gebhart/patrepeval huggingface dataset:
A phase I/II study to assess the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) infusion of MB07133 in subjects with unresectable hepatocellular carcinoma (HCC) (2006)

2054 Background: MB07133 is a novel cytarabine (araC) prodrug that uses the HepDirect technology to target production of the active form of araC, araC triphosphate (araCTP), to the liver. The study objectives were to determine the maximum tolerated dose, toxicity profile (NCI-CTC 2.0), PK &amp; antitumor activity of MB07133 in patients (pts) with unresectable HCC. MB07133 was given as a continuous IV infusion at escalating doses during the first 7 days of a 28-day cycle until disease progression or unacceptable toxicity occurred. To date, 22 pts with Child-Pugh Class A liver function have been enrolled in 4 cohorts (300, 600, 1200, 1800 mg/m 2 /d, D1–7), with 3–6 pts/cohort. Enrolled pts had a median age of 57 yrs (range 20–67) &amp; consisted of 21 males, 1 female, 19 Asians &amp; 3 Caucasians. A total of 66 cycles have been administered (maximum 10 cycles in 1 pt) with no dose-limiting toxicities associated with therapy. Most drug-related toxicities (67%) were mild to moderate (gr 1–2 neutropenia, thrombocytopenia &amp; increased ALT). There was 1 gr 3 ascites unrelated to study drug and no gr 4 toxicity. Six pts experienced 10 serious adverse events, all unrelated or unlikely related to study drug. The very low araC concentrations in the plasma (see table ) were consistent with previous animal studies, which demonstrated MB07133 to target araCTP production in the liver. 36% of pts who had ≥ 2 cycles of MB07133 had disease stabilization. Conclusions: MB07133 is well tolerated at doses up to 1800 mg/m 2 /d in pts with unresectable HCC. Enrollment of a 2400 mg/m 2 cohort is ongoing. The disease stabilization observed in this study, although preliminary, warrants further investigation in Phase 2. [Table: see text] [Table: see text]
Ideal efficiency of monolithic, series‐connected multijunction solar cells (2002)

Abstract Two‐terminal, monolithic tandem solar cells represent the most interesting implementation of tThe multijunction photovoltaic array capable of very high efficiency. Radiative coupling among the cells, and between the cells and the substrate, along with series interconnection are features present in this approach. Their effect on efficiency is quantified for arrays with a small number of cells in the radiative limit and compared with the best experimental cells to assess their potential improvement. Finally, it is shown that they do not lower the limiting efficiency of the infinite tandem array, which is determined by the emission losses through the illuminated face. Copyright © 2002 John Wiley &amp; Sons, Ltd.
The cytoplasmic domain of CD28 is both necessary and sufficient for costimulation of interleukin-2 secretion and association with phosphatidylinositol 3'-kinase. (1994)

T-cell activation requires two signaling events. One is provided by the engagement of the T-cell antigen receptor, and the second represents a costimulatory signal provided by antigen-presenting cells. CD28 mediates a costimulatory signal by binding its ligands, B7-1 and B7-2, on antigen-presenting cells, but the signaling pathway activated by CD28 has not been identified. A homologous molecule, CTLA-4, expressed on activated T cells, also binds to B7-1 and B7-2, but whether it has a signaling function is not known. We performed a structure-function analysis of CD28 to identify the functional domain which activates signal transduction. Truncation of the 40-amino-acid CD28 cytoplasmic tail abrogated costimulatory signaling. Chimeric constructs containing the extracellular and transmembrane regions of CD8 linked to the cytoplasmic region of CD28 had a costimulatory signaling function. Similar chimeras containing the cytoplasmic tail of CTLA-4 did not signal. Thus, the cytoplasmic region of CD28, but not CTLA-4, is sufficient to mediate costimulatory signaling. In addition, after CD28 stimulation, the p85 subunit of phosphatidylinositol 3'-kinase and phosphatidylinositol 3'-kinase activity were found in CD28 immunoprecipitates. The CD8-CD28 chimera, which has a costimulatory signaling function, associates with p85, while the nonfunctioning CD8-CTLA-4 chimera and a CD8-zeta chimera do not associate with p85. These results suggest that phosphatidylinositol 3'-kinase is specifically activated by CD28 and may mediate proximal events in the costimulatory signaling pathway regulated by CD28.
Human IgG1 antibodies antagonizing activating receptor NKG2D on natural killer cells (2009)

