gebhart/patrepeval huggingface dataset:
Sequence of the Human Glycogen-Associated Regulatory Subunit of type 1 Protein Phosphatase and Analysis of Its Coding Region and mRNA Level in Muscle From Patients With NIDDM (1994)

Impaired insulin-stimulated glycogen synthesis of peripheral tissues is a characteristic feature of many patients with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives with normal glucose tolerance, suggesting putative inherited defects in this metabolic pathway. In previous studies, we have failed to reveal mutations in the coding regions of the muscle-specific glycogen synthase gene and the three genes that encode the catalytic subunits of protein phosphatase 1 (PP1) as frequent causes of insulin resistance. Because the glycogen-associated regulatory subunit of protein phosphatase 1 (PP1 G-subunit) plays a key role in the insulin stimulation of glycogen synthesis and the activity of PP1 is decreased in insulin-resistant subjects, we have now cloned the human G-subunit cDNA to search for abnormalities in the corresponding gene (designated PPP1R3 in the human genome nomenclature) in patients with NIDDM. The human cDNA was isolated from a skeletal muscle cDNA library and was found to encode a 126-kDa protein, which shows 73% amino acid identity to the rabbit PP1 G-subunit. The human G-subunit cDNA from 30 insulin-resistant NIDDM patients was analyzed for genetic variations in the G-subunit by using single-stranded conformation polymorphism (SSCP) scanning of reversely transcribed mRNA. One variant SSCP profile was detected in the region encoding the COOH-terminal part of the PP1 G-subunit in only one NIDDM patient, and subsequent nucleotide sequencing showed a C to A transversion on one allele at base position 2792. This change predicts an amino acid substitution from alanine to glutamic acid. The carrier of this mutation was characterized by reduced insulin-stimulated nonoxidative glucose metabolism when examined with the euglycemic hyperinsulinemic clamp. SSCP scanning of the 2584–2844 nucleotide fragment of PP1 G-subunit cDNA from an additional 22 NIDDM patients and 29 control subjects did not reveal additional genetic variants. To indirectly screen for abnormalities in PP1 G-subunit gene regulation, we measured the mRNA level of the G-subunit in skeletal muscle. However, no difference in the abundance of mRNA of PP1 G-subunit was found between patients with diabetes and control subjects.
Regularized linear discriminant analysis and its application in microarrays (2006)

In this paper, we introduce a modified version of linear discriminant analysis, called the "shrunken centroids regularized discriminant analysis" (SCRDA). This method generalizes the idea of the "nearest shrunken centroids" (NSC) (Tibshirani and others, 2003) into the classical discriminant analysis. The SCRDA method is specially designed for classification problems in high dimension low sample size situations, for example, microarray data. Through both simulated data and real life data, it is shown that this method performs very well in multivariate classification problems, often outperforms the PAM method (using the NSC algorithm) and can be as competitive as the support vector machines classifiers. It is also suitable for feature elimination purpose and can be used as gene selection method. The open source R package for this method (named "rda") is available on CRAN (http://www.r-project.org) for download and testing.
Erratum to: CoMEt: a statistical approach to identify combinations of mutually exclusive alterations in cancer (2016)

