gebhart/patrepeval huggingface dataset:
A New Route for the Synthesis of 1,4-Dicarbonyl Compounds: Synthesis of Jasmone, Dlhydrojasmone and a Prostaglandin Intermediate (1984)

Abstract 1,4-Dicarbonyl compounds are versatile intermediates for the synthesis of a variety of natural products such as jasmonoids, prostanoids, steroids and terpenoids having a cyclopentenone or furan ring system. Although many synthetic routes for the preparation of these compounds are known and continue to appear1, most of the existing methods involve lengthy procedures and are limited to the synthesis of 1,4-diketones. Herein, we report a convenient three step approach for the synthesis of 1,4-dicarbonyl compounds starting from tosyl methyl isocyanide2 (TosMIC). This method is general for the preparation of 1,4-ketoaldehydes as well as 1,4-diketones.
Exploiting parallel microprocessor microarchitectures with a compiler code generator (1988)

With advances in VLSI technology, microprocessor designers can provide more microarchitectural parallelism to increase performance. We have identified four major forms of such parallelism: multiple microoperations issued per cycle, multiple result distribution buses, multiple execution units, and pipelined execution units. The experiments reported in this paper address two important issues: The effects of these forms and the appropriate balance among them. A central microarchitecture is identified as the comparison basis. We separately vary each form of the microarchitectural parallelism in the central to measure their individual effects on performance. In addition, we vary two forms of the microarchitectural parallelism in the central to derive an appropriate balance between them. To make fair comparisons, our compiler generates different code sequences optimized for different microarchitectural configurations. For each given set of technology constraints, these experiments can be used to derive a cost-effective microarchitecture to execute each given set of workload programs at high speed.
The GuideCane-a computerized travel aid for the active guidance of blind pedestrians (2002)

This paper introduces the GuideCane, a novel device designed to help blind or visually impaired travellers to navigate safely and quickly among obstacles and other hazards faced by blind pedestrians. The GuideCane, currently under development at the University of Michigan's Mobile Robotics Lab, comprises of a long handle and a "sensor head" unit that is attached at the distal end of the handle. The sensor head is mounted on a steerable but unpowered two-wheeled steering axle. During operation, the user pushes the lightweight GuideCane ahead of him/her. Ultrasonic sensors mounted on the sensor head detect obstacles and steer the device around it. The user feels the steering command as a very noticeable physical force through the handle and is able to follow the GuideCane's path easily and without any conscious effort.
Prediction of Cell-Penetrating Peptides (2005)

Cell-penetrating peptides, CPPs, are used as delivery vectors for pharmacologically interesting substances, such as antisense oligonucleotides, proteins and peptides. We present a general principle for designing cell-penetrating peptides derived from naturally occurring proteins as well as from randomly generated polyamino acid sequences. Thereby, we introduce a novel pharmacological principle for identification of cell-penetrating peptides for which the applications can be numerous, including cellular transduction vectors and mimics of intracellular protein–protein interactions. The methods of identifying a CPP comprises assessing the averaged bulk property values of the defined sequence, and ensuring that they fall within the bulk property value interval obtained from the training set. Despite this simplistic approach, the search criteria proved useful for finding CPP properties in either proteins or random sequences. We have experimentally verified cell-penetrating properties of 10–20-mer peptides derived from naturally occurring proteins as well as from random poly-amino acids. We note that since CPPs can be found in part of the protein sequences that may govern protein interactions, it is possible to produce cell-penetrating protein agonists or antagonists.
Inhibition of Tumor Growth Progression by Antiandrogens and mTOR Inhibitor in a Pten -Deficient Mouse Model of Prostate Cancer (2009)

Androgen receptors have been shown to play a critical role in prostate cancer. We used ultrasound imaging techniques to track tumor response to antiandrogen and rapamycin treatment in a prostate-specific Pten-deleted mouse model of cancer. Depletion of androgens by either surgical or chemical castration significantly inhibited tumor growth progression without altering the activation of Akt and mammalian target of rapamycin (mTOR). We also showed for the first time that targeting mTOR along with antiandrogen treatment exhibited additive antitumor effects in vivo when compared with single agents. Our preclinical data suggest that combination of antiandrogens with mTOR inhibitors might be more effective in treating androgen-dependent prostate cancer patients.
Regulated expression on human macrophages of endoglin, an Arg‐Gly‐Asp‐containing surface antigen (1992)

