gebhart/patrepeval huggingface dataset:
TRAP transporters: a new family of periplasmic solute transport systems encoded by the dctPQM genes of Rhodobacter capsulatus and by homologs in diverse gram-negative bacteria (1997)

The dct locus of Rhodobacter capsulatus encodes a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. The nucleotide sequence of the region downstream of the previously sequenced dctP gene (encoding a periplasmic C4-dicarboxylate-binding protein) was determined. Two open reading frames (ORFs) of 681 bp (dctQ) and 1,320 bp (dctM) were identified as additional dct genes by insertional mutagenesis and complementation studies. DctQ (24,763 Da) and DctM (46,827 Da) had hydropathic profiles consistent with the presence of 4 and 12 potential transmembrane segments, respectively, and were localized in the cytoplasmic membrane fraction after heterologous expression of the dctQM ORFs in Escherichia coli. DctP, DctQ, and DctM were found to be unrelated to known transport proteins in the ABC (ATP-binding cassette) superfamily but were shown to be homologous with the products of previously unidentified ORFs in a number of gram-negative bacteria, including Bordetella pertussis, E. coli, Salmonella typhimurium, Haemophilus influenzae, and Synechocystis sp. strain PCC6803. An additional ORF (rypA) downstream of dctM encodes a protein with sequence similarity to eukaryotic protein-tyrosine phosphatases, but interposon mutagenesis of this ORF did not result in a Dct- phenotype. Complementation of a Rhizobium meliloti dctABD deletion mutant by heterologous expression of the dctPQM genes from R. capsulatus demonstrated that no additional structural genes were required to form a functional transport system. Transport via the Dct system was vanadate insensitive, and in uncoupler titrations with intact cells, the decrease in the rate of succinate transport correlated closely with the fall in membrane potential but not with the cellular ATP concentration, implying that the proton motive force, rather than ATP hydrolysis, drives uptake. It is concluded that the R. capsulatus Dct system is a new type of periplasmic secondary transporter and that similar, hitherto-unrecognized systems are widespread in gram-negative bacteria. The name TRAP (for tripartite ATP-independent periplasmic) transporters is proposed for this new group.
Gate-length biasing for runtime-leakage control (2006)

Leakage power has become one of the most critical design concerns for the system level chip designer. While lowered supplies (and consequently, lowered threshold voltage) and aggressive clock gating can achieve dynamic power reduction, these techniques increase the leakage power and, therefore, causes its share of total power to increase. Manufacturers face the additional challenge of leakage variability: Recent data indicate that the leakage of microprocessor chips from a single 180-nm wafer can vary by as much as 20/spl times/. Previously proposed techniques for leakage-power reduction include the use of multiple supply and gate threshold voltages, and the assignment of input values to inactive gates, such that leakage is minimized. The additional design space afforded by the biasing of device gate lengths to reduce chip leakage power and its variability is studied. It is well known that leakage power decreases exponentially and delay increases linearly with increasing gate length. Thus, it is possible to increase gate length only marginally to take advantage of the exponential leakage reduction, while impairing performance only linearly. From a design-flow standpoint, the use of only slight increases in gate length preserves both pin and layout compatibility; therefore, the authors' technique can be applied as a postlayout enhancement step. The authors apply gate-length biasing only to those devices that do not appear in critical paths, thus assuring zero or negligible degradation in chip performance. To highlight the value of the technique, the multithreshold voltage technique, which is widely used for leakage reduction, is first applied and then gate-length biasing is used to show further reduction in leakage. Experimental results show that gate-length biasing reduces leakage by 24%-38% for the most commonly used cells, while incurring delay penalties of under 10%. Selective gate-length biasing at the circuit level reduces circuit leakage by up to 30% with no delay penalty. Leakage variability is reduced significantly by up to 41%, which may lead to substantial improvements in the manufacturing yield and the product cost. The use of gate-length biasing for leakage optimization of cell instances is also assessed, in which: 1) not all timing arcs are timing critical and/or 2) the rise and fall transitions are not both timing critical at the same time.
Effects of Phytic Acid on Renal Stone Formation in Rats (1998)

The effects of phytic acid and phytic acid/zinc mixtures on renal urolith development in an animal model of nephrolitiasis were studied. Male rats were divided into four groups of 15, 10, 10 and 12 rats each. The rats of Group I were treated with ethylene glycol; of Group II with ethylene glycol plus zinc; of Group III with ethylene glycol phytic acid; and of Group IV with ethylene glycol plus a mixture of phytic acid/zinc. Urine analysis (24 h) was carried out to determine the levels of calcium, oxalate, citrate, zinc and phytic acid in each group. At the end of the experiment all kidneys were removed and examined macroscopically and microscopically for possible crystal/stone locations and the total calcium amount in the renal papillary tissue was evaluated. In the rats treated with the aqueous phytic acid and phytic acid/zinc mixture, the number of calcifications on the papillary tips and the total calcium amount of the papillary tissue were significantly reduced compared with the controls treated exclusively with ethylene glycol or ethylene glycol plus zinc. Consequently, phytic acid and mixtures of phytic acid/zinc may be a useful agent in the treatment of patients with calcic urolithiasis.
Antibodies to viral citrullinated peptide in rheumatoid arthritis. (2006)

