gebhart/patrepeval huggingface dataset:
Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus (1996)

In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect in cells infected with HSV-1 or HSV-2 was assessed and compared with the cellular uptake of the analog. We found that antisense S-ODNs showed the most potent antiherpetic activity, with 50% inhibitory concentrations of 5 microM for HSV-1 and 0.25 microM for HSV-2. The antiviral effect of antisense S-ODNs was stronger and longer acting than that of acyclovir. Cell association of S-ODNs was the highest and paralleled antiviral activity. Furthermore, some fluorescein isothiocyanate (FITC)-labeled S-ODNs were recognized in the nuclei in HSV-1 infected cells by confocal laser scanning microscopy. S-ODNs located in the nucleus could access the targeted mRNA, which might be responsible for the antiviral activities. Although our study also showed non-sequence-specific activity, which implies that multiple mechanisms are involved, S-ODNs are a promising novel anti-herpetic agent.
Estimation and Control in Semiconductor Etch: Practice and Possibilities (2010)

Semiconductor wafer etching is, to a large extent, an open-loop process with little direct feedback control. Most silicon chip manufacturers rely on the rigorous adherence to a ¿recipe¿ for the various etch processes, which have been built up based on considerable historical experience. However, residue buildup and difficulties in achieving consistent preventative maintenance operations lead to drifts and step changes in process characteristics. This paper examines the particular technical difficulties encountered in achieving consistency in the etching of semiconductor wafers and documents the range of estimation and control techniques currently available to address these difficulties. An important feature of such an assessment is the range of measurement options available if closed-loop control is to be achieved.
Broadband hyperspectral stimulated Raman scattering microscopy with a parabolic fiber amplifier source (2018)

Hyperspectral stimulated Raman scattering (hsSRS) microscopy has recently emerged as a powerful non-destructive technique for the label-free chemical imaging of biological samples. In most hsSRS imaging experiments, the SRS spectral range is limited by the total bandwidth of the excitation laser to ~300 cm<sup>-1</sup> and a spectral resolution of ~25 cm<sup>-1</sup>. Here we present a novel approach for broadband hsSRS microscopy based on parabolic fiber amplification to provide linearly chirped broadened Stokes pulses. This novel hsSRS instrument provides >600 cm<sup>-1</sup> spectral coverage and ~10 cm<sup>-1</sup> spectral resolution. We further demonstrated broadband hsSRS imaging of the entire Raman fingerprint region for resolving the distribution of major biomolecules in fixed cells. Moreover, we applied broadband hsSRS in imaging amyloid plaques in human brain tissue with Alzheimer's disease.
A chronically implanted system for automatic defibrillation in active conscious dogs. Experimental model for treatment of sudden death from ventricular fibrillation. (1978)

Ventricular defibrillation was acheived in active conscious dogs with a chronically implanted automatic system composed of a defibrillator and an alternating current fibrillator. The hermetically sealed defibrillator is encased in titanium, weighs 250 g and has a volume of 145 ml. The sensor continuously monitors ventricular electircal activity and recognizes fibrillation by the absence of isoelectric potential segments. Fibrillation is induced by placing a magnet over the implanted fibrillator. The resulting syncope closely resembles the clinical entity of sudden death, while the defibrillator automatically restores normal rhythm with a truncated exponential pulse of 30 J, 15 seconds after the onset of the arrhythmia. The operational status of the defibrillator can be tested in vitro and noninvasively in vivo with an external analyzer. This experimental model allows for the first time a long-term study of the automatic implantable defibrillator approach to prevent sudden death from ventricular fibrillation under a variety of physiopathologic conditions.
Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. (1994)

ngiotensin-converting enzyme (ACE) inhibitors are commonly used drugs in the management of a variety of cardiovascular diseases. They are effective antihypertensive agents.1-3 Early studies have demonstrated reductions in mortality and symptoms of heart failure in patients with severe congestive heart failure.4 More recently, clinical trials have demon- strated reductions in mortality and in hospitalizations for heart failure when these agents were used in pa- tients with moderate left ventricular dysfunction, with and without overt heart failure, further expanding the clinical value of these drugs in the management of patients with cardiac diseases. These benefits have been observed consistently in several trials,5-7 in patients with ischemic and nonischemic causes for the left ventricular dysfunction and with or without recent myocardial infarction. The reductions in progressive heart failure and mortality in these patients are at least partly related to a beneficial effect on left ventricular remodeling and reductions in left ventricular enlargement.8-10 Other potential beneficial effects of these agents, such as regression of left ventricular hypertrophy and retarda- tion of the rate of loss of renal function in patients with diabetic nephropathy, have been brought into focus by recent trials and also by experimental studies that explore their mechanisms of action.
Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains (2009)

