gebhart/patrepeval huggingface dataset:
The CRISPR/Cas Immune System Is an Operon Regulated by LeuO, H-NS, and Leucine-Responsive Regulatory Protein in Salmonella enterica Serovar Typhi (2011)

Prokaryotes have developed multiple strategies to survive phage attack and invasive DNA. Recently, a novel genetic program denominated the CRISPR/Cas system was demonstrated to have a role in these biological processes providing genetic immunity. This defense mechanism is widespread in the Archaea and Bacteria, suggesting an ancient origin. In the last few years, progress has been made regarding the functionality of the CRISPR/Cas system; however, many basic aspects of the system remain unknown. For instance, there are few studies about the conditions and regulators involved in its transcriptional control. In this work, we analyzed the transcriptional organization of the CRISPR/Cas system as well as the positive and negative regulators involved in its genetic expression in Salmonella enterica serovar Typhi. The results obtained show that in S. Typhi the CRISPR/Cas system is a LeuO-dependent operon silenced by the global regulator LRP, in addition to the previously known nucleoid-associated protein H-NS; both LRP and H-NS bind upstream and downstream of the transcriptional start site of casA. In this study, relevant nucleotides of the casA regulatory region that mediate its LeuO transcriptional activation were identified. Interestingly, specific growth conditions (N-minimal medium) were found for the LeuO-independent expression of the CRISPR/Cas system in S. Typhi. Thus, our work provides evidence that there are multiple modulators involved in the genetic expression of this immune system in S. Typhi IMSS-1.
[Biotransformation of 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo-[5.2.1.0-2, 6endo] dec-8-en-3one in the rat]. (1988)

The metabolism of the analgesic compound 4-oxa-5-exo-(N-methylcarbamoyloxy)-tricyclo-[5.2.1.0-2. 6endo]dec-8-en-3one (Lu 253) was investigated after oral application in male Wistar rats. From urine, faeces, bile, and plasma epoxidized, rearranged, and N-desmethylated metabolites were isolated. The main reaction was the epoxidation of the double bond. The structure of most of the biotransformation products was proved by synthetic compounds.
Get Out of my Picture! Internet-based Inpainting (2009)

We present a method to replace a user specified target region of a photograph by using other photographs of the same scene downloaded from the Internet via viewpoint invariant image search.Each of the retrieved images is first geometrically then photometrically registered with the query photograph.Geometric registration is achieved using multiple homographies and photometric registration is performed using a global affine transformation on image intensities.Each retrieved image proposes a possible solution for the target region.In the final step we combine these proposals into a single visually consistent result, using a Markov random field optimisation to choose seams between proposals, followed by gradient domain fusion.We demonstrate removal of objects and people in challenging photographs of Oxford landmarks containing complex image structures.
Imaging endogenous dopamine competition with [11C]raclopride in the human brain (1994)

This study images dopamine release in response to a neurochemically specific challenge with the psychostimulant drug methylphenidate. Changes in synaptic dopamine induced by methylphenidate were evaluated with positron emission tomography and [11C]raclopride, a D2 receptor radioligand that is sensitive to endogenous dopamine. Methylphenidate significantly decreased striatal [11C]raclopride binding. The decrease was variable and was negatively correlated with age. Mood and anxiety at baseline, were also correlated with methylphenidate-induced DA changes. This strategy provides a tool to investigate the responsiveness of the dopamine system in the normal and diseased human brain and to investigate the neurochemical correlates of behavior.
A New Approach to Reducing Output Ripple in Switched-Capacitor-Based Step-Down DC&amp;ndash;DC Converters (2006)

Rapidly dropping power supply voltages and tight voltage regulation requirements for integrated circuits challenges power supply designers. A novel interleaved discharging (ID) approach is presented to reduce the output ripple in step-down switched-capacitor (SC) dc-dc converters. Simulation and experimental results of a four-stage SC dc-dc converter show that the ID approach can reduce the output ripple by a factor of three. The proposed approach also improves the converter efficiency by 7%. The ID method provides flexibility in the design optimization of step-down SC dc-dc converters
Dynamic x-ray imaging system based on an amorphous silicon thin-film array (1998)

