gebhart/patrepeval huggingface dataset:
Synthesis and selective cleavage of an oligodeoxynucleotide containing a bridged intemucleotide 5′-phosphorothioate linkage (1991)

A self complementary oligodeoxynucleotide dodecamer containing an achiral bridged 5'-phosphorothioate linkage 3'-O-P-S-5' has been prepared using the solid phase phosphoramidite procedure. For the incorporation of the phosphorothioate link we have used a 5'-(S-trityl)-mercapto-5'-deoxythymidine-3'-phosphoramidite. After coupling this building block the S-trityl group was removed by silver ions. The free thiol moiety was then coupled with a standard phosphoramidite in the presence of tetrazole. After oxidation of the 5'-phosphorothioite with iodine/water the synthesis was continued with standard building blocks up to the desired dodecamer. This backbone modified dodecamer can be cleaved selectively and quantitatively at the P-S bond by silver or mercuric ions under very mild conditions.
Myasthenia Gravis Seronegative for Acetylcholine Receptor Antibodies (2008)

Antibodies to muscle-specific kinase (MuSK) are found in a variable proportion of patients with myasthenia without typical acetylcholine receptor (AChR) antibodies, but their characteristics and pathogenic mechanisms are not fully understood. We discuss the incidence and pathogenicity of MuSK antibodies and how clinical studies, animal models, and cultured cell lines can be used to elucidate their pathogenic mechanisms. Patients without either AChR or MuSK antibodies (seronegative myasthenia) appear to present another disease subtype that is highly similar to that of typical myasthenia gravis. We demonstrate a new method that detects AChR antibodies in these patients and show that these low-affinity AChR antibodies are predominantly IgG1 and can activate complement C3b deposition. Similarly MuSK antibodies, although mainly IgG4, are partially IgG1 and can activate C3b deposition. Overall, these results suggest that complement-activation may be an important pathogenic mechanism even in patients without conventional AChR antibodies.
Docetaxel (Taxotere®) a review of preclinical and clinical experience. Part I (1995)

Docetaxel is a taxoid which is currently in phase II/III clinical trials in Europe, the US and Japan. It was found to promote tubulin assembly in microtubules and to inhibit their depolymerization. In vitro, the docetaxel concentrations required to reduce murine and human cell survival by 50% ranged from 4 to 35 ng/ml and the cytotoxic effects were greater on proliferating than on non-proliferating cells. It was also found to be cytotoxic on fresh human tumor biopsies. In vivo, the drug was found to be schedule independent. A total of 13/14 murine transplantable tumors were found very sensitive to i.v. docetaxel and complete regressions of advanced stage tumors were obtained. Activity was also observed in 15/16 human tumor xenografts in nude mice at an advanced stage. In combination studies, synergism was observed in vivo with 5-fluorouracil, cyclophosphamide and etoposide. Pharmacokinetic evaluation revealed linear pharmacokinetics in tumor-bearing mice. There was a good tumor retention with a 22 h elimination half-life. Plasma protein binding ranged from 76 to 89%. Preclinical toxicology evaluation of docetaxel included single-dose toxicity in rats, mice and dogs, 5-day toxicity in mice and dogs, intermittent-dose toxicity in rats, dogs and monkeys, genetic and reproductive toxicity, as well as investigation of the irritation and sensitization potential. The principal toxicities were hematopoietic (all species), gastrointestinal (dog, monkey) and neuromotor (mice). Dogs appeared to be the most sensitive species. The clinical entry dose of 5 mg/m2 was based on one-third of the 'toxic dose low' in dogs (15 mg/m2).
Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals (2005)

The immunodeficiency that follows HIV infection is related to the virus-mediated killing of infected CD4(+) T cells, the chronic activation of the immune system, and the impairment of T cell production. In this study we show that in HIV-infected individuals the loss of IL-7R (CD127) expression defines the expansion of a subset of CD8(+) T cells, specific for HIV as well as other Ags, that show phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in activated and/or proliferating cells) as well as functional (i.e., production of IFN-gamma, but not IL-2, decreased ex vivo proliferative potential and increased susceptibility to apoptosis) features of effector T cells. Importantly, in HIV-infected individuals the levels of CD8(+)CD127(-) T cells are directly correlated with the main markers of disease progression (i.e., plasma viremia and CD4(+) T cell depletion) as well as with the indices of overall T cell activation. In all, these results identify the expansion of CD8(+)CD127(-) effector-like T cells as a novel feature of the HIV-associated immune perturbation. Further studies are thus warranted to determine whether measurements of CD127 expression on CD8(+) T cells may be useful in the clinical management of HIV-infected individuals.
The Epidemiology and Attributable Outcomes of Candidemia in Adults and Children Hospitalized in the United States: A Propensity Analysis (2005)