Endoglin is an endothelial homodimeric membrane antigen containing the tripeptide arginine-glycine-aspartic acid (RGD), which is a recognition motif for adhesion receptors of the integrin family. We have investigated the expression of endoglin by monocyte/macrophage cells from different tissue compartments and at different stages of cell differentiation. Although endoglin is absent from peripheral blood monocytes, it is expressed by in vitro differentiated monocytes as determined by flow cytometry using the endoglin-specific monoclonal antibody 44G4 and 8E11. Furthermore, Northern blot analyses revealed a correlation between the presence of endoglin mRNA and the surface expression of the antigen by in vitro differentiated monocytes. Immunostaining of frozen tissue sections with the 8E11 monoclonal antibody demonstrated the presence of endoglin not only in the endothelium of all the tissues studied, but also on the interstitial macrophages present in the red pulp of the spleen. Using as a model of macrophage differentiation monocytic cell lines treated with phorbol esters, we found that the reactivity of the 8E11 monoclonal antibody is greatly increased on U-937 and HL-60 cells during their PMA-induced differentiation. These findings clearly demonstrate for the first time the regulated expression of the putative adhesion molecule endoglin by macrophages.
Analysis of reflection-type optical switches with intersecting waveguides (1988)

The reflection phenomenon of the guided mode in optical switches with intersecting single-mode waveguides is investigated by the wave approach. The guided mode is expanded into an infinite spectrum of plane waves and the condition of total internal reflection is applied. The power reflectivity of the guided mode is calculated and is used to estimate the extinction ratios. It is found that at refractive index variation of about 1 percent, large extinction ratios (>30 dB) are achievable if the refractive index difference between the waveguide core and cladding is smaller than the voltage induced refractive index variation by about one order of magnitude. The intersecting angle is found to be limited to about the critical angle and is required to be large enough to prevent degradation of the extinction ratios and to keep scattering losses small. It is also indicated that by displacing the electrode, to account for the Goos Haenschen shift, it is possible to further reduce the scattering losses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Continuous Carbon Nanotube Reinforced Composites (2008)

Carbon nanotubes are considered short fibers, and polymer composites with nanotube fillers are always analogues of random, short fiber composites. The real structural carbon fiber composites, on the other hand, always contain carbon fiber reinforcements where fibers run continuously through the composite matrix. With the recent optimization in aligned nanotube growth, samples of nanotubes in macroscopic lengths have become available, and this allows the creation of composites that are similar to the continuous fiber composites with individual nanotubes running continuously through the composite body. This allows the proper utilization of the extreme high modulus and strength predicted for nanotubes in structural composites. Here, we fabricate such continuous nanotube polymer composites with continuous nanotube reinforcements and report that under compressive loadings, the nanotube composites can generate more than an order of magnitude improvement in the longitudinal modulus (up to 3,300%) as well as damping capability (up to 2,100%). It is also observed that composites with a random distribution of nanotubes of same length and similar filler fraction provide three times less effective reinforcement in composites.
Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C (2016)

Enteroviruses (EVs) represent many important pathogens of humans. Unfortunately, no antiviral compounds currently exist to treat infections with these viruses. We screened the Prestwick Chemical Library, a library of approved drugs, for inhibitors of coxsackievirus B3, identified pirlindole as a potent novel inhibitor, and confirmed the inhibitory action of dibucaine, zuclopenthixol, fluoxetine, and formoterol. Upon testing of viruses of several EV species, we found that dibucaine and pirlindole inhibited EV-B and EV-D and that dibucaine also inhibited EV-A, but none of them inhibited EV-C or rhinoviruses (RVs). In contrast, formoterol inhibited all enteroviruses and rhinoviruses tested. All compounds acted through the inhibition of genome replication. Mutations in the coding sequence of the coxsackievirus B3 (CV-B3) 2C protein conferred resistance to dibucaine, pirlindole, and zuclopenthixol but not formoterol, suggesting that 2C is the target for this set of compounds. Importantly, dibucaine bound to CV-B3 protein 2C in vitro, whereas binding to a 2C protein carrying the resistance mutations was reduced, providing an explanation for how resistance is acquired.
WIP, a protein associated with Wiskott–Aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells (1997)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency caused by mutations that affect the WAS protein (WASP) and characterized by cytoskeletal abnormalities in hematopoietic cells. By using the yeast two-hybrid system we have identified a proline-rich WASP-interacting protein (WIP), which coimmunoprecipitated with WASP from lymphocytes. WIP binds to WASP at a site distinct from the Cdc42 binding site and has actin as well as profilin binding motifs. Expression of WIP in human B cells, but not of a WIP truncation mutant that lacks the actin binding motif, increased polymerized actin content and induced the appearance of actin-containing cerebriform projections on the cell surface. These results suggest that WIP plays a role in cortical actin assembly that may be important for lymphocyte function.
A study of growth hormone release in man after oral administration of amino acids (1981)

