gebhart/patrepeval huggingface dataset:
Troglitazone metabolism and transporter effects in chimeric mice: a comparison between chimeric humanized and chimeric murinized FRG mice (2014)

1. The biotransformation, hepatic transporter and blood chemistry effects of troglitazone were investigated following 7 days of dosing at 600 mg/kg/day to chimeric murinized or humanized FRG mice, Mo-FRG and Hu-FRG mice, respectively. 2. Clinical chemistry and histopathology analysis revealed a significant drop in humanization over the time course of the study for the Hu-FRG mice but no significant changes associated with troglitazone treatment in either the Mo-FRG or the Hu-FRG models. No changes in transporter expression in livers of these mice were observed. Oxidative and conjugative metabolic pathways were identified with a 15- to 18-fold increase in formation of troglitazone sulfate in the Hu-FRG mice compared with the Mo-FRG mice in blood and bile, respectively. This resembles the troglitazone metabolism in human and these data are comparable with the formation of this metabolite in the chimeric uPA(+/+)/SCID mice. 3. However, larger amounts of troglitazone glucuronide were also observed in the Hu-FRG mouse compared with the Mo-FRG mouse which may be an effect of the drop in humanization of the Hu-FRG mouse during the study. 4. Highly humanized mice have a considerable potential in providing a useful first insight into circulating human metabolites of candidate drugs metabolized in the liver.
Studies on Organic Insecticides (1970)

A variety of the thiolsulfonates (III) of dihydronereistoxin and its homologs were synthesized. The thioltosylates (III: R4 = Ts) were converted into the 1,2-dithiolanes (IV) on treatment with alkali.
Transient Gene Transfer of IL-12 Regulates Chemokine Expression and Disease Severity in Experimental Arthritis (1998)

Murine collagen-induced arthritis (CIA) is characterized by pannus formation, cell infiltration, and cartilage erosion, and shares histologic and immunologic features with rheumatoid arthritis. Numerous cytokines are reportedly associated with RA and/or CIA; however, their mechanistic role is not clear. To determine the role of IL-12 in CIA, DBA/1 LacJ mice were administered 3 x 10(8) plaque-forming units of mIL-12 i.p. in a nonreplicating adenoviral vector (AdIL-12) on day 25 following primary type II collagen immunization. Our studies demonstrated that systemic transient overexpression of IL-12 accelerated disease progression and augmented the arthritis severity relative to mice expressing a replication-deficient, E1-deleted Ad5 construct. A likely mechanism for this increase in pathology was the increase in the expression of cytokines and chemokines known to play a proinflammatory role in disease. In particular, levels of murine IFN-gamma were significantly increased in mice overexpressing AdIL-12 relative to the replication-deficient, E1-deleted Ad5 construct. Interestingly, the C-X-C chemokine murine macrophage inflammatory protein-2, as well as the C-C chemokines murine monocyte chemoattractant protein-1 and murine macrophage inflammatory protein-1alpha were up-regulated by AdIL-12 relative to controls. In an additional set of studies, neutralization of endogenous IL-12 in CIA mice was shown to delay disease onset and attenuate disease severity. IFN-gamma levels in the mice receiving anti-IL-12 were significantly decreased in joint homogenates. These studies demonstrate that IL-12 is an important cytokine involved in controlling the production of chemokines/cytokines leading to the evolution of experimental arthritis.
Linear CMOS transconductance element for VHF filters (1989)

A differential transconductance element based on CMOS inverters is presented. With this circuit a linear, tunable integrator for very high-frequency continuous-time integrated filters can be made. This integrator has good linearity properties (THD < 0.04%, Vipp = 1.8 V), nondominant poles in the gigahertz range and a 40 dB DC gain.
Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients (2012)

Neutralizing antibodies against factor VIII (FVIII) remain the major complication in the replacement therapy of hemophilia A patients. To better understand the evolution of these antibodies it is important to generate comprehensive datasets which include both neutralizing and nonneutralizing antibodies, their isotypes, and IgG subclasses. We developed sensitive ELISAs to analyze FVIII-binding antibodies in different cohorts of hemophilia A patients and in healthy individuals. Our data reveal the prevalence of FVIII-binding antibodies among healthy individuals (n = 600) to be as high as 19%, with a prevalence of antibody titers > or =1:80 of 2%. The prevalence of FVIII-binding antibodies was 34% (5% for titers > or =1:80) in patients without FVIII inhibitors (n = 77), 39% (4% for titers > 1:80) in patients after successful immune tolerance induction therapy (n = 23), and 100% (n = 20, all titers > or =1:80) in patients with FVIII inhibitors. We found significant differences for IgG subclasses of FVIII-binding antibodies between the different study cohorts. IgG4 and IgG1 were the most abundant IgG subclasses in patients with FVIII inhibitors. Strikingly, IgG4 was completely absent in patients without FVIII inhibitors and in healthy subjects. These findings point toward a distinct immune regulatory pathway responsible for the development of FVIII-specific IgG4 associated with FVIII inhibitors.
RADIAL OPTIC NEUROTOMY FOR CENTRAL RETINAL VEIN OCCLUSION (2001)

