gebhart/patrepeval huggingface dataset:
The Beneficence of Neonatal Hematopoiesis (1989)

THE fetus and the newborn are highly endowed with the capacity to produce blood,1 and the site-specific stages and switches through which the accelerated blood production moves during development2 are becoming particularly fascinating as the regulatory proteins that influence them are identified.3 The production of red cells begins in the yolk sac only a few weeks after conception. Yolk-sac erythrocytes are very large nucleated cells that uniquely express the products of certain genes, such as embryonic globin. When hematopoiesis is completed in the yolk sac, it moves on to the liver, and that organ fills with nucleated red cells. Relatively . . .
Duration modeling in large vocabulary speech recognition (2002)

This paper presents a study of different methods for phoneme duration modeling in large vocabulary speech recognition. We investigate the employment of phoneme duration and the effect of context, speaking rate and lexical stress in the duration of phoneme segments in a large vocabulary speech recognition system. The duration models are used in a postprocessing phase of BYBLOS, our baseline HMM-based recognition system, to rescore the N-Best hypotheses. We describe experiments with the 5 K word ARPA Wall Street Journal (WSJ) corpus. The results show that integration of duration models that take into account context and speaking rate can improve the word accuracy of the baseline recognition system.
Human-Induced Pluripotent Stem Cells Produced Under Xeno-Free Conditions (2009)

Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. While cell differentiation protocols have been successfully developed, and animal models of human disease have proved that these cells have the potential to treat human diseases and conditions produced as a consequence of aging, degeneration, injury, and birth defects, logistical issues still remain unsolved and hamper the possibility of testing these cells in human clinical trials. Among them is the widely spread use of animal products for the generation and culture of iPSCs. We report here a xeno-free iPSC generation system that addresses all the steps of iPSCs production including the isolation and culture of adult skin fibroblasts, and iPSCs generation, expansion, and maintenance. iPSCs generated with a polycistronic lentiviral vector under xeno-free conditions displayed markers of pluripotency and gave rise to embryoid bodies (EBs) displaying indicators of the 3 primary germ layers. Xeno-free iPSCs injected into nude mice produced classic teratomas, and teratoma explants cultured under conditions favoring fibroblastic cells gave rise to cells morphologically indistinguishable from input cells. Protocols here described will facilitate the implementation of new cellular therapies for preclinical and clinical studies, potentially reducing the regulatory burden without compromising the differentiation potential of the cells.
Biomarkers in idiopathic pulmonary fibrosis (2012)

The peripheral blood contains disease presence and outcome relevant information, and suggests distinct biologically defined outcome trajectories in patients with IPF. Although recently identified biomarkers should still be validated in multiple clinical contexts, there is sufficient evidence to suggest that collection of peripheral blood biomarkers needs to be incorporated in the design of drug studies and that some of these markers be clinically evaluated in lung transplant prioritization.
In Vivo Reversal of Amyloid-β Lesions in Rat Brain (2000)

Cerebral amyloid-beta (Abeta) deposition is central to the neuropathological definition of Alzheimer disease (AD) with Abeta related toxicity being linked to its beta-sheet conformation and/or aggregation. We show that a beta-sheet breaker peptide (iAbeta5) dose-dependently and reproducibly induced in vivo disassembly of fibrillar amyloid deposits, with control peptides having no effect. The iAbeta5-induced disassembly prevented and/or reversed neuronal shrinkage caused by Abeta and reduced the extent of interleukin-1beta positive microglia-like cells that surround the Abeta deposits. These findings suggest that beta-sheet breakers, such as iAbeta5 or similar peptidomimetic compounds, may be useful for reducing the size and/or number of cerebral amyloid plaques in AD, and subsequently diminishing Abeta-related histopathology.
Conservation of waterlogged timbers from the Batavia 1629 (1990)

The problems associated with determination of longitude in the seventeenth century have led to the recovery of a fine collection of artefacts from the wrecks of the Dutch East lndiamen Batavia 1629 and the Vergulde Draeck 1656. From the analysis of materials recovered from the wrecks, an insight into the industrial technology of seventeenth century metal and woodworking industries has been obtained (MacLcod, 1987; Baker and Green, 1977 and Green, 1989). Since records of construction techniques arc essentially non-existent for the period in question, the structure that is being revealed in the rebuilding of the Batavia at the Western Australian Maritime Museum is providing a real insight into the 'stale-of-the-art' technique used in Dutch yards in the 1620s (Hundley, 1983 and Green and Parthesius, 1989).
Arthrotomography of the temporomandibular joint: new technique and preliminary observations (1979)

