gebhart/patrepeval huggingface dataset:
Acute virulence in mice is associated with markers on chromosome VIII in Toxoplasma gondii (1996)

Toxoplasma gondii has an unusual population structure consisting of three widely distributed clonal lineages. Acute virulence in mice is strictly observed in type I strains, indicating that a genetic determinant(s) unique to this lineage controls acute pathogenesis. We have analyzed several naturally occurring recombinant strains of T. gondii that carry allele 1 at the SAG1 locus; this allele is characteristic of the type I strains and was previously found to be 100% correlated with the acute virulence phenotype. Recombinant strains G622-M and ROD both had a predominantly type III genotype, with the significant exception of allele 1 at the SAG1 locus. Although these two strains had virtually identical multilocus genotypes, they differed in their virulence in mice. Strain ROD was virulent whereas strain G622-M was nonvirulent, thus demonstrating that the presence of allele 1 at SAG1 is not alone sufficient to confer acute virulence. Several sequence polymorphisms upstream of SAG1 were found to be highly correlated with the acutely virulent lineages. Collectively, these results suggest that acute virulence is regulated by a region linked to the SAG1 locus on chromosome VIII in T. gondii.
Airport infrastructure : the emerging role of the private sector : recent experiences based on 10 case studies (1995)

During the coming years, air transport infrastructure needs to be expanded and modernized to accommodate the growing demand for international travel and transport of goods and merchandise. Developing countries need to invest large amounts of resources in airport related infrastructure in order to connect into the global air transport industry. Increased demands placed on developing countries public finances are inducing policy-makers to find alternatives to replace the government's role in the financing and management of airport infrastructure. This study is intended for developing country policy makers. Designed to function as a helpful reference work, it provides practical information, context and strategies to foster private sector participation in the airport sector. The study, built on 10 case studies encompassing diverse continents and national income levels, addresses a large number of issues including privatization mechanisms, regulatory and legal structures, project finance schemes and cross subsidization concerns among different countries. It presents the trends and lessons, derived from existing and on-going privatization cases, relevant to the policy-maker.
FAN Stimulates TNFα-Induced Gene Expression, Leukocyte Recruitment, and Humoral Response (2009)

Factor associated with neutral sphingomyelinase activation (FAN) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression. Approximately 70% of TNF-induced genes exhibited lower expression levels in FAN-deficient than in wild-type fibroblasts. Of particular interest, TNF-induced expression of cytokines/chemokines, such as IL-6 and CXCL-2, was impaired in FAN-deficient cells. This was confirmed by real time RT-PCR and ELISA. Upon i.p. TNF or thioglycollate injection, neutrophil recruitment into the peritoneal cavity was reduced by more than 50% in FAN-deficient mice. Nevertheless, FAN-deficient animals did not exhibit an increased susceptibility to different microorganisms including bacteria and parasites, indicating that FAN is not essential for pathogen clearance. Specific Ab response to BSA was substantially impaired in FAN-deficient mice and this was associated with a reduced content of leukocytes in the spleen of BSA-challenged FAN-deficient mice as compared with their wild-type counterparts. Altogether, our results indicate the involvement of FAN in TNF-induced gene expression and leukocyte recruitment, contributing to the establishment of the specific immune response.
Comprehensive molecular profiling of lung adenocarcinoma (2014)

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
High expression of L‐type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas (2014)

Oncocytic L-type amino acid transporter (LAT) 1 may be a prognostic indicator and target of new molecular therapeutic agents against malignancies. To investigate whether LAT1 expression influence the outcomes of patients with bile duct cancer, the expression of LAT1, LAT2, CD98, and Ki-67 was investigated immunohistochemically in 134 surgically resected bile duct adenocarcinomas, including 84 distal extrahepatic bile duct adenocarcinomas, 21 hilar cholangiocarcinomas, 15 intrahepatic cholangiocarcinomas, and 14 ampullary adenocarcinomas. LAT1 expression was weakly correlated with CD98 expression and Ki-67 labeling index (LI). Kaplan-Meier analysis showed a significant difference in prognosis between patients with bile duct adenocarcinomas having LAT1-high and -low scores, whereas LAT2 and CD98 expression and Ki-67 LI were not predictive of poor prognosis. Prognosis tended to be worse in patients having tumors with LAT1-high/LAT2-low than LAT1-low/LAT2-high scores (P = 0.0686). Multivariable analyses revealed that LAT1 expression, surgical margin, pT stage were independent prognostic factors. In conclusion, aberrant overexpression of LAT1 in bile duct adenocarcinoma predicts poor prognosis, suggesting that LAT1 may be a potential target of anticancer therapy.
Design of Underactuated Steerable Electrode Arrays for Optimal Insertions (2013)

