gebhart/patrepeval huggingface dataset:
Software acceleration using programmable hardware devices (1996)

Traditionally the hardware and software subsystems for an application have been designed independently, and subsequently integrated during the testing phase of the design cycle. In recent years there has been a resurgence of interest in the design and implementation of embedded systems, where the constituent hardware and software subsystems are developed concurrently to meet specified performance and cost constraints. This is known as hardware/software codesign. The paper presents a development environment for the design, cosynthesis and performance evaluation of general purpose hardware/software systems. In particular, we are concerned with accelerating the performance of time critical regions of programs which are being executed on a conventional microcomputer. The behaviour of an application is defined by a C program and an interactive profiling tool helps identify these critical regions. The original program is subsequently partitioned into hardware and software subsystems, where a critical region is now implemented using a programmable hardware device for improved performance. An overview of the development process is presented and the significance of our approach is demonstrated in a number of examples.
Human hematopoietic prostaglandin D synthase inhibitor complex structures (2012)

In mast and Th2 cells, hematopoietic prostaglandin (PG) D synthase (H-PGDS) catalyses the isomerization of PGH(2) in the presence of glutathione (GSH) to produce the allergic and inflammatory mediator PGD(2). We determined the X-ray structures of human H-PGDS inhibitor complexes with 1-amino-4-{4-[4-chloro-6-(2-sulpho-phenylamino)-[1,3,5]triazin-2-ylmethyl]-3-sulpho-phenylamino}-9,10-dioxo-9,10-dihydro-anthracene-2-sulphonic acid (Cibacron Blue) and 1-amino-4-(4-aminosulphonyl) phenyl-anthraquinone-2-sulphonic acid (APAS) at 2.0 Å resolution. When complexed with H-PGDS, Cibacron Blue had an IC(50) value of 40 nM and APAS 2.1 μM. The Cibacron Blue molecule was stabilized by four hydrogen bonds and π-π stacking between the anthraquinone ring and Trp104, the ceiling of the active site H-PGDS pocket. Among the four hydrogen bonds, the Cibacron Blue terminal sulphonic group directly interacted with conserved residues Lys112 and Lys198, which recognize the PGH(2) substrate α-chain. In contrast, the APAS anthraquinone ring was inverted to interact with Trp104, while its benzenesulphonic group penetrated the GSH-bound region at the bottom of the active site. Due to the lack of extended aromatic rings, APAS could not directly hydrogen bond with the two conserved lysine residues, thus decreasing the total number of hydrogen bond from four to one. These factors may contribute to the 50-fold difference in the IC(50) values obtained for the two inhibitors.
mRNA structure, in situ, as assessed by microscopic techniques (1993)

The secondary and tertiary structure of RNA, in situ, is thought to be involved in distinct functions such as directing association of the RNA with the cytoskeleton, enzymatic activity of some RNAs, and the control of translation. In situ transcription (IST), a procedure by which cDNA is synthesized in situ, has been used to assess mRNA structure in situ using fixed cells or tissues. Distinct banding patterns were noted for mouse and rat POMC. Unique IST banding patterns were observed when an oligonucleotide complementary to a putative POMC stem-loop structure was used to prime IST. Indeed local changes in banding patterns could be elicited by pharmacological agents which modulate POMC translation. Inhibition of POMC synthesis with NaF or dexamethasone decreased the number of POMC mRNAs in the polysome fractions and increased the intensity of high molecular weight IST-derived bands. Forskolin, a stimulator of POMC synthesis, had the opposite effect. One mechanism by which translational control is thought to occur is by regulation of ribosome movement down the mRNA by specific binding of cytosolic proteins to RNA structure. Cytosolic protein fractions from AtT20 pituitary cells have been shown to specifically bind to the IST-predicted RNA structure. These findings suggest that 1) mRNA structure can be assessed in situ, 2) translation may be altered by the secondary and tertiary structure of mRNAs, and 3) a predicted stem-loop structure exists in situ in the 5'-end of POMC mRNA.
Optimized magnet for a 250 MeV proton radiotherapy cyclotron (2001)

