gebhart/patrepeval huggingface dataset:
Increased expression of interleukin-1alpha and cyclooxygenase-2 in human gastric cancer: a possible role in tumor progression. (2005)

Our data demonstrated that IL-1alpha and COX-2 mRNA were frequently co-expressed in human gastric cancer tissues, and suggested that the IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating cancer cell proliferation.
Gene transfer by retrovirus-derived shuttle vectors in the generation of murine bispecific monoclonal antibodies. (1990)

The present study reports on the use of gene transfer by retrovirus-derived shuttle vectors in the generation of hybrid hybridomas secreting bispecific monoclonal antibodies. neo- and dhfr- genes were infected into distinct murine hybridomas, thus conferring a dominant resistance trait to geneticin (G418) and to methotrexate. The vectors employed were replication-deficient and dependent on complementation by a helper virus provided by the irradiated packaging lines. After cocultivation with the relevant packaging cell lines, stable hybridoma lines expressing the selectable markers were easily obtained and were then suitable for conventional somatic fusion. This high-efficiency method was used to generate two bispecific monoclonal antibodies simultaneously targeting molecules expressed on cytotoxic cells (i.e., T lymphocytes and natural killer cells) against a human melanoma-associated antigen.
Modulating protein stability – directed evolution strategies for improved protein function (2013)

Protein engineering is widely used to generate proteins with novel or enhanced function. However, manipulating protein function in the laboratory can prove laborious, protracted and challenging. Recent developments in the understanding of protein evolutionary dynamics have unveiled the full extent by which the evolution of function is limited by protein stability - a revelation that may be applied to protein engineering on a whole. Thus, strategies that modulate protein stability and reduce its constraining effects may facilitate the engineering of protein function. A combinatorial approach involving the introduction of compensatory mutations and manipulation of the stability threshold by chaperone buffering during directed evolution can improve the functional adaptation of a protein, thereby fostering our ability to attain ever-more ambitious protein functions in the laboratory.
Gene transfer into human lymphocytes by a defective human immunodeficiency virus type 1 vector (1991)

Human immunodeficiency virus type 1 (HIV-1) proviruses containing deletions between nucleotides 301 and 319 express viral proteins but exhibit marked attenuation in the packaging of viral RNA into virions (A. Lever, H. Gottlinger, W. Haseltine, and J. Sodroski, J. Virol. 63:4085-4087, 1989; A. Aldovini and R. A. Young, J. Virol. 64:1920-1926, 1990). Here we report that such packaging-defective proviruses can provide trans-acting viral elements required for the transfer of a HIV-1 vector to Jurkat human lymphocytes. The transferred vector was unable to encode HIV-1 genes, indicating that the long terminal repeats and the immediate flanking viral sequences are sufficient for packaging, reverse transcription, and integration. The generation of replication-competent viruses in this system was reduced to undetectable levels by providing the trans-acting viral functions on two separate expression plasmids. This defective retroviral vector provides a means of efficiently introducing desired genetic elements, in the absence of HIV-1 genes, into HIV-1 target cells.
2015 American Journal of Gastroenterology Lecture: How Digital Health Will Transform Gastroenterology (2016)

Our patients spend most of their lives far away from an examination room. If we are truly going to capture our patients' attention and engage them in their care, then we must reach beyond the four walls of the clinic, hospital, or endoscopy suite. This is the vision of the digital health movement-an effort to monitor patients remotely and dynamically with mobile health ("mHealth") smartphone applications, electronic health record portals, social media, and wearable biosensors to improve health care outside of the clinical trenches. This article explores how advances in digital health may improve health-care delivery, focusing on gastroenterology and hepatology. It describes how technology can monitor patients remotely, improve face-to-face care, drive clinical decisions, and offer value to health-care organizations, their patients, and their staff. The article also describes pitfalls and shortcomings of digital technologies and concludes by describing a new model for how digital health can be deployed at scale to improve coordination and outcomes of care.
<title>Accurate reconstruction of three-dimensional shape and focused image from a sequence of noisy defocused images</title> (1997)

A new approach is proposed for highly accurate reconstruction of 3D shape and focused image of an object from a sequence of noisy defocused images. This approach unifies the two approaches: image focus analysis and image defocus analysis, which have been treated separately in the research literature so far. In the new unified approach, high accuracy is attained at the cost of increased data acquisition and computation. This approach is based on modeling the sensing of defocused images in a camera system. A number of images are acquired at different levels of defocus. The resulting data is treated as a function sampled in the 3D space where x and y are the image spatial coordinates and d is a parameter representing the level off defocus. The concept of a '3D point spread function' in the space is introduced. The problem of 3D shape and focused image reconstruction is formulated as an optimization problem where the difference between the observed image data and the estimated image data is minimized. The estimated image data is obtained from the image sensing model and the current best known solutions to the 3D shape and focused image. An initial estimation to the solutions is obtained through traditional shape-from-focus methods. This solution is improved iteratively by a gradient descent approach. This approach reduces the errors in shape and focused image introduced by the image-overlap problem and the non- smoothness of the object's 3D shape. Experimental results are presented to show that the new method yields improved accuracy.
Overview of Therapeutic Ultrasound Applications and Safety Considerations (2012)