The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children.
Detection of mitochondrial genome depletion by a novel cDNA in renal cell carcinoma. (1996)

A cDNA isolated by a subtractive hybridization procedure detected loss of mtDNA and the mRNA coding for NADH dehydrogenase subunit 3 in 8 of 13 tumor kidney tissues obtained from patients with renal cell carcinoma. Sequencing revealed a stretch of nucleotides homologous to the mitochondrial NADH dehydrogenase subunit 3 gene in the middle of the cDNA. The depletion phenomenon was also observed in five of six renal carcinoma cell lines. In the case of a benign renal oncocytoma, however, the mtDNA content was increased 200% more than that of the adjacent normal tissue. The frequency with which this phenomenon occurs in renal cell carcinomas, but not in other types of cancers, suggests that this may be an important phenotype associated with renal cell neoplastic transformation. However, the absence of any structural alterations within the mitochondrial genome suggests that the depletion may be a secondary event associated with the oncogenic transformation process.
Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease (1998)

Brain imaging techniques have the potential to characterize neurobiological changes that precede the onset of cognitive impairment in persons at risk for Alzheimer's disease. As previously described, positron emission tomography (PET) was used to compare 11 cognitively normal persons 50 to 62 years of age who were homozygous for the epsilon4 allele of apolipoprotein E and 22 persons without the epsilon4 allele with a reported family history of Alzheimer's dementia who were matched for sex, age, and level of education. The epsilon4 homozygotes had significantly reduced glucose metabolism in the same brain regions as patients with Alzheimer's dementia; the largest reduction was in the posterior cingulate cortex. As described here, magnetic resonance imaging (MRI) was used to compare hippocampal volumes in the same subject groups. The epsilon4 homozygotes showed nonsignificant trends for smaller left and right hippocampal volumes; overall, smaller hippocampal volumes were associated with reduced performance on a long-term memory test. Whereas PET measurements of cerebral glucose metabolism begin to decrease before the onset of memory decline, MRI measurements of hippocampal volume begin to decrease in conjunction with memory decline in cognitively normal persons at risk for Alzheimer's disease.
Clinical development of therapeutic recombinant proteins (2003)

Only a small subset of the therapeutics that enter clinical studies will prove to be safe and effective in humans and gain approval for marketing. The success of the products and, by inference, the sponsoring companies can be measured by tracking advancement through the clinical phase and review transitions to marketing approval. To determine phase transition probabilities and approval success rates for recombinant protein (rDNA) therapeutics, the Tufts Center for the Study of Drug Development collected data for 271 rDNA therapeutics that entered clinical study between 1980 and 2002. The data were stratified into eight therapeutic categories. Approval success rates were calculated for rDNA therapeutics with two possible fates: (i) approval in any country and (ii) U.S. approval only. Global approval success rates ranged from 23% to 63%, and U.S. approval success rates ranged from 17% to 58%. Trends in clinical phase lengths over five time periods and an overview of the rDNA therapeutics currently under Food and Drug Administration review are discussed.
THE EFFECTS OF THE PERFUSION OF VARIOUS SOLUTIONS ON THE NO-REFLOW PHENOMENON IN EXPERIMENTAL FREE FLAPS (1978)

The effects of solution perfusion in the free epigastric flap of the rabbit, after normothermic ischemic periods of 8 hours or 12 hours, have been examined by operative microscopic and histological methods. A smaller group of animals was also studied in which the perfusion was done before the ischemic insult. An ischemia-related obstruction to the peripheral blood flow occurred in the absence of stagnant ischemic blood in this model. Although the 3 perfusion fluids studied were shown to penetrate to all levels of a flap after such an ischemic period, none of them had a beneficial effect on skin survival. However, the solution containing mannitol did have a protective effect on fat survival. Analogies between these experimental findings and the clinical situation are made, and the importance of the early diagnosis and treatment of ischemia in a flap is emphasized.
Complex halides of the transition metals. 24. Reactions of dimeric molybdenum(II) halide complexes containing strong metal-metal bonds with bidentate tertiary phosphines and arsines. Evidence for the staggered configuration in dimers of molybdenum(II) (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComplex halides of the transition metals. 24. Reactions of dimeric molybdenum(II) halide complexes containing strong metal-metal bonds with bidentate tertiary phosphines and arsines. Evidence for the staggered configuration in dimers of molybdenum(II)Steven A. Best, Thomas J. Smith, and Richard A. WaltonCite this: Inorg. Chem. 1978, 17, 1, 99–104Publication Date (Print):January 1, 1978Publication History Published online1 May 2002Published inissue 1 January 1978https://pubs.acs.org/doi/10.1021/ic50179a022https://doi.org/10.1021/ic50179a022research-articleACS PublicationsRequest reuse permissionsArticle Views244Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer's Disease-Related Pathology (2012)

