gebhart/patrepeval huggingface dataset:
A unique population of bone marrow cells migrates to skeletal muscle via hepatocyte growth factor/c-met axis (2005)

Cells expressing the CD45-associated hematopoietic marker are predominantly present in the mammalian bone marrow (BM), but have recently been shown to also reside in the skeletal muscle and potentially participate in muscle repair. Despite the consistent observations, the specific relationship and potential migration of CD45+ cells in the BM versus CD45+ cells residing in the muscle remain unclear, in addition to any understanding of the factors that may regulate the trafficking of CD45+-derived BM cells to skeletal muscle upon i.v. transplantation. Here, transplantation of BM-derived cells fully replaced the CD45+ fraction of skeletal muscle, but gave rise to progenitor cells with distinct hematopoietic lineage capacity from CD45+ cells residing in the BM. Using transwell migration assays, a subset of BM cells was shown to migrate exclusively to mature skeletal muscle cells and not BM-derived stromal cells. Unlike migration of BM cells to stroma, myofiber induced migration of BM-derived cells was not affected by stromal-derived factor-1 (SDF-1) neutralization or CXCR4-blocking antibody, but could be reduced by addition of c-met-blocking antibody and augmented by hepatocyte growth factor (HGF), the putative ligand for c-met. We suggest that the BM compartment consists of a functionally complex population of CD45+ progenitors that includes a subset of HGF/c-met responsive cells capable of migration to skeletal muscle. This previously unappreciated basis for cellular tracking now aids in defining regulatory networks that distinguish the stem cell niche of the BM versus skeletal muscle microenvironments.
Premise: traditional disease-modifying antirheumatic drugs are less effective and safe than targeted therapy with biologic response modifiers in rheumatoid arthritis (2003)

Apoptosis is a principal mechanism in metazoans by which superfluous or potentially harmful cells are eliminated. Deregulation of this process leads to a variety of diseases such as cancer and autoimmune diseases. Stimuli that can induce apoptosis are relatively diverse, and include the death factors (Fas ligand, tumor necrosis factor and TRAIL), DNA damage, and oxidative stress. Regardless of the origin of the apoptotic stimulus, commitment to apoptosis leads to activation of caspases, a family of cysteine proteases. Cleavage of a select group of cellular substrates by caspases is responsible for the morphological and biochemical changes that characterize apoptotic cell death. The degradation of nuclear DNA into nucleosomal units is one of the features of apoptotic cell death, and is mediated by a caspase-activated DNase (CAD). Cells deficient in CAD undergo cell death without the DNA fragmentation, but CAD-null mice did not show any adverse phenotypes. A close examination of the apoptotic cells in these mice indicated that apoptotic cells are always in macrophages. It seems that at an early stage of apoptosis, the dying cells present an 'eat me signal' on their surface. This signal is recognized by macrophages for engulfment, and DNase II in the lysosomes of macrophages degrades DNA of apoptotic cells. Mice deficient in both CAD and DNase II genes were established, and the development of various organs was found to be severely impaired in these mutant mice. The mice accumulated a large amount of undigested DNA in macrophages in various tissues during development. This accumulation of DNA in macrophages activated the innate immunity to induce the expression of the interferon gene. The interferon thus produced seems to be responsible for the impaired tissue development. These results indicate that the degradation of DNA during apoptotic cell death is an essential step of apoptosis to maintain mammalian homeostasis.
Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses (2003)

The concern about bioterrorism with smallpox has raised the possibility of widespread vaccination, but the greater prevalence of immunocompromised individuals today requires a safer vaccine, and the mechanisms of protection are not well understood. Here we show that, at sufficient doses, the protection provided by both modified vaccinia Ankara and NYVAC replication-deficient vaccinia viruses, safe in immunocompromised animals, was equivalent to that of the licensed Wyeth vaccine strain against a pathogenic vaccinia virus intranasal challenge of mice. A similar variety and pattern of immune responses were involved in protection induced by modified vaccinia Ankara and Wyeth viruses. For both, antibody was essential to protect against disease, whereas neither effector CD4+ nor CD8+ T cells were necessary or sufficient. However, in the absence of antibody, T cells were necessary and sufficient for survival and recovery. Also, T cells played a greater role in control of sublethal infection in unimmunized animals. These properties, shared with the existing smallpox vaccine, provide a basis for further evaluation of these replication-deficient vaccinia viruses as safer vaccines against smallpox or against complications from vaccinia virus.
Effects of Fenretinide (4-HPR) on Dark Adaptation (1998)

The dose of fenretinide used in this study produced clearly measurable, but not severe, changes in night vision, which were rarely symptomatic.
Engineering of osteoinductive grafts by isolation and expansion of ovine bone marrow stromal cells directly on 3D ceramic scaffolds (2005)

