gebhart/patrepeval huggingface dataset:
IMVAMUNE®: modified vaccinia Ankara strain as an attenuated smallpox vaccine (2008)

Smallpox vaccines based on replicating vaccinia virus are known to elicit rare yet serious adverse events, particularly in human populations with immune deficiency, atopic dermatitis and at the extremes of age. A vaccine that induces protective immune responses equivalent to first-generation smallpox vaccines while reducing the risk for severe adverse events is critical for a national stockpile of smallpox vaccines. Modified vaccinia Ankara (MVA) has been proposed as an immediate solution for vaccination of high-risk individuals. Bavarian Nordic's vaccine MVA-BN (IMVAMUNE) is a MVA strain that is replication incompetent in mammalian cell lines. IMVAMUNE has been administered to more than 1900 human subjects to date, including high-risk populations (e.g., people diagnosed with atopic dermatitis or infected with HIV) in which standard replicating vaccines are contraindicated. We review the Phase I clinical trial safety profile and immune responses and compare them with other smallpox vaccines, including ACAM2000 and Dryvax.
A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system (2009)

We report a novel facile method for preparing stable nanoparticles with inner spherical solid spheres and an outer hydrogel matrix using a hot O/W hydrogel-thickened microemulsion with spontaneous stability. The nanoparticles with average diameters of about 30.0 nm and 100.0 nm were constructed by cooling the hot hydrogel-thickened microemulsion at different temperatures, respectively. We explained the application of these nanoparticles by actualizing the cutaneous delivery of drug-loaded nanoparticles. The in vitro skin permeation studies showed that the nanoparticles could significantly reduce the penetration of model drugs through skin and resulted in their dermal uptakes in skin. The sol-gel process of TEOS was furthermore used in the template of HTM to regulate the particle size of nanoparticles. The coating of silica on the surface of nanoparticles could regulate the penetration of drug into skin from dermal delivery to transdermal delivery. This strategy provides a facile method to produce nanoparticles with long-term stability and ease of manufacture, which might have a promising application in drug delivery.
Potential roles of IL-9 in the pathogenesis of systemic lupus erythematosus. (2012)

T helper (Th) cells and their cytokines play a pleiotropic role in the pathogenesis of systemic lupus erythematosus (SLE). Recently, a new effector T cell subset, Th9 cells, which preferentially secrete IL-9, has been identified. IL-9 is mainly produced by several T cell subsets including Th9 and Th17, and effective on the functions of Th cells and mast cell. However, there are no unambiguous conclusions that IL-9 contributes to the pathogenesis of SLE. Recently, IL-9 was reported to mediate profound anti-inflammatory effects in several cells or experimental autoimmune models. In particular, IL-9 production seemed to be important in mast cell recruitment. Defect in IL-9/IL-9R axis exhibited a more severe course of Experimental Autoimmune Encephalomyelitis (EAE) and enhanced activity of Tregs, phenotypes reminiscent of SLE. Consistently, IL-9 was implicated in the proliferation of several types of CD4+ T cells, indicating that IL-9 may be therapeutically relevant in SLE. In this article, we briefly discuss the biological features of IL-9 and summarize recent advances on the role of IL-9 in the pathogenesis and treatment of SLE.
Treatment of invasive fungal sinusitis with liposomal amphotericin B: a report of four cases. (2001)

