gebhart/patrepeval huggingface dataset:
Approaches to the synthesis of 2′-thio analogues of pyrimidine ribosides (1990)

2′-Deoxy-2′-mercaptouridine (1) was obtained in 75% isolated yield by heating 2′-deoxy-2′-(4-methoxybenzylthio)uridine (4a) with phenol in trifluoroacetic acid solution. When triphenylmethanol or 9-phenylxanthen-9-ol (5) was added to the products before work-up, compound (4c) or (4d) was obtained. Compound (4d) was also obtained in satisfactory overall yield from crude (1), prepared in two steps from 2′-deoxy-2′-(t-butylthio)uridine (4b). Treatment of compound (4d) first with acetic anhydride in pyridine and then with phosphoryl trichloride, triethylamine, and 1,2,4-triazole in acetonitrile gave the triazolo compound (10) in 73% overall yield. Reaction between compound (10) and ammonia in dichloromethane [or dimethylamine in dioxane] followed by methanolic ammonia gave the cytidine derivative (11a)[or (11b)] in good yield. When compounds (11a) and (11b) were allowed to react with hydrochloric acid in 2-mercaptoethanol solution at room temperature, the hydrochloride salts of 2′-deoxy-2′-mercaptocytidine (2a) and its 4,4-di-N-methyl derivative (2b) were obtained in high isolated yields. The latter compounds readily underwent aerial oxidation in the presence of triethylamine in methanol solution to give the corresponding dimeric disulphides (12a) and (12b). The NMR spectra of the synthetic products are discussed.
Toward carbon free energy (1999)

In this paper the authors describe how heavy reliance on coal in huge countries like China and India threatens the whole world's climate. They state how they believe that the utmost ingenuity will be needed to minimize adverse effects of that dependence.
Lectin Intravital Perfusion Studies in Tumor-bearing Mice: Micrometer-resolution, Wide-area Mapping of Microvascular Labeling, Distinguishing Efficiently and Inefficiently Perfused Microregions in the Tumor (1998)

Intravital lectin perfusion was combined with computer-guided scanning digital microscopy to map the perfused elements of the vasculature in tumor-bearing mice. High-precision composite images (spatial precision 1.3 micron and optical resolution 1.5 micron) were generated to permit exact positioning, reconstruction, analysis, and mapping of entire tumor cross-sections (c. 1 cm in diameter). Collation of these mosaics with nuclear magnetic resonance maps in the same tumor plane identified sites of rapid contrast medium uptake as tumor blood vessels. Digitized imaging after intravital double labeling allowed polychromatic visualization of two different types of mismatched staining. First, simultaneous application of two lectins, each bearing a different fluorochrome, revealed organ-specific differential processing in the microvascular wall. Second, sequential application of two boluses of one lectin, bearing different fluorochromes successively, distinguished between double-labeled microvessels, representing efficiently perfused vascular segments, and single-labeled microvessels, with inefficient or intermittent perfusion. Intravital lectin perfusion images of blood vessels in the vital functional state thus highlighted biologically significant differences in vessel function and served as high-resolution adjuncts to MR imaging.
Response : Protein and Nucleic Acid Sequence Data and Phylogeny (1979)

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Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria (2006)

Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine beta-synthase (CBS). The major clinical symptoms of this disease are mental retardation, lens dislocation, vascular disease with life-threatening thromboembolisms, and skeletal deformities. The major treatments for CBS deficiency include pharmacologic doses of pyridoxine or dietary restriction of methionine. There is currently no effective long-term treatment to lower the elevated plasma levels of homocysteine. However, gene therapy could be an effective novel approach for the treatment of homocystinuria. A recombinant adeno- associated virus vector carrying human CBS cDNA (rAAV-hCBS) was constructed and administered to CBS-/- mice by intramuscular (IM) and intraperitoneal (IP) injections. Serum homocysteine concentrations significantly decreased in treated mice compared with age-matched controls two weeks after treatment. The treated CBS-/- mice had life spans 3-7 days longer compared with untreated CBS-/- mice. In CBS-/- mice treated with rAAV-hCBS via IP injection, the vector was detected in all organs examined including liver, spleen, and kidney, and CBS gene expression was observed by immunohistochemical staining in the liver. These results indicate the efficacy of gene delivery and demonstrate the possibility of gene therapy mediated by AAV gene transfer in this mouse model of homocystinuria.
Controlled assembly of zinc oxide nanowires using dielectrophoresis (2007)

