gebhart/patrepeval huggingface dataset:
Prohibitin Is a Novel Target Gene of Vitamin D Involved in Its Antiproliferative Action in Breast Cancer Cells (2006)

Previously, we showed that N-methyl-N-nitrosourea-transformed MCF12F breast epithelial cells exhibited differential expression of several genes, including up-regulation of prohibitin and elevated sensitivity to a relatively noncalcemic vitamin D analogue, 1alpha-hydroxyvitamin D5 [1alpha(OH)D5]. In this report, we evaluated the functional significance of prohibitin in relation to the cellular response to vitamin D. The in silico screening for putative transcription factor binding sites identified two vitamin D receptor (VDR)/retinoid X receptor binding sites in the 1-kb promoter region of prohibitin. Prohibitin up-regulation by 1alpha(OH)D5 treatment at both transcriptional and translational levels was confirmed by real-time reverse transcription-PCR and Western blot analysis in breast cancer cells, identifying prohibitin as a vitamin D target gene. Confocal microscopic analysis showed that prohibitin was localized in the nuclei of MCF-7 cells and a portion of prohibitin was colocalized with VDR, but direct physical interaction between VDR and prohibitin in cell lysates was not detectable. In MCF-7 cells expressing tetracycline-inducible prohibitin (Tet-On model), the overexpression of prohibitin inhibited cell proliferation and enhanced vitamin D-induced antiproliferative activity. Knockdown of prohibitin was accompanied by increased number of cells incorporating bromodeoxyuridine in the whole population and increased cell distribution in the S phase of cell cycle. In addition, prohibitin level had no significant effect on the vitamin D-induced transactivation of CYP24, a VDR target gene. This is the first report to suggest that prohibitin serves as a novel vitamin D target gene, which is involved in the antiproliferative action of vitamin D without affecting CYP24 transactivation in breast cancer cells.
Gene inoculation generates immune responses against human immunodeficiency virus type 1. (1993)

Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.
Automatic Alignment of Local Representations (2002)

We present an automatic alignment procedure which maps the disparate internal representations learned by several local dimensionality reduction experts into a single, coherent global coordinate system for the original data space. Our algorithm can be applied to any set of experts, each of which produces a low-dimensional local representation of a high dimensional input. Unlike recent efforts to coordinate such models by modifying their objective functions, our algorithm is invoked after training and applies an efficient eigensolver to post-process the trained models. The post-processing has no local optima and the size of the system it must solve scales with the number of local models rather than the number of original data points, making it more efficient than model-free algorithms such as Isomap or LLE.
Effect of Tacrolimus Hydrate (FK506) Ointment on Spontaneous Dermatitis in NC/Nga Mice (1998)

The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.
Novel Design for a Wearable, Rapidly Deployable, Wireless Noninvasive Triage Sensor (2005)

This paper presents a unique design for a low-power, continuous non-invasive sensor capable of remotely monitoring the five major vital signs of a patient. In particular, the sensor is designed for rapid attachment to the fingerbase of a patient by utilizing a clip-type mechanism and is comprised of a photoplethysmograph (PPG), a MEMS accelerometer, a temperature sensor, and a wireless node. Although hastily placed by a medic, the finger sensor will automatically find the location of a digital artery and acquire a clear, pulse signal: a micro-sensor array accommodates the location of the sensor attachment. Additionally, the PPG signal, although corrupted with the patient's motion in chaotic environment, will be recovered by using the MEMS accelerometer and an Active Noise Cancellation algorithm.
Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study (2010)

Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in the patients of group A, compared to those of group B. In group A norepinephrine was necessary in fewer patients (p = 0.002) and with a lower mean dose (p = 0.0001), additive infusion of epinephrine was needed in fewer patients (p = 0.001), while both were infused for a significant shorter infusion-period (p = 0.0001). Vasopressin administration (for group A) was associated with a higher 24 hour diuresis) (0.0001).In conclusion, low-dose of infused vasopressin during cardiopulmonary bypass and for the next 4 hours is beneficial for its postoperative hemodynamic profile, reduces the doses of requirements of catecholamines and contributes to prevention of the postcardiotomy vasoplegic shock in the patient with low ejection fraction who is receiving ACE preoperatively.
Telomere shortening and apoptosis in telomerase-inhibited human tumor cells (1999)