Invasive fungal sinusitis increasingly causes significant morbidity and mortality in immunocompromised patients. It is difficult to treat. Despite standard treatment by surgical debridement and intravenous amphotericin B, morbidity and mortality remain high. Conventional amphotericin B is the standard drug but its use is limited by dose-related nephrotoxicity and infusion-related acute toxicity. Liposomal amphotericin B has proven to be as effective as conventional amphotericin B with less nephrotoxicity and infusion reaction. We report four cases of invasive fungal sinusitis who were treated with liposomal amphotericin B after having severe side effects from conventional amphotericin B. There were two cases of mucormycosis and two cases of aspergillosis. All patients had diabetes millitus. One patient had systemic lupus erythematosus and another was receiving immunosuppressive drugs after kidney transplantation. All cases needed multiple operations for sinus surgery. Two cases had acute reaction to amphotericin B infusion, one had active lupus nephritis with renal insufficiency, and one was considered treatment failure from amphotericin B. The patients received liposomal amphotericin B at the total doses of 4.55-8.85 g. Two cases of mucormycosis were considered to be successfully treated. In cases of aspergillosis, one was considered improved and another one with immunocompromised status died with active disease. From our experience, surgery is the main treatment for patients with invasive fungal sinusitis and liposomal amphotericin B is an effective alternative drug for adjuvant medical treatment. However, the degree of immunosuppression of the patients, the extension of fungal sinusitis and perhaps the species of fungus are important factors determining the clinical response.
Stimulation of Lipolysis by Tumor Necrosis Factor-α in 3T3-L1 Adipocytes Is Glucose Dependent (2004)

Tumor necrosis factor-alpha (TNF-alpha) and hyperglycemia both impair insulin sensitivity in vivo. This may be secondary to stimulation of adipose tissue lipolysis and consequent increased circulating free fatty acids (FFAs). Here we report that neither TNF-alpha nor glucose alone has a pronounced effect on lipolysis in 3T3-L1 adipocytes. However, the combination of TNF-alpha plus glucose markedly stimulates lipolysis. Glucose does not affect the ability of isoproterenol to stimulate lipolysis. Alternative substrates such as acetate, pyruvate, and lactate do not allow the TNF-alpha effect. Mannose was almost as effective as glucose; fructose was marginally effective, but galactose was ineffective. The effectiveness of the sugars corresponded with production of lactate, i.e., the cells readily produced lactate from glucose or mannose, slightly from fructose, and not at all from galactose. The ability of TNF-alpha to phosphorylate extracellular signal-regulated kinase 1 (ERK1) and ERK2 and to downregulate perilipin (which has been implicated in the lipolytic effect of TNF-alpha) was not affected by glucose. We conclude that the lipolytic action of TNF-alpha is influenced by glucose in 3T3-L1 adipocytes. The findings suggest that glucose metabolism is required for the lipolytic response to TNF-alpha but not for early signaling events. These findings suggest novel mechanisms by which TNF-alpha and hyperglycemia raise FFA levels and induce insulin resistance.
The Effects of Interactive Latency on Exploratory Visual Analysis (2014)

To support effective exploration, it is often stated that interactive visualizations should provide rapid response times. However, the effects of interactive latency on the process and outcomes of exploratory visual analysis have not been systematically studied. We present an experiment measuring user behavior and knowledge discovery with interactive visualizations under varying latency conditions. We observe that an additional delay of 500 ms incurs significant costs, decreasing user activity and data set coverage. Analyzing verbal data from think-aloud protocols, we find that increased latency reduces the rate at which users make observations, draw generalizations and generate hypotheses. Moreover, we note interaction effects in which initial exposure to higher latencies leads to subsequently reduced performance in a low-latency setting. Overall, increased latency causes users to shift exploration strategy, in turn affecting performance. We discuss how these results can inform the design of interactive analysis tools.
Optimization of OpenStreetMap Building Footprints Based on Semantic Information of Oblique UAV Images (2018)

Building footprint information is vital for 3D building modeling. Traditionally, in remote sensing, building footprints are extracted and delineated from aerial imagery and/or LiDAR point cloud. Taking a different approach, this paper is dedicated to the optimization of OpenStreetMap (OSM) building footprints exploiting the contour information, which is derived from deep learning-based semantic segmentation of oblique images acquired by the Unmanned Aerial Vehicle (UAV). First, a simplified 3D building model of Level of Detail 1 (LoD 1) is initialized using the footprint information from OSM and the elevation information from Digital Surface Model (DSM). In parallel, a deep neural network for pixel-wise semantic image segmentation is trained in order to extract the building boundaries as contour evidence. Subsequently, an optimization integrating the contour evidence from multi-view images as a constraint results in a refined 3D building model with optimized footprints and height. Our method is leveraged to optimize OSM building footprints for four datasets with different building types, demonstrating robust performance for both individual buildings and multiple buildings regardless of image resolution. Finally, we compare our result with reference data from German Authority Topographic-Cartographic Information System (ATKIS). Quantitative and qualitative evaluations reveal that the original OSM building footprints have large offset, but can be significantly improved from meter level to decimeter level after optimization.
Major depression is a risk factor for seizures in older adults (2000)

