic conductivity study of LiI-Ga2S3-GeS2 chalcogenide glasses using a random-walk approach (2014)

Abstract Electrical properties of a set of lithium-ion conducting sulfide glasses with general formula 20LiI- x Ga 2 S 3 -(80- x )GeS 2 ( x = 10, 15 and 20) is studied in the present article. The experimental data obtained using impedance spectroscopy are analyzed by means of a random-walk ( RW ) model assuming that the conduction takes place by a random motion of Li + ions. The influences of added gallium on the structural network and on the conductivity of prepared glasses are also analyzed using the RW model. The results are further confirmed by Raman spectral analysis. The results obtained by the random-walk model and by a conventional equivalent electric circuit model are in a good agreement. We observed that the addition of Ga 2 S 3 contributed to phase separation in the prepared glassy system and negatively influenced the conductivity of the studied glasses. Factors contributing to the total conductivity with respect to the amount of both LiI and Ga 2 S 3 are also reported.
PixelDefend: Leveraging Generative Models to Understand and Defend against Adversarial Examples (2017)

Adversarial perturbations of normal images are usually imperceptible to humans, but they can seriously confuse state-of-the-art machine learning models. What makes them so special in the eyes of image classifiers? In this paper, we show empirically that adversarial examples mainly lie in the low probability regions of the training distribution, regardless of attack types and targeted models. Using statistical hypothesis testing, we find that modern neural density models are surprisingly good at detecting imperceptible image perturbations. Based on this discovery, we devised PixelDefend, a new approach that purifies a maliciously perturbed image by moving it back towards the distribution seen in the training data. The purified image is then run through an unmodified classifier, making our method agnostic to both the classifier and the attacking method. As a result, PixelDefend can be used to protect already deployed models and be combined with other model-specific defenses. Experiments show that our method greatly improves resilience across a wide variety of state-of-the-art attacking methods, increasing accuracy on the strongest attack from 63% to 84% for Fashion MNIST and from 32% to 70% for CIFAR-10.
Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap (2018)

The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.
Cytotoxic response of ovarian cancer cell lines to IFN-γ is associated with sustained induction of IRF-1 and p21 mRNA (1999)

Interferon-gamma (IFN-gamma) has some anti-tumour activity in human ovarian cancer. This cytokine inhibited proliferation in three of four ovarian cancer cell lines in vitro. We then compared the action of IFN-gamma in two cell lines, one sensitive and one resistant to its growth inhibitory effects. IFN-gamma signalling appeared normal in both cell lines, with stat1 DNA binding activity detectable at 30 min. Continuous exposure to IFN-gamma for 2-3 days was necessary for an irreversible effect on cell growth and apoptosis in cells sensitive to growth inhibition. During this time there was an increase in mRNA for the CKI p21, but no alterations in mRNA levels for other members of the CKI family. Maintenance of p21 mRNA required continuous mRNA synthesis. mRNA for the transcription factor IRF-1 was also induced in growth inhibited cells with similar kinetics to those observed for p21. Maximal induction of both p21 and IRF-1 mRNA was observed after 2-3 days IFN-gamma exposure as the cells became committed to cell death. There was also a rapid increase in p21 and IRF-1 mRNA in cells resistant to the growth inhibitory effects of IFN-gamma, but this increase was not maintained. Thus, continuous interaction with the IFN-gamma receptor, together with a sustained induction of p21 and IRF-1, is associated with growth inhibitory and apoptotic effects of IFN-gamma in ovarian cancer cells.
Effects of Temperature and Geometry on the Flow Field of the Melt Blowing Process (2004)

Converging plane jets are used commercially to produce polymeric fibers in the melt blowing process. The behavior of the air flow below the die face is critical for the production process. The die configuration can affect this flow field. Previous work has studied the effects of changing the angle of convergence of the two jets for blunt and sharp die faces, as well as the case of recess or excess (inset or outset) positioning of the sharp die nose for isothermal flow conditions. This study utilized a computational fluid dynamics approach that was validated through experimental data to investigate the effects of nonisothermal conditions on the air flow. The Reynolds stress model was used to simulate the turbulence, and the model parameters were calibrated with the experimental data. The behavior of alternative die designs was also correlated to the die configuration. It was found that, similarly to the isothermal case, the sharper the angle of convergence, the higher the mean air velocity under the die and the higher the intensity of the turbulent velocity fluctuations. The flow field exhibits a self-similar region beyond the point at which the flow from the two jets merges. It was found that the mean temperature and the mean velocity field beyond the merging distance can each be described by a single correlation. In these correlations, the merging distance was used as the length scale, and the mean flow velocity at the merging point was used as the velocity scale.
Etude en microscopie electronique du glissement pyramidal {1122} 〈1123〉 dans le magnesium (1972)

Abstract Electron Microscope Study of Pyramidal Slip {112} 〈113〉 in Magnesium We have investigated {112} 〈113〉 pyramidal slip in magnesium whose CRSS exhibits an anomalous dependence on temperature and increases between 270 and 375 K. Typical dislocation configurations were investigated by TEM in various temperature ranges. A model is proposed based on the thermally activated blocking of edge ⅓{113} dislocations. The blocking may be due to the dissociation of the ⅓{113} dislocation into two ⅙{203} partials. Our observations on magnesium are compared with those made on zinc and cadmium by other authors.
Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery (2005)

