gebhart/patrepeval huggingface dataset:
Proteomic technologies for prenatal diagnostics: advances and challenges ahead (2009)

Proteomics-based identification of biomarkers for fetal abnormalities in maternal plasma, amniotic fluid and reproductive fluids has made significant progress in the past 5 years. This is attributed mainly to advances in various technology platforms associated with mass spectrometry-based techniques. As these techniques are highly sensitive and require only small quantities of body fluids, it is hoped that they will pave the way for the development of effective noninvasive approaches, without subjecting the developing fetus to the same degree of harm as current invasive procedures (e.g., amniocentesis). It is possible that these developments will include same-day analyses, thereby permitting rapid intervention when necessary. To date, a host of body fluids, such as maternal serum and plasma, amniotic fluid, cervical fluid, vaginal fluid, urine, saliva or fetal material, such as placental trophoblast, fetal membranes or cord blood, have been used successfully in the quest to develop markers for a number of pregnancy-related pathologies. In the current review update we focus on the emergence of proteomics as a major platform technology in studying various types of fetal conditions and developing markers for pregnancy-related disorders, such fetal aneuploidy, preterm birth, preeclampsia, intra-amniotic infection and fetal stress. Should the development of these markers be successful, then it is to be envisaged that proteomic approaches will become standard of care for a number of disease conditions associated with feto-maternal health.
Comparative effectiveness of full‐length and B‐domain deleted factor VIII for prophylaxis – a meta‐analysis (2003)

Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.
Mutational analysis of alpha-subunit of protein farnesyltransferase. Evidence for a catalytic role. (1993)

Protein farnesyltransferase from rat brain is composed of tightly associated alpha- and beta-subunits of 377 and 437 amino acids that migrate on SDS-polyacrylamide gels with apparent molecular masses of 49 and 46 kDa, respectively. The enzyme attaches farnesyl groups to cysteines in p21ras and other proteins that contain cysteine residues at the fourth position from the COOH terminus. Production of stable enzyme in animal cells requires the simultaneous synthesis of both subunits, and all activity is lost when the subunits are dissociated chemically. The beta-subunit functions in the Zn(2+)-dependent binding of the protein substrate. The role of the alpha-subunit is unknown. In the current studies we used in vitro mutagenesis and transfection of cloned cDNAs to define the parts of the alpha-subunit that are necessary to stabilize the beta-subunit and to support farnesyl transfer. Deletion of 51 amino acids at the NH2 terminus of the alpha-subunit allowed normal stabilization of the beta-subunit and production of normal enzyme activity, but deletion of 106 amino acids abolished both of these properties. A proline-rich region at residues 12-34 of the alpha-subunit is not required for activity, but its presence explains the anomalously slow migration of the polypeptide on SDS-polyacrylamide gels. Deletion of only 5 amino acids at the COOH terminus of the alpha-subunit reduced activity appreciably. Substitution of asparagine for a conserved lysine at position 164 produced an alpha-subunit that stabilized the beta-subunit normally and permitted normal binding of the two substrates, farnesyl pyrophosphate and p21H-ras. Nevertheless, the rate of transfer of the bound farnesyl group to p21H-ras was markedly reduced. The latter finding suggests that the alpha-subunit plays a direct role in the catalytic reaction in addition to its role in the stabilization of the beta-subunit.
Visible Light-Gated Cobalt Catalysis for a Spatially and Temporally Resolved [2+2+2] Cycloaddition (2016)

The ability to exert spatial and temporal control over a transition-metal catalyst offers diverse opportunities for the fabrication of functional materials. Using an external stimulus such as visible light to toggle a catalyst between an active and dormant state has proven to be an effective approach for controlled, radical methodologies. Outside of radical bond formation, there is a dearth of evidence that suggests traditional transition metal catalysis can similarly be controlled with visible light energy. Many cobalt complexes that catalyze the [2+2+2] cycloaddition are assisted by UV photolysis, but strict photocontrolled methods are unattainable due to high levels of thermally driven reactivity. Herein, we disclose the first light-controlled, cobalt-catalyzed [2+2+2] cycloaddition via a dual cobalt and photoredox catalyst manifold. We demonstrate the power of this method with a spatially and temporally resolved technique for arene formation using photolithography.
Available instruction-level parallelism for superscalar and superpipelined machines (1989)

