gebhart/patrepeval huggingface dataset:
Microorganisms as Antineoplastic Agents in CNS Tumors (1983)

In two patients, malignant tumors unexpectedly regressed following infections. I reviewed the extensive body of literature, both experimental and clinical, concerning the antineoplastic potential of bacteria and viruses. Substantial evidence exists to indicate that microorganisms may, by growing in or near tumors, completely or partially inhibit tumor growth, or alternatively may have no effect at all. In fact, oncolysis may occur only when a specific organism infects a specific tumor.
Rapid Transcriptome Changes Induced by Cytosolic Ca2+ Transients Reveal ABRE-Related Sequences as Ca2+-ResponsivecisElements inArabidopsis (2006)

The regulation of gene expression by cellular calcium is crucial for plant defense against biotic and abiotic stresses. However, the number of genes known to respond to specific transient calcium signals is limited, and as yet there is no definition of a calcium-responsive cis element in plants. Here, we generated specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings and linked them to early transcriptome changes, followed by bioinformatic analysis of the responsive genes. A cytosolic calcium transient induced by calmodulin antagonists and blocked by lanthanides was characterized using aequorin-based luminometry and photon imaging. Analysis of transcriptome changes revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were downregulated. These include known early stress-responsive genes as well as genes of unknown function. Analysis of their upstream regions revealed, exclusively in the upregulated genes, a highly significant occurrence of a consensus sequence (P < 10(-13)) comprising two abscisic acid-specific cis elements: the abscisic acid-responsive element (ABRE; CACGTG[T/C/G]) and its coupling element ([C/A]ACGCG[T/C/G]) [corrected] Finally, we show that a tetramer of the ABRE cis element is sufficient to confer transcriptional activation in response to cytosolic Ca(2+) transients. Thus, at least for some specific Ca(2+) transients and motif combinations, ABREs function as Ca(2+)-responsive cis elements.
Dexmedetomidine Premedication Attenuates Ketamine-induced Cardiostimulatory Effects and Postanesthetic Delirium (1995)

These results suggest that premedication with 2.5 micrograms/kg dexmedetomidine is effective in attenuating the cardiostimulatory and postanesthetic delirium effects of ketamine. However, because of its propensity to cause bradycardia, routine use of an anticholinergic drug should be considered.
Non-obese diabetic–recombination activating gene-1 (NOD–Rag 1 null) interleukin (IL)-2 receptor common gamma chain (IL 2 rγnull) null mice: a radioresistant model for human lymphohaematopoietic engraftment (2008)

Immunodeficient hosts engrafted with human lymphohaematopoietic cells hold great promise as a preclinical bridge for understanding human haematopoiesis and immunity. We now describe a new immunodeficient radioresistant non-obese diabetic mice (NOD) stock based on targeted mutations in the recombination activating gene-1 (Rag1(null)) and interleukin (IL)-2 receptor common gamma chain (IL2rgamma(null)), and compare its ability to support lymphohaematopoietic cell engraftment with that achieved in radiosensitive NOD.CB17-Prkdc(scid) (NOD-Prkdc(scid)) IL2rgamma(null) mice. We observed that immunodeficient NOD-Rag1(null) IL2rgamma(null) mice tolerated much higher levels of irradiation conditioning than did NOD-Prkdc(scid) IL2rgamma(null) mice. High levels of human cord blood stem cell engraftment were observed in both stocks of irradiation-conditioned adult mice, leading to multi-lineage haematopoietic cell populations and a complete repertoire of human immune cells, including human T cells. Human peripheral blood mononuclear cells also engrafted at high levels in unconditioned adult mice of each stock. These data document that Rag1(null) and scid stocks of immunodeficient NOD mice harbouring the IL2rgamma(null) mutation support similar levels of human lymphohaematopoietic cell engraftment. NOD-Rag1(null) IL2rgamma(null) mice will be an important new model for human lymphohaematopoietic cell engraftment studies that require radioresistant hosts.
Generalized Transmissibilities for Distorted Grids in Reservoir Simulation (1986)

Abstract Distorted grids or "corner point geometry" have received increased attention as a means of enhancing the modelling flexibility of finite difference type reservoir simulators. Non-rectangular grids permit better alignment with reservoir boundaries and faults and may lead to fewer grid blocks and therefore less computational efforts in simulation of complex reservoirs. This paper shows that caution should be used as regards the transmissibility calculations for distorted grids. Specifically, it is demonstrated by simulation experiments that methods which try to maintain (for 2-D problems) the five-point connectivity of standard finite differences may lead to serious errors. A generalized nine-point scheme is constructed and shown to be more appropriate for distorted grids. For instance, the scheme seems to preserve the accuracy of a square nine-point scheme if the distortion is kept within certain limits. Although based on finite element techniques, the scheme is given a finite difference type form, and can therefore easily be implemented in more general-purpose finite difference type reservoir simulators.
Propagation of femtosecond pulses in large-mode-area, higher-order-mode fiber (2006)