Applications of ultrasound in medicine for therapeutic purposes have been accepted and beneficial uses of ultrasonic biological effects for many years. Low-power ultrasound of about 1 MHz has been widely applied since the 1950s for physical therapy in conditions such as tendinitis and bursitis. In the 1980s, high-pressure-amplitude shock waves came into use for mechanically resolving kidney stones, and "lithotripsy" rapidly replaced surgery as the most frequent treatment choice. The use of ultrasonic energy for therapy continues to expand, and approved applications now include uterine fibroid ablation, cataract removal (phacoemulsification), surgical tissue cutting and hemostasis, transdermal drug delivery, and bone fracture healing, among others. Undesirable bioeffects can occur, including burns from thermal-based therapies and severe hemorrhage from mechanical-based therapies (eg, lithotripsy). In all of these therapeutic applications of ultrasound bioeffects, standardization, ultrasound dosimetry, benefits assurance, and side-effect risk minimization must be carefully considered to ensure an optimal benefit to risk ratio for the patient. Therapeutic ultrasound typically has well-defined benefits and risks and therefore presents a manageable safety problem to the clinician. However, safety information can be scattered, confusing, or subject to commercial conflicts of interest. Of paramount importance for managing this problem is the communication of practical safety information by authoritative groups, such as the American Institute of Ultrasound in Medicine, to the medical ultrasound community. In this overview, the Bioeffects Committee of the American Institute of Ultrasound in Medicine outlines the wide range of therapeutic ultrasound methods, which are in clinical use or under study, and provides general guidance for ensuring therapeutic ultrasound safety.
Thalidomide mimics uridine binding to an aromatic cage in cereblon (2014)

Thalidomide and its derivatives lenalidomide and pomalidomide are important anticancer agents but can cause severe birth defects via an interaction with the protein cereblon. The ligand-binding domain of cereblon is found, with a high degree of conservation, in both bacteria and eukaryotes. Using a bacterial model system, we reveal the structural determinants of cereblon substrate recognition, based on a series of high-resolution crystal structures. For the first time, we identify a cellular ligand that is universally present: we show that thalidomide and its derivatives mimic and compete for the binding of uridine, and validate these findings in vivo. The nature of the binding pocket, an aromatic cage of three tryptophan residues, further suggests a role in the recognition of cationic ligands. Our results allow for general evaluation of pharmaceuticals for potential cereblon-dependent teratogenicity.
High electron mobility in strained Si channel of heterostructure with abrupt interface (1998)

heterostructures with high electron mobility were grown by molecular beam epitaxy (MBE) combined with solid-phase epitaxy (SPE). The SPE growth completely suppressed Ge segregation in the layer on top of the Si channel layer. High-resolution cross-sectional transmission electron microscopy observation revealed that the heterointerfaces formed by the SPE growth technique were very flat compared with those for the MBE-grown samples. The electron mobility for an SPE-grown sample with a graded buffer layer was nearly one order of magnitude higher than without such a layer. A high electron mobility of was obtained at 15 K for the sample with a graded buffer layer ().
THE LYSIS-LYSOGENY DECISION OF PHAGE λ: EXPLICIT PROGRAMMING AND RESPONSIVENESS (1980)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More
La identidad científica de la educación especial: marcando el sendero de la inclusión educativa (2011)

Our first purpose in this paper is to analyse the formation process of Special Needs Education as a scientific subject from a multidimensional perspective which endows it with a cross-curricular character, as a concept that makes reference to the findings of different subjects with which it constructs its knowledge collaboratively. Then, we tackle the epistemological justification of Special Needs Education on the understanding that this subject has both theoretical and practical interests, related to the teaching of students with special educational needs, which allows considering it as an applied science, as a science concerned with a human practical activity in order to take
Identification of a small molecule inhibitor of Sir2p (2001)

Sir2p is an NAD(+)-dependent histone deacetylase required for chromatin-dependent silencing in yeast. In a cell-based screen for inhibitors of Sir2p, we identified a compound, splitomicin, that creates a conditional phenocopy of a sir2 deletion mutant in Saccharomyces cerevisiae. Cells grown in the presence of the drug have silencing defects at telomeres, silent mating-type loci, and the ribosomal DNA. In addition, whole genome microarray experiments show that splitomicin selectively inhibits Sir2p. In vitro, splitomicin inhibits NAD(+)-dependent histone deacetylase activity (HDA) of the Sir2 protein. Mutations in SIR2 that confer resistance to the drug map to the likely acetylated histone tail binding domain of the protein. By using splitomicin as a chemical genetic probe, we demonstrate that continuous HDA of Sir2p is required for maintaining a silenced state in nondividing cells.
Isolation, Sequencing, and Structure−Activity Relationships of Cyclotides (2010)