A structure similar to a field effect transistor with two isolated top electrodes comprising the source and drain and a lower substrate electrode as the gate was used for the dielectrophoresis-based assembly of zinc oxide nanowires. The results reveal that the assembly of nanowires is significantly affected by the gap distance between the two top electrodes as well as the magnitude and frequency of the applied electric field. Gate assisted assemblies using direct current and alternating current dielectrophoresis were also investigated and determined to improve the assembly effect of nanowires.
Senescence in adipose-derived stem cells and its implications in nerve regeneration (2014)

Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-derived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) or environmental cues (e.g., stressful stimuli or diseases), which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can influence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.
Diagnosing Insulin Resistance in the General Population (2001)

A weighted combination of two routine laboratory measurements, i.e., fasting insulin and triglycerides, provides a simple means of screening for insulin resistance in the general population.
Clock rate versus IPC (2000)

The doubling of microprocessor performance every three years has been the result of two factors: more transistors per chip and superlinear scaling of the processor clock with technology generation. Our results show that, due to both diminishing improvements in clock rates and poor wire scaling as semiconductor devices shrink, the achievable performance growth of conventional microarchitectures will slow substantially. In this paper, we describe technology-driven models for wire capacitance, wire delay, and microarchitectural component delay. Using the results of these models, we measure the simulated performance-estimating both clock rate and IPCof an aggressive out-of-order microarchitecture as it is scaled from a 250nm technology to a 35nm technology. We perform this analysis for three clock scaling targets and two microarchitecture scaling strategies: pipeline scaling and capacity scaling. We find that no scaling strategy permits annual performance improvements of better than 12.5%, which is far worse than the annual 50-60% to which we have grown accustomed.
Granular cell tumor in breast: a case report (2017)

This is a case of interest because GCT located in the breast is very unusual and knowledge of GCT is required for the differential diagnosis with breast cancer.
Antibody Repertoires in Humanized NOD-scid-IL2Rγnull Mice and Human B Cells Reveals Human-Like Diversification and Tolerance Checkpoints in the Mouse (2012)

Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null) engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null) mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H)-J(H) pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments.
Hepatitis B virus core-preS2 particles expressed by recombinant vaccinia virus. (1997)

Vaccinia virus (VV) recombinants expressing hepatitis B virus (HBV) surface (HBsAg) or core (HBcAg) antigens (Kunke et al., Virology 195, 132 - 139 (1993)] have been shown to raise specific antibodies in mice, nevertheless the levels of antibodies reactive with the preS2 and S antigens were low. In an attempt to enhance the immunogenicity of HBsAg-preS2, a fused C-preS2 gene was constructed. The fusion protein was expressed in E. coli and displayed both HBcAg and preS2 antigen as demonstrated by enzyme-linked immunosorbent assay (ELISA). The same gene was then expressed using recombinant VV and chimerical particles whose size and density were similar to those of native HBV core particles produced in CV-1 cells infected with recombinant VV. Unlike HBcAg, preS2 antigen could not be detected on these particles by ELISA but was revealed by immunoblot analysis only. The immunogenicity of the recombinant VV was evaluated in mice. Antibodies to HBcAg and VV antigen but not to preS2 antigen were found in sera of animals inoculated with 10(7) PFU of the recombinant VV. Presumably, HBcAg-preS2 particles produced in E. coli and in eukaryotic cells have a different conformation, and the presence of preS2 antigen on the surface of chimerical particle might be necessary for a pronounced antibody response.
Acyloxymethyl Carbonochloridates. New Intermediates in Prodrug Synthesis (1990)