NKG2D is a surface receptor expressed on NK cells but also on CD8(+) T cells, gammadelta T cells, and auto-reactive CD4(+)/CD28(-) T cells of patients with rheumatoid arthritis. Various studies suggested that NKG2D plays a critical role in autoimmune diseases, e.g., in diabetes, celiac disease and rheumatoid arthritis (RA), rendering the activating receptor a potential target for antibody-based therapies. Here, we describe the generation and characteristics of a panel of human, high-affinity anti-NKG2D IgG1 monoclonal antibodies (mAbs) derived by phage display. The lead molecule mAb E4 bound with an affinity (KD) of 2.7 +/- 1.4 x 10(-11) M to soluble and membrane-bound human NKG2D, and cross-reacted with NKG2D from cynomolgus macaque, indicating potential suitability for studies in a relevant primate model. MAb E4 potently antagonized the cytolytic activity of NKL cells against BaF/3-MICA cells expressing NKG2D ligand, and blocked the NKG2D ligand-induced secretion of TNFalpha, IFNgamma and GM-CSF, as well as surface expression of CRTAM by NK cells cultured on immobilized MICA or ULBP-1 ligands. The antibody did not show a detectable loss of binding to NKG2D after seven days in human serum at 37 degrees C, and resisted thermal inactivation up to 70 degrees C. Based on these results, anti-human NKG2D mAb E4 provides an ideal candidate for development of a novel therapeutic agent antagonizing a key receptor of NK and cytotoxic T cells with implications in autoimmune diseases.
Therapeutic approaches in myelofibrosis (2011)

Three categories of drugs have proved to have significant activity in MPN-associated myelofibrosis. Up to a 40% response rate on anemia has been reported with the immunomodulator, pomalidomide. The m-TOR inhibitor RAD-001 and various JAK2 inhibitors have documented a profound effect on splenomegaly and constitutional symptoms, with some also having activity on anemia. These new drugs will give physicians more options to tailor therapeutic choice in this challenging disease.
Tissue and Zonal-Specific Expression of an Olfactory Receptor Transgene (1998)

Discrimination of odorants is thought to arise from the selective expression of one of a small number of individual receptors in any single olfactory neuron. Receptor genes are expressed in a small subset of neurons throughout a zonally restricted region of the sensory epithelium. We demonstrate that a 6.7 kb region upstream of the M4 olfactory receptor coding region was sufficient to direct expression in olfactory epithelium. Moreover, reporter expression recapitulated the zonal restriction and distributed neuronal expression observed for endogenous olfactory receptors. Transgenic lines were obtained that directed expression in two different receptor zones, one of which was identical to the endogenous M4 receptor. When the reporter was expressed in the same zone as the endogenous M4 receptor, the two expression patterns were, in large part, nonoverlapping. These results suggest a model in which important regulatory elements are located in close proximity to transcription initiation sites of the olfactory receptor genes and receive information defining zonal patterning via long-range processes.
Immunosuppressive and anti-proliferative effects of a macrotetrolide antibiotic, tetranactin. (1988)

The macrotetrolide tetranactin suppressed the appearance of experimental autoimmune uveoretinitis induced in Lewis rats with a soluble retinal antigen (S-antigen). The drug at 1 ng/ml inhibited the mitogen activation of unfractionated lymphocytes; incorporation of radiolabelled precursors such as thymidine, uridine and leucine into the cells was markedly reduced. The synthesis and release of IL-2 by mitogen-activated lymphocytes was significantly suppressed in the presence of tetranactin. Incorporation of 45Ca was also inhibited, while intracellular Na+ levels were increased. In view of the ionophore property of tetranactin, it was suggested that the drug might demonstrate its immunosuppressive effect by affecting intracellular cation concentrations.
Reversal of natural killer cell exhaustion by TIM-3 blockade (2014)

