gebhart/patrepeval huggingface dataset:
A fluorescence in situ hybridization study of ETV6‐NTRK3 fusion gene in secretory breast carcinoma (2004)

The translocation t(12;15)(p13;q25), in which the ETV6 gene from chromosome 12 is rearranged with the NTRK3 gene from chromosome 15, has recently been identified in secretory breast carcinoma (SBC). This fusion gene was initially described in congenital fibrosarcoma and congenital mesoblastic nephroma. The biological consequence of this translocation is the expression of a chimeric protein tyrosine kinase with potent transforming activity. To assess the frequency of t(12;15)(p13;q25) in breast cancer, we developed complementary probe sets (fusion and split-apart probes) for the detection of this translocation by fluorescence in situ hybridization (FISH) in paraffin-embedded, formalin-fixed tissue sections. We tested four histologically confirmed cases of SBC for the presence of the ETV6-NTRK3 gene fusion and then applied the FISH assay to tissue microarrays (TMAs) in order to screen 481 cases of formalin-fixed, paraffin-embedded invasive breast carcinomas of various histologic subtypes. Three of the four cases of SBC revealed fusion signals. Of the 481 cases in the TMAs, 202 gave signals of sufficient quality for screening by FISH, and only one case showed fusion signals in most or all of the tumor cells. On review of the histology of this case, SBC was confirmed. On the other hand, none of the fusion-negative breast cancers revealed SBC histology. In all cases, the results from the fusion and split-apart FISH assays for the ETV6-NTRK3 fusion genes were concordant. Our data suggest that the ETV6-NTRK3 fusion gene is a specific genetic alteration in SBC.
Trypanosoma brucei CTP synthetase: A target for the treatment of African sleeping sickness (2001)

The drugs in clinical use against African sleeping sickness are toxic, costly, or inefficient. We show that Trypanosoma brucei, which causes this disease, has very low levels of CTP, which are due to a limited capacity for de novo synthesis and the lack of salvage pathways. The CTP synthetase inhibitors 6-diazo-5-oxo-l-norleucine (DON) and alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) reduced the parasite CTP levels even further and inhibited trypanosome proliferation in vitro and in T. brucei-infected mice. In mammalian cells, DON mainly inhibits de novo purine biosynthesis, a pathway lacking in trypanosomes. We could rescue DON-treated human and mouse fibroblasts by the addition of the purine base hypoxanthine to the growth medium. For treatment of sleeping sickness, we propose the use of CTP synthetase inhibitors alone or in combination with appropriate nucleosides or bases.
3. Similarity searching: Indexing, nearest neighbor finding, dimensionality reduction, and embedding methods for applications in multimedia databases (2008)

Similarity searching is usually achieved by means of nearest neighbor finding. Existing methods for handling similarity search in this setting fall into one of two classes. The first is based on mapping to a low-dimensional vector space which is then indexed using representations such as k-d trees, R-trees, quadtrees, etc. The second directly indexes the the objects based on distances using representations such as the vp-tree, M-tree, etc. Mapping from a high-dimensional space into a low-dimensional space is known as dimensionality reduction and is achieved using SVD, DFT, etc. At times, when we just have distance information, the data objects are embedded in a vector space so that the distances of the embedded objects as measured by the distance metric in the embedding space approximate the actual distance. The search in the embedding space uses conventional indexing methods which are often coupled with dimensionality reduction. Some commonly known embedding methods are multidimensional scaling, Lipschitz embeddings, and Fast Map. This tutorial is organized into five parts that cover the five basic concepts outlined above: indexing low and high dimensional spaces, distance-based indexing, dimensionality reduction, embedding methods, and nearest neighbor searching.
Acute unilateral renal denervation in rats with extracellular volume expansion (1977)

