gebhart/patrepeval huggingface dataset:
Quantifying ChIP-seq data: a spiking method providing an internal reference for sample-to-sample normalization (2014)

Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments are widely used to determine, within entire genomes, the occupancy sites of any protein of interest, including, for example, transcription factors, RNA polymerases, or histones with or without various modifications. In addition to allowing the determination of occupancy sites within one cell type and under one condition, this method allows, in principle, the establishment and comparison of occupancy maps in various cell types, tissues, and conditions. Such comparisons require, however, that samples be normalized. Widely used normalization methods that include a quantile normalization step perform well when factor occupancy varies at a subset of sites, but may miss uniform genome-wide increases or decreases in site occupancy. We describe a spike adjustment procedure (SAP) that, unlike commonly used normalization methods intervening at the analysis stage, entails an experimental step prior to immunoprecipitation. A constant, low amount from a single batch of chromatin of a foreign genome is added to the experimental chromatin. This "spike" chromatin then serves as an internal control to which the experimental signals can be adjusted. We show that the method improves similarity between replicates and reveals biological differences including global and largely uniform changes.
Discovery of short, 3'-cholesterol-modified DNA duplexes with unique antitumor cell activity. (1994)

A new class of modified oligodeoxynucleotides with unique, selective cytotoxic properties has been discovered. Self-complementary, 3'-cholesterol-modified oligodeoxynucleotides caused morphology changes and death in certain cancer cell lines, whereas other cell lines were unaffected. Susceptible cells were killed in a dose-dependent manner at submicromolar concentrations. Optimum potency was exhibited by phosphodiester duplexes approximately 10 base pairs in length, and base composition was important only in the context of duplex stability. Phosphorothioate analogues were less potent. Although the molecular mechanism of action of these unique compounds is not yet known, they offer potential applications in cancer therapy and in studies of cell death. In addition, the path toward elucidation of the structure-based biological activity of these oligonucleotides should be especially instructive for researchers studying sequence-specific effects.
Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis (2011)

Myostatin, a member of the transforming growth factor (TGF)-β superfamily, plays a potent inhibitory role in regulating skeletal muscle mass. Inhibition of myostatin by gene disruption, transgenic (Tg) expression of myostatin propeptide, or injection of propeptide or myostatin antibodies causes a widespread increase in skeletal muscle mass. Several peptides, in addition to myostatin propeptide and myostatin antibodies, can bind directly to and neutralize the activity of myostatin. These include follistatin and follistatin-related gene. Overexpression of follistatin or follistatin-related gene in mice increased the muscle mass as in myostatin knockout mice. Follistatin binds to myostatin but also binds to and inhibits other members of the TGF-β superfamily, notably activins. Therefore, follistatin regulates both myostatin and activins in vivo. We previously reported the development and characterization of several follistatin-derived peptides, including FS I-I (Nakatani M, Takehara Y, Sugino H, Matsumoto M, Hashimoto O, Hasegawa Y, Murakami T, Uezumi A, Takeda S, Noji S, Sunada Y, Tsuchida K. FASEB J 22: 477-487, 2008). FS I-I retained myostatin-inhibitory activity without affecting the bioactivity of activins. Here, we found that inhibition of myostatin increases skeletal muscle mass and decreases fat accumulation in FS I-I Tg mice. FS I-I Tg mice also showed decreased fat accumulation even on a control diet. Interestingly, the adipocytes in FS I-I Tg mice were much smaller than those of wild-type mice. Furthermore, FS I-I Tg mice were resistant to high-fat diet-induced obesity and hepatic steatosis and had lower hepatic fatty acid levels and altered fatty acid composition compared with control mice. FS I-I Tg mice have improved glucose tolerance when placed on a high-fat diet. These data indicate that inhibiting myostatin with a follistatin-derived peptide provides a novel therapeutic option to decrease adipocyte size, prevent obesity and hepatic steatosis, and improve glucose tolerance.
Mutagenesis and Gene Transfer Define Site-Specific Roles of the Gonadotropin Oligosaccharides (1989)