A study was carried out in 15 male volunteers to evaluate qualitatively the secretion of growth factors following stimulation by oral amino acids. The results showed that oral administration of a combination of two amino acids (1200 mg 1-lysine plus 1200 mg 1-arginine) provoked a release of pituitary somatotropin and insulin. This phenomenon was reproducible and the growth hormone secreted in response to this stimulation had biological activity (as demonstrated by a radioreceptor assay and somatomedin induction). The effect appeared to be specific to the combination of the two amino acids; neither of the amino acids demonstrated appreciable stimulating activity when administered alone, even at the same doses.
Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease (2006)

Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by, and binding to, immune cells. Crohn's disease is a chronic debilitating disease characterized by severe T helper 1 (Th1)-driven inflammation of the gastrointestinal tract. The aim of this study is to investigate the therapeutic effect of cortistatin in a murine model of colitis. Cortistatin treatment significantly ameliorated the clinical and histopathologic severity of the inflammatory colitis, abrogating body weight loss, diarrhea, and inflammation and increased the survival rate of the colitic mice. The therapeutic effect was associated with down-regulation of inflammatory and Th1-driven autoimmune response, including the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of regulatory IL-10-secreting T cells in this therapeutic effect was demonstrated. Importantly, cortistatin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. This work identifies cortistatin as an antiinflammatory factor with the capacity to deactivate the intestinal inflammatory response and restore mucosal immune tolerance at multiple levels. Consequently, cortistatin represents a multistep therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.
Photoreceptor structure and function is maintained in organotypic cultures of mouse retinas. (2010)

Mouse retinal structure is maintained in retina-RPE organ cultures. The RPE in organ cultures produces sufficient amounts of 11-cis retinal to promote cone development and support signal transmission in the rod pathway. Organ cultures may be a powerful low-throughput screening tool to identify novel agents to promote photoreceptor cell survival and signaling.
VH gene expression and regulation in the mutant Alicia rabbit. Rescue of VHa2 allotype expression (1993)

Rabbits of the Alicia strain, derived from rabbits expressing the VHa2 allotype, have a mutation in the H chain locus that has a cis effect upon the expression of VHa2 and VHa- genes. A small deletion at the most J-proximal (3') end of the VH locus leads to low expression of all the genes on the entire chromosome in heterozygous ali mutants and altered relative expression of VH genes in homozygotes. To study VH gene expression and regulation, we used the polymerase chain reaction to amplify the VH genes expressed in spleens of young and adult wild-type and mutant Alicia rabbits. The cDNA from reverse transcription of splenic mRNA was amplified and polymerase chain reaction libraries were constructed and screened with oligonucleotides from framework regions 1 and 3, as well as JH. Thirty-three VH-positive clones were sequenced and analyzed. We found that in mutant Alicia rabbits, products of the first functional VH gene (VH4a2), (or VH4a2-like genes) were expressed in 2- to 8-wk-olds. Expression of both the VHx and VHy types of VHa- genes was also elevated but the relative proportions of VHx and VHy, especially VHx, decreased whereas the relative levels of expression of VH4a2 or VH4a2-like genes increased with age. Our results suggest that the appearance of sequences resembling that of the VH1a2, which is deleted in the mutant ali rabbits, could be caused by alterations of the sequences of the rearranged VH4a2 genes by gene conversions and/or rearrangement of upstream VH1a2-like genes later in development.
Expression of inducible nitric oxide synthase is increased in patients with heart failure due to ischemic disease (2004)

