gebhart/patrepeval huggingface dataset:
Variations in HSPA1B at 6p21.3 Are Associated with Lung Cancer Risk and Prognosis in Chinese Populations (2011)

The heat shock protein Hsp70 is crucial for regulating cellular homeostasis in stressed cells. Although the tumorigenic potential and prognostic applications of Hsp70 have been widely investigated, it remains unclear whether genetic variations of the human isoforms HSPA1L, HSPA1A, and HSPA1B are associated with cancer risk and prognosis. In this study, we genotyped six tagSNPs in these genes in 1,152 paired patients with lung cancer and controls, and then validated the results in additional cohorts of 1,781 patients with lung cancer and 1,038 controls. In addition, we evaluated the associations of these tagSNPs with survival in 330 patients with advanced non-small cell lung cancer (NSCLC) with additional validation in another 331 patients with advanced NSCLC. Functions of the risk variants identified were investigated using cell-based reporter assays. We found that the HSPA1B rs6457452T allele was associated with increased lung cancer risk compared with the rs6457452C allele in both data sets and also pooled analysis (adjusted OR = 1.41; P = 2.8 × 10(-5)). The HSPA1B rs2763979TT genotype conferred poor survival outcomes for patients with advanced NSCLC in two independent cohorts and pooled analysis [adjusted hazard ratio (HR) = 1.80, 1.61, and 1.66; P = 0.013, 0.036, and 0.002, respectively]. Lastly, we also found that the rs2763979T and rs6457452T alleles were each sufficient to reduce expression of transcriptional reporter constructs, when compared with the rs2763979C and rs6457452C alleles, respectively. Taken together, our findings define that functional HSPA1B variants are associated with lung cancer risk and survival. These Hsp70 genetic variants may offer useful biomarkers to predict lung cancer risk and prognosis.
Mesh saliency (2005)

Research over the last decade has built a solid mathematical foundation for representation and analysis of 3D meshes in graphics and geometric modeling. Much of this work however does not explicitly incorporate models of low-level human visual attention. In this paper we introduce the idea of mesh saliency as a measure of regional importance for graphics meshes. Our notion of saliency is inspired by low-level human visual system cues. We define mesh saliency in a scale-dependent manner using a center-surround operator on Gaussian-weighted mean curvatures. We observe that such a definition of mesh saliency is able to capture what most would classify as visually interesting regions on a mesh. The human-perception-inspired importance measure computed by our mesh saliency operator results in more visually pleasing results in processing and viewing of 3D meshes. compared to using a purely geometric measure of shape. such as curvature. We discuss how mesh saliency can be incorporated in graphics applications such as mesh simplification and viewpoint selection and present examples that show visually appealing results from using mesh saliency.
Identification of d -Peptide Ligands Through Mirror-Image Phage Display (1996)

Genetically encoded libraries of peptides and oligonucleotides are well suited for the identification of ligands for many macromolecules. A major drawback of these techniques is that the resultant ligands are subject to degradation by naturally occurring enzymes. Here, a method is described that uses a biologically encoded library for the identification of D-peptide ligands, which should be resistant to proteolytic degradation. In this approach, a protein is synthesized in the D-amino acid configuration and used to select peptides from a phage display library expressing random L-amino acid peptides. For reasons of symmetry, the mirror images of these phage-displayed peptides interact with the target protein of the natural handedness. The value of this approach was demonstrated by the identification of a cyclic D-peptide that interacts with the Src homology 3 domain of c- SRC. Nuclear magnetic resonance studies indicate that the binding site for this D-peptide partially overlaps the site for the physiological ligands of this domain.
Adenovirus–Mediated Overexpression of Follistatin Enlarges Intact Liver of Adult Rats (2003)