We tested the hypothesis that major depression meeting DSM-III-R criteria or medical therapies for depression increase the risk for unprovoked seizures. Major depression was associated with a sixfold increased risk for unprovoked seizures (95% CI, 1.56-22). The risk remained increased even when controlling for age, sex, length of medical follow-up, and medical therapies for depression. In the absence of known prior neurological insult, major depression is associated with an increased risk for unprovoked seizures.
Vandetanib (VAN) in locally advanced or metastatic medullary thyroid cancer (MTC): A randomized, double-blind phase III trial (ZETA). (2010)

5503 Background: VAN is a once-daily oral inhibitor of RET, VEGFR, and EGFR signaling. VAN 300 mg/day has previously shown antitumor activity in a phase II study of patients (pts) with advanced hereditary MTC. Methods: Eligible pts had unresectable measurable, locally advanced or metastatic MTC (hereditary or sporadic). The primary objective was to determine if VAN prolonged PFS versus placebo (P), as determined by independent central RECIST assessments. Secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), biochemical response (changes in serum calcitonin [CTN] and carcinoembryonic antigen [CEA]) and overall survival (OS). Results: Between Dec 2006 and Nov 2007, 331 pts (mean age 52 yrs; 57% male; 90% sporadic; 95% metastatic; RET mutation status: Pos 56%; Neg 2%; Unknown 41%) were randomized 2:1 to VAN (n=231) or P (n=100). Pt characteristics were similar in both arms. At data cutoff (July 2009), median follow-up was 24 mths; 48% pts randomized to VAN continued blinded treatment, 37% pts progressed, 15% were dead. Statistically significant PFS prolongation was observed for VAN vs P (HR 0.45, 95% CI 0.30–0.69); statistically significant advantages for VAN were also seen for ORR, DCR and biochemical response (Table). The adverse event (AE) profile was similar to previous VAN studies. Common AEs (any grade) more frequent with VAN included diarrhea (56% vs. 26%), rash (45% vs. 11%), nausea (33% vs. 16%), hypertension (32% vs. 5%), and headache (26% vs. 9%). Dosing was reduced in 35% (VAN) vs. 3% (P) pts. Conclusions: This study met its primary objective of significant PFS prolongation with VAN vs. P. VAN is the first therapy to demonstrate efficacy in a phase III trial in pts with advanced MTC, a disease for which there is no standard effective therapy. PFS HR 0.45 95% CI 0.30–0.69 p = 0.0001 Median PFS: not reached (VAN); 19.8 mths (P) ORR Odds ratio = 5.4 95% CI 2.99–10.79 p < 0.0001 DCR (>24 wks) Odds ratio = 2.64 95% CI 1.48–4.69 p = 0.001 Biochemical response CTN Odds ratio = 54.1 95% CI 21.6–181.7 p < 0.0001 CEA Odds ratio = 50.3 95% CI 15.4–309.4 p < 0.0001 OS* HR 0.89 99.98% CI 0.28–2.85 p = 0.712 HR <1 favors VAN; odds ratio >1 favors VAN*OS data immature—final OS analysis when 50% pts dead. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Amgen, AstraZeneca, Bayer, Eisai, Exelixis, Genzyme Genzyme AstraZeneca, Eisai, Genzyme Genzyme Genzyme
A New, Mild Heterogeneous Catalyst for the Tetrahydropyranylation of Alcohols and Phenols (1988)

The hydrochloride salt of a cross-linked macroreticular poly(4-vinylpyridine) resin in bead form is an effective, yet mild acid catalyst for the tetrahydropyranylation of alcohols (primary, secondary, and tertiary) and phenols. The reaction is carried out in the presence of excess dihydropyran without the formation of troublesome oligomeric pyrans. High yields of the desired ethers are obtained even in reactions with alcohols having steric restrictions or acid sensitive amine functionalities.
Aqueous solubility and dissolution rate does not adequately predict in vivo performance: A probe utilizing some N‐acyloxymethyl phenytoin prodrugs (1999)