A technique for arthrography of the temporomandibular joint using multidirectional tomography is described that greatly simplifies interpretation. In 21 attempts, 20 successful arthrograms were obtained in patients complaining of pain, tenderness, and clicking and locking of the joint who had not responded to conservative therapy. Abnormalities demonstrated were perforation of the meniscus, anterior dislocation and subluxation of the meniscus; and redundancy of the bilaminar zone. In all 11 patients who underwent surgical meniscoplasty, disc abnormalities included thinning, perforation, flaccidity, and bilaminar redundancy. No permanent complications of the arthrographic procedure occurred, but temporary postprocedure discomfort was frequent. This preliminary experience with temporomandibular joint arthrotomography suggests this easily performed procedure offers reliable information about disc function and integrity that may assist in a selection of patients for meniscoplasty and other surgical treatment.
The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice (2009)

Recombinant adeno-associated viruses (AAVs) have been used widely for in vivo gene therapy. However, adaptive immune responses to AAV have posed a significant hurdle in clinical application of AAV vectors. Recent advances have suggested a crucial role for innate immunity in shaping adaptive immune responses. How AAV activates innate immunity, and thereby promotes AAV-targeted adaptive immune responses, remains unknown. Here we show that AAV activates mouse plasmacytoid DCs (pDCs) via TLR9 to produce type I IFNs. In vivo, the TLR9-MyD88 pathway was crucial to the activation of CD8+ T cell responses to both the transgene product and the AAV capsid, leading to loss of transgene expression and the generation of transgene product-specific and AAV-neutralizing antibodies. We further demonstrate that TLR9-dependent activation of adaptive immunity targeting AAV was mediated by type I IFNs and that human pDCs could be activated in vitro to induce type I IFN production via TLR9. These results reveal an essential role for the TLR9-MyD88-type I IFN pathway in induction of adaptive immune responses to AAV and suggest that strategies that interfere with this pathway may improve the outcome of AAV-mediated gene therapy in humans.
A Mass Spectrometry-based Proteomic Approach for Identification of Serine/Threonine-phosphorylated Proteins by Enrichment with Phospho-specific Antibodies (2002)

Although proteins phosphorylated on tyrosine residues can be enriched by immunoprecipitation with anti-phosphotyrosine antibodies, it has been difficult to identify proteins that are phosphorylated on serine/threonine residues because of lack of immunoprecipitating antibodies. In this report, we describe several antibodies that recognize phosphoserine/phosphothreonine-containing proteins by Western blotting. Importantly, these antibodies can be used to enrich for proteins phosphorylated on serine/threonine residues by immunoprecipitation, as well. Using these antibodies, we have immunoprecipitated proteins from untreated cells or those treated with calyculin A, a serine/threonine phosphatase inhibitor. Mass spectrometry-based analysis of bands from one-dimensional gels that were specifically observed in calyculin A-treated samples resulted in identification of several known serine/threonine-phosphorylated proteins including drebrin 1, alpha-actinin 4, and filamin-1. We also identified a protein, poly(A)-binding protein 2, which was previously not known to be phosphorylated, in addition to a novel protein without any obvious domains that we designate as Frigg. Frigg is widely expressed and was demonstrated to be a protein kinase A substrate in vitro. We identified several in vivo phosphorylation sites by tandem mass spectrometry using Frigg protein immunoprecipitated from cells. Our method should be applicable as a generic strategy for enrichment and identification of serine/threonine-phosphorylated substrates in signal transduction pathways.
Writing Windows VxDs and Device Drivers (1996)

Software developer and author Karen Hazzah expands her original treatise on device drivers in the second edition of Writing Windows VxDs and Device Drivers. The book and companion disk include the author's library of wrapper functions that allow the progr
Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors (2016)

Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.
TRP channels as potential drug targets (2004)

Calcium (Ca2+) is an ubiquitous intracellular signal that is responsible for a plethora of cellular processes including fertilization, secretion, contraction, neuronal signaling and learning. In addition, changes in intracellular Ca2+ have been known to influence cell proliferation and differentiation for more than three decades. Recent studies have indicated that members of the transient receptor potential (TRP) family of ion channels which respond to many different modes of stimulation both from within and outside the cell may be a primary mode of cation and Ca2+ entry into cells and may have roles in growth control. Moreover, changes in the expression of these channels may contribute to certain cancers. In the following, recent results concerning the expression and function of members of this family of ion channels are summarized.
Cosmetic and Clinical Applications of Botulinum Toxin (2003)

