gebhart/patrepeval huggingface dataset:
Toward controlling gene expression at will: Specific regulation of the erbB - 2 / HER - 2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks (1998)

To create a universal system for the control of gene expression, we have studied methods for the construction of novel polydactyl zinc finger proteins that recognize extended DNA sequences. Elsewhere we have described the generation of zinc finger domains recognizing sequences of the 5'-GNN-3' subset of a 64-member zinc finger alphabet. Here we report on the use of these domains as modular building blocks for the construction of polydactyl proteins specifically recognizing 9- or 18-bp sequences. A rapid PCR assembly method was developed that, together with this predefined set of zinc finger domains, provides ready access to 17 million novel proteins that bind the 5'-(GNN)6-3' family of 18-bp DNA sites. To examine the efficacy of this strategy in gene control, the human erbB-2 gene was chosen as a model. A polydactyl protein specifically recognizing an 18-bp sequence in the 5'-untranslated region of this gene was converted into a transcriptional repressor by fusion with Kr uppel-associated box (KRAB), ERD, or SID repressor domains. Transcriptional activators were generated by fusion with the herpes simplex VP16 activation domain or with a tetrameric repeat of VP16's minimal activation domain, termed VP64. We demonstrate that both gene repression and activation can be achieved by targeting designed proteins to a single site within the transcribed region of a gene. We anticipate that gene-specific transcriptional regulators of the type described here will find diverse applications in gene therapy, functional genomics, and the generation of transgenic organisms.
Novel Adeno-Associated Virus Serotypes Efficiently Transduce Murine Photoreceptors (2007)

Severe inherited retinal diseases, such as retinitis pigmentosa and Leber congenital amaurosis, are caused by mutations in genes preferentially expressed in photoreceptors. While adeno-associated virus (AAV)-mediated gene transfer can correct retinal pigment epithelium (RPE) defects in animal models, approaches for the correction of photoreceptor-specific diseases are less efficient. We evaluated the ability of novel AAV serotypes (AAV2/7, AAV2/8, AAV2/9, AAV2rh.43, AAV2rh.64R1, and AAV2hu.29R) in combination with constitutive or photoreceptor-specific promoters to improve photoreceptor transduction, a limiting step in photoreceptor rescue. Based on a qualitative analysis, all AAV serotypes tested efficiently transduce the RPE as well as rod and cone photoreceptors after subretinal administration in mice. Interestingly, AAV2/9 efficiently transduces Müller cells. To compare photoreceptor transduction from different AAVs and promoters in both a qualitative and quantitative manner, we designed a strategy based on the use of a bicistronic construct expressing both enhanced green fluorescent protein and luciferase. We found that AAV2/8 and AAV2/7 mediate six- to eightfold higher levels of in vivo photoreceptor transduction than AAV2/5, considered so far the most efficient AAV serotype for photoreceptor targeting. In addition, following subretinal administration of AAV, the rhodopsin promoter allows significantly higher levels of photoreceptor expression than the other ubiquitous or photoreceptor-specific promoters tested. Finally, we show that AAV2/7, AAV2/8, and AAV2/9 outperform AAV2/5 following ex vivo transduction of retinal progenitor cells differentiated into photoreceptors. We conclude that AAV2/7 or AAV2/8 and the rhodopsin promoter provide the highest levels of photoreceptor transduction both in and ex vivo and that this may overcome the limitation to therapeutic success observed so far in models of inherited severe photoreceptor diseases.
Pulmonary Congestion Predicts Cardiac Events and Mortality in ESRD (2013)

Pulmonary congestion is highly prevalent and often asymptomatic among patients with ESRD treated with hemodialysis, but whether its presence predicts clinical outcomes is unknown. Here, we tested the prognostic value of extravascular lung water measured by a simple, well validated ultrasound B-lines score (BL-US) in a multicenter study that enrolled 392 hemodialysis patients. We detected moderate-to-severe lung congestion in 45% and very severe congestion in 14% of the patients. Among those patients with moderate-to-severe lung congestion, 71% were asymptomatic or presented slight symptoms of heart failure. Compared with those patients having mild or no congestion, patients with very severe congestion had a 4.2-fold risk of death (HR=4.20, 95% CI=2.45-7.23) and a 3.2-fold risk of cardiac events (HR=3.20, 95% CI=1.75-5.88) adjusted for NYHA class and other risk factors. Including the degree of pulmonary congestion in the model significantly improved the risk reclassification for cardiac events by 10% (P<0.015). In summary, lung ultrasound can detect asymptomatic pulmonary congestion in hemodialysis patients, and the resulting BL-US score is a strong, independent predictor of death and cardiac events in this population.
What Does Microseismicity Tell Us About Hydraulic Fracturing? (2011)

