gebhart/patrepeval huggingface dataset:
R (+) Etomidate and the Photoactivable R (+) Azietomidate Have Comparable Anesthetic Activity in Wild-Type Mice and Comparably Decreased Activity in Mice with a N265M Point Mutation in the Gamma-Aminobutyric Acid Receptor ??3 Subunit (2005)

A photoactivable diazirine derivative of etomidate, azietomidate, shares many actions of etomidate, including a capacity to abolish the righting reflexes in tadpoles and enhance gamma-aminobutyric acid (GABA)-induced currents. Azietomidate's usefulness in studies of mechanisms of anesthesia depends on the assumption that it shares a site of action with etomidate. Mice bearing an N265M beta3 subunit point mutation in GABA(A) receptors have a markedly decreased sensitivity to loss of righting reflexes induced by etomidate over a range of doses. Accordingly, in the present study we measured the time to recovery of righting reflexes of wild type and mutant mice as a function of dose given as an IV bolus. Analysis of the data for azietomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 10.0 +/- 0.9 min and 3.0 +/- 1.6 min for wild type and mutant mice, respectively (mean +/- sd). A similar analysis for etomidate yielded mean times to recovery of righting reflexes at a dose of 7.5 mg/kg of 12.0 +/- 1.3 min and 4.0 +/- 0.7 min for wild type and mutant mice respectively. Thus, at this dose a single mutation, N265M on the beta3 subunit of the GABA(A) receptor, approximately halved the time to recovery of righting reflexes for both etomidate and azietomidate (by 7.6 +/- 1.5 min and 7.2 +/- 1.8 min, respectively), emphasizing the contribution of this residue as a determinant of a behavioral response of azietomidate in mice.
Functional brain imaging using near-infrared technology (2007)

We will describe the working principles of fNIR and how the hemodynamic signals are extracted from the raw fNIR measurements using the modified Beer-Lambert Law. We will also introduce the fNIR system that we have developed and used in our studies. Current results from the augmented cognition research conducted in our laboratory are also presented, and the merits of optical imaging in augmented cognition are summarized.
Microarray Gene Expression Data Analysis (2004)

This chapter contains sections titled: Introduction Normalization of Microarray Gene Expression Data Data Analysis Identification of Differentially Expressed Genes Identification of Coexpressed Genes Applications of Gene Expression Data Analysis for Pathway Inference Summary
Plasma Cell-Free DNA Levels Are Elevated in Acute Puumala Hantavirus Infection (2012)

The plasma levels of cf-DNA are elevated during acute PUUV infection and correlate with the apoptotic cf-DNA-band intensity. The plasma cf-DNA concentration correlates with some variables reflecting the severity of the disease. The urinary excretion of cf-DNA does not reflect the degree of inflammation in the kidney.
Recent advances in the development of farnesoid X receptor agonists. (2015)

Farnesoid X receptors (FXRs) are nuclear hormone receptors expressed in high amounts in body tissues that participate in bilirubin metabolism including the liver, intestines, and kidneys. Bile acids (BAs) are the natural ligands of the FXRs. FXRs regulate the expression of the gene encoding for cholesterol 7 alpha-hydroxylase, which is the rate-limiting enzyme in BA synthesis. In addition, FXRs play a critical role in carbohydrate and lipid metabolism and regulation of insulin sensitivity. FXRs also modulate live growth and regeneration during liver injury. Preclinical studies have shown that FXR activation protects against cholestasis-induced liver injury. Moreover, FXR activation protects against fatty liver injury in animal models of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and improved hyperlipidemia, glucose intolerance, and insulin sensitivity. Obeticholic acid (OCA), a 6α-ethyl derivative of the natural human BA chenodeoxycholic acid (CDCA) is the first-in-class selective FXR agonist that is ~100-fold more potent than CDCA. Preliminary human clinical trials have shown that OCA is safe and effective. In a phase II clinical trial, administration of OCA was well-tolerated, increased insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with type II diabetes mellitus and NAFLD. In two clinical trials of OCA in patients with primary biliary cirrhosis (PBC), a progressive cholestatic liver disease, OCA significantly reduced serum alkaline phosphatase (ALP) levels, an important disease marker that correlates well with clinical outcomes of patients with PBC. Together, these studies suggest that FXR agonists could potentially be used as therapeutic tools in patients suffering from nonalcoholic fatty and cholestatic liver diseases. Larger and Longer-term studies are currently ongoing.
Controlling the Shape and Alignment of Mesopores by Confinement in Colloidal Crystals:  Designer Pathways to Silica Monoliths with Hierarchical Porosity (2007)