Natural killer (NK) cells are innate immune cells that become progressively exhausted in advanced stage cancer, crippling their ability to execute antitumor functions. We previously characterized the nature of NK cell exhaustion in metastatic melanoma patients, reporting a correlation with high expression of TIM-3. Blockade of this immune checkpoint molecule reversed the exhausted phenotype and improved NK cell function.
Metabolic effects of exhaustive training of athletes. (1984)

Sixteen athletes (11 men, 5 women), averaging 21 years of age, were studied before and after four weeks of daily exhaustive exercise (six days/week) during an endurance training course. In comparing blood chemistries before and after training, concentrations of blood glucose, total serum lipids, serum triglycerides, and serum cholesterol were significantly reduced; serum free fatty acid ( SFFA ) level was significantly increased; and serum protein and serum phospholipid concentrations remained unchanged. It was concluded that exhaustive training produces reduced blood glucose (but not clinically significant hypoglycemia) with increased fat utilization as a result of depletion of carbohydrate storage and that such training reduces the resting levels of serum cholesterol and serum triglycerides. The increased hematocrit, serum Na+, and serum K+ concentrations observed were presumably due to plasma water loss from excessive perspiration. Concentrations of blood urea nitrogen (BUN) and serum glutamic-oxaloacetic transaminase (SGOT) were increased significantly; serum glutamic-pyruvic transaminase (SGPT) and serum creatinine showed no significant changes. None of the athletes showed evidences of water-electrolyte deficiency syndrome, renal dysfunction, or liver cell damage, despite a persistent mild degree of dehydration and catabolic state noted after training.
ON THE STIMULATION OF NEW BONE-FORMATION WITH PARATHYROID EXTRACT AND IRRADIATED ERGOSTEROL (1932)

We have indicated in a previous paper (1) that parathyroid hormone overdosage does not always lead to bone-resorption, but may sometimes produce bone apposition. We were able to show that rats receiving parathyroid hormone in daily injections over long periods have markedly denser bones than their untreated litter mates. The pathological picture of these bones is very suggestive of marble-bone disease, as described by Albers-Schoenberg. The apposition of new bone tissue is in fact most active in the metaphysis of the long bones just as in marble-bone disease, the shaft being practically normal. Therefore we suggested that marble-bone disease may be due to a special form of hyperparathyroidism. This theory seems to be supported also by a recent publication of Pehu, Policard and Dufourt (2). These authors describe a case of typical marble-bone disease combined with an enlargement of the parathyroids. The bone-marrow of this case showed fibrous transformation in some places, which also indicates a condition of hyperparathyroidism.
A negative regulatory element in the human papillomavirus type 16 genome acts at the level of late mRNA stability (1991)

A negative regulatory element present in the human papillomavirus type 16 genome has been characterized. Deletion analysis has localized the 5' end of the element to the late region of the genome at the extreme 3' end of the coding region of the L1 open reading frame, around the L1 stop codon, with the element extending into the L1 3' untranslated region. For the cell lines used, the element's function was independent of cell type, tissue, or species of origin, unlike papillomavirus infection, which is very dependent on such factors. By using an mRNA decay assay, we have determined that polyadenylated RNA containing the element is much less stable than polyadenylated RNA lacking the element. This indicates that the element acts as an mRNA instability element. The significance of A-rich, GU-rich, and AUG-rich sequences for the functioning of this human papillomavirus type 16 instability element is discussed.
Enhanced Tumorigenicity and Invasion-Metastasis by Hepatocyte Growth Factor/Scatter Factor-Met Signalling in Human Cells Concomitant with Induction of the Urokinase Proteolysis Network (1996)

Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of cells expressing the Met tyrosine kinase receptor. Although HGF/SF is synthesized by mesenchymal cells and acts predominantly on epithelial cells, we have recently demonstrated that human sarcoma cell lines often inappropriately express high levels of Met and respond mitogenically to HGF/SF. In the present report we show that HGF/SF-Met signalling in the human leiomyosarcoma cell line SK-LMS-1 enhances its in vivo tumorigenicity, an effect for which the mitogenicity of this signalling pathway is likely to play a role. In addition, we found that HGF/SF-Met signalling dramatically induces the in vitro invasiveness and in vivo metastatic potential of these cells. We have studied the molecular basis by which HGFSF-Met signalling mediates the invasive phenotype. A strong correlation has previously been demonstrated between the activation of the urokinase plasminogen activator (uPA) proteolysis network and the acquisition of the invasive-metastatic phenotype, and we show here that HGF/SF-Met signalling significantly increases the protein levels of both uPA and its cellular receptor in SK-LMS-1 cells. This results in elevated levels of cell-associated uPA and enhanced plasmin-generating ability by these cells. These studies couple HGF/SF-Met signalling to the activation of proteases that mediate dissolution of the extracellular matrix-basement membrane, and important property for cellular invasion-metastasis.
A programmable clock generator with 50 to 350 MHz lock range for video signal processors (2002)

Using 0.5-/spl mu/m CMOS triple-layer Al technology, a programmable clock generator based on a PLL (phase-locked loop) circuit has been developed for use as an on-chip clock generator in a 300-MHz video signal processor. It generates an internal clock whose frequency is an integral multiple of an external clock frequency, and its oscillating frequency ranges from 50 to 350 MHz. Experimental results show that the clock generator generates a 297-MHz clock with jitter reduced to 180 ps with a 27-MHz input clock, and that it oscillates at up to 348 MHz with a 31.7-MHz input clock.
Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction (2012)

Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial effects against myocardial ischemia-reperfusion injury. Little is known about the role of apelin in the homing of vascular progenitor cells (PCs) and cardiac functional recovery postmyocardial infarction (post-MI). The present study investigated whether apelin affects PC homing to the infarcted myocardium, thereby mediating repair and functional recovery post-MI. Mice were infarcted by coronary artery ligation, and apelin-13 (1 mg·kg(-1)·day(-1)) was injected for 3 days before MI and for 14 days post-MI. Homing of vascular PCs [CD133(+)/c-Kit(+)/Sca1(+), CD133(+)/stromal cell-derived factor (SDF)-1α(+), and CD133(+)/CXC chemokine receptor (CXCR)-4(+)] into the ischemic area was examined. Myocardial Akt, endothelial nitric oxide synthase (eNOS), VEGF, jagged1, notch3, SDF-1α, and CXCR-4 expression were assessed at 24 h and 14 days post-MI. Functional analyses were performed on day 14 post-MI. Mice that received apelin-13 treatment demonstrated upregulation of SDF-1α/CXCR-4 expression and dramatically increased the number of CD133(+)/c-Kit(+)/Sca1(+), CD133(+)/SDF-1α(+), and c-Kit(+)/CXCR-4(+) cells in infarcted hearts. Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated VEGF, jagged1, and notch3 expression in ischemic hearts. This was accompanied by a significant reduction of myocardial apoptosis. Furthermore, treatment with apelin-13 promoted myocardial angiogenesis and attenuated cardiac fibrosis and hypertrophy together with a significant improvement of cardiac function at 14 days post-MI. Apelin-13 increases angiogenesis and improves cardiac repair post-MI by a mechanism involving the upregulation of SDF-1α/CXCR-4 and homing of vascular PCs.
Temperature Effects in NAND Flash Memories: A Comparison Between 2-D and 3-D Arrays (2017)

This letter investigates the major differences between planar (2-D) and vertical-channel (3-D) NAND Flash memory arrays in terms of their temperature dependences. Attention is focused on three relevant parameters for memory array operation, namely, cell threshold-voltage, string saturation current, and width of the random telegraph noise distribution. Results highlight that the transition from 2-D to 3-D arrays introduced non-negligible changes in the temperature behavior of these parameters, whose origin is traced back to the different channel material of the technologies, i.e., monocrystalline versus polycrystalline silicon.
Cardiovascular Magnetic Resonance Assessment of Human Myocarditis (2004)

Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology. Myocarditis occurs predominantly in the lateral free wall. Contrast CMR is a valuable tool for the evaluation and monitoring of inflammatory heart disease.
Titration of igg antibodies against varicella zoster virus before bone marrow transplantation is not predictive of future zoster (1989)