Inducing destruction of specific mRNA using small interfering RNA (siRNA) is a powerful tool in analysis of protein function, but its use as a therapeutic modality has been limited by inefficient or impractical delivery systems. We have used siRNA incorporated into the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) for efficient in vivo siRNA delivery. In nude mice bearing i.p. ovarian tumors, nonsilencing siRNA tagged with the fluorochrome Alexa 555 was encapsulated into DOPC liposomes and shown to be taken up by the tumor as well as many major organs. Furthermore, DOPC-encapsulated siRNA targeting the oncoprotein EphA2 was highly effective in reducing in vivo EphA2 expression 48 hours after a single dose as measured by both Western blot and immunohistochemistry. Therapy experiments in an orthotopic mouse model of ovarian cancer were initiated 1 week after injection of either HeyA8 or SKOV3ip1 cell lines. Three weeks of treatment with EphA2-targeting siRNA-DOPC (150 microg/kg twice weekly) reduced tumor growth when compared with a nonsilencing siRNA (SKOV3ip1: 0.35 versus 0.70 g; P = 0.020; HeyA8: 0.98 versus 1.51 g; P = 0.16). When EphA2-targeting siRNA-DOPC was combined with paclitaxel, tumor growth was dramatically reduced compared with treatment with paclitaxel and a nonsilencing siRNA (SKOV3ip1: 0.04 versus 0.22 g; P < 0.001; HeyA8: 0.21 versus 0.84 g; P = 0.0027). These studies show the feasibility of siRNA as a clinically applicable therapeutic modality.
Switching on and off with RNA (2000)

With advancements in stem cell technology, in vitro models using iPSC (induced pluripotent stem cells)-derived cardiomyocytes (iPSC-CM) and engineered heart tissues (EHT) can serve as powerful tools for disease modeling and drug screening. ...Fluorescent reporters of cardiac electrophysiology provide valuable information on heart cell and tissue function. However, motion artifacts caused by cardiac muscle contraction interfere with accurate measurement of fluorescence signals. Although drugs ...
The disease intersection of susceptibility and exposure: Chemical exposures and neurodegenerative disease risk (2014)

Alzheimer's disease, Parkinson's disease, and motor neuron disease, the most common of the late-life neurodegenerative disorders, are in most cases thought to have complex etiologies. Common features among these disorders include insidious onset, pathological findings of protein aggregates and selected neuronal degeneration, and resulting characteristic clinical syndromes. The number of elders in the United States, including aging veterans, is increasing. Investigation of causes and preventive interventions for neurodegenerative disorders is increasingly relevant. Recent epidemiological and laboratory studies suggest that exposures years or decades before diagnosis can trigger the processes that ultimately result in a neurodegenerative disease. If this is correct, preventive measures may be needed in midlife or earlier. This article will focus on putative risk factors relevant to military service.
An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue (2003)

The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to the generation of human benign and malignant tumours of mesenchymal origin. However, only a few data on the expression of HMGA2 in malignant tumour originating from epithelial tissue are available. In this study, we examined the HMGA2 expression level in pancreatic carcinoma, and investigated whether alterations in the HMGA2 expression level are associated with a malignant phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein expression was determined in eight surgically resected specimens of non-neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) techniques and immunohistochemical staining, respectively. Reverse transcriptase-polymerase chain reaction analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma. Immunohistochemical analysis indicated that the presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT-PCR reflects its abundant expression in islet cells, together with its focal expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2 immunoreactivity was noted in all the pancreatic carcinoma examined. A strong correlation between HMGA2 overexpression and the diagnosis of carcinoma was statistically verified. Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignant cells from non-neoplastic pancreatic exocrine cells.
SYNTHESIS OF CARBOCYCLIC ANALOGS OF 2′,3′-DIDEOXYSANGIVAMYCIN, 2′,3′-DIDEOXYTOYOCAMYCIN, AND 2′,3′-DIDEOXYTRICIRIBINE (2001)

Syntheses and antiviral activity of new carbocyclic analogs of 2', 3'-dideoxysangivamycin, 2',3'-dideoxytoyocamycin and 2',3'-dideoxytriciribine is described. The key intermediate, carbocyclic 4-chloro-5-iodopyrrolopyrimidine. was synthesized in good yield via a novel iodination method using I2 and CF3COOAg. This carbocyclic 4-chloro-5-iodopyrrolopyrimidine then allowed for a concise synthesis of the desired 4,5-disubstituted carbocyclic nucleosides.
Myocardial transfection of hypoxia-inducible factor-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction (2014)

These findings suggest that myocardial transfection of HIF-1α and co-transplantation of mesenchymal stem cells enhance cardiac repair in myocardial infarction, indicating the feasibility and preliminary safety of a combination of myocardial transfection of HIF-1α and MSC transplantation to treat myocardial infarction.
On the Use of Semantic Blocking Techniques for Data Cleansing and Integration (2007)

Record linkage (RL) is an important component of data cleansing and integration. For years, many efforts have focused on improving the performance of the RL process, either by reducing the number of record comparisons or by reducing the number of attribute comparisons, which reduces the computational time, but very often decreases the quality of the results. However, the real bottleneck of RL is the post-process, where the results have to be reviewed by experts that decide which pairs or groups of records are real links and which are false hits. In this paper, we show that exploiting the relationships (e.g. foreign key) established between one or more data sources, makes it possible to find a new sort of semantic blocking method that improves the number of hits and reduces the amount of review effort.