After the publication of this work [1] it has been brought to our attention that the descriptions of the generation of the two simulated datasets were confusing. In the section 'Benchmarking of methods for individual gene sets', the first sentence of the second paragraph should specify the number of genes included in the gene set as 100, and it should read: "We compared CoMEt to the other methods on datasets with m= 100 genes and n = 500 samples and with implanted pathways with coverages ? ranging from 0.1 to 1.0." In the section 'Benchmarking identification of collections of gene sets', the first paragraph should specify that genes mutated in fewer than 1% of total samples (that is in fewer than 5 out of 500 samples) were removed from the simulation, and the sixth sentence in this paragraph should read: "Third, we include m= 20,000 genes and remove those genes that are mutated in fewer than 1% of total samples (that is in fewer than 5 out of 500 samples) (Additional file 1: Figure S2)." Additionally, these descriptions are also included in the Additional file 1, section S3, and should read: "We generated two different versions of the simulated datasets, depending on whether we implanted a single or multiple gene sets. We describe the method for generating datasets with multiple implanted gene sets in the main text. For all simulated datasets, we used n = 500, |C| = 5, ?C = (0.67, 0.49, 0.29, 0.29, 0.2), and q = 0.0027538462.1 We used μP = (0.5, 0.35, 0.15) for the single pathway simulations." We also updated the description of our procedure for assessing the convergence of the MCMC algorithm in Additional file 1, section S2, which should read: "To assess the convergence of the MCMC algorithm, we ran multiple chains with different initializations. For one of these initializations, we used the collection output by Multi-Dendrix [21] (using the same values of the parameters t and k as in CoMEt). The remaining initializations were random collections. We ran the MCMC algorithm with these initializations, running each chain for a given number of iterations. We consider the chains converged if the mean total variation distance between the chains is smaller than 0.005. Otherwise, we increase the number of iterations by a factor of 1.5. We repeat this process until the chains converge or the total number of iterations per chain reaches a maximum number of iterations, which we set as 1 billion. The output of the MCMC algorithm is the union of the sampling distributions from the different initializations." The corrected Additional file 1 is included in this Erratum.
Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents (2008)

Although Akt is known as a survival kinase, inhibitors of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway do not always induce substantial apoptosis. We show that silencing Akt1 alone, or any combination of Akt isoforms, can suppress the growth of tumors established from phosphatase and tensin homologue-null human cancer cells. Although these findings indicate that Akt is essential for tumor maintenance, most tumors eventually rebound. Akt knockdown or inactivation with small molecule inhibitors did not induce significant apoptosis but rather markedly increased autophagy. Further treatment with the lysosomotropic agent chloroquine caused accumulation of abnormal autophagolysosomes and reactive oxygen species, leading to accelerated cell death in vitro and complete tumor remission in vivo. Cell death was also promoted when Akt inhibition was combined with the vacuolar H(+)-adenosine triphosphatase inhibitor bafilomycin A1 or with cathepsin inhibition. These results suggest that blocking lysosomal degradation can be detrimental to cancer cell survival when autophagy is activated, providing rationale for a new therapeutic approach to enhancing the anticancer efficacy of PI3K-Akt pathway inhibition.
A New Water‐soluble Camptothecin Derivative, DX‐8951f, Exhibits Potent Antitumor Activity against Human Tumors in vitro and in vivo (1995)

CPT-11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT-11 is a pro-drug that is converted to an active metabolite, SN-38, in vivo by enzymes such as carboxylesterase. We synthesized a water-soluble and non-pro-drug analog of camptothecin, DX-8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti-proliferative activity of DX-8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN-38 or SK&F 10486-A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX-8951f administered i.v. at 4-day intervals against human gastric adenocarcinoma SC-6 xenografts was greater than that of CPT-11 or SK&F 10486-A. Moreover, it overcame P-glycoprotein-mediated multi-drug resistance. These data suggest that DX-8951f has a high antitumor activity and is a potential therapeutic agent.
Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors (2002)

Transgenic mice expressing a stabilized beta-catenin in neural precursors develop enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Brains from transgenic animals have enlarged lateral ventricles lined with neuroepithelial precursor cells, reflecting an expansion of the precursor population. Compared with wild-type precursors, a greater proportion of transgenic precursors reenter the cell cycle after mitosis. These results show that beta-catenin can function in the decision of precursors to proliferate or differentiate during mammalian neuronal development and suggest that beta-catenin can regulate cerebral cortical size by controlling the generation of neural precursor cells.
Molecular and cellular biology of interleukin-6 and its receptor (1996)

Interleukin-6 (IL-6) is a member of the family of cytokines collectively termed "the interleukin-6 type cytokines." Among its many functions, IL-6 plays an active role in immunology, bone metabolism, reproduction, arthritis, neoplasia, and aging. IL-6 expression is regulated by a variety of factors, including steroidal hormones, at both the transcriptional and post-transcriptional levels. IL-6 achieves its effects through the ligand-specific IL-6 receptor (IL-6R). Unlike most other cytokine receptors, the IL-6R is active in both membrane bound and soluble forms. Defining mechanisms to control IL-6 or IL-6R expression may prove useful for therapy of the many clinical disorders in IL-6 plays a role.
FAST SEMANTIC SEGMENTATION OF 3D POINT CLOUDS WITH STRONGLY VARYING DENSITY (2016)

