Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanolipidgel for Enhanced Skin Deposition and Improved Antifungal Activity

The purpose of the research was to prepare and evaluate a topical nanolipidgel (NLH) of terbinafine hydrochloride (TRB), an antimycotic agent, for enhanced skin deposition and improved antifungal activity. Topical solid lipid nanoparticles (SLN) based nanolipidgel was formulated and evaluated. TRB-loaded SLNs were formulated by high-pressure homogenization technique. The stable TRB SLN dispersion was incorporated into a gel using 1% Carbopol 980 NF. Rheological evaluation and texture analysis of the TRB NLH was carried out. Skin permeation, skin deposition, antifungal activity, and occlusivity studies of the nanolipidgel formulation were carried out. The safety of the TRB NLH gel was evaluated using acute skin irritation test on New Zealand White rabbits. The SLN dispersion containing 10% of glyceryl monostearate, 3% of Tween 80, and 1% Plurol Oleique was the most stable. The optimized TRB SLN had a particle size and zeta potential value of 148.6 ± 0.305 nm and −20.4 ± 1.2 mV, respectively. TRB NLH had excellent rheological and texture properties to facilitate its topical application. TRB NLH showed increased skin deposition of the drug over plain (3-fold) and marketed TRB formulation (2-fold). TRB NLH had significantly enhanced antifungal activity against Candida albicans. TRB NLH showed efficient occlusivity and was non-irritant to the rabbit skin with no signs of erythema or edema. Solid lipid nanoparticles-based topical nanolipidgel of terbinafine can be an efficient, industrially scalable, and cost-effective alternative to the existing conventional formulations.
Performance Evaluation of a Solar Wind-Ventilated Cabinet Dryer

This work is an attempt to utilise the benefits of using forced convection solar dryers through the use of a rotary wind ventilator in the remote areas where electricity and other power sources are non-existent. The solar wind-ventilated cabinet dryer was designed, constructed and tested in Nigeria on latitude 7.5o N. The results obtained show that the temperatures inside the dryer and the air-heater were higher than the ambient temperature during most hours of the day-light. The drying of food items in the dryer was compared with open air-drying of similar items. Comparatively, drying with the solar cabinet dryer showed better results than open air-drying. The results also revealed the dependence of the dryer performance on the proper air circulation through the system. The system efficiency increased as the air velocity through the system increased. During the period of test, the average air velocity through the solar dryer was 1.62 m/s and the average daylight efficiency of the system was 46.7%.
The contribution of multiple scattering to Love wave generation in the secondary microseism

S U M M A R Y The observed secondary microseismic wavefield is composed by Rayleigh and Love waves. While the presence and amount of Rayleigh waves is well understood, the generation of Love waves is still under debate. We investigate multiple scattering of surface waves as a possible mechanism that could be responsible for the generation of Love waves in the secondary microseism. We assume that the secondary microseism source generates mainly vertically polarized waves, and that the Love waves are produced during the propagation of the wavefield. To study this hypothesis, we model the wavefield in a highly heterogeneous 3-D half-space with a free surface. To understand the relationship between the surface wave types and the random medium properties, we perform a parameter study. We alter the model fluctuation strength, the correlation length and the layering structure of the medium. We find that the fluctuation strength has a major influence on the Love to Rayleigh ratio. We observe that the Love to Rayleigh ratio reaches a maximum value of 0.4 after approximately 4 scattering mean free paths. This value does not explain the observed Love to Rayleigh ratios in the secondary microseism, which lies between 0.6 and 1.2. Moreover, we would need an unrealistically strongly scattering medium to reach this value. Considering scattering properties similar to those encountered in oceanic crust for wavefields around 0.2 Hz, we obtain a Love to Rayleigh ratio of 0.1, which is significantly below the typically observed ratio of 0.6–1.2.
Avian Thermoregulation in the Heat: Resting Metabolism, Evaporative Cooling and Limits to Activity in Sonoran Desert Birds

Birds in subtropical deserts face significant thermoregulatory challenges as environmental temperatures regularly exceed avian body temperature. To understand the differing susceptibility of desert birds to increasing temperatures, this dissertation initially examined thermoregulatory performance in seven passerine bird species varying in body mass from 10 to 70g – Lesser Goldfinch, House Finch, Pyrrhuloxia, Cactus Wren, Northern Cardinal, Abert’s Towhee and Curve-billed Thrasher – and three larger Sonoran Desert nesting bird species – Mourning Dove (104 g), White-winged Dove (147 g) and Gambel’s Quail (161 g).
Snow Drought Risk and Susceptibility in the Western United States and Southwestern Canada