Cyclotides are a topologically fascinating family of miniproteins discovered over the past decade that have expanded the diversity of plant-derived natural products. They are approximately 30 amino acids in size and occur in plants of the Violaceae, Rubiaceae, and Cucurbitaceae families. Despite their proteinaceous composition, cyclotides behave in much the same way as many nonpeptidic natural products in that they are resistant to degradation by enzymes or heat and can be extracted from plants using methanol. Their stability arises, in large part, due to their characteristic cyclic cystine knot (CCK) structural motif. Cystine knots are present in a variety of proteins of insect, plant, and animal origin, comprising a ring formed by two disulfide bonds and their connecting backbone segments that is threaded by a third disulfide bond. In cyclotides, the cystine knot is uniquely embedded within a head-to-tail cyclized peptide backbone, leading to the ultrastable CCK structural motif. Apart from the six absolutely conserved cysteine residues, the majority of amino acids in the six backbone loops of cyclotides are tolerant to variation. It has been predicted that the family might include up to 50,000 members; although, so far, sequences for only 140 have been reported. Cyclotides exhibit a variety of biological activities, including insecticidal, nematocidal, molluscicidal, antimicrobial, antibarnacle, anti-HIV, and antitumor activities. Due to their diverse activities and common structural core from which variable loops protrude, cyclotides can be thought of as combinatorial peptide templates capable of displaying a variety of amino acid sequences. They have thus attracted interest in drug design as well as in crop protection applications.
CD46 Plays a Key Role in Tailoring Innate Immune Recognition of Apoptotic and Necrotic Cells (2005)

Complement is the canonical innate immune system involved in host defense and tissue repair with the clearance of cell debris. In contrast to the robust armory mounted against microbial nonself-pathogens, complement is selectively activated on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise by poorly characterized mechanisms. Our data shed new light on the role of complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat T cell membranes and in driving C3 opsonization but without the lytic membrane attack complex. DNA/RNase-treated apoptotic cells failed to activate complement. We found that several other apoptotic cell models, including senescent keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46 from nuclear and membrane stores was found to cluster into blebs and shed into microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical and alternative pathways of complement were involved in the recognition of H2O2-treated necrotic cells. Membrane attack complex was detected on necrotic cells possibly as a result of CD46 and CD59 shedding into soluble forms. Our data highlight a novel and universal paradigm whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-NA and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites.
A murine stromal cell line allows the proliferation of very primitive human CD34++/CD38- progenitor cells in long-term cultures and semisolid assays (1993)

Analysis of molecular mechanisms associated with stem cell commitment and differentiation requires an in vitro assay that identifies the most primitive hematopoietic stem cells in human bone marrow. Such primitive stem cells usually do not form colonies in short-term semisolid assays and are best identified by their ability to initiate sustained hematopoiesis when they are cocultured with competent stromal cells. In this study, we investigated whether a murine marrow stromal cell line (MS-5) that supports colony-forming unit-spleen (CFU-S) maintenance would permit, both in short-term colony assays and long-term cultures, the development of primitive human stem cells sorted on the basis of their high expression of CD34 and lack of expression of CD38 antigen. In short-term colony assays, this population included almost exclusively primitive progenitor cells. MS-5 cells synergized with any combination of interleukin-3, Steel factor, granulocyte colony- stimulating factor, agar-leukocyte conditioned medium, and erythropoietin and increased at least twofold both the cloning efficiency of CD34++/CD38- cells and the size of the colonies. Furthermore, MS-5 cells triggered the development of multipotent blast cell progenitors with a high proliferative potential, which in these conditions represented 1% to 2% of CD34++/CD38- cells. When MS-5 cells were substituted by human stromal cells or when growth factor combinations were used in the absence of stromal cells, much lower numbers of CFU-blast were detected. This selective action of MS-5 on early progenitors was also observed when MS-5 cells were used as feeders in long-term cultures of CD34++/CD38- cells. Murine cells promoted the expansion of high proliferative potential primitive progenitor cells up to 3 months, although they did not support their differentiation in mature clonogenic progenitors or terminally differentiated cells. Sustained hematopoiesis in these longterm cultures was accounted for by 2% to 5% of initial CD34++/CD38- cells as estimated by limiting dilution experiments. Mechanisms by which murine stromal cells act specifically on human primitive stem cells are unclear, but from our data this effect is unlikely to be explained solely by known species cross-reactive growth factors. Further manipulation of this long-term coculture system should prove useful in identifying stromal molecules regulating commitment and differentiation of early human progenitor cells.
Comparative binding, endocytosis, and biodistribution of antibodies and antibody‐coated carriers for targeted delivery of lysosomal enzymes to ICAM‐1 versus transferrin receptor (2012)