Abstract Interpreting hydraulic fracture geometry isn't the only proven value application of microseismic imaging. With careful geophysical analysis, the microseismic deformation can also be determined in terms of the fracture strain that results in the source of the observed microseismic signals. The microseismic strain or deformation is potentially of interest, since the deformation associated with the hydraulic fracture controls the fracture dilation and complexity and ultimately the effectiveness of the stimulation. However, evidence is presented here which points to the microseismic being primarily a fast, shearing deformation in contrast to the relatively slow and tensile hydraulic fracture growth. Comparing the deformation energy balance between the recorded microseismic and the hydraulic fracture indicates that the microseismic is a very small component of total deformation. The majority of the fracture deformation is aseismic, beyond what is captured with conventional microseismic monitoring. The microseismic and hydraulic fracture deformations can be rationalized through a geomechanical model that honors the fracture mechanics and mass balance to simulate fracture growth. A workflow is presented that describes calibrating a geomechanical model using the location, timing and strains of the recorded microseismic to match the modeled interaction between the hydraulic fracture and pre-existing fractures. A rock physics model is also required to define synthetic microseismic data from the geomechanical model, for comparison with the observed microseismic data. The simplest form of calibration is a qualitative match between the relative microseismic density of either number of events or source strength. However, more advanced quantitative matches can also be made between the simulated and monitored microseismicity, by matching the microseismic displacements and mechanisms with the additional constraint of matching the energy balance. Through such a calibrated geomechanical model, the interrelation between stress, fractures, and injected fluid can be examined and used to characterize the hydraulic fracture growth. The validated hydraulic fracture model can then be incorporated into a reservoir simulator to ultimately predict the associated production characteristics. Therefore, beyond hydraulic fracture geometry, microseismic source deformation can be used to constrain a geomechanical model of the hydraulic fracture growth and thereby help describe the overall effectiveness of the stimulation.
All-Solid-State Rocking Chair Lithium Battery on a Flexible Al Substrate (1999)

All‐solid‐state thin film rocking chair lithium batteries were fabricated on thick, flexible aluminum foil substrates with the cell configuration of using sequential thin film deposition techniques. The total thickness of the device was . The battery cells incorporated thin film electrodes of highly lithiated vanadium oxide as an anode and vanadium oxide as a cathode. By controlling the lithium concentration in the lithiated vanadium oxide anode, an operating voltage ranging from 3 to was obtained. These cells with a active area delivered a discharge capacity of at room temperature and showed negligible capacity fade from the second cycle to more than 5800 cycles at a current density of . ©1999 The Electrochemical Society
Identification of membrane-bound CR1 (CD35) in human urine: evidence for its release by glomerular podocytes. (1994)

Complement receptor 1 (CR1) is present on erythrocytes (E-CR1), various leucocytes, and renal glomerular epithelial cells (podocytes). In addition, plasma contains a soluble form of CR1 (sCR1). By using a specific ELISA, CR1 was detected in the urine (uCR1) of normal individuals (excretion rate in 12 subjects, 3.12 +/- 1.15 micrograms/24 h). Contrary to sCR1, uCR1 was pelleted by centrifugation at 200,000 g for 60 min. Analysis by sucrose density gradient ultracentrifugation showed that uCR1 was sedimenting in fractions larger than 19 S, whereas sCR1 was found as expected in fractions smaller than 19 S. The addition of detergents reduced the apparent size of uCR1 to that of sCR1. After gel filtration on Sephacryl-300 of normal urine, the fractions containing uCR1 were found to be enriched in cholesterol and phospholipids. The membrane-association of uCR1 was demonstrated by analyzing immunoaffinity purified uCR1 by electron microscopy which revealed membrane-bound vesicles. The apparent molecular mass of uCR1 was 15 kD larger than E-CR1 and sCR1 when assessed by SDS-PAGE and immunoblotting. This difference in size could not be explained on the basis of glycosylation only, since pretreatment with N-glycosidase F reduced the size of all forms of CR1; however, the difference in regular molecular mass was not abrogated. The structural alleles described for E-CR1 were also found for uCR1. The urine of patients who had undergone renal transplantation contained alleles of uCR1 which were discordant with E-CR1 in 7 of 11 individuals, indicating that uCR1 originated from the kidney. uCR1 was shown to bind C3b-coated immune complexes, suggesting that the function of CR1 was not destroyed in urine. A decrease in uCR1 excretion was observed in 3 of 10 patients with systemic lupus erythematosus, corresponding to the three who had severe proliferative nephritis, and in three of three patients with focal sclerosis, but not in six other patients with proteinuria. Taken together, these data suggest that glomerular podocytes release CR1-coated vesicles into the urine. The function of this release remains to be defined, but it may be used as a marker for podocyte injury.
Navigating the Next-Generation Application Architecture (2009)

