gebhart/patrepeval huggingface dataset:
The KSI tentacle manipulator (2002)

Robotic tentacles provide an interesting alternative to conventional rigid-link robotic arms; in certain situations, they may even be more capable. Kinetic Sciences Inc. has developed a hybrid electric-pneumatic tentacular robot called the KSI tentacle manipulator. It has variable compliance, can bend independently in two or more regions, and can extend to more than five times its contracted length. In total, the Tentacle has six degrees of freedom-or seven with the addition of a distal wrist-rotate joint. The Tentacle's unusual kinematics and inherent compliance demand new approaches to control. Three schemes are considered here: joystick-based teleoperation, inverse kinematics-based tendon length control, and machine vision-based fine position control. Under control, the Tentacle has broad potential in many applications, including teleoperated vacuuming and spray washing (for nuclear hot cell decontamination), general materials handling, agricultural harvesting, robotic refueling, and endoscopy.
On a hybrid network system of circuit switching and packet switching (1982)

Abstract This paper describes the architecture of a hybrid switching network employing both circuit switching and packet switching. The network usually operates in a packet switching mode, but, depending on the traffic conditions, it can use special control packets to temporarily change certain lines to a circuit switching mode. The change between the two switching modes is performed dynamically depending on the traffic load of the network. Also described in this paper is the concept of metapacket which can be employed in some relatively small‐scale networks to average the load of packets and to reduce data transmission time.
Evolution of Plant Defense Mechanisms (1999)

Pinoresinol-lariciresinol and isoflavone reductase classes are phylogenetically related, as is a third, the so-called "isoflavone reductase homologs." This study establishes the first known catalytic function for the latter, as being able to engender the NADPH-dependent reduction of phenylcoumaran benzylic ethers. Accordingly, all three reductase classes are involved in the biosynthesis of important and related phenylpropanoid-derived plant defense compounds. In this investigation, the phenylcoumaran benzylic ether reductase from the gymnosperm, Pinus taeda, was cloned, with the recombinant protein heterologously expressed in Escherichia coli. The purified enzyme reduces the benzylic ether functionalities of both dehydrodiconiferyl alcohol and dihydrodehydrodiconiferyl alcohol, with a higher affinity for the former, as measured by apparent Km and Vmax values and observed kinetic 3H-isotope effects. It abstracts the 4R-hydride of the required NADPH cofactor in a manner analogous to that of the pinoresinol-lariciresinol reductases and isoflavone reductases. A similar catalytic function was observed for the corresponding recombinant reductase whose gene was cloned from the angiosperm, Populus trichocarpa. Interestingly, both pinoresinol-lariciresinol reductases and isoflavone reductases catalyze enantiospecific conversions, whereas the phenylcoumaran benzylic ether reductase only shows regiospecific discrimination. A possible evolutionary relationship among the three reductase classes is proposed, based on the supposition that phenylcoumaran benzylic ether reductases represent the progenitors of pinoresinol-lariciresinol and isoflavone reductases.
PCR (Polymerase Chain Reaction) Testing for Leishmaniasis (1993)

Abstract : The disease Leishmaniasis, endemic in Africa, South West Asia, and South America, is caused by transmission of a parasite of the Leishmania species via the bite of an infected sandfly. The severity of the disease ranges from cutaneous lesions to a frequently fatal visceralization of the internal organs unless treated at an early stage. Detection of the parasiteis made difficult due to very low numbers of infected cells in peripheral blood. Existing tests for Leishmania parasite are time consuming and have high (50%) false negative rates. We report here the development of a rapid polymerase chain reaction (PCR) based diagnostic capable of detecting 1 infected cell in more than 5 mls of peripheral blood. The test has an accuracy greater than 92%, and a false negative rate of less than 8% when validated against known clinical samples. Leishmania, Polymerase chain reaction, Test, RAD I.
Characterization of a Targeting Motif for a Flagellar Membrane Protein in Leishmania enriettii (1999)