This paper addresses the design of wire actuated steerable electrode arrays for optimal insertions in cochlear implant surgery. These underactuated electrode arrays are treated as continuum robots which have an embedded actuation strand inside their flexible medium. By pulling on the actuation strand, an electrode array assumes a minimum-energy shape. The problems of designing optimal actuation strand placement are addressed in this paper. Based on the elastic modeling of the steerable electrode arrays proposed in this paper, an analytical solution of the strand placement is solved to minimize the shape discrepancy between a bent electrode array and a given target curve defined by the anatomy. Using the solved strand placement inside the steerable electrode array, an optimized insertion path planning with robotic assistance is proposed to execute the insertion process. Later, an optimization algorithm is presented to minimize the shape discrepancy between an inserted electrode array and a given target curve during the whole insertion process. Simulations show a steerable electrode array bending using the elastic model and robot insertion path planning with optimized strand placement. Two experiments have been conducted to validate the elastic model and algorithms.
Stereotactic and Functional Neurosurgery (2015)

Stereotactic and Functional Neurosurgery is the single and comprehensive source of developments in the most rapidly advancing subspecialty within neurosurgery. Technological advances in computer-assisted surgery, robotics, imaging, and neurophysiology are being applied to clinical problems with ever-increasing rapidity in stereotaxis more than any
An energy-efficient random number generator for stochastic circuits (2016)

Stochastic circuits provide very high efficiency in terms of gate area and power consumption compared with conventional binary logic. However, they require random bit streams generated by stochastic number generators (SNGs), which account for a significant portion of area and energy offsetting their merits. In this paper, we propose a new SNG that significantly reduces area and energy while improving accuracy in progressive precision. Experimental results show that the proposed SNG reduces energy by more than 72% compared to the state-of-the-art designs.
Construction and selection of bead-bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing (2002)

Chemically synthesized combinatorial libraries of unmodified or modified nucleic acids have not previously been used in methods to rapidly select oligonucleotides binding to target biomolecules such as proteins. Phosphorothioate oligonucleotides (S-ODNs) or phosphorodithioate oligonucleotides (S2-ODNs) with sulfurs replacing one or both of the non-bridging phosphate oxygens bind to proteins more tightly than unmodified oligonucleotides and have the potential to be used as diagnostic reagents and therapeutics. We have applied a split synthesis methodology to create one-bead one-S-ODN and one-bead one-S2-ODN libraries. Binding and selection of specific beads to the transcription factor NF-kappaB p50/p50 protein were demonstrated. Sequencing both the nucleic acid bases and the positions of any 3'-O-thioate/dithioate linkages was carried out by using a novel PCR-based identification tag of the selected beads. This approach allows us to rapidly and conveniently identify S-ODNs or S2-ODNs that bind to proteins.
Identifying Risk Factors for Tardive Dyskinesia Among Long-term Outpatients Maintained With Neuroleptic Medications (1993)

For outpatients maintained for many years with neuroleptics, dose should be minimized to reduce the risk of TD. This strategy does not appear to be negated by prescribing frequent changes in dosage. Although the TD rate is greatest during the first 5 years of neuroleptic treatment, new persistent cases continue to occur many years after first exposure.
Activation of the Pro-survival Phosphatidylinositol 3-Kinase/AKT Pathway by Transforming Growth Factor-β1 in Mesenchymal Cells Is Mediated by p38 MAPK-dependent Induction of an Autocrine Growth Factor (2004)

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine involved in differentiation, growth, and survival of mesenchymal cells while inhibiting growth/survival of most other cell types. The mechanism(s) of pro-survival signaling by TGF-beta1 in mesenchymal cells is unclear. In this report, we demonstrate that TGF-beta1 protects against serum deprivation-induced apoptosis of mesenchymal cells isolated from patients with acute lung injury and of normal human fetal lung fibroblasts (IMR-90). TGF-beta receptor(s)-activated signaling in these cells involves rapid activation of the Smad and p38 MAPK pathways within minutes of TGF-beta1 treatment followed by a more delayed activation of the pro-survival phosphatidylinositol 3-kinase-protein kinase B (PKB)/Akt pathway. Pharmacological inhibition of p38 MAPK with SB203580 or expression of a p38 kinase-deficient mutant protein inhibits TGF-beta1-induced PKB/Akt phosphorylation. Conditioned medium from TGF-beta1-treated cells rapidly induces PKB/Akt activation in an SB203580- and suramin-sensitive manner, suggesting p38 MAPK-dependent production of a secreted growth factor that activates this pro-survival pathway by an autocrine/paracrine mechanism. Inhibition of the phosphatidylinositol 3-kinase-PKB/Akt pathway blocks TGF-beta1-induced resistance to apoptosis. These results demonstrate the activation of a novel TGF-beta1-activated pro-survival/anti-apoptotic signaling pathway in mesenchymal cells/fibroblasts that may explain cell-specific actions of TGF-beta1 and provide mechanistic insights into its pro-fibrotic and tumor-promoting effects.
The Role of the Peripheral Benzodiazepine Receptor in Photodynamic Activity of Certain Pyropheophorbide Ether Photosensitizers: Albumin Site II as a Surrogate Marker for Activity¶ (2002)

