gebhart/patrepeval huggingface dataset:
Localization microscopy coming of age: from concepts to biological impact (2013)

Super-resolution fluorescence imaging by single-molecule photoactivation or photoswitching and position determination (localization microscopy) has the potential to fundamentally revolutionize our understanding of how cellular function is encoded at the molecular level. Among all powerful, high-resolution imaging techniques introduced in recent years, localization microscopy excels because it delivers single-molecule information about molecular distributions, even giving absolute numbers of proteins present in subcellular compartments. This provides insight into biological systems at a molecular level that can yield direct experimental feedback for modeling the complexity of biological interactions. In addition, efficient new labeling methods and strategies to improve localization are emerging that promise to achieve true molecular resolution. This raises localization microscopy as a powerful complementary method for correlative light and electron microscopy experiments.
Kinetic evidence for a (4-amino-2-methyl-5-pyrimidinyl)methyl-enzyme intermediate in the thiaminase I reaction (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic evidence for a (4-amino-2-methyl-5-pyrimidinyl)methyl-enzyme intermediate in the thiaminase I reactionGustav E. LienhardCite this: Biochemistry 1970, 9, 15, 3011–3020Publication Date (Print):July 21, 1970Publication History Published online1 May 2002Published inissue 21 July 1970https://pubs.acs.org/doi/10.1021/bi00817a012https://doi.org/10.1021/bi00817a012research-articleACS PublicationsRequest reuse permissionsArticle Views76Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A tutorial on visual servo control (1996)

This article provides a tutorial introduction to visual servo control of robotic manipulators. Since the topic spans many disciplines our goal is limited to providing a basic conceptual framework. We begin by reviewing the prerequisite topics from robotics and computer vision, including a brief review of coordinate transformations, velocity representation, and a description of the geometric aspects of the image formation process. We then present a taxonomy of visual servo control systems. The two major classes of systems, position-based and image-based systems, are then discussed in detail. Since any visual servo system must be capable of tracking image features in a sequence of images, we also include an overview of feature-based and correlation-based methods for tracking. We conclude the tutorial with a number of observations on the current directions of the research field of visual servo control.
The influence of oxygen tension on the long‐term growth in vitro of haematopoietic progenitor cells from human cord blood (1986)

Growth of low density human cord blood cells in long-term suspension culture was evaluated at incubation conditions of 5% carbon dioxide in approximately 20% (normal incubator) oxygen tension or in 5% (low) oxygen tension. During the first 5 weeks there was no difference in the numbers of morphologically recognizable cells grown at either oxygen tension, while growth was superior from weeks 5 to 8 at approximately 20% oxygen tension. For the first 5 weeks, growth of granulocyte-macrophage progenitors (CFU-GM) was superior at 5% oxygen tension during the long-term and semi-solid culture phases and least impressive in the long-term and semi-solid cultures incubated at approximately 20% oxygen. This trend was reversed after 5 weeks and after 8 weeks there were no detectable CFU-GM in suspension cultures at 5% oxygen while steady state levels of CFU-GM were maintained for greater than 12 weeks in suspension cultures at approximately 20% oxygen. Semi-solid cultures for erythroid (BFU-E) and multipotential (CFU-GEMM) progenitors were incubated at approximately 20% oxygen only. During the first 4 weeks, the growth of BFU-E and CFU-GEMM was superior at 5% oxygen during long-term culture. Numbers of these cells decreased by week 5 and at this time growth was better in the long-term cultures grown at approximately 20% oxygen. By week 6, no BFU-E or CFU-GEMM were detectable. Thus, growth of cord blood at low oxygen tension gives an initial enhancement in output of progenitor cells, but this appears to be at the expense of continued production.
MUSCLE DAMAGE IN MDX (DYSTROPHIC) MICE: ROLE OF CALCIUM AND REACTIVE OXYGEN SPECIES (2006)

1. Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease caused by a genetic mutation that leads to the complete absence of the cytoskeletal protein dystrophin in muscle fibres. 2. The present review provides an overview of some of the physiological pathways that may contribute to muscle damage and degeneration in DMD, based primarily on experimental findings in the mdx mouse, an animal model of this disease. 3. A rise in intracellular calcium is widely thought to be an important initiating event in the dystrophic pathogenesis. The pathway(s) leading to increased intracellular calcium in dystrophin deficient muscle is uncertain, but recent work from our laboratory provides evidence that stretch-activated channels are an important source of the calcium influx. Other possible routes of calcium entry are also discussed. 4. The consequences of elevated cytosolic calcium may include activation of proteases, such as calpain, and increased production of reactive oxygen species (ROS), which can cause protein and membrane damage. 5. Another possible cause of damage in dystrophic muscle involves inflammatory pathways, such as those mediated by neutrophils, macrophages and associated cytokines. There is recent evidence that increased ROS may be important in both the activation of and the damage caused by this inflammatory pathway in mdx muscle.
Synthesis and in Vivo Evaluation of Prodrugs of 9-[2-(Phosphonomethoxy)ethoxy]adenine (1995)

A number of esters and amides of the anti-HIV nucleotide analogue 9-[2-(phosphonomethoxy)-ethoxy]adenine (1) have been synthesized as potential prodrugs and evaluated for oral bioavailability in mice. Dialkyl esters 17-20 were prepared via a Mitsunobu coupling of alcohols 8-11 with 9-hydroxypurine 12 whereas (acyloxy)alkyl esters 25-33 and bis-[(alkoxycarbonyl)methyl] and bis(amidomethyl) esters 34-39 were obtained by reaction of 1 with a suitable alkylating agent. Phosphonodichloridate chemistry was employed for the preparation of dialkyl and diaryl esters 42-65, and bis(phosphonoamidates) 66 and 67. Following oral administration to mice, most of the dialkyl esters 17-20 were well-absorbed and then converted to the corresponding monoesters, but minimal further metabolism to 1 occurred. Bis[(pivaloyloxy)methyl] ester 25 displayed an oral bioavailability of 30% that was 15-fold higher than the bioavailability observed after dosing of 1. Methyl substitution at the alpha carbon of the bis[(pivaloyloxy)methyl] ester 25 (33) increased the oral bioavailability of 1 to 74%. Some of the diaryl esters also showed improved absorption properties in comparison with that of 1. In particular, the crystalline hydrochloride salt of diphenyl ester 55 was well-absorbed and efficiently converted to the parent compound with an oral bioavailability of 50%. On the basis of these results as well as the physicochemical properties of the prodrugs and their stability in mouse duodenal contents, the hydrochloride salt of diphenyl ester 55 was identified as the preferred prodrug of 1.
The rise, fall and subsequent triumph of thalidomide: lessons learned in drug development (2011)

Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses.
Pharmacogenetics and Pharmacogenomics in Oncology Therapeutic Antibody Development (2005)

Pharmacogenetics and pharmacogenomics are keys to the success of personalized medicine, prescribing drugs based on a patient's individual genetic and biological profile. In this review, we will focus on the application of pharmacogenetics and pharmacogenomics in developing monoclonal antibody (MAb) therapeutics in oncology. The significance of pharmacogenomics in MAb therapeutics is highlighted by the association between polymorphisms in Fc receptors and clinical response to anti-CD20 MAb rituximab (Rituxan) or anti-ganglioside GD2 MAb 3F8, as well as the potential link between polymorphisms in HER2 and cardiac toxicity in patients treated with the anti-HER2 MAb trastuzumab (Herceptin). The dependence on gene copy number or expression levels ofHER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile. In addition, a better understanding of target mutation status and biological consequences will benefit MAb development and may guide clinical development and use of these innovative therapeutics. The application of pharmacogenetics and pharmacogenomics in developing MAb therapeutics will be largely dependent on the discovery of novel surrogate biomarkers and identification of disease- and therapeutics-relevant polymorphisms. Challenges and opportunities in biomarker discovery and validation, and in implementing clinical pharmacogenetics and pharmacogenomics in oncology MAb development and clinical practice will also be discussed.
Low-Density Parity-Check (LDPC) Codes Constructed from Protographs (2003)

We introduce a new class of low-density parity-check (LDPC) codes constructed from a template called a protograph. The protograph serves as a blueprint for constructing LDPC codes of arbitrary size whose performance can be predicted by analyzing the protograph. We apply standard density evolution techniques to predict the performance of large protograph codes. Finally, we use a randomized search algorithm to find good protographs. I.
Role of CCR5 in infection of primary macrophages and lymphocytes by macrophage-tropic strains of human immunodeficiency virus: resistance to patient-derived and prototype isolates resulting from the delta ccr5 mutation (1997)