The surface membranes of eukaryotic flagella and cilia are contiguous with the plasma membrane. Despite the absence of obvious physical structures that could form a barrier between the two membrane domains, the lipid and protein compositions of flagella and cilia are distinct from the rest of the cell surface membrane. We have exploited a flagellar glucose transporter from the parasitic protozoan Leishmania enriettii as a model system to characterize the first targeting motif for a flagellar membrane protein in any eukaryotic organism. In this study, we demonstrate that the flagellar membrane-targeting motif is recognized by several species of Leishmania. Previously, we demonstrated that the 130 amino acid NH(2)-terminal cytoplasmic domain of isoform 1 glucose transporter was sufficient to target a nonflagellar integral membrane protein into the flagellar membrane. We have now determined that an essential flagellar targeting signal is located between amino acids 20 and 35 of the NH(2)-terminal domain. We have further analyzed the role of specific amino acids in this region by alanine replacement mutagenesis and determined that single amino acid substitutions did not abrogate targeting to the flagellar membrane. However, individual mutations located within a cluster of five contiguous amino acids, RTGTT, conferred differences in the degree of targeting to the flagellar membrane and the flagellar pocket, implying a role for these residues in the mechanism of flagellar trafficking.
Interaction of CD4:lck with the T cell receptor/CD3 complex induces early signaling events in the absence of CD45 tyrosine phosphatase (1992)

Antibody-mediated ligation of the CD3/T cell antigen receptor (TcR) activates phospholipase C (PLC) via a tyrosine kinase signaling pathway that requires expression of the transmembrane tyrosine phosphatase CD45. In normal T cells, CD3-mediated PLC activation is significantly augmented by co-ligation of CD3 with the CD4 co-receptor; however, unlike CD3-associated tyrosine kinases, antibody-induced activation of the CD4-associated tyrosine kinase p56lck does not require CD45 expression. To explore the role of CD45 in the CD3 and CD4 activation pathways further, we examined the effect of CD3/CD4 cross-linking on tyrosine phosphorylation and activation of phospholipase C in CD45- mutant cells of the T cell leukemia line HPB.ALL. In accord with previous observations, anti-CD3 stimulation of the CD45-deficient cells failed to activate tyrosine kinases, or PLC as measured by mobilization of intracellular calcium. However, we show here that ligation of CD3 with CD4 leads to tyrosine phosphorylation of PLC gamma 1 and elevation in the intracellular free Ca2+ concentration in CD45- cells that is in excess of that seen in CD45+ cells. Since CD4 stimulation alone did not activate PLC, a component of the CD3 signaling pathway must be independent of CD45. Anti-CD4-induced tyrosine phosphorylation and activation of CD4-associated lck was also enhanced in CD45- cells, suggesting that increased lck activation compensates for the defect in CD3/TcR signaling, such that interaction of the CD3 signaling pathway with the CD4-associated pathway activates PLC even in the absence of CD45. The data demonstrate that the requirement for CD45 in coupling CD3/TcR to the PI-PLC activation cascade is not absolute, but rather substantiates a role for CD45 in modifying molecular interactions that control T cell activation.
Biosynthesis of the C-terminal amide in peptide hormones (1987)

Recent developments in the study of peptide amidation are reviewed. The main areas covered are assay procedures, purification of amidating enzymes, co-factors and regulation, mechanism and specificity of the amidating reaction, and multiple forms of the amidating enzyme and glycosylation. Discussion is presented on aspects that are poorly understood and new areas open to investigation are indicated.
Gemcitabine and nab-paclitaxel retreatment as a third-line therapy following second-line FOLFIRINOX for advanced pancreatic adenocarcinoma. (2019)