Inside Cosmetic and Clinical Applications of Botulinum Toxin, readers will learn everything there is know about this effective treatment for active lines of facial expression. The storage, reconstitution and mechanism of action of BOTOX are all thoroughly explained. A thorough analysis is provided detailing the underlying facial muscle anatomy that is required and physicians can integrate this procedure into their current practice. An additional section is also included detailing cosmetic filler agents, a more effective form of treatment for lines that are present at rest. As the demand for less invasive facial rejuvenation products and treatments continue increase, botulinum toxin or BOTOX injections are emerging as the popular choice. While the initial public reaction was guarded, the procedure is now common, as millions of individuals around the world are pursuing the cosmetic application of BOTOX for wrinkle reduction. The text utilizes a how to approach in teaching the ways BOTOX can remedy many functional disorders and conditions. Specific illustrations and photographs are used clearly convey a variety of injection techniques. Anyone interested in expanding their clinical practice by integrating botulinum toxin and dermal filler agents should greatly benefit from this insightful resource.
Contribution of Atrial Fibrillation to Incidence and Outcome of Ischemic Stroke (2005)

We found a high prevalence of AF in patients with a first-ever ischemic stroke, especially among elderly women. The overall contribution of AF to stroke mortality was relevant, suggesting that together with new strategies to prevent the development of the arrhythmia more appropriate treatments are needed, mostly in elderly women.
Linking electronic journals (1998)

The Open Journal project has completed its three year period of funding by the UK Electronic Libraries(eLib) programme. During that time, the number of journals that are available electronically leapt from a few tens to a few thousand. Some of these journals are now developing the sort of features the project has been advocating, in particular the use of links within journals, between different primary journals, with secondary journals data, and to non-journal sources. Assessing the achievements of the project and considering some of the difficulties it faced, we report on the different approaches to linking that the project developed, and summarise the important user responses that indicate what works and what does not. Looking ahead, there are signs of change, not just to simple linking within journals but to schemes in which links are the basis of journals, where information may be shared and documents built from different sources. The significance has yet to be appreciated, but this would be a major change from printed journals. If projects such as this and others have provided the initial impetus, the motivation for distributed journals comes, perhaps surprisingly, from within certain parts of the industry, as the paper shows.
Unsupervised Video Object Segmentation for Deep Reinforcement Learning (2018)

We present a new technique for deep reinforcement learning that automatically detects moving objects and uses the relevant information for action selection. The detection of moving objects is done in an unsupervised way by exploiting structure from motion. Instead of directly learning a policy from raw images, the agent first learns to detect and segment moving objects by exploiting flow information in video sequences. The learned representation is then used to focus the policy of the agent on the moving objects. Over time, the agent identifies which objects are critical for decision making and gradually builds a policy based on relevant moving objects. This approach, which we call Motion-Oriented REinforcement Learning (MOREL), is demonstrated on a suite of Atari games where the ability to detect moving objects reduces the amount of interaction needed with the environment to obtain a good policy. Furthermore, the resulting policy is more interpretable than policies that directly map images to actions or values with a black box neural network. We can gain insight into the policy by inspecting the segmentation and motion of each object detected by the agent. This allows practitioners to confirm whether a policy is making decisions based on sensible information.
Correlation of Activities of the Enzymes α-Phosphoglucomutase, UDP-Galactose 4-Epimerase, and UDP-Glucose Pyrophosphorylase with Exopolysaccharide Biosynthesis by Streptococcus thermophilus LY03 (2000)

The effects of different carbohydrates or mixtures of carbohydrates as substrates on bacterial growth and exopolysaccharide (EPS) production were studied for the yoghurt starter culture Streptococcus thermophilus LY03. This strain produces two heteropolysaccharides with the same monomeric composition (galactose and glucose in the ratio 4:1) but with different molecular masses. Lactose and glucose were fermented by S. thermophilus LY03 only when they were used as sole energy and carbohydrate sources. Fructose was also fermented when it was applied in combination with lactose or glucose. Both the amount of EPS produced and the carbohydrate source consumption rates were clearly influenced by the type of energy and carbohydrate source used, while the EPS monomeric composition remained constant (galactose-glucose, 4:1) under all circumstances. A combination of lactose and glucose resulted in the largest amounts of EPS. Measurements of the activities of enzymes involved in EPS biosynthesis, and of those involved in sugar nucleotide biosynthesis and the Embden-Meyerhof-Parnas pathway, demonstrated that the levels of activity of alpha-phosphoglucomutase, UDP-galactose 4-epimerase, and UDP-glucose pyrophosphorylase are highly correlated with the amount of EPS produced. Furthermore, a weaker relationship or no relationship between the amounts of EPS and the enzymes involved in either the rhamnose nucleotide synthetic branch of the EPS biosynthesis or the pathway leading to glycolysis was observed for S. thermophilus LY03.
Silencing of RNA Polymerases II and III-Dependent Transcription by the KRAB Protein Domain of KOX1, a Krüppel-Type Zinc Finger Factor (1997)

