gebhart/patrepeval huggingface dataset:
Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule (2004)

The potential benefits of extended rituximab treatment have been investigated in a randomized trial comparing the standard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma (FL). All patients received standard treatment (rituximab 375 mg/m(2) weekly x 4). In 185 evaluable patients, the overall response rate was 67% in chemotherapy-naive patients and 46% in pretreated cases (P &lt;.01). Patients responding or with stable disease at week 12 (n = 151) were randomized to no further treatment or prolonged rituximab administration (375 mg/m(2) every 2 months for 4 times). At a median follow-up of 35 months, the median event-free survival (EFS) was 12 months in the no further treatment versus 23 months in the prolonged treatment arm (P =.02), the difference being particularly notable in chemotherapy-naive patients (19 vs 36 months; P =.009) and in patients responding to induction treatment (16 vs 36 months; P =.004). The number of t(14;18)-positive cells in peripheral blood (P =.0035) and in bone marrow (P =.0052) at baseline was predictive for clinical response. Circulating normal B lymphocytes and immunoglobulin M (IgM) plasma levels decreased for a significantly longer time after prolonged treatment, but the incidence of adverse events was not increased. In patients with FL, the administration of 4 additional doses of rituximab at 8-week intervals significantly improves the EFS.
Modulation of Vascular Smooth Muscle Contraction by the Endothelium (1986)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans (2002)

Polyunsaturated fatty acids (PUFAs) are important membrane components and precursors of signaling molecules. To investigate the roles of these fatty acids in growth, development, and neurological function in an animal system, we isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct analysis of fatty acid composition. C. elegans possesses all the desaturase and elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from saturated fatty acid precursors. In our screen we identified mutants with defects in each fatty acid desaturation and elongation step of the PUFA biosynthetic pathway. The fatty acid compositions of the mutants reveal the substrate preferences of the desaturase and elongase enzymes and clearly demarcate the steps of this pathway. The mutants show that C. elegans does not require n3 or Delta5-unsaturated PUFAs for normal development under laboratory conditions. However, mutants with more severe PUFA deficiencies display growth and neurological defects. The mutants provide tools for investigating the roles of PUFAs in membrane biology and cell function in this animal model.
Flexible cross layer optimization for fixed and mobile broadband telecommunication networks and beyond (2014)

In der heutigen Zeit, in der das Internet im Allgemeinen und Telekommunikationsnetze im Speziellen kritische Infrastrukturen erreicht haben, entstehen hohe Anforderungen und neue Herausforderungen an den Datentransport in Hinsicht auf Effizienz und Flexibilität. Heutige Telekommunikationsnetze sind jedoch rigide und statisch konzipiert, was nur ein geringes Maß an Flexibilität und Anpassungsfähigkeit der Netze ermöglicht und darüber hinaus nur im begrenzten Maße die Wichtigkeit von Datenflüssen im wiederspiegelt. Diverse Lösungsansätze zum kompletten Neuentwurf als auch zum evolutionären Konzept des Internet wurden ausgearbeitet und spezifiziert, um diese neuartigen Anforderungen und Herausforderungen adäquat zu adressieren. Einer dieser Ansätze ist das Cross Layer Optimierungs-Paradigma, welches eine bisher nicht mögliche direkte Kommunikation zwischen verteilten Funktionalitäten unterschiedlichen Typs ermöglicht, um ein höheres Maß an Dienstgüte zu erlangen. Ein wesentlicher Indikator, welcher die Relevanz dieses Ansatzes unterstreicht, zeichnet sich durch die Programmierbarkeit von Netzwerkfunktionalitäten aus, welche sich aus der Evolution von heutigen hin zu zukünftigen Netzen erkennen lässt. Dieses Konzept wird als ein vielversprechender Lösungsansatz für Kontrollmechanismen von Diensten in zukünftigen Kernnetzwerken erachtet. Dennoch existiert zur Zeit der Entstehung dieser Doktorarbeit kein Ansatz zur Cross Layer Optimierung in Festnetz-und Mobilfunknetze, welcher der geforderten Effizienz und Flexibilität gerecht wird. Die übergeordnete Zielsetzung dieser Arbeit adressiert die Konzeptionierung, Entwicklung und Evaluierung eines Cross Layer Optimierungsansatzes für Telekommunikationsnetze. Einen wesentlichen Schwerpunkt dieser Arbeit stellt die Definition einer theoretischen Konzeptionierung und deren praktischer Realisierung eines Systems zur Cross Layer Optimierung für Telekommunikationsnetze dar. Die durch diese Doktorarbeit analysierten wissenschaftlichen Fragestellungen betreffen u.a. die Anwendbarkeit von Cross Layer Optimierungsansätzen auf Telekommunikationsnetzwerke; die Betrachtung neuartiger Anforderungen; existierende Konzepte, Ansätze und Lösungen; die Abdeckung neuer Funktionalitäten durch bereits existierende Lösungen; und letztendlich den erkennbaren Mehrwert des neu vorgeschlagenen Konzepts gegenüber den bestehenden Lösungen. Die wissenschaftlichen Beiträge dieser Doktorarbeit lassen sich grob durch vier Säulen skizzieren: Erstens werden der Stand der Wissenschaft und Technik analysiert und bewertet, Anforderungen erhoben und eine Lückenanalyse vorgenommen. Zweitens werden Herausforderungen, Möglichkeiten, Limitierungen und Konzeptionierungsaspekte eines Modells zur Cross Layer Optimierung analysiert und evaluiert. Drittens wird ein konzeptionelles Modell - Generic Adaptive Resource Control (GARC) - spezifiziert, als Prototyp realisiert und ausgiebig validiert. Viertens werden theoretische und praktische Beiträge dieser Doktorarbeit vertiefend analysiert und bewertet.
Adaptation of the Yeast URA3 Selection System to Gram-Negative Bacteria and Generation of a Δ betCDE Pseudomonas putida Strain (2005)