The synthesis of a number of stable acyloxymethyl carbonochloridates 7 has been accomplished in four steps from chloromethyl carbonochloridate 3. Each step has been optimized with propanoyloxymethyl carbonochloridate 7c as a model compound (64% overall yield). Diethyl ether-boron trifluoride catalyzes the conversion of carbonothioate 6cc to the carbonochloridate 7c by chlorination with sulfuryl chloride. Acylation of a few compounds containing hydroxy or amino groups by 7c is described.
Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators (2002)

Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E 2 (PGE 2 ) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p &lt; 0.006 and p &lt; 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
A novel product of the Duchenne muscular dystrophy gene which greatly differs from the known isoforms in its structure and tissue distribution (1990)

A novel transcript of the Duchenne muscular dystrophy gene has been identified. This 6.5 kb mRNA contains sequences from the 3' untranslated region of dystrophin mRNA and from the regions coding for the C-terminal and the cysteine-rich domains. However, probes for the regions encoding the spectrin-like repeats and the actin-binding domain, as well as probes for the first exons of the muscle- and brain-type dystrophin mRNA, did not hybridize with this new mRNA. Significant amounts of the 6.5 kb mRNA were found in a variety of non-muscle tissues, such as liver, testis, lung and kidney, but not in skeletal muscle. The abundance of this mRNA in the brain is at least as high as that of the previously described 14 kb brain-type dystrophin mRNA.
Universal precautions in the operating department. (1993)

Those operating theatre personnel who aim to keep up to date by reading the professional journals may well be confused and feel uninformed about the concept of universal precautions. While some authors focus on universal precautions, they do not mention operating theatres. Others continue to discuss the Human Immunodeficiency Virus (HIV), the Hepatitis B Virus (HBV) and high risk patient's. Furthermore the practical aspects of the implementation of universal precautions have not, to date, been thoroughly documented, other than the vague advice of 'treat every patient the same'. This article aims to clarify the concept of universal precautions, consider why they are needed, and suggest a possible pathway for their implementation. The three main changes in practice will also be discussed.
From Sherwin Bailey to Gay Marriage: Some Significant Developments in Christian Thought Since 1955 (2013)

Derrick Sherwin Bailey (1910-1984) produced his influential Homosexuality and the Western Christian Tradition in 1955, making the theological case for the decriminalisation of male homosexual acts in Britain. This was achieved in 1967. Bailey was content that the Church continued to view homosexual acts as grave moral errors. This article rehearses the heart of Bailey's argument, and, in the light of five developments since Bailey, suggests that it is now time for the Church to take a step as momentous as the State now proposes, by dealing with all sexual relationships on exactly the same terms.
17q23 amplifications in breast cancer involve the PAT1, RAD51C, PS6K, and SIGma1B genes. (2000)

Amplification of the 17q23 region occurs frequently in breast tumors. To characterize the structure of 17q23 amplicons and to identify oncogene targets associated with this alteration, we performed a copy number analysis of 87 17q23 localized expressed sequence tags in seven breast cancer cell lines. Three major regions of amplification were detected in the MCF7 and BT474 cell lines. Amplification of at least one of four known genes (PAT1, PS6K, RAD51C, and SIGMA1B) was detected in the cell lines and in 28% of 94 breast tumors. In most cases, these four genes were overexpressed when amplified, but there was a particularly good association between amplification of the SIGMA1B gene and elevated expression in tumors, which suggested a possible role for this gene in tumor progression. Our data show that this region contains at least four independent targets of amplification, which suggests that there is considerable variability in the structure of the 17q23 amplicon.
Construction and Validation of Tissue Microarrays of Ductal Carcinoma In Situ and Terminal Duct Lobular Units Associated With Invasive Breast Carcinoma (2006)

Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of approximately 80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, >or=50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.
Lesions in two Escherichia coli type 1 pilus genes alter pilus number and length without affecting receptor binding (1992)