In today's Internet environment, hyperconnectivity and new and complex technologies require a shift from individualized proprietary enterprise applications to a more open and dependent world of cloud computing. This article identifies changes IT professionals must understand to make the necessary adjustments to practices in today's evolving development space.
Exhibit: Recollections of a Cartoonist (2017)

Special Collections & University Archives’ new exhibit, “Recollections of a Cartoonist: The Glenn “Marty” Stein Collection of Cartoon Art, 1955-2013” is now up in the department’s fifth floor exhibit area. The exhibit – based on Stein’s unpublished manuscript, “Recollections of a Cartoonist: Creating in Different World” – uses sketches, political cartoons, comic strips, and other artwork by Stein to highlight his career as a cartoonist. The bulk of the materials are from his manuscript collection housed in Special Collections & University Archives.
Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing (2003)

Neuropeptide Y (NPY), a 36-aa peptide, is widely distributed in the brain and peripheral tissues. Whereas physiological roles of NPY as a hormoneneurotransmitter have been well studied, little is known about its other peripheral functions. Here, we report that NPY acts as a potent angiogenic factor in vivo using the mouse corneal micropocket and the chick chorioallantoic membrane (CAM) assays. Unlike vascular endothelial growth factor (VEGF), microvessels induced by NPY had distinct vascular tree-like structures showing vasodilation. This angiogenic pattern was similar to that induced by fibroblast growth factor-2, and the angiogenic response was dose-dependent. In the developing chick embryo, NPY stimulated vascular sprouting from preexisting blood vessels. When [Leu(31)Pro(34)]NPY, a NPY-based analogue lacking high affinity for the NPY Y(2) receptor but capable of stimulating both Y(1) and Y(5) receptors, was used in the corneal model, no angiogenic response could be detected. In addition, NPY failed to induce angiogenesis in Y(2) receptor-null mice, suggesting that this NPY receptor subtype was mediating the angiogenic signal. In support of this finding, the Y(2) receptor, but not Y(1), Y(4), or Y(5) receptors, was found to be widely expressed in newly formed blood vessels. Further, a delay of skin wound healing with reduced neovascularization was found in Y(2) receptor-null mice. These data demonstrate that NPY may play an important role in the regulation of angiogenesis and angiogenesis-dependent tissue repair.
Data dependence speculation using data address prediction and its enhancement with instruction reissue (1998)

Introduces an instruction reissue mechanism in order to enhance dynamic data dependence speculation using data address prediction. Since instructions which are not data-dependent upon speculatively executed instructions are not squashed, the effect of data dependence speculation is enhanced. We extend the register update unit to reissue misspeculated instructions. The overhead caused by the extension is small, and thus it does not have any impact on processor cycle time. From the experimental evaluation, we have found that instruction reissue with dynamic data dependence speculation improves the processor performance even for those application programs whose performance is degraded when instruction squashing is used.
Involvement of Maize Dof Zinc Finger Proteins in Tissue-Specific and Light-Regulated Gene Expression (1998)