Under normal physiologic conditions, liver size is under strict regulatory control. Activin, a member of the transforming growth factor beta (TGF-beta) superfamily, is expressed in the intact adult liver and is an inhibitor of hepatocyte growth. However, the exact role played by endogenous activin in maintaining the size of a normal adult liver has yet to be completely examined in vivo. Here, we report the development of an adenoviral vector (AdexCAFS288) that expressed human follistatin-288, which binds to activin and neutralizes its biologic activities. AdexCAGFP, a control virus, expressed green fluorescent protein. AdexCAFS288 effectively expressed follistatin-288, as measured both in HepG2 cell lysate and conditioned medium and blocked activin signaling and its biologic functions in vitro. Intraperitoneal injection of AdexCAFS288 in vivo resulted in significant liver growth (146% of control) in intact liver of adult male rats 12 days following treatment without significant dysfunctions. The increase in liver size was attributed to increased hepatocyte proliferation, as monitored by the mitotic index. Furthermore, there was a significant correlation between serum follistatin levels and liver weight. In conclusion, our results suggest that activin plays a critical role in maintaining optimal liver size and implicates the endogenous activin system as a therapeutic target in the treatment of liver disease.
Statistical Applications of the Multivariate Skew Normal Distribution (1999)

Summary Azzalini and Dalla Valle have recently discussed the multivariate skew normal distribution which extends the class of normal distributions by the addition of a shape parameter. The first part of the present paper examines further probabilistic properties of the distribution, with special emphasis on aspects of statistical relevance. Inferential and other statistical issues are discussed in the following part, with applications to some multivariate statistics problems, illustrated by numerical examples. Finally, a further extension is described which introduces a skewing factor of an elliptical density.
Model‐based vehicle tracking from image sequences with an application to road surveillance (1996)

This paper proposes a model-based approach to vehicle tracking which is applied to a highway traffic surveillance problem. A detection and tracking algorithm is developed that achieves good performance with complexity low enough for real-time implementation using microprocessors.
Serum tumor necrosis factor alpha receptors p55/p75 ratio and ovarian cancer detection (2005)

Serum TNF alpha p55/p75 ratio showed promising value in ovarian cancer detection.
A new approach to geophysical real-time measurements on a deep-sea floor using decommissioned submarine cables (2014)

In order to better understand earthquake generation, tectonics at plate boundaries, and better image the Earth’s deep structures, real-time geophysical measurements in the ocean are required. We therefore attempted to use decommissioned submarine cables, TPC-1 and TPC-2. An OBS was successfully linked to the TPC-1 on the landward slope of the Izu-Bonin Trench in 1997. The OBS detected co-seismic and gradual changes during a Mw 6.1 earthquake just below the station at 80 km depth on November 11, 1997. A pressure sensor co-registered a change equivalent to 50 cm sea-level change. This suggests a high possibility detecting silent earthquakes or earthquake precursors if they exist. A multi-disciplinary geophysical station has been developed for deep-sea floor using TPC-2 since 1995. The station comprises eight instrument sets: broadband seismometers, geodetic measurements, hydrophone array, deep-sea digital camera, CTD, etc. These activities are examples that decommissioned submarine cables can be great global resources for real-time cost-effective geophysical measurements on a deep-sea floor.
Development of Prodrug 4-Chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl Benzoate (TG100801): A Topically Administered Therapeutic Candidate in Clinical Trials for the Treatment of Age-Related Macular Degeneration (2008)

Age-related macular degeneration (AMD) is one of the leading causes of loss of vision in the industrialized world. Attenuating the VEGF signal in the eye to treat AMD has been validated clinically. A large body of evidence suggests that inhibitors targeting the VEGFr pathway may be effective for the treatment of AMD. Recent studies using Src/YES knockout mice suggest that along with VEGF, Src and YES play a crucial role in vascular leak and might be useful in treating edema associated with AMD. Therefore, we have developed several potent benzotriazine inhibitors designed to target VEGFr2, Src, and YES. One of the most potent compounds is 4-chloro-3-{5-methyl-3-[4-(2-pyrrolidin-1-yl-ethoxy)phenylamino]benzo[1,2,4]triazin-7-yl}phenol ( 5), a dual inhibitor of both VEGFr2 and the Src family (Src and YES) kinases. Several ester analogues of 5 were prepared as prodrugs to improve the concentration of 5 at the back of the eye after topical administration. The thermal stability of these esters was studied, and it was found that benzoyl and substituted benzoyl esters of 5 showed good thermal stability. The hydrolysis rates of these prodrugs were studied to analyze their ability to undergo conversion to 5 in vivo so that appropriate concentrations of 5 are available in the back-of-the-eye tissues. From these studies, we identified 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate ( 12), a topically administered prodrug delivered as an eye drop that is readily converted to the active compound 5 in the eye. This topically delivered compound exhibited excellent ocular pharmacokinetics and poor systemic circulation and showed good efficacy in the laser induced choroidal neovascularization model. On the basis of its superior profile, compound 12 was advanced. It is currently in a clinical trial as a first in class, VEGFr2 targeting, topically applied compound for the treatment of AMD.
Tumor measurement in the nude mouse (1986)

