gebhart/patrepeval huggingface dataset:
Angiotensin II–dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis (2013)

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by a high risk for aneurysm and dissection throughout the arterial tree and phenotypically resembles Marfan syndrome. LDS is caused by heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result in diminished TGF-β signaling; however, aortic surgical samples from patients show evidence of paradoxically increased TGF-β signaling. We generated 2 knockin mouse strains with LDS mutations in either Tgfbr1 or Tgfbr2 and a transgenic mouse overexpressing mutant Tgfbr2. Knockin and transgenic mice, but not haploinsufficient animals, recapitulated the LDS phenotype. While heterozygous mutant cells had diminished signaling in response to exogenous TGF-β in vitro, they maintained normal levels of Smad2 phosphorylation under steady-state culture conditions, suggesting a chronic compensation. Analysis of TGF-β signaling in the aortic wall in vivo revealed progressive upregulation of Smad2 phosphorylation and TGF-β target gene output, which paralleled worsening of aneurysm pathology and coincided with upregulation of TGF-β1 ligand expression. Importantly, suppression of Smad2 phosphorylation and TGF-β1 expression correlated with the therapeutic efficacy of the angiotensin II type 1 receptor antagonist losartan. Together, these data suggest that increased TGF-β signaling contributes to postnatal aneurysm progression in LDS.
Homozygous deletions within chromosomal bands 9p21-22 in bladder cancer. (1994)

The loss of DNA sequences on chromosomal bands 9p21-22 has been documented in a variety of malignancies including leukemias, gliomas, lung cancers, and melanomas. Because of the high incidence of monosomy 9 detected by both cytogenetics and loss of heterozygosity studies in bladder cancer, we examined seven bladder cancer cell lines for deletions in this region. Using seven DNA probes that span the region of 9p21-22 as well as a functional assay for methylthioadenosine phosphorylase (MTAP), which maps to 9p21, we found four cell lines that had small homozygous deletions. These deletions map centromeric to the interferon (IFN) gene cluster and telomeric to D9S171. Only one of the cell lines with deletions had a cytogenetically evident lesion in this chromosomal region. Preliminary loss of heterozygosity studies with 10 primary bladder cancer specimens using 10 markers spanning chromosome 9 revealed loss of heterozygosity at the IFN locus with retention of heterozygosity with more centromeric 9p markers and all informative 9q markers in the tumor of one patient. These data suggest that loss of a tumor suppressor gene on 9p21-22, which may represent a general pathway of oncogenesis, is important in bladder cancer development.
Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease (2013)

Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.
Cranioplasty for Large Skull Defects with PMMA (Polymethylmethacrylate) or Tutoplast® Processed Autogenic Bone Grafts (2007)

Cosmetic results were more satisfactory with Tutoplast processed autografts, and the operating time for unilateral surgery was shorter. Complication rates were similar. Resorption occurred in all children and adolescents, but was rare in adults. Thus, Tutoplast processed autogenic bone grafts can be a reasonable alternative to other methods of cranioplasty in adult patients with large craniotomy defects. Cranioplasty in children and adolescents remains an unsolved problem.
Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. (1986)

There is considerable evidence in animal tumor systems that antitumor immunity is modulated by suppressor T-lymphocytes, and that the cytotoxic drug cyclophosphamide (CY) can abrogate that suppression. We measured the acquisition of delayed-type hypersensitivity (DTH) to autologous melanoma cells in 19 patients with metastatic malignant melanoma. The patients were treated with an autologous melanoma cell vaccine, either given alone, or given 3 days after the administration of CY, 300 mg/m2 i.v. The DTH responses of CY-pretreated patients were significantly greater than those of control (vaccine only) patients. Thus, after two vaccine treatments, the median DTH responses (mm induration) were as follows: controls, 4 mm; CY pretreated, 11 mm; P = 0.034, Mann-Whitney U test, 2-tailed. Whereas seven of eight CY-pretreated patients developed DTH to autologous melanoma cells of at least 5 mm, only two of seven controls did so (P = 0.034, Fisher's exact test). Two patients had significant antitumor responses to treatment with CY plus vaccine, consisting of complete disappearance of skin metastases and a pulmonary nodule in one, and regression of s.c. and liver metastases in the other. Both patients remain free of melanoma after 42 and 33 mo, respectively.
Polarization insensitive all-optical up-conversion for ROF systems based on parallel pump FWM in a SOA (2009)