Abstract. We describe an effective and efficient method for point-wise semantic classification of 3D point clouds. The method can handle unstructured and inhomogeneous point clouds such as those derived from static terrestrial LiDAR or photogammetric reconstruction; and it is computationally efficient, making it possible to process point clouds with many millions of points in a matter of minutes. The key issue, both to cope with strong variations in point density and to bring down computation time, turns out to be careful handling of neighborhood relations. By choosing appropriate definitions of a point’s (multi-scale) neighborhood, we obtain a feature set that is both expressive and fast to compute. We evaluate our classification method both on benchmark data from a mobile mapping platform and on a variety of large, terrestrial laser scans with greatly varying point density. The proposed feature set outperforms the state of the art with respect to per-point classification accuracy, while at the same time being much faster to compute.
Elastomeric Optics (1996)

This paper describes optical components prepared using poly(dimethylsiloxane) elastomers and liquid metals as constituent materials. Most optical components are fabricated from rigid materials such as glass, rigid polymers, or metals. By contrast, the elastomeric optics described here are designed to be deformable. Because the structure of the optical surface can be deformed easily, a single elastomeric optical component can be adapted to several applications. This paper provides procedures for the fabrication of elastomeric diffraction gratings, mirrors, and lenses and characterizes some basic properties of these optical elements.
Noble Metal/W(111) Single-Atom Tips and Their Field Electron and Ion Emission Characteristics (2006)

We have developed a simple, reliable and reproducible method for preparing single-atom tips. With electrochemical techniques, a very small amount of a noble metal is plated on the surface of a clean W&lt;111&gt; tip. Upon annealing the tip at an appropriate temperature in vacuum, a three-sided {211} pyramid with a single-atom sharpness is formed spontaneously at the tip apex by adsorbate-induced faceting. This tip is both thermally and chemically stable, and can be regenerated several ten times when accidentally damaged. We use a field ion microscope to examine the atomic structure of the tip apex layer by layer and characterize the corresponding electron emission in the field emission mode. Some properties of Ne + ions emitted from a single-atom tip are also measured, indicating a high brightness and a small extension angle. Many desirable features make the single-atom tips very promising for future particle beam applications in nanoscience and nanotechnology.
A One-Step Procedure for the Monoacylation of Symmetrical 1,2-Diols (2002)

A series of lanthanide (III) salts have been shown to catalyze the monoacylation of symmetrical 1,2-diols by carboxylic acid anhydrides with surprisingly high selectivity.
MALAR IMPLANTS FOR IMPROVEMENT OF THE FACIAL APPEARANCE (1975)

Esthetic correction of flat malar eminences may contribute to the harmony of facial proportions by making the face more oval and by giving a more youthful appearance. Zygomatic augmentation may also be indicated for the treatment of congenital hypoplasias, asymmetries, or traumatic depressions of the malar region. We have used the procedure in 52 cases since 1964. For augmentation we use a perforated soft, silicone rubber implant. The technique and results are described. The results have been satisfactory, for both the patients and the surgeon.
A phase I trial for the treatment of purine analog-refractory chronic lymphocytic leukemia using autologous T cells genetically targeted to the B cell specific antigen CD19 (2008)