Recently, a CTX-M-15 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli O25b-ST131 clone, belonging to the B2 phylogenetic group and with a high virulence potential, has been reported all over the world, representing a major public health problem. The present study was carried out to develop a rapid and simple detection assay that identifies members of this clone. A total of 627 E. coli isolates of which 373 produced an ESBL, collected across four continents, were screened using a O25b-ST131 clone allele-specific PCR for the pabB gene. One hundred and forty-three ESBL isolates were found positive with the assay. These isolates were all of O25b type and, when studied by multilocus sequence typing (25 cases), were all of ST131. The O25b-ST131 clone was found to produce ESBLs other than CTX-M-15, specifically CTX-M-2, -3, -14, -27, -32 and -61 as well as TEM-24. This clone represents 3% of non-ESBL B2 isolates originating from urinary tract infections in Paris. We have developed a PCR-based assay that easily identifies a clone with high likelihood of producing ESBLs, including CTX-M-15.
Growing Old Together (2001)

Simple evolutionary arguments don't demand that organisms share mechanisms of aging. But new work is strengthening the case that common processes control the life-spans of biology's favorite model systems
Decoupled access/execute computer architectures (1982)

An architecture for improving computer performance is presented and discussed. The main feature of the architecture is a high degree of decoupling between operand access and execution. This results in an implementation which has two separate instruction streams that communicate via queues. A similar architecture has been previously proposed for array processors, but in that context the software is called on to do most of the coordination and synchronization between the instruction streams. This paper emphasizes implementation features that remove this burden from the programmer. Performance comparisons with a conventional scalar architecture are given, and these show that considerable performance gains are possible. Single instruction stream versions, both physical and conceptual, are discussed with the primary goal of minimizing the differences with conventional architectures. This would allow known compilation and programming techniques to be used. Finally, the problem of deadlock in such a system is discussed, and one possible solution is given.
Sacral Neuromodulation Therapy (2012)

Sacral neuromodulation appears to be a promising new treatment option in adolescents with refractory functional constipation not responding to intensive conservative therapy. Larger randomized studies with long-term follow-up are required.
Platelet‐rich plasma and bovine porous bone mineral combined with guided tissue regeneration in the treatment of intrabony defects in humans (2002)

The results of this study suggest that PRP and BPBM provide an added regenerative effect to GTR in promoting the clinical resolution of intrabony defects on patients with severe periodontitis.
Understanding the Pro- and Anti-Inflammatory Properties of IL-27 (2004)

The recent identification of IL-27 (IL-27p28/EBV-induced gene 3) and IL-27R (WSX-1/gp130) has provided new insights for the biology of IL-6/IL-12 family cytokines. Initial studies indicated that IL-27 can directly regulate T cell functions and suggested an important role for it in promoting Th1 type responses. However, subsequent studies have revealed that IL-27R signaling influences a variety of immune cell types and can inhibit either Th1 or Th2 type responses. Though elucidation of the Jak/STAT signaling pathways activated by IL-27R ligation has unveiled some of the molecular mechanisms used by IL-27 to promote inflammation, little is known about the anti-inflammatory activities of this cytokine. Thus, the aim of this review is to discuss the pleotropic nature of the IL-27/IL-27R interaction and attempt to reconcile the pro- and anti-inflammatory properties of this immunomodulator.
Restless legs syndrome (1996)

Despite recent attempts to better characterize restless legs syndrome (RLS), this neurologic disorder remains poorly understood. The relationship between idiopathic and secondary and between familial and sporadic (nonfamilial) cases have not been previously defined. We studied 54 patients (29 women and 25 men) who satisfied the diagnostic criteria for RLS. The mean age of the patients was 62.69 +/- 13.82 years, and the mean age at onset was 34.13 +/- 20.30 years. We found that 92% of patients with idiopathic RLS (without neuropathy) had a family history of RLS, whereas only 13% of those with neuropathic RLS (associated with peripheral neuropathy) had a positive family history. The sporadic/neuropathic patients were older at symptom onset and tended to have a more rapid progression than the familial/idiopathic patients. There were no other significant differences between the subgroups. Levodopa and dopamine agonists were the most effective treatments. We conclude that there are two major etiologic subgroups of RLS but that the two share central pathophysiologic mechanisms.
A Neutral Magnesium-dependent Sphingomyelinase Isoform Associated with Intracellular Membranes and Reversibly Inhibited by Reactive Oxygen Species (2000)

