gebhart/patrepeval huggingface dataset:
β-catenin is regulated by USP9x and mediates resistance to TRAIL-induced apoptosis in breast cancer (2015)

To investigate the regulatory mechanisms of decoy receptor expression in TRAIL-resistant breast cancer MCF-7 cells, cytotoxicity and apoptosis assays were applied to examine sensitivity to TRAIL in breast cancer cells. Immunofluorescence and immunoprecipitation were used to detect the co-localization and interaction of USP9x and β-catenin. Luciferase assay was used to examine activity of the DcR1/DcR2/OPG reporter. Overexpression/silencing of β-catenin was performed to confirm β-catenin mediated transcription of the decoy receptors. Additionally, silencing of USP9x was performed to prove that USP9X stabilizes β-catenin and mediates TRAIL-resistance. It was found that USP9x interacted with β-catenin and inhibited the degradation of β-catenin through the deubiquitination of β-catenin. Luciferase reporter assays showed induction of DcR1/DcR2/OPG reporter activity observed upon co-transfection of β-catenin and Tcf-4. The overexpression/silencing of β-catenin further confirmed the role of β-catenin in the regulation of transcription of the decoy receptors. Silencing of USP9x directly evidenced that USP9x affected the protein expression level of β-catenin, the transcription level of the decoy receptors, and reversed TRAIL-resistance of MCF-7 cells. In conclusion, USP9x interacted with and stabilized β-catenin through deubiquitination to mediate transcription of the decoy receptors in breast cancer cells. Our results offer new insights into the mechanisms of resistance to TRAIL, and USP9x could potentially be a therapeutic target for TRAIL-resistant breast cancers.
The Structural Biology of Expression and Function of Tissue Factor (1991)

Analysis of the structural biology of TF provides insights into the both the expression of the gene and the function of this cell surface receptor in the initiation of the coagulation protease cascades. The advance of information may permit inferential hypotheses for the structural biology of other cofactor regulated catalytic steps in blood coagulation.
Gap junctions in the vertebrate retina (1995)

The vertebrate retina is a highly laminated assemblage of specialized neuronal types, many of which are coupled by gap junctions. With one interesting exception, gap junctions are not directly responsible for the 'vertical' transmission of visual information from photoreceptors through bipolar and ganglion cells to the brain. Instead, they mediate 'lateral' connections, coupling neurons of a single type or subtype into an extended, regular array or mosaic in the plane of the retina. Such mosaics have been studied by several microscopic techniques, but new evidence for their coupled nature has recently been obtained by intracellular injection of biotinylated tracers, which can pass through gap junctional assemblies that do not pass Lucifer Yellow. This evidence adds momentum to an existing paradigm shift towards a population-based view of the retina, which can now be envisaged both as an array of semi-autonomous vertical processing modules, each extending right through the retina, and as a multi-layered stack of interacting planar mosaics, bearing some resemblance to a set of interleaved neural networks. Junctional conductance across mosaics of horizontal cells is known to be controlled dynamically with a circadian rhythm, and other dynamically-regulated conductance changes are also likely to make important contributions to signal processing. The retina is an excellent system in which to study such changes because many aspects of its structure and function are already well understood. In this review, we summarize the microscopic appearance, coupling properties and functions of gap junctions for each cell type of the neural retina, the regulatory properties that could be provided by selective expression of different connexin proteins, and the evidence for gap junctional coupling in retina development.
Model-based sequential base calling for Illumina sequencing (2010)

In this paper, we study the efficacy of a model-based base-calling approach for Illumina's sequencing platforms. In particular, we investigate Genome Analyzer I reads and provide a detailed biochemical model of the sequencing process, incorporating various non-idealities evident in such systems. Parameters of the model are estimated via a supervised learning based on the particle swarm optimization technique. A computationally efficient sequential decoding method is proposed for base-calling. It is demonstrated that the performance of the proposed approach is comparable to Illumina's base-calling method.
Single acquisition electrical property mapping based on relative coil sensitivities: A proof‐of‐concept demonstration (2014)

