gebhart/patrepeval huggingface dataset:
Endothelin Receptor Blockade Potentiates FasL-Induced Apoptosis in Colon Carcinoma Cells Via The Protein Kinase C-Pathway (2000)

An imbalance between proliferation and apoptosis is important in tumor progression. Endothelin-1 (ET-1) has vasoconstricting and mitogenic activities and may be involved in apoptosis regulation. We found that ET-1 and FasL systems were colocalized in human colon tumors and that ET-1 was secreted by human (HT-29, SW480) and rat (PROb, REGb) colon carcinoma cell lines. Bosentan, a mixed endothelin-A- and -B- (ET(A)/ET(B)) receptor antagonist, potentiated FasL- (APO-1, CD95) induced apoptosis in these cells. The specific inhibition of enzymes involved in ceramide production did not restore survival of cells exposed to FasL and bosentan. Inhibition of PKC with bisindolylmaleimide IX enhanced FasL-induced apoptosis in HT-29, PROb and REGb cells in the absence of bosentan. These results suggest that ET-1 is an autocrine survival factor able to protect colon carcinoma cells against FasL-induced apoptosis, involving the protein kinase C (PKC) but not the sphingomyelin-ceramide signaling transduction pathways.
Current research and treatment for gastrointestinal stromal tumors (2017)

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest, especially in the last two decades. GISTs are driven by mutations commonly found in the <i>KIT</i> gene and less commonly in the platelet-derived growth factor receptor alpha gene, <i>BRAF</i> gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential, and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure, targeted therapy in the form of tyrosine kinase inhibitors (TKIs) has revolutionized the management options. As the first-line TKI, imatinib offers treatment for advanced and metastatic GISTs, adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options, including prolonging the first-line TKI from 1 to 3 years, increasing the dose of TKI or switching to second-line TKI. Other newer TKIs, such as sunitinib and regorafenib, may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated, such as inhibitors of BRAF, heat shock protein 90, glutamine and mitogen-activated protein kinase signaling, as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe, North America and Asia are highlighted.
Wireless Biomedical Sensing (2006)

Abstract Wireless biomedical sensing is a technique that measures physiological signals of humans or animals from a distance without a wire connection. Its basic components are sensor/transducer, transmitter, and receiver with an electromagnetic wave as the most widely adopted transmission medium. The theory of wireless communication with an enhanced biomedical aspect is presented. The current status and future trends of this field are also discussed.
Nonlinear Identification of Process Dynamics Using Neural Networks (1992)

The nonlinear identification of process dynamics encountered in nuclear power plant components is addressed, in an input/output sense, using artificial neural systems. A hybrid feedforward/feedback neural network, namely, a recurrent multilayer perceptron, is used as the model structure to be identified. The feedforward portion of the network architecture provides its well-known interpolation property, while through recurrency and cross-talk, the local information feedback enables representation of temporal variations in the system nonlinearities. The standard backpropagation learning algorithm is modified, and it is used for the supervised training of the proposed hybrid network. The performance of recurrent multilayer perceptron networks in identifying process dynamics is investigated via the case study of a U-tube steam generator. The response of a representative steam generator is predicted using a neural network, and it is compared to the response obtained from a sophisticated computer model based on first principles. The transient responses compare well, although further research is warranted to determine the predictive capabilities of these networks during more severe operational transients and accident scenarios.
Antigens on human monocytes identified by monoclonal antibodies. (1981)

Two antigens (Mo1 and Mo2) present on human peripheral blood monocytes have been defined by lytic IgM monoclonal antibodies. Both antigens are present on greater than 70% of adherent mononuclear cells (predominantly monocytes). Mo1 is expressed by monocytes, granulocytes, and Null cells, but is absent from T and B lymphocytes. Mo2, on the other hand, appears specific for peripheral blood monocytes. Neither antigen is present on Ia-positive B cell lines or on tumor cells from patients with B cell lymphoproliferative malignancies, further excluding the possibility that Mo1 and Mo2 are Ia antigens. Mo1 and Mo2 are, however, present on a significant number of blast cells from patients with monocytic leukemia (both myelomonocytic and pure monocytic variants), but relatively infrequently expressed by cells from patients with acute granulocytic leukemia. These results indicate that Mo1 and Mo2 are unique antigens that may represent distinct stages of late monocyte-granulocyte differentiation.
Activation of melanoma antigen tumor antigens occurs early in lung carcinogenesis. (2001)