Monolithic pieces of hierarchically structured silica, containing both periodic macropores and mesopores with well-controlled architecture, are synthesized by dual templating methods. Colloidal crystal templating with close-packed arrays of poly(methyl methacrylate) spheres yields regular, highly interconnected macropores a few hundred nanometers in diameter, and templating with nonionic surfactants produces mesoporosity (2.5−5.1 nm pore diameters) in the macropore walls. Several distinct mesostructures can be achieved within the silica skeleton, depending on the choice of surfactant, co-surfactant, and processing conditions. In the three-dimensional (3D) confinement of the colloidal crystal template, wormlike channels, cubic (Pm3n), or two-dimensional (2D) hexagonal (P6mm) mesostructures are produced with the surfactant Brij 56 (C16H33(OCH2CH2)nOH (n ∼ 10) and dodecane as cosurfactant. In the 2D hexagonal structure, channels are oriented perpendicular to the polymer spheres, thereby connecting adjacent macropores through the silica walls. This orientation contrasts with channel alignment parallel to latex spheres when the polymeric surfactant Pluronic P123 (EO20PO70EO20) is used. On the basis of high-resolution 3D transmission electron microscopy, scanning electron microscopy, small-angle X-ray scattering, and nitrogen sorption measurements, structural and textural properties of the monoliths are described in detail as a function of the synthesis parameters. The control over the mesoarchitecture of these silica−surfactant systems in 3D confinement is explained by considering the relative dimensions of the mesostructures with respect to the interstitial space in the latex template, interfacial interactions, entropic effects, and structural frustration.
Adaptive deblocking filter (2003)

This paper describes the adaptive deblocking filter used in the H.264/MPEG-4 AVC video coding standard. The filter performs simple operations to detect and analyze artifacts on coded block boundaries and attenuates those by applying a selected filter.
Toward a Genetic Analysis of Cell-Matrix Adhesion (1992)

The interactions of cells with their neighbors and with the extracellular matrix play crucial roles in development and in numerous physiological and pathological processes (Hay 1991; Hynes and Lander 1992). Studies of cell adhesion during the past decade and more have uncovered the existence of a large number of cell adhesion molecules. These include cell-surface receptors involved in cell-cell adhesion, such as the cadherins (Takeichi 1988, 1990, 1991), members of the immunoglobulin superfamily (Jessell 1988; Grumet 1991), and selectins (Bevilacqua et al. 1991; Lasky and Rosen 1992). Each of these families of receptors includes multiple related molecules. The same is true for cell-matrix adhesion, which is most frequently mediated by the family of adhesion receptors known as integrins (Hynes 1987, 1992; Albelda and Buck 1990; Hemler 1990).
TRIGEMINAL NERVE STIMULATION FOR EPILEPSY: LONG-TERM FEASIBILITY AND EFFICACY (2009)

Neurostimulation has emerged as a viable alternative for intractable epilepsy. Trigeminal nerve stimulation (TNS), a novel form of neurostimulation, has an antiepileptic effect in a rodent model.1 The superficial location of trigeminal branches allows for minimally invasive approaches, allowing assessment of response prior to a permanent device.2 We report the long-term safety and efficacy of external TNS for epilepsy.

### Methods.

Research committee approval was obtained for an open study of external TNS in epilepsy. Informed consent was obtained before enrollment. Inclusion/exclusion criteria were age 18–65 years, ≥3 complex-partial/generalized tonic-clonic seizures/month, no progressive medical conditions, and exposure to ≥2 antiepileptic drugs (AEDs). Subjects enrolled in a 4-week pretreatment baseline, and were evaluated at 1, 2, 3, 6, and 12 months. AEDs remained unchanged unless essential for patient safety. Neurostimulation was initially supplied using the analog EMS Model 400, and later a digital EMS model 7500.2 Stimulation settings were as follows: frequency 120 Hz, 250 μs, ≤30 seconds on, ≤30 seconds off for 12–24 hours/day, and 1.25-inch disposable, silver-gel, adhesive electrodes were utilized, spaced 2 inches …
Cytotoxic T lymphocytes specific for murine type II collagen do not trigger arthritis in B10 mice (1996)