Anti-VCP antibodies are helpful in discriminating RA from other chronic arthritides or connective tissue disorders. The level of positivity is positively correlated with the anti-CCP level, suggesting that VCP can be considered a novel substrate to detect anti-citrullinated peptide/protein antibodies (ACPA). The reactivity of RA-specific antibodies with a viral citrullinated antigen raises questions on the role of EBV in the induction of ACPA.
Antibody Array Analysis with Label-based Detection and Resolution of Protein Size (2008)

Elements from DNA microarray analysis, such as sample labeling and micro-spotting of capture reagents, have been successfully adapted to multiplex measurements of soluble cytokines. Application in cell biology is hampered by the lack of mono-specific antibodies and the fact that many proteins occur in complexes. Here, we incorporated a principle from Western blotting and resolved protein size as an additional parameter. Proteins from different cellular compartments were labeled and separated by size exclusion chromatography into 20 fractions. All were analyzed with replicate antibody arrays. The elution profiles of all antibody targets were compiled to color maps that resemble Western blots with bands of antibody reactivity across the size separation range (670-10 kDa). A new solid phase designed for processing in microwell plates was developed to handle the large number of samples. Antibodies were bound to protein G-coupled microspheres surface-labeled with 300 combinations of four fluorescent dyes. Fluorescence from particle color codes and the protein label were measured by high-speed flow cytometry. Cytoplasmic protein kinases were detected as bands near predictable elution points. For proteins with atypical elution characteristics or multiple contexts, two or more antibodies were used as internal references of specificity. Membrane proteins eluted near the void volume, and additional bands corresponding to intracellular forms were detected for several targets. Elution profiles of cyclin-dependent kinases (cdks), cyclins, and cyclin-dependent kinase inhibitors, were compatible with their occurrence in complexes that vary with the cell cycle phase and subcellular localization. A two-dimensional platform circumvents the need for mono-specific capture antibodies and extends the utility of antibody array analysis to studies of protein complexes.
The Role of Lysyl Oxidase in SRC-Dependent Proliferation and Metastasis of Colorectal Cancer (2011)

LOX showed an important role in CRC cell proliferation and metastasis and was dependent on the activation of SRC. These results have the potential to identify patients with high SRC activity, who may benefit from dasatinib treatment.
A Biomechanical Analysis of an Engineered Cell-Scaffold Implant for Cartilage Repair (2001)

This study evaluated the biomechanical and physical properties of newly formed cartilage engineered from isolated chondrocytes in combination with matrix components. Four groups of constructs were studied. Group A consisted of lyophilized articular cartilage chips mixed with a cell-fibrinogen solution and thrombin to obtain constructs made of fibrin glue, chondrocytes, and cartilage chips. Group B constructs were prepared using fibrin glue and cartilage chips without cells. Group C contained chondrocytes in fibrin glue without chips, and group D comprised constructs of fibrin glue alone. Specimens were implanted in the subcutaneous tissue of nude mice for 9 weeks. At necropsy the specimens were examined grossly, physically, biomechanically, and histologically. The original, preimplantation mass of the constructs was retained only in experimental group A. Histological analysis of specimens in experimental groups A and C demonstrated the presence of newly formed cartilaginous matrix, whereas only fibrotic tissue was observed in control groups B and D. Biomechanical analysis demonstrated higher mean values of equilibrium modulus in the experimental samples of group A with respect to all control groups. This study demonstrated that adding lyophilized cartilage chips to a fibrin glue-engineered cartilage construct maintains the biomechanical properties and the original mass after medium-/long-term in vivo transplantation.
An Amyloid-Like C-Terminal Domain of Thrombospondin-1 Displays CD47 Agonist Activity Requiring Both VVM Motifs (2003)