In this paper we address design concepts and performance characterization with our laboratory x-ray detector system. Key component is a 1k<SUP>2</SUP> pixel TFT switched photodiode array with a pixel pitch of 200 micrometer. It is built of a-Si:H with a CsI:Tl scintillator layer. The detector system can be used for radiography and fluoroscopy applications with up to 30 images/s. It shows a S/N-ratio better than 23dB at a dose of 10nGy/frame and reaches a value for DQE of more than 60% at low spatial frequencies. We have developed a new evaporation process for CsI:Tl deposition directly on the array. It yields an x-ray sensitivity close to the theoretical limit and a spatial resolution on a sufficiently high level. An optimized plate design in combination with a dedicated charge sensitive readout amplifier chip lead to a very low level of electronic noise. In particular sources and properties of electronic noise and signal crosstalk have shown to be crucial for the clinical use of the new technology. The visual impression of the remaining noise in the images from our system is isotropic. This means especially that synchronous noise has been reduced to the edge of visibility.
A proposed structural model of endothelin. (1992)

We have assessed the hydropathic nature, secondary structure, and flexibility of endothelin and report a testable model for the structure of this 21-amino acid vasoconstrictor peptide. The proposed model consists of a rigid (disulfide bonded), hydrophilic amino-terminal half of the molecule with two turns, and an extended hydrophobic sheet structure comprising the C-terminal half of the molecule. The extended structure may be stabilized by intermolecular hydrogen bonding, leading to dimers or higher order aggregates, and is hydrophobic enough to partition into an organic solvent such as ether, as long as the molecule can keep its hydrophilic amino terminus in an aqueous phase. To test this model, partitioning measurements were made on bioactive synthetic endothelin. It was found to partition at the interface of an ether/water system in a concentration- and surface area-dependent manner. A further indication as to the amphipathic nature of the molecule is that microcrystals of synthetic endothelin tend to grow at an organic-aqueous interface in a two-phase system.
Pex Gene Deletions in Gy and Hyp Mice Provide Mouse Models for X-Linked Hypophosphatemia (1997)

X-linked hypophosphatemic rickets in humans is caused by mutations in the PEX gene which codes for a protein homologous to neutral endopeptidases. Hyp and Gy mice both have X-linked hypophosphatemic rickets, although genetic data and the different phenotypic spectra observed have previously suggested that two different genes are mutated. In addition to the metabolic disorder observed in Hyp mice, male Gy mice are sterile and show circling behavior and reduced viability. We now report the cloning of the mouse homolog of PEX which is highly conserved between man and mouse. The 3' end of this gene is deleted in Hyp mice. In Gy mice, the first three exons and the promotor region are deleted. Thus, Hyp and Gy are allelic mutations and both provide mouse models for X-linked hypophosphatemia.
Major Interference from Leukocytes in Reverse Transcription-PCR Identified as Neurotoxin Ribonuclease from Eosinophils: Detection of Residual Chronic Myelogenous Leukemia from Cell Lysates by Use of an Eosinophil-depleted Cell Preparation (1999)

The depletion of eosinophils during the preparation of leukocyte samples for RT-PCR efficiently reduces the risk of mRNA degradation by ribonucleases, enabling RT-PCR analysis directly from cell lysates with a better signal than can be obtained by RNA extraction.
Wetting of a Polymer Brush by a Chemically Identical Polymer Melt (1997)

