gebhart/patrepeval huggingface dataset:
Evaluation of Standard Chemotherapy in the Guinea Pig Model of Tuberculosis (2010)

The purpose of this study was 2-fold. First, we evaluated standard chemotherapy in the guinea pig model of tuberculosis to determine if this animal species could productively be used for this purpose. Second, given the similarities of the pathology of disease in guinea pigs and humans, we wished to evaluate additional parameters, including magnetic resonance imaging, microscopy, and cytokine expression and lymphocyte phenotypes, in response to an infection treated with drug therapy. This study shows that conventional rifampin-isoniazid-pyrazinamide chemotherapy significantly decreased the numbers of the highly virulent Erdman K01 strain of Mycobacterium tuberculosis, with most of the bacilli being eliminated in a month. Despite this result, bacteria could still be detected in the lungs and other tissues for at least another 3 to 4 months. Resolution of the nonnecrotic granulomas in the lungs and lymph nodes could be clearly visualized by magnetic resonance imaging at the macroscopic level. Microscopically, the majority of the pulmonary and extrapulmonary inflammation resolved spontaneously, leaving residual lesions composed of dystrophic calcification and fibrosis marking the site of necrosis of the primary lesion. Residual calcified lesions, which were also associated with pulmonary lymphangitis, contained acid-fast bacilli even following aggressive chemotherapy. The presence of intact extracellular bacilli within these lesions suggests that these could serve as the primary sites of disease reactivation. The chemotherapy reduced the level of T-cell influx into infected tissues and was accompanied by a large and sustained increase in TH1 cytokine expression. Chemotherapy also prevented the emergence in lung tissues of high levels of interleukin-10 and Foxp3-positive cells, known markers of regulatory T cells.
Antiparallel, intramolecular triplex DNA stimulates homologous recombination in human cells. (1995)

The DNA motif 5'-AAGGGAGAAXGGGTATAGGGYAAGAGGGAA-3' (named XY32) is an H-palindrome and has been shown to undergo a superhelix-induced, pH-dependent structural transition to H-form (pyrimidine purineo pyrimidine triplex) DNA when X = Y = A (AA32) or X = Y = G (GG32), but when X = A and Y = G (AG32) or X = G and Y = A (GA32), the transition is much more difficult [Mirkin, S. (1987) Nature (London) 330, 495-497]. Furthermore, AA32, GG32, and GA32 triplexes have the proper sequence structure to potentially form pyrimidineopurineopurine (*H-form) triplexes, but AG32 does not [Beal, P. A. & Dervan, P. B. (1992) Nucleic Acids Res. 20, 2773-2776]. Using an in vivo plasmid-plasmid recombination assay system in cultured human cells, we have found that AA32, GA32, and GG32 stimulate homologous recombination between plasmids 3- to 5-fold when both recombination substrates contain these triplex-forming sequences, whereas AG32, which differs from the others by only 1 or 2 bp, does not significantly affect the frequency of recombination. Double-strand breaks, which destroy supercoiling, nullify the stimulation. Therefore, stimulation of homologous recombination between plasmids containing these sequences correlates with their triplex-forming potential. Crosses in which the triplex-forming sequence is inserted into only one substrate exhibit an intermediate stimulation, suggesting that the inserts are acting alone as intramolecular triplexes.
Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells in leukapheresis product and bone marrow for clinical transplantation: a comparison of three methods. (2006)

Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells (HSCs) is widely used for evaluation of graft adequacy of peripheral blood and bone marrow stem cell grafts. In the present study, we review and compare the major counting techniques of stem and progenitor cells. The methods are: the Milan/Mullhouse protocol, two-platform ISHAGE (International Society of Hematotherapy and Graft Engineering) and single-platform ISHAGE analysis system. According to the Milan/Mulhouse protocol, HSCs are identified by CD34 antibody staining and easy gating strategy. The ISHAGE guidelines for detection of CD34+ cells are based on a four-parameter flow cytometry method (CD34PE/CD45PerCP staining, side and forward angle light scatter) thus employing multiparameter gating strategy. With two-platform ISHAGE protocol, an absolute CD34+ count is generated by incorporating the leukocyte count from an automated hematology analyser. The single-platform ISHAGE method to determine the absolute CD34+ count directly from a flow cytometer includes the use of Trucount tubes (Becton Dickinson) with a known number of fluorescent beads. CD34+ cells were quantified in mobilized peripheral blood, collected by leukapheresis, and bone marrow from 42 samples from patients with hematological malignancies. The differences against the means display low disagreement between the Milan/Mulhouse and ISHAGE protocols, with discrepancies of up to 2.5% (two-platform ISHAGE)--2.6% (single-platform ISHAGE) in enumeration of CD34+ cells in leukapheresis product and 4.8% (two-platform ISHAGE)--4.9% (single-platform ISHAGE) in bone marrow. Our results show high correlation among all three methods. Since the three protocols are compatible, choosing the most convenient in terms of costs, simplicity and compliance with clinical results appears to be a logical consequence.
The law of photochemical equivalence and the place of the quantum theory in relation to the atomic theory and energetics (1926)

D. Berthelot and H. Borns, Trans. Faraday Soc., 1926, 21, 463 DOI: 10.1039/TF9262100463
Defects in GaInNAs: What We've Learned So Far (2003)

We show results from a number of experimental and theoretical investigations on GaInNAs in an attempt to provide a more complete picture of defects in this material than is currently available. Much has been learned in recent years, including the effects of impurities such as hydrogen and carbon, the behavior of GaInNAs on annealing, and the defects that cause a degradation of material properties, including photoluminescence intensity and, especially important for solar cells, minority-carrier lifetimes. Much of our current understanding stems from a comparison of GaInNAs grown by both MOCVD and MBE. This comparison, along with the use of several characterization techniques and theoretical modeling, has allowed us to understand the roles of various defects and to identify a signature for the defect that reduces the minority-carrier lifetime.
The Salmonella typhimurium nadC gene: sequence determination by use of Mud-P22 and purification of quinolinate phosphoribosyltransferase (1993)

The Salmonella typhimurium nadC gene and its product, quinolinic acid phosphoribosyltransferase (QAPRTase), were characterized at the molecular and biochemical levels. Fusions of Mud-lac elements isolated in the nadC gene were converted to Mud-P22 insertions. Starting with six original Mud-lac fusions, the entire sequence of the nadC gene was readily obtained. The sequence shows a long open reading frame with two potential initiator methionines, one of which is preceded by the Shine-Dalgarno sequence GGAG-7-nucleotide-ATG. The protein predicted from this second open reading frame is 297 residues in length. The nadC gene was subcloned into a T7-based expression system, allowing for facile purification of the QAPRTase (EC 2.4.2.19) protein to homogeneity. Upon gel filtration, the protein gave an M(r) of 72,000, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a subunit M(r) of 35,000. Automated Edman degradation of several tryptic peptides confirmed the amino acid sequence predicted from the DNA sequence. Chromatography of the apparently homogeneous enzyme on reverse-phase high-performance liquid chromatography resolved two protein species. One of these species failed to give an amino-terminal sequence, while the other yielded the amino-terminal sequence predicted by the second open reading frame and lacked the initiator methionine. The mass of the mature protein, predicted from its DNA sequence, was 32,428 Da. Electrospray mass spectrometry gave masses of 32,501 and 32,581 Da for the two peptides. Steady-state kinetics on the purified QAPRTase indicated Km values of 32 microM for 5-phosphoribosyl-1-pyrophosphate and 20 microM for quinolinate. Vmax was 0.9 U/mg, similar to values reported for this enzyme by other sources.
Efficient and flexible drift-free video bitstream switching at predictive frames (2002)