A general procedure for efficient generation of gene knockouts in gram-negative bacteria by the adaptation of the Saccharomyces cerevisiae URA3 selection system is described. A Pseudomonas putida strain lacking the URA3 homolog pyrF (encoding orotidine-5'-phosphate decarboxylase) was constructed, allowing the use of a plasmid-borne copy of the gene as the target of selection. The delivery vector pTEC contains the pyrF gene and promoter, a conditional origin of replication (oriR6K), an origin of transfer (mobRK2), and an antibiotic selection marker flanked by multiple sites for cloning appropriate DNA segments. The versatility of pyrF as a selection system, allowing both positive and negative selection of the marker, and the robustness of the selection, where pyrF is associated with uracil prototrophy and fluoroorotic acid sensitivity, make this setup a powerful tool for efficient homologous gene replacement in gram-negative bacteria. The system has been instrumental for complete deletion of the P. putida choline-O-sulfate utilization operon betCDE, a mutant which could not be produced by any of the other genetic strategies available.
Definition of a domain of GLVR1 which is necessary for infection by gibbon ape leukemia virus and which is highly polymorphic between species (1993)

Expression of human GLVR1 in mouse cells confers susceptibility to infection by gibbon ape leukemia virus (GALV), while the normally expressed mouse Glvr-1 does not. Since human and murine GLVR1 proteins differ at 64 positions in their sequences, some of the residues differing between the two proteins are critical for infection. To identify these, a series of hybrids and in vitro-constructed mutants were tested for the ability to confer susceptibility to infection. The results indicated that human GLVR1 residues 550 to 551, located in a cluster of seven of the sites that differ between the human and mouse proteins, are the only residues differing between the two which must be in the human protein form to allow infection. Sequencing of a portion of GLVR1 from the rat (which is infectible) confirmed the importance of this cluster in that it contained the only notable differences between the rat and mouse proteins. This region, which also differs substantially between the rat and the human proteins, therefore exhibits a pronounced tendency for polymorphism.
The Study of High-Affinity TCRs Reveals Duality in T Cell Recognition of Antigen: Specificity and Degeneracy (2006)