Human chorionic gonadotropin (hCG), luteinizing hormone (LH), follicle-stimulating hormone and thyroid-stimulating hormone are a family of glycoprotein hormones that share a common alpha subunit but differ in their hormone-specific beta subunits. Using site-directed mutagenesis and gene-transfer, we analyzed the role of the N-linked oligosaccharides of alpha and chorionic gonadotropin (CG)beta in the secretion, assembly, and biologic activity of hCG. Absence of carbohydrate at alpha asparagine (Asn) 52 decreased combination with CG beta but did not alter monomer secretion. Absence of the alpha Asn78 oligosaccharide increased the degradation of the alpha subunit, but the presence of CG beta stabilized this alpha mutant in an efficiently formed dimer complex. Alternatively, absence of both alpha oligosaccharides slowed both secretion and dimer formation but allowed an intermediate level of alpha secreted or dimerized compared to the single-site mutants. Analysis of the CG beta glycosylation mutants revealed that absence of the Asn30 oligosaccharide, but not Asn13, slowed secretion but not assembly, whereas absence of both oligosaccharides slowed both secretion and dimer formation. Analysis of the receptor binding of the hCG glycosylation mutants showed that absence of any or all of the hCG N-linked oligosaccharides had only a minor effect on receptor affinity of the derivatives. However, the absence of alpha Asn52, but not the alpha Asn78 or the CG beta carbohydrate units, reduced the steroidogenic effect, unmasked differences in the beta oligosaccharides, and converted the deglycosylated derivatives into antagonists.
Loads as a Resource: Frequency Responsive Demand (2014)

Frequency control plays an important role in preserving the power balance of a multi-machine power system. Generators modify their power output when a non-zero frequency deviation is presented in order to restore power balance across the network. However, with plans for large-scale penetration of renewable energy resources, performing primary frequency control using only supply-side resources becomes not only prohibitively expensive, but also technically difficult. Frequency control from the demand side or load control presents a novel and viable way for providing the desired frequency response. Loads can measure frequency locally and change their power consumption after a non-zero frequency deviation is presented in order to achieve power balance between generation and consumption. The specific objectives of this project are to: •Provide a framework to facilitate large-scale deployment of frequency responsive end-use devices •Systematically design decentralized frequency-based load control strategies for enhanced stability performance •Ensure applicability over wide range of operating conditions while accounting for unpredictable end-use behavior and physical device constraints •Test and validate control strategy using large-scale simulations and field demonstrations •Create a level-playing field for smart grid assets with conventional generators
Modern tanning chemistry (1997)

The range of chemistries used for tanning leather is reviewed; traditional methods of tanning are explained and the newer processes are described. The areas of tanning include: vegetable tanning with plant polyphenols, mineral tanning with metal salts, in particular chromium(III), oil and aldehyde tannages, synthetic tanning agents and organic tannages based on natural polyphenols or synthetic organic oligomers. The fundamental nature of the tanning reaction and the origin of hydrothermal stability are discussed.
IMMUNOHISTOCHEMICAL DETECTION OF CRIPTO-1, AMPHIREGULIN AND TRANSFORMING GROWTH-FACTOR-ALPHA IN HUMAN GASTRIC CARCINOMAS AND INTESTINAL METAPLASIAS (1994)