We propose an efficient and flexible coding scheme inspired by the SP picture technique in H.26L TML; it can achieve drift-free bitstream switching at predictive frames. Firstly, the proposed scheme improves the coding efficiency of the SP frames in H.26L TML by (1) reducing the number of quantization modules in the encoding path; (2) eliminating the mismatch between references for the prediction and the reconstruction; (3) outputting a high quality image for display purpose before the quantization step in the reconstruction loop. Secondly, the proposed scheme allows independent quantization parameters for up-switching and down-switching bitstreams. It can further reduce the switching bitstream size while keeping the coding efficiency of the normal bitstreams. It allows more rapid and frequent down-switching than up-switching. Furthermore, the size of the down-switching bitstream can be much smaller than that of the up-switching one. This is a very desirable feature for any TCP-friendly protocols currently used in most existing streaming systems.
An unobtrusive behavioral model of "gross national happiness" (2010)

I analyze the use of emotion words for approximately 100 million Facebook users since September of 2007. "Gross national happiness" is operationalized as a standardized difference between the use of positive and negative words, aggregated across days, and present a graph of this metric. I begin to validate this metric by showing that positive and negative word use in status updates covaries with self-reported satisfaction with life (convergent validity), and also note that the graph shows peaks and valleys on days that are culturally and emotionally significant (face validity). I discuss the development and computation of this metric, argue that this metric and graph serves as a representation of the overall emotional health of the nation, and discuss the importance of tracking such metrics.
Robustness of Reconstructed Ancestral Protein Functions to Statistical Uncertainty (2016)

Hypotheses about the functions of ancient proteins and the effects of historical mutations on them are often tested using ancestral protein reconstruction (APR)-phylogenetic inference of ancestral sequences followed by synthesis and experimental characterization. Usually, some sequence sites are ambiguously reconstructed, with two or more statistically plausible states. The extent to which the inferred functions and mutational effects are robust to uncertainty about the ancestral sequence has not been studied systematically. To address this issue, we reconstructed ancestral proteins in three domain families that have different functions, architectures, and degrees of uncertainty; we then experimentally characterized the functional robustness of these proteins when uncertainty was incorporated using several approaches, including sampling amino acid states from the posterior distribution at each site and incorporating the alternative amino acid state at every ambiguous site in the sequence into a single "worst plausible case" protein. In every case, qualitative conclusions about the ancestral proteins' functions and the effects of key historical mutations were robust to sequence uncertainty, with similar functions observed even when scores of alternate amino acids were incorporated. There was some variation in quantitative descriptors of function among plausible sequences, suggesting that experimentally characterizing robustness is particularly important when quantitative estimates of ancient biochemical parameters are desired. The worst plausible case method appears to provide an efficient strategy for characterizing the functional robustness of ancestral proteins to large amounts of sequence uncertainty. Sampling from the posterior distribution sometimes produced artifactually nonfunctional proteins for sequences reconstructed with substantial ambiguity.
Biologic effects after a single dose of poly(I):poly(C12U) in healthy volunteers (1993)

Poly(I):poly(C12U) (mismatched double-stranded RNA; atvogen), an interferon inducer, is active against human immunodeficiency virus in vitro. To determine the extent and duration of the biologic effects of poly(I):poly(C12U), we administered a single dose of the drug to healthy volunteers in a randomized, double-blind, placebo-controlled 2-week crossover study. We analyzed blood for alpha and gamma interferons, neopterin, 2',5'-oligoadenylate synthetase, lymphocyte surface markers, lymphocyte proliferation after exposure to soluble antigens and mitogens, and natural killer cell activity. Minimal biologic effects were observed after administration of a single 200-mg dose to four volunteers; therefore, the dose was increased to 600 mg in 10 subjects. Only neopterin levels and symptoms were greater after administration of 600 mg of poly(I):poly(C12U) than after administration of placebo (Wilcoxon signed rank sum test, P = 0.06). A definite response in 2',5'-oligoadenylate synthetase activity, however, was seen in a few subjects. Neither alpha nor gamma interferon was detectable in serum after poly(I):poly(C12U) dosing. The neopterin changes after administration of poly(I):poly(C12U) were similar at both poly(I):poly(C12U) dose levels, with an early decrease at 6 h, a peak at 1 day, and a gradual decrease toward the baseline over the following 3 days. A mild flu-like syndrome occurred in one-half of the subjects following administration of poly(I):poly(C12U) and in only one subject following administration of placebo. This syndrome resolved within 16 h after poly(I):poly(C12U) dosing. We conclude that poly(I):poly(C12U) does not induce measurable levels of interferon and causes only minimal biologic or toxic effects among those parameters measured after administration of a single dose in the 200- to 600-mg dose range in health volunteers.
Unique Emission from Polymer Based Lanthanide Alloys (2005)