The melanoma antigen (MAGE)-encoding genes are expressed in various tumor types, including lung, and are thought to be silent in all normal tissues except testis. In search of biomarkers for early lung cancer detection and cancer risk assessment, we investigated frequencies of expressional activation of MAGE-A1, -A3, and -B2 genes in non-small cell lung cancers (NSCLCs). Expression of these genes was evaluated by reverse transcription-PCR (RT-PCR) in 20 primary NSCLC samples and corresponding normal lung tissues as well as in 20 bronchial brush specimens from former smokers without lung cancer. mRNA in situ hybridization was done to confirm the gene expression pattern at the cellular level. Methylation-specific PCR was performed to evaluate the hypomethylation status of CpG sites in the promoter regions of these genes. Among the 20 primary NSCLC samples analyzed, 14 (70%) expressed MAGE-A1 and 17 (85%) each expressed MAGE-A3 and MAGE-B2. A substantial number of normal lung tissues adjacent to NSCLC also had a detectable level of MAGE expression (65, 75, and 80% for MAGE-A1, -A3, and -B2, respectively). We found that 7 (35%), 10 (50%), and 11 (55%) of the adjacent normal lung tissue samples exhibited promoter hypomethylation at MAGE-A1, -A3, and -B2, respectively, compared with 15 (75%), 16 (80%), and 16 (80%) of the NSCLC samples. Among the 20 bronchial epithelium samples from former smokers, 7 (35%), 10 (50%), and 12 (60%) had also detectable -A1, -A3, and -B2 expression, respectively. Activation of MAGE-A1, -A3, and -B2 genes is common not only in NSCLC but also in bronchial epithelium with severe carcinogen insult. These results suggest that MAGE genes may be activated very early in lung carcinogenesis and may be considered as targets for lung cancer prevention.
An analytical least-squares solution to the odometer-camera extrinsic calibration problem (2012)

In order to fuse camera and odometer measurements, we first need to estimate their relative transformation through the so-called odometer-camera extrinsic calibration. In this paper, we present a two-step analytical least-squares solution for the extrinsic odometer-camera calibration that (i) is not iterative and finds the least-squares optimal solution without any initialization, and (ii) does not require any special hardware or the presence of known landmarks in the scene. Specifically, in the first step, we estimate a subset of the 3D relative rotation parameters by analytically minimizing a least-squares cost function. We then back-substitute these estimates in the measurement constraints, and determine the rest of the 3D transformation parameters by analytically minimizing a second least-squares cost function. Simulation and experimental results are presented that validate the efficiency and accuracy of the proposed algorithm.
Nucleotides, Part LXV, Synthesis of 2′-Deoxyribonucleoside 5′-Phosphoramidites: New Building Blocks for the Inverse (5′-3′)-Oligonucleotide Approach (2000)

The syntheses of the 3′-O-(4,4′-dimethoxytrityl)-protected 5′-phosphoramidites 25 – 28 and 5′-(hydrogen succinates) 29 – 32, which can be used as monomeric building blocks for the inverse (5′-3′)-oligodeoxyribonucleotide synthesis are described (Scheme). These activated nucleosides and nucleotides were obtained by two slightly different four-step syntheses starting with the base-protected nucleosides 13 – 20. For the protection of the aglycon residues, the well-established 2-(4-nitrophenyl)ethyl (npe) and [2-(4-nitrophenyl)ethoxy]carbonyl (npeoc) groups were used. The assembly of the oligonucleotides required a slightly increased coupling time of 3 min in application of the common protocol (see Table 1). The use of pyridinium hydrochloride as an activator (instead of 1H-tetrazole) resulted in an extremely shorter activation time of 30 seconds. We established the efficiency of this inverse strategy by the synthesis of the oligonucleotide 3′-conjugates 33 and 34 which carry lipophilic caps derived from cholesterol and vitamin E, respectively, as well as by the formation of (3′-3′)- and (5′-5′)-internucleotide linkages (see Table 2).
The chakragati mouse: A mouse model for rapid in vivo screening of antipsychotic drug candidates (2007)

