gebhart/patrepeval huggingface dataset:
Identification of Highly Attenuated Mutants of Simian Immunodeficiency Virus (1998)

Deletion mutants of the pathogenic clone of simian immunodeficiency virus isolate 239 (SIVmac239) were derived that are missing nef, vpr, and upstream sequences (US) in the U3 region of the LTR (SIVmac239 delta3), nef, vpx, and US (SIVmac239 delta3x), and nef, vpr, vpx, and US (SIVmac239 delta4). These multiply deleted derivatives replicated well in the continuously growing CEMx174 cell line and were infectious for rhesus monkeys. However, on the basis of virus load measurements, strength of antibody responses, and lack of disease progression, these mutants were highly attenuated. Measurements of cell-associated viral load agreed well with assays of plasma viral RNA load and with the strengths of the antibody responses; thus, these measurements likely reflected the extent of viral replication in vivo. A derivative of SIVmac239 lacking vif sequences (SIVmac239 delta vif) could be consistently grown only in a vif-complementing cell line. This delta vif virus appeared to be very weakly infectious for rhesus monkeys on the basis of sensitive antibody tests only. The weak antibody responses elicited by SIVmac239 delta vif were apparently in response to low levels of replicating virus since they were not elicited by heat-inactivated virus and the anti-SIV antibody responses persisted for greater than 1 year. These results, and the results of previous studies, allow a rank ordering of the relative virulence of nine mutant strains of SIVmac according to the following order: delta vpr > delta vpx > delta vpr delta vpx approximately delta nef > delta3 > delta3x > or = delta4 > delta vif > delta5. The results also demonstrate that almost any desired level of attenuation can be achieved, ranging from still pathogenic in a significant proportion of animals (delta vpr and delta vpx) to not detectably infectious (delta5), simply by varying the number and location of deletions in these five loci.
Affinity Labelling of Enzymes with Triazine Dyes (2005)

Horse liver alcohol dehydrogenase is irreversibly inactivated by Procion blue MX-R, a dichlorotriazinyl structural analogue of Cibacron blue F3G-A, with over 90% loss of activity within 30 min at pH 8.5 and 37 degrees C at a reactive dye concentration of 1 mM and enzyme subunit concentration of 5 microM. Methoxylated Procion blue MX-R does not inactivate the enzyme. The inactivation of horse liver alcohol dehydrogenase by Procion blue MX-R is competitively inhibited by the pyridine nucleotides NAD+ and NADH. Quantitatively inhibited horse liver alcohol dehydrogenase contains 1 mol dye/mol subunit of Mr 40 000. Chymotryptic digestion and resolution of the peptides by reverse-phase high-performance liquid chromatography yields a single blue peptide which on sequencing and analysis yields an amino acid sequence of: (formula; see text) with the affinity label, Procion blue MX-R, unambiguously identified as being attached to the thiol side chain of Cys-174 in the catalytic domain of the enzyme. The specific active-site-directed reaction of Procion blue MX-R with horse liver alcohol dehydrogenase is interpreted in terms of the known crystallographic structure of the enzyme.
Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. (1988)

The art gene product of the human immunodeficiency virus is required for the expression of virion capsid and envelope gene proteins. The experiments presented here show that sequences located within the coding region of the envelope gene exert a negative effect on the expression of heterologous genes and that the negative effect of these sequences can be relieved by the art gene product. This region in the env gene contains negative regulatory sequences that inhibit gene expression, as well as a sequence necessary for the art gene product-dependent relief of repression. The experiments define the cis- and trans-acting components of a regulatory system that permits differential expression of human immunodeficiency virus virion structural and regulatory proteins.
Repair of DNA Containing Interstrand Crosslinks in Escherichia coli: Sequential Excision and Recombination (1973)