We present a theoretical study of the conformations of a polymer brush (made of linear macromolecules chemically anchored to a flat, solid interface) when it is exposed to a molten, compatible polymer. At large brush grafting densities σ and melt molecular weights P, the melt only penetrates the brush over a distance λ that is small, compared to the brush thickness. For P > N2/3σ-2/3, the penetration length λ ≈ aσ-1/3N1/3 (Leibler et al. Proceedings of the OUMS Conference, Osaka, Japan, June, 1993) is associated with partial wetting. For P < N2/3σ-2/3, although wetting is complete (as was predicted by Leibler et al), we find that penetration is still partial: λ = aσ-1NP-1. There should be implications in interfacial rheology and in wetting dynamics.
Novel cytokines and cytokine-producing T cells in allergic disorders (2011)

Allergic diseases reflect various pathways of T lymphocyte inflammation and largely comprise T helper (Th) 2-associated processes. Recent investigations have identified pathways involved in promoting Th2 responses. Additionally, novel T-cell subtypes, each with its own distinct cytokine profile, contribute to the heterogeneous presentations of allergic diseases. This article focuses on recent developments including novel effector (nuocytes, Th9, and Th22) and regulatory T-cell (Treg) families of lymphocytes as well as cytokines that are central in driving Th2 differentiation (interleukin [IL]-4, IL-9, IL-25, thymic stromal lymphopoietin [TSLP], and IL-33). Recent literature and investigations were reviewed. Unregulated IL-25, TSLP, and IL-33 activity results in activation of Th2 cells, mast cells, dendritic cells, eosinophils, and basophils, leading to inflammatory processes that define allergic disease. As such, these cytokines are central mediators capable of instigating the inflammatory processes responsible for allergen-mediated diseases. The previous paradigm of Th1/Th2 imbalance driving allergic disease is expanded by identification of novel T helper families (nuocytes, Th9, Th17, and Th22) with their signature cytokines, which provide alterative avenues for investigation of neutrophil-predominant asthma and other heterogeneous presentations of allergic diseases. IL-25, TSLP, and IL-33 are attractive targets for therapeutics designed to ameliorate Th2-mediated diseases such as allergic rhinitis and asthma. Moreover, the ability to delineate novel regulatory and effector T-cell lineages among CD4(+) T cells challenges the Th1/Th2 paradigm of allergic disease and invites further avenues of investigation into the role of these cells in allergic disease.
Regulation of aleurone development in cereal grains (2010)

The aleurone layer of cereal grains is important biologically as well as nutritionally and economically. Here, current knowledge on the regulation of aleurone development is reviewed. Recent reports suggest that the control of aleurone development is more complex than earlier models portrayed. Multiple levels of genetic regulation control aleurone cell fate, differentiation, and organization. The hormones auxin and cytokinin can also influence aleurone development. New technical advances promise to facilitate future progress.
Calmodulin Antagonists Inhibit Human Immunodeficiency Virus-Induced Cell Fusion but Not Virus Replication (1994)

We have reported that amphipathic helical segments in the cytoplasmic domain of the HIV-1 envelope glycoproteins bind to calmodulin (CaM) with high affinity, and inhibit calmodulin-regulated proteins. To investigate the possible role of calmodulin activity in HIV-1 replication, we investigated the anti-HIV activity of various CaM antagonists--trifluoperazine and naphthalenesulfonamide W13 or W7--in HeLa T4 cells, PBMCs, and various T lymphocytic cell lines. The different CaM antagonists were found to inhibit the proliferation of the different cell types to varying extent. Also, the CaM antagonists were found to exert a greater antiproliferative effect on H9/HIV-1IIIB, as compared to uninfected H9 cells, suggesting a deficit of CaM function in HIV-infected cells. The CaM antagonists inhibited virus-induced cell fusion in HeLa T4 cells infected with a recombinant vaccinia virus expressing HIV-1 envelope proteins at threshold concentrations that do not inhibit cell proliferation. The fusion-inhibitory effects of the CaM antagonists were also observed in cocultures of HIV-infected (H9/HIV-1IIIB) and uninfected H9 cells. Under these conditions, the synthesis and surface expression of the viral glycoproteins were not affected, although the kinetics of processing of HIV envelope precursor was delayed. Virus production from both HIV-infected peripheral blood mononuclear cell (PBMC) and MT-2 cell cultures was inhibited by CaM antagonists at concentrations that were inhibitory to cell proliferation. Surprisingly, threshold concentrations of CaM antagonists that do not inhibit cell proliferation were found to enhance virus production from HIV-infected MT-2 cells, but not PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Cost-effectiveness of asenapine in the treatment of schizophrenia in Canada (2014)