Sodium reabsorption along the nephron was studied before and after acute unilateral denervation of the left kidney in anesthetized rats with extracellular volume expansion. Studies were also performed before and after sham denervation. Denervation increased urine volume (V) from the left kidney from 35.2 to 59.2 mul min-1 (P less than 0.001) and urinary sodium excretion (UNaV) from 6.9 to 11.8 mueq min-1 (P less than 0.001). The control right kidney showed a simultaneous 45% decrease in V and UNaV. Inulin clearance (GFR) and renal plasma flow (RPF) remained unchanged after denervation in both kidneys. Left kidney late proximal (F/P)m decreased from 1.50 to 1.24 (P less than 0.01); single-nephron GFR (SNGFR) remained unchanged. (F/P)m ratios were also decreased in early distal (3.87-2.65, P less than 0.005) and late distal (5.48-3.83, P less than 0.02) convolutions. Fractional and absolute Na reabsorption in the distal convolution did not decrease. GFR, RPF, V, UNa, late proximal (F/P)m, and SNGFR were unchanged in sham-denervated rats. The increases in V and UNa V produced by acute renal denervation in the volume-expanded anesthetized animal are thus caused by further depression of proximal tubular salt and water reabsorption.
Stat3 is required for the development of skin cancer (2004)

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is constitutively activated in a variety of human malignancies, including prostate, lung, brain, breast, and squamous cell carcinomas. Inhibition of activated Stat3 leads to decreased proliferation and apoptosis of many cancer-derived cell lines, while the introduction of a constitutively activated form of Stat3 into immortalized human breast epithelial cells and rodent fibroblasts results in cellular transformation. Collectively, these data suggest a role for Stat3 in oncogenesis. A new study from Chan et al. (see related article beginning on page 720) is the first to demonstrate a requirement for Stat3 in de novo epithelial carcinogenesis in vivo. Using the two-step model of chemically induced skin carcinogenesis, the authors demonstrated that mice deficient in Stat3 were completely resistant to skin tumor development.
Edito (2012)

n'est autorise que dans les limites des conditions gnrales d'utilisation du site ou, le cas chant, des conditions gnrales de la licence souscrite par votre tablissement.
Photolithographic Fabrication of Microapertures with Well-Defined, Three-Dimensional Geometries for Suspended Lipid Membrane Studies (2013)

Robust and high-density biosensors incorporating suspended lipid membranes require microfabricated apertures that can be readily integrated into complex analysis systems. Apertures with well-defined, three-dimensional geometries enable the formation of suspended lipid membranes and facilitate reduced aperture size compared to vertical-walled apertures. Unfortunately, existing methods of producing apertures with well-defined, three-dimensional geometries are based on complex and expensive fabrication procedures, some of which yield apertures in excessively fragile thin-film materials. Here, we describe a microfabrication method utilizing incline and rotate lithography that achieves sloped-wall microapertures in SU-8 polymer substrates with precision control of the aperture diameter, substrate thickness, and wall angle. This approach is simple, is of low cost, and is readily scaled up to allow highly reproducible parallel fabrication. The effect of the incident angle of UV exposure and the size of photomask features on the aperture geometry were investigated, yielding aperture diameters as small as 7 μm and aperture wall angles ranging from 8° to 36° measured from the normal axis. Black lipid membranes were suspended across the apertures and showed normalized conductance values of 0.02-0.05 pS μm(-2) and breakdown voltages of 400-600 mV. The functionality of the resulting sloped-wall microapertures was validated via measurement of reconstituted α-hemolysin activity and the voltage-gated channel activity of alamethicin.
Quantum Generative Adversarial Learning (2018)

Generative adversarial networks represent a powerful tool for classical machine learning: a generator tries to create statistics for data that mimics those of a true data set, while a discriminator tries to discriminate between the true and fake data. The learning process for generator and discriminator can be thought of as an adversarial game, and under reasonable assumptions, the game converges to the point where the generator generates the same statistics as the true data and the discriminator is unable to discriminate between the true and the generated data. This Letter introduces the notion of quantum generative adversarial networks, where the data consist either of quantum states or of classical data, and the generator and discriminator are equipped with quantum information processors. We show that the unique fixed point of the quantum adversarial game also occurs when the generator produces the same statistics as the data. Neither the generator nor the discriminator perform quantum tomography; linear programing drives them to the optimal. Since quantum systems are intrinsically probabilistic, the proof of the quantum case is different from-and simpler than-the classical case. We show that, when the data consist of samples of measurements made on high-dimensional spaces, quantum adversarial networks may exhibit an exponential advantage over classical adversarial networks.
On Steroids. Part 418. Synthetic Approach to 5?-Pregnanolone 19-[O-(Carboxymethyl)oxime] Derivatives. (2005)