TCRs exhibit a high degree of Ag specificity, even though their affinity for the peptide/MHC ligand is in the micromolar range. To explore how Ag specificity is achieved, we studied murine T cells expressing high-affinity TCRs engineered by in vitro evolution for binding to hemoglobin peptide/class II complex (Hb/I-Ek). These TCRs were shown previously to maintain Ag specificity, despite having up to 800-fold higher affinity. We compared the response of the high-affinity TCRs and the low-affinity 3.L2 TCR toward a comprehensive set of peptides containing single substitutions at each TCR contact residue. This specificity analysis revealed that the increase in affinity resulted in a dramatic increase in the number of stimulatory peptides. The apparent discrepancy between observed degeneracy in the recognition of single amino acid-substituted Hb peptides and overall Ag specificity of the high-affinity TCRs was examined by generating chimeric peptides between the stimulatory Hb and nonstimulatory moth cytochrome c peptides. These experiments showed that MHC anchor residues significantly affected TCR recognition of peptide. The high-affinity TCRs allowed us to estimate the affinity, in the millimolar range, of immunologically relevant interactions of the TCR with peptide/MHC ligands that were previously unmeasurable because of their weak nature. Thus, through the study of high-affinity TCRs, we demonstrated that a TCR is more tolerant of single TCR contact residue substitutions than other peptide changes, revealing that recognition of Ag by T cells can exhibit both specificity and degeneracy.
Differential Regulation ofSalmonella typhimuriumType III Secreted Proteins by Pathogenicity Island 1 (SPI-1)-Encoded Transcriptional Activators InvF and HilA (1999)

Salmonella enterica encodes a type III protein secretion system within a pathogenicity island (SPI-1) that is located at centisome 63 of its chromosome. This system is required for the ability of these bacteria to stimulate cellular responses that are essential for their pathogenicity. Expression of components and substrates of this system is subject to complex regulatory mechanisms. These mechanisms involve the function of HilA and InvF, two transcriptional regulatory proteins encoded within SPI-1. In this study, we examined the functional relationship between these two regulatory proteins. We found that strains carrying loss-of-function mutations in either hilA or invF differ in their ability to stimulate cellular responses. An S. typhimurium hilA mutant strain retained considerable signaling capacity that resulted in significant levels of internalization into host cells. In contrast, introduction of a nonpolar loss-of-function mutation in invF rendered S. typhimurium significantly impaired in its ability to enter host cells. Consistent with these different phenotypes, we found that HilA and InvF control the expression of different genes. HilA regulates the expression of components of the type III secretion machinery, whereas InvF controls the expression of type III secreted proteins encoded outside of SPI-1. We also found that the expression of secreted proteins encoded within SPI-1 are under the control of both HilA and InvF. Our results therefore indicate that InvF and HilA differentially control the expression of components and substrates of the invasion-associated type III secretion system.
The cell cycle of parasitic protozoa: potential for chemotherapeutic exploitation. (2003)

There is an urgent need to develop new drugs against eukaryotic parasitic protozoa such as Plasmodium, Trypanosoma and Leishmania, which cause the diseases malaria, trypanosomiasis and the leishmaniases respectively. The biology of these organisms has many unusual facets that might be exploited for drug design, and the recent availability of parasite genome sequence data has facilitated the search for novel drug targets. Here we review current understanding of the cell cycle in these parasites and show that important structural and functional differences exist between parasite and mammalian cell cycle control machineries and signal transduction pathways, which might be utilised for rational drug design. Potential targets include protein kinases from the cyclin-dependent kinase, cAMP-dependent kinase and mitogen activated protein kinase families.
Economic Change and the Redistribution of Power Among Women in Yemen: A Focus on the Treatment of Domestic Workers (2015)

A shared female identity does not promise solidarity among women in capitalist society. Exploring the prejudices held by Yemeni women over domestic workers exposes class related inequities among women. Recent economic change in Yemen showcases the crystallization of class while local gender identities morph in accordance to overarching capitalist demands. The presence of marginalized domestic workers in upper-class Yemeni homes demonstrates the mutually informative relationship between class status and gender identity. Paralleling greater Yemeni hierarchical and patriarchal society, Yemeni women assert class privilege over low-income domestic workers. Of extreme relevance to better understanding gender and Islam, I argue that Yemeni women of distinguished class status possess and exercise control over the lives of migrant women, thus challenging perceived Yemeni gender roles that acknowledge men as dominant and women as submissive. Cemented by a preexisting drive to preserve familiar honor and fueled by recent economic change, upper-class Yemeni women problematize the “cultural closeness” of lower-class migrant, domestic workers through the formation of stereotypes.
The P2Y(2) receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat. (2002)