In this work, we investigated whether osteoinductive constructs can be generated by isolation and expansion of sheep bone marrow stromal cells (BMSC) directly within three-dimensional (3D) ceramic scaffolds, bypassing the typical phase of monolayer (2D) expansion prior to scaffold loading. Nucleated cells from sheep bone marrow aspirate were seeded into 3D ceramic scaffolds either by static loading or under perfusion flow and maintained in culture for up to 14 days. The resulting constructs were exposed to enzymatic treatment to assess the number and lineage of extracted cells, or implanted subcutaneously in nude mice to test their capacity to induce bone formation. As a control, BMSC expanded in monolayer for 14 days were also seeded into the scaffolds and implanted. BMSC could be isolated and expanded directly in the 3D ceramic scaffolds, although they proliferated slower than in 2D. Upon ectopic implantation, the resulting constructs formed a higher amount of bone tissue than constructs loaded with the same number of 2D-expanded cells. Constructs cultivated for 14 days generated significantly more bone tissue than those cultured for 3 days. No differences in bone formation were found between samples seeded by static loading or under perfusion. In conclusion, the culture of bone marrow nucleated cells directly on 3D ceramic scaffolds represents a promising approach to expand BMSC and streamline the engineering of osteoinductive grafts.
Estrogen sulfamates: a new approach to oral estrogen therapy (2001)

Sulfamate substitution (-O-SO2-NH2) at carbon atom 3 of the steroid skeleton leads to orally active prodrugs of estrogens with much higher systemic, but lower hepatic, estrogenic activity than their parent steroids. This dissociation is achieved by first passage through the liver in erythrocytes, followed by systemic hydrolysis which releases the 'parent' estrogen. In the rat, orally administered tritiated estradiol sulfamate, unlike estradiol, appears in the circulation at high concentrations. At Cmax, approximately one third of the administered dose forms a depot in the circulation (98% in erythrocytes, 2% in plasma). Significant estradiol, estrone and estrone sulfate concentrations were recorded in plasma during depletion of the red blood cell pool. Estradiol sulfamate (J995) has no estrogen receptor affinity per se or estrogenic activity in vitro ( i.e. without hydrolysis). Its oral uterotropic activity in rats is approximately 100 times greater than that of estradiol, however, its hepatotropic activity is only marginally elevated. These functions include bile secretion, the secretion of angiotensinogen, lipoproteins (total and high-density lipoprotein cholesterol) and insulin-like growth factor I (IGF-I). Orally administred estradiol sulfamate led to systemic estrogenic effects without significant hepatic responses, whereas estradiol and other 'conventional' estrogens exerted parallel systemic and hepatic estrogenic effects. Sulfamate technology represents an approach to the use of natural estrogens for fertility control and hormone replacement therapy in both genders. In this context, reduced effects on hemostatic factors, angiotensinogen, bile and IGF-I secretion seem the most important aspects. In addition, blood concentrations of estrogens are less variable than with conventional estrogens.
DNA sampling and informed consent. (1989)

Standard consent forms for blood and tissue sampling are inadequate for DNA sampling. However, creating new and separate forms for each type of activity associated with DNA analysis (banking, linkage analysis and genetic diagnosis) tends to dissociate the participant from what is essentially a medical continuum. Furthermore, DNA sampling involves the sharing of samples and data among centres. To ensure patient control throughout this multifaceted process, we have developed an integrated approach to obtaining consent for DNA sampling at each level of participation. Movement from one level to another is reflected in the choices offered to participants. This inclusive approach is based on the underlying principle of informed consent, namely the respect for individuality, confidentiality and freedom of choice. This approach should help practitioners of medical genetics recognize the medical context of DNA sampling.
Sensitizer for EUV Chemically Amplified Resist: Metal versus Halogen (2019)

Extreme Ultraviolet (EUV) lithography utilizes photons of 91.6 eV energy to ionize resists, generating secondary electrons, thus enabling electron-driven reactions. Unlike photolithography, where photons below 7 eV selectively activate photoactive compounds, photons at 91.6 eV ionize all materials, subsequently generating secondary electrons. The energy and the numbers of secondary electrons generated after ionization are determined by the material chemistry. Several metals are reported to have high secondary electron generation capability and high EUV absorption, therefore metals can be one of the solution to deal with the insufficient photon density in resist. Halogen atoms like iodine and fluorine also provide high absorption which would be suitable alternative sensitizer to the metal salts sensitizer. In this work, we study metal salt sensitizers with different cations and anions as well as halogenated sensitizer in both polymer and PAG. Total electron yields are increased with increased resist absorption for both metal and halogen sensitizer. Sensitivity of resists with metal salt sensitizers increase, resulting in increased LCDU. However, halogenated sensitizers do not show positive correlation between sensitivity and electron yield as metal sensitizer. Through this study, we expect to explore materials that enable both high absorption and high photoelectron generation efficiency at 91.6 eV.
Deep Graphical Feature Learning for the Feature Matching Problem (2019)