Some physicochemical properties of N-acyloxyalkyl prodrugs of phenytoin were reported previously.(1,2) It was shown that despite their lower aqueous solubilities relative to phenytoin, these lower-melting prodrugs with apparently disrupted crystalline structures gave either comparable or enhanced in vitro solubility and dissolution rate in simulated intestinal media made up of bile salts and lecithin (SIBLM).(2) The current objective was to compare the in vivo behavior of two of these prodrugs to phenytoin in dogs and attempt to correlate the in vitro behavior to their in vivo behavior. The oral bioavailability of phenytoin after administration of phenytoin (1) and the selected prodrugs, 3-pentanoyloxymethyl 5, 5-diphenylhydantoin (2) and 3-octanoyloxymethyl 5, 5-diphenylhydantoin (3), in fed and fasted beagle dogs were compared to intravenously administered phenytoin. Phenytoin and its prodrugs showed improvement in fed-state phenytoin bioavailability relative to the fasted state indicating that food enhanced the delivery of phenytoin from phenytoin and its prodrugs. The increased bioavailability in the fed state may be due to stimulation of bile release by food and, for the prodrugs, possible catalysis of their dissolution by lipases.(3) In both, fasted and fed states, prodrugs 2 and 3 gave higher AUC values of phenytoin than the parent compound. The enhanced bioavailability of phenytoin after oral administration were more obvious in fed dogs. Although enhanced, AUC values of phenytoin from the prodrugs relative to phenytoin were not statistically different (at 95% confidence level) in fasted state, but were different in fed state. Although the aqueous solubilities and dissolution of both prodrugs were lower than phenytoin, dissolution of 2 and 3 was equivalent and greater, respectively, relative to phenytoin in SIBLM. As expected, the in vivo behavior correlated better with the in vitro SIBLM dissolution behavior. These results indicate that aqueous solubility per se does not adequately predict in vivo behavior.
Palladium and Platinum Nanoparticles Attenuate Aging-Like Skin Atrophy via Antioxidant Activity in Mice (2014)

Cu-Zn superoxide dismutase (Sod1) loss causes a redox imbalance as it leads to excess superoxide generation, which results in the appearance of various aging-related phenotypes, including skin atrophy. Noble metal nanoparticles, such as palladium (Pd) and platinum (Pt) nanoparticles, are considered to function as antioxidants due to their strong catalytic activity. In Japan, a mixture of Pd and Pt nanoparticles called PAPLAL has been used to treat chronic diseases over the past 60 years. In the present study, we investigated the protective effects of PAPLAL against aging-related skin pathologies in mice. Transdermal PAPLAL treatment reversed skin thinning associated with increased lipid peroxidation in Sod1-/- mice. Furthermore, PAPLAL normalized the gene expression levels of Col1a1, Mmp2, Has2, Tnf-α, Il-6, and p53 in the skin of the Sod1-/- mice. Pt nanoparticles exhibited marked SOD and catalase activity, while Pd nanoparticles only displayed weak SOD and catalase activity in vitro. Although the SOD and catalase activity of the Pt nanoparticles significantly declined after they had been oxidized in air, a mixture of Pd and Pt nanoparticles continued to exhibit SOD and catalase activity after oxidation. Importantly, a mixture of Pd and Pt nanoparticles with a molar ratio of 3 or 4 to 1 continued to exhibit SOD and catalase activity after oxidation, indicating that Pd nanoparticles prevent the oxidative deterioration of Pt nanoparticles. These findings indicate that PAPLAL stably suppresses intrinsic superoxide generation both in vivo and in vitro via SOD and catalase activity. PAPLAL is a potentially powerful tool for the treatment of aging-related skin diseases caused by oxidative damage.
Near Infrared Reflectance Spectrophotometric Analysis of Agricultural Products (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNear Infrared Reflectance Spectrophotometric Analysis of Agricultural ProductsC. A. WatsonCite this: Anal. Chem. 1977, 49, 9, 835A–840APublication Date (Print):August 1, 1977Publication History Published online24 May 2012Published inissue 1 August 1977https://pubs.acs.org/doi/10.1021/ac50017a782https://doi.org/10.1021/ac50017a782research-articleACS PublicationsRequest reuse permissionsArticle Views111Altmetric-Citations45LEARN 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
An In vivo Platform for Translational Drug Development in Pancreatic Cancer (2006)

Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype. Resected pancreatic cancers from 14 patients were xenografted and expanded in successive groups of nude mice to develop cohorts of tumor-bearing mice suitable for drug therapy in simulated early clinical trials. The xenografted tumors maintain their fundamental genotypic features despite serial passages and recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform is useful for integrating drug screening with biomarker discovery. Passages of tumors in successive cohorts of mice do not change their susceptibility to anticancer agents and represent a perpetual live bank, facilitating the application of new technologies that will result in the creation of an integrated stable database of tumor-drug response data and biomarkers.
A Broadly Cross-Reactive Monoclonal Antibody Against an Epitope on the N-terminus of Meningococcal fHbp (2012)

Meningococcal factor H binding protein (fHbp) is an important vaccine antigen for prevention of disease caused by capsular group B strains. The protein has been sub-classified into three variant groups. Most anti-fHbp antibodies are variant group-specific and recognize epitopes on the C-terminal domain. We report a murine IgG1 mAb, JAR 41, which broadly cross-reacted with fHbp sequence variants from all variant groups. The mAb bound to the surface of live meningococci with fHbp from each of the three variant groups. In combination with second non-bactericidal anti-fHbp mAbs, JAR 41 elicited complement-mediated bactericidal activity in vitro, and augmented passive protection against meningococcal bacteremia in human fH transgenic rats. The epitope was located on a conserved region of the N-terminal portion of the fHbp molecule opposite that of fH contact residues. The data underscore the importance of broadly cross-reactive, surface-exposed epitopes on the N-terminal domain in the design of protective fHbp vaccines.
Exponential Megapriming PCR (EMP) Cloning—Seamless DNA Insertion into Any Target Plasmid without Sequence Constraints (2012)

We present a fast, reliable and inexpensive restriction-free cloning method for seamless DNA insertion into any plasmid without sequence limitation. Exponential megapriming PCR (EMP) cloning requires two consecutive PCR steps and can be carried out in one day. We show that EMP cloning has a higher efficiency than restriction-free (RF) cloning, especially for long inserts above 2.5 kb. EMP further enables simultaneous cloning of multiple inserts.
Depth-Resolved Chemical Modification of Porous Silicon by Wavelength-Tuned Irradiation (2012)

The ability to impart discrete surface chemistry to the inside and outside of mesoporous silicon is of great importance for a range of biomedical applications, from selective (bio)sensing to tissue-specific drug delivery. Here we present a generic strategy toward achieving depth-resolved functionalization of the external and internal porous surfaces by a simple change in the wavelength of the light being used to promote surface chemical reactions. UV-assisted hydrosilylation, limited by the penetration depth of UV light, is used to decorate the outside of the mesoporous structure with carboxylic acid molecules, and white light illumination triggers the attachment of dialkyne molecules to the inner porous matrix.
Identification of α-Enolase as an Autoantigen in Lung Cancer: Its Overexpression Is Associated with Clinical Outcomes (2006)

Our data strongly support a prognostic role of ENO1 in determining tumor malignancy of patients with NSCLC.
SSIDs in the wild: Extracting semantic information from WiFi SSIDs (2015)

WiFi networks are becoming increasingly ubiquitous. In addition to providing network connectivity, WiFi finds applications in areas such as indoor and outdoor localisation, home automation, and physical analytics. In this paper, we explore the semantics of one key attribute of a WiFi network, SSID name. Using a dataset of approximately 120,000 WiFi access points and their corresponding geo-locations, we use a set of similarity metrics to relate SSID names to known business venues such as cafes, theatres, and shopping centres. Such correlations can be exploited by an adversary who has access to smartphone users preferred networks lists to build an accurate profile of the user and thus can be a potential privacy risk to the users.