The repair of DNA containing interstrand crosslinks induced by psoralen-plus-light in E. coli cells has been investigated. During a 30-minute incubation after psoralen-plus-light treatment, crosslinks were excised and the cellular DNA was cut into discrete pieces. The molecular weight of these pieces corresponds to about twice the single-strand distance between crosslinks, as measured by sedimentation velocity in alkaline sucrose. During further incubation, these DNA fragments were covalently joined into high molecular weight DNA. This joining did not occur in cells carrying a mutation at recA; in these strains the DNA was further degraded to smaller polynucleotides and acid-soluble material. The possibility that repair of crosslinked DNA involves strand exchanges between homologous duplexes was investigated. Cells were grown in (13)C,(15)N-containing medium for several generations, then switched to medium of normal density that also contained [(3)H]thymidine for about 0.5 generation. After the crosslinking treatment, the cells were incubated in medium of normal density in order for repair to occur. The DNA was extracted and centrifuged in alkaline CsCl density gradients, where the light and heavy strands were separated. Molecules of intermediate density that contained (3)H accumulated during repair in wild-type cells, but not in control cells or treated recA(-) cells. After molecular weight reduction of the intermediate-density DNA, the (3)H could be separated from the heavy strands, demonstrating that covalent joining between heavy and light strands of homologous duplexes accompanies repair. A mechanism involving sequential excision and genetic recombination is proposed for the repair of DNA containing interstrand crosslinks.
Maximum Likelihood Reconstruction for Emission Tomography (1982)

Previous models for emission tomography (ET) do not distinguish the physics of ET from that of transmission tomography. We give a more accurate general mathematical model for ET where an unknown emission density lambda = lambda(x, y, z) generates, and is to be reconstructed from, the number of counts n(*)(d) in each of D detector units d. Within the model, we give an algorithm for determining an estimate lambdainsertion mark of lambda which maximizes the probability p(n(*)|lambda) of observing the actual detector count data n(*) over all possible densities lambda. Let independent Poisson variables n(b) with unknown means lambda(b), b = 1, ..., B represent the number of unobserved emissions in each of B boxes (pixels) partitioning an object containing an emitter. Suppose each emission in box b is detected in detector unit d with probability p(b, d), d = 1, ..., D with p(b,d) a one-step transition matrix, assumed known. We observe the total number n(*) = n(*)(d) of emissions in each detector unit d and want to estimate the unknown lambda = lambda(b), b = 1, ..., B. For each lambda, the observed data n(*) has probability or likelihood p(n(*)|lambda). The EM algorithm of mathematical statistics starts with an initial estimate lambda(0) and gives the following simple iterative procedure for obtaining a new estimate lambdainsertion mark(new), from an old estimate lambdainsertion mark(old), to obtain lambdainsertion mark(k), k = 1, 2, ..., lambdainsertion mark(new)(b)= lambdainsertion mark(old)(b)Sum of (n(*)p(b,d) from d=1 to D/Sum of lambdainsertion mark()old(b('))p(b('),d) from b(')=1 to B), b=1,...B.
Effect of hexamethylene bisacetamide and cyclosporin A on recovery of herpes simplex virus type 2 from the in vitro model of latency in a human neuroblastoma cell line. (1990)

The goal of the present work was to examine whether hexamethylene bisacetamide (HMBA) and cyclosporin A affect the recovery of herpes simplex virus type 2 (HSV-2) from an in vitro model of HSV-2 latency in human neuroblastoma cell line IMR-32. IMR-32 cells were infected with HSV-2 at a multiplicity of infection of 0.1 plaque-forming units/cell and were cultured at 40 degrees C for 14 days, resulting in the establishment of a model of HSV-2 latency in IMR-32 cells. When the cultivation temperature was shifted down from 40 to 37 degrees C, recovery of virus growth began to occur after an incubation period of 2 days. During the time of shift-down of the incubation temperature, the latently infected cells were further cultured at 37 degrees C in the presence or absence of 5 mM HMBA or 0.5 micrograms/ml cyclosporin A, which does not affect stability of HSV-2 nor proliferation of IMR-32 cells. Consequently, the rate of HSV-2 recovery from the latently infected cells cultured in the presence of 5 mM HMBA was significantly increased, as compared with the untreated controls. In addition, the DNA methylation level of the latently infected IMR-32 cells cultured in the presence of HMBA was significantly decreased when compared to the level in the untreated controls. On the other hand, the cultivation of the latently infected cells in the presence of 0.5 micrograms/ml cyclosporin A resulted in a significant decrease in the rate of HSV-2 recovery. These findings indicate that the recovery of HSV-2 from the model of latency in IMR-32 cells is enhanced by HMBA treatment, which induces a significant decrease of total genomic DNA methylation level, and is inhibited by cyclosporin A treatment.
Rattle‐Type Fe3O4@SiO2 Hollow Mesoporous Spheres as Carriers for Drug Delivery (2009)