A study has been carried out to define the importance of the peripheral benzodiazepine receptor (PBR) as a binding site for a series of chlorin-type photosensitizers, pyropheophorbide-a ethers, the subject of a previous quantitative structure-activity relationship study by us. The effects of the PBR ligand PK11195 on the photodynamic activity have been determined in vivo for certain members of this series of alkyl-substituted ethers: two of the most active derivatives (hexyl and heptyl), the least active derivative (dodecyl [C12]) and one of intermediate activity (octyl [C8]). The photodynamic therapy (PDT) effect was inhibited by PK11195 for both of the most active derivatives, but no effect on PDT activity was found for the less active C12 or C8 ethers. The inhibitory effects of PK11195 were predicted by the binding of only the active derivatives to the benzodiazepine site on albumin, ie. human serum albumin (HSA)-Site II. Thus, as with certain other types of photosensitizers, it has been demonstrated with this series of pyropheophorbide ethers that in vitro binding to HSA-Site II is a predictor of both optimal in vivo activity and binding to the PBR in vivo.
Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor. (1994)

We undertook these studies to explore the intracellular signaling mechanisms activated by a newly described human brain melanocortin receptor (hMC3R). Hepa cells transfected with the hMC3R gene responded to stimulation with alpha-melanocyte stimulation hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) with dose-dependent increases in cellular content of cyclic 3',5'-adenosine monophosphate (cAMP) reaching a maximum of over 1500% of control cells at the 10(-8) M dose (EC50 = 10(-11) M). In contrast, the production of [3H]inositol phosphates in cells prelabeled with myo-[2-3H]inositol exhibited a biphasic dose-response curve with increases as high as 155% of basal at 10(-11) M alpha-MSH or ACTH, but beyond that a dose-dependent decrease was observed. The inhibitory component of the dose-response curve could be abolished by pretreatment of transfected cells with the cAMP antagonist (Rp)-adenosine 3',5'-monophosphorothioate (Rp-cAMP) or the protein kinase A inhibitor H-89. Increases in intracellular calcium induced in transfected cells by alpha-MSH in doses ranging from 10(-11) to 10(-7) M could not be observed unless the cells were pretreated with H-89. By replacing the third intracytoplasmic loop of the canine H2-histamine receptor with that of hMC3R the biphasic characteristic of agonist-induced production of [3H]inositol phosphates was conferred to the chimeric receptor. These data indicate that the hMC3R is coupled to both cAMP and inositol phospholipid/Ca(2+)-mediated post-receptor signaling systems and that the latter response is regulated by protein kinase A activity.
[Expression and correlation of CIP2A and OPN in bladder cancer]. (2014)

The expression levels of CIP2A and OPN in tissue of bladder cancer are higher than those of normal controls. And CIP2A and OPN may be used as indicators of biological behaviors and serve as new molecular diagnostic markers for bladder cancer.
Fabrication of multi-layer, high-density micro-electrode arrays for neural stimulation and bio-signal recording (2007)

The electrode-tissue interface is of principal importance in neuroprosthesis. Indeed the successes of the cochlear implant and other therapeutic devices are directly attributable to the design and fabrication techniques of their interfaces with neural tissue, that is, the electrode or electrode array. Traditional fabrication techniques are often labor-intensive and do not lend themselves to automation thereby increasing the cost of the electrode, and owing to fabrication variability, potentially compromising the reliability of the devices incorporating them. Exacerbating the difficulties in electrode fabrication further is the fact that only a handful of materials have been demonstrated to be biologically inert. These same materials are often among the most difficult to utilize in the fabrication of neural electrodes. In the present paper, a new methodology for automated fabrication of high-density electrode arrays is presented. Using exclusively biologically-inert raw materials, laser machining techniques combined with multiple layer structuring is shown to achieve feature sizes of the order of 25 mum. As an illustrative example, a 98 electrode array for interfacing with surviving retinal tissue through a visual prosthesis for the blind is presented. Overall dimensions of the array are of the order of 8.7 times 9.4 mm, consistent with approximately 25 degrees of visual field.
[Simvastatin versus gemfibrozil in the treatment of primary hypercholesterolemia in hypertensive patients treated with hydrochlorothiazide]. (1990)