e15794 Background: First-line and second line treatment for advanced pancreatic adenocarcinoma typically involves therapy with gemcitabine plus nab-paclitaxel, FOLFIRINOX or as per the recent phase III trial (NAPOLI-1), the combination of nal-irinotecan with 5-fluorouracil and leucovorin. Despite these advances, there remains minimal amount of data regarding the options for, or efficacy of, third-line treatment in these patients. We have previously reported our experience of twenty patients who received effective third-line therapy with gemcitabine plus nab-paclitaxel retreatment after receiving FOLFIRINOX as second-line treatment. This retrospective analysis assessed the updated data of the use of gemcitabine plus nab-paclitaxel as a third-line treatment option in a single hospital setting. Methods: We conducted a retrospective analysis using an electronic database of patients with locally advanced or metastatic pancreatic adenocarcinoma who received first-line gemcitabine and nab-paclitaxel, second line FOLFIRINOX and third-line retreatment with gemcitabine and nab-paclitaxel between January 2013 and December 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Twenty-six patients were reviewed. Median age of 73 (range, 45 – 81). 73% of the studied patients had locally advanced cancer at diagnosis. The median OS from diagnosis was 39.0 months (95% CI, 34.0 – 66.0). The median OS from third-line re-initiation of gemcitabine plus nab-paclitaxel was 18.0 months (95% CI, 9.0 – 32.0). Conclusions: This is one of the first retrospective studies to show the efficacy of third-line treatment with gemcitabine plus nab-paclitaxel in advanced pancreatic cancer. It demonstrated that retreatment with gemcitabine plus nab-paclitaxel is feasible, tolerable and effective in patients with a good performance status. We suggest a formal phase 3 study to confirm our data and potentially establish a formal new standard of care for third line chemotherapy in this previously disadvantaged group.
Robot-assisted 3D-TRUS guided prostate brachytherapy: System integration and validation (2004)

Current transperineal prostate brachytherapy uses transrectal ultrasound (TRUS) guidance and a template at a fixed position to guide needles along parallel trajectories. However, pubic arch interference (PAI) with the implant path obstructs part of the prostate from being targeted by the brachytherapy needles along parallel trajectories. To solve the PAI problem, some investigators have explored other insertion trajectories than parallel, i.e., oblique. However, parallel trajectory constraints in current brachytherapy procedure do not allow oblique insertion. In this paper, we describe a robot-assisted, three-dimensional (3D) TRUS guided approach to solve this problem. Our prototype consists of a commercial robot, and a 3D TRUS imaging system including an ultrasound machine, image acquisition apparatus and 3D TRUS image reconstruction, and display software. In our approach, we use the robot as a movable needle guide, i.e., the robot positions the needle before insertion, but the physician inserts the needle into the patient's prostate. In a later phase of our work, we will include robot insertion. By unifying the robot, ultrasound transducer, and the 3D TRUS image coordinate systems, the position of the template hole can be accurately related to 3D TRUS image coordinate system, allowing accurate and consistent insertion of the needle via the template hole into the targeted position in the prostate. The unification of the various coordinate systems includes two steps, i.e., 3D image calibration and robot calibration. Our testing of the system showed that the needle placement accuracy of the robot system at the "patient's" skin position was 0.15 mm+/-0.06 mm, and the mean needle angulation error was 0.07 degrees. The fiducial localization error (FLE) in localizing the intersections of the nylon strings for image calibration was 0.13 mm, and the FLE in localizing the divots for robot calibration was 0.37 mm. The fiducial registration error for image calibration was 0.12 mm and 0.52 mm for robot calibration. The target registration error for image calibration was 0.23 mm, and 0.68 mm for robot calibration. Evaluation of the complete system showed that needles can be used to target positions in agar phantoms with a mean error of 0.79 mm+/-0.32 mm.
Requirement for p38 and p44/p42 Mitogen-Activated Protein Kinases in RAGE-Mediated Nuclear Factor-κB Transcriptional Activation and Cytokine Secretion (2001)

Advanced glycation end product (AGE) activation of the signal-transducing receptor for AGE (RAGE) has been linked to a proinflammatory phenotypic change within cells. However, the precise intracellular signaling pathways involved have not been elucidated. We demonstrate here that human serum albumin modified with N(epsilon)-(carboxymethyl)lysine (CML), a major AGE adduct that progressively accumulates with aging, diabetes, and renal failure, induced nuclear factor (NF)-kappaB-driven reporter gene expression in human monocytic THP-1 cells. The NF-kappaB response was blocked with a synthetic peptide corresponding to the putative ligand-binding domain of RAGE, with anti-RAGE antiserum, and by coexpression of truncated receptors lacking the intracellular domain. Signal transduction from RAGE to NF-kappaB involved the generation of reactive oxygen species, since reporter gene expression was blocked with the antioxidant N-acetyl-L-cysteine. CML-modified albumin produced rapid transient activation of tyrosine phosphorylation, extracellular signal-regulated kinase 1 and 2, and p38 mitogen-activated protein kinase (MAPK), but not c-Jun NH(2)-terminal kinase. RAGE-mediated NF-kappaB activation was suppressed by the selective p38 MAPK inhibitor SB203580 and by coexpression of a kinase-dead p38 dominant-negative mutant. Activation of NF-kappaB by CML-modified albumin increased secretion of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and monocyte chemoattractant protein-1) severalfold, and inhibition of p38 MAPK blocked these increases. These results indicate that p38 MAPK activation mediates RAGE-induced NF-kappaB-dependent secretion of proinflammatory cytokines and suggest that accelerated inflammation may be a consequence of cellular activation induced by this receptor.
Large‐Scale Synthesis of H‐Antigen Oligosaccharides by Expressing Helicobacter pylori α1,2‐Fucosyltransferase in Metabolically Engineered Escherichia coli Cells (2006)