Surgical decompression of CRVO via RON is a technically feasible and initially safe procedure that is associated with rapid reperfusion of the retina. Resolution of the intraretinal hemorrhage, edema, and ischemia may improve the visual prognosis in patients with this common retinal disorder.
Poly(dimethylsiloxane)‐Supported Ionogels with a High Ionic Liquid Loading (2014)

The immiscibility of poly(dimethylsiloxane) (PDMS) and ionic liquids (ILs) was overcome to create PDMS-supported IL gels (ionogels) with IL loadings of up to 80% by mass through a simple sol-gel reaction at room temperature. By stirring a mixture of a functionalized PDMS oligomer, formic acid, and an IL (or lithium-in-IL solution), a resin was formed that could be cast to create a freestanding, flexible ionogel. PDMS-supported ionogels exhibited favorable ionic conductivity (ca. 3 mS cm(-1)) and excellent mechanical behavior (elastic modulus: ca. 60 kPa; fatigue life: >5000 cycles; mechanically stable at temperatures up to 200 °C). The activation energy of ionic conductivity was shown to be nearly identical for the ionogel and the neat IL, in contrast to ionogel systems wherein the scaffold material is miscible with the IL. This similarity indicates that IL/scaffold chemical interactions are key to the understanding of ionogel electrical performance, especially at elevated temperatures.
Highly Reversible Lithium/Dissolved Polysulfide Batteries with Carbon Nanotube Electrodes (2013)

On paper: A lithium/dissolved polysulfide cell is developed utilizing a self-weaving, free-standing multiwalled carbon nanotube (MWCNT) “paper” as a host for the dissolved polysulfide active material and the reaction products. Exceptionally high capacities of 1600 mAh g−1 initially and 1411 mAh g−1 after 50 cycles (based on the mass of sulfur) are obtained at a rate of C/10.
Blocking temperature distribution and long-term stability of spin-valve structures with Mn-based antiferromagnets (2000)

We have determined the blocking temperature distribution Tb(T) in spin-valve sheet films with FeMn, IrMn, PtMn, NiMn and CrPdMn antiferromagnetic layers (AFM). We find a clear dependence of Tb(T) on the field applied during the measurement, which we link to the reversal state of the pinned layer through the torque applied on the AFM. Using fields large enough to fully reverse the pinned layer, NiMn and PtMn show little or no components of the blocking temperature below 150 °C, whereas both IrMn and CrPdMn (the latter in a “synthetic” AFM design) exhibit important low-temperature trailing edges of the distribution. Accelerated annealing experiments in a low reversed field equivalent to the self-demagnetizing field in a micron-size head allows us to access the time to failure and the failure activation energy from which the expected lifetime can be assessed. We find a general correlation between the expected lifetime and the fraction of loose (e.g., unblocked) AFM spins at any given temperature. Accordingly, only NiMn and PtMn are found to exhibit a sufficient long-term stability for disk-drive operations.
The Evaluation of a Biphasic Osteochondral Implant Coupled with an Electrospun Membrane in a Large Animal Model (2009)

Conventional clinical therapies are unable to resolve osteochondral defects adequately; hence, tissue engineering solutions are sought to address the challenge. A biphasic implant that was seeded with mesenchymal stem cells (MSCs) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a polycaprolactone (PCL) cartilage scaffold and a PCL-tricalcium phosphate osseous matrix. Autologous MSCs were seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL-collagen electrospun mesh, which served as a substitute for periosteal flap in preventing cell leakage. Controls without either implanted MSCs or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by superior glycosaminoglycan maintenance. This positive morphological outcome was supported by a higher relative Young's modulus, which indicated functional cartilage restoration. Bone ingrowth and remodeling occurred in all groups, with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover, healing was inferior at the patellar groove when compared with the medial condyle and this was attributed to the native biomechanical features.
Hypoxia abolishes transience of the heat-shock response in the methylotrophic yeast Hansenula polymorpha (2005)