In western North America (WNA), mountain snowpack supplies much of the water used for irrigation, municipal, and industrial uses. Thus, snow droughts (a lack of snow accumulation in winter) can have drastic ecological and socioeconomic impacts. In this study, the historical (1951–2013) frequency, severity, and risk (frequency × severity) of dry, warm, and warm and dry snow droughts are quantified at the grid‐cell and ecoregion scale for snow‐dominated regions in the western United States and southwestern Canada (sWNA). Based on multiple linear regression analysis, relationships between mean winter temperature, snow drought risk, and snow water equivalent sensitivity are explored. Piecewise linear regression is used to identify temperature thresholds for mapping temperature‐related snow drought susceptibility. Results highlight spatial differences in snow drought regimes across sWNA and reveal that temperature thresholds exist at −3.1 °C (±0.3 °C) and 1.4 °C (±0.3 °C), above which the warm snow drought risk increases more rapidly. Approximately 3% of the nonglaciated snow storage in this region has high susceptibility to temperature‐related snow drought, representing 11 km3 of water, or approximately one third the capacity of Lake Mead. Under a +2 °C climate scenario, an additional 8% (28 km3) of this snow storage volume will transition to high susceptibility.
Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study

Background Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. Methodology/Principal Findings Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8–8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2–8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. Conclusion Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of serological response, should be monitored. This group could be considered as a target for chemoprophylaxis.
Human Serum Amyloid P Functions as a Negative Regulator of the Innate and Adaptive Immune Responses to DNA Vaccines

The utility of DNA vaccines has been limited by their failure to elicit sufficiently potent immune responses in many human applications, whereas DNA vaccinations in mice have been very successful. However, the underlying mechanisms remain unknown. We hypothesize that serum amyloid P component (SAP), which has a species-specific, DNA-binding ability, contributes to the differences between human and mice and then limits DNA vaccine’s efficacy in vivo. In our study, DNA vaccine-induced adaptive immune responses were also significantly decreased in the human SAP (hSAP) transgenic mice. Using human promonocytic cell line THP-1–derived macrophages as a cell model, we found that cells incubated with a hSAP–DNA complex showed significant defects in innate immune activations, whereas mouse SAP had similar, albeit very weak, activities. hSAP also significantly inhibited the functions of two identified DNA sentinels, high-mobility group B protein 1 and antimicrobial peptide LL37, and redirected DNA update to FcRs leading to endocytosis and endosomal degradation. We also found that a chemical SAP inhibitor strongly recovered the suppressed innate immune responses to DNA in the presence of human serum and enhanced the immunogenicity of DNA vaccines in vivo. Our data indicated that SAP is a key negative regulator for innate immune responses to DNA and may be partly responsible for the insufficient immune responses after DNA vaccinations in humans. SAP suppression may be a novel strategy for improving efficacy of human DNA vaccines and requires further clinical investigations.
Lactational Exposure to Polychlorinated Biphenyls, Dichlorodiphenyltrichloroethane, and Dichlorodiphenyldichloroethylene and Infant Neurodevelopment: An Analysis of the Pregnancy, Infection, and Nutrition Babies Study

Background Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) are persistent, bioaccumulative, and toxic pollutants that were broadly used in the United States until the 1970s. Common exposure to PCBs, DDT, and dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of DDT, may influence children’s neurodevelopment, but study results are not consistent. Objectives We examined the associations between lactational exposure to PCBs, DDT, and DDE and infant development at 12 months, using data from the Pregnancy, Infection, and Nutrition Babies Study, 2004–2006. Methods We measured PCBs, DDT, and DDE in breast milk at the third month postpartum. Lactational exposure of these chemicals was estimated by the product of chemical concentrations and the duration of breast-feeding. Infant development at 12 months of age was measured by the Mullen Scales of Early Learning (n = 231) and the Short Form: Level I (infant) of the MacArthur–Bates Communicative Development Indices (n = 218). Results No consistent associations were observed between lactational exposure to PCBs, DDT, and DDE through the first 12 months and the measures of infant development. However, DDE was associated with scoring below average on the gross motor scale of the Mullen among males only (adjusted odds ratio = 1.9; 95% confidence interval, 1.1–3.3). Conclusion Infant neurodevelopment at 12 months of age was not impaired by PCBs, DDT, and DDE at the concentrations measured here, in combination with benefits from long duration of breast-feeding in this population.
Primary Amyloidosis: A Review