The proposed methodology allows to quantitatively determine the electrical properties of a sample using any MR contrast, with the only constraint being the need to have 4 or more receive coils and high SNR. Magn Reson Med 74:185-195, 2015. © 2014 Wiley Periodicals, Inc.
Highly Uniform and Monodisperse β-NaYF4:Ln3+ (Ln = Eu, Tb, Yb/Er, and Yb/Tm) Hexagonal Microprism Crystals:  Hydrothermal Synthesis and Luminescent Properties (2007)

beta-NaYF4:Ln3+ (Ln = Eu, Tb, Yb/Er, and Yb/Tm) hexagonal microprisms with remarkably uniform morphology and size have been synthesized via a facile hydrothermal route. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and photoluminescence (PL) spectra as well as kinetic decays were used to characterize the samples. It is found that sodium citrate as a shape modifier introduced into the reaction system plays a critical role in the shape evolution of the final products. Furthermore, the shape and size of the products can be further manipulated by adjusting the molar ratio of citrate/RE3+ (RE represents the total amount of Y3+ and the doped rare earth elements such as Eu3+, Tb3+, Yb3+/Er3+, or Yb3+/Tm3+). Under the excitation of 397 nm ultraviolet light, NaYF4:xEu3+ (x = 1.5, 5%) shows the emission lines of Eu3+ corresponding to 5D0-3 --> 7FJ (J = 0-4) transitions from 400 to 700 nm (whole visible spectral region) with different intensity, resulting in yellow and red down-conversion (DC) light emissions, respectively. When doped with 5% Tb3+ ions, the strong DC fluorescence corresponding to 5D4 --> 7FJ (J = 6, 5, 4, 3) transitions with 5D4 --> 7F5 (green emission at 544 nm) being the most prominent group that has been observed. In addition, under 980 nm laser excitation, the Yb3+/Er3+- and Yb3+/Tm3+-codoped beta-NaYF4 samples exhibit bright green and whitish blue up-conversion (UC) luminescence, respectively. The luminescence mechanisms for the doped lanthanide ions were thoroughly analyzed.
Nanomolar Small Molecule Inhibitors for αvβ6, αvβ5, and αvβ3 Integrins (2002)

Integrin adhesion receptors frequently recognize a core amino acid sequence, Arg-Gly-Asp, in their target ligands. Inhibitors with the ability to inhibit one or a small subset of such RGD-dependent integrins have been invaluable in defining their biological function. Here, we have characterized low molecular weight inhibitors for their ability to specifically inhibit alphav(beta)6 integrin, a fibronectin/tenascin receptor. As of yet, no nonpeptidic inhibitor of alphav(beta)6 was known. New peptidomimetic and nonpeptidic compounds were examined in isolated integrin binding assays and in cell adhesion assays for their ability to block alphav(beta)6, alphav(beta)3, alphav(beta)5, and alphalIb(beta)3 integrins. The compounds are based on an aromatically substituted beta amino acid or glutaric acid derivative as an acidic center and an aminopyridyl or guanidyl residue as a basic mimetic. We found several classes of inhibitors with different selectivities, especially mono- or biselectivity on the alpha(v)-integrins alphav(beta)6 and alphav(beta)3, and nanomolar activity. Furthermore, nearly all compounds are inactive on alphaIIb(beta)3. Compound 11 is the first specific, peptidomimetic inhibitor of the alphav(beta)6 integrin receptor.
Synthesis of Possible Antiparkinsonian Compounds. Part X Synthesis of 2,6,8 Trisubstituted Benzoxazinones and their Corresponding 3-Hydroxy-quinazolinones (1975)

<em>Manuscript received 18 November 1974; accepted 21 February 1975</em> Some new benzoxazinones and quinazolinones have been synthesised with a view to testing their anti-parkinsonism activity.
Acute inflammation is the harbinger of glomerulosclerosis in anti-glomerular basement membrane nephritis (1995)