Two VVM-containing peptides in the C-terminal domain (CBD) of thrombospondin-1 function as CD47 agonists. A recombinant form of the CBD (rCBD) has been expressed that contains both VVM sites and exhibits CD47-dependent binding of C32 melanoma cells when coated at concentrations 100x lower than the peptide 4N1K (kRFYVVMWKk). Circular dichroism and thioflavin T binding of a recombinant form of the C-terminal domain (rCBD) of thrombospondin-1 indicated a species highly enriched in beta-sheet secondary structure, with spectra similar to those of amyloid proteins. Reduction of the CD signal with progressively higher concentrations of guanidine hydrochloride was correlated with a loss of cell-binding activity. Melanoma cell spreading on vitronectin was strongly stimulated by immobilized rCBD co-coated at concentrations more than 50x lower than 4N1K, and the effect was blocked by treatment with pertussis toxin, consistent with the known mediation of CD47 signaling by trimeric G(i). Mutations of either or both VV sequences of rCBD (1037-38 and 1123-24 of TSP1) to GG had a modest effect on cell binding, a component of which was inhibited by heparin. However, all three mutants dramatically reduced the signaling-dependent stimulation of cell spreading, indicating that the VVM motifs of rCBD are structurally linked in CD47 activation.
Developmental learning on a humanoid robot (2005)

This paper addresses a broad spectrum of machine learning problems. Actions by embodied agents automatically generate training data for the learning mechanisms, so that a humanoid robot develops categorization autonomously. Cognitive capabilities of the humanoid robot are developmentally created, starting from abilities for detecting, segmenting, and recognizing objects. Such mature abilities are integrated with the deeper developmental learning mechanisms required to create those abilities out of the robot's physical experiences. This work presents strategies for learning task sequences and to recognize objects employed on such tasks from human-robot interaction cues. Learning strategies are also presented for the control of both oscillatory and non-oscillatory movements for the execution of these learned tasks. Self-exploration of the world automatically introduces the robot to new training data.
Increased rrn Gene Dosage Causes Intermittent Transcription of rRNA in Escherichia coli (1999)

When the number of rRNA (rrn) operons in an Escherichia coli cells is increased by adding an rrn operon on a multicopy plasmid, the rate of rRNA expression per operon is reduced to maintain a constant concentration of rRNA in the cell. We have used electron microscopy to examine rRNA transcription in cells containing a multicopy plasmid carrying rrnB. We found that there were fewer RNA polymerase molecules transcribing the rrn genes, as predicted from previous gene dosage studies. Furthermore, RNA polymerase molecules were arranged in irregularly spaced groups along the operon. No apparent pause or transcription termination sites that would account for the irregular spacing of the groups of polymerase molecules were observed. We also found that the overall transcription elongation rate was unchanged when the rrn gene dosage was increased. Our data suggest that when rrn gene dosage is increased, initiation events, or promoter-proximal elongation events, are interrupted at irregular time intervals.
Determining the Physical Properties of Molecules with Nanometer-Scale Pores (2018)

Nanometer-scale pores have been developed for the detection, characterization, and quantification of a wide range of analytes (e.g., ions, polymers, proteins, anthrax toxins, neurotransmitters, and synthetic nanoparticles) and for DNA sequencing. We describe the key requirements that made this method possible and how the technique evolved. Finally, we show that, despite sound theoretical work, which advanced both the conceptual framework and quantitative capability of the method, there are still unresolved questions that need to be addressed to further improve the technique.
The cytoplasmic and transmembrane domains of the vaccinia virus B5R protein target a chimeric human immunodeficiency virus type 1 glycoprotein to the outer envelope of nascent vaccinia virions (1997)

The outer envelope of the extracellular form of vaccinia virus (EEV) is derived from the Golgi membrane and contains at least six viral proteins. Transfection studies indicated that the EEV protein encoded by the B5R gene associates with Golgi membranes when synthesized in the absence of other viral products. A domain swapping strategy was then used to investigate the possibility that the B5R protein contains an EEV targeting signal. We constructed chimeric genes encoding the human immunodeficiency virus (HIV) type 1 glycoprotein with the cytoplasmic and transmembrane domains replaced by the corresponding 42-amino-acid C-terminal segment of the B5R protein. Recombinant vaccinia viruses that stably express a chimeric B5R-HIV protein or a control HIV envelope protein with the original cytoplasmic and transmembrane domains were isolated. Cells infected with recombinant vaccinia viruses that expressed either the unmodified or the chimeric HIV envelope protein formed syncytia with cells expressing the CD4 receptor for HIV. However, biochemical and microscopic studies demonstrated that the HIV envelope proteins with the B5R cytoplasmic and transmembrane domains were preferentially targeted to the EEV. These data are consistent with the presence of EEV localization signals in the cytoplasmic and transmembrane domains of the B5R protein.
Mechanisms of Persistent Airway Inflammation in Asthma. A Role for T Cells and T-Cell Products (1995)