Dof is a novel family of plant proteins that share a unique and highly conserved DNA binding domain with one C2-C2 zinc finger motif. Although multiple Dof proteins associated with diverse gene promoters have recently been identified in a variety of plants, their physiological functions and regulation remain elusive. In maize, Dof1 (MNB1a) is constitutively expressed in leaves, stems, and roots, whereas the closely related Dof2 is expressed mainly in stems and roots. Here, by using a maize leaf protoplast transient assay, we show that Dof1 is a transcriptional activator, whereas Dof2 can act as a transcriptional repressor. Thus, differential expression of Dof1 and Dof2 may permit leaf-specific gene expression. Interestingly, in vivo analyses showed that although DNA binding activity of Dof1 is regulated by light-dependent development, its transactivation activity and nuclear localization are not. Moreover, in vivo transcription and in vitro electrophoretic mobility shift assays revealed that Dof1 can interact specifically with the maize C4 phosphoenolpyruvate carboxylase gene promoter and enhance its promoter activity, which displays a light-regulated expression pattern matching Dof1 activity. We propose that the evolutionarily conserved Dof proteins can function as transcriptional activators or repressors of tissue-specific and light-regulated gene expression in plants.
Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection (1997)

Eradication of E. bieneusi from the intestinal tract of patients with HIV infection and persistent immunosuppression is an achievable goal. Our study allowed the identification of oral fumagillin as a potential treatment for intestinal microsporidiosis due to E. bieneusi.
Effect of antioxidants on the motility and viability of cooled stallion spermatozoa. (2000)

The aim of the present study was to determine whether antioxidants in semen extenders help to maintain the motility and viability of stallion spermatozoa incubated for 48 h at 5 degrees C. Semen samples were collected from ten stallions and washed to remove the seminal plasma. Five antioxidant treatments (control, xanthurenic acid, glutathione, taurine and hypotaurine) were prepared in each of three different semen extenders (skimmed milk, skimmed milk + egg yolk, and cream gel extenders). The spermatozoa were suspended in 15 treatments (three extenders x five treatments). Sub-samples from each sample were analysed for sperm motility and viability at t = 0, 24 and 48 h. Significantly higher percentages of motile spermatozoa were maintained over 48 h in the skimmed milk + egg yolk extender compared with the other treatments. The percentage of progressively motile spermatozoa in the skimmed milk + egg yolk extender was significantly higher at t=0 and 24 h (P < 0.05) and tended to be higher after 48 h of incubation compared with the other treatments. Addition of xanthurenic acid to media maintained higher percentages of progressive motility and higher sperm velocities after 24 and 48 h incubation than did the other antioxidants (P < 0.05). The percentages of live spermatozoa in each of the three extenders were similar after 0 and 24 h incubation. However, the highest percentages of live spermatozoa were maintained in the skimmed milk + egg yolk extender and the lowest percentages of live spermatozoa were maintained in the cream gel extender after 48 h incubation (P < 0.05). Addition of the antioxidant xanthurenic acid to stallion sperm extender improved the motility of stallion spermatozoa incubated for 48 h at 5 degrees C compared with control media.
Estrogen suppression of erbB2 expression is associated with increased growth rate of ZR‐75‐1 human breast cancer cells in vitro and in nude mice (1991)

Amplification and enhanced expression of the erbB2/HER-2/neu gene has been associated with an increased growth rate and poor prognosis of human breast cancer. We have studied the relationship between erbB2 expression and the regulation of cell growth by estrogen and anti-estrogens in the human breast cancer cell line ZR-75-1 in vitro and in athymic nude mice, pS2 being used as a marker gene for estrogen-stimulated gene expression. Only low amounts of erbB2 mRNA were seen in the cells grown in vitro in the presence of estrogen which stimulated the cells to proliferate rapidly and induced the expression of pS2 mRNA. Upon hormone withdrawal, erbB2 mRNA and protein increased, while pS2 mRNA declined to an undetectable level and cell proliferation slowed down. Opposite but more rapid changes were observed upon estrogen addition. The anti-estrogens toremifene and tamoxifen inhibited estrogen induction of pS2 expression, down-regulation of erbB2 expression and proliferation of the ZR-75-I cells in a concentration-dependent manner. Similar results were obtained in nude mice. ZR-75-I cells formed tumors only in mice carrying estrogen pellets. In these tumors little erbB2 mRNA was seen. Concomitant administration of toremifene or tamoxifen increased erbB2 mRNA and abolished pS2 mRNA. Our results show that enhanced expression of erbB2 is associated with hormone deprivation and growth arrest of the estrogen-dependent breast cancer cell line ZR-75-I. Thus, in mammary epithelial cells, erbB2 may have important estrogen-regulated functions which are not related to cell proliferation.
Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. (1986)