The degree of glomerular inflammation and injury during immune-mediated glomerulonephritis is felt to be critical to the eventual development of glomerulosclerosis, although the relative contributions of acute and chronic inflammation are uncertain. By grading the initial dose of antibody in accelerated anti-glomerular basement membrane nephritis, we observed that only animals with the most substantial acute inflammation (in terms of neutrophil influx and acute proteinuria) developed sustained proteinuria followed by an increase in serum creatinine and evidence of severe glomerulosclerosis. Chronic inflammation (i.e., glomerular macrophage influx and evidence of glomerular cell proliferation), in contrast, was evident without the development of glomerulosclerosis. Decreasing the degree of acute inflammation during severe nephritis by complement depletion diminished both the initial and sustained proteinuria and the influx of neutrophils, prevented the terminal increase in serum creatinine, and attenuated the evolution of glomerulosclerosis. Complement depletion, however, did not affect peak proteinuria, macrophage influx, or glomerular cell proliferation. Regression analysis of the entire data set demonstrated that acute (day 1) proteinuria was predictive of the eventual histopathological index, more so than chronic (day 7) proteinuria. To recapitulate, glomerulosclerosis following antiglomerular basement membrane nephritis appears to be substantially dependent on the degree of acute inflammatory injury.
Increased circulating skin-homing cutaneous lymphocyte-associated antigen (CLA)+ type 2 cytokine-producing cells, and decreased CLA+ type 1 cytokine-producing cells in atopic dermatitis (2000)

These results provide evidence for the expansion of skin-homing type 2 cytokine-secreting T cells, associated with a reduction in skin-homing type 1 cytokine-producing T cells, in peripheral blood of AD patients.
Antioxidant Behaviors of Vitamin E Analogues in Unilamellar Vesicles (1996)

The antioxidant behaviors of vitamin E and its analogues, 2,2,5,7,8-pentamethyl-6-hydroxychroman and 1,2-diacyl-sn-glycero3-phospho-2'-(hydroxyethyl)-2'- 5',7',8'-tetramethyl-6'-hydroxychroman, were studied in unilamellar vesicles. The two analogues scavenged aqueous radicals generated from azo compounds more efficiently than vitamin E. On the other hand, vitamin E scavenged the lipid peroxyl radicals preferentially. It is concluded that the superior antioxidant activity of vitamin E is attributed to its location suitable for breaking the chain propagation reaction.
The integrin α 4 β 7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1 (2009)

Both activated and resting CD4(+) T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin alpha(4)beta(7) (alpha(4)beta(7)), the gut mucosal homing receptor. We find that alpha(4)beta(7)(high) CD4(+) T cells are more susceptible to productive infection than are alpha(4)beta(7)(low-neg) CD4(+) T cells in part because this cellular subset is enriched with metabolically active CD4(+) T cells. alpha(4)beta(7)(high) CD4(+) T cells are CCR5(high) and CXCR4(low); on these cells, alpha(4)beta(7) appears in a complex with CD4. The specific affinity of gp120 for alpha(4)beta(7) provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission.
Photon-to-digital photodiode imaging array (2001)

MOSAD&copy;, Multiplexed OverSample Analog to Digital conversion, is a low power on focal plane analog to digital, A/D, process that places an oversample A/D at each pixel site. Two designs for a visible light staring array were developed with this approach. One used a silicon photo diode and the other used a photo gate for detection. The array was designed with a 320 X 240 format with the pixels placed on 16 micron centers. There are a total of 76,800 A/D's on the chip. The device is a monolithic integrated circuit that includes the sensors, A/D's and readout circuitry. A production 1.2 micron CCD/CMOS process was used in it construction. The A/D uses charge well switching at the pixel to convert the accumulated analog signal to digital data. There was negligible impact on the pixel area due to the A/D such that a fill factor of 73% was achieved with front side illumination for both approaches. At 400 samples per second, measured on chip power consumption is under 10 milliwatts. Noise measurements at sample rates from 400 samples per second to 1,600 samples per second were taken for both parts. It was found that the photo gate noise performance was four times better than the photo diode. At a nominal 28 times oversample, the photo diode obtained 8 to 9 bits performance and the photo gate achieved 10 to 11 bits. Nonuniformity variation was below the noise floor. No explanation for the difference in noise performance has yet been determined. This development was sponsored by NASA under a SBIR program.
O0121 ANTI-INTERLEUKIN-12 ANTIBODY TREATS ACTIVE CROHN???S DISEASE (2004)