Despite a strong correlation between telomerase activity and malignancy, the outcome of telomerase inhibition in human tumor cells has not been examined. Here, we have addressed the role of telomerase activity in the proliferation of human tumor and immortal cells by inhibiting TERT function. Inducible dominant-negative mutants of hTERT dramatically reduced the level of endogenous telomerase activity in tumor cell lines. Clones with short telomeres continued to divide, then exhibited an increase in abnormal mitoses followed by massive apoptosis leading to the loss of the entire population. This cell death was telomere-length dependent, as cells with long telomeres were viable but exhibited telomere shortening at a rate similar to that of mortal cells. It appears that telomerase inhibition in cells with short telomeres lead to chromosomal damage, which in turn trigger apoptotic cell death. These results provide the first direct evidence that telomerase is required for the maintenance of human tumor and immortal cell viability, and suggest that tumors with short telomeres may be effectively and rapidly killed following telomerase inhibition.
Latency lags bandwith (2004)

As I review performance trends, I am struck by a consistent theme across many technologies: bandwidth improves much more quickly than latency. Here, I list a half-dozen performance milestones to document this observation, many reasons why it happens, a few ways to cope with it, a rule of thumb to quantify it, plus an example of how to design systems differently based on this observation.
Analysis of carbohydrate-protein interactions with synthetic N-linked neoglycoconjugate probes (1993)

Recently we have describe a simple efficient chemical method of generating an asparagine side-chain linker with beta-stereochemistry at the anomeric position of neutral oligosaccharides. We now report the 1-N-glycyl beta-derivatization of sialylated saccharides. Several neoglycoconjugates formed using these N-linked inter-mediates were investigated for their usefulness in probing carbohydrate-protein interactions. First, biotinyl derivatives of two xylose/fucose class plant-type oligosaccharides purified from horseradish peroxidase were effective in demonstrating the carbohydrate specificity of polyclonal anti-(horseradish peroxidase) antibodies. Secondly, a fluorescein-labelled asialo- and digalactosylated biantennary complex sugar was synthesized and shown to bind to a Ricinus communis agglutinin column. This galactose-specific recognition was abolished by treating this fluorescein-labelled oligosaccharide with jack bean beta-galactosidase. Finally, two 1-N-glycyl beta-saccharide derivatives were modified with thiophosgene to form their corresponding isothiocyanate derivatives. Coupling of these isothiocyanate derivatives of sugars to BSA, amino-derivatized polystyrene plates and glass-fibre discs resulted in multiple sugar presentation. The binding of an anti-N-acetylglucosamine monoclonal antibody to N,N'-diacetylchitobiose residues presented on BSA and solid supports was shown by e.l.i.s.a. Similarly the binding of concanavalin A to asialo-, agalactosylated biantennary complex oligosaccharide residues attached to BSA was demonstrated by a competitive e.l.i.s.a. Our results demonstrate that N-linked neoglycoconjugates could be made readily available and they are valuable tools for the detailed analyses of carbohydrates and carbohydrate-binding proteins.
Looking beyond the imaging plane: 3D needle tracking with a linear array ultrasound probe (2017)

Ultrasound is well suited for guiding many minimally invasive procedures, but its use is often precluded by the poor visibility of medical devices. When devices are not visible, they can damage critical structures, with life-threatening complications. Here, we developed the first ultrasound probe that comprises both focused and unfocused transducer elements to provide both 2D B-mode ultrasound imaging and 3D ultrasonic needle tracking. A fibre-optic hydrophone was integrated into a needle to receive Golay-coded transmissions from the probe and these data were processed to obtain tracking images of the needle tip. The measured tracking accuracy in water was better than 0.4 mm in all dimensions. To demonstrate the clinical potential of this system, insertions were performed into the spine and the uterine cavity, in swine and pregnant ovine models in vivo. In both models, the SNR ranged from 13 to 38 at depths of 22 to 38 mm, at out-of-plane distances of 1 to 15 mm, and at insertion angles of 33 to 42 degrees relative to the probe surface normal. This novel ultrasound imaging/tracking probe has strong potential to improve procedural outcomes by providing 3D needle tip locations that are co-registered to ultrasound images, while maintaining compatibility with current clinical workflow.
De novo design of an RNA tile that self-assembles into a homo-octameric nanoprism (2015)