Recent pharmacological studies confirmed the role of hypercholesterolemia in the pathogenesis of coronary atherosclerosis. A 10% reduction in cholesterol levels can reduce the risk of coronary heart disease by 15%. However many hypercholesterolemic patients often suffer from arterial hypertension and drugs such as thiazide diuretics cause an imbalance in lipid metabolism. The efficacy and the tolerability of simvastatin (a inhibitor of HGM-CoA reductase) with that of gemfibrozil (a fibric acid derivative, which can reduce the VLDL level) were compared in a placebo-controlled study in 2 groups of patients with primary hypercholesterolemia and mild-to-moderate essential hypertension treated with hydrochlorothiazide. After 10 weeks standard hypolipidemic diet and hydrochlorothiazide (25 mg od) therapy, 30 patients whose cholesterol levels were still greater than or equal to 250 mg/100 ml and whose diastolic blood pressure was less than 95 mmHg were randomized to one of the following treatments: simvastatin, 20 mg od, gemfibrozil, 600 mg bid or placebo, while continuing dietetic and diuretic treatment. After 24 weeks treatment, simvastatin induced a 37% reduction in cholesterol plasma levels, a 9% increase of HDL and a 16% reduction of LDL. APO-A1 showed a 4% increase, while APO-B showed a 3% reduction. Gemfibrozil induced a 20% reduction in plasma triglycerides and a 13% decrease in plasma cholesterol, with a significant 19% increase in HDL and a 11% reduction in LDL. No significant variations in any of the lipid parameters monitored were observed in the placebo group. Treatment with simvastatin or gemfibrozil in hypertensive patients in hydrochlorothiazide monotherapy can reduce total cholesterol and LDL-cholesterol plasma levels, while significantly increasing HDL plasma levels compared to placebo. Simvastatin, however, resulted more efficient than gemfibrozil on total cholesterol or cholesterol fractions.
A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project (2015)

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.
The organization of human postural movements: A formal basis and experimental synthesis (1985)

Abstract A scheme for understanding the organization of human postural movements is developed in the format of a position paper. The structural characteristics of the body and the geometry of muscular actions are incorporated into a three-dimensional graphical representation of human movement mechanics in the sagittal plane. A series of neural organizational hypotheses limit a theoretically infinite number of combinations of muscle contractions and associated movement trajectories for performing postural corrections: (1) Controls are organized to use the minimum number of muscles; (2) frequently performed movements are organized to require a minimum of neural decision-making. These hypotheses lead to the prediction that postural movements are composed of muscle contractile strategies derived from a limited set of distinct contractile patterns. The imposition of two mechanical constraints related to the configuration of support and to requirements for body stability with respect to gravity predict the conditions under which individual movement strategies will be deployed. A complementary organizational scheme for the senses is developed. We show that organization of postural movements into combinations of distinct strategies simplifies the interpretation of sensory inputs. The fine-tuning of movement strategies can be accomplished by breaking down the complex array of feedback information into a series of scalar quantities related to the parameters of the movement strategies. For example, the magnitude, aim, and curvature of the movement trajectory generated by an individual strategy can be adjusted independently. The second half of the report compares theoretical predictions with a series of actual experimental observations on normal subjects and patients with known sensory and motor disorders. Actual postural movements conform to theoretical predictions about the composition of individual movement strategies and the conditions under which each strategy is used. Observations on patients suggest how breakdowns in individual steps within the logical process of organization can lead to specific movement abnormalities. Discussion focuses on the areas needing further experimentation and on the implications of the proposed organizational scheme. We conclude that although our organizational scheme is not new in demonstrating the need for simplifying the neural control of movement, it is perhaps original in imposing discrete logical control upon a continuous mechanical system. The attraction of the scheme is that it provides a framework compatible with both mechanical and physiological information and amenable to experimental testing.
FTY720 modulates human oligodendrocyte progenitor process extension and survival (2007)

FTY720 induces time-dependent modulation of S1P receptors on human OPCs with consequent functional responses that are directly relevant for the remyelination process.