The alpha-chemokine receptor fusin (CXCR-4) and beta-chemokine receptor CCR5 serve as entry cofactors for T-cell (T)-tropic and macrophage (M)-tropic human immunodeficiency virus type 1 (HIV-1) strains, respectively, when expressed with CD4 in otherwise nonpermissive cells. Some M-tropic and dual-tropic strains can also utilize other beta-chemokine receptors, such as CCR2b and CCR3. A mutation of CCR5 (delta ccr5) was recently found to be common in certain populations and appears to confer protection against HIV-1 in vivo. Here, we show that this mutation results in a protein that is expressed intracellularly but not on the cell surface. Primary CD4 T cells from delta ccr5 homozygous individuals were highly resistant to infection with prototype M-tropic HIV-1 strains, including an isolate (YU-2) that uses CCR5 and CCR3, but were permissive for both a T-tropic strain (3B) and a dual-tropic variant (89.6) that uses CXCR-4, CCR5, CCR3, or CCR2b. These cells were also resistant to M-tropic patient isolates but were readily infected by T-tropic patient isolates. Primary macrophages from delta ccr5 homozygous individuals were also resistant to infection with M-tropic strains, including YU-2, but the dual-tropic strain 89.6 was able to replicate in them even though macrophages are highly resistant to CXCR-4-dependent T-tropic isolates. These data show that CCR5 is the essential cofactor for infection of both primary macrophages and T lymphocytes by most M-tropic strains of HIV-1. They also suggest that CCR3 does not function for HIV-1 entry in primary lymphocytes or macrophages, but that a molecule(s) other than CCR5 can support entry into macrophages by certain virus isolates. These studies further define the cellular basis for the resistance to HIV-1 infection of individuals lacking functional CCR5.
Next Generation Catalogues (2010)

Convergence is one of the dominant trends in the 21st century, and this is shown in the information sector by improvements in catalogues, in particular enhanced searching, more functions and greater user participation.
Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs (2012)

Splicing remains an incompletely understood process. Recent findings suggest that chromatin structure participates in its regulation. Here, we analyze the RNA from subcellular fractions obtained through RNA-seq in the cell line K562. We show that in the human genome, splicing occurs predominantly during transcription. We introduce the coSI measure, based on RNA-seq reads mapping to exon junctions and borders, to assess the degree of splicing completion around internal exons. We show that, as expected, splicing is almost fully completed in cytosolic polyA+ RNA. In chromatin-associated RNA (which includes the RNA that is being transcribed), for 5.6% of exons, the removal of the surrounding introns is fully completed, compared with 0.3% of exons for which no intron-removal has occurred. The remaining exons exist as a mixture of spliced and fewer unspliced molecules, with a median coSI of 0.75. Thus, most RNAs undergo splicing while being transcribed: "co-transcriptional splicing." Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA fractions and other nonspliceosomal snRNAs. CoSI scores decrease along the gene, pointing to a "first transcribed, first spliced" rule, yet more downstream exons carry other characteristics, favoring rapid, co-transcriptional intron removal. Exons with low coSI values, that is, in the process of being spliced, are enriched with chromatin marks, consistent with a role for chromatin in splicing during transcription. For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases.
Dosage requirement of Pitx2 for development of multiple organs (1999)

Pitx2 is a homeodomain transcription factor that is mutated in Rieger syndrome, a haploinsufficiency disorder affecting eyes and teeth. Pitx2 also has a postulated role in left-right axis determination. We assessed the requirements for Pitx2 directly by generating hypomorphic and null alleles. Heterozygotes for either allele have eye abnormalities consistent with Rieger syndrome. The ventral body wall fails to close in embryos homozygous for the null allele, leaving the heart and abdominal organs externalized and the body axis contorted. In homozygotes for either allele, the heart tube undergoes normal, rightward looping and the stomach is positioned normally. In contrast, homozygotes for both alleles exhibit right isomerization of the lungs. Thus, Pitx2 is required for left-right asymmetry of the lungs but not other organs. Homozygotes for either allele exhibit septal and valve defects, and null homozygotes have a single atrium proving that a threshold level of Pitx2 is required for normal heart development. Null homozygotes exhibit arrest of pituitary gland development at the committed Rathke pouch stage and eye defects including optic nerve coloboma and absence of ocular muscles. This allelic series establishes that Pitx2 is required for the development of mulitple organs in a dosage-sensitive manner.
Function and Structure of Complex II of the Respiratory Chain (2003)