Rational, de novo design of RNA nanostructures can potentially integrate a wide array of structural and functional diversities. Such nanostructures have great promises in biomedical applications. Despite impressive progress in this field, all RNA building blocks (or tiles) reported so far are not geometrically well defined. They are generally flexible and can only assemble into a mixture of complexes with different sizes. To achieve defined structures, multiple tiles with different sequences are needed. In this study, we design an RNA tile that can homo-oligomerize into a uniform RNA nanostructure. The designed RNA nanostructure is characterized by gel electrophoresis, atomic force microscopy and cryogenic electron microscopy imaging. We believe that development along this line would help RNA nanotechnology to reach the structural control that is currently associated with DNA nanotechnology.
Large B-cell Lymphoma Manifesting as an Invasive Cardiac Mass: Sustained Local Remission after Combination of Methotrexate and Rituximab (2002)

Cardiac tumor is an infrequent but serious manifestation of lymphoma and optimal management has not been well defined in these rare cases. Here we describe a patient who after autologous transplant for large B-cell lymphoma, relapsed with an invasive cardiac tumor, infiltrating the full thickness of the right myocardial wall. During therapy, she developed hemodynamic collapse due to complex atrial arrhythmias and had to be treated and stabilized in the intensive cardiac care unit. Despite initial significant regression of the cardiac tumor, new extranodal sites of lymphoma soon appeared in the skin, stomach and nervous system. Because of poor compliance, she was given salvage therapy with weekly four i.v. infusions of methotrexate and rituximab followed by monthly four maintenance cycles of rituximab alone. This produced an unexpected prolonged complete remission lasting 12 months, but she then developed a fatal leukemic phase. The relapse spared the heart and no cardiac abnormality was evident clinically or by any imaging technique. To the best of our knowledge this case, unique in terms of tumor size and extent of invasion, represents the first report of the treatment of invasive cardiac lymphoma using a combination of modest chemotherapy and rituximab.
Storage challenges at Los Alamos National Lab (2012)

There yet exist no truly parallel file systems. Those that make the claim fall short when it comes to providing adequate concurrent write performance at large scale. This limitation causes large usability headaches in HPC. Users need two major capabilities missing from current parallel file systems. One, they need low latency interactivity. Two, they need high bandwidth for large parallel IO; this capability must be resistant to IO patterns and should not require tuning. There are no existing parallel file systems which provide these features. Frighteningly, exascale renders these features even less attainable from currently available parallel file systems. Fortunately, there is a path forward.
Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. (1992)

In the skin, wounding initiates a complex array of physiological processes mediated by growth factors and inflammatory mediators which stimulate tissue repair and protect against infection. We report that primary cultures of human keratinocytes and a mouse keratinocyte cell line respond to the inflammatory stimuli gamma-interferon and lipopolysaccharide or tumor necrosis factor-alpha by producing nitric oxide and hydrogen peroxide, two reactive mediators that are important in nonspecific host defense. Nitric oxide is produced by the l-arginine- and NADPH-dependent enzyme, nitric oxide synthase. In murine keratinocytes, optimal enzymatic activity was found to be dependent on Ca2+ and calmodulin as well as on glutathione. Inflammatory mediators were also found to inhibit the growth of keratinocytes, an effect that could be reversed by a nitric oxide synthase inhibitor. Epidermal growth factor (EGF), which promotes wound healing by stimulating cellular proliferation, was found to be a potent antagonist of reactive nitrogen and reactive oxygen intermediate production by keratinocytes. EGF also reversed the growth inhibitory actions of the inflammatory mediators. These data suggest that nitric oxide produced by keratinocytes is important in the control of cellular proliferation during wound healing. Our findings that EGF effectively regulates the production of free radicals by keratinocytes may represent an important pathway by which this growth factor not only stimulates epidermal cell proliferation but also facilitates the resolution of inflammation following wounding.
Multi-Lateral Well Planning (1997)

