gebhart/patrepeval huggingface dataset:
Pharmacokinetics of Subcutaneously Administered CB2679d/ISU304 in Wild-Type and Hemophilia B Mice (2016)

Abstract The rapid clearance of factor IX (FIX) necessitates frequent intravenous IV administrations to achieve effective prophylaxis for patients with hemophilia B (HB). Subcutaneous (SC) administration would be a preferred route of administration but has been limited by low bioavailability and potency of the marketed FIX products. CB2679d/ISU304 with enhanced biological properties was developed using a rational protein design approach and has resistance to inhibition by ATIII, increased affinity for FVIIIa, increased catalytic activity and resultant 20-fold enhanced potency in vitro (clotting activity) and in vivo (the tail clip model) and 8-fold increased duration of aPTT activity in vivo compared to recombinant wild-type FIX dosed at the same mass. ISU304 (4622 IU/mg) was injected into HB mice SC with a single dose ISU304 at 0.02, 0.05 or 0.15 mg/kg and sampled at 4, 6, 8, 24 hours. Groups of wild-type mice received ISU304 0.02, 0.05 or 0.15 mg/kg SC and BeneFIX (273 IU/mg) 0.15 mg/kg SC, and sampled at 0.25, 1, 4, 8, 24, 48, 72, and 96 hours. Daily SC injection in HB mice of ISU304 at 0.05 mg/kg was sampled at 24, 48, 72 and 96 hours. FIX antigen was measured using a sandwich ELISA and FIX activity was measured using a one-stage clotting assay on Stago Compact. Pharmacokinetics of FIX was performed using PKSolver. There was a dose-dependent increase of plasma FIX antigen with SC ISU304. Mass-based pharmacokinetic profiles of ISU304 (t1/2, 18 hours; Tmax,8 hours, Bioavailability, 19-22%) were similar to those of BeneFIX (t1/2, 20 hours; Tmax, 8 hours, Bioavailability, 16%). Due to ISU304 high specific activity, SC dose of ISU304 yields much higher FIX activities in mouse plasma compared with the same mass dose of BeneFIX. Daily SC dosing of ISU304 230 IU/kg reached steady-state plateau FIX 8% activity after three injections. The bioavailability and increased potency of CB2679d/ISU304 facilitates the initiation of the Phase 1 subcutaneous dosing study in individuals with hemophilia B. Figure 1 Figure 1. Table 1 Table 1. Figure 2 Figure 2. Disclosures Hong: ISU Abxis: Employment. Levy:Catalyst Biosciences: Employment. Jung:ISU Abxis: Employment. Park:ISU Abxis: Employment. Seo:ISU Abxis: Employment. Seo:ISU Abxis: Employment. Madison:Catalyst Biosciences: Employment, Equity Ownership, Patents &amp; Royalties.
Role of tissue optics and pulse duration on tissue effects during high-power laser irradiation (1993)

The primary zone of deposition of optical energy is called here the optical zone. The tissue absorption, tissue scattering, laser-beam diameter, or size of pigmented structures can specify the size of the optical zone. The initial optical zone may be altered by the formation of char during high-irradiance laser exposure, and a spectrum of char absorbance is presented. The relationship between the optical zone and the pulse duration specifies the type of laser-tissue interaction that may occur. Short laser pulses can confine thermal energy and/or stress energy within the optical zone, which maximizes photothermal and photomechanical mechanisms of interaction.
Photochemical preparation of luminescent platinum(IV) complexes via oxidative addition on luminescent platinum(II) complexes (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemical preparation of luminescent platinum(IV) complexes via oxidative addition on luminescent platinum(II) complexesL. Chassot, A. Von Zelewsky, D. Sandrini, M. Maestri, and V. BalzaniCite this: J. Am. Chem. Soc. 1986, 108, 19, 6084–6085Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://doi.org/10.1021/ja00279a092RIGHTS & PERMISSIONSArticle Views702Altmetric-Citations104LEARN 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 InReddit PDF (251 KB) Get e-Alerts Get e-Alerts
Mapping the Structural Determinants Responsible for Enhanced T Cell Activation to the Immunogenic Adeno-Associated Virus Capsid from Isolate Rhesus 32.33 (2013)