This study initiates an effort to develop a safe vaccine against the acquired immunodeficiency syndrome (AIDS) that is caused by infection with a retrovirus designated human immunodeficiency virus (HIV) [formerly human T-cell lymphotropic virus type III (HTLV-III)]. Other retrovirus models have shown that purified external glycoprotein subunits are immunogenic. The external envelope glycoprotein of HIV (gp120) has a molecular size of 120 kDa, is responsible for virus infectivity, and induces strong antibody response in humans. Purified HIV virus preparations contain relatively little gp120 so HIV-infected cells were used as the antigen source. The gp120 was localized on cell membranes and was solubilized with low levels of nonionic detergent. The glycoprotein was further purified by immunoaffinity chromatography over a resin prepared from IgGs isolated from patients. Homogeneity was achieved following extensive dialysis and polyacrylamide gel electrophoresis. The gp120 isolated from infected cells was shown to be structurally identical by peptide maps to virion gp120 and the amino-terminal amino acid sequence confirmed that the molecule was specified by the HIV genome. Goat, horse, and rhesus monkey (Macaca mulatta) immune sera to gp120 precipitated the homologous antigen and neutralized the in vitro infectivity of HIV. The induction of neutralizing antibody indicates that a gp120 subunit vaccine against HIV is theoretically possible.
Increase in cytosolic free Ca2+ in corticotropin-stimulated white adipocytes (1994)

The mechanism of the adrenal corticotropin hormone (ACTH)-stimulated increase in cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in rat white adipocytes. ACTH at concentrations > 10 mU/ml caused a rapid and transient increase in [Ca2+]i followed by a small but sustained elevation of [Ca2+]i. A similar phenomenon was also induced by alpha-adrenergic or synthetic ACTH stimulation. The effect of norepinephrine (NE) plus ACTH on [Ca2+]i was nearly additive. Pertussis toxin completely blocked the ability of ACTH or NE to increase [Ca2+]i. NE but not ACTH caused a significant increase in inositol 1,4,5-trisphosphate levels. ACTH caused a rapid and transient accumulation of [3H]arachidonic acid (AA) and a marked loss of [3H]AA from phosphatidylinositol (PI) and phosphatidylcholine (PC) 10 s after stimulation. Neither a lipoxygenase inhibitor nor a dual inhibitor of cyclooxygenase and lipoxygenase blocked the increases in [Ca2+]i and the accumulation of [3H]AA in response to ACTH. On the other hand, either pertussis toxin or phospholipase A2 inhibitor drastically blocked both parameters in response to ACTH. These results indicate that ACTH stimulates AA release from PC and PI via the activation of phospholipase A2 coupled with pertussis toxin-sensitive GTP-binding protein(s), which leads to an increase in [Ca2+]i in rat white adipocytes.
Latinamerican intellectual courses : Nuestra América from José Martí and Ariel from José Enrique Rodó : the condition of production and the backwash processo of the identity though (2004)

Esse artigo aborda os textos de José Martí e José Enrique Rodó, produzidos entre o final do século XIX e início do século XX, sobre os problemas enfrentados pelos países latino-americanos naquela época. Tem como objetivo descobrir a existência de “redes intelectuais” na América Latina e analisar os processos de produção e repercussão dessas reflexões originais, antiimperialistas, antiutilitaristas e genuinamente latino-americanas.
A severe case of mandibuloacral dysplasia in a girl (1992)

We report on a 16-year-old girl with mandibuloacral dysplasia, a rare progeroid syndrome. She presented at age 2 years with thin skin on the limbs, characteristic face with prominent eyes, a pinched nose, micrognathia, and small mouth. Hair was sparse and brittle. The terminal phalanges were hypoplastic and showed acroosteolysis. On follow-up, hands and feet showed progressive camptodactyly of fingers and toes with total loss of subcutaneous tissue. The clavicles were hypoplastic. Intelligence was normal. We review the literature on the subject and discuss differential diagnosis.