Rattle-type Fe(3)O(4)@SiO(2) hollow mesoporous spheres with different particle sizes, different mesoporous shell thicknesses, and different levels of Fe(3)O(4) content are prepared by using carbon spheres as templates. The effects of particle size and concentration of Fe(3)O(4)@SiO(2) hollow mesoporous spheres on cell uptake and their in vitro cytotoxicity to HeLa cells are evaluated. The spheres exhibit relatively fast cell uptake. Concentrations of up to 150 microg mL(-1) show no cytotoxicity, whereas a concentration of 200 microg mL(-1) shows a small amount of cytotoxicity after 48 h of incubation. Doxorubicin hydrochloride (DOX), an anticancer drug, is loaded into the Fe(3)O(4)@SiO(2) hollow mesoporous spheres, and the DOX-loaded spheres exhibit a somewhat higher cytotoxicity than free DOX. These results indicate the potential of Fe(3)O(4)@SiO(2) hollow mesoporous spheres for drug loading and delivery into cancer cells to induce cell death.
Universal interaction with networked home appliances (2003)

We propose universal interaction for networked home appliances, which is a simple mechanism to fill the gap between traditional user interface systems and advanced user interaction devices. Our system enables us to control appliances in a uniform way at any place, and the system allows us to select suitable input and output devices according to our preferences and situations. Also, the devices can be changed dynamically according to a user's preferences.
Ten years' experience with enterocystoplasty. (1993)

Eighteen augmentation cystoplasties and 18 substitution cystoplasties were performed during the last 10 yrs. The indications for augmentation cystoplasty were tuberculous cystitis, interstitial cystitis, detrusor hyperreflexia, and a poor compliant neuropathic bladder. The indications for substitution cystoplasty were a neuropathic bladder and carcinoma of the bladder. Voiding was satisfactory in 11 cases of the augmentation cystoplasty group and in 14 cases of the substitution cystoplasty group. The remaining patients required clean intermittent self catheterization. Revision of the bladder neck was necessary after augmentation cystoplasty in 2 cases. Incontinence of urine occurred in 1 case of each group, both being neuropathic bladder cases with poor sphincter function. Incontinence from detrusor hyperreflexia present before the operation was improved after "clam" enterocystoplasty in all of the 3 cases. Enuresis occurred in 11 cases of the substitution cystoplasty group. Early complications included troublesome mucus plugs, perforation of the neobladder, a persistent suprapubic fistula and one perioperative death. A total of 23 patients were available for follow-up for an average of 17 months (range 6 months to 8 yrs). Thirteen were alive and well, 5 were alive with poor health. Late complications included uretero-vesical junction obstruction, vesico-ureteric reflux, vesical stones, recurrent urinary tract infection, entero-vesical junction narrowing, renal deterioration, gut obstruction, death from chronic renal failure, and death from progression of carcinoma of the bladder. The reoperation rate for complications was 7/23 or 30.43 per cent. The entero-cystoplasty is an operation not to be taken lightly because of the complications and reoperation rate.
Database Similarity Search in Metric Spaces: Limitations and Opportunities (2004)