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that selectively attenuates proinflammatory cytokine production at low doses. MW-151 was tested in an APP/PS1 knock-in mouse model that exhibits increases in AD-relevant pathology progression with age, including increases in proinflammatory cytokine levels. Drug was administered during two distinct but overlapping therapeutic time windows of early stage pathology development. MW-151 treatment attenuated the increase in microglial and astrocyte activation and proinflammatory cytokine production in the cortex and yielded improvement in neurologic outcomes, such as protection against synaptic protein loss and synaptic plasticity impairment. The results also demonstrate that the therapeutic time window is an important consideration in efficacy studies of drugs that modulate glia biological responses involved in pathology progression and suggest that such paradigms should be considered in the development of new therapeutic regimens that seek to delay the onset or slow the progression of AD.
Prebiotic fibre‐incorporated whey protein crisps processed by supercritical fluid extrusion (2013)

Summary Prebiotic soluble fibre (fructooligosaccharides)‐incorporated whey protein crisps were produced by low‐shear supercritical fluid extrusion ( SCFX ), which utilises supercritical CO 2 as an expansion agent instead of steam. Protein crisps with desirable qualities were obtained with a formulation containing 8% prebiotic fibre and 60% whey protein concentrate ( WPC ‐80), which gave the final product with a protein content of 49.6% (w/w). A maximum of 70% WPC ‐80 and 8% prebiotic fibre could be incorporated to produce expanded protein crisps; however, increasing WPC ‐80 from 50% to 70% decreased the end‐product expansion ratio from 3.1 to 1.2 and increased the product hardness and piece density from 1.3 to 2.8 kN and 0.63 to 0.75 g mL −1 , respectively. Addition of 8% prebiotic fibre did not affect the textural qualities of final products. The process produced an expanded protein matrix with unique internal microstructure of uniformly distributed closed cells. Amino acid analysis indicated that 90% of the total lysine and 92% of the total essential amino acids were retained after SCFX processing and oven‐drying, indicating the preservation of protein nutritional quality during the process.
Acquiring Multiview C-Arm Images to Assist Cardiac Ablation Procedures (2010)

CARTO XP is an electroanatomical cardiac mapping system that provides 3D color-coded maps of the electrical activity of the heart; however it is expensive and it can only use a single costly magnetic catheter for each patient intervention. Our approach consists of integrating fluoroscopic and electrical data from the RF catheters into the same image so as to better guide RF ablation, shorten the duration of this procedure, increase its efficacy, and decrease hospital cost when compared to CARTO XP. We propose a method that relies on multi-view C-arm fluoroscopy image acquisition for (1) the 3D reconstruction of the anatomical structure of interest, (2) the robust temporal tracking of the tip-electrode of a mapping catheter between the diastolic and systolic phases and (3) the 2D/3D registration of color coded isochronal maps directly on the 2D fluoroscopy image that would help the clinician guide the ablation procedure much more effectively. The method has been tested on canine experimental data.
The thyroid hormone-induced tail resorption program during Xenopus laevis metamorphosis. (1996)

Genes that are up- and down-regulated by thyroid hormone in the tail resorption program of Xenopus laevis have been isolated by a gene expression screen, sequenced, and identified in the GenBank data base. The entire program is estimated to consist of fewer than 35 up-regulated and fewer than 10 down-regulated genes; 17 and 4 of them, respectively, have been isolated and characterized. Up-regulated genes whose function can be predicted on the basis of their sequence include four transcription factors (including one of the thyroid hormone receptors), an extracellular matrix component (fibronectin) and membrane receptor (integrin), four proteinases, a deiodinase that degrades thyroid hormone, and a protein that binds the hypothalamic corticotropin-releasing factor, which has been implicated in controlling thyroid hormone synthesis in Xenopus tadpoles. All four down-regulated genes encode extracellular proteins that are expressed in tadpole epidermis. This survey of the program provides insights into the biology of metamorphosis.
Inkjet-Mediated Gene Transfection into Living Cells Combined with Targeted Delivery (2008)