For Abstract see ChemInform Abstract in Full Text.
E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction (2016)

Inhibiting E-selectin attenuated inflammation in atherosclerotic plaques, likely by reducing leukocyte recruitment into plaques and by mitigating hematopoietic stem and progenitor cell activation in the spleen of mice with MI.
Attenuation of serum inducibility of immediate early genes by oncoproteins in tyrosine kinase signaling pathways. (1993)

Immediate early genes involved in controlling cell proliferation are rapidly and transiently induced following stimulation of susceptible cells with serum. To study how oncoproteins regulate immediate early genes, we examined serum inducibility of these genes in cells transformed by various oncoproteins. We found that induction of the immediate early gene, c-fos, by serum stimulation was markedly attenuated in four independent cell lines stably transformed by the v-Src tyrosine kinase. Cells chronically transformed by other oncoproteins implicated in tyrosine kinase signaling pathways, including v-Sis, v-Ras, and v-Raf, showed the same pattern of attenuation. In contrast, serum inducibility of c-fos was not attenuated in cells transformed by simian virus 40, which is thought to transform cells through a different pathway. Cell cycle analyses showed that proliferation of these transformed cell lines could be arrested effectively in 0.1% serum, demonstrating that the attenuation was not simply due to continuous cycling of transformed cells after serum deprivation. Moreover, serum inducibility of other immediate early genes, including c-jun, junB, egr-1, and NGFI-B, also was strikingly attenuated by these same oncoproteins. Nuclear run-on transcription assays established that this attenuation of serum inducibility occurred at the transcriptional level. Finally, flow cytometric analysis demonstrated that serum-starved v-Src-transformed cells were viable and able to progress into S phase of the cell cycle after serum stimulation, even though the induction of immediate early genes was greatly attenuated in these cells. Our results suggest that activation of immediate early genes is repressed by chronic stimulation of tyrosine kinase signaling pathways in transformed cells.
Hepatocyte Growth Factor Attenuates Collagen Accumulation in a Murine Model of Pulmonary Fibrosis (2000)

We investigated the in vivo effects of recombinant human hepatocyte growth factor (HGF) on epithelial cell proliferation in normal mouse lung and on the repair process that follows bleomycin-induced lung injury. Intratracheal administration of 100 micrograms of rhHGF to C57BL/6 mice led to proliferation of bronchial and alveolar epithelial cells as indicated by an increased number of cells staining for proliferating cell nuclear antigen (PCNA). The effect of HGF on the lung repair process was examined by administration of 100 micrograms of rhHGF on Day 3 and Day 6 after intratracheal injection of bleomycin to mice. We found that HGF significantly attenuated collagen accumulation induced by bleomycin as determined by quantitation of hydroxyproline content and by scoring of the extent of fibrosis. To explore the potential mechanisms involved in the beneficial effects of HGF, we performed in vitro studies with A549 pulmonary epithelial cells and found that HGF enhanced cell surface plasmin generation, expression of u-PA activity, and cell migration. In summary, HGF has potent in vivo and in vitro effects on epithelial cells, which suggests it may have a role in the therapy of pulmonary fibrosis.
Presence of alpha 2-macroglobulin in normal but not in malignant human syncytiotrophoblasts. (1981)

alpha 2-Macroglobulin (alpha 2M) was demonstrated in normal syncytiotrophoblasts of both early and full-term human placentas using immunocytological staining. alpha 2M was also detected in hydatidiform moles, the benign tumors of proliferating syncytiotrophoblasts. In contrast, no alpha 2M was detected in invasive moles or choriocarcinomas. In culture conditions, both normal syncytiotrophoblasts and choriocarcinoma cells, identified by production of human chorionic gonadotropin, were negative when stained for alpha 2M or when studied using metabolic labeling and immunoprecipitation or radioimmunoassay. However, alpha 2M was taken up from added human serum by the cultured syncytiotrophoblasts, whereas choriocarcinoma cells remained negative also under these conditions. The possible role of alpha 2M in the regulation of proteolysis in cell invasion is considered.
An Antagonist IL-15/Fc Protein Prevents Costimulation Blockade-Resistant Rejection (2001)

