gebhart/patrepeval huggingface dataset:
Optimal Functional-Unit Assignment for Heterogeneous Systems Under Timing Constraint (2017)

In high-level synthesis for real-time systems, it typically employs heterogeneous functional-unit types to achieve high-performance and low-cost designs. In the design phase, it is critical to determine which functional-unit type to be mapped for each operation in a given application such that the total cost is minimized while the deadline can be met. For a path or tree structured application, existing approaches can obtain the minimum-cost assignment, called “optimal assignment”, under which the resultant system satisfies a given timing constraint. However, it is still an open question whether there exist efficient algorithms to obtain the optimal assignment for the directed acyclic graph (DAG), or more generally, the data-flow graph with cycles (cyclic DFG). For DAGs, by analyzing the property of the problem, this paper designs an efficient algorithm to obtain the optimal assignments. For cyclic DFGs, we approach this problem with the combination of retiming technique to thoroughly explore the design space. We formulate a Mixed Integer Linear Programming (MILP) model to give the optimal solution. But because of the high degree of its time complexity, we devise a practical algorithm to obtain near-optimal solutions within a minute. Experimental results show the effectiveness of our algorithms. Specifically, compared with existing techniques, we can achieve 25.70 and 30.23 percent reductions in total cost on DAGs and cyclic DFGs, respectively.
Recombinant interleukin 2 therapy in severe combined immunodeficiency disease. (1989)

Severe combined immunodeficiency disease (SCID) is a congenital disorder of severe B- and T-lymphocyte dysfunction in which several pathogenic mechanisms have been identified. The present study describes a female child with SCID who had a primary defect in the ability of T cells to secrete interleukin 2 (IL-2). B- and T-cell numbers were normal, but their functions were severely deficient. Mitogen and antigen-driven lymphoproliferative responses were diminished but were correctable in vitro with recombinant IL-2 (rIL-2). The patient's phytohemagglutinin-stimulated lymphocytes expressed IL-2 receptors normally. Despite the presence of the gene for IL-2, the patient's cells were grossly deficient in messenger RNA for IL-2 and endogenous IL-2 production. Pokeweed mitogen-driven B-cell differentiation was decreased and was not corrected by the addition of normal T cells to the B cells. Two attempts at immune reconstitution by haploidentical bone marrow transplantation failed. Therapy with rIL-2 (30,000 units/kg, given daily i.v.) resulted in marked clinical improvement as well in improved T-cell functions. The child, now 3 yr old, has been on rIL-2 therapy for 2 yr and receives rIL-2 (30,000 units/kg) three times weekly at home. This case study points to a new direction in the treatment of such disorders with rIL-2.
Evaluation of the Protective Efficacy of the Killed Coccidioides immitis Spherule Vaccine in Humans (1993)

A vaccine consisting of formaldehyde-killed spherules of Coccidioides immitis, previously shown to provide protection against development of lethal coccidioidomycosis in laboratory animals, was evaluated in humans. This double blind "Phase 3" study, conducted during the period 1980 to 1985, involved 2,867 healthy subjects with no history of coccidioidomycosis and negative skin tests. Randomized into vaccine (n = 1,436) or placebo (n = 1,431) groups, the former received three intramuscular injections of 1.75 mg (dry weight) of spherules, the latter received three injections of sterile 0.85% NaCl solution. Compatible clinical presentation with cultural or serologic findings permitted detection of coccidioidomycosis. Of those receiving vaccine, nine developed coccidioidomycosis and nine additional were suspected of having the disease. Of the group receiving placebo, 12 developed coccidioidomycosis, and 13 additional were suspected of having the disease. All cases and suspected cases were mild. Under the conditions of this study, a slight but statistically insignificant reduction in the incidence of coccidioidomycosis was noted in the vaccinated group compared with that in the placebo group, and there was no discernible difference in severity of disease between these groups.
Structure and catalytic mechanism of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MECDP) synthase, an enzyme in the non-mevalonate pathway of isoprenoid synthesis (2002)