The heat-shock response is conserved amongst practically all organisms. Almost invariably, the massive heat-shock protein (Hsp) synthesis that it induces is subsequently down-regulated, making this a transient, not a sustained, stress response. This study investigated whether the heat-shock response displays any unusual features in the methylotrophic yeast Hansenula polymorpha, since this organism exhibits the highest growth temperature (49-50 degrees C) identified to date for any yeast and grows at 47 degrees C without either thermal death or detriment to final biomass yield. Maximal levels of Hsp induction were observed with a temperature upshift of H. polymorpha from 30 degrees C to 47-49 degrees C. This heat shock induces a prolonged growth arrest, heat-shock protein synthesis being down-regulated long before growth resumes at such high temperatures. A 30 degrees C to 49 degrees C heat shock also induced thermotolerance, although H. polymorpha cells in balanced growth at 49 degrees C were intrinsically thermotolerant. Unexpectedly, the normal transience of the H. polymorpha heat-shock response was suppressed completely by imposing the additional stress of hypoxia at the time of the 30 degrees C to 49 degrees C temperature upshift. Hypoxia abolishing the transience of the heat-shock response appears to operate at the level of Hsp gene transcription, since the heat-induced Hsp70 mRNA was transiently induced in a heat-shocked normoxic culture but displayed sustained induction in a culture deprived of oxygen at the time of temperature upshift.
Activation of nuclear factor-κB during orthotopic liver transplantation in rats is protective and does not require kupffer cells (1999)

Reperfusion after liver transplantation results in the induction of tumor necrosis factor-alpha (TNFalpha) as well as activation of the stress-associated signaling proteins, c-Jun N-terminal kinase (JNK), activating protein-1 (AP-1), and nuclear factor-kappaB (NF-kappaB). To test the hypothesis that Kupffer cells are involved in the activation of signal transduction cascades during rat liver transplantation, Kupffer cells were depleted from donor liver using gadolinium chloride (GdCl3), and then the activation of JNK, AP-1, and NF-kappaB were assessed after transplantation. The results showed that GdCl3 treatment did not inhibit the activation of these stress signals, although transplanted livers were depleted of Kupffer cells and partially protected from reperfusion injury. Interleukin-6 (IL-6) and IL-10 messenger RNAs (mRNAs) were induced by transplantation, and the induction was suppressed by Kupffer cell depletion. The induction of TNFalpha mRNA and serum protein during liver transplantation was unaffected by GdCl3. These results show that Kupffer cells are not a major source of TNFalpha production after liver transplantation and that stress-signaling protein activation occurs independently of Kupffer cells. Transplantation strongly activates the transcription factor NF-kappaB, which blocks TNFalpha-mediated apoptosis in hepatocytes in vitro. To assess the role of NF-kappaB activation during liver transplantation, the IkappaBalpha superrepressor was expressed in donor livers using adenoviral-mediated gene transfer. Inhibition of NF-kappaB resulted in increased serum alanine aminotransferase levels after 3 hours of transplantation. In addition, the blockade of NF-kappaB resulted in increased histological tissue injury and increased hepatic terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, indicating apoptosis. These results show that NF-kappaB activation has a protective role in the transplanted liver.
Effect of Dispersant on Asphaltene Suspension Dynamics: Aggregation and Sedimentation (2010)

When oil is mixed with light alkanes, asphaltenes can precipitate out of oil solutions in a multistep process that involves the formation of nano and colloidal scale particles, the aggregation of asphaltene colloids, and their eventual sedimentation. Amphiphilic dispersants can greatly affect this process. The mechanism of the dispersant action in colloidal asphaltene suspensions in heptane has been shown through previous work to be due in part to a reduction in the size of the colloidal asphaltene particles with the addition of dispersant. However, previous studies of the sedimentation behavior revealed evidence of aggregation processes in the colloidal asphaltenes in heptane that has yet to be investigated fully. We investigate the effect of dispersants on this aggregation behavior through the use of dynamic light scattering, showing that both the amount of dispersant and the amount of heptane dilution can slow the onset of aggregation in colloidal asphaltene suspensions. An effective dispersant acts by suppressing colloidal aggregation in asphaltene suspensions, as shown by light scattering, and therefore also slows separation from the bulk, as revealed through macroscopic sedimentation experiments.
Clinical experience with bevacizumab in colorectal cancer. (2005)

Angiogenesis, the process of generating new capillary blood vessels, is a fundamental requirement for normal physiological processes including embryogenesis, reproductive function and wound healing. Angiogenesis is also implicated in various pathological conditions including age-related retinal macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis and cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against VEGF, has shown initial preclinical and clinical activity. This review discusses the critical role of VEGF and summarizes the available data on the use of bevacizumab in colorectal cancer.
Sulfophenylation of Polysulfones for Proton-Conducting Fuel Cell Membranes (2002)

Polysulfone has been sulfophenylated by lithiation and anionic reaction with 2-sulfobenzoic acid cyclic anhydride. This provides a new convenient method to modify polysulfones by attaching pendant sulfonated phenyl groups via ketone links. Membranes of the sulfophenylated polysulfones show promise for use in proton-exchange-membrane fuel cells. For example, a membrane with 0.9 sulfophenyl units per repeating polysulfone unit and 30 wt.-% water was found to have a proton conductivity of 32 mS/cm at 60°C.
Loss of HSulf-1 Up-regulates Heparin-binding Growth Factor Signaling in Cancer (2003)