IL-15 is a powerful T cell growth factor (TCGF) with particular importance for the maintenance of CD8(+) T cells. Because costimulation blockade does not result in universal tolerance, we hypothesized that "escape" from costimulation blockade might represent a CD8(+) and IL-15/IL-15R(+)-dependent process. For this analysis, we have used an IL-15 mutant/Fcgamma2a protein, a potentially cytolytic protein that is also a high-affinity receptor site specific antagonist for the IL-15Ralpha receptor protein, as a therapeutic agent. The IL-15-related fusion protein was used as monotherapy or in combination with CTLA4/Fc in murine islet allograft models. As monotherapies, CTLA4/Fc and an IL-15 mutant/Fcgamma2a were comparably effective in a semiallogeneic model system, and combined treatment with IL-15 mutant/Fcgamma2a plus CTLA4/Fc produced universal permanent engraftment. In a fully MHC-mismatched strain combination known to be refractory to costimulation blockade treatment, combined treatment with both fusion proteins proved to be highly effective; >70% of recipients were tolerized. The analysis revealed that the IL-15 mutant/Fc treatment confers partial protection from both CD4(+) and CD8(+) T cell graft infiltration. In rejections occurring despite CTLA4/Fc treatment, concomitant treatment with the IL-15 mutant/Fcgamma2a protein blocked a CD8(+) T cell-dominated rejection processes. This protection was linked to a blunted proliferative response of alloreactive T cells as well silencing of CTL-related gene expression events. Hence, we have demonstrated that targeting the IL-15/IL-15R pathway represents a new and potent strategy to prevent costimulation blockade-resistant CD8(+) T cell-driven rejection.
A Randomized, Double-blind, Placebo-Controlled Trial of Subcutaneously Injected Apomorphine for Parkinsonian Off-State Events (2001)

Apomorphine by intermittent subcutaneous injection is effective and safe for outpatient use to reverse off-state events that occur despite optimized oral therapy.
Computational methods in protein structure prediction (2007)

This review presents the advances in protein structure prediction from the computational methods perspective. The approaches are classified into four major categories: comparative modeling, fold recognition, first principles methods that employ database information, and first principles methods without database information. Important advances along with current limitations and challenges are presented.
Treatment of Colonic and Rectal Adenomas with Sulindac in Familial Adenomatous Polyposis (1993)

Sulindac reduces the number and size of colorectal adenomas in patients with familial adenomatous polyposis, but its effect is incomplete, and it is unlikely to replace colectomy as primary therapy.
Sweetening the Pot: Adding Glycosylation to the Biomarker Discovery Equation (2009)

The future of carbohydrate-based biomarker studies has arrived. At all stages, from discovery through verification and deployment into clinics, glycosylation should be considered a primary readout or a way of increasing the sensitivity and specificity of protein-based analyses.
Regulation of eIF-4E BP1 Phosphorylation by mTOR (1997)

The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin. Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain. In contrast, mutants of p70 S6 kinase rendered intrinsically resistant to inhibition by rapamycin in situ are not able to protect coexpressed eIF-4E BP1 from rapamycin-induced dephosphorylation. We conclude that mTOR is an upstream regulator of eIF-4E BP1 as well as the p70 S6 kinase; moreover, these two mTOR targets are regulated in a parallel rather than sequential manner.
Requirement of a Thymus Dependent Immune Response for Bcg-mediated Antitumor Activity (1987)