Serum antibodies to varicella zoster virus (VZV) were measured in 77 patients about to undergo allogeneic bone marrow transplantation, and in 65 of their donors. Ten patients developed zoster within the first 6 months following transplant. There was no significant difference in the mean pretransplant antibody titre between those patients who did or did not subsequently develop zoster. Likewise, the level of antibody to VZV amongst donors had no effect on the subsequent development of zoster. We conclude that the pretransplant level of antibody to VZV is not predictive of subsequent zoster infection, and would not be helpful in identifying patients for trials of antiviral prophylaxis. These results contrast with those previously found for another herpesvirus, herpes simplex (HSV), where antibody level pretransplant is predictive of future HSV recurrence.
Bit-interleaved coded modulation with iterative decoding (1997)

A simple iterative decoding technique using hard-decision feedback is presented for bit-interleaved coded modulation (BICM). With an 8-state, rate-2/3 convolutional code, and 8-PSK modulation, the improvement over the conventional BICM scheme exceeds 1 dB for a fully-interleaved Rayleigh flat-fading channel and exceeds 1.5 dB for a channel with additive white Gaussian noise. This robust performance makes BICM with iterative decoding suitable for both types of channels.
Noise Reduction and Edge Enhancement Based on Band-Pass Epsilon-filter (2009)

Band-pass bilateral filter is an improved bilateral filter which does not have low-pass characteristics but has band-pass characteristics to enhance image contrast around edges. However, the computation time is relatively large due to Gaussian calculation in all pixels. To reduce the calculation cost, we look to a nonlinear filter called epsilon-filter and propose an advanced epsilon-filter which does not have low-pass charactersitics but has band-pass characteristics to enhance the image contrast around edge, namely band-pass epsiv-filter. Due to its simple design, the calculation cost is relatively small the same as epsiv-filter. To show the effectiveness of the proposed method, we also report the results of some comparative experiments concerning the filter characteristics and computational cost.
Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection (2010)

Inhibitory receptors play a crucial role in regulating CD8 T-cell function during chronic viral infection. T-cell Ig- and mucin-domain-containing molecule-3 (Tim-3) is well known to negatively regulate T-cell responses, but its role in CD8 T-cell exhaustion during chronic infection in vivo remains unclear. In this study, we document coregulation of CD8 T cell exhaustion by Tim-3 and PD-1 during chronic lymphocytic choriomeningitis virus infection. Whereas Tim-3 was only transiently expressed by CD8 T cells after acute infection, virus-specific CD8 T cells retained high Tim-3 expression throughout chronic infection. The majority (approximately 65% to 80%) of lymphocytic choriomeningitis virus-specific CD8 T cells in lymphoid and nonlymphoid organs coexpressed Tim-3 and PD-1. This coexpression of Tim-3 and PD-1 was associated with more severe CD8 T-cell exhaustion in terms of proliferation and secretion of effector cytokines such as IFN-gamma, TNF-alpha, and IL-2. Interestingly, CD8 T cells expressing both inhibitory receptors also produced the suppressive cytokine IL-10. Most importantly, combined blockade of Tim-3 and PD-1 pathways in vivo synergistically improved CD8 T cell responses and viral control in chronically infected mice. Taken together, our study defines a parameter for determining the severity of CD8 T cell dysfunction and for identifying virus-specific CD8 T cells that produce IL-10, and shows that targeting both PD-1 and Tim-3 is an effective immune strategy for treating chronic viral infections.
Selective Electroless Metal Deposition for Integrated Circuit Fabrication (1989)

Selective electroless metal deposition process was studied for its applications in integrated circuit fabrication. Compared to selective metal deposition by CVD process, such as the selective tungsten deposition process, the selective electroless deposition process is more attractive due to its simplicity as well as process flexibility. A variety of material such as Ni, Co, Pd, and Cu were studied for contact filling, via filling, and for conductor patterns. These materials were selectively deposited on a variety of surfaces such as silicon, silicide, Al‐Si, through patterned CVD silicon dioxide, CVD silicon oxynitride, and photoresist. Although this process is still in its early stage of development, very promising results have already been achieved. The experimental conditions and results for selectively filled contact holes, via holes, and conductor patterns are described using actual examples.