We describe the characterization of two genes, fimF and fimG (also called pilD), that encode two minor components of type 1 pili in Escherichia coli. Defined, in-frame deletion mutations were generated in vitro in each of these two genes. A double mutation that had deletions identical to both single lesions was also constructed. Examination of minicell transcription and translation products of parental and mutant plasmids revealed that, as predicted from the nucleotide sequence and previous reports, the fimF gene product was a protein of ca. 16 kDa and that the fimG gene product was a protein of ca. 14 kDa. Each of the constructions was introduced, via homologous recombination, into the E. coli chromosome. All three of the resulting mutants produced type 1 pili and exhibited hemagglutination of guinea pig erythrocytes. The latter property was also exhibited by partially purified pili isolated from each of the mutants. Electron microscopic examination revealed that the fimF mutant had markedly reduced numbers of pili per cell, whereas the fimG mutant had very long pili. The double mutant displayed the characteristics of both single mutants. However, pili in the double mutant were even longer than those seen in the fimG mutant, and the numbers of pili were even fewer than those displayed by the fimF mutant. All three mutants could be complemented in trans with a single-copy-number plasmid bearing the appropriate parental gene or genes to give near-normal parental piliation. On the basis of the phenotypes exhibited by the single and double mutants, we believe that the fimF gene product may aid in initiating pilus assembly and that the fimG product may act as an inhibitor of pilus polymerization. In contrast to previous studies, we found that neither gene product was required for type 1 pilus receptor binding.
Sodium Benzoate in the Treatment of Acute Hepatic Encephalopathy: A Double–Blind Randomized Trial (1992)

A prospective randomized double-blind study was conducted to evaluate the efficacy of sodium benzoate in the treatment of acute portal-systemic encephalopathy. Seventy-four consecutive patients with cirrhosis or surgical portasystemic anastomosis and hepatic encephalopathy of less than 7 days duration were randomized to receive lactulose (dose adjusted for 2 or 3 semiformed stools/day) or sodium benzoate (5 gm twice daily). Assessment of response included mental status, asterixis, arterial ammonia level, electroencephalogram and number-connection test. Each was given a score between 0 and 4+. A portal-systemic encephalopathy index was calculated with these scores. Visual, auditory and somatosensory evoked potentials and a battery of psychometric tests for intelligence and memory were also performed to assess improvement. Thirty-eight patients received sodium benzoate; 36 took lactulose. Thirty patients (80%) receiving sodium benzoate and 29 (81%) receiving lactulose recovered; the remaining patients died. Improvement in portal-systemic encephalopathy parameters occurred in both treatment groups and was similar (p greater than 0.1). Electroencephalogram and evoked potentials were not as helpful as mental status in assessing of recovery. Psychometric test scores remained abnormal after recovery of mental status (21 to 42 days) and were probably too sensitive for monitoring of these patients. The incidence of side effects was similar in the two treatment groups. The cost of lactulose for one course of therapy was 30 times that of sodium benzoate. We conclude that sodium benzoate is a safe and effective alternative to lactulose in the treatment of acute portasystemic encephalopathy.
Snakes, shapes, and gradient vector flow (1998)

Snakes, or active contours, are used extensively in computer vision and image processing applications, particularly to locate object boundaries. Problems associated with initialization and poor convergence to boundary concavities, however, have limited their utility. This paper presents a new external force for active contours, largely solving both problems. This external force, which we call gradient vector flow (GVF), is computed as a diffusion of the gradient vectors of a gray-level or binary edge map derived from the image. It differs fundamentally from traditional snake external forces in that it cannot be written as the negative gradient of a potential function, and the corresponding snake is formulated directly from a force balance condition rather than a variational formulation. Using several two-dimensional (2-D) examples and one three-dimensional (3-D) example, we show that GVF has a large capture range and is able to move snakes into boundary concavities.
Increased CSF F 2 -isoprostane concentration in probable AD (1999)

Increased CSF F2-isoprostanes are not an inevitable consequence of neurodegeneration and suggest that increased brain oxidative damage may occur early in the course of AD.