Abstract Multi-lateral drilling and completion techniques involving cased primary and lateral well-bores have become increasingly prevalent in the oil and gas industry over the past five years. The experience gained in this time has permitted technological advances which now allow operators the flexibility to plan for increasingly complex multi-lateral applications. An effective planning process is essential to the successful drilling and completion of every multi-lateral project, whether it be a single open hole lateral application with no re-entry or isolation requirements or a complex combination of multiple laterals in different formations requiring fully selective reentry and isolation capabilities. This paper discusses the many technical issues which must be considered when planning the drilling and completion of multi-lateral wells. Consideration is given to the selection of the optimum drilling and completion systems for particular applications, and includes a comparison of the advantages and disadvantages of pre-milled casing window systems with those of downhole window milling techniques. Various drilling and completion issues are then discussed in detail as they relate to the planning of multi-lateral wells. These issues include well profile considerations; cementing options; re-entry and isolation requirements; well control considerations; constraints imposed by the technology and the importance of contingency planning. A case history which serves to illustrate the importance of a comprehensive planning process is presented. The paper presents a set of guidelines which are based on a continually increasing level of experience gained during the installation of over 100 casing window systems in various applications worldwide in addition to the extensive bench testing which has been carried out on these systems. This experience has resulted in enhanced planning processes which lead to reduced risk when implementing multi-lateral systems.
Molecular Cloning of Human and Rat Complementary DNA Encoding Androgen Receptors (1988)

Complementary DNAs (cDNAs) encoding androgen receptors were obtained from human testis and rat ventral prostate cDNA libraries. The amino acid sequence deduced from the nucleotide sequences of the cDNAs indicated the presence of a cysteine-rich DNA-binding domain that is highly conserved in all steroid receptors. The human cDNA was transcribed and the RNA product was translated in cell-free systems to yield a 76-kilodalton protein. The protein was immunoprecipitable by human autoimmune antibodies to the androgen receptor. The protein bound androgens specifically and with high affinity.
Role of the transcriptional activator, VirF, and temperature in the expression of the pYV plasmid genes of Yersinia enterocolitica (1992)

Upon incubation at 37°C in the absence of Ca<sup>2+</sup> ions, pathogenic yersiniae release high amounts of pYV plasmid-encoded proteins called Yops, involved in pathogenesis. Yersinia enterocolitica also express two outer membrane proteins, an adhesin called YadA and a lipoprotein called YIpA. The production of the Yops is co-ordinately regulated by a 20kb region of the plasmid referred to as the 'Ca<sup>2+</sup> dependence region' and containing at least four loci called virA, virB, virC, and virF. The 8.5kb virC region, involved in the specific transport of the Yops, is a single operon containing 13 open reading frames called yscA to yscM. Gene virF encodes a key transcriptional activator of the yop, yadA and ylpA genes. It is only transcribed at 37°C and its expression is modulated by a chromosome-encoded histone-like protein called YmoA. We show here that virF also controls the virC operon. By contrast, VirF is not essential for the induction of virA and virB. The VirF protein binds specifically to yop promoters. In particular, it protects the region spanning nucleotides -64 to -34 of yopH. In order to analyse the role of temperature in the induction of the yop regulon, we constructed Y. enterocolitica strains expressing virF from the tac promoter. In spite of the fact that virF was transcribed at 25°C, neither the Yops nor YadA were expressed at that temperature. This poor response to VirF at 25°C was at least partially due to a weak and slow transcription of the genes controlled by virF. Surprisingly, when cloned on pACYC184, gene yadA was expressed even in absence of VirF, but remained thermodependent. Hence temperature and virF are both required for the induction of the yop regulon. Among other possible roles, temperature could modify the structure of either the activator itself or the yop promoter. The fact that VirF binds in vitro to yop promoters at 25°C rules out the first hypothesis. In order to test the second hypothesis, we studied, in vivo, the activity of the yopH promoter in ymoA mutants. The yopH promoter became active in the absence of VirF, indicating that yop promoter activity depends upon chromatin structure. We conclude from these two observations that, in vivo, temperature is required to modify the DNA structure of the yop promoters in order to allow the action of the transcriptional activator.