These findings indicate that INS37217 stimulates the RPE fluid "pump" function in vitro by activating P2Y(2) receptors at the apical membrane. In vivo INS37217 enhances the rates of subretinal fluid reabsorption in experimentally induced retinal detachments in rats and may be therapeutically useful for treating a variety of retinal diseases that result in fluid accumulation in the subretinal space.
An overview of biochemical markers in acute coronary syndromes (2001)

The cardiac troponins (cTns), cTnT and cTnI, are currently regarded as being the most useful diagnostic and prognostic biochemical markers of myocardial damage in patients with suspected acute coronary syndromes (ACSs). In spite of the evidence-based nature of this observation, the uptake of serum cTn measurement in routine clinical practice--in both the UK and elsewhere, is patchy, indeed, there still exists wide variability in the range of testing and sampling strategies involving usage of the many existing cardiac markers. For evaluating suspected acute myocardial infarction (AMI) and other ACSs, international opinion favours either serum cTnT or cTnI (measured 12-24 h after admission to the emergency room)--together with a short-time window marker such as serum creatine kinase (CK) (measured on admission and perhaps again within the 12-24 h window). Translation of this strategy into universal clinical practice would require not only formulation of, but also strict adherence to, agreed clinical decision-making protocols which, in turn, would need to be backed by adequate funding.
Streptokinase for Acute Ischemic Stroke With Relationship to Time of Administration (1996)

<h3>Objectives.</h3> —To determine whether the administration of 1.5 million units of streptokinase intravenously within 4 hours of the onset of acute ischemic stroke would reduce morbidity and mortality at 3 months and whether outcomes may be better for those receiving therapy within 3 hours of stroke onset compared with those receiving it after 3 hours. <h3>Design.</h3> —Randomized, double-blind, placebo-controlled trial with 3-month follow-up. <h3>Participants.</h3> —A total of 340 patients, aged 18 to 85 years, with moderate to severe strokes were randomized from 40 centers throughout Australia from June 1992 to November 1994. <h3>Intervention.</h3> —Administration of 1.5 million units of streptokinase or placebo intravenously in 100 mL of normal saline over 1 hour. <h3>Main Outcome Measure.</h3> —Combined death and disability score (Barthel index &lt;60) 3 months after the stroke. <h3>Results.</h3> —Using an intention-to-treat analysis with a combined death and disability score at 3 months after stroke as the primary end point, we found a nonsignificant overall trend toward unfavorable outcomes for streptokinase vs placebo (relative risk [RR] of unfavorable outcome, 1.08; 95% confidence interval [CI], 0.74-1.58) and an excess of hematomas (13.2% [12.6% symptomatic] in the treated group, 3% [2.4% symptomatic] for placebo [<i>P</i>&lt;.01] ). However, poor outcomes were confined to patients receiving therapy more than 3 hours after stroke onset (RR of unfavorable outcome, 1.22; 95% CI, 0.80-1.86). In contrast, among the 70 patients who were entered into the trial within 3 hours of stroke onset, there was a trend toward improved outcomes for those who received streptokinase (RR of unfavorable outcome, 0.66; 95% CI, 0.28-1.58), and this outcome pattern was significantly better than for those receiving therapy after 3 hours (<i>P</i>=.04). Streptokinase administration resulted in excess deaths in the group treated after 3 hours (RR, 1.98; 95% CI, 1.18-3.35), but not among those treated within 3 hours (RR, 1.11; 95% CI, 0.38-3.21). <h3>Conclusion.</h3> —The administration of streptokinase within 4 hours of acute ischemic stroke increased morbidity and mortality at 3 months. While treatment within 3 hours of stroke was safer and associated with significantly better outcomes than later treatment, it showed no significant benefit over placebo. The timing of thrombolytic therapy for acute stroke is critical.
Immunostimulatory DNA induces degranulation and NADPH-oxidase activation in human neutrophils while concomitantly inhibiting chemotaxis and phagocytosis (2002)