The chakragati (ckr) mouse is a serendipitously discovered insertional transgenic mutant that exhibits circling and hyperactivity. Studies of social behavior, sensorimotor gating and ventricular anatomy suggest that the ckr mouse models aspects of schizophrenia. The underlying genetic and neurodevelopmental mechanisms remain to be elucidated but appear to result in a hemispheric asymmetry in striatal D(2)-like dopamine receptors. The circling is inhibited by administration of antipsychotic drugs and so lends itself to in vivo prospective screening for novel molecules with antipsychotic-like activity. Using the ckr mouse we have applied an in vivo first approach to screening for antipsychotic drug candidates. This offers the advantage of early indication of central nervous system bioavailability and potential toxicological concerns. Additionally, in vivo first screening in the ckr mouse is not biased by any particular neurotransmitter hypothesis of the disease, and so has the potential to identify compounds modifying the behavioral output by novel mechanisms of interaction with the underlying brain circuitry. Thus, in contrast to the classical strategy of hypothesis-driven in vitro screening for drugs fitting a "receptor model" of the disease, the ckr mouse screen has greater potential to identify lead molecules for a new generation antipsychotics with novel mechanisms of action.
Expression of Transforming Growth Factor (TGF)-β1, -β2, and -β3 Isoforms and TGF-β Type I and Type II Receptors in Multiple Sclerosis Lesions and Human Adult Astrocyte Cultures (1999)

It is known that the pleiotropic cytokine transforming growth factor beta (TGF-beta) has a regulatory role in the process of tissue repair and remodelling following injury. As reports on these molecules in multiple sclerosis (MS) lesion with different lesional activity are rare, we studied the cellular localization of TGF-beta1, -beta2, and -beta3 isoforms, and TGF-beta receptor type I (TGF-betaR-I) and TGF-betaR-II expression by immunohistochemistry on postmortem brain tissue from MS and normal control cases. To validate the TGF-beta staining results we demonstrated that cultured human adult astrocytes that produce biological active TGF-beta2, and to a lesser extent TGF-beta1, were immunoreactive for all 3 TGF-beta isoforms. Moreover, at mRNA level TGF-beta1 was detected in MS and normal control brain tissue. In normal control brain tissue, TGF-beta isoforms were expressed in ramified microglia and TGF-beta2, and -beta3 on neuronal cells in the gray matter TGF-betaR-I and TGF-betaR-II expression was found on endothelial cells, astrocytes, microglia, and neurons. In active demyelinating MS lesions a strong to intense immunoreactivity was detected for all 3 TGF-beta isoforms in perivascular and parenchymal (foamy) macrophages and in hypertrophic astrocytes. Strong immunoreactivity for TGF-betaR-I and TGF-betaR-II was found on macrophages in both parenchymal and perivascular areas and on hypertrophic astrocytes and endothelial cells in active demyelinating MS lesions. In chronic active and inactive MS lesions, all 3 TGF-beta isoforms and their receptors were strongly expressed in hypertrophic astrocytes. Our findings strongly suggest that the expression of the various TGF-beta isoforms and their receptor types found in MS lesions with different cellular activity participate in reactive processes leading to the formation of chronic MS lesions.
Dynamic state of collagen: pathways of collagen degradation in vivo and their possible role in regulation of collagen mass (1987)