The so-called KRAB domain, which is present in about one third of the vertebrate Kruppel-type zinc finger factors, has previously been shown to inhibit transcription in cis when tethered to promoter regions. Here we analyze this effect with fusions of the KRAB domain derived from KOX1/ZNF10 zinc finger protein to the heterologous DNA binding domains of both LexA and GAL4 factors. In transfected human cells, repression of reporter gene transcription is observed not only from proximal promoter positions, but also when KRAB is tethered to DNA at a remote position more than 1.8 kb downstream of the initiation site of transcription. Furthermore, KRAB-mediated silencing over short and long distances is not restricted to RNA polymerase II, since transcription by RNA polymerase III is also repressed. However, transcription by RNA polymerase I and by phage T7 RNA polymerase in mammalian cells are not significantly influenced by the KRAB domain. These latter results may indicate that repression by the KRAB domain, at least under our assay conditions, involves specific inhibition of some component(s) of RNA polymerase II and III transcription, rather than inducing some gross physical alteration of template chromatin structure.
Synthesis of Comb Block Copolymers by ROMP, ATRP, and ROP and Their Assembly in the Solid State (2005)

This article reports the synthesis of comb block copolymers with backbones from exo-norbornene esters via ring-opening metathesis polymerizations (ROMP) and arms composed of polystyrene and polylactide. These polymers represent an exciting new architecture of polymers that have applications in the fabrication of photonic materials and nanofluidic systems. The living polymerization of block copolymers by ROMP with degrees of polymerization up to 2000 units and polydispersities less than 1.2 are described. This result is important as it extends the range of block copolymers that can be synthesized by ROMP to include those with high molecular weights. Comb block copolymers were grown from these block copolymers as they displayed initiators for the ring-opening polymerization of lactide and the atom transfer radical polymerization of styrene. Comb block copolymers with polystyrene and polylactide arms were synthesized with molecular weights up to 63 000 000 g mol-1. The polystyrene arms had narrow polydispersities and molecular weights in excess of 10 000 g mol-1; this result showed that the polymerization of styrene was well controlled. The sizes and shapes of these comb polymers were characterized by multiangle laser light scattering and scanning probe microscopy and demonstrated that some of these polymers were shaped as rigid rods with lengths in excess of 300 nm. To demonstrate their potential as photonic materials, an example of a comb block copolymer was assembled in the solid state with domain sizes exceeding 100 nm and characterized by scanning electron microscopy.
Systemic Administration of C-Type Natriuretic Peptide as a Novel Therapeutic Strategy for Skeletal Dysplasias (2009)

Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.
Biomechanical stress in coronary atherosclerosis: emerging insights from computational modelling (2016)

10.1093/eurheartj/ehv689
X‐ray microscopy of plant cells by using LiF crystal as a detector (2008)

A lithium fluoride (LiF) crystal has been utilized as a new soft X-ray detector to image different biological samples at a high spatial resolution. This new type of image detector for X-ray microscopy has many interesting properties: high resolution (nanometer scale), permanent storage of images, the ability to clear the image and reuse the LiF crystal, and high contrast with greater dynamic range. Cells of the unicellular green algae Chlamydomonas dysosmos and Chlorella sorokiniana, and pollen grains of Olea europea have been used as biological materials for imaging. The biological samples were imaged on LiF crystals by using the soft X-ray contact microscopy and contact micro-radiography techniques. The laser plasma soft X-ray source was generated using a Nd:YAG/Glass laser focused on a solid target. The X-ray energy range for image acquisition was in the water-window spectral range for single shot contact microscopy of very thin biological samples (single cells) and around 1 keV for multishots microradiography. The main aim of this article is to highlight the possibility of using a LiF crystal as a detector for the biological imaging using soft X-ray radiation and to demonstrate its ability to visualize the microstructure within living cells.