To investigate the role of cytotoxic T lymphocytes (CTL) in arthritis, we set out to induce CTL specific for murine type II collagen (mCII) in a mouse model. The primary protein sequence of the murine pro-alpha 1(II) was screened for fragments bearing H-2 Db or Kb binding motifs. Six fragments were identified and the corresponding peptides synthesized. One of these peptides, peptide P201 (amino acid 199-208 in the C-propeptide of the murine pro-alpha 1(II), was found to be a strong binder to H-2 Db. When used to treat RMA-S cells at 26 degrees C, peptide P201 induced a four-fold increase of surface expression of H-2 Db. Administration of the P201-treated RMA-S cells into B10 mice (H-2b) induced strong CTL responses against the immunizing collagen peptide. Despite the high frequencies of mCII-specific CTL precursors in the periphery, however, the immunized mice showed no sign of arthritis up to 16 weeks after immunization. Implications of these data for autoimmunity and arthritis are discussed.
Human liver fibronectin complementary DNAs: identification of two different messenger RNAs possibly encoding the .alpha. and .beta. subunits of plasma fibronectin (1986)

Human fibronectin polymorphism arises from variation in the C-terminal region [e.g., Sekiguchi, K., Siri, A., Zardi, L., & Hakomori, S. (1985) J. Biol. Chem. 260, 5105-5114]. In order to verify the chemical basis of the fibronectin polymorphism, cDNAs encoding the C-terminal region of human liver fibronectin have been isolated, sequenced, and compared with cDNAs encoding so-called "cellular fibronectin" (i.e., fibronectin produced by cultured cells in vitro). Among the five independent cDNAs thus isolated, two cDNAs, named pLF2 and pLF4, differed in the nucleotide sequence at the "type III connecting segment" (IIIcs) region. pLF4 contained 192 bases in this region whereas pLF2 completely lacked these bases. S1 mapping analysis indicated that both cDNAs with and without the 192 bases are faithful copies of two fibronectin mRNA species abundantly present in human liver. Comparison of the liver cDNAs with those coding for cellular fibronectin indicates that the latter cDNAs contain the 75-base and/or 93-base extra segments at the 5' and 3' boundaries of the 192-base IIIcs region. These extra segments have the consensus sequences for the 3' splice sites at their 3' ends, suggesting that fibronectin mRNAs with partial or complete deletion of the IIIcs sequence result from alternative splicing of a primary RNA transcript. Liver fibronectin cDNAs also lacked the 270-based "extra domain" (ED) segment present in some, but not all, cDNAs encoding cellular fibronectin. Thus, cellular fibronectin appears to have three extra peptide segments, encoded by the 75-base and 93-base segments in the IIIcs region and by the 270-base ED region, that are mostly absent in the liver fibronectin.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinetic studies on decomposition of glutathione. III. Peptide bond cleavage and desulfurization in aqueous solution. (1980)

Kinetic studies on the peptide bond (γ-glutamyl bond) cleavage and desulfurization of glutathione (GSH) in anaerobic aqueous solution were performed in the range of pH 1-12 at 60°. The desulfurization of GSH in neutral solution was very slow, but the rate increased markedly with increase of pH. In the range of pH 10-12, the pH of the reaction solution had little effect on the desulfurization rate. The cleavage rate of γ-glutamyl bond showed a minimum in the range of pH 5-6, a maximum at pH 8.5 and a plateau in the range of pH 10-12. The effects of ionic strength and dielectric constant on both γ-glutamyl bond cleavage and desulfurization were almost negligible. The apparent activation energy for cleavage of the γ-glutamyl bond was 19-21 kcal/mol and that for desulfurization was about 21 kcal/mol. The apparent first-order rate constants of both reactions were related to the mole fractions of ionic species of GSH and could be expressed as a function of hydrogen ion activity at arbitrary pH. In the range of pH 6.5-10, the pH profile of the logarithmic cleavage rate constant of the γ-glutamyl bond was bell-shaped ; it is likely that cleavage of the γ-glutamyl bond is accelerated, at least in the range of pH 7.5-10, by intramolecular catalysis involving the NH2 and SH groups of GSH.
Treatment options for hydroxyurea‐refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt (2010)

Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension.
RAC1 P29S regulates PD‐L1 expression in melanoma (2015)

Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5-9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies.
Limited Propsects for Privatization of Public Lands: Presidio and Valles Caldera May Be as Good as It Gets (2004)