Generic database similarity search is one of the most challenging problems in current database research. Generic data are not simply structured data with several keys of numeric or alphabetic types. Traditional search algorithms that only check specified fields and keys are not effective. Similarity searches find the objects that are similar to a target using a specified similarity criterion. Tree-structured indexing techniques based on metric spaces are widely used to solve this problem. Existing methods can be divided into two categories: approaches based upon Voronoi partitions and approaches based upon reference points. The later one is the focus of this research. The problem of database similarity search using reference points in metric spaces is formulated, and the key issues are addressed. This research focuses upon two broad sets of open problems: Analysis of the limitations of approaches to similarity search using metric spaces, and development of criteria that can be and to evaluate the opportunities for new design methods. The performance limitations of similarity search based on metric spaces are analyzed and proved to be imposed by statistical characteristics of the data collection. A new concept, range threshold, is defined to evaluate the feasibility of tree-structured indexing techniques based upon reference points in metric spaces. A method to estimate the range threshold is provided, which makes it possible to check the feasibility of this approach for a data set prior to implementation. The opportunities for different approaches are evaluated by criteria based on search efficiency and utility. Comparison of different Minkowski metrics and data extraction methods using PCA (principle component analysis) are presented. Search utilities are demonstrated by examples. Several issues related to index tree structure are addressed. iv Experimental results show that a taller tree yields better performance. All these results indicate that the approaches based upon reference points in metric spaces are promising.
A ferrocene-based carbon–iron lithium fluoride nanocomposite as a stable electrode material in lithium batteries (2010)

A nanocomposite comprising carbon–iron LiF was prepared by pyrolysis of a mixture of ferrocene and LiF at 700 °C under an argon atmosphere for 2 h. The structure and morphology of the material was characterized by high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), BET analysis, and Mössbauer spectroscopy. The composite consists of multi-walled carbon nanotubes and onion-type graphite structures in which Fe and Fe3C nanoparticles are encapsulated, and LiF is dispersed within the carbon matrix. The sample contains both micro- (0.025 cm3 g−1) and mesopores (0.14 cm3 g−1), and has a total specific surface area of 82 m2 g−1. Its charge/discharge performances were studied in the potential range 0.5 V to 4.3 V at a current density of 20.83 mA g−1 at 25 °C. It exhibited an initial discharge capacity of 324 mAh g−1 with respect to the active mass of FeF3. After five cycles the capacity reached 280 mAh g−1 and is maintained at about 270 mAh g−1 over 200 cycles. A reversible specific capacity of about 170 mAh g−1 was realized when the potential range was between 1.3 and 4.3 V.
A polymorphism at the miR‐502 binding site in the 3′‐untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome (2011)

MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analyzed a single-nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region for the 3'-UTR of SET8 in Chinese patients with hepatocellular carcinoma (HCC). The SET8 CC genotype was independently associated with longer postoperative survival in patients with HCC by multivariate analysis (relative risk, 0.175; 95% CI = 0.053-0.577; p = 0.004). The SET8 CC genotype was associated with reduced SET8 protein levels based on the immunostaining of 51 HCC tissue samples. We also found that the low SET8 levels were associated with longer HCC survival. Our data suggest that SET8 modifies HCC outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. The analysis of genetic polymorphisms in miRNA binding sites can help to identify patient subgroups that are at high risk for poor disease outcomes.
Small Molecule Inhibitors as Probes for Estrogen and Androgen Receptor Action (2010)

Because activated estrogen (ER) and androgen (AR) receptors stimulate cell proliferation in breast and prostate cancer, inhibiting their actions represents a major therapeutic goal. Most efforts to modulate ER and AR activity have focused on inhibiting the synthesis of estrogens or androgens or on the identification of small molecules that act by competing with agonist hormones for binding in the ligand-binding pocket of the receptor. An alternative approach is to implement screens for small molecule inhibitors that target other sites in the pathway of steroid receptor action. Many of these second-site inhibitors directly target ER or AR; others have still unknown sites of action. Small molecule inhibitors that target second sites represent new leads with clinical potential; they serve as novel modulators of receptor action; and they can reveal new and as yet unidentified interactions and pathways that modulate ER and AR action.
The CryIA(c) Receptor Purified from Manduca sexta Displays Multiple Specificities (1995)