In this study, the pitfalls of tumor measurement in the nude mouse were evaluated. Regarding intermethod variation, diameters of subcutaneous tumors in nude mice were expressed as length, area, and volume; tumor weights were also recorded. These measurements were all compared to a reference standard: water displacement volume. Estimates of area and volume derived from caliper measurements correlated well with water displacement volume (r = 0.97 and 0.98, respectively). At necropsy, tumor weight was the most consistent and reproducible reflection of tumor volume (r = 1.0000). Regarding interobserver variation, mean absolute difference among volumes determined by several investigators who measured the same tumors in living animals was determined. This averaged 15% of the mean calculated volume. Regarding intraobserver variation, observers measured four separate masses in nude mice eight times each. The observers were prevented from realizing that the same animals were being repeatedly evaluated. Volumes were compared in order to quantify the average variation that occurs when a single investigator repeatedly measures the same mass. When large masses were measured, this error was 7%; when small masses were measured, the error was 27%. Recommendations are made for future work employing tumor measurement.
Influence of heart rate on systolic time intervals: Effects of atrial pacing versus dynamic exercise (1981)

The effects of atrial pacing and dynamic exercise in the supine position on systolic time intervals (STI) were compared in 10 normals. In another group of 13 normals, the effect of exercise alone on STI was tested. A linear shortening of electromechanical systole (QS2) and left ventricular ejection time (LVET) with increasing heart rate was demonstrated with right atrial pacing and dynamic exercise in the frequency range between 60 and 140 beats/min. However, the shortening of LVET was significantly less (p less than 0.01) with exercise compared to pacing. This is explained by an increase in left ventricular stroke volume with exercise. The preejection period (PEP) was significantly (p less than 0.001) shortened with exercise, but there was no change with atrial pacing. Thus, changes in heart rate (HR) alone, without changes in the dynamic state of the heart, did not influence PEP. It is suggested that PEP at rest should not be corrected for heart rate. The supine exercise regression equations for correction of heart rate for LVET and PEP differ from both the resting and the upright exercise regression equations. With exercise a frequency correction of STI using regression equations should be abandoned. Instead, uncorrected STI at standard heart rates (e.g., 100, 110, and 130 beats/min) should be taken for comparison. Heart rate standardization should be employed using the formula: Formula (See Text).
Stabilin‐mediated cellular internalization of phosphorothioate‐modified Antisense Oligonucleotides (ASOs) (2016)

Introduction Antisense oligonucleotides (ASOs) are short chemically modified oligonucleotides (5–7.4 kDa) that can produce a pharmacological effect by binding to RNA and affecting intermediary metabolism. Over 35 phosphorothioate (PS) ASOs are at various stages of clinical development for use as therapeutic agents and pharmacological tools. Antisense therapy is a progressing area of research, as these small strands of nucleotide oligomers can be produced to silence genes that aggravate chronic disorders or infections. An important distinction for ASOs compared to DNA is the substitution of the phosphodiester (PO) backbone with the PS modification. This sulfur substitution allows for these polar polyanionic molecules to have high stability in biological fluids and selective binding to cell surfaces. Although there is a premium for clinical development of these short chain molecules, the current understanding of the pathways for their ability to traverse plasma membranes remains unresolved. Injected gymnotic ASOs have been shown to accumulate in the liver via the organ's functional scavenging mechanism in highly endocytically active sinusoidal endothelial cells (SECs) and Kupffer cells (KC) compared to hepatocytes. Our work outlines how a non‐DNA binding class of scavenger receptors known as Stabilins binds to, and internalizes these small PS ASOs. Methods Primary cells from rat and mouse were isolated and cultured with 125 I‐ASOs. Stable cell lines expressing Stabilin‐1 and two Stabilin‐2 isoforms (315‐HARE and 190‐HARE), were used to analyze binding affinity, endocytosis and degradation of 125 I‐ASOs in the cell. Co‐localization was also done to analyze trafficking of ASOs once internalized within the cell by use of fluorescent ASO and lysotracker. Results It was determined that PS ASOs bind with high affinity to the Stabilin class receptors with the majority of internalization performed by clathrin‐mediated endocytosis. Binding was determined to be dependent on proper folding of the receptor, along with relying on salt‐bridge formation. Once inside the cell via the Stabilin receptors, co‐localization analysis showed ASOs being trafficked for degradation in the lysosome. Increased internalization rates of an ASO targeting the non‐coding RNA of malat‐1, in the Stabilin‐expressing cell lines reduced malat‐1 expression more efficiently, indicating not all ASOs are trafficked to the lysosome after internalization. Conclusion Our work shows that ASOs are internalized into the cells of the liver through clathrin‐mediated endocytosis. The understanding of the pathway(s) for chemically modified ASO internalization and trafficking with cell surface receptors will aid in future clinical design of ASOs as therapeutic agents. Support or Funding Information National Institutes of Health – NHLBI R01 5R01HL094463‐07 University of Nebraska Undergraduate Creative Activities and Research Experience
Caveolin-1 Facilitates Mechanosensitive Protein Kinase B (Akt) Signaling In Vitro and In Vivo (2005)