The objective of the present study was to determine the relationship between nitric oxide synthases (NOS) and heart failure in cardiac tissue from patients with and without cardiac decompensation. Right atrial tissue was excised from patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) <35% (N = 10), and from patients with CAD and LVEF >60% (N = 10) during cardiac surgery. NOS activity was measured by the conversion of L-[H(3)]-arginine to L-[H(3)]-citrulline. Gene expression was quantified by the competitive reverse transcription-polymerase chain reaction. Both endothelial NOS (eNOS) activity and expression were significantly reduced in failing hearts compared to non-failing hearts: 0.36 +/- 0.18 vs 1.51 +/- 0.31 pmol mg-1 min-1 (P < 0.0001) and 0.37 +/- 0.08 vs 0.78 +/- 0.09 relative cDNA absorbance at 320 nm (P < 0.0001), respectively. In contrast, inducible NOS (iNOS) activity and expression were significantly higher in failing hearts than in non-failing hearts: 4.00 +/- 0.90 vs 1.54 +/- 0.65 pmol mg-1 min-1 (P < 0.0001) and 2.19 +/- 0.27 vs 1.43 +/- 0.13 cDNA absorbance at 320 nm (P < 0.0001), respectively. We conclude that heart failure down-regulates both eNOS activity and expression in cardiac tissue from patients with LVEF <35%. In contrast, iNOS activity and expression are increased in failing hearts and may represent an alternative mechanism for nitric oxide production in heart failure due to ischemic disease.
Synthesis of Copolymers Containing an Active Ester of Methacrylic Acid by RAFT:  Controlled Molecular Weight Scaffolds for Biofunctionalization (2006)

We report the controlled radical copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with a monomer containing an active ester, N-methacryloyloxysuccinimide (NMS), by reversible addition fragmentation chain transfer (RAFT). The large difference in the reactivity ratios of HPMA and NMS resulted in significant variations in copolymer composition with increasing conversion during batch copolymerization. The use of a semi-batch copolymerization method, involving the gradual addition of the more reactive NMS, allowed uniformity of copolymer composition to be maintained during the polymerization. We synthesized polymers in a wide range of molecular weights (M(n) = 3000-50,000 Da) with low polydispersities (1.1-1.3). The effect of the ratio of monomer to chain transfer agent (CTA) on the molecular weight of the polymer was investigated. Given the numerous applications of poly(HPMA)-based conjugates in designing polymeric therapeutics, these controlled molecular weight activated polymers represent attractive scaffolds for biofunctionalization. As a demonstration, we attached a peptide to the activated polymer backbone to synthesize a potent controlled molecular weight polyvalent inhibitor of anthrax toxin.
Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells (2012)

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.
African green monkey kidney (Vero) cells provide an alternative host cell system for influenza A and B viruses (1996)

The preparation of live, attenuated human influenza virus vaccines and of large quantities of inactivated vaccines after the emergence or reemergence of a pandemic influenza virus will require an alternative host cell system, because embryonated chicken eggs will likely be insufficient and suboptimal. Preliminary studies indicated that an African green monkey kidney cell line (Vero) is a suitable system for the primary isolation and cultivation of influenza A viruses (E. A. Govorkova, N. V. Kaverin, L. V. Gubareva, B. Meignier, and R. G. Webster, J. Infect. Dis. 172:250-253, 1995). We now demonstrate for the first time that Vero cells are suitable for isolation and productive replication of influenza B viruses and determine the biological and genetic properties of both influenza A and B viruses in Vero cells; additionally, we characterize the receptors on Vero cells compared with those on Madin-Darby canine kidney (MDCK) cells. Sequence analysis indicated that the hemagglutinin of Vero cell-derived influenza B viruses was identical to that of MDCK-grown counterparts but differed from that of egg-grown viruses at amino acid positions 196 to 198. Fluorescence-activated cell sorting analysis showed that although Vero cells possess predominantly alpha2,3 galactose-linked sialic acid, they are fully susceptible to infection with either human influenza A or B viruses. Moreover, all virus-specific polypeptides were synthesized in the same proportions in Vero cells as in MDCK cells. Electron microscopic and immunofluorescence studies confirmed that infected Vero cells undergo the same morphological changes as do other polarized epithelia] cells. Taken together, these results indicate that Vero cell lines could serve as an alternative host system for the cultivation of influenza A and B viruses, providing adequate quantities of either virus to meet the vaccine requirements imposed by an emerging pandemic.