Avoiding activation of immunity to vector-encoded proteins is critical to the safe and effective use of adeno-associated viral (AAV) vectors for gene therapy. While commonly used serotypes, such as AAV serotypes 1, 2, 7, 8, and 9, are often associated with minimal and/or dysfunctional CD8(+) T cell responses in mice, the threshold for immune activation appears to be lower in higher-order species. We have modeled this discrepancy within the mouse by identifying two capsid variants with differential immune activation profiles: AAV serotype 8 (AAV8) and a hybrid between natural rhesus isolates AAVrh32 and AAVrh33 (AAVrh32.33). Here, we aimed to characterize the structural determinants of the AAVrh32.33 capsid that augment cellular immunity to vector-encoded proteins or those of AAV8 that may induce tolerance. We hypothesized that the structural domain responsible for differential immune activation could be mapped to surface-exposed regions of the capsid, such as hypervariable regions (HVRs) I to IX of VP3. To test this, a series of hybrid AAV capsids was constructed by swapping domains between AAV8 and AAVrh32.33. By comparing their ability to generate transgene-specific T cells in vivo versus the stability of transgene expression in the muscle, we confirmed that the functional domain lies within the VP3 portion of the capsid. Our studies were able to exclude the regions of VP3 which are not sufficient for augmenting the cellular immune response, notably, HVRs I, II, and V. We have also identified HVR IV as a region of interest in conferring the efficiency and stability of muscle transduction to AAVrh32.33.
Polysaccharide−Poly(ethylene glycol) Star Copolymer as a Scaffold for the Production of Bioactive Hydrogels (2005)

The production of polysaccharide-derivatized surfaces, polymers, and biomaterials has been shown to be a useful strategy for mediating the biological properties of materials, owing to the importance of polysaccharides for the sequestration and protection of bioactive proteins in vivo. We have therefore sought to combine the benefits of polysaccharide derivatization of polymers with unique opportunities to use these polymers for the production of bioactive, noncovalently assembled hydrogels. Accordingly, we report the synthesis of a heparin-modified poly(ethylene glycol) (PEG) star copolymer that can be used in the assembly of bioactive hydrogel networks via multiple strategies and that is also competent for the delivery of bioactive growth factors. A heparin-decorated polymer, synthesized by the reaction of thiol end-terminated four-arm star PEG (M(n) = 10 000) with maleimide functionalized low molecular weight heparin (LMWH, M(r) = 3000), has been characterized via (1)H NMR spectroscopy and size-exclusion chromatography; results indicate attachment of the LMWH with at least 73% efficiency. Both covalently and noncovalently assembled hydrogels can be produced from the PEG-LMWH conjugate. Viscoelastic noncovalently assembled hydrogels have been formed on the basis of the interaction of the PEG-LMWH with a PEG polymer bearing multiple heparin-binding peptide motifs. The binding and release of therapeutically important proteins from the assembled hydrogels have also been demonstrated via immunochemical assays, which demonstrate the slow release of basic fibroblast growth factor (bFGF) as a function of matrix erosion. The combination of these results suggests the opportunities for producing polymer-polysaccharide conjugates that can assemble into novel hydrogel networks on the basis of peptide-saccharide interactions and for employing these materials in delivery applications.
In vitro activity of some glucosinolates and their reaction products toward a population of the nematode Heterodera schachtii (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIn vitro activity of some glucosinolates and their reaction products toward a population of the nematode Heterodera schachtiiL. Lazzeri, R. Tacconi, and S. PalmieriCite this: J. Agric. Food Chem. 1993, 41, 5, 825–829Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 May 1993https://pubs.acs.org/doi/10.1021/jf00029a028https://doi.org/10.1021/jf00029a028research-articleACS PublicationsRequest reuse permissionsArticle Views424Altmetric-Citations114LEARN 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-Alertsclose Get e-Alerts
Development and evaluation of efficient recombinant Escherichia coli strains for the production of 3‐hydroxypropionic acid from glycerol (2009)

3-Hydroxypropionic acid (3-HP) is a commercially valuable chemical with the potential to be a key building block for deriving many industrially important chemicals. However, its biological production has not been well documented. Our previous study demonstrated the feasibility of producing 3-HP from glycerol using the recombinant Escherichia coli SH254 expressing glycerol dehydratase (DhaB) and aldehyde dehydrogenase (AldH), and reported that an "imbalance between the two enzymes" and the "instability of the first enzyme DhaB" were the major factors limiting 3-HP production. In this study, the efficiency of the recombinant strain(s) was improved by expressing DhaB and AldH in two compatible isopropyl-thio-beta-galactoside (IPTG) inducible plasmids along with glycerol dehydratase reactivase (GDR). The expression levels of the two proteins were measured. It was found that the changes in protein expression were associated with their enzymatic activity and balance. While cloning an alternate aldehyde dehydrogenase (ALDH), alpha-ketoglutaric semialdehyde dehydrogenase (KGSADH), instead of AldH, the recombinant E. coli SH-BGK1 showed the highest level of 3-HP production (2.8 g/L) under shake-flask conditions. When an aerobic fed-batch process was carried out under bioreactor conditions at pH 7.0, the recombinant SH-BGK1 produced 38.7 g 3-HP/L with an average yield of 35%. This article reports the highest level of 3-HP production from glycerol thus far.
Down-regulation of NF-κB Transcriptional Activity in HIV-associated Kidney Disease by BRD4 Inhibition (2012)