Sugar production: A microbiological method has been developed for the production of fucosyl α1,2-linked carbohydrates from lactose. The syntheses of 2′-fucosyllactose and lacto-N-neofucopentaose-1 (see structure), which contain the H-2 antigen (Fucα-2Galβ-4R), were achieved by cultivating Escherichia coli strains that overexpressed the appropriate heterologous genes.
Effect of staphylococcal alpha-toxin on intracellular Ca2+ in polymorphonuclear leukocytes (1988)

Staphylococcal alpha-toxin, a channel-forming protein, stimulates leukotriene B4 formation in rabbit polymorphonuclear leukocytes (PMN) (N. Suttorp, W. Seeger, J. Zucker-Reimann, L. Roka, and S. Bhakdi, Infect. Immun. 55:104-110, 1987). The concept was advanced that transmembrane toxin pores act as Ca2+ gates allowing passive Ca2+ influx into the cell, thus initiating stimulus response coupling. A critical step in this hypothesis is the demonstration of an increase in the cytosolic free Ca2+ concentration [( Ca2+]i). [Ca2+]i and membrane-associated Ca2+ were therefore monitored in quin-2- or chlorotetracycline-loaded PMN exposed to alpha-toxin. The effects of the Ca2+ ionophore ionomycin and the chemotactic tripeptide formylmethionyl-leucylphenylalanine (fMLP) were studied in parallel. All stimuli increased [Ca2+]i in dose- and time-dependent manner. In the presence of an EDTA excess there was a decrease of [Ca2+]i due to an efflux of Ca2+ in alpha-toxin- and ionomycin-treated cells, while addition of fMLP still induced an increase of [Ca2+]i. In the presence of verapamil, a Ca2+ channel blocker, [Ca2+]i was reduced after stimulation with fMLP but not with alpha-toxin or ionomycin. Addition of fMLP and ionomycin but not of alpha-toxin to PMN resulted in a rapid and substantial mobilization of membrane-associated Ca2+. The collective data demonstrate that exposure of PMN to staphylococcal alpha-toxin results in an increase in [Ca2+]i which is due to an influx of extracellular Ca2+ and not to a mobilization of intracellularly stored Ca2+. The concept of initiating stimulus response coupling by Ca2+ influx through transmembrane pores may be generally applicable to other channel-forming cytolysins.
The reduction by training of CO2 output during exercise. (1979)

5 men underwent a 10-wk endurance training programme which resulted in an 18% increase in max VO2 from a mean of 3.1 l/min. Measurements were made at 2 submaximal O2 intakes of 1.2 and 2.0 l/min to examine the physiological interdependence of mechanisms changed by training. At both levels of VO2, reductions were observed following training in cardiac frequency (fc), CO2 output (VCO2), respiratory exchange ratio (R), ventilation (VE), alveolar-arterial PO2 difference (A-aPO2) and blood lactate (La); the changes were statistically significant at the higher VO2. No change was observed in cardiac output, blood free fatty acids (FFA) and blood glycerol (gly). A small increase was found in arterial PCO2 (PaCO2) and HCO3-. Changes in fc were not significantly related to changes in other variables. The reductions in La were related to falls in VCO2 and VE, and inversely related to increases in PaCO2. Only a portion of the fall in R could be ascribed to increased usage of fat as a fuel, the main factor being a fall in lactate production. Reductions in A-aPO2 were due to decreases in PAO2 and falls in R, with no change in venous admixture. Changes in FFA and gly were small and not related to changes in other variables. Training led to an increased usage of aerobic metabolic pathways. The resultant fall in lactic acid production led to a fall in VCO2 and maintained HCO3-. These changes accounted for a marked reduction in VE following training.
Maintenance and break of immune tolerance against human factor VIII in a new transgenic hemophilic mouse model (2011)