Targeting lysosomal enzymes to receptors involved in transport into and across cells holds promise to enhance peripheral and brain delivery of enzyme replacement therapies (ERTs) for lysosomal storage disorders. Receptors being explored include those associated with clathrin-mediated pathways, yet other pathways seem also viable. Well characterized examples are that of transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1), involved in iron transport and leukocyte extravasation, respectively. TfR and ICAM-1 support ERT delivery via clathrin- vs. cell adhesion molecule-mediated mechanisms, displaying different valency and size restrictions. To comparatively assess this, we used antibodies vs. larger multivalent antibody-coated carriers and evaluated TfR vs. ICAM-1 binding and endocytosis in endothelial cells, as well as in vivo biodistribution and delivery of a model lysosomal enzyme required in peripheral organs and brain: acid sphingomyelinase (ASM), deficient in types A-B Niemann Pick disease. We found similar binding of antibodies to both receptors under control conditions, with enhanced binding to activated endothelium for ICAM-1, yet only anti-TfR induced endocytosis efficiently. Contrarily, antibody-coated carriers showed enhanced binding, engulfment, and endocytosis for ICAM-1. In mice, anti-TfR enhanced brain targeting over anti-ICAM, with an opposite outcome in the lungs, while carriers enhanced ICAM-1 targeting over TfR in both organs. Both targeted carriers enhanced ASM delivery to the brain and lungs vs. free ASM, with greater enhancement for anti-ICAM carriers. Therefore, targeting TfR or ICAM-1 improves lysosomal enzyme delivery. Yet, TfR targeting may be more efficient for smaller conjugates or fusion proteins, while ICAM-1 targeting seems superior for multivalent carrier formulations.
Scalable shared-buffering ATM switch with a versatile searchable queue (1997)

The shared-buffering architecture is promising to make a large-scale ATM switch with small buffer size. However, there are two important problems, namely, memory-access speed and complex-control implementation. Advanced 0.5 /spl mu/m CMOS technology now makes it possible to integrate a huge amount of memory, and enables us to apply more sophisticated architecture than ever before. We propose the funnel-structured expandable architecture with shared multibuffering and the advanced searchable-address queueing scheme for these two problems. The funnel structure gives a flexible capability to build various sizes of ATM switches which are proportional to the number of LSI chips. The searchable-address queue, in which all the addresses of the stored cells for different output ports are queued in a single-FIFO hardware and the earliest address is found by the search function provided inside the queue, can reduce the total memory capacity drastically, and enables the address queue to be contained inside the LSI chip. This technique also has a great advantage for implementing the multicast and multilevel priority-control functions. A 622 Mbit/s 32/spl times/8 ATM switch LSI chip set, which consists of a BX-LSI and a CX-LSI, is developed using 0.5 /spl mu/m pure CMOS technology. By using four chip sets, a 622 Mbit/s 32/spl times/32 switch can be installed on one board.
The clinical spectrum of coronary artery disease and its surgical and medical management, 1974-1979. The Coronary Artery Surgery study. (1982)

Data from the National Heart, Lung, and Blood Institute's Coronary Artery Surgery Study (CASS) are used to describe the types of persons who undergo coronary angiography for possible coronary artery bypass surgery, the reasons patients receive coronary bypass surgery, and operative mortality results, as well as changing trends in the therapy assigned. The review is designed to provide background material for those assessing coronary artery bypass technology.
Alveolar Bone Response to Submerged Bisphosphonate‐Complexed Hydroxyapatite Implants (2000)

This study contributes to the understanding of the biological properties of hydroxyapatite implants as carriers for the bone-modulating agent bisphosphonate. Our study suggests that normal osteoconduction and repair occurred in alveolar bone around the highly bisphosphonate-complexed hydroxyapatite implants.
The Biochemistry of Gene Therapy for AIDS (1998)

Gene therapy has enormous potential and could in the near future involve the clinical biochemist in monitoring its efficacy. The involvement of clinical biochemists in this field could be not only in evaluating the impact of a gene-based strategy on disease progression, but also in measuring the expression of the products of therapeutic genes in treated individuals. Indeed, gene therapy presents new possibilities for the treatment of many diseases and, in particular, merits consideration in the treatment of a fatal disease like AIDS. The aim of this paper is to review the biochemical basis and clinical relevance of the gene therapy approaches directed towards the inhibition of human immunodeficiency virus type-1. We discuss the goals which have been achieved, the problems which have occurred and the efforts that are being made to solve them. In this regard, particular attention is paid to new strategies targeting 'therapeutic' enzymes to human immunodeficiency virus type-1 nucleic acids.