Surgical adjuvant intravesical bacille Calmette-Guerin (BCG) therapy is an effective method of treating superficial transitional cell carcinoma of the bladder. The role of the immune response in the antitumor activity of intravesical BCG is not known. We investigated the requirement of a thymus-dependent immune response for the inhibition of the growth of the intravesically implanted mouse bladder tumor, MBT-2. Intravesical BCG had no antitumor activity when administered to athymic nude mice bearing MBT-2 tumors. In two experiments tumor outgrowth in control and BCG-treated mice was identical. Adoptive transfer of BCG sensitized splenocytes (one spleen equivalent per mouse injected intravenously immediately prior to the first BCG treatment) syngeneic to the MBT-2 tumor transferred delayed hypersensitivity reactivity to BCG antigens and restored the antitumor activity of intravesical BCG. In two separate experiments mice receiving splenocytes plus BCG had 0 and 20% tumor outgrowth compared with 100% in control mice (p less than .02 and p less than .05, respectively). These results demonstrate that the antitumor activity of intravesical BCG therapy requires a thymus-dependent immune response.
Interleukin‐9 and interleukin‐17C in chronic rhinosinusitis (2016)

Inflammatory cell expression of IL-9 and IL-17C were increased in CRS, particularly with allergy and asthma. These interleukins may contribute to the pathogenesis of CRSwNP as well as atopy and may serve as therapeutic targets for disease management.
Intraoperative measurement of the graft oxygenation state in living related liver transplantation by near infrared spectroscopy (1995)

Abstract Graft oxygenation plays an important role in successful liver transplantation. Intraoperative changes in the oxygenation state of the liver graft were measured by near infrared spectroscopy in 28 cases of living related liver transplantation. Oxygen saturation of hemoglobin in the liver (hepatic SO2) changed from 81.2%± 1.5% (mean ± SEM) before donation (in the donor) to 49.7%± 4.2% after portal reflow, to 58.4%± 5.0% after arterial reflow, and then to 71.4%± 3.9% before closure. Mean hepatic SO2 was positively correlated with portal flow rate as measured by duplex Doppler sonography. Cases with low portal flow rate showed a high coefficient of variation (SD/mean) of hepatic SO2, indicating heterogeneous tissue oxygenation. Though graft size was expected to affect the graft oxygenation state, hepatic SO2 was fairly independent of the graft-to-recipient weight ratio. In two cases with markedly low hepatic SO2, postoperative graft dysfunction occurred. This study suggest that the method of near infrared spectroscopy is reliable and useful for assessing the graft oxygenation state in liver transplantation.
THE CONTRASTING MECHANISMS OF COLONIC COLLAGEN DAMAGE BETWEEN PHOTODYNAMIC THERAPY and THERMAL INJURY (1987)

Abstract The colon is protected from disruption and bursting pressures by the submucosal collagen layer. Photodynamic therapy with aluminium sulphonated phthalocyanine (AlSPc) does not cause perforation or reduction in the bursting strength of the rodent colon despite causing full thickness damage. Thermal injury also produces full thickness necrosis but causes perforation and considerably reduces the bursting strength of the colon. The differing mechanisms of damage were examined. Using transmission electron microscopy we examined collagen from undamaged normal rodent colon, colon damaged by photodynamic therapy and thermally injured colon. Following photodynamic therapy collagen maintained its architecture and periodicity. Thermally damaged collagen became grossly swollen and lost its fibrillary architecture. We have concluded that photodynamic therapy with AlSPc is collagen sparing.
Characterizing the effects of nonlinear amplifiers on linear modulation for digital portable radio communications (2003)

The design and performance of linear modulation techniques and RF power amplifiers for digital portable radio communications are discussed. Various types of power amplifiers are used in the comparison of out-of-band radiation and power efficiency simulation. The designs focus on high-frequency silicon bipolar power amplifiers suitable for portable radio applications. Two different 4-ary quadrature amplitude modulation schemes are compared. It is shown that power efficiency as high as 40% can be achieved using a dynamically biased amplifier operating near saturation. The effects of nonlinear distortions from power amplifiers on adjacent interference as well as bit and block error rate performance are also investigated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>