Superscalar machines can issue several instructions per cycle. Superpipelined machines can issue only one instruction per cycle, but they have cycle times shorter than the latency of any functional unit. In this paper these two techniques are shown to be roughly equivalent ways of exploiting instruction-level parallelism. A parameterizable code reorganization and simulation system was developed and used to measure instruction-level parallelism for a series of benchmarks. Results of these simulations in the presence of various compiler optimizations are presented. The average degree of superpipelining metric is introduced. Our simulations suggest that this metric is already high for many machines. These machines already exploit all of the instruction-level parallelism available in many non-numeric applications, even without parallel instruction issue or higher degrees of pipelining.
Introduction to protein crystallization (2013)

Protein crystallization was discovered by chance about 150 years ago and was developed in the late 19th century as a powerful purification tool and as a demonstration of chemical purity. The crystallization of proteins, nucleic acids and large biological complexes, such as viruses, depends on the creation of a solution that is supersaturated in the macromolecule but exhibits conditions that do not significantly perturb its natural state. Supersaturation is produced through the addition of mild precipitating agents such as neutral salts or polymers, and by the manipulation of various parameters that include temperature, ionic strength and pH. Also important in the crystallization process are factors that can affect the structural state of the macromolecule, such as metal ions, inhibitors, cofactors or other conventional small molecules. A variety of approaches have been developed that combine the spectrum of factors that effect and promote crystallization, and among the most widely used are vapor diffusion, dialysis, batch and liquid-liquid diffusion. Successes in macromolecular crystallization have multiplied rapidly in recent years owing to the advent of practical, easy-to-use screening kits and the application of laboratory robotics. A brief review will be given here of the most popular methods, some guiding principles and an overview of current technologies.
Investigations into the antibacterial activities of phytotherapeutics against Helicobacter pylori and Campylobacter jejuni (2009)

The prevalence of gastric diseases is increasing with H. pylori, the causative agent of acute and chronic gastritis, being a major predisposing factor for peptic ulcer disease and gastric carcinoma. C. jejuni is the most common cause of enteric infections, particularly among children, resulting in severe diarrhoea. Increasing drug resistance of these bacteria against standard antibiotics, and the more widespread use of herbal medicines, favours investigations into additional anti-Helicobacter and anti-Campylobacter effects of phytotherapeutics that are already used for their beneficial effects on bowel and digestive functions. Twenty-one hydroethanol herbal extracts and four essential oils were screened for antibacterial activity using a modification of a previously described micro-dilution assay and compared with the inhibitory effects of antibiotics. The herbal extracts showing the highest growth inhibition of C. jejuni were Calendula officinalis, Matricaria recutita, Zingiber officinale, Salvia officinalis, Foeniculum vulgare and Silybum marianum. Agrimonia eupatoria, Hydrastis canadensis, Filipendula ulmaria and Salvia officinalis were the most active herbal extracts in inhibiting the growth of H. pylori. This study provides evidence for additional beneficial effects of phytotherapeutics marketed for their gastrointestinal effects and identifies new beneficial antibacterial effects for some herbal medicines not currently recommended for gastrointestinal problems.
An observational assessment method for aging laboratory rats. (2010)

The rapid growth of the aging human population highlights the need for laboratory animal models to study the basic biologic processes of aging and susceptibility to disease, drugs, and environmental pollutants. Methods are needed to evaluate the health of aging animals over time, particularly methods for efficiently monitoring large research colonies. Here we describe an observational assessment method that scores appearance, posture, mobility, and muscle tone on a 5-point scale that can be completed in about 1 min. A score of 1 indicates no deterioration, whereas a score of 5 indicates severe deterioration. Tests were applied to male Brown Norway rats between 12 and 36 mo of age (n = 32). The rats were participating concurrently in experiments on the behavioral effects of intermittent exposure (approximately every 4 mo) to short-acting environmental chemicals. Results demonstrated that aging-related signs of deterioration did not appear before 18 mo of age. Assessment scores and variability then increased with age. Body weights increased until approximately 24 mo, then remained stable, but decreased after 31 mo for the few remaining rats. The incidence of death increased slightly from 20 to 28 mo of age and then rose sharply; median survival age was approximately 30 mo, with a maximum of 36 mo. The results indicate that our observational assessment method supports efficient monitoring of the health of aging rats and may be useful in studies on susceptibility to diseases, drugs, and toxicants during old age.
Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir (1997)