The kinetic binding characteristics of four Bacillus thuringiensis CryI insecticidal crystal proteins to a Cry-binding protein, purified from Manduca sexta brush-border vesicles, were analyzed by an optical biosensor. This 120-kilodalton binding protein, previously determined to be aminopeptidase N, was converted to a 115-kilodalton water-soluble form by removing the attached glycosylphosphatidylinositol anchor with phospholipase C. The solubilized form recognized the three major subclasses of CryIA toxins but not CryIC even though all four CryI proteins are toxic to larvae of M. sexta. CryIA(a) and CryIA(b) toxins bound to a single site on the solubilized aminopeptidase N molecule whereas CryIA(c) bound to two distinct sites. Apparent kinetic rate constants were determined for each binding reaction. All three CryIA toxins exhibited moderately fast on rates (approximately 10(-5) M-1 s-1) and a slow reversible off rate (approximately 10(-3) s-1). Although the second CryIA(c)-binding site retained a moderately fast association rate, it was characterized by a rate of dissociation from the amino-peptidase an order of magnitude faster than observed for the other CryIA-binding sites. CryIA(c) binding to both sites was strongly inhibited in the presence of N-acetylgalactosamine (IC50 = 5 mM) but not N-acetylglucosamine, mannose, or glucose. CryIA(a) and CryIA(b) binding were unaffected in the presence of the same sugars. Our results serve to illustrate both the complexity and the diverse nature of toxin interactions with Cry-binding proteins.
Early Dose Assessment Following Severe Radiation Accidents (1997)

Early treatment of victims of high level acute whole-body x-ray or gamma exposure has been shown to improve their likelihood of survival. However, in such cases, both the magnitude of the exposure and the dosimetry profile(s) of the victim(s) are often not known in detail for days to weeks. A simple dose-prediction algorithm based on lymphocyte kinetics as documented in prior radiation accidents is presented here. This algorithm provides an estimate of dose within the first 8 h following an acute whole-body exposure. Early lymphocyte depletion kinetics after a severe radiation accident follow a single exponential, L(t) = L(o)e(-k(D¿t), where k(D) is a rate constant, dependent primarily on the average dose, D. Within the first 8 h post-accident, K(D) may be calculated utilizing serial lymphocyte counts. Data from the REAC/TS Radiation Accident Registry were used to develop a dose-prediction algorithm from 43 gamma exposure cases where both lymphocyte kinetics and dose reconstruction were felt to be reasonably reliable. The inverse relationship D(K) may be modeled by a simple two parameter curve of the form D = a/(1 + b/K) in the range 0 < or = D < or = 15 Gy, with fitting parameters (mean +/- SD): a = 13.6 +/- 1.7 Gy, and b = 1.0 +/- 0.20 d(-1). Dose estimated in this manner is intended to serve only as a first approximation to guide initial medical management.
Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. (1998)

The thrombospondins are a family of extracellular calcium-binding proteins that modulate cellular phenotype. Thrombospondin-1 (TSP-1) reportedly regulates cellular attachment, proliferation, migration, and differentiation in vitro. To explore its function in vivo, we have disrupted the TSP-1 gene by homologous recombination in the mouse genome. Platelets from these mice are completely deficient in TSP-1 protein; however, thrombin-induced platelet aggregation is not diminished. TSP-1-deficient mice display a mild and variable lordotic curvature of the spine that is apparent from birth. These mice also display an increase in the number of circulating white blood cells, with monocytes and eosinophils having the largest percent increases. The brain, heart, kidney, spleen, stomach, intestines, aorta, and liver of TSP-1-deficient mice showed no major abnormalities. However, consistent with high levels of expression of TSP-1 in lung, we observe abnormalities in the lungs of mice that lack the protein. Although normal at birth, histopathological analysis of lungs from 4-wk-old TSP-1-deficient mice reveals extensive acute and organizing pneumonia, with neutrophils and macrophages. The macrophages stain for hemosiderin, indicating that diffuse alveolar hemorrhage is occurring. At later times, the number of neutrophils decreases and a striking increase in the number of hemosiderin-containing macrophages is observed associated with multiple-lineage epithelial hyperplasia and the deposition of collagen and elastin. A thickening and ruffling of the epithelium of the airways results from increasing cell proliferation in TSP-1-deficient mice. These results indicate that TSP-1 is involved in normal lung homeostasis.