The role of T cells in human allergic inflammation is just beginning to be understood. However, the data presented indicate how the T cell may be a pivotal cell to direct features of allergic inflammation in asthma, how the T cell may be able to transfer hyperresponsiveness, which is a feature of bronchial asthma, what some of the genetic factors are that may determine this process, and how an important precipitant of asthma, viral respiratory infections, may participate in this process. Its cells are isolated from patients with asthma and studied for their ability to generate proinflammatory failure. An expanded understanding of the chronic, persistent nature of asthma will become apparent.
Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC) (2021)

EudraCT 2019-002734-37 ; NCT04617457 .
Electrical Energy Storage for the Grid: A Battery of Choices (2011)

The increasing interest in energy storage for the grid can be attributed to multiple factors, including the capital costs of managing peak demands, the investments needed for grid reliability, and the integration of renewable energy sources. Although existing energy storage is dominated by pumped hydroelectric, there is the recognition that battery systems can offer a number of high-value opportunities, provided that lower costs can be obtained. The battery systems reviewed here include sodium-sulfur batteries that are commercially available for grid applications, redox-flow batteries that offer low cost, and lithium-ion batteries whose development for commercial electronics and electric vehicles is being applied to grid storage.
Evaluation of the Transfer and Expression in Mice of an Enzyme-Encoding Gene Using a Human Adenovirus Vector (1990)

Mutant mice of the Spf-ash strain have an inherited defect in ornithine transcarbamylase (OTC) protein synthesis, and were used to ascertain the potential of recombinant adenoviruses for introducing and expressing the normal gene lacking in these mice. These OTC mutant mice are characterized by a reduction in the amount of OTC activity, resulting in hyperammonemia, pronounced orotic aciduria, growth retardation, and sparse fur until weaning. A recombinant adenovirus that harbors the rat OTC cDNA under the control of the viral major late promoter (MLP) was constructed and injected into such newborn mice. The effect of the virus was analyzed by monitoring the hepatic OTC enzyme during several months after the injection. An increase in OTC activity was detected and was accompanied by a diminution of orotic acid in the urine. The observation of MLP-OTC mRNA transcripts over 1 year following the injection attests to the relatively long-term presence of the transferred gene. In those mice showing the greatest OTC activity, a normalization of the fur was also observed. The experiments reported here document the feasibility of using adenovirus for the direct delivery in vivo of a gene to restore an impaired metabolism.
Dissociated neurons from normal and mutant Drosophila larval central nervous system in cell culture (1983)

A primary dissociated cell culture of Drosophila larval central nervous system is reported. Divisions of neuroblasts and vigorous outgrowth of neurites could be observed in culture. Within 24 hr cultured cells exhibited characteristic neuronal morphology and unimpaired ability to synthesize and accumulate acetylcholine. This cell culture system renders easy access to experimental analysis of normal neuronal properties and the altered mechanisms in neurological mutants. Single-channel currents induced by acetylcholine and regenerative action potentials were studied in the somata of the dissociated neurons. The appearance of Na channels in these cultured neurons was demonstrated by the cell lethality induced by veratridine and inhibition of the effect by tetrodotoxin. Dissociated neurons from a temperature-sensitive paralytic mutant napts, in which nerve conduction fails at high temperature, were studied in culture. Neuronal growth was not affected by this mutation, nor by tetrodotoxin. However, napts neurons showed greatly reduced sensitivity to veratridine even at 21 degrees C, a temperature at which napts individuals behave normally. This finding indicates expression of the napts phenotype at a level of isolated single cells and provides independent evidence that napts affects Na channel function.
Transcriptional control at regulatory checkpoints by histone deacetylases: molecular connections between cancer and chromatin (2001)

Cancer cells exhibit a set of unique properties that distinguish them from their normal counterparts. Among these features are increased growth rates, loss of differentiation, escape from cell death pathways, evasion of anti-proliferative signals, a decreased reliance on exogenous growth factors and escape from replicative senescence. Acquisition of these features by malignant cells requires impairment of normal cellular control mechanisms. Over the past few years, it has become increasingly apparent that an important subset of the molecular changes commonly found in cancer cells involves inappropriate regulation of gene expression. This review will address regulatory pathways whose disruption contributes to the malignant phenotype. The failure to deacetylate and thus repress transcription by the Class I histone deacetylases HDAC1 and HDAC2 due to disruption of the Rb family of proteins has been firmly established as a mechanism leading to increases in growth rate and cellular proliferation. Recent data suggest that this regulatory circuit also executes G(1) checkpoint arrest downstream of DNA damage, cellular senescence and contact inhibition. In contrast to this failure to deacetylate, it now seems probable that changes in differentiation status may result in part from inappropriate deacetylation and concomitant transcriptional repression mediated by the Class II histone deacetylases. This inappropriate deacetylation by HDAC4, HDAC5 and HDAC6 follows their relocalization from the cytoplasm to the nucleus. Thus, multiple classical features of cancer cells can be manifested by improper histone deacetylation.