Activation of neutral sphingomyelinase(s) and subsequent generation of ceramide has been implicated in a wide variety of cellular responses. Although this enzyme(s) has not been purified and cloned from higher organisms, one mammalian cDNA has been previously isolated based on its similarity to the bacterial enzyme. To further elucidate the function of this neutral sphingomyelinase, we studied its relationship with enzymes present in mammalian cells and tissues, its subcellular localization, and properties that could be important for the regulation of its activity. Using specific antibodies, it is suggested that the enzyme could represent one of several forms of neutral sphingomyelinases present in the extract from brain particulate fraction. In PC12 cells, the enzyme is localized in the endoplasmic reticulum and is not present in the plasma membrane. The same result has been obtained in several cell lines transfected or microinjected with plasmids encoding this enzyme. The molecular and enzymatic properties of the cloned neutral magnesium-dependent sphingomyelinase, produced using baculovirus or bacterial expression systems, have been analyzed, demonstrating the expected ion dependence and substrate specificity. The enzyme activity also has a strong requirement for reducing agents and is reversibly inhibited by reactive oxygen species and oxidized glutathione. The studies demonstrate that the cellular localization and some properties of this enzyme are distinct from properties previously associated with neutral magnesium-dependent sphingomyelinases in crude or partially purified preparations.
Total RNA extraction from strawberry tree (Arbutus unedo) and several other woody-plants (2008)

Studies of plant gene expression today need pure preparations of high-yielding undegraded RNA. This is not easily accomplished when working with plants and tissues like strawberry tree (Arbutus unedo) leaves that accumulate large amounts of polysaccharides and polyphenolic compounds, which co-purify with RNA. An improved leaf-tissue protocol developed for gene expression studies on Arbutus unedo yields for the first time a purity of RNA extract that makes possible cDNA synthesis and qPCR analysis in this plant species. When tested on material considered recalcitrant (leaves, roots, fruit flesh, fruit peel and styles from Pyrus communis, Prunus avium, Prunus persica and Cydonia oblonga), the method was able to extract RNA with good yield and high purity. This scalable, phenol-free, fast and easy-to-use RNA extraction protocol is effective on Arbutus unedo leaves as well as on awide range of different species and tissues, thus resulting particularly useful for gene expression analysis in non-model species for molecular biology.
Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells (2008)

The contribution of Fc-mediated effector functions to the therapeutic efficacy of some monoclonal antibodies has motivated efforts to enhance interactions with Fcgamma receptors (FcgammaR). Although an early goal has been enhanced FcgammaRIIIa binding and natural killer (NK) cell antibody-dependent cell-mediated cytotoxicity (ADCC), other relevant cell types such as macrophages are dependent on additional activating receptors such as FcgammaRIIa. Here, we describe a set of engineered Fc variants with diverse FcgammaR affinities, including a novel substitution G236A that provides selectively enhanced binding to FcgammaRIIa relative to FcgammaRIIb. Variants containing this substitution have up to 70-fold greater FcgammaRIIa affinity and 15-fold improvement in FcgammaRIIa/FcgammaRIIb ratio and mediate enhanced phagocytosis of antibody-coated target cells by macrophages. Specific double and triple combination variants with this substitution are simultaneously capable of exhibiting high NK-mediated ADCC and high macrophage phagocytosis. In addition, we have used this unique set of variants to quantitatively probe the relative contributions of individual FcgammaR to effector functions mediated by NK cells and macrophages. These experiments show that FcgammaRIIa plays the most influential role for macrophages and, surprisingly, that the inhibitory receptor FcgammaRIIb has little effect on effector function. The enhancements in phagocytosis described here provide the potential to improve the performance of therapeutic antibodies targeting cancers.
Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. (1997)

Selective induction of vascular damage within tumors represents an emerging approach to cancer treatment. Histological studies have shown that several tubulin-binding agents can induce vascular damage within tumors but only at doses approximating the maximum tolerated dose, which has limited their clinical applicability. In this study, we show that the combretastatin A-4 prodrug induces vascular shutdown within tumors at doses less than one-tenth of the maximum tolerated dose. In vitro studies indicate that a short drug exposure results in profound long-term antiproliferative/cytotoxic effects against proliferating endothelial cells but not cells that are quiescent prior to and during drug exposure. Vascular shutdown, within experimental and human breast cancer models in vivo following systemic drug administration, was demonstrated with a reduction in functional vascular volume of 93% at 6 h following drug administration and persisted over the next 12 h, with corresponding histology consistent with hemorrhagic necrosis resulting from vascular damage. These actions against tumor vasculature and the broad therapeutic window demonstrate the clinical potential of these drugs and warrant further study to elucidate the mechanisms responsible for the antivascular effects of combretastatin A-4.
Fabrication of highly porous scaffold materials based on functionalized oligolactides and preliminary results on their use in bone tissue engineering (2002)