There is now evidence that collagen turnover in normal tissues can occur at rapid rates. In skin of adult rats, the mean rate lies between 3 and 5%/day, but rates of greater than 10%/day have been reported in some tissues, such as lung and periodontal ligament. The major sites of this degradation are still uncertain. Intracellular degradation, which occurs within minutes of synthesis, may be extensive, but its magnitude varies between tissues. This process may have evolved to allow the adaptive advantages of rapid turnover without compromising the supportive role of fibrillar collagen. There is now abundant evidence that changes in collagen degradation play an important role in the regulation of collagen mass. Increased breakdown of extracellular collagens may be required whether the mass is increased or decreased. However, preliminary evidence suggests that the degradation of newly synthesized collagen may be up- or down-regulated, depending on the direction of the change in content.
Mobile camera-based adaptive viewing (2005)

In this paper, we present an approach for facilitating user interaction on mobile devices, focusing on camera-enabled mobile phones. A user interacts with an application by moving their device. An on-board camera is used to capture incoming video and the scrolling direction and magnitude are estimated using a computer vision-based algorithm. The direction is used as the scroll direction in the application, and the magnitude is used to set the zoom level. The camera is treated as a pointing device and zoom level control in applications. Our approach generates mouse events, so any application that is mouse-driven can make use of this technique. The user is free to browse through large data sets on a limited size display with one hand, ideal for the mobile domain.
An Emerging Strategy for Cancer Treatment Targeting Aberrant Glycogen Synthase Kinase 3β (2009)

Improvement in the outcome of cancer patients who are refractory to currently available treatments relies on the development of target-directed therapies. One group of molecular targets with potential clinical relevance is a set of protein tyrosine kinases encoded mostly by proto-oncogenes and that are frequently deregulated in cancer. Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, has emerged as a therapeutic target for common chronic diseases including type 2 diabetes mellitus, neurodegenerative disorders, inflammation and osteoporosis. This is based on its currently known functions and primary pathologic causalities. GSK3beta has well characterized roles in the regulation of gene transcription and in oncogenic signaling. We have shown that deregulated GSK3beta promotes gastrointestinal, pancreatic and liver cancers and glioblastomas. Furthermore, we have demonstrated that inhibition of GSK3beta attenuates cell survival and proliferation, induces cell senescence and apoptosis and sensitizes tumor cells to chemotherapeutic agents and ionizing radiation. This has led us to propose GSK3beta as a potential therapeutic target in cancer. The anti-tumor effects of GSK3beta inhibition are mediated by changes in the expression and phosphorylation of molecules critical to the regulation of cell cycling, proliferation and apoptosis and underlie the pathological role for GSK3beta in cancer. Investigation of the mechanisms responsible for deregulation of GSK3beta and the consequent downstream pathologic effects in cancer cells has shed light on the molecular pathways leading to tumorigenesis. This will allow exploration of novel therapeutic strategies for cancer that target aberrant GSK3beta.
Hepatitis B Virus RNA-Binding Proteins Associated with Cytokine-Induced Clearance of Viral RNA from the Liver of Transgenic Mice (1999)

Hepatitis B virus (HBV) gene expression is downregulated in the liver of HBV transgenic mice by a posttranscriptional mechanism that is triggered by the local production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) during intrahepatic inflammation (hepatitis). The molecular basis for this antiviral effect is unknown. In this study, we identified three HBV RNA-binding liver nuclear proteins (p45, p39, and p26) the relative abundance of which correlates with the abundance of HBV RNA in response to the induction of IFN-gamma and TNF-alpha. All three proteins bind to a 91-bp element located at the 5' end of a previously defined posttranscriptional regulatory element that is thought to mediate the nuclear export of HBV RNA. The presence of p45 correlates directly with the presence of HBV RNA, being detectable under baseline conditions when the viral RNA is abundant and undetectable when the viral RNA disappears in response to IFN-gamma and TNF-alpha. In contrast, p26 is inversely related to HBV RNA, being detectable only when the viral RNA disappears following cytokine activation. Finally, p39 is constitutively expressed, and its abundance and mobility appear to be slightly increased by cytokine activation. These results suggest a model in which hepatocellular HBV RNA content might be controlled by the stabilizing and/or destabilizing influences of these RNA-binding proteins whose activity is regulated by cytokine-induced signaling pathways.
Transgenic Animals (1988)