The incorporation of metal-ligand interactions into macromolecules imparts them with unique and potentially useful properties. We report novel macromolecules prepared via ATRP that contain activated esters for subsequent incorporation of terpyridine. The addition of lanthanide ions (Eu3+ and Tb3+) gave metal functionalized polymers that exhibited excellent emission of either pink (Eu3+) or green (Tb3+) light. A unique yellow luminescence was generated when these two different metal ions were incorporated into the same molecular backbone at a 1:1 ratio, producing an alloy. Upon heating above 50 degrees C, selective thermochromism, from yellow to orange/pink, was observed.
Design, Synthesis, and Evaluations of Substituted 3-[(3- or 4-Carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as Inhibitors of VEGF, FGF, and PDGF Receptor Tyrosine Kinases (1999)

Receptor tyrosine kinases (RTKs) have been implicated as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, cardiovascular diseases including arterial restenosis, and fibrotic diseases of the lung, liver, and kidney. Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs. Some of the compounds were found to inhibit the tyrosine kinase activity associated with isolated vascular endothelial growth factor receptor 2 (VEGF-R2) [fetal liver tyrosine kinase 1 (Flk-1)/kinase insert domain-containing receptor (KDR)], fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R) tyrosine kinase with IC(50) values at nanomolar level. Thus, compound 1 showed inhibition against VEGF-R2 (Flk-1/KDR) and FGF-R1 tyrosine kinase activity with IC(50) values of 20 and 30 nM, respectively, while compound 16f inhibited the PDGF-R tyrosine kinase activity with IC(50) value of 10 nM. Structural models and structure-activity relationship analysis of these compounds for the target receptors are discussed. The cellular activities of these compounds were profiled using cellular proliferation assays as measured by bromodeoxyuridine (BrdU) incorporation. Specific and potent inhibition of cell growth was observed for some of these compounds. These data provide evidence that these compounds can be used to inhibit the function of these target receptors.
Arginine vasopressin in septic shock: supplement or substitute for norepinephrine? (2009)

In the current issue of Critical Care, Simon and coworkers investigated the effects of first-line arginine vasopressin (AVP) on organ function and systemic metabolism compared with norepinephrine in a pig model of fecal peritonitis. AVP was titrated according to the mean arterial pressure suggesting a vasopressor rather than a hormone replacement therapy. The study provides some evidence for the safety of this therapeutic approach. It needs to be determined whether AVP is most beneficial as a constant low-dose infusion to supplement norepinephrine or in higher doses than currently recommended to substitute norepinephrine. In addition, future studies are warranted to evaluate whether a first-line therapy of AVP is superior to a last-resort administration.
Depletion of LAG-3 Positive Cells in Cardiac Allograft Reveals Their Role in Rejection and Tolerance (2007)

Targeting LAG-3-positive cells with cytotoxic antibodies is immunosuppressive in transplantation by depleting effectors T cells and therefore may represent a treatment for rejection episodes focused only on pathogenic cells. However, it might not be compatible with tolerance-induction strategies.
Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy (2007)