Emerging data suggest that signaling by heparin-binding growth factors is influenced by the sulfation state of N-acetylglucosamine residues of heparan sulfate proteoglycans (HSPGs). Here we report that the recently identified protein HSulf-1, a heparin-degrading endosulfatase, encodes a cell surface-associated enzyme that diminishes sulfation of cell surface HSPGs. The message encoding this enzyme is readily detectable in a variety of normal tissues, including normal ovarian surface epithelial cells, but is undetectable in 5 of 7 ovarian carcinoma cell lines and markedly diminished or undetectable in approximately 75% of ovarian cancers. Similar down-regulation is also observed in breast, pancreatic, renal cells, and hepatocellular carcinoma lines. Re-expression of HSulf-1 in ovarian cancer cell lines resulted in diminished HSPG sulfation, diminished phosphorylation of receptor tyrosine kinases that require sulfated HSPGs as co-receptors for their cognate ligands, and diminished downstream signaling through the extracellular signal-regulated kinase pathway after treatment with fibroblast growth factor-2 or heparin-binding epidermal growth factor. Consistent with these changes, HSulf-1 re-expression resulted in reduced proliferation as well as sensitivity to induction of apoptosis by the broad spectrum kinase inhibitor staurosporine and the chemotherapeutic agent cisplatin. Collectively, these observations provide evidence that HSulf-1 modulates signaling by heparin-binding growth factors, and HSulf-1 down-regulation represents a novel mechanism by which cancer cells can enhance growth factor signaling.
Design and realization of optimal color filters for multi-illuminant color correction (1995)

A method of selecting optimal color filters to perform accurate multi-illuminant color correction is reviewed. The transmittances for a set of filters obtained by the method were provided to a color filter manufacturer. The manufacturer used a dichroic filter modeling program to produce transmittances that satisfied the physical constraints of the manufacturing process and approximated the optimal filter transmittances. The ideal and manufacturable filters are compared through computer simulation and their accuracy assessed during the CIE 1 ELab measure. The results show that the unconventional shapes of the optimal filters can be weil approximated by actual filters with slight degradation in performance.
A 1.5 V, 10-bit, 14 MS/s CMOS pipeline analog-to-digital converter (2002)

A 1.5 V, 10-bit, 14.3 MS/s pipeline analog-to-digital converter was implemented in a 0.6 /spl mu/m CMOS technology. Emphasis was placed on observing device reliability constraints at low voltage. MOS switches were implemented without low-threshold devices by using a bootstrapping technique that does not subject the devices to large terminal voltages. The converter achieved a peak SNDR of 58.5 dB, maximum DNL of 0.51 LSB, maximum INL of 0.66 LSB and a power consumption of 36 mW.
Copper-Catalyzed Direct Amination of Nitrobenzenes with <i>O</i>-Alkylhydroxylamines (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCopper-Catalyzed Direct Amination of Nitrobenzenes with O-AlkylhydroxylaminesShinzo Seko and Norio KawamuraView Author Information Organic Synthesis Research Laboratory, Sumitomo Chemical Co., Ltd., Tsukahara, Takatsuki, Osaka 569-11, Japan Cite this: J. Org. Chem. 1996, 61, 2, 442–443Publication Date (Web):January 26, 1996Publication History Received26 October 1995Published online26 January 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/jo951903rhttps://doi.org/10.1021/jo951903rrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1479Altmetric-Citations42LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Catalysts,Copper,Organic reactions,Substitution reactions Get e-Alerts
The <i>Schmidtea mediterranea</i> database as a molecular resource for studying platyhelminthes, stem cells and regeneration (2002)

Platyhelminthes are excellent models for the study of stem cell biology, regeneration and the regulation of scale and proportion. In addition, parasitic forms infect millions of people worldwide. Therefore, it is puzzling that they remain relatively unexplored at the molecular level. We present the characterization of approximately 3,000 non-redundant cDNAs from a clonal line of the planarian Schmidtea mediterranea. The obtained cDNA sequences, homology comparisons and high-throughput whole-mount in situ hybridization data form part of the S. mediterranea database (SmedDb; http://planaria.neuro.utah.edu). Sixty-nine percent of the cDNAs analyzed share similarities with sequences deposited in GenBank and dbEST. The remaining gene transcripts failed to match sequences in other organisms, even though a large number of these (approximately 80%) contained putative open reading frames. Taken together, the molecular resources presented in this study, along with the ability of abrogating gene expression in planarians using RNA interference technology, pave the way for a systematic study of the remarkable biological properties displayed by Platyhelminthes.
The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease (2016)

Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS) mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS), which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.