Despite the short time horizon, the lack of compliance data and the assumptions made, this economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most of the atypical antipsychotics frequently used in Canada.
LASER SHORT PULSE HEATING WITH CONVECTIVE BOUNDARY CONDITION (2000)

Laser short pulse heat can be applied widely in industry. The modelling of laser heat is fruitful when exploring the physical process involved during interaction between laser and workpiece. In this study, a modelling of laser short pulse heating is considered with convection boundary conditions. Electron kinetic theory and the Fourier heating model are taken into account when modelling the heating process. The governing equations are nondimensionalized and the numerical method employing a finite difference scheme is introduced for solving the governing equations. The range of Biot number ( Bi ) values is considered to account for the convection loss from the surface during the heating process. The predictions of electron kinetic theory and the Fourier heating model are compared with the two-equation model predictions. It is found that the effect of the Bi is significant on the temperature rise in the surface vicinity. The electron kinetic theory predictions at high Bi approach the Fourier heating model findings as the heating progresses.
Cell addressing and trapping using novel optoelectronic tweezers (2004)

We present novel optoelectronic tweezers (OET) that are capable of trapping and transporting multiple biological cells. This is based on a new mechanism called light induced dielectrophoresis proposed by our group. OET allows a focused optical beam to create a virtual electrode on a photoconductive surface, producing a highly non-uniform electric field. This enables optical addressing of dielectrophoresis forces with a spatial resolution of /spl sim/1 /spl mu/m. The optical intensity required is three orders of magnitudes lower than that of conventional optical tweezers. By scanning the laser beam, the trapped cells can be moved to any position on a 2D surface. Experimentally, we have successfully demonstrated the concentration and transport of multiple E. coli cells using a HeNe laser with a focused spot size of 17 /spl mu/m. Optical power as low as 8 /spl mu/W is sufficient trap the E coli cells.
Next-Generation Optical Access Networks (2007)

The main bandwidth bottleneck in today's networks is in the access segment. To address that bottleneck, broadband fiber access technologies such as passive optical networks (PONs) are an indispensable solution. The industry has selected time-division multiplexing (TDM) for current PON deployments. To satisfy future bandwidth demands, however, next-generation PON systems are being investigated to provide even higher performance. In this paper, we first review current TDM-PONs; we designate them as generation C. Next, we review next-generation PON systems, which we categorize into C+1 and C+2 generations. We expect C+1 systems to provide economic near-term bandwidth upgrade by overlaying new services on current TDM-PONs. For the long term, C+2 systems will provide more dramatic system improvement using wavelength division multiplexing technologies. Some C+2 architectures require new infrastructures and/or equipment, whereas others employ a more evolutionary approach. We also review key enabling components and technologies for C+1 and C+2 generations and point out important topics for future research.
Anti-HLA-DR Monoclonal Antibody Evokes a Novel Non-Apoptotic Cell Death Pathway In Acute Lymphoblastic Leukemia (2010)