The feature matching problem is a fundamental problem in various areas of computer vision including image registration, tracking and motion analysis. Rich local representation is a key part of efficient feature matching methods. However, when the local features are limited to the coordinate of key points, it becomes challenging to extract rich local representations. Traditional approaches use pairwise or higher order handcrafted geometric features to get robust matching; this requires solving NP-hard assignment problems. In this paper, we address this problem by proposing a graph neural network model to transform coordinates of feature points into local features. With our local features, the traditional NP-hard assignment problems are replaced with a simple assignment problem which can be solved efficiently. Promising results on both synthetic and real datasets demonstrate the effectiveness of the proposed method.
Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9 (2015)

Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.
DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis (2007)

The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.
Peptide Conjugates of Oligonucleotide Analogs and siRNA for Gene Expression Modulation (2006)

18.1 The Challenge of Delivery of Oligonucleotide Analogs and siRNA into Cells in Culture and In Vivo 313 18.2 Chemical Synthesis of Peptide–Oligonucleotide Conjugates 314 18.2.1 Synthesis of CPP Conjugates to Phosphate-Containing Oligonucleotides 315 18.2.2 Synthesis of PNA–Peptide Conjugates 318 18.3 Gene Expression Modulation by Peptide Conjugates of Antisense or Steric Block Oligonucleotides 318 18.3.1 Anionic Oligonucleotide Analog Conjugates with CPPs ........ 318 18.3.2 Charge-Neutral PNA and PMO Oligonucleotide Conjugates with CPPs 320 18.4 Gene Expression Inhibition by Peptide Conjugates of siRNA 323 18.5 Future Perspectives 324 Acknowledgments 325 References 325
Diagnosis of Heparin-induced Thrombocytopenia:Still a Journey, Not Yet a Destination (1995)

Journal Article Diagnosis of Heparin-induced Thrombocytopenia: Still a Journey, Not Yet a Destination Get access John G. Kelton, MD, John G. Kelton, MD Search for other works by this author on: Oxford Academic Google Scholar Theodore E. Warkentin, MD Theodore E. Warkentin, MD Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 104, Issue 6, 1 December 1995, Pages 611–613, https://doi.org/10.1093/ajcp/104.6.611 Published: 01 December 1995
Remote 3D Medical Consultation (2005)

Two-dimensional (2D) video-based telemedical consultation has been explored widely in the past 15--20 years. Two issues that seem to arise in most relevant case studies are the difficulty associated with obtaining the desired 2D camera views, and poor depth perception. To address these problems we are exploring the use of a small array of cameras to reconstruct a real-time, on-line 3D computer model of the real environment and events. We call this 3D medical consultation (3DMC). The idea is to give remote users what amounts to an infinite set of stereoscopic viewpoints, simultaneously addressing the visibility and depth perception problems associated with 2D video. Here we describe our current prototype system, some of the methods we use, and some early experimental results.
Subcellular localization of the human immunodeficiency virus trans-acting art gene product (1988)

The genome of the human immunodeficiency virus is distinguished from other animal retroviruses by the presence of several additional open reading frames. The protein product of one of these novel genes, which has been termed art or trs, is required for the expression of the virus structural genes but not for the expression of virus encoded regulatory proteins. Immunocytochemistry and subcellular fractionation demonstrate that the art protein is located predominantly in the nucleus. Therefore, any proposed mechanism for the function of art is likely to involve nuclear events.
Extended theory of selective photothermolysis (2001)

Based on this new theory, the treatment pulsewidth for non-uniformly pigmented targets is significantly longer than the target thermal relaxation time (TRT). The theory provides new recommendations for photoepilation and photosclerotherapy parameters.
pH‐Switchable Cesium Nitrate Extraction with Calix[4]arene Mono andbis(Benzo‐crown‐6) Ethers Bearing Amino Functionalities (2004)