The expression and localization of cripto-1 (CR-1), amphiregulin (AR) and transforming growth factor alpha (TGFalpha) were assessed by immunocytochemistry in 37 primary human gastric tumors, 30 noninvolved gastric mucosa samples that were adjacent to carcinoma but exhibited intestinal metaplasia and 37 adjacent, noninvolved gastric mucosa samples. Seventeen (46%), nineteen (51%) and twenty-one (57%) carcinomas showed staining for CR-1, AR and TGFalpha, respectively; whereas sixteen (53%), eight (26%) and five (17%) intestinal metaplasias were reactive with the anti-CR-1, anti-AR and anti-TGFalpha antibodies, respectively. In contrast, none of the normal, noninvolved gastric mucosa samples reacted with the TGFalpha antibody and only 1 (3%) of these samples showed weak staining with the anti-CR-1 antibody. However, 8 (21%) of the normal gastric mucosa samples showed moderate levels of staining with the AR antibody. Within the carcinomas, there was a slight trend for association between TGFalpha and CR-1 expression (p<0.05), but no correlation was found between epidermal growth factor receptor and CR-1 expression. Staining for p53 was observed in 26 (70%) of the carcinomas, 3 (10%) intestinal metaplasias and none of the gastric mucosa samples. This data demonstrate that CR-1, like TGFalpha, may be a tumor marker for a subset of gastric carcinomas in addition to being an important factor in the early stages of gastric cancer development.
Rotational Mobility of Single Molecules Affects Localization Accuracy in Super-Resolution Fluorescence Microscopy (2013)

The asymmetric nature of single-molecule (SM) dipole emission patterns limits the accuracy of position determination in localization-based super-resolution fluorescence microscopy. The degree of mislocalization depends highly on the rotational mobility of SMs; only for SMs rotating within a cone half angle α > 60° can mislocalization errors be bounded to ≤10 nm. Simulations demonstrate how low or high rotational mobility can cause resolution degradation or distortion in super-resolution reconstructions.
Coupling of Bulky, Electron-Deficient Partners in Aryl Amination in the Preparation of Tridentate Bis(oxazoline) Ligands for Asymmetric Catalysis (2002)

A new class of tridentate bis(oxazoline) ligands 7, in which an N-phenylaniline unit links the two oxazoline rings, has been prepared. The key step in their synthesis is a Hartwig-Buchwald type Pd-catalyzed aryl amination between the two bulky o-substituted coupling partners, 2-(2'-bromophenyl)oxazolines 8 and 2-(o-aminophenyl)oxazolines 9. By varying the substituent on the coupling partners, a range of 10 ligands has been prepared in good yield. During the synthesis of 2-(o-aminophenyl)oxazolines 9a-d, a number of products of unexpected side reactions were isolated in two of the three steps. Alternatively, the required 2-(o-aminophenyl)oxazolines 9 were obtained by a DAST-promoted cyclodehydration of hydroxyamides 12a-d without formation of any byproducts.
TSPAN12 Is a Norrin Co-receptor that Amplifies Frizzled4 Ligand Selectivity and Signaling (2017)

Accessory proteins in Frizzled (FZD) receptor complexes are thought to determine ligand selectivity and signaling amplitude. Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular β-catenin signaling in different CNS structures. In the retina, the tetraspanin TSPAN12 and the ligand norrin (NDP) mediate angiogenesis, and both genes are linked to familial exudative vitreoretinopathy (FEVR), yet the molecular function of TSPAN12 remains poorly understood. Here, we report that TSPAN12 is an essential component of the NDP receptor complex and interacts with FZD4 and NDP via its extracellular loops, consistent with an action as co-receptor that enhances FZD4 ligand selectivity for NDP. FEVR-linked mutations in TSPAN12 prevent the incorporation of TSPAN12 into the NDP receptor complex. In vitro and in Xenopus embryos, TSPAN12 alleviates defects of FZD4 M105V, a mutation that destabilizes the NDP/FZD4 interaction. This study sheds light on the poorly understood function of accessory proteins in FZD signaling.
Imaging of Small Bowel Tumors (2010)

Tumors of the small bowel are rare, accounting for less than 5% of all gastrointestinal tumors.1 Small bowel tumors are mostly solitary; however, multiple tumors may be seen in association with certain syndromes such as intestinal polyposis syndrome. There is a wide spectrum of benign and malignant small bowel tumors; rarely, benign tumors (i.e., adenomas, leiomyomas) may demonstrate malignant degeneration over time. Most small bowel tumors are clinically asymptomatic for long periods of time; nearly half of all benign small bowel tumors are found incidentally either during surgery or by cross-sectional imaging performed for other reasons. Symptoms can be chronic and/or intermittent and include abdominal pain, nausea, weight loss, and gastrointestinal bleeding. Larger tumors generally present with symptoms of bowel obstruction. This CME activity will help improve the diagnostic radiologist's ability to provide an accurate diagnosis of small bowel tumors, both benign and malignant, which in turn should lead to appropriate, timely treatment.
A Bayesian Approach to Learning Bayesian Networks with Local Structure (2013)