NF-κB-mediated inflammation is the major pathology in chronic kidney diseases, including HIV-associated nephropathy (HIVAN) that ultimately progresses to end stage renal disease. HIV infection in the kidney induces NF-κB activation, leading to the production of proinflammatory chemokines, cytokines, and adhesion molecules. In this study, we explored selective inhibition of NF-κB transcriptional activity by small molecule blocking NF-κB binding to the transcriptional cofactor BRD4, which is required for the assembly of the productive transcriptional complex comprising positive transcription elongation factor b and RNA polymerase II. We showed that our BET (Bromodomain and Extra-Terminal domain)-specific bromodomain inhibitor MS417, designed to block BRD4 binding to the acetylated NF-κB, effectively attenuates NF-κB transcriptional activation of proinflammatory genes in kidney cells treated with TNFα or infected by HIV. MS417 ameliorates inflammation and kidney injury in HIV-1 transgenic mice, an animal model for HIVAN. Our study suggests that BET bromodomain inhibition, targeting at the proinflammatory activity of NF-κB, represents a new therapeutic approach for treating NF-κB-mediated inflammation and kidney injury in HIVAN.
DNA Markers for Nervous System Diseases (1984)

Recombinant DNA technology has provided a vast new source of DNA markers displaying heritable sequence variation in humans. These markers can be used in family studies to identify the chromosomal location of defective genes causing nervous system disorders. The discovery of a DNA marker linked to Huntington's disease has opened new avenues of research into this disorder and may ultimately permit cloning and characterization of the defective gene.
Comfortable power assist control method for walking aid by HAL-3 (2003)

We have developed the power assist suit HAL (Hybrid Assistive Leg) which provide the self-walking aid for gait disorder persons or aged persons. The power assist was performed according to the operator's intention by using myoelectricity(EMG) signal as the primary command signal. However, there remains the problem that the operator senses the discomfort while the power assist is performed by EMG-based control. The scope of the present research is to propose the control methods to reduce the discomfort which the operator sense while the EMG-based power assist is performed in walking and standing up respectively; 1) the control method that the integrated motion between HAL-3 and the operator corresponds with the particularity of operator's musculo-skeletal system while in the power assist walking, 2) the predictive control method applying feedforward controller to remove the discomfort while in standing up. As the result, the power assist walking was performed corresponding to the joint kinematics of the normal walking without the assistance. Applying feedforward controller realized the quick response while in standing up power assist. These control methods enabled HAL-3 to realize the power assist that the operator sensed the reduce of discomfort.
Novel Polarized Photoluminescent Films Derived from Sequential Self-organization, Induced-Orientation, and Order-Transfer Processes (2003)

Mechanical shearing of N,N‘-bis(N,N-diethylaminoethyl)perylene-3,4:9,10-bis(dicarboximide) dihydrochloride in a lyotropic liquid-crystalline phase produced oriented solid films that exhibit highly anisotropic fluorescence emission. The highest emission intensity is observed when the shearing direction of the film is perpendicular to the polarization axes of the excitation and emission light.
Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target (2002)

Phagocytosis is an actin-based process used by macrophages to clear particles greater than 0.5 microm in diameter. In addition to its role in immunological responses, phagocytosis is also necessary for tissue remodeling and repair. To prevent catastrophic autoimmune reactions, phagocytosis must be tightly regulated. It is commonly assumed that the recognition/selection of phagocytic targets is based solely upon receptor-ligand binding. Here we report an important new criterion, that mechanical parameters of the target can dramatically affect the efficiency of phagocytosis. When presented with particles of identical chemical properties but different rigidity, macrophages showed a strong preference to engulf rigid objects. Furthermore, phagocytosis of soft particles can be stimulated with the microinjection of constitutively active Rac1 but not RhoA, and with lysophosphatidic acid, an agent known to activate the small GTP-binding proteins of the Rho family. These data suggest a Rac1-dependent mechanosensory mechanism for phagocytosis, which probably plays an important role in a number of physiological and pathological processes from embryonic development to autoimmune diseases.
The battle against SARS and MERS coronaviruses: Reservoirs and Animal Models (2018)

In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus (SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus (MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.
Oral vaccination of monkeys with an invasive Escherichia coli K-12 hybrid expressing Shigella flexneri 2a somatic antigen (1984)