We demonstrate propagation of 14 nJ femtosecond pulses through a large-mode-area, higher-order-mode (HOM) fiber with an effective area of 2100 microm2. The pulses propagate stably in the LP07 mode of the fiber through lengths as long as 12 m. The strongly chirped pulses exiting the amplifier fiber are dechirped by the high-order-mode fiber, resulting in pulses with a peak power of 61 kW after propagation in 5 m of the positive-dispersion fiber. A small amount of self-phase modulation is observed in the compressed pulses and is described well by a nonlinear Schrödinger equation model that takes into account the measured effective area and dispersion of the HOM fiber.
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling (1999)

Bone resorption and remodeling is an intricately controlled, physiological process that requires the function of osteoclasts. The processes governing both the differentiation and activation of osteoclasts involve signals induced by osteoprotegerin ligand (OPGL), a member of tumor necrosis factor (TNF) superfamily, and its cognate receptor RANK. The molecular mechanisms of the intracellular signal transduction remain to be elucidated. Here we report that mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Using in vitro assays, we demonstrate that TRAF6 is crucial not only in IL-1 and CD40 signaling but also, surprisingly, in LPS signaling. Furthermore, like TRAF2 and TRAF3, TRAF6 is essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.
Photo-Cross-Linked Triphenylenes as Novel Insoluble Hole Transport Materials in Organic LEDs (1999)

A series of new hexaalkoxytriphenylenes having 1, 2, or even 3 lateral attached acrylate moieties as polymerizable groups were synthesized and characterized. The conditions for the photopolymerization of these monomers in thin film were evaluated and tested. The bisacrylates and trisacrylates were used to build insoluble networks. When a mask is used during the irradiation, patterned films could be prepared. The polymerization reaction was controlled by GPC and FTIR spectroscopy. The networks and patterned structure were confirmed by UV spectroscopy, surface profiles, and SEM photographs. Since hexaalkoxytriphenylenes are known as excellent photoconductors, the photopolymerized films were utilized as hole transport layers in two layered organic light-emitting diodes (LEDs) with Alq3. The LED preparation, characterization, and performance are described.
Electrical contacts to carbon nanotubes down to 1nm in diameter (2005)

Rhodium (Rh) is found similar to Palladium (Pd) in making near-Ohmic electrical contacts to single-walled carbon nanotubes (SWNTs) with diameters d&amp;gt;∼1.6nm. Non-negligible positive Schottky barriers (SBs) exist between Rh or Pd and semiconducting SWNTs (S-SWNTs) with d&amp;lt;∼1.6nm. With Rh and Pd contacts, the characteristics of SWNT field-effect transistors and SB heights at the contacts are largely predictable based on the SWNT diameters, without random variations among devices. Surprisingly, electrical contacts to metallic SWNTs (M-SWNTs) also appear to be diameter dependent especially for small SWNTs. Ohmic contacts are difficult for M-SWNTs with diameters ⩽∼1.0nm possibly due to tunnel barriers resulted from large perturbation of contacting metal to very small diameter SWNTs due to high chemical reactivity of the latter.
Device-Orientation Effects on Multiple-Bit Upset in 65 nm SRAMs (2008)

The effects of device orientation on heavy ion-induced multiple-bit upset (MBU) in 65 nm SRAMs are examined. The MBU response is shown to depend on the orientation of the device during irradiation. The response depends on the direction of the incident ion to the n- and p-wells of the SRAM. The MBU response is simulated using Monte Carlo methods for a space environment. The probability is calculated for event size. Single-bit upsets in the space environment account for 90% of all events with exponentially decreasing probabilities of larger MBU events.
The effect of detector performance on high count rate PET imaging with a tomograph based on position-sensitive detectors (1988)

Emission-computed tomography systems using large position-sensitive detectors must handle high event rates per detector during dynamic studies. To determine the ability of their positron-emission tomograph (PET) to perform high-count-rate scans, the authors have studied detector performance up to single rates in excess of 2 million counts per second per detector. To evaluate the quality of images resulting from data acquired at these rates, signal-to-noise ratio analyses were applied to both simulated and experimental high-count-rate images of a cold-spot phantom. Changes in image quality were quantitated, allowing the testing of combinations of high-count-rate event processing techniques to produce optimal high-count-rate images. It was found that severe image degradation occurs when the centroid positioning algorithm is used, due to the long tails in the detector point speed function that result at high count rates. Image quality is greatly improved when the local centroid event-positioning algorithm is used to eliminate the tails. Further improvements are possible with shorter integration time and an upper-level energy discriminator set at 600 keV, close to the photopeak.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge (2017)

Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4 mg kg<sup>-1</sup> of mRNA into mice results in ∼170 μg ml<sup>-1</sup> VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1 mg kg<sup>-1</sup> of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 μg ml<sup>-1</sup>. Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases.
GSK3β: role in therapeutic landscape and development of modulators (2010)

Glycogen synthase kinase-3 beta (GSK3beta) is a multifunctional serine/threonine kinase which was originally identified as a regulator of glycogen metabolism. It plays a key role in the regulation of numerous signalling pathways including cellular process such as cell cycle, inflammation and cell proliferation. Over the last few years there is a considerable rise in the number of journals and patents publication by different workers worldwide. Many pharmaceutical companies are focusing on GSK3beta as a therapeutic target for the treatment of disease conditions. The present review is focused on signalling pathways of different disease conditions where GSK3beta is implicated. In this review, we present a comprehensive map of GSK3beta signalling pathways in disease physiologies. Structural analysis of GSK3beta along with molecular modelling reports from numerous workers are reviewed in context of design and development of GSK3beta inhibitors. Patent landscape of the small molecule modulators is profiled. The chemo space for small molecule modulators extracted from public and proprietary Kinase Chembiobase for GSK3beta are discussed. Compounds in different clinical phases of discovery are analysed. The review ends with the overall status of this important therapeutic target and challenges in development of its modulators.
Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. (1996)

Manganese superoxide dismutase (SOD2) converts superoxide to oxygen plus hydrogen peroxide and serves as the primary defense against mitochondrial superoxide. Impaired SOD2 activity in humans has been associated with several chronic diseases, including ovarian cancer and type I diabetes, and SOD2 overexpression appears to suppress malignancy in cultured cells. We have produced a line of SOD2 knockout mice (SOD2m1BCM/SOD2m1BCM) that survive up to 3 weeks of age and exhibit several novel pathologic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, and progressive motor disturbances characterized by weakness, rapid fatigue, and circling behavior. In addition, SOD2m1BCM/SOD2m1BCM mice older than 7 days exhibit extensive mitochondrial injury within degenerating neurons and cardiac myocytes. Approximately 10% of SOD2m1BCM/SOD2m1BCM mice exhibit markedly enlarged and dilated hearts. These observations indicate that SOD2 deficiency causes increased susceptibility to oxidative mitochondrial injury in central nervous system neurons, cardiac myocytes, and other metabolically active tissues after postnatal exposure to ambient oxygen concentrations. Our SOD2-deficient mice differ from a recently described model in which homozygotes die within the first 5 days of life with severe cardiomyopathy and do not exhibit motor disturbances, central nervous system injury, or ultrastructural evidence of mitochondrial injury.
Analysis of the α‐amylase gene of Schwanniomyces occidentalis and the secretion of its gene product in transformants of different yeast genera (1989)

We have cloned and characterized the alpha-amylase gene (AMY1) of the yeast Schwanniomyces occidentalis. A cosmid gene library of S. occidentalis DNA was screened in Saccharomyces cerevisiae for alpha-amylase secretion. The positive clone contained a DNA fragment harbouring an open reading frame of 1536 nucleotides coding for a 512-amino-acid polypeptide with a calculated Mr of 56,500. The deduced amino acid sequence reveals significant similarity to the sequence of the Saccharomycopsis fibuligera and Aspergillus oryzae alpha-amylases. The AMY l gene was found to be expressed from its original promoter in S. cerevisiae, Kluyveromyces lactis and Schizo-saccharomyces pombe leading to an active secreted gene product and thus enabling the different yeast transformants to grow on starch as a sole carbon source.
Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia (2019)

Thus, our study suggests that the global loss of 5-hmC, accompanied by its significant increase at the gene regulatory regions, constitute a novel hallmark of CLL pathogenesis. Our combined analysis of 5-mC and 5-hmC sequencing provided insights into the potential role of 5-hmC in modulating gene expression changes during CLL pathogenesis.
Overview of interleukin‐2 as an immunotherapeutic agent (1989)

Interleukin-2 (IL-2) is a lymphokine which has a variety of in vivo immunomodulatory effects. The administration of IL-2 can mediate enhancement of cellular immune responses, induction of lymphocyte proliferation, production of cytokines, and regression of established tumor in animal models. The availability of large quantities of recombinant IL-2 has enabled investigators to examine its therapeutic potential in the treatment of human cancer. Several studies have documented the ability of IL-2 administration to cause durable tumor regression in patients with advanced melanoma and renal cell cancer. Toxicity of therapy is dose related and is mediated by a vascular capillary leak syndrome, lymphocytic infiltration, and the release of cytokines secreted in response to IL-2 administration. The side effects are completely reversible upon cessation of therapy. Future efforts are aimed at increasing the antitumor efficacy and decreasing the toxicity of IL-2 administration.
Structure and function of VEGF receptors (2009)

Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development and homeostasis. VEGFs are predominantly produced by endothelial, hematopoietic, and stromal cells in response to hypoxia and upon stimulation by growth factors such as transforming growth factor beta (TGFbeta), interleukins, or platelet-derived growth factors (PDGFs). VEGFs specifically interact with one or several receptor tyrosine kinases (RTKs), VEGF receptor-1, -2, and -3 (VEGFR-1, -2, -3), and with distinct coreceptors such as neuropilins or heparan sulfate glycosaminoglycans. VEGF receptors are classified as type V RTKs whose extracellular domains consists of seven immunoglobulin-like (Ig-like) domains. VEGF receptors are activated upon ligand-mediated dimerization. However, little was known about the mechanism of receptor activation at the structural level until recently. New data published by several labs for VEGF and the related type III RTKs now suggest that both ligand-receptor as well as homotypic receptor-receptor interactions stabilize ligand-induced receptor dimers. These data support the idea that structural changes induced in the extracellular domain upon ligand binding instigate transmembrane signaling by properly positioning the intracellular kinase domains in active receptor dimers.
Abstract 4831: The A2B Adenosine Receptor Contributes to Post-Infarction Heart Failure (2008)

Recent studies have been directed at understanding the role of the A 2B receptor in regulating cardioprotection, coronary blood flow, fibroblast function, and inflammation. Unlike the other adenosine receptor subtypes, the A 2B receptor is emerging as a promoter of inflammation in chronic diseases such as asthma and conditions associated with tissue fibrosis. In this study, we used A 2B receptor gene “knock-out” (A 2B −/− ) mice to test the role of the A 2B receptor in infarction-induced heart failure and cardiac remodeling. A 2B −/− mice or wild-type (WT) littermates were subjected to permanent ligation of the left coronary artery or sham surgery. Cardiac morphology and function were assessed at 4 and 8 weeks after surgery by echocardiography. At the end of the study, systemic arterial and left ventricular pressures were obtained, after which the hearts were removed and histologically assessed for infarct size and fibrosis. WT hearts experienced significant left ventricular dilation and reduced systolic (fractional area shortening, myocardial performance index, and +dP/dt max ) and diastolic (end-diastolic pressure [EDP] elevated from 3.2 ± 0.8 mmHg in sham mice to 8.8 ± 1.5 mmHg in infarcted mice and tau was prolonged from 11.6 ± 1.7 ms to 22.3 ± 2.0 ms) function at 8 weeks after coronary artery ligation. Compared to WT mice, there were no significant differences in measures of post-infarction systolic function in A 2B −/− mice. However, EDP and tau were significantly improved (2.5 ± 1.5 mmHg and 17 ± 1.4 ms, respectively) and were not worsened compared to sham-operated A 2B −/− mice (2.7 ± 2.1 mmHg and 14.5 ± 1.8 ms, respectively). Moreover, interstitial fibrosis was elevated in the non-infarcted myocardium of WT mice subjected to coronary ligation, but not in A 2B −/− mice. Importantly, infarct size (WT = 39 ± 2% of the left ventricle; A 2B −/− = 43 ± 3%) and systemic blood pressure were not significantly different between WT and A 2B −/− mice. The data suggest that absence of the A 2B receptor results in preservation of diastolic function and decreased development of reactive fibrosis following myocardial infarction. These findings support the concept that adenosine signaling via the A 2B receptor contributes to post-infarction heart failure and adverse cardiac remodeling. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Platelet rich plasma (PRP) enhances anabolic gene expression patterns in flexor digitorum superficialis tendons (2006)

Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Tendons were cultured in explant fashion with blood, plasma, PRP, PPP, or BMA at concentrations of 100%, 50%, or 10% in serum-free DMEM with amino acids. Quantitative RT-PCR for expression of collagen type I (COL1A1), collagen type III (COL3A1), cartilage oligomeric matrix protein (COMP), decorin, matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) was performed as were DNA and total soluble collagen assays. TGF-beta1 and PDGF-BB concentrations were higher in PRP compared to all other blood products tested. Tendons cultured in 100% PRP showed enhanced gene expression of the matrix molecules COL1A1, COL3A1, and COMP with no concomitant increase in the catabolic molecules MMP-3 and MMP-13. These findings support in vivo investigation of PRP as an autogenous, patient-side treatment for tendonitis.
Phase Ib study of NGR–hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours (2009)

NGR-hTNF plus doxorubicin was administered safely and showed promising activity in patients pre-treated with anthracyclines. The dose level of 0.8 microg m(-2) NGR-hTNF plus doxorubicin 75 mg m(-2) was selected for phase II development.