Tissue engineering offers a promising new approach to repair bone defects. Its practical realisation is connected with the development of suitable scaffold materials. In the present work, functionalized oligolactides have been prepared and used as macromers for the scaffold fabrication The developed fabrication process leads to highly porous scaffolds, available in various shapes and sizes, with an open inter-connective pore structure and porosities up to 90%. Degradable or even osteoconductive components as well as biocompatible co-monomers can be used as additives to modulate the scaffold properties. Under in vitro conditions, the scaffolds exhibit a continuous degradation with varying degradation rates depending on their material composition. In vitro studies on the cultivation of osteoblasts on the scaffolds were performed and revealed their excellent biocompatibility. Cell growth on the scaffold surfaces and inside the scaffolds, formation of extracellular matrix and starting mineralization were detected by microscopical and histological analyses. Based on these results the developed materials are well-suited candidates for the design of tailor-made matrices in bone tissue engineering
Monoclonal antibody to the gastrin receptor on parietal cells recognizes a 78-kDa protein. (1987)

Four monoclonal antibodies reactive by immunofluorescence and by flow microfluorimetry with canine and porcine gastric parietal cell membranes were produced by fusion of mouse NS-1 myeloma cells with splenocytes from mice immunized with a population of canine gastric mucosal cells containing 60-70% parietal cells. One of these, an IgM antibody designated 2C1, reacted with the surface membranes of parietal cells by immunofluorescence, flow microfluorimetry, and immunogold electron microscopy; competed with 125I-labeled gastrin for binding to gastric cells; and inhibited by 56% maximal gastrin stimulation of [14C]aminopyrine uptake in parietal cells. The antibody immunoprecipitated 125I-labeled samples of a 78-kDa gastrin-binding protein purified from membrane extracts of porcine gastrin mucosa but did not recognize the same protein labeled covalently with 125I-labeled gastrin-(2-17)-hexadecapeptide. These observations suggest that the previously identified 78-kDa gastrin-binding protein is the gastrin receptor and that the antibody 2C1 is directed against the gastrin binding site of the gastrin receptor.
A physiological approach for continuously modeling user emotion in interactive play environments (2008)

Computer games have grown during recent years into a popular entertainment form with a wide variety of game types and a large consumer group spread across the world. As researchers develop novel play environments, computer and console game markets continue to grow rapidly, outperforming the film industry in terms of total revenues in many regions [6]. Although gaming technology has continued to evolve, researchers and computer game developers suffer from a lack of effective evaluation methods. My research interest is in how to quantify emotional experience when engaged with play technologies, by developing an evaluation methodology for entertainment environments that is as robust as methods for evaluating productivity. This paper summarizes a series of experiments used to design this new evaluative methodology.
Current status of intestinal and multivisceral transplantation (2016)

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1-3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.
Human Cytomegalovirus UL130 Protein Promotes Endothelial Cell Infection through a Producer Cell Modification of the Virion (2005)

Human cytomegalovirus (HCMV) growth in endothelial cells (EC) requires the expression of the UL131A-128 locus proteins. In this study, the UL130 protein (pUL130), the product of the largest gene of the locus, is shown to be a luminal glycoprotein that is inefficiently secreted from infected cells but is incorporated into the virion envelope as a Golgi-matured form. To investigate the mechanism of the UL130-mediated promotion of viral growth in EC, we performed a complementation analysis of a UL130 mutant strain. To provide UL130 in trans to viral infections, we constructed human embryonic lung fibroblast (HELF) and human umbilical vein endothelial cell (HUVEC) derivative cell lines that express UL130 via a retroviral vector. When the UL130-negative virus was grown in UL130-complementing HELF, the infectivity of progeny virions for HUVEC was restored to the wild-type level. In contrast, the infectivity of the UL130-negative virus for UL130-complementing HUVEC was low and similar to that of the same virus infecting control noncomplementing HUVEC. The UL130-negative virus, regardless of whether or not it had been complemented in the prior cycle, could form plaques only on UL130-complementing HUVEC, not control HUVEC. Because (i) both wild-type and UL130-transcomplemented virions maintained their infectivity for HUVEC after purification, (ii) UL130 failed to complement in trans the UL130-negative virus when it was synthesized in a cell separate from the one that produced the virions, and (iii) pUL130 is a virion protein, models are favored in which pUL130 acquisition in the producer cell renders HCMV virions competent for a subsequent infection of EC.