A living oral vaccine, designed to protect against Shigella flexneri 2a infections, was constructed by using Escherichia coli K-12 as a carrier strain. The hybrid strain, designated EC104, contained both chromosomal and plasmid genes from S. flexneri donor strains. In addition to expressing the S. flexneri 2a somatic antigen, it had inherited the property of epithelial-cell invasion. After the oral administration to rhesus monkeys, EC104 was isolated from the feces for up to 3 days, but by day 4 all stool cultures were negative. The serum antibody response against S. flexneri 2a somatic antigen was variable, but the vaccine conferred significant protection against an oral challenge with virulent S. flexneri 2a.
What's the hard return on employee wellness programs? (2010)

Employee wellness programs have often been viewed as a nice extra, not a strategic imperative. But the data demonstrate otherwise, according to Berry, of Texas A&M University; Mirabito, of Baylor University; and Baun, of the University of Texas MD Anderson Cancer Center. Their research shows that the ROI on comprehensive, well-run employee wellness programs is impressive, sometimes as high as six to one. To achieve those kinds of results, employers cannot merely offer workers afew passes to a fitness center and nutrition information in the cafeteria. The most successful wellness programs are supported by six essential pillars: engaged leadership at multiple levels; strategic alignment with the company's identity and aspirations; a design that is broad in scope and high in relevance and quality; broad accessibility; internal and external partnerships; and effective communications. Companies in a variety of industries--including Johnson & Johnson, Lowe's, H-E-B, and Healthwise--have built their employee wellness programs on all six pillars and have reaped big rewards in the form of lower costs, greater productivity, and higher morale. Those benefits are not easy to achieve, and verifiable paybacks are never a certainty. But the track record inspires emulation, especially when you see the numbers.
Prospective detection of preclinical lung cancer: results from two studies of heterogeneous nuclear ribonucleoprotein A2/B1 overexpression. (1997)

The United States lung cancer epidemic has not yet been controlled by present prevention and treatment strategies. Overexpression of a Mr 31,000 protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, had shown promise as a marker of lung cancer. In a pilot study of archived preneoplastic sputum specimens, hnRNP A2/B1 overexpression more accurately detected preclinical lung cancer than standard cytomorphology. In separate, ongoing prospective studies, sputum is collected annually from stage I resected non-small cell lung cancer patients at high risk of developing a second primary lung cancer and Yunnan tin miners at high risk of primary lung cancer. After the first year of follow-up, preclinical detection of lung cancer by routine cytology was compared with hnRNP A2/B1 overexpression as measured by quantitative densitometry of immunostained slides. Up-regulation of hnRNP A2/B1 in sputum specimens accurately predicted the outcome in 32 of 40 primary lung cancer and control patients within 12 months, whereas cytological change suggestive of lung cancer was found in only 1 patient. In the primary lung cancer study, overexpressed hnRNP A2/B1 accurately predicted the outcome in 69 of 94 primary lung cancer and control miners, whereas only 10 with primary lung cancer were diagnosed cytologically. These two prospective studies accurately predicted that 67 and 69% of those with hnRNP A2/B1 up-regulation in their sputum would develop lung cancer in the first year of follow-up, compared with background lung cancer risks of 2.2 and 0.9% (35- and 76-fold increase, respectively). Using sputum cells to monitor hnRNP A2/B1 expression may greatly improve the accuracy of preclinical lung cancer detection.
Development of a Field Enzyme‐Linked Immunosorbent Assay (ELISA) for Detection of α‐Amylase in Preharvest‐Sprouted Wheat (1999)

ABSTRACT A sandwich enzyme‐linked immunosorbent assay (ELISA) has been developed for detection of α‐amylase in preharvest sprouted wheat and adapted to rapid field‐use formats requiring 15–20 min to perform. Polyclonal and monoclonal antibodies were prepared to detect a mixture of high and low pI isozymes of α‐amylase and high pI isozymes only. All antibodies detected α‐amylase on immunoblots of either a crude wheat extract or of purified enzyme, but only the polyclonal antibodies functioned in a sandwich ELISA. Depending on the antibody combination, the tube ELISA detected either the high and low pI isozymes of α‐amylase or the high pI isozymes only with a detection limit of ≈0.5–1.0 ng/mL of amylase. Wheats with falling numbers (FN) of &lt;350 sec could be discriminated from sound wheats, with decreasing FN producing increasing assay color. Using 130 wheat grain samples, ELISA absorbances for detection of both high and low pI isozymes and of high pI isozymes only were highly positively correlated with amylase enzyme activity and negatively correlated with FN. The correlations were similar for detection of both isozyme families and for detection of high pI isozymes only. Analyses of three sets of wheat samples from different environments demonstrated that the relationship between ELISA absorbance and FN had little dependence on wheat cultivar. The precision of sample analysis using the field ELISA was similar to the precision of FN test apparatus.