Precursors for isoprenoid synthesis are essential in all organisms. These compounds are synthesized by one of two known routes: the well characterized mevalonate pathway or a recently discovered non-mevalonate route which is used in many bacteria and human pathogens. Since the second pathway is both vital and unlike any found in humans, enzymes catalysing reactions along this synthetic route are possible drug targets. The structure of one such enzyme from the thermophilic bacterium Thermus thermophilus has been solved to high resolution in the presence of substrate and with a substrate analogue. Enzyme co-crystallized with substrate shows only one product, cytosine monophosphate (CMP), in the active site. At the high resolution of the refinement (1.6 A) the positions and coordination of the magnesium ions in the active site are clearly seen.
Fibronectin binding determinants of the Staphylococcus aureus fibronectin receptor (1991)

Synthetic peptide analogs mimicking a repeated motif within the Staphylococcus aureus fibronectin receptor inhibit binding of the bacteria to fibronectin (Signäs, C., Raucci, G., Jonsson, K., Lindgren, P. E., Anantharamaiah, G. M., Höök, M., and Lindberg, M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 699-703). In this study, we have further localized the fibronectin-binding determinant within the 37 amino acid D3 peptide. Chemical modification of the carboxyl side chains of the glutamic and aspartic residues in D3 abolished fibronectin-binding activity, whereas modifications of lysine or tyrosine residues had little effect. An active peptide encompassing residues 15-36 was isolated from a trypsin digest of D3, and a synthetic peptide S16-36 had activity comparable with that of intact D3. Scrambling the amino acid sequence of S16-36 or replacing the aspartic and glutamic residues with asparagine and glutamine resulted in loss of activity. Therefore, one or more of the acidic residues are essential for activity. However, additional sequence is required. Reduction in the size of S16-36 from either the N- or C-terminal end resulted in peptides with greatly diminished activity. These data suggest that the amino acids essential for binding fibronectin are contained within residues 21-33 of the D3 peptide and that the flanking N- and C-terminal amino acids are necessary for the peptide to acquire a conformation that is favorable for fibronectin binding.
Computerized image analysis of distinct cell marker parameters of glial fibrillary acidic protein: intensity of immunofluorescence and topography in human glioma cultures. (1992)

Glial fibrillary acidic protein (GFAP) is a 49 kDa component of 8 nanometers glial intermediate filaments. It is a definitive marker of both neoplastic and non-neoplastic glial cells. Malignant gliomas are heterogeneous in their structure and their expression of GFAP. Subjective visual impression of glioma cell cultures in early passage after explantation suggested two types of heterogeneity among the cells: 1) Indirect anti-GFAP immunofluorescence (IF) signal intensity appeared to vary among cells. 2). Sizes and shapes of cells appeared to vary. While many cultures lost GFAP+ cells by passage 2, some retained sufficient cells for study. Computerized microdensitometry and image analysis precisely assessed signal intensity, size and shape of glial cells from these latter cultures in passage 2 of cell culture. A Zeiss ICM 405 epi-illuminated fluorescent microscope with photographic interface to a Bio-Quant computerized microdensitometer measured IF signal intensity for GFAP. Normalized to the most intense reactivity, the mean intensity of GFAP expression of 26 glioma cells was 66.2%. The range of 5.2% to 100% around this mean reflected a high degree of heterogeneity of expression of GFAP by these cells. The effects of quenching of the fluorescent signal by the excitation beam were minimized in the following manner: a) Rhodamine anti-GFAP was substituted for more labile fluoresceine. b) A fluorescent filter and lens combination was selected to provide a high signal to quench ratio. c) The signal acquisition time was minimized and fixed to one standard interval. The image analysis system employed the described optics and computer.(ABSTRACT TRUNCATED AT 250 WORDS)
Absence of a barrier to backwards rotation of the bacterial flagellar motor demonstrated with optical tweezers (1997)