This review is concerned mainly with " primary amyloidosis. " It is necessary to stress at the outset that there are important misconceptions of what the term primary amyloidosis denotes, and that the problems of primary amyloidosis cannot profitably or realistically be separated from the problems of amyloidosis in general. The term " primary amyloidosis " refers to those cases of amyloidosis in which no predisposing cause is found. Amyloidosis which occurs in association with a predisposing cause is now usually described as "secondary amyloidosis. " The descriptions " primary " and " secondary " should not be interpreted as having definitive aetiological significance or as precluding an even closer relationship between these forms of amyloidosis than is yet apparent. No other criterion than the absence of a recognizable predisposing cause is needed in order to designate any case of amyloidosis as primary amyloidosis. It is a common misconception that this diagnosis necessarily implies a particular and unusual distribution of amyloid, that the amyloid presents anomalous staining reactions, and that the disease has a characteristic clinical picture. On the other hand, it is true that the gross distribution of amyloid in most cases of primary amyloidosis differs remarkably from that in typical cases of secondary amyloidosis, that the staining reactions of the amyloid in primary and secondary amyloidosis may differ, and that in some cases of primary amyloidosis a foreign-body giant-cell reaction develops around the amyloid, or calcium is laid down in it: however, none of these characteristics is of absolute diagnostic significance. In fact, the varieties of amyloidosis cannot properly be defined in terms of the location, form, or tinctorial characteristics of the amyloid material, nor is there any clinical manifestation or syndrome associated with amyloidosis which occurs exclusively in one or another form of the disease. There are cases of primary amyloidosis which, except for the
Periodically-forced finite networks of heterogeneous coupled oscillators: a low-dimensional approach

We study a network of 500 coupled modified van der Pol oscillators. The value of a parameter associated with each oscillator is drawn from a normal distribution, giving a heterogeneous network. For strong enough coupling the oscillators all have the same period, and we consider periodic forcing of the network when it is in this state. By exploiting the correlations that quickly develop between the state of an oscillator and the value of its parameter we obtain an approximate low-dimensional description of the system in terms of the first few coefficients in a polynomial chaos expansion. Standard bifurcation analysis can then be performed on this low-dimensional system, and the results obtained from this predict very well the behaviour of the high-dimensional system for any set of realisations of the random parameter. Situations in which the method begins to fails are also discussed.
Does Safe Dosing of Iodinated Contrast Prevent Contrast-Induced Acute Kidney Injury?

Background—Previous work on contrast-induced acute kidney injury (CI-AKI) has identified contrast volume as a risk factor and suggested that there is a maximum allowable contrast dose (MACD) above which the risk of CI-AKI is markedly increased. We hypothesized that there is a relationship between contrast volume and CI-AKI and that there might be reason to track incremental contrast volumes above and below the MACD limit. Methods and Results—Consecutive patients undergoing percutaneous coronary intervention (PCI) were prospectively enrolled from 2000 to 2008 (n=10 065). Patients on dialysis before PCI were excluded (n=155). MACD was defined as (5 mL×body weight [kg])/baseline serum creatinine [mg/dL]) and divided into categories in which 1.0 reflects the MACD limit: ⩽MACD ratios (<0.5, 0.5 to 0.75, and 0.75 to 1.0) and >MACD (1.0 to 1.5, 1.5 to 2.0, and >2.0). CI-AKI was defined as a ≥0.3 (mg/dL) or ≥50% increase in serum creatinine from baseline or new dialysis. Multivariable regression was conducted to evaluate the effect of exceeding the MACD on CI-AKI. Twenty percent of patients exceeded the MACD. Risk-adjusted CI-AKI increased by an average of 45% for each category exceeding the MACD (odds ratio, 1.45; 95% confidence interval, 1.29 to 1.62) Adjusted odds ratios for each category exceeding the MACD were 1.60 (95% confidence interval, 1.29 to 1.97), 2.02 (95% confidence interval, 1.45 to 2.81), and 2.94 (95% confidence interval, 1.93 to 4.48). CI-AKI for contrast dose <MACD showed no statistical difference (P=0.5). Conclusions—Contrast volume is a key risk factor for CI-AKI and matters the most in the highest-risk patient. The incremental use of contrast beyond the MACD is associated with an increased risk of CI-AKI.
FastPros: screening of reaction knockout strategies for metabolic engineering

Motivation: Although constraint-based flux analysis of knockout strains has facilitated the production of desirable metabolites in microbes, current screening methods have placed a limitation on the number knockouts that can be simultaneously analyzed. Results: Here, we propose a novel screening method named FastPros. In this method, the potential of a given reaction knockout for production of a specific metabolite is evaluated by shadow pricing of the constraint in the flux balance analysis, which generates a screening score to obtain candidate knockout sets. To evaluate the performance of FastPros, we screened knockout sets to produce each metabolite in the entire Escherichia coli metabolic network. We found that 75% of these metabolites could be produced under biomass maximization conditions by adding up to 25 reaction knockouts. Furthermore, we demonstrated that using FastPros in tandem with another screening method, OptKnock, could further improve target metabolite productivity. Availability and implementation: Source code is freely available at http://www-shimizu.ist.osaka-u.ac. jp/shimizu_lab/FastPros/, implemented in MATLAB and COBRA toolbox. Contact: chikara.furusawa@riken.jp or shimizu@ist.osaka-u.ac. jp Supplementary information: Supplementary data are available at Bioinformatics online.
Overexpression of ATP-activated P2X7 Receptors in the Intestinal Mucosa Is Implicated in the Pathogenesis of Crohn's Disease