3045 Background: We have developed a novel immunotherapy strategy based on the genetic modification of patient T cells to recognize the B cell-specific cellular antigen CD19, expressed on B cell tumors, through the retroviral expression of a chimeric antigen receptor (CAR) specific for CD19 (19–28z). Methods: We have initiated a clinical trial utilizing 19–28z+ autologous T cells in patients with purine analog-refractory chronic lymphocytic leukemia (CLL) (IRB #06–138). Enrolled patients initially undergo a leukopheresis procedure in order to obtain T cells. T cells are isolated and activated using Dynabeads ClinExVivo CD3/CD28 magnetic beads. Activated T cells are subsequently transduced with the CD19 specific 19–28z CAR using cGMP gammaretroviral vector stocks generated in our facility, and expanded utilizing a WaveTM bioreactor platform-based rapid expansion protocol. To assess safety, patients enrolled in the first cohort of this trial received an infusion of the lowest planned dose of modified T cells alone, subsequent cohorts will receive infusions of 19–28z+ T cells at the lowest planned dose level following escalating doses of cyclophosphamide chemotherapy followed by escalating doses of T cells after cyclophosphamide. Results: Patients treated in the first cohort with the lowest modified T cell dose alone experienced grade 2 fevers and rigors during infusion but no dose limiting toxicities. Treated patients variably experienced decrease in lymph node size, decreased CD19+ B cell numbers in the peripheral blood, and a decreased dependence on red blood cell transfusions. Conclusions: Infusion of genetically modified T cells targeted to CD19 is well tolerated in patients with refractory CLL with objective evidence of anti-tumor responses. We plan to enroll patients on the second planned cohort of this trial wherein patients will receive prior lymphodepleting chemotherapy with cyclophosphamide. The trial presented here is both the first to utilize gene modified autologous T cells for the treatment of CLL, as well as the first to target CD19+ tumors utilizing a rapid T cell expansion protocol, which represents a promising and novel treatment approach for patients with B cell malignancies. No significant financial relationships to disclose.
Chiral reagents for asymmetric synthesis (2003)

Preface. Introduction. Recent Review Articles and Monographs. Organic Synthesis Procedures Featuring Chiral, Non-Racemic Reagent Preparation. List of Contributors. Reagent Formula Index. Subject Index.
Pancreatic microvascular permeability in caerulein-induced acute pancreatitis (1991)

Microvascular permeability was studied in the isolated perfused rat pancreas using a rapid multiple indicator-dilution technique. Capillary extractions, permeability-surface area products (PS), and extravascular volumes of distribution (EVV) were determined for 22Na+, 51Cr-labeled EDTA, [57Co]-cyanocobalamin (B12), and 125I-labeled insulin at various perfusion flows. Permeability to albumin was negligible. PS for Na+ and EDTA increased with increasing flow, whereas PS for cyanocobalamin and insulin approached diffusion-limited exchange at flows greater than 3 ml.min-1.g-1. Permeability coefficients for Na+, EDTA, B12, and insulin were 36, 22, 11, and 3.48 x 10(-5) cm/s, respectively, and the permeability ratio for B12/insulin (3.16) indicated restricted diffusion to insulin. In the presence of unlabeled B12 and insulin EVV (0.15-0.19 ml/g) for EDTA, B12 and insulin approximated the interstitial volume. Caerulein-induced pancreatitis or treatment with the synthetic protease inhibitor camostate had no significant effects on permeability. In caerulein-treated rats, EVV for B12 was elevated (0.17 +/- 0.01 vs. 0.28 +/- 0.06; P less than 0.01), reflecting the interstitial edema associated with this model of pancreatitis. Permeability of the rat pancreatic microvasculature is similar to that of other fenestrated tissues, but it is 10- to 20-fold greater than that of continuous capillaries. Contrary to previous assumptions, permeability does not appear to be increased after induction of acute interstitial pancreatitis.
CIEL: a universal execution engine for distributed data-flow computing (2011)

This paper introduces CIEL, a universal execution engine for distributed data-flow programs. Like previous execution engines, CIEL masks the complexity of distributed programming. Unlike those systems, a CIEL job can make data-dependent control-flow decisions, which enables it to compute iterative and recursive algorithms.We have also developed Skywriting, a Turing-complete scripting language that runs directly on CIEL. The execution engine provides transparent fault tolerance and distribution to Skywriting scripts and high-performance code written in other programming languages. We have deployed CIEL on a cloud computing platform, and demonstrate that it achieves scalable performance for both iterative and non-iterative algorithms.
Wireless Communication Standards: A Study of IEEE 802.11, 802.15, and 802.16 (2004)