A cell of the bacterium Escherichia coli was tethered covalently to a glass coverslip by a single flagellum, and its rotation was stopped by using optical tweezers. The tweezers acted directly on the cell body or indirectly, via a trapped polystyrene bead. The torque generated by the flagellar motor was determined by measuring the displacement of the laser beam on a quadrant photodiode. The coverslip was mounted on a computer-controlled piezo-electric stage that moved the tether point in a circle around the center of the trap so that the speed of rotation of the motor could be varied. The motor generated approximately 4500 pN nm of torque at all angles, regardless of whether it was stalled, allowed to rotate very slowly forwards, or driven very slowly backwards. This argues against models of motor function in which rotation is tightly coupled to proton transit and back-transport of protons is severely limited.
Asenapine for bipolar disorder (2015)

Asenapine (Saphris(®)) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.
Drug addiction. Part III. Pharmacotherapy of addiction. (2002)

The last decade brought a considerable progress in pharmacotherapy of addiction. Basing on recently gained knowledge of mechanisms of development of addiction and the physiology of the brain reward system, several therapeutic strategies have evolved. The strategies aimed at targeting the basic mechanisms of addiction rely on the premises that addiction is caused by adaptive changes in the central nervous system and that craving, which is the main cause of relapse, depends on dopaminergic mechanisms and requires high general excitability. The pharmacological approach involves drugs that reduce neuronal adaptability by inhibiting the calcium entry to neurons both through voltage-gated channels (e.g. nimodipine) and NMDA receptors (e.g. memantine), and drugs that stimulate the inhibitory GABAergic system (gamma-vinyl-GABA, baclofen), Particular attention is paid to the compounds that may attenuate dopaminergic hyperactivity, without considerable suppression of tonic activity of dopaminergic neurons (e.g. BP 897, a partial dopamine D3 receptor antagonist). Specific strategies are aimed at interference with the action of particular drugs of addiction. An important group includes the agonistic therapies (known also as substitution or maintenance therapies) in which a long-acting agonist is used in order to reduce the action of the drugs of high addictive potential (e.g. methadone against heroin addiction or vanoxerine (GBR 12909) against psychostimulants). Other specific strategies aimed at reduction of the transport of molecules of addictive substances into the brain: the approaches involve preparation of antibodies that form complexes unable to cross blood-brain barrier or enzymes accelerating the metabolism of the compounds in the blood (e.g. variants of butyrylcholinesterase). A considerable progress has been made in combating the abuse of legal addictive substances, alcohol (naltrexone, acamprosate) and tobacco (bupropion). The prospects for developing effective pharmacotherapies against addiction are bright. Unfortunately, ideological and social implications, as well as the conflict of interest with illegal narcotic manufacturers and distributors, may considerably hamper the progress in combating addiction (e.g. difficulties in introduction of methadone).
Cloud Data Protection for the Masses (2012)

Offering strong data protection to cloud users while enabling rich applications is a challenging task. Researchers explore a new cloud platform architecture called Data Protection as a Service, which dramatically reduces the per-application development effort required to offer data protection, while still allowing rapid development and maintenance.
Biodistribution and Metabolism of a Mixed Backbone Oligonucleotide (GEM 231) Following Single and Multiple Dose Administration in Mice (2000)

Biodistribution and metabolism of a mixed backbone oligonucleotide (MBO), GEM 231, targeted to the RIalpha subunit of protein kinase A has been studied in normal and tumor xenografted mice. The study has been carried out using [35S]-labeled MBO following single and multiple administrations of doses varying from 2 to 50 mg/kg. MBO showed wide tissue distribution following intravenous and subcutaneous administration. The highest concentration of MBO was in the kidney and liver. The general disposition of MBO was followed by digitized autoradiographic pictures of tumored mice and further confirmed wide tissue disposition and also showed defined intratumor uptake of MBO. Multiple dose administration showed increased disposition in the majority of the tissues/organs, with the exception of the kidneys. Analysis of the extracted MBO by polyacrylamide gel electrophoresis (PAGE) showed the presence of primarily intact MBO along with its degraded forms. Based on our radioactivity levels, the primary route of excretion was in urine, analysis of which showed mainly degraded forms of MBO.
ChemInform Abstract: Palladium‐Catalyzed Amination of Aryl Bromides Utilizing Arene—Chromium Complexes as Ligands. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Application of Oligo-(14-amino-3,6,9,12-tetraoxatetradecanoic acid) Lipid Conjugates as Steric Barrier Molecules in Liposomal Formulations (1999)