Introduction: The mucosal inflammation observed in Crohn’s disease (CD) has been shown to be associated with a skewed Th1 (IL-12, IFN-g, TNF-a ) cytokine response. IL-12 is a key cytokine driving this Th1 inflammatory response. Prior studies have demonstrated that experimental murine models of intestinal inflammation which mimic characteristics of CD have responded in a dramatic manner to the administration of antibodies (Ab) to IL-12. Methods: A double-blind, placebo-controlled, international trial of a human anti-IL-12 (anti-p40) monoclonal Ab (ABT-874/J695 Wyeth Research and Abbott Laboratories) was conducted in 79 patients with active CD (CDAI of 220–450) to evaluate treatment safety and efficacy. Patients were randomly assigned to receive seven weekly subcutaneous injections of 1 or 3mg/kg of Ab or a placebo with either a four week interval between the first and second injection (Cohort 1) or no interruption in the weekly injections (Cohort 2). Outcomes included rates of adverse events, changes in CDAI scores and in lamina propria mononuclear cell (LPMC) cytokine secretion levels. Results: Patients receiving 3mg/kg on a weekly injection schedule (Cohort 2) showed striking benefit from treatment: The rates of clinical response (reduction of at least 100 CDAI points) compared to placebo were 75% vs 25% (p = 0.032) at the end of treatment and 69% vs 13% (p = 0.033) after 12 weeks of follow-up; The rates of remission (CDAI of less than 150) for this treatment group (3 mg/kg) versus placebo were 38% vs 0% (p = 0.066) at the end of treatment and 50% vs 0% (p = 0.022) after 12 weeks of follow-up. The beneficial effects of Ab treatment were durable through 18 weeks of follow-up and observed in some patients unresponsive/intolerant to anti-TNF-a. Antibody-related adverse events were comparable to placebo except for some local injection reactions. Rates of clinical response and remission for 1mg/kg Ab treatment in both Cohorts as compared to placebo did not achieve statistical difference. In those patients in which a clinical improvement was observed an accompanying notable decrease in Th1 cytokines secreted by LPMC cells (pg/ml) at the end of treatment as compared to pre-treament levels was demonstrated: IL-12: 153 + 51 (mean+SD) to 2.8 + 2.6 (p =0.028); IFN-g, 9,835 + 3,555 to 1,078 + 354 (p = 0.05); TNF-a, 3,486 + 576 to 1062 + 281 (p<0.01). Conclusion: Treatment with 3mg/kg anti-IL-12 monoclonal Ab induced a clinical improvement in a great majority of patients with active CD. These clinical data concomitant with the cytokine results, support the hypothesis of a Th-1-driven inflammatory process in CD and give rise to the promise of Anti-IL-12 Ab therapy as a valuable new approach to treating CD.
The Potential Role of Curcumin in Cancer Prevention and Treatment. (2013)

Most drugs currently available for the treatment of cancer have limited potential because they are very toxic, highly inefficient in treating cancer, or highly expensive and thus beyond the reach of the majority. Treatments without these disadvantages are needed. Curcumin is one such agent; derived from turmeric (Curcumin longa), it has been used for thousands of years in the orient as a healing agent for variety of illnesses. Research over the last few decades has shown that curcumin is a potent antiinflammatory agent with strong therapeutic potential against a variety of cancers. Curcumin has been shown to suppress transformation, proliferation, and metastasis of tumors. These effects are mediated through its regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin has been shown to have protective and therapeutic effects against cancers of the blood, skin, oral cavity, lung, pancreas, and intestinal tract, and to suppress angiogenesis and metastasis in rodents. Curcumin's ability to affect gene transcription and to induce apoptosis in preclinical models is likely to be of particular relevance to cancer chemoprevention and chemotherapy in patients. The current review focuses on the molecular mechanisms by which curcumin mediates its effects against various cancers.
Sequential Intensification of Metformin Treatment in Type 2 Diabetes With Liraglutide Followed by Randomized Addition of Basal Insulin Prompted by A1C Targets (2012)

Supplementation of metformin with liraglutide and then insulin detemir was well tolerated in the majority of patients, with good glycemic control, sustained weight loss, and very low hypoglycemia rates.
Effects of ecto-5'-nucleotidase on human breast cancer cell growth in vitro and in vivo (2007)