Arterial tissues collected from Ossabaw swine bearing metabolic syndrome-induced cardiovascular plaques are characterized by multimodal nonlinear optical microscopy that allows coherent anti-Stokes Raman scattering, second-harmonic generation, and two-photon excitation fluorescence imaging on the same platform. Significant components of arterial walls and atherosclerotic lesions, including endothelial cells, extracellular lipid droplets, lipid-rich cells, low-density lipoprotein aggregates, collagen, and elastin are imaged without any labeling. Emission spectra of these components are obtained by nonlinear optical microspectrometry. The nonlinear optical contrast is compared with histology of the same sample. Multimodal nonlinear optical imaging of plaque composition also allows identification of atherosclerotic regions that are vulnerable to rupture risk. The demonstrated capability of nonlinear optical microscopy for label-free molecular imaging of atherosclerotic lesions with 3-D submicrometric resolution suggests its potential application to the diagnosis of atherosclerotic plaques, determination of their rupture risk, and design of individualized drug therapy based on plaque composition.
The effects of single dose anxiolytic medication on the CO2 models of anxiety: differentiation of subjective and objective measures (2008)

This was a double blind, placebo-controlled, 4-way cross-over study in 12 healthy volunteer subjects of the acute effects of three drugs each of which are used in the clinic to treat some forms of anxiety: propranolol 40 mg, hydroxyzine 25 mg, flupentixol 0.5 mg and placebo. Each test session consisted of inhalation of air for 20 min, 10-min rest, inhalation of CO2 7.5% for 20 min, 10-min rest, followed by a single vital capacity inhalation of 35% CO2. The CO2 7.5% was administered at peak drug effect. Subjective effects were measured using Visual Analogue Scales (VAS), the Panic Symptom Inventory and the Generalised Anxiety Disorder Assessment inventory. Twelve subjects participated (eight men), with a mean age of 25.9 years. The expected subjective effects of CO2 were seen and these were significantly different from effects of peak air. However, there were no statistically significant differences between the drugs or between drugs and placebo, indeed there was a trend for some VAS anxiety scores to be higher than placebo in the drug groups. There were some significant differences in cardiovascular responses to CO2, with propranolol significantly decreasing heart rate and flupentixol increasing blood pressure when compared with placebo. The lack of subjective anxiolytic actions of the three drugs contrasts with our previous findings with acute benzodiazepines and chronic selective serotonin reuptake inhibitor administration. It may be that prolonged treatment with these agents would be required to show anxiolytic effects, although it may also be that their efficacy is insufficient to be demonstrated in this model. The lack of anxiolytic actions of propranolol, despite a significant reduction in heart rate, is a further support for a central action of CO2 to produce anxiety.
Induction of CD4 + Human Cytolytic T Cells Specific for HIV-Infected Cells by a Gp160 Subunit Vaccine (1990)

Cytolytic T lymphocyte (CTL) responses were evaluated in humans immunized with recombinant human immunodeficiency virus type 1 (HIV) envelope glycoprotein gp160. Some vaccinees had gp160-specific CTLs that were shown by cloning to be CD4+. Although induced by exogenous antigen, most gp160-specific CTL clones also recognized gp160 synthesized endogenously in target cells. These clones lysed autologous CD4+ T lymphoblasts infected with HIV. Of particular interest were certain vaccine-induced clones that lysed HIV-infected cells, recognized gp160 from diverse HIV isolates, and did not participate in "innocent bystander" killing of noninfected CD4+ T cells that had bound gp120.
Recent Applications of Liposomes in Ophthalmic Drug Delivery (2011)

Liposomal formulations were significantly explored over the last decade for the ophthalmic drug delivery applications. These formulations are mainly composed of phosphatidylcholine (PC) and other constituents such as cholesterol and lipid-conjugated hydrophilic polymers. Liposomes are biodegradable and biocompatible in nature. Current approaches for topical delivery of liposomes are focused on improving the corneal adhesion and permeation by incorporating various bioadhesive and penetration enhancing polymers. In the case of posterior segment disorders improvement in intravitreal half life and targeted drug delivery to the retina is achieved by liposomes. In this paper we have attempted to summarize the applications of liposomes in the field of ophthalmic drug delivery by citing numerous investigators over the last decade.