In the majority of cases, the mechanism underlying the resistance to acyclovir (ACV) of herpes simplex viruses (HSVs) is thymidine kinase (TK) deficiency. Plaque isolates from eight ACV-resistant (ACVr) clinical isolates from AIDS patients, of which five reactivated, were sequenced to determine the genetic lesion within the tk gene conferring resistance and whether this may have correlated with reactivation potential. Mutations were clustered within two homopolymer nucleotide stretches. Three plaque isolates (1737-14, 90-150-3, and 89-650-5) had insertion mutations within a stretch of 7 guanosines, while two isolates (89-063-1 and 89-353-1) had frameshift mutations within a stretch of 6 cytosines (a deletion and an insertion, respectively). Mutations resulted in premature termination codons, and the predicted 28- and 32-kDa truncated TK products were detected by Western blot analysis of virus-infected cell extracts. The repair of one homopolymer frameshift mutation (in isolate 1737-14) restored TK activity, demonstrating that this mutation is the basis of TK deficiency. Of the five reactivated isolates, four were TK deficient and contained frameshift mutations while the fifth retained TK activity because of its altered-TK or Pol- phenotype. These data demonstrate that the majority of ACVr clinical isolates contain frameshift mutations within two long homopolymer nucleotide stretches which function as hot spots within the HSV tk gene and produce nonfunctional, truncated TK proteins.
Rituximab-Dependent Cytotoxicity by Natural Killer Cells (2004)

The FCGR3A gene dimorphism generates two allotypes: FcgammaRIIIa-158V and FcgammaRIIIa-158F. The genotype homozygous for FcgammaRIIIa-158V (VV) is associated with higher clinical response to rituximab, a chimeric anti-CD20 IgG1 used in the treatment of B lymphoproliferative malignancies. Our objective was to determine whether this genetic association relates to rituximab-dependent cytotoxicity mediated by FcgammaRIIIa/CD16a+ cells. The number of CD16+ circulating monocytes, T cells, and natural killer (NK) cells in 54 donors was first shown to be unrelated to FCGR3A polymorphism. We then demonstrated that FcgammaRIIIa-158V displays higher affinity for rituximab than FcgammaRIIIa-158F by comparing rituximab concentrations inhibiting the binding of 3G8 mAb (anti-CD16) with VV NK cells and NK cells homozygous for FcgammaRIIIa-158F (FF). VV and FF NK cells killed Daudi cells similarly after FcgammaRIIIa engagement by saturating concentrations of rituximab or 3G8. However, the rituximab concentration resulting in 50% lysis (EC(50)) observed with NK cells from VV donors was 4.2 times lower than that observed with NK cells from FF donors (on average 0.00096 and 0.00402 microg/ml, respectively, P = 0.0043). Finally, the functional difference between VV and FF NK cells was restricted to rituximab concentrations weakly sensitizing CD20. This study supports the conclusion that FCGR3A genotype is associated with response to rituximab because it affects the relationship between rituximab concentration and NK cell-mediated lysis of CD20+ cells. Rituximab administration could therefore be adjusted according to FCGR3A genotype.
Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III) (2014)

Bortezomib is an active agent in AL amyloidosis and responses to this drug in combination with cyclophosphamide and dexamethasone are both rapid and deep. Here we present an international, multicenter series of 60 patients with Mayo Clinic stage III cardiac amyloidosis to assess the impact of this regimen in improving outcomes in this poor-risk group. The median follow-up for the entire cohort is 11.8 months. The overall response rate was 68%. In a landmark analysis, examining patients who survived more than 3 months, the overall response rate was 86%. A cardiac response was seen in 32% of patients. The estimated 1-year survival rate for the whole cohort was 57% and 24 patients (40%) died while on therapy. Although unable to save the poorest risk patients, the combination of bortezomib, cyclophosphamide and dexamethasone can achieve a high number of hematologic and cardiac responses, likely improving overall survival and justifying a prospective trial.
Novel Orally Swallowable IntelliCap® Device to Quantify Regional Drug Absorption in Human GI Tract Using Diltiazem as Model Drug (2014)

Typically, colonic absorption of a drug is mandatory for a sustained release formulation to hold the drug's plasma level for more than 12 or 24 h above the minimum therapeutic plasma concentration (efficacy). According to Drugs@FDA, only 7.4% of the oral drugs are extended release forms probably showing colonic absorption. Therefore an early determination of a drug's colonic absorption using the IntelliCap® in animals or humans will provide the mandatory information to initiate or stop a SR form development. Diltiazem (60 mg) is used in the oral swallowable IntelliCap® and the marketed SR form from Mylan (coated beads). A human study with 14 healthy volunteers compared the Mylan formulation with the IntelliCap® device that releases the drug identical to the in-vitro dissolution of the Mylan product. The plasma profiles of IntelliCap® and Mylan formulation are highly similar. The mean AUC (bioequivalence fulfilled) and mean Cmax of IntelliCap® shows only a difference of +15% and -12%, respectively. But the PK profile of the Mylan formulation shows a broader peak around Cmax. About 81.8% diltiazem was absorbed in the colon (IntelliCap®) comparable to former publications. The Mylan is a SR diffusion coated beads form whereas the IntelliCap® is a monolithic capsule. The beads are transported in the gut and spread which results in a longer Tmax and a broader Cmax peak. The IntelliCap® device can quantitatively measure the colonic absorption of a drug in excellent accordance to a standard oral SR dosage form.
Insulin resistance: an independent risk factor for cardiovascular disease? (1999)