Recently several researchers have investigated techniques for using data to learn Bayesian networks containing compact representations for the conditional probability distributions (CPDs) stored at each node. The majority of this work has concentrated on using decision-tree representations for the CPDs. In addition, researchers typically apply non-Bayesian (or asymptotically Bayesian) scoring functions such as MDL to evaluate the goodness-of-fit of networks to the data. In this paper we investigate a Bayesian approach to learning Bayesian networks that contain the more general decision-graph representations of the CPDs. First, we describe how to evaluate the posterior probability that is, the Bayesian score of such a network, given a database of observed cases. Second, we describe various search spaces that can be used, in conjunction with a scoring function and a search procedure, to identify one or more high-scoring networks. Finally, we present an experimental evaluation of the search spaces, using a greedy algorithm and a Bayesian scoring function.
A multicast routing protocol for multihop wireless networks (2003)

We propose a new protocol, clustered group multicast (CGM), for multicasting in multihop wireless networks. In CGM, there is a set of forwarding nodes (called multicast backbone) which are responsible for forwarding multicast datagrams. Unlike the multicasting protocols in wired networks (e.g. Internet) which construct and maintain a shortest path tree for every multicast (source, group) pair, the connectivity among the nodes in the backbone is of no longer importance. Thus, there is no tree maintenance overhead. In addition, a key feature of CGM is the use of the advertising agents to reduce advertising traffic to the system. An advertising agent acts as both a server and a client for the purpose of advertising join requests on behalf of its local clients. Because in CGM multicast traffic is only allowed to be delivered over the backbone, CGM restricts the amount of hosts participating in the backbone to decrease the impact of multicast traffic to the system. From the simulation results, the multicast group management traffic and multicast datagram traffic are much less than the other protocols. This is particularly important for wireless networks which lacks bandwidth.
V-region-related and -unrelated immunosupression accompanying infections (1992)

This paper discusses current evidence for the relationship between polyclonal lymphocyte activation, specific immunosuppression with decreased resistance, and autoimmune pathology, that are all often found associated with infections by a variety of virus, bacteria and parasites. The central question of class determination of immune effector activities is considered in the context of the cellular targets for nonspecific mitogenic activities associated with infection. A model is presented to integrate these findings: mitogens produced by the microorganism or the infected cells are preferentially active on CD5 B cells; the resulting over-production of IL-10 will tend to bias all immune activities into a Th2-mode of effector functions, with high titers of polyclonal antibodies and little or no production of gamma IFN and other "inflammatory" lymphokines that often mediate resistance. In turn, these conditions allow for parasite persistence and the corresponding long-term disregulation of self-directed immune reactivities, resulting in autoimmunity in the chronic phase. This model would predict that selective immunization with the mitogenic principles involved in deregulation, could stand better chances than strategies of vaccination based on immunopotentiation against other, functionally neutral antigenic epitopes. It is argued, however, that the complexity of immune responses and their regulation, together with our ignorance on the genetic controls of class-determination, offer poor prospects for a scientifically-based, rational development of vaccines in the near future. It is suggested that empirically-based and technologically developed vaccines might succeed, while basic scientific approaches are reinforced and given the time to provide a better understanding of those processes.
The murine local lymph node assay for identification of contact allergens: a preliminary evaluation of in situ measurement of lymphocyte proliferation (1989)

A murine local lymph node assay for the identification of contact allergens has been developed. Contact sensitizing activity is measured as a function of lymphocyte proliferation in the draining lymph node following repeated application of the test agent to the dorsum of the ear. In original studies, lymphocyte proliferative activity was measured in vitro. In an attempt to remove the requirement for tissue culture, and thereby enhance the utility of the local lymph node assay as a predictive screening method, a new protocol has been evaluated in which proliferation in draining nodes is measured following i.v. injection of 3H-thymidine.
Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates (1994)