Complex II is the only membrane-bound component of the Krebs cycle and in addition functions as a member of the electron transport chain in mitochondria and in many bacteria. A recent X-ray structural solution of members of the complex II family of proteins has provided important insights into their function. One feature of the complex II structures is a linear electron transport chain that extends from the flavin and iron-sulfur redox cofactors in the membrane extrinsic domain to the quinone and b heme cofactors in the membrane domain. Exciting recent developments in relation to disease in humans and the formation of reactive oxygen species by complex II point to its overall importance in cellular physiology.
Antioxidants and physical performance (1995)

Performance of strenuous physical activity can increase oxygen consumption by 10- to 15-fold over rest to meet energy demands. The resulting elevated oxygen consumption produces an "oxidative stress" that leads to the generation of free radicals and lipid peroxidation. A defense system of free radical scavengers minimizes these dangerous radicals. Indirect measurements of free radicals generated during exercise include assessing products of lipid peroxidation that appear in the blood (e.g., malondialdehyde and conjugated dienes) or expired in the breath (pentane). Changes in antioxidant scavengers and associated enzymes (e.g., glutathione, tocopherol, glutathione peroxidase) also provide clues about demands on the defense system. Physical training has been shown to result in an augmented antioxidant system and a reduction in lipid peroxidation. Supplementation with antioxidants appears to reduce lipid peroxidation but has not been shown to enhance exercise performance. The "weekend athlete" may not have the augmented antioxidant defense system produced through continued training. This may make them more susceptible to oxidative stress. Whether athletes or recreational exercisers should take antioxidant supplements remains controversial. However, it is important that those who exercise regularly or occasionally ingest foods rich in antioxidants.
Synthesis of CdSe nanoparticles using various organometallic cadmium precursors (2001)

Investigations into replacing Me2Cd as a common precursor for the synthesis of CdSe nanoparticles by pyrolysis in a hot coordinating solvent have proven that more stable, less volatile or even crystalline organometallic cadmium compounds can be used instead of Me2Cd. Dineopentylcadmium, bis(3-diethylaminopropyl)cadmium and (2,2′-bipyridine)dimethylcadmium have been used successfully as cadmium sources for the preparation of tri-n-octylphosphine oxide (TOPO)-capped CdSe nanoparticles. The resulting nanocrystallites have been characterized by UV–VIS and IR spectroscopy, photoluminescence spectroscopy (PL), mass spectrometry and transmission electron microscopy (TEM). They consist of separated, well defined spherical particles and show a small size distribution as well as a characterisitic blue shift due to quantum confinement in their optical spectra. The replacement of Me2Cd by less dangerous organometallic precursors thus results in nanocrystallites that show no reduction in quality when compared to the standard method.
Control of TCF-4 Expression by VDR and Vitamin D in the Mouse Mammary Gland and Colorectal Cancer Cell Lines (2009)

Although it is generally assumed that binding of beta-catenin to members of the TCF/LEF family is cancer-promoting, recent studies have indicated that TCF-4 functions instead as a transcriptional repressor that restricts breast and colorectal cancer cell growth. Consequently, we conclude that the 1,25(OH)2D3/VDR-mediated increase in TCF-4 may have a protective role in colon cancer as well as diabetes and Crohn's disease.
Wireless communication with implanted medical devices using the conductive properties of the body (2011)

Many medical devices that are implanted in the body use wires or wireless radiofrequency telemetry to communicate with circuitry outside the body. However, the wires are a common source of surgical complications, including breakage, infection and electrical noise. In addition, radiofrequency telemetry requires large amounts of power and results in low-efficiency transmission through biological tissue. As an alternative, the conductive properties of the body can be used to enable wireless communication with implanted devices. In this article, several methods of intrabody communication are described and compared. In addition to reducing the complications that occur with current implantable medical devices, intrabody communication can enable novel types of miniature devices for research and clinical applications.