Lipid conjugates of oligo-(14-amino-3,6,9,12-tetraoxatetradecanoic acid) (ATTAn) were synthesized as monodisperse analogues of poly(ethylene glycol) (PEG) derivatives used in liposomal drug delivery systems. The new lipids were shown to be at least equivalent to MePEGA-2000-DSPE in assays designed to evaluate the effectiveness of polymers as steric barrier molecules in liposomes. Liposomes containing 1-5% of ATTA8-DSPE (octamer) showed comparable long circulation behavior relative to PEG-2000-DSPE analogues. Surprisingly, the shorter ATTA4-DSPE (tetramer) appeared to be quite effective in reducing clearance. Liver enzyme levels and systemic single dose tolerability of ATTA8-DSPE liposomes were comparable to controls, suggesting that the new materials are nontoxic. Prolonged exposure of ATTA8-DSPE liposomes to splenocytes in vitro showed no evidence of mitogenicity relative to controls or MePEGA-2000-DSPE liposomes. ATTA8-DSPE was as effective as MePEGC-2000-DSPE in preventing complement activation by cationic liposome systems. Repeat dosage in vivo regimes in ICR mice using DSPC/cholesterol liposomes, with and without 5% ATTA8-DSPE and MePEGC-2000-DSPE, showed no evidence of enhanced clearance on successive doses. Splenocytes recovered after repeat doses showed no significant evidence of mitogenicity on restimulation with liposomes. Cellular differentiation and activation marker levels in splenocytes recovered after the fourth in vivo administration were at normal levels. These results suggest that ATTAn oligomers do not induce an immune response in isolation. It was demonstrated that ATTA8-DSPE could be used to replace PEG-lipids in the formulation of doxorubicin, plasmid DNA and oligonucleotides using a variety of formulation techniques. The study demonstrates that ATTAn oligomers can be safely and effectively used in place of poly(ethylene glycol) as well-defined biomaterials in liposomal applications where reproducible behavior is critical.
Light-Harvesting Metal–Organic Frameworks (MOFs): Efficient Strut-to-Strut Energy Transfer in Bodipy and Porphyrin-Based MOFs (2011)

A pillared-paddlewheel type metal-organic framework material featuring bodipy- and porphyrin-based struts, and capable of harvesting light across the entire visible spectrum, has been synthesized. Efficient-essentially quantitative-strut-to-strut energy transfer (antenna behavior) was observed for the well-organized donor-acceptor assembly consituting the ordered MOF structure.
Quantitation of genomic DNA in plasma and serum samples: higher concentrations of genomic DNA found in serum than in plasma (2001)

Most cell-free DNA in serum samples is generated during the process of clotting in the original collection tube. The concentration of cell-free genomic DNA in fresh plasma is probably the same as that in circulation. Consequently, while serum samples should not be used to monitor the concentration of cell-free DNA in a patient's circulation, serum collected from sample tubes containing clots (i.e., without anticoagulant), 3 to 5 days after the date of phlebotomy, could be useful as a source of DNA with which to screen for posttransfusion microchimerism.
Involvement of PYK2 in Angiotensin II Signaling of Vascular Smooth Muscle Cells (1999)