We have proposed and experimentally investigated polarization insensitive all-optical up-conversion for ROF system based on FWM in a semiconductor optical amplifier (SOA). The parallel pump is generated based on odd-order optical sidebands and carrier suppression using an external intensity modulator and a cascaded optical filter. Therefore, the two pumps are always parallel and phase locked, which makes system polarization insensitive. After FWM in a SOA and optical filtering, similar to single sideband (SSB) 40 GHz optical millimeter-wave is generated only using 10 GHz RF as local oscillator (LO). The receiver sensitivity at a BER of 10(-9) for the up-converted signals is -28.4 dBm. The power penalty for the up-converted downstream signals is smaller than 1 dBm after 20 km SSMF-28 transmission.
Ultrasoft and High Magnetic Moment NiFe Film Electrodeposited From a Cu$^2+$Contained Solution (2006)

We report a methodology to fabricate ultrasoft NiFe films via electrodeposition in a sulfate solution. With a little addition of Cu <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2+</sup> into the solution, NiFe films become extremely soft: typically, the film coercivities in the hard and easy axes are 0.03 and 0.15 Oe, respectively. The maximum relative permeability is also significantly increased to the order of 1times10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> . Meanwhile, these achieved ultrasoft NiFe films show a small but finite anisotropic field and high magnetic moments ranging from 1.1 to 1.65 T. These kinds of films can be potentially applied in current and future magnetic recording systems as well as biotechnological and microelectronic devices
Tailoring Hydrogel Adhesion to Polydimethylsiloxane Substrates Using Polysaccharide Glue (2013)

Hydrogel meets silicone: The chemical functionalization of a polydimethylsiloxane (PDMS) surface with polysaccharide “glue” induces a strong, permanent adhesion between the hydrogel and PDMS. This hydrogel-coated silicone substrate was useful for controlling cellular organization under mechanical stretching (see picture) and also in fabricating microfluidic devices filled with the gel.
Upregulation of MMP-2 by HMGA1 Promotes Transformation in Undifferentiated, Large-Cell Lung Cancer (2009)

Although lung cancer is the leading cause of cancer death worldwide, the precise molecular mechanisms that give rise to lung cancer are incompletely understood. Here, we show that HMGA1 is an important oncogene that drives transformation in undifferentiated, large-cell carcinoma. First, we show that the HMGA1 gene is overexpressed in lung cancer cell lines and primary human lung tumors. Forced overexpression of HMGA1 induces a transformed phenotype with anchorage-independent cell growth in cultured lung cells derived from normal tissue. Conversely, inhibiting HMGA1 expression blocks anchorage-independent cell growth in the H1299 metastatic, undifferentiated, large-cell human lung carcinoma cells. We also show that the matrix metalloproteinase-2 (MMP-2) gene is a downstream target upregulated by HMGA1 in large-cell carcinoma cells. In chromatin immunoprecipitation experiments, HMGA1 binds directly to the MMP-2 promoter in vivo in large-cell lung cancer cells, but not in squamous cell carcinoma cells. In large-cell carcinoma cell lines, there is a significant, positive correlation between HMGA1 and MMP-2 mRNA. Moreover, interfering with MMP-2 expression blocks anchorage-independent cell growth in H1299 large-cell carcinoma cells, indicating that the HMGA1-MMP-2 pathway is required for this transformation phenotype in these cells. Blocking MMP-2 expression also inhibits migration and invasion in the H1299 large-cell carcinoma cells. Our findings suggest an important role for MMP-2 in transformation mediated by HMGA1 in large-cell, undifferentiated lung carcinoma and support the development of strategies to target this pathway in selected tumors.
Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice (1994)

Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and morphology. In contrast to previous and concurrent studies with adult human bone marrow (BM), treatment with human cytokines was not required to establish high-level human cell engraftment, suggesting that neonatal cells either respond differently to the murine microenvironment or they provide their own cytokines in a paracrine fashion. Committed and multipotential myelo-erythroid progenitors were detected using in vitro colony assays and FACS analysis of the murine BM showed the presence of immature CD34+ cells. In addition, human hematopoiesis was maintained for at least 14 weeks providing further evidence that immature hematopoietic precursors had engrafted the murine BM. This in vivo model for human cord blood-derived hematopoiesis will be useful to gain new insights into the biology of neonatal hematopoietic cells and to evaluate their role in gene therapy. There is growing evidence that there are ontogeny-related changes in immature human hematopoietic cells, and therefore, the animal models we have developed for adult and neonatal human hematopoiesis provide useful tools to evaluate these changes in vivo.
Investigating Matrix/Fracture Transfer via a Level Set Method for Drainage and Imbibition (2009)

Summary Multiphase flow and transport phenomena within fractures are important because fractures often represent primary flow conduits in otherwise low-permeability rock. Flows within the fracture, between the fracture and the adjacent matrix, and through the pore space within the matrix typically happen on different length and time scales. Capturing these scales experimentally is difficult. It is, therefore, useful to have a computational tool that establishes the exact position and shape of fluid/fluid interfaces in realistic fracture geometries. The level set method (LSM) is such a tool. Our progressive quasistatic (PQS) algorithm based on the level set method finds detailed, pore-level fluid configurations satisfying the Young-Laplace equation at a series of prescribed capillary pressures. The fluid volumes, contact areas, and interface curvatures are readily extracted from the configurations. The method automatically handles topological changes of the fluid volumes as capillary pressure varies. It also accommodates arbitrarily complicated shapes of confining solid surfaces. Here, we apply the PQS method to analytically defined fracture faces and aperture distributions, to geometries of fractures obtained from high-resolution images of real rocks, and to idealized fractures connected to a porous matrix. We also explicitly model a fracture filled with proppant, using a cooperative rearrangement algorithm to construct the proppant bed and the surrounding matrix. We focus on interface movement between matrix and fracture, and snap-off of nonwetting phase into the fracture during imbibition in particular. The extent to which nonwetting phase is trapped in fracture/enclosed gaps is very sensitive to the direction of the displacement. Simulated drainage curves in matrix differ systematically from drainage curves in fracture and matrix with transfer between them. In a reservoir simulation, the latter might serve as an upscaled drainage curve input for a fractured medium.
A differential detection scheme for transmit diversity (2003)

We present a transmission scheme for exploiting diversity given by two transmit antennas when neither the transmitter nor the receiver has access to channel state information. The new detection scheme can use PSK constellations and encoding is simple. At the receiver, decoding is achieved with low decoding complexity. The transmission provides full spatial diversity and requires no channel state side information at the receiver. The scheme can be thought as the extension of differential detection schemes to two transmit antennas.
The Novel Antiarrhythmic Drug Dronedarone: Comparison with Amiodarone (2006)

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.
Simultaneous two-photon spectral and lifetime fluorescence microscopy (2004)

When a fluorescence photon is emitted from a molecule within a living cell it carries a signature that can potentially identify the molecule and provide information on the microenvironment in which it resides, thereby providing insights into the physiology of the cell. To unambiguously identify fluorescent probes and monitor their physiological environment within living specimens by their fluorescent signatures, one must exploit as much of this information as possible. We describe the development and implementation of a combined two-photon spectral and lifetime microscope. Fluorescence lifetime images from 16 individual wavelength components of the emission spectrum can be acquired with 10-nm resolution on a pixel-by-pixel basis. The instrument provides a unique visualization of cellular structures and processes through spectrally and temporally resolved information and may ultimately find applications in live cell and tissue imaging.
Hepcidin for Clinicians (2009)

Despite the use of erythropoiesis-stimulating agents (ESAs), the anemia of chronic kidney disease (CKD) can be resistant to therapy. Both absolute and functional iron deficiency along with inflammation can contribute to ESA resistance and can be difficult to identify with current-day markers of iron storage. Hepcidin, a small peptide produced by the liver, is a recently discovered key regulator of iron homeostasis. Via regulation of ferroportin, hepcidin inhibits intestinal iron absorption and iron release from macrophages and hepatocytes. Because of its renal elimination and regulation by inflammation, it is possible that progressive renal insufficiency leads to altered hepcidin metabolism, subsequently affecting enteric absorption of iron and the availability of iron stores. Thus, hepcidin likely plays a major role in the anemia of CKD as well as ESA resistance. This article discusses the biologic actions and regulation of hepcidin along with reviewing studies of hepcidin in CKD.
Identification and Monitoring of Host Cell Proteins by Mass Spectrometry Combined with High Performance Immunochemistry Testing (2013)