In this study a novel method of simultaneous gene transfection and cell delivery based on inkjet printing technology is described. Plasmids encoding green fluorescent protein (GFP) were coprinted with living cells (porcine aortic endothelial [PAE] cells) through the ink cartridge nozzles of modified commercial inkjet printers. Agarose gel electrophoresis analysis showed there was no obvious structural alteration or damage to these plasmids after printing. Transfection efficiency of the printed cells, determined by GFP expression, was over 10%, and posttransfection cell viability was over 90%. We showed that printing conditions, such as plasmid concentration, cartridge model, and plasmid size, influenced gene transfection efficiency. Moreover, genetically modified PAE cells were accurately delivered to target sites within a three-dimensional fibrin gel scaffold and expressed GFP in vitro and in vivo when implanted into mice. These results demonstrate that inkjet printing technology is able to simultaneously transfect genes into cells as well as precisely deliver these cell populations to target sites. This technology may facilitate the development of effective cell-based therapies by combining gene therapy with living cells that can be delivered to target sites.
High throughput genotyping technologies (2002)

A comprehensive genetic map containing several hundred microsatellite markers resulted from a large microsatellite mapping project. This was the first real study that introduced high throughput methods to the genetic community. This map and the concurrent technological advances, which will briefly be reviewed, led to further numerous mapping investigations of simple and complex diseases. The annotated draft sequence of approximately three billion base pairs (bp) of the human genome has been completed much sooner than many imagined, due to considerable technological advancements and the international enterprise that resulted. This was a major development for the genetics community, but is only the precursor to the next phase of studying and understanding the variation within the human genome. The awareness of the differences may help us understand the effects on the genetics of the variation between individuals and disease. It is these variations at the nucleotide level that determine the physiological differences, or phenotypes of each individual, including all biological functions at the cellular and body level. Single nucleotide polymorphisms (SNPs) will provide the next high density map, and be the genetic tool to study these genetic variations. There are many sources of SNPs and exhaustive numbers of methods of SNP detection to be considered. The focus in this paper will be on the merits of selected, varied SNP typing methodologies that are emerging to genotype many individuals with the required huge number of SNPs to make the study of complex diseases and pharmacogenomics a practical and economically viable option.
MicroRNAs as Potential Agents to Alter Resistance to Cytotoxic Anticancer Therapy (2007)

Tumor cells use preexisting prosurvival signaling pathways to evade the damaging and cytotoxic effects of anticancer agents. Radiation therapy is a primary form of cytotoxic anticancer treatment, but agents that successfully modify the radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene regulators that play critical roles in oncogenesis and have been found to regulate prosurvival pathways. However, there is little understanding of how cellular miRNA expression affects the response of a cancer to cytotoxic therapy and ultimately outcome. The let-7 family of miRNAs regulates expression of oncogenes, such as RAS, and is specifically down-regulated in many cancer subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer. Here, we report that the let-7 family of miRNAs is overrepresented in a class of miRNAs exhibiting altered expression in response to radiation. More strikingly, we also can create a radiosensitive state when the select let-7 family of miRNAs is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis elegans model of radiation-induced cell death, whereas decreasing their levels causes radioresistance. In C. elegans, we show that this is partly through control of the proto-oncogene homologue let-60/RAS and genes in the DNA damage response pathway. These findings are the first direct evidence that miRNAs can suppress resistance to anticancer cytotoxic therapy, a common feature of cancer cells, and suggest that miRNAs may be a viable tool to augment current cancer therapies.
Random access quantum information processors (2017)

Qubit connectivity is an important property of a quantum processor, with an ideal processor having random access -- the ability of arbitrary qubit pairs to interact directly. Here, we implement a random access superconducting quantum information processor, demonstrating universal operations on a nine-bit quantum memory, with a single transmon serving as the central processor. The quantum memory uses the eigenmodes of a linear array of coupled superconducting resonators. The memory bits are superpositions of vacuum and single-photon states, controlled by a single superconducting transmon coupled to the edge of the array. We selectively stimulate single-photon vacuum Rabi oscillations between the transmon and individual eigenmodes through parametric flux modulation of the transmon frequency, producing sidebands resonant with the modes. Utilizing these oscillations for state transfer, we perform a universal set of single- and two-qubit gates between arbitrary pairs of modes, using only the charge and flux bias of the transmon. Further, we prepare multimode entangled Bell and GHZ states of arbitrary modes. The fast and flexible control, achieved with efficient use of cryogenic resources and control electronics, in a scalable architecture compatible with state-of-the-art quantum memories is promising for quantum computation and simulation.