Abstract Abstract 3245 Whilst modern treatment approaches cure a high number of patients with acute lymphoblastic leukemia (ALL), little progress has been made in the treatment of refractory and relapsed ALL and new treatment approaches are needed. We recently demonstrated that anti-HLA-DR class II monoclonal antibody (mAb) L243 induces a novel non-apoptotic mode of cell death in B-cell lymphoma lines, defined by homotypic adhesion (HA), actin reorganisation and lysosomal activity (Ivanov et al. J Clin Invest, 2009). Here, we extend these important observations and examine whether this novel form of mAb induced cell death occurs in pre-B ALL cell lines. Expression of HLA-DR was determined using flow cytometry in a panel of ALL cell lines (REH, SupB15 and SD1). HLA-DR was expressed at high levels on each of the cell lines. The ability of L243 to induce HA and cell death (Annexin V/PI positivity) was assessed using microscopy and flow cytometry respectively. L243 was able to evoke both strong HA and cell death in all of the ALL cell lines (e.g. in SupB15 cells 46±1.7% death versus 7±0.5% in controls, p&lt;0.001 by Student's t-test). Inhibitors of actin polymerization (cytochalasin D, latrunculin B) were used to assess the role of actin in cell death and HA induced by L243. These inhibitors of actin polymerization inhibited both HA and cell death elicited by L243 (e.g. in SupB15 cells 24±0.5% death versus 10.3±0.8% with Latrunculin B, p&lt;0.001), demonstrating the dependence of HA and cell death on actin reorganisation. The importance of cell to cell contact in this form of antibody induced cell death was confirmed by the addition of low-melting point agarose which physically blocked cell to cell contact and markedly attenuated cell death induced by L243. In contrast using the pan-caspase inhibitor QVD OPH had no effect on cell death induced by L243, indicating that this mode of death is non-apoptotic. These findings demonstrate that anti-HLA DR mAb L243 induces a novel model of cell death in ALL cell lines that is independent of caspase activation and dependent on actin reorganization. This data suggests that this novel mAb induced death pathway is independent of apoptosis and potentially exploitable in the clinic in leukemias resistant to chemotherapy apoptosis induction. Disclosures: No relevant conflicts of interest to declare.
Eukaryotic Elongation Factor 1A Interacts with the Upstream Pseudoknot Domain in the 3′ Untranslated Region of Tobacco Mosaic Virus RNA (2002)

The genomic RNA of tobacco mosaic virus (TMV), like that of other positive-strand RNA viruses, acts as a template for both translation and replication. The highly structured 3' untranslated region (UTR) of TMV RNAs plays an important role in both processes; it is not polyadenylated but ends with a tRNA-like structure (TLS) preceded by a conserved upstream pseudoknot domain (UPD). The TLS of tobamoviral RNAs can be specifically aminoacylated and, in this state, can interact with eukaryotic elongation factor 1A (eEF1A)/GTP with high affinity. Using a UV cross-linking assay, we detected another specific binding site for eEF1A/GTP, within the UPDs of TMV and crucifer-infecting tobamovirus (crTMV), that does not require aminoacylation. A mutational analysis revealed that UPD pseudoknot conformation and some conserved primary sequence elements are required for this interaction. Its possible role in the regulation of tobamovirus gene expression and replication is discussed.
Signal relays in the VEGF system (1999)

A considerable progress has been made during the past years in elucidating the molecular actors of angiogenesis. Vascular endothelial growth factor turned out to represent the major inducer of angiogenesis. Optional splicing of its pre messenger RNA generates various isoforms which differ not only by their storage in the extracellular matrix but also by their signaling pathways. VEGF binds and activates two tyrosine kinase receptors called VEGFR1 and VEGFR2 and neuropilin-1. The elucidation of the transduction pathways of each receptor suggests that VEGFR1 mediates cell migration whereas VEGFR2 mediates cell proliferation. The construction of internal images of VEGF by the anti-idiotypic antibody strategy allowed us to determine that quiescent endothelial cells need to be activated by so far unknown factors to become competent to respond to mitogenic signals and acquire an angiogenic phenotype. The discovery of the mechanisms of action of the VEGF system has allowed the design of promising drugs which already entered the pre-clinical or clinical assays.
Immune evasion in cancer: Mechanistic basis and therapeutic strategies (2015)

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.