Abstract Results obtained in this work show that four calix[4]arene mono and bis(benzo‐crown‐6) ethers functionalized with primary amine groups feature markedly enhanced cesium stripping under acidic conditions compared with nonfunctionalized analogs. The four amine‐derivatized calixarenes were surveyed in nitrobenzene diluent at 25°C, demonstrating the effect under controlled conditions, where it was seen that the amino functionalization entailed at most a mild sacrifice of cesium extraction strength or selectivity. Limited solubility of the protonated forms of the extractants appears to be a potential issue for future development, however. In the best case, calix[4]arene bis[4‐(2‐ethylhexyl)benzo‐crown‐6], possessing an aminomethyl group on the upper rim, (AMBEHB) exhibited a cesium extraction strength comparable to that of a control system containing calix[4]arene bis(tert‐octylbenzo‐crown‐6) (BOB) under alkaline conditions, whereas stripping of the cesium from AMBEHB was 56‐fold more effective than BOB. A proof‐of‐principle extraction, scrubbing, and stripping (ESS) cycle using AMBEHB in Isopar L modified with 0.75 M 1‐(2,2,3,3‐tetrafluoropropoxy)‐3‐(4‐sec‐butylphenoxy)‐2‐propanol (Cs‐7SB) showed that a greater than three‐fold more efficient stripping may be obtained with AMBEHB vs. its nonfunctionalized control BEHB. A slope analysis of systematic extraction data under caustic and acidic conditions confirmed that the extraction of cesium nitrate by AMBEHB in dodecane modified by 0.5 M Cs‐7SB involves the formation of a 1:1:1 metal:ligand:nitrate organic species. Keywords: Cesium extractionSolvent extractionAminocalixareneCalix[4]arene‐crown‐6 Acknowledgments This research was sponsored by the Environmental Management Science Program of the Offices of Science and Environmental Management, U.S. Department of Energy, under contract number DE‐AC05‐00OR22725 with Oak Ridge National Laboratory, managed by UT‐Battelle, LLC. The participation of M.G.G. was made possible by an appointment to the Oak Ridge National Laboratory Postgraduate Program administrated by the Oak Ridge Associated Universities.
Techniques for Optimum Placement of Interval Control Valve(s) in an Intelligent Well (2006)

Abstract Intelligent Well (IW) Technology improves well and field performance management by combining zonal production control using Interval Control Valves (ICVs) with the installation of flow monitoring devices. The "Added Value" for an IW is dependent on the number and location of the ICV controlled zones. Too many valves lead to unnecessary and excessive cost as well as the potential for reduced reliability. Too few valves will not provide sufficient flexibility for efficient control. We previously showed 1 that a minimum degree of un-even fluid-front progression needs to be induced in order for effective ICV control to be observed to "Add" sufficient "Value" to justify the costs and risks involved in installing this relatively new technology. ICV(s) can balance the fluid-front provided they are placed correctly. A typical example would be their installation across zones showing early water or gas break-though. This allows "Value" being "Added" to the reservoir management process by controlling the unwanted fluid. Optimum ICV placement requires prediction of these zones. The extent of reservoir layer / zone connection thus needs to be quantified. In practice, the available information is often limited to (local) information gained from measurement at or very near the wellbore during the drilling of the well, together with exploration seismic and (global) reservoir geological studies. A systematic study of the "Added ICV Value" for a range of reservoir models has been completed. The number of ICVs installed and the zonal length were varied. Emphasis was given to studying the more complex (e.g. channelised) reservoir models where prediction of the extent of reservoir layer / zone connection is more difficult. This study provides optimum ICV placement guidelines for different well and reservoir geometries with a variety of reservoir drive mechanisms. Results from this study highlight the importance of correct ICV placement. The results can be used as a screening and decision making tool for deciding on the optimum number of the ICV(s) and their placement.
3DLigandSite: predicting ligand-binding sites using similar structures (2010)

3DLigandSite is a web server for the prediction of ligand-binding sites. It is based upon successful manual methods used in the eighth round of the Critical Assessment of techniques for protein Structure Prediction (CASP8). 3DLigandSite utilizes protein-structure prediction to provide structural models for proteins that have not been solved. Ligands bound to structures similar to the query are superimposed onto the model and used to predict the binding site. In benchmarking against the CASP8 targets 3DLigandSite obtains a Matthew's correlation co-efficient (MCC) of 0.64, and coverage and accuracy of 71 and 60%, respectively, similar results to our manual performance in CASP8. In further benchmarking using a large set of protein structures, 3DLigandSite obtains an MCC of 0.68. The web server enables users to submit either a query sequence or structure. Predictions are visually displayed via an interactive Jmol applet. 3DLigandSite is available for use at http://www.sbg.bio.ic.ac.uk/3dligandsite.
Optimal Control of Blood Glucose: The Diabetic Patient or the Machine? (2010)

In this issue of Science Translational Medicine, El-Khatib et al. describe a "closed-loop" bihormonal artificial pancreas, designed to avert episodes of low blood sugar in patients with insulin-dependent diabetes. We discuss the benefits and challenges of therapy directed at tight control of blood glucose and ask whether this and similar technological breakthroughs can address as yet unanswered questions in the biology of diabetes.