The ability to introduce foreign genes into the germ line and the successful expression of the inserted gene in the organism have allowed the genetic manipulation of animals on an unprecedented scale. The information gained from the use of the transgenic technology is relevant to almost any aspect of modern biology including developmental gene regulation, the action of oncogenes, the immune system, and mammalian development. Because specific mutations can be introduced into transgenic mice, it becomes feasible to generate precise animal models for human genetic diseases and to begin a systematic genetic dissection of the mammalian genome.
Molecular Cloning and Characterization of a cDNA, CHEMR1, Encoding a Chemokine Receptor With a Homology to the Human C-C Chemokine Receptor, CCR-4 (1997)

Chemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites. These are known to bind to seven-transmembrane-domain containing receptors. A cDNA clone, CHEMR1, resembling the typical G protein-coupled receptor, was isolated from a mouse cytotoxic T-lymphocyte (CTL) library. Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells, including T cells, B cells, and macrophages. The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1alpha (MIP-1alpha) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside. Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4. Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1alpha, RANTES, or MIP-1beta, whereas CCR-1 binds MIP-1alpha and RANTES. Our result is different from the reported properties of human CCR-4. This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1alpha.
Divorcing Gender From Marriage: A Feminist Perspective on the Jurisprudence of Transgendered Marriage (2015)

Sex is an immutable characteristic; says who? As transgendered people and LGBTQQ (lesbian, gay, bisexual, transgender, queer, questioning) issues gain more traction and recognition, the clear contours of sex and gender are fading, and a more fluid concept of gender is emerging. However, the American legal system lags behind the mutability of gender in an environment where the conceptualization and understanding of gender is becoming ever more nuanced and complex. This is most apparent in the law’s treatment of transgendered marriage: a marriage involving at least one person who identifies as transgendered. A transgendered person can be defined as a person who identifies as a gender that is different than the gender assigned based on his or her sex at birth, inclusive of those who have or have not transitioned, had sex-reassignment surgery, executed a name change, or modified the gender marker on his or her legal documents. The law’s rigid response to the complications that transgendered marriage presents in the wake of unlawful same-sex marriage, is to wholly negate the importance of recognizing gender, and instead, to look primarily to a person’s sex for guidance. This article explores the jurisprudence underpinning lawful and null transgendered marriages from a feminist perspective. Specifically, it describes the history and current state of jurisprudence as it relates to transgendered marriage. This review of the legal landscape identifies the law’s sex-based thresholds for defining gender, which result in the validation or invalidation of a transgendered marriage. Analyzing these thresholds implicates the way in which the law serves to control gender identity and reinforces traditional gender roles in society. This in turn reveals the insidious undercurrent of bias and patriarchy permeating the annals of the justice system as it relates to gender and transgendered identity. Ultimately, this article exposes the woefully inadequate state of jurisprudence today as it relates to transgendered marriage and gender, and posits that this is due in large part to non-lgbptqq identifying, white male dominance.
First place — resident clinical science award 1993: A comparison of cocaine vs. lidocaine with oxymetazoline for use in nasal procedures (1993)

This study compared the degree of vasoconstriction and anesthesia obtained with cocaine vs. that obtained with a mixture of lidocaine and oxymetazoline (lido/oxy) in healthy, male volunteers. Blood flow was evaluated by laser Doppler flowmetry. Anesthesia was measured with Semmes-Weinstein monofilaments, testing both sensation threshold and pain perception. A greater decrease in blood flow was seen after the administration of lido/oxy than after the administration of cocaine. Pain perception change was not significantly different between treatment groups at 10 minutes after removal of the medication-soaked pledget, but lido/oxy caused a greater decrease in pain perception than cocaine after 50 minutes. No significant difference in sensation threshold change was seen between treatment groups. Lidocaine with oxymetazoline is, therefore, believed to be an effective alternative to cocaine for nasal procedures.