Biotherapeutics are often produced in non-human host cells like Escherichia coli, yeast, and various mammalian cell lines. A major focus of any therapeutic protein purification process is to reduce host cell proteins to an acceptable low level. In this study, various E. coli host cell proteins were identified at different purifications steps by HPLC fractionation, SDS-PAGE analysis, and tryptic peptide mapping combined with online liquid chromatography mass spectrometry (LC-MS). However, no host cell proteins could be verified by direct LC-MS analysis of final drug substance material. In contrast, the application of affinity enrichment chromatography prior to comprehensive LC-MS was adequate to identify several low abundant host cell proteins at the final drug substance level. Bacterial alkaline phosphatase (BAP) was identified as being the most abundant host cell protein at several purification steps. Thus, we firstly established two different assays for enzymatic and immunological BAP monitoring using the cobas® technology. By using this strategy we were able to demonstrate an almost complete removal of BAP enzymatic activity by the established therapeutic protein purification process. In summary, the impact of fermentation, purification, and formulation conditions on host cell protein removal and biological activity can be conducted by monitoring process-specific host cell proteins in a GMP-compatible and high-throughput (> 1000 samples/day) manner.
Evaluation of a live attenuated, cold-adapted parainfluenza virus type 3 vaccine in children (1992)

Cold passage 18 (CP18) parainfluenza virus type 3 (PIV-3) vaccine was evaluated in a double-blind, randomized, placebo-controlled study of 95 infants and young children. None of 19 seropositive older children 41 to 124 months old became infected when 10(6) 50% tissue culture infective doses (TCID50) of vaccine virus was administered intranasally. Two of nine and seven of twenty-four young seropositive children given 10(5) or 10(6) TCID50 of CP18 PIV-3, respectively, became infected. Each of four seronegative young children became infected, as indicated by virus shedding and antibody response, when given 10(6) TCID50 of CP18 PIV-3 intranasally. Illness was not observed in seropositive children. Two of the four seronegative children developed a mild illness characterized by rhinorrhea and wheezing on auscultation; none had fever. In one case, vaccine virus spread from a vaccine to a sibling control but did not cause illness. The vaccine is attenuated relative to wild-type PIV-3, but additional attenuation will be required to achieve a satisfactory PIV-3 vaccine.
The Potential Effects of Climate Change on the Productivity, Costs, and Returns of U.S. Dairy Production (2011)

Climate change could affect the costs and returns of livestock production by altering the thermal environment of animals thereby affecting animal health, reproduction, and the efficiency by which livestock convert feed into retained products (especially meat and milk). In the United States, concentrated livestock operations are located in a variety of climatic regions, suggesting that the industry could adapt to future changes in temperature and weather patterns resulting from global warming. However, this adaption could be costly. We use nationally representative data on dairy producers coupled with finely-scaled climate data to empirically examine how producers’ costs, returns, and production systems vary across U.S. regions as a function of the local climate.
A STUDY OF THE INHIBITORY EFFECTS OF SCH 28080 ON GASTRIC SECRETION IN MAN (1982)

1 SCH 28080 (2-methyl-8-(phenyl methoxy) imidazo-(1-2-a) pyrine-3-acetonitrile) is a novel drug unrelated to existing anti-ulcer agents. 2 The effect of placebo and increasing doses of the drug on gastric acid output and peptic activity was examined in four healthy men, in the resting state and following pentagastrin stimulation. 3 Significant inhibition of gastric acid secretion and peptic activity occurred with the 50 mg dose in both the stimulated and unstimulated states. Approximately 90% inhibition of acid output was achieved with the 200 mg dose. 4 Antisecretory activity of SCH 28080 is confirmed in man. This drug or an analogue may have potential in anti-ulcer therapy.