Wireless Communications Standards: A Study of IEEE 802.11, 802.15, and 802, is one of the latest books in the IEEE Standards Wireless Networks Series, and it is the only book of its kind that covers all of the current 802 wireless standards! Presented in a clear style, by Dr. Todor Cooklev of San Francisco State University, the book is accessible to a wide audience. It is aimed at engineers, computer scientists, managers, and marketing specialists. It can also be used as the primary textbook for a one-semester advanced undergraduate/graduate level course on wireless communication standards, or as a complementary textbook for a course in wireless communications
Antimicrobials and the Skin Physiological and Pathological Flora (2006)

Healthy human skin is regularly colonized by nonpathogenic microorganisms. Bacterial genera isolated are coagulase-negative staphylococci and diphtheroid rods on the skin surface and propionibacteria in the infundibulum of the sebaceous glands. As for fungi, Pityrosporum (Malassezia spp.) is regularly present. The distribution and density of the flora is dependent on age and environmental factors such as sebum secretion, occlusion, temperature and humidity. Odor production in the axilla is related to the activity of aerobic diphtheroids. Antimicrobials may reduce the density of the skin resident flora, but they do not completely eliminate it. While antimicrobials may cause irritant and allergic contact dermatitis, no evidence exists that the use of antimicrobial substances may change the ecology of resident bacteria on the skin thereby leading to the overgrowth of pathogenic bacteria.
Microsporidian Encephalitozoon cuniculi, a unicellular eukaryote with an unusual chromosomal dispersion of ribosomal genes and a LSU rRNA reduced to the universal core (1998)

Microsporidia are eukaryotic parasites lacking mitochondria, the ribosomes of which present prokaryote-like features. In order to better understand the structural evolution of rRNA molecules in microsporidia, the 5S and rDNA genes were investigated in Encephalitozoon cuniculi. The genes are not in close proximity. Non-tandemly arranged rDNA units are on every one of the 11 chromosomes. Such a dispersion is also shown in two other Encephalitozoon species. Sequencing of the 5S rRNA coding region reveals a 120 nt long RNA which folds according to the eukaryotic consensus structural shape. In contrast, the LSU rRNA molecule is greatly reduced in length (2487 nt). This dramatic shortening is essentially due to truncation of divergent domains, most of them being removed. Most variable stems of the conserved core are also deleted, reducing the LSU rRNA to only those structural features preserved in all living cells. This suggests that the E.cuniculi LSU rRNA performs only the basic mechanisms of translation. LSU rRNA phylogenetic analysis with the BASEML program favours a relatively recent origin of the fast evolving microsporidian lineage. Therefore, the prokaryote-like ribosomal features, such as the absence of ITS2, may be derived rather than primitive characters.
The polymorphism of the C3b/C4b receptor in the normal population and in patients with systemic lupus erythematosus. (1987)

One hundred and sixty-two unrelated, healthy normals and 118 unrelated SLE patients were subdivided by sex, race, and disease, and each group was in Hardy-Weinberg equilibrium for autosomal codominant expression of the four CR1 alleles. There were no significant phenotypic differences between males and females (P greater than 0.3) or between normals and SLE patients (P greater than 0.2). However, gene frequencies among whites (A:0.87; B:0.12; C:0; D:0.01), blacks (A:0.74; B:0.22; C:0.04; D:0) and orientals (A:0.98; B:0.02; C:0; D:0) were significantly different (P less than 0.05). We had previously reported that SLE patients of phenotype AC had higher relative expression of the C allele than normals and this was confirmed: 61% (SLE, n = 5) vs 22% (normals, n = 3; P = 0.014). Total CR1/E in the AC group (193 in SLE vs 393 in normals 0.05 less than P less than 0.10), was suggestive of the decreased CR1 number seen in larger SLE populations regardless of phenotype. In one large three-generation family with SLE and the C allele, an association between SLE and the C allele is suggested by the presence of the C allele in all three females with SLE versus 3 of 13 healthy females. In informative families in which receptor phenotype and CR1 number/E were determined, it was possible to assign a receptor number to an allele. These data provide evidence for a cis-acting regulatory element that is inherited in association with the CR1 structural gene.