The NSCL accelerator group in 1993 carried out an extensive design study [1] for a K250 superconducting cyclotron for advanced cancer therapy. A private company ACCEL now offers cyclotrons based on this study on a commercial basis, and actual construction of a first such cyclotron is likely in the near future. In view of this, further optimization of the design of the superconducting magnet is currently underway. The configuration of the cyclotron has many similarities with previous NSCL-built superconducting cyclotrons—notable differences are the peak average field of 3 T (required by the focusing limit for protons) vs the 5 tesla of other MSU designs, and the use of four sectors rather than three to avoid the νr=3/2 stopband. The further optimization of the magnetic design described here keys on using the true 3D magnetic field program to more precisely match the design to an optimized orbital frequency configuration and to explore reducing the amount of spiral in the hills which then shortens the linear length of the rf elements and therefore reduces capacity and power consumption.
Nrf2-regulated PPARγ Expression Is Critical to Protection against Acute Lung Injury in Mice (2010)

Results indicate for the first time that Nrf2-driven PPARgamma induction has an essential protective role in pulmonary oxidant injury. Our observations provide new insights into the therapeutic potential of PPARgamma in airway oxidative inflammatory disorders.
Bottom-up Assembly of RNA Arrays and Superstructures as Potential Parts in Nanotechnology (2004)

DNA and protein have been extensively scrutinized for feasibility as parts in nanotechnology, but another natural building block, RNA, has been largely ignored. RNA can be manipulated to form versatile shapes, thus providing an element of adaptability to DNA nanotechnology, which is predominantly based upon a double-helical structure. The DNA-packaging motor of bacterial virus phi29 contains six DNA-packaging RNAs (pRNA), which together form a hexameric ring via loop/loop interaction. Here we report that this pRNA can be redesigned to form a variety of structures and shapes, including twins, tetramers, rods, triangles, and 3D arrays several microns in size via interaction of programmed helical regions and loops. Three dimensional RNA array formation required a defined nucleotide number for twisting of the interactive helix and a palindromic sequence. Such arrays are unusually stable and resistant to a wide range of temperatures, salt concentrations, and pH.
Asymmetric hydrogenation of unsaturated carboxylic acids catalyzed by BINAP-ruthenium(II) complexes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric hydrogenation of unsaturated carboxylic acids catalyzed by BINAP-ruthenium(II) complexesTetsuo Ohta, Hidemasa Takaya, Masato Kitamura, Katsunori Nagai, and Ryoji NoyoriCite this: J. Org. Chem. 1987, 52, 14, 3174–3176Publication Date (Print):July 1, 1987Publication History Published online1 May 2002Published inissue 1 July 1987https://pubs.acs.org/doi/10.1021/jo00390a043https://doi.org/10.1021/jo00390a043research-articleACS PublicationsRequest reuse permissionsArticle Views4551Altmetric-Citations307LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Modulation of Serum Brain-Derived Neurotrophic Factor by a Single Dose of Ayahuasca: Observation From a Randomized Controlled Trial (2019)

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (<i>N</i> = 45) and patients with treatment-resistant depression (<i>N</i> = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (<i>N</i> = 35) when compared to placebo (<i>N</i> = 34). Furthermore, at D2 just patients treated with ayahuasca (<i>N</i> = 14), and not with placebo (<i>N</i> = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).
Automating the design of computer systems (1993)

A hierarchical select-and-interconnect methodology for system-level design is described. It extends the flexibility of previous approaches by allowing dynamic subproblem ordering, which is essential for this domain. The design model of M1, a knowledge-based system that implements this approach for small computer systems, is presented. M1's design space covers five microprocessor families, and it has generated hundreds of designs, three of which were built. A set of experiments showing that M1 can be used successfully to design in this complex domain and provides a substantial increase in designer productivity is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Triptolide promotes spinal cord repair by inhibiting astrogliosis and inflammation (2010)

Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Traumatic SCI directly damages the cell bodies and/or processes of neurons and triggers a series of endogenous processes, including neuroinflammatory response and reactive astrogliosis. In this study, we found that triptolide, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, inhibited astrogliosis and inflammation and promoted spinal cord repair. Triptolide was shown to prevent astrocytes from reactive activation by blocking the JAK2/STAT3 pathway in vitro and in vivo. Furthermore, astrocytic gliosis and glial scar were greatly reduced in injured spinal cord treated with triptolide. Triptolide treatment was also shown to decrease the ED-1 or CD11b-positive inflammatory cells at the lesion site. Using neurofilament staining and anterograde tracing, a significantly greater number of regenerative axons were observed in the triptolide-treated rats. Importantly, behavioral tests revealed that injured rats receiving triptolide had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan open-field scoring, grid-walk, and foot-print analysis. These results suggested that triptolide promoted axon regeneration and locomotor recovery by attenuating glial scaring and inflammation, and shed light on the potential therapeutic benefit for SCI.
Panoply of Utilities in Taverna (2006)

The Taverna e-Science Workbench is a central component of myGrid, a loosely coupled suite of middleware services designed to support in silico experiments in biology. Taverna enables the construction and enactment of complex workflows over resources on local and remote machines, allowing the automation of otherwise labour-intensive multi-step bioinformatics tasks. As the Taverna user community has grown, so has the demand for new features and additions. This paper outlines the functional requirements that have become apparent over the last year of working with domain scientists, along with the solutions implemented in both the Taverna workbench and the Freefluo enactment engine to address concerns relating to workflow construction and enactment, respectively
Achieving High-Current Carbon Nanotube Emitters (2005)

When a carbon nanotube emitter is operated at high currents (typically above 1 microA per emitter), a small voltage drop ( approximately few volts) along its length or at its contact generates a reverse/canceling electric field that causes a saturation-like deviation from the classical Fowler-Nordheim behavior with respect to the applied electric field. We present a correction to the Fowler-Nordheim equation to account for this effect, which is experimentally verified using field emission and contact electrical measurements on individual carbon nanotube emitters. By using rapid thermal annealing to improve both the crystallinity of the carbon nanotubes and their electrical contact to the substrate, it is possible to reduce this voltage drop, allowing very high currents of up to 100 microA to be achieved per emitter with no significant deviation from the classical Fowler-Nordheim behavior.
Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. (1990)

Spleen dendritic cells (DC) and epidermal Langerhans cells (LC) belong to the same family of dendritic leukocytes and are considered to be prototypes of lymphoid DC and nonlymphoid DC, respectively. These cells are active APC in vitro and play a key role in the induction of primary T cell dependent immune responses in vivo. Two functional states of LC have been characterized in vitro, freshly isolated LC and cultured LC (cLC). That cLC closely resemble spleen DC in phenotype and function, has led to the hypothesis that LC undergo maturation toward DC while in culture, an event that has been correlated with the emigration of LC from skin into lymphoid organs. To date, however, DC have been studied only after overnight culture. To better understand the relationship between LC and DC, we examined DC shortly after their isolation from spleen, and after 24 h of culture. Freshly isolated DC (fDC) express high levels of MHC molecules and low levels of Fc gamma RII and C3biR; fDC also uniformly express the Ag recognized by the mAb 33D1, NLDC-145, and J11d. After culture, DC display a marked increase in the expression of MHC molecules, and they are induced to express the low affinity receptor for IL-2. By contrast, the expression of Fc gamma RII and F4/80 decreases with culture. With respect to function, fDC can efficiently present keyhole limpet hemocyanin to Ag-specific T cells, whereas cultured DC exhibit a marked reduction in this capacity. Finally, both fDC and cultured DC are capable of endocytosing surface Ia molecules, but only fDC are able to deliver them into acidic compartments. Our data indicate that fDC from spleen resemble freshly isolated LC from epidermis and that both cells undergo parallel changes during culture. These results suggest that LC and DC possess analogous attributes in vivo and respond similarly to external influences.
Activation of cellular immunity after intracavitary monoclonal antibody therapy of ovarian cancer (1994)

Mouse MoAbs administered to patients with cancer can lead to the generation of T-cells, which can recognize these MoAbs as antigens and therefore refocus the host's cellular immune response against the targeted tumor. The main proliferating population appears to be CD4+ T-lymphocytes, which after stimulation can release IL-2. Multiple treatments may lead to the generation of T-cells with specificity for the idiotypic component of the administered MoAb.
In vitro release and antiinflammatory activity of topical formulations of ketoprofen. (2000)

Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical practice for the control of acute and chronic pain of soft tissues and skeletal muscle system. The importance of KP in the therapeutic field, has stimulated the development of topical dosage forms to improve its percutaneous absorption through the application site. Moreover they could provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, typical side effect of NSAID oral administration. Since the topical formulation efficiency depends on vehicle characteristics, some different ointments, at 1% and 5% concentrations of KP, were evaluated by in vitro and in vivo studies. Among tested ointments, 1% Carbopol cream and 5% Carbopol gel showed the best fluxes of drug through regenerated cellulose membrane. The in vivo percutaneous absorption of KP, evaluated by carrageenan-induced paw edema in rats, showed a good correlation with the in vitro results about considered creams, but the gels in vivo activity was not in according to their in vitro behaviour. The extemporaneous Carbopol cream was able to produce a better edema inhibition than the commercial one, taken as a reference and widely utilized as a topical therapeutic item. About gels, the obtained results were nearly the maximum response considered possible for a topical antiinflammatory drug.
Mice lacking functional TRPV1 are protected from pressure overload cardiac hypertrophy (2011)

TRPV1 (transient receptor potential cation channel, subfamily V, member 1) is best studied in peripheral sensory neurons as a pain receptor; however TRPV1 is expressed in numerous tissues and cell types including those of the cardiovascular system. TRPV1 expression is upregulated in the hypertrophic heart, and the channel is positioned to receive stimulatory signals in the hypertrophic heart. We hypothesized that TRPV1 has a role in regulating cardiac hypertrophy. Using transverse aortic constriction to model pressure overload cardiac hypertrophy we show that mice lacking functional TRPV1, compared to wild type, have improved heart function, and reduced hypertrophic, fibrotic and apoptotic markers. This suggests that TRPV1 plays a role in the progression of cardiac hypertrophy, and presents a possible therapeutic target for the treatment of cardiac hypertrophy and heart failure.
Specific targeting strategies of cancer gene therapy using a single-chain variable fragment (scFv) with a high affinity for CEA. (2000)

Two specific targeting strategies of cancer gene therapy using carcinoembryonic antigen (CEA) as a target are briefly reviewed here. One method is the specific targeting of suicide genes to CEA-expressing tumor cells by a retrovector displaying anti-CEA single-chain variable fragment (scFv). We reconstructed a recombinant retroviral vector that displays both anti-CEA scFv-expressing chimeric and normal envelope proteins and carries the inducible nitric oxide synthase (iNOS) gene. This recombinant retrovirus specifically bound, infected and killed only CEA-expressing tumor cells, indicating the cell specific retroviral vector delivery of the iNOS gene. Another novel method is the specific redirecting of cytotoxic T-cells to CEA-expressing tumor cells through chimeric receptors. We also reconstructed a chimeric receptor gene which encoded an anti-CEA scFv antibody and the zeta-chain of human TCR/CD3 complex and expressed it on T-cell surface. When incubated with CEA-expressing tumor cells in vitro, the transduced T-cells tended to make a rosette-like formation around the tumor cells, suggesting the cell specific targeting of T-cells.
Cutaneous and Pulmonary Infections Caused by Mycobacterium vaccae (1996)

Mycobacterium vaccae is a rapidly growing mycobacterial species that was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease, and three patients had cavitary lung disease. Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin.
T Cell Receptor-mediated Activation of p38α by Mono-phosphorylation of the Activation Loop Results in Altered Substrate Specificity (2009)

p38 MAPKs are typically activated by upstream MAPK kinases that phosphorylate a Thr-X-Tyr motif in the activation loop. An exception is the T cell antigen receptor signaling pathway, which bypasses the MAPK cascade and activates p38alpha and p38beta by phosphorylation of Tyr-323 and subsequent autophosphorylation of the activation loop. Here we show that, unlike the classic MAPK cascade, the alternative pathway results primarily in mono-phosphorylation of the activation loop residue Thr-180. Recombinant mono-phosphorylated and dual phosphorylated p38alpha differed widely with regard to activity and substrate preference. Altered substrate specificity was reproduced in T cells in which p38 was activated by the alternative or classical MAPK pathways. These findings suggest that T cells have evolved a mechanism to utilize p38 in a specialized manner independent of and distinct from the classical p38 MAPK signaling cascade.