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.
Crystal Structure of a Partly Self-Complementary Peptide Nucleic Acid (PNA) Oligomer Showing a Duplex−Triplex Network (2005)

The X-ray structure of a partly self-complementary peptide nucleic acid (PNA) decamer (H-GTAGATCACT-l-Lys-NH(2)) to 2.60 A resolution is reported. The structure is mainly controlled by the canonical Watson-Crick base pairs formed by the self-complementary stretch of four bases in the middle of the decamer (G(4)A(5)T(6)C(7)). One right- and one left-handed Watson-Crick duplex are formed. The two PNA units C(9)T(10) change helical handedness, so that each PNA strand contains both a right- and a left-handed section. The changed handedness in C(9)T(10) allows formation of Hoogsteen hydrogen bonding between C(9)T(10) and G(4)A(5) of a PNA strand in an adjacent Watson-Crick double helix of the same handedness. Thereby, a PNA-PNA-PNA triplex is formed. The PNA unit A(3) forms a noncanonical base pair with A(8) in a symmetry-related strand of opposite handedness; the base pair is of the A-A reverse Hoogsteen type. The structural diversity of this PNA demonstrates how the PNA backbone is able to adapt to structures governed by the stacking and hydrogen-bonding interactions between the nucleobases. The crystal structure further shows how PNA oligomers containing limited sequence complementarity may form complex hydrogen-bonding networks.
An Experience of Using the Harmony Test for Genomics-Based Non-Invasive Prenatal Testing (2015)

, (nucal translucency)
Behavioral correlates of dehydroepiandrosterone and dehydroepiandrosterone sulfate (1998)

The actions of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) on the central nervous system have been described as neurotropic, excitatory, and neuromodulator and may form the basis of various psychological effects in humans. Two research strategies help to define a possible role for DHEA and DHEAS in human behavior: first, to correlate endogenous hormone levels with measures of well-being, mood, aggression, and memory and, second, to administer DHEA and to observe any resulting behavioral changes. A few controlled studies and quite an amount of correlational evidence from very heterogeneous studies on females and males from 4 years of age to senescence suggest weak positive effects of DHEA and DHEAS on well-being and memory functions. Levels of aggression in males are associated with higher DHEA and DHEAS concentrations. However, in women, the antiaggressive effect, predicted from brain research and animal studies, has been partly confirmed. Effects on mood are inconsistent, but DHEA substitution may be beneficial in middle-aged and elderly individuals with decreased endogenous DHEA and DHEAS levels.
Angiographic prevalence of high-risk coronary artery disease in patient subsets (CASS). (1981)

The prevalence of coronary artery stenoses greater than or equal to 70% or left main stenosis greater than or equal to 50% was evaluated in 20,391 patients who underwent angiography in the Coronary Artery Surgery Study from 1975-1979. After the patients with unstable angina or myocardial infarction were excluded, the disease prevalence in the 8157 patients with definite angina, probable angina, and nonspecific chest pain was 93%, 66% and 14% in men and 72%, 36% and 6% in women (p less than 0.001). The age and sex of the patients and character of chest pain were important determinants of disease prevalence and severity. Left main or three-vessel coronary disease occurred in more than 50% of middle-aged men and older women with definite angina and in more than 50% of men who had probable angina and were older than 60 years of age. In contrast, left main coronary disease occurred in less than 2% of 1282 men and less than 1% of 1397 women with nonspecific chest pain regardless of age. In this latter patient subset, less than 5% of men and less than 1% of women in each decade under 60 years had left main or three-vessel coronary artery disease. Thus, high-risk coronary disease is common in middle-aged patients with definite angina and older patients with probable angina, but is rare in patients with nonspecific chest pain. Indications and guidelines for diagnostic noninvasive tests and coronary angiography could be based on these results.