Replacement of the missing factor VIII (FVIII) is the current standard of care for patients with hemophilia A. However, the short half-life of FVIII makes frequent treatment necessary. Current efforts focus on the development of longer-acting FVIII concentrates by introducing chemical and genetic modifications to the protein. Any modification of the FVIII protein, however, risks increasing its immunogenic potential to induce neutralizing antibodies (FVIII inhibitors), and this is one of the major complications in current therapy. It would be highly desirable to identify candidates with a high risk for increased immunogenicity before entering clinical development to minimize the risk of exposing patients to such altered FVIII proteins. In the present study, we describe a transgenic mouse line that expresses a human F8 cDNA. This mouse is immunologically tolerant to therapeutic doses of native human FVIII but is able to mount an antibody response when challenged with a modified FVIII protein that possesses altered immunogenic properties. In this situation, immunologic tolerance breaks down and antibodies develop that recognize both the modified and the native human FVIII. The applicability of this new model for preclinical immunogenicity assessment of new FVIII molecules and its potential use for basic research are discussed.
A malonyl‐CoA‐dependent switch in the bacterial response to a dysfunction of lipid metabolism (2008)

Bacteria stringently regulate the synthesis of their membrane phospholipids, but the responsible regulatory mechanisms are incompletely understood. Bacillus subtilis FabF, the target of the mycotoxin cerulenin, catalyses the condensation of malonyl-ACP with acyl-ACP to extend the growing acyl chain by two carbons. Here we show that B. subtilis strains containing the fabF1 allele, which codes for the cerulenin-insensitive protein FabF[I108F], overexpressed several genes involved in fatty acid and phospholipid biosynthesis (the fap regulon) and had significantly elevated levels of malonyl-CoA. These results pinpointed FabF[I108F] as responsible for the increased malonyl-CoA production, which in turn acts as an inducer of the fap regulon by impairing the binding of the FapR repressor to its DNA targets. Synthesis of acyl-ACPs by a cell-free fatty acid system prepared from fabF1 cells showed the accumulation of short- and medium-chain acyl-ACPs. These results indicate that the acyl-ACP chain length acceptance of FabF[I108F] is biased towards shorter acyl-ACPs. We also provide evidence that upregulation of FabF[I108F] is essential for survival and for resistance to cerulenin of fabF1 cells. These findings indicate that malonyl-CoA is a key molecule to monitor lipid metabolism functioning and trigger appropriate genetic and biochemical adjustments to relieve dysfunctions of this essential metabolic pathway.
The RNA Processing Enzyme RNase MRP Is Identical to the Th RNP and Related to RNase P (1989)

Sera from patients with autoimmune diseases often contain antibodies that bind ribonucleoproteins (RNPs). Sera from 30 such patients were found to immunoprecipitate ribonuclease P (RNase P), an RNP enzyme required to process the 5' termini of transfer RNA transcripts in nuclei and mitochondria of eukaryotic cells. All 30 sera also immunoprecipitated the nucleolar Th RNP, indicating that the two RNPs are structurally related. Nucleotide sequence analysis of the Th RNP revealed it was identical to the RNA component of the mitochondrial RNA processing enzyme known as RNase MRP. Antibodies that immunoprecipitated the Th RNP selectively depleted murine and human cell extracts of RNase MRP activity, indicating that the Th and RNase MRP RNPs are identical. Since RNase P and RNase MRP are not associated with each other during biochemical purification, we suggest that these two RNA processing enzymes share a common autoantigenic polypeptide.
ECAI 2002 : 15th European Conference on Artificial Intelligence, July 21-26, 2002, Lyon,France : including Prestigious Applications of Intelligent Systems (PAIS 2002) : proceedings (2002)

This volume contains the papers accepted for presentation at the 15th European Conference on Artificial Intelligence (ECAI'02). The 137 papers cover topics such as multi-agent research, machine learning and reasoning under uncertainty. The volume covers not only academic work, but also contains a section of 11 papers on Prestigious Applications of Intelligent Systems (PAIS).