Mechanotransduction represents an integral part of vascular homeostasis and contributes to vascular lesion formation. Previously, we demonstrated a mechanosensitive activation of phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt) resulting in p27Kip1 transcriptional downregulation and cell cycle entry of vascular smooth muscle cells (VSMC). In this study, we further elucidated the signaling from outside-in toward PI3-K/Akt in vitro and in an in vivo model of elevated tensile force. When VSMC were subjected to cyclic stretch (0.5 Hz at 125% resting length), PI3-K, Akt, and Src kinases were found activated. Disrupting caveolar structures with beta-cyclodextrin or transfection of VSMC with caveolin-1 antisense oligonucleotides (ODN) prevented PI3-K and Akt activation and cell cycle entry. Furthermore, PI3-K and Akt were resistant to activation when Src kinases were inhibited pharmacologically or by overexpression of a kinase-dead c-Src mutant. alpha(V)beta3 integrins were identified to colocalize with PI3-K/caveolin-1 complexes, and blockade of alpha(V)beta3 integrins prevented Akt activation. The central role of caveolin-1 in mechanotransduction was further examined in an in vivo model of elevated tensile force. Interposition of wild-type (WT) jugular veins into WT carotid arteries resulted in a rapid Akt activation within the veins that was almost abolished when veins of caveolin-1 knockout (KO) mice were used. Furthermore, late neointima formation within the KO veins was significantly reduced. Our study provides evidence that PI3-K/Akt is critically involved in mechanotransduction of VSMC in vitro and within the vasculature in vivo. Furthermore, caveolin-1 is essential for the integrin-mediated activation of PI3-K/Akt.
Emerging Raf inhibitors (2009)

Various Raf inhibitors have been developed and are being clinically used to treat patients with melanoma, thyroid, hepatocellular and renal cell cancers. Some 'Raf-kinase inhibitors' affect other kinases which are also expressed on malignant cells; yet, these inhibitors have proven useful in the therapy of certain cancer patients. Other more recently developed Raf specific inhibitors have shown success in the treatment of tumors bearing Raf mutations. The development of Raf inhibitors has significantly advanced cancer therapy in the past decade.
Impurity-related photoluminescence from InGaN LED material (2002)

Summary form only given. In this paper, we explain quantitatively the nature of the major emission band in Nichia LEDs. The experimental low-temperature (20 K) and room-temperature (RT) spectra were obtained by photoluminescence (PL). A broad impurity-related PL band, with an undulated envelope centered at 465 nm (2.67 eV), was observed at both low and room temperatures when the pump beam illuminated the active region.
Simultaneous Measurement of Strain and Temperature Incorporating a Long-Period Fiber Grating Inscribed on a Polarization-Maintaining Fiber (2004)