We examined the effects of oligodeoxynucleotides (ODN) with different structures and sequences on human neutrophil function. In lymphocytes and monocytes, the CpG-mediated immunostimulation is dependent on motif content, flanking sequences and DNA backbone composition. In neutrophils, however, native phosphodiester ODN were without effect regardless of CpG content, while backbone-substituted phosphorothioate ODN (PS-ODN) modulated neutrophil function in a sequence-independent manner. The neutrophil respiratory burst and degranulation of the specific and gelatinase granules were markedly increased by PS-ODN, as was the shedding of L-selectin. In contrast, neutrophil chemotaxis and phagocytosis were inhibited by PS-ODN. In summary, PS-ODN have both stimulatory and inhibitory effects on neutrophil function. This impact of PS-ODN on neutrophil function is unique and distinct from that exerted on other immune cells, with respect to both the identity of the activating DNA molecules and the regulation of the effector functions. These findings may have implications for the development of DNA-based immunotherapy and vaccination.
Optimized extract preparation methods and reaction conditions for improved yeast cell‐free protein synthesis (2013)

Cell-free protein synthesis (CFPS) has emerged as a powerful platform technology to help satisfy the growing demand for simple, affordable, and efficient protein production. In this article, we describe a novel CFPS platform derived from the popular bio-manufacturing organism Saccharomyces cerevisiae. By developing a streamlined crude extract preparation protocol and optimizing the CFPS reaction conditions we were able to achieve active firefly luciferase synthesis yields of 7.7 ± 0.5 µg mL(-1) with batch reactions lasting up to 2 h. This duration of synthesis is the longest ever reported for a yeast CFPS batch reaction. Furthermore, by removing extraneous processing steps and eliminating expensive reagents from the cell-free reaction, we have increased relative product yield (µg protein synthesized per $ reagent cost) over an alternative commonly used method up to 2000-fold from ∼2 × 10(-4) to ∼4 × 10(-1) µg $(-1) , which now puts the yeast CPFS platform on par with other eukaryotic CFPS platforms commercially available. Our results set the stage for developing a yeast CFPS platform that provides for high-yielding and cost-effective expression of a variety of protein therapeutics and protein libraries.
Progress towards the easier use of P450 enzymes (2006)

The cytochrome P450 enzymes (P450s or CYPs) form a large family of heme proteins involved in drug metabolism and in the biosynthesis of steroids, lipids, vitamins and natural products. Their remarkable ability to catalyze the insertion of oxygen into non-activated C-H bonds has attracted the interest of chemists for several decades. Very few chemical methods exist that directly hydroxylate aliphatic or aromatic C-H bonds, and most of them are not selective or of limited scope. Biocatalysts such as P450s represent a promising alternative: however, their applications have been limited by substrate specificity, low activity, poor stability and the need for cofactors. This review covers the attempts to overcome these limitations using approaches such as mutagenesis, chemical modifications, conditions engineering and immobilization.
Use of Cell-SELEX to Generate DNA Aptamers as Molecular Probes of HPV-Associated Cervical Cancer Cells (2012)

Using AC-SELEX we have generated several aptamers that have high affinity and specificity to the nontumorigenic, revertant of HPV-transformed cervical cancer cells. These aptamers can be used to identify new biomarkers that are related to carcinogenesis. Panels of aptamers, such as these may be useful in predicting the tumorigenic potential and properties of cancer biopsies and aid in the effective management of pathological conditions (diagnosis, predicted outcome, and treatment options).
The 'elephant trunk' manipulator, design and implementation (2002)

Over that last several years, research in the area of hyper-redundant robots and those robots based on tentacle/trunk type manipulators has become of great interest. Though much progress has been obtained in both the areas of robot construction and robot kinematics, there has been little progress in the implementation of a kinematic model for motion on a physical robot. We review both our 'elephant trunk' robot's construction and our previously designed kinematic model. We provide experimental results verifying not only the legitimacy of our kinematic model, but also the real time implementation of the model on the physical robot.