report interesting and revealing stories of the Presidio Trust and the Valles Caldera National Preserve.The stories are interesting as political theater and revealing of the likely roles for market approaches on the stage of public lands management.Although the market is the star in the Presidio Trust drama, its role is tightly constrained.Only time and perspective will tell wvhether it is hero or villain.In the Valles Caldera, the market has only a bit part.If markets are meant to be the main plot in these two stories, in the end there is a subplot that steals the show.While markets are constricted in both tales and pushed to the sidelines in Valles Caldera, decentralization of government authority emerges as a central theme in both.Although decentralized government does not bring all of the benefits of markets, it allows resource management decisions to be made closer to those most directly affected.The first act of the Valles Caldera plot is simple, and recurrent in public lands history.Competing federal agencies covet control of land.In the second act, however, private investors intervene by purchasing the land in question with development in mind.Although some development takes place, in the final act the acquisitive government agency persists and eventually acquires the land to serve as a "model for sustainable land development and use."'Rather than integrate the land into a larger management unit, Congress decides to pursue an experiment in public lands management and create the Valles Caldera Trust.The Presidio's story is more complicated, although the theme of competing government agencies is again central to the plot.As the name suggests, the military occupied the land for many decades.It was included in a national recreation area in the early 1970s, 2 but the military held its ground for the most part.Then in a brief moment of selfimposed reason and discipline, Congress enacted base closure legislation that engulfed the Presidio along with several other military
Fcγ receptors in autoimmune diseases (2001)

Fcgamma-receptors (Fcgamma-R) recognise the Fc portion of IgG and thus form a link between humoral and cellular immunity. These receptors are expressed by a variety of immune cells, and they function in the binding of immune complexes or IgG-opsonised particles, such as microbial pathogens. The are three major types of Fcgamma-R, namely Fcgamma-RI (CD64), Fcgamma-RII (CD32) and Fcgamma-RIII (CD16), and these differ in their ability to bind IgG and complexes. There are many isoforms of these receptors and a number of recently identified polymorphisms in their structure. This review describes the structure and function of these Fcgamma-Rs, and highlights how gene deficiencies and polymorphisms may contribute to the pathology of human diseases.
Factor Analysis of Four Measures of Prefrontal Lobe Functioning (1998)

The Wisconsin Card Sorting Test, Stroop Test, Verbal Fluency (FAS), and Auditory Consonant Trigrams are commonly used measures of prefrontal lobe dysfunction. However, insufficient data are available regarding the specific functions assessed by these tests and the relationship of the tests to each other. These four tests, as well as measures of IQ, memory, attention, and processing speed, were administered to 250 subjects (138 patients and 112 controls). Factor analysis yielded three factors, and a higher order frontal lobe factor, using a dimensional factor analytic methodology. Present findings revealed modest correlations among the prefrontal tests, suggesting that the tests tap somewhat different abilities and are not redundant. Adequate assessment of prefrontal lobe abilities appears to require use of more than one test.
Bile acid structure-activity relationship: evaluation of bile acid lipophilicity using 1-octanol/water partition coefficient and reverse phase HPLC. (1990)

Two independent methods have been developed and compared to determine the lipophilicity of a representative series of naturally occurring bile acids (BA) in relation to their structure. The BA included cholic acid (CA), chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), hyodeoxycholic acid (HDCA), ursocholic acid (UCA), hyocholic acid (HCA), as well as their glycine and taurine amidates. Lipophilicity was determined using a 1-octanol/water shake-flask procedure and the experiments were performed at different pH and ionic strengths and at initial BA concentrations below their critical micellar concentrations (CMC) and the water solubility of the protonated form. The experimental data show that both the protonated (HA) and ionized (A-) forms of BA can distribute in 1-octanol, and consequently a partition coefficient for HA (logP' HA) and for A- (logP' A-) must be defined. An equation to predict a weighted apparent distribution coefficient (D) value as a function of pH and pKa has been developed and fits well with the experimental data. Differences between logP for protonated and ionized species for unconjugated BA were in the order of 1 log unit, which increased to 2 for glycine-amidate BA. The partition coefficient of the A- form increased with Na+ concentration and total ionic strength, suggesting an ion-pair mechanism for its partition into 1-octanol. Lipophilicity was also assessed using reverse phase chromatography (C-18-HPLC), and a capacity factor (K') for ionized species was determined. Despite a broad correlation with the logP data, some BA behaved differently. The logP values showed that the order of lipophilicity was DCA greater than CDCA greater than UDCA greater than HDCA greater than HCA greater than CA greater than UCA for both the protonated and ionized unconjugated and glycine-amidate BA, while the K' data showed an inversion for some BA, i.e., DCA greater than CDCA greater than CA greater than HCA greater than UDCA greater than HDCA greater than UCA. The logP data fitted well with other indirect measurements of BA monomeric lipophilicity such as albumin binding or accessible total hydrophobic surface area data calculated by energy minimization and molecular computer graphics. Differences between unconjugated and amidated BA are consistent with the presence of an amide bond and a lower pKa when pH dependence was studied. Capacity factors, on the other hand, were related to properties of BA micelles such as cholesterol-solubilizing capacity and membrane disruption, reflecting the BA detergency.(ABSTRACT TRUNCATED AT 400 WORDS)