Simultaneous measurement of strain and temperature was demonstrated by using a long-period fiber grating inscribed on a polarization-maintaining fiber (PM-LPG). The spectral sensitivities of the two adjacent resonant dips of the PM-LPG were measured with respect to strain and temperature. The sensitivities of each resonant dip for strain and temperature were different in magnitude and sign, which makes this PM-LPG have a capability of simultaneously sensing strain and temperature. Experimental results show root mean square deviations of 15.6 μ/spl epsiv/ and 0.7/spl deg/C for strain and temperature, respectively.
Novel, ligation-dependent PCR assay for detection of hepatitis C in serum (1996)

A simple, sensitive, and specific ligation-dependent PCR (LD-PCR) method for the detection of hepatitis C virus (HCV) RNA in serum is described. The assay uses two DNA capture probes for RNA isolation and two DNA hemiprobes for subsequent PCR. Each capture probe has a 3' sequence complementary to the conserved 5' untranslated region of HCV RNA and a biotin moiety at the 5' end capable of interacting with streptavidin-coated paramagnetic beads. Each hemiprobe contains a sequence complementary to the 5' untranslated region in juxtaposition to one another and a common sequence for PCR primer binding. In guanidinium thiocyanate solutions, the capture probes and the hemiprobes form a hybrid with their target, and the hybrid can be isolated from serum by the binding of the capture probes to the paramagnetic beads in the presence of a magnetic field. The hemiprobes can then be linked to each other by incubation with T4 DNA ligase to form a full probe that serves as a template for a PCR. When serial 10-fold dilutions of synthetic HCV RNA (10(7) to 10 molecules) were tested, there was a good correlation between the amount of PCR product and the initial number of RNA molecules, with a sensitivity of 100 HCV RNA molecules per reaction. Twenty-four specimens that had been tested by either a branched DNA probe (bDNA) assay (13 specimens) or a reverse transcription PCR (RT-PCR) assay (11 specimens) were also analyzed by LD-PCR. The results showed a good correlation among LD-PCR, RT-PCR, and the bDNA assay. However, both LD-PCR and RT-PCR were more sensitive than the bDNA assay when the HCV titer was low.
Calphostin-C Induction of Vascular Smooth Muscle Cell Apoptosis Proceeds through Phospholipase D and Microtubule Inhibition (2004)

Calphostin-C, a protein kinase C inhibitor, induces apoptosis of cultured vascular smooth muscle cells. However, the mechanisms are not completely defined. Because apoptosis of vascular smooth muscle cells is critical in several proliferating vascular diseases such as atherosclerosis and restenosis after angioplasty, we decided to investigate the mechanisms underlying the calphostin-C-induced apoptotic pathway. We show here that apoptosis is inhibited by the addition of exogenous phosphatidic acid, a metabolite of phospholipase D (PLD), and that calphostin-C inhibits completely the activities of both isoforms of PLD, PLD1 and PLD2. Overexpression of either PLD1 or PLD2 prevented the vascular smooth muscle cell apoptosis induced by serum withdrawal but not the calphostin-C-elicited apoptosis. These data suggest that PLDs have anti-apoptotic effects and that complete inhibition of PLD activity by calphostin-C induces smooth muscle cell apoptosis. We also report that calphostin-C induced microtubule disruption and that the addition of exogenous phosphatidic acid inhibits calphostin-C effects on microtubules, suggesting a role for PLD in stabilizing the microtubule network. Overexpressing PLD2 in Chinese hamster ovary cells phenocopies this result, providing strong support for the hypothesis. Finally, taxol, a microtubule stabilizer, not only inhibited the calphostin-C-induced microtubule disruption but also inhibited apoptosis. We therefore conclude that calphostin-C induces apoptosis of cultured vascular smooth muscle cells through inhibiting PLD activity and subsequent microtubule polymerization.
A hierarchical Dirichlet language model (1995)

Abstract We discuss a hierarchical probabilistic model whose predictions are similar to those of the popular language modelling procedure known as ‘smoothing’. A number of interesting differences from smoothing emerge. The insights gained from a probabilistic view of this problem point towards new directions for language modelling. The ideas of this paper are also applicable to other problems such as the modelling of triphomes in speech, and DNA and protein sequences in molecular biology. The new algorithm is compared with smoothing on a two million word corpus. The methods prove to be about equally accurate, with the hierarchical model using fewer computational resources.