Population-based studies have shown that patients with type 2 diabetes have a higher cardiovascular morbidity and mortality and an increased all-cause mortality compared with non-diabetic subjects. In non-diabetic subjects, hyperinsulinaemia not only has been associated with an increased cardiovascular risk, but is also related with a number of other cardiovascular risk factors--hyperglycaemia, hypertension, dyslipidaemia, and a central body fat distribution--that constitute the insulin resistance syndrome and are also characteristic of type 2 diabetes. After 23 years of follow-up in the Paris Prospective Study, both fasting and 2-h insulin concentrations were related with all-cause mortality in a U-shaped fashion, with low and high concentrations being associated with an increased risk, independently of other risk factors; in contrast, while high insulin levels carried an increased risk for cardiovascular and coronary heart disease mortality, this was not independent of other risk factors.
Robust Face Localisation Using Motion, Colour and Fusion. (2003)

Abstract. Face detection is fundamental for several important applications, such as, face recognition and human-computer interaction. This paper details a novel hierarchical face detector which combines motion, colour and late fusion. Motion segmentation is employed to eliminate background clutter and to reduce the initial search space. Subsequently, skin segmentation is used to determine a candidate face. Five simple eye-detection algorithms are fused to robustly localise the eyes within the candidate. Fusion is beneficial because the large amount of variation within the face makes it difficult for any individual technique to perform well under all conditions. The resulting system is capable of localising faces from still images in real-time with an accuracy of 93.75%. 1
Concurrency Control in Distributed Database Systems (1981)

article Free Access Share on Concurrency Control in Distributed Database Systems Authors: Philip A. Bernstein Computer Corporation of America, Cambridge, Massachusetts Computer Corporation of America, Cambridge, MassachusettsView Profile , Nathan Goodman Computer Corporation of America, Cambridge, Massachusetts Computer Corporation of America, Cambridge, MassachusettsView Profile Authors Info & Claims ACM Computing SurveysVolume 13Issue 2June 1981 pp 185–221https://doi.org/10.1145/356842.356846Online:01 June 1981Publication History 796citation11,051DownloadsMetricsTotal Citations796Total Downloads11,051Last 12 Months568Last 6 weeks91 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Reed-Sternberg Cell Genome Expression Supports a B-Cell Lineage (1999)

The malignant Reed-Sternberg cell of Hodgkin's disease, first described a century ago, has resisted in-depth analysis due to its extreme rarity in lymphomatous tissue. To directly study its genome-wide gene expression, approximately 11,000,000 bases (27,518 cDNA sequences) of expressed gene sequence was determined from living single Reed-Sternberg cells, Hodgkin's tissue, and cell lines. This approach increased the number of genes known to be expressed in Hodgkin's disease by 20-fold to 2,666 named genes. The data here indicate that Reed-Sternberg cells from both nodular sclerosing and lymphocyte predominant Hodgkin's disease were derived from an unusual B-cell lineage based on a comparison of their gene expression to approximately 40,000,000 bases (10(5) sequences) of expressed gene sequence from germinal center B cells (GCB) and dendritic cells. The data set of expressed genes, reported here and on the World Wide Web, forms a basis to understand the genes responsible for Hodgkin's disease and develop novel diagnostic markers and therapies. This study of the rare Reed-Sternberg cell, concealed in its heterogenous cellular context, also provides a formidable test case to advance the limit of analysis of differential gene expression to the single disease cell.
Advances of Cancer Therapy by Nanotechnology (2009)

Recent developments in nanotechnology offer researchers opportunities to significantly transform cancer therapeutics. This technology has enabled the manipulation of the biological and physicochemical properties of nanomaterials to facilitate more efficient drug targeting and delivery. Clinical investigations suggest that therapeutic nanoparticles can enhance efficacy and reduced side effects compared with conventional cancer therapeutic drugs. Encouraged by rapid and promising progress in cancer nanotechnology, researchers continue to develop novel and efficacious nanoparticles for drug delivery. The use of therapeutic nanoparticles as unique drug delivery systems will be a significant addition to current cancer therapeutics.