-PYK2, a recently identified Ca2+-sensitive tyrosine kinase, has been implicated in extracellular signal-regulated kinase (ERK) activation via several G protein-coupled receptors. We have reported that angiotensin II (Ang II) induces Ca2+-dependent transactivation of the epidermal growth factor receptor (EGFR) which serves as a scaffold for preactivated c-Src and downstream adaptors (Shc/Grb2), leading to ERK activation in cultured rat vascular smooth muscle cells (VSMC). Herein we demonstrate the involvement of PYK2 in this cascade. Ang II rapidly induced tyrosine phosphorylation of PYK2, whose effect was completely inhibited by an AT1 receptor antagonist and an intracellular Ca2+ chelator. A Ca2+ ionophore also induced PYK2 tyrosine phosphorylation to a level comparable with that by Ang II, whereas phorbol ester-induced phosphorylation was less than that by Ang II. Moreover, PYK2 formed a complex coprecipitable with catalytically active c-Src after Ang II stimulation. Although a selective EGFR kinase inhibitor completely abolished Ang II-induced recruitment of Grb2 to EGFR and markedly attenuated Ang II-induced ERK activation, it had no effect on Ang II-induced PYK2 tyrosine phosphorylation or its association with c-Src and Grb2. These data suggest that the AT1 receptor uses Ca2+-dependent PYK2 to activate c-Src, thereby leading to EGFR transactivation, which preponderantly recruits Grb2 in rat VSMC.
Mutations of p53 and K-ras genes as prognostic factors for non-small cell lung cancer. (1998)

To evaluate the importance of mutations of p53 and K-ras genes in the prognosis of patients with non-small cell lung cancer, one hundred and forty-four patients who underwent surgery were studied. DNA was extracted from frozen specimens. Polymerase chain reaction-single strand conformation polymorphism and sequencing were performed to investigate mutations of p53 from exon 5 to 8, and mutations of exon 1 of K-ras. Mutations of p53 gene occurred in 35. 4% of patients, and mutations of the K-ras gene in 8.3%. The overall survival rate of non-small cell lung cancer patients with wild-type K-ras was better than that of patients whose tumors had mutations of K-ras (P=0.0330). Among patients with adenocarcinoma of the lung, the overall survival rate of patients with wild-type p53 was strikingly better than that of patients whose tumors had mutations of p53 (P=0.0234). Multivariate analysis with the Cox regression model of all patients with non-small cell lung cancer and those with adenocarcinoma indicated that mutations of K-ras best correlated with the overall survival rate (P=0.0005 and P=0.0361, respectively). In conclusion, evaluation of mutations of both the p53 and K-ras genes in the lung tumors might be useful for assessing the prognosis, especially in patients with adenocarcinoma.
Assessing the unmet treatment need in partial‐onset epilepsy: Looking beyond seizure control (2010)

Patients with resistant epilepsy are often coprescribed multiple medications and are more likely to experience drug-drug interactions and adverse events (AEs). A new generation of antiepileptic drugs (AEDs) has been developed with improved safety/tolerability profiles. To evaluate the unmet treatment needs in epilepsy, a comprehensive search of the English-language literature was conducted on Medline and other databases using the terms "partial epilepsy" and "focal seizure," focusing on newer AEDs. Sixty-nine articles were identified. Most patients experienced AEs, which were generally mild-moderate in severity. Drug-drug interactions existed for 6 of 11 AEDs for which data were available. There is evidence for depressive symptoms being associated with zonisamide, and mood-stabilizing effects were shown for lamotrigine and pregabalin. Levetiracetam and eslicarbazepine improved cognitive function. Vigabatrin may increase the risk of developing psychosis. Health-related quality of life (HRQoL) was inversely correlated with seizure frequency. Discontinuation rates were often high, although treatment retention improved with slower dose titration. Adjunctive therapy with newer AEDs has the potential to enhance HRQoL and treatment continuation in patients with partial epilepsy. There remains room for improvement in the management of epilepsy, and better treatments and longer-term trials are needed to meet the special requirements of refractory patients.