Ecto-5'-nucleotidase (CD73) is an essential enzyme that generates adenosine, an essential molecule for cell growth. CD73 increases significantly in many breast cancers. In this study, alpha,beta-methylene adenosine-5'-diphosphate (APCP), a specific CD73 inhibitor was used to block the hydrolase's activity. Effects of CD73 were examined on human breast cancer cells MDA-MB-231 in culture for proliferation, cell cycle progression, and apoptosis before and after APCP treatment. The in vivo effect of CD73 was examined on MDA-MB-231 tumor xenograft growth in nude mice. Cell growth curve, cell cycle and apoptosis were observed with MTT assays and flow cytometry, respectively. Microvessel density (MVD) and lymph vessel density (LVD) of implanted tumor tissues was analyzed by immunohistochemistry for CD31 and VEGFR-3 staining respectively. Our results showed that APCP inhibited MDA-MB-231 viability in a dose-dependent manner. APCP (12 microM) increased the percentage of G0/G1 phase cells from 49.75 to 59.16% while it decreased S phase and G2/M cells from 24.85 and 18.65% to 21.65 and 12.55%, respectively. The percentages of early and late apoptotic cells were also decreased after APCP treatment. However, APCP treatment did not affect the percentage of normal cells. Xenograft of MDA-MB-231 cells in the APCP treatment group had lower volume and weight than those of control group (2.70+/-1.14 vs 1.41+/-0.39 cm(3) and 2.7+/-0.5 vs 1.3+/-0.2 g), accompanied with less vessel formation with a MVD of 5+/-1 compared to the control group's 10+/-2 and an LVD of 4+1 vs 7+2. Our results suggest that CD73 may promote tumor growth and serve as a marker of breast cancer progression.
Intramuscular immunisation withMUC1 cDNA can protect C57 mice challenged with MUC1-expressing syngeneic mouse tumour cells (1996)

Much interest is currently being shown in immunotherapy as a treatment for cancer since several tumour-associated antigens have been identified and the genes encoding them cloned. One such molecule is the tumour-associated human MUC1 gene product. In this report we describe tumour rejection studies in a C57B1 murine model system with syngeneic MUC1-expressing tumour cells designed to examine the efficacy of MUC1 cDNA as an immunogen. Intra-muscular immunisation with 100 microgram MUC1 cDNA 3 times at 3-weekly intervals resulted in tumour protection in approximately 80% of mice. Tumour protection was dose-dependent, with 50-100 microgram being the most effective dose. Both humoral and cell-mediated MUC1-specific immune responses were detected. Anti-MUC1 antibodies were detected after immunisation with DNA alone, indicating that the injected DNA was expressed. Humoral immune responses did not correlate with tumour rejection. Tumour challenge with syngeneic tumour cells expressing MUC1 appeared to be a pre-requisite for the generation of MUC1-specific cytotoxic T lymphocytes.
Sparse distributed memory and related models (1993)

Described here is sparse distributed memory (SDM) as a neural-net associative memory. It is characterized by two weight matrices and by a large internal dimension - the number of hidden units is much larger than the number of input or output units. The first matrix, A, is fixed and possibly random, and the second matrix, C, is modifiable. The SDM is compared and contrasted to (1) computer memory, (2) correlation-matrix memory, (3) feet-forward artificial neural network, (4) cortex of the cerebellum, (5) Marr and Albus models of the cerebellum, and (6) Albus' cerebellar model arithmetic computer (CMAC). Several variations of the basic SDM design are discussed: the selected-coordinate and hyperplane designs of Jaeckel, the pseudorandom associative neural memory of Hassoun, and SDM with real-valued input variables by Prager and Fallside. SDM research conducted mainly at the Research Institute for Advanced Computer Science (RIACS) in 1986-1991 is highlighted.
In-Tube DNA Methylation Profiling by Fluorescence Melting Curve Analysis (2001)

Integration of PCR and fluorescence melting analysis may be useful for simple and cost-effective detection of aberrant methylation patterns.
Retinal capillary basement membrane thickening in a porcine model of diabetes mellitus. (2002)

The rapid development of retinal capillary basement membrane thickening in diabetic pigs makes this animal model useful for early intervention and mechanistic studies for this diabetes-associated microvascular change.