Background:Extracellular nucleotides released in conditions of cell stress alert the immune system from tissue injury or inflammation. We hypothesized that the P2X7 receptor (P2X7-R) could regulate key elements in inflammatory bowel disease pathogenesis. Methods:Colonoscopy samples obtained from patients with Crohn's disease (CD), ulcerative colitis, and controls were used to analyze P2X7-R expression by RT and real-time PCR, immunohistochemistry, and confocal microscopy. Inflammatory response was determined by the levels of cytokines by enzyme-linked immunosorbent assay in cultures of intestinal explants. Apoptosis was determined by the TUNEL assay. P2X7-R−/− C57BL/6 mice were treated with trinitrobenzene sulfonic acid or dextran sulfate sodium (DSS) for inducing colitis. Results:P2X7-R was expressed in higher levels in inflamed CD epithelium and lamina propria, where it colocalizes more with dendritic cells and macrophages. Basal levels of P2X7-R mRNA were higher in CD inflamed mucosa compared with noninflamed CD and controls and were upregulated after interferon-&ggr; in controls. Apoptotic rates were higher in CD epithelium and lamina propria compared with ulcerative colitis and controls. Levels of tumor necrosis factor-&agr;, interleukin (IL)-1&bgr;, and IL-17 were higher, whereas IL-10 was lower in CD compared with controls. Levels of tumor necrosis factor-&agr;-&agr; and interleukin-1&bgr; increased after adenosine-triphosphate and decreased after KN62 treatment in CD. P2X7-R−/− animals did not develop trinitrobenzene sulfonic acid or DSS colitis. Conclusions:The upregulation of P2X7-R in CD inflamed mucosa is consistent with the involvement of purinoceptors in inflammation and apoptosis. These observations may implicate purinergic signaling in the pathogenesis of intestinal inflammation, and the P2X7-R may represent a novel therapeutic target in CD.
How Much Nubia‐Eurasia Convergence Is Accommodated by the NE End of the Eastern Betic Shear Zone (SE Spain)? Constraints From GPS Velocities

We present the first GPS‐derived geodetic observations from the NE end of the Eastern Betic Shear Zone obtained from the Bajo Segura GPS network (SE Spain). The network has 11 GPS sites and was sampled four times between 1999 and 2013. Despite the low signal‐to‐noise ratio of the residual velocities obtained, the velocities are nonzero at 95% confidence level. We postulate that the GPS data point to the partitioning of deformation into the NNW–SSE shortening and a N70E left‐lateral component. The maximum deformation rates are located along the two main active faults in the study area. The maximum shortening rates (north component) in the southern region of the Bajo Segura Basin vary from west to east, ranging from 0.2 to 0.7 mm/year along the Bajo Segura Fault Zone. On the northern border of the basin, along the Crevillente Fault Zone, left‐lateral displacement varies between 0.4 and 0.7 mm/year in the E‐W direction. The GPS‐based regional geodynamic models of the Western Mediterranean indicate that the residual shortening of the Eurasia‐Nubia plate convergence is accommodated in the eastern part of the Iberian Peninsula and the Algero‐Balearic Basin. Our results indicate that part of this residual deformation occurs at the NE end of the Eastern Betic Shear Zone, but significant deformation must be accommodated also to the north (External Betics) and to the south (Cartagena Basin and offshore area). We postulate that Eurasia‐Nubia plate convergence is transferred to the Eastern Betics because of the thin and rigid (potentially oceanic) crust of the Algero‐Balearic Basin, which acts as an indenter.
What's Happening

areas. Topics of interest include: artificial intelligence techniques for CGF, nonmilitary applications of CGF, driving simulation, representation of specific tactical doctrines, machine learning, automated planning, and CGF implementation. Daniel E. Mullally Institute for Simulation and Training 3280 Progress Drive Orlando, Florida 32826 Tel: 407-658-5000 E-mail: dmullaly@ucflvm.cc. ucf.edu
&bgr;2-Adrenergic Receptor Polymorphisms and Risk of Incident Cardiovascular Events in the Elderly

Background—Genetic polymorphisms at codons 16 and 27 of the &bgr;2-adrenergic receptor have been associated with altered response to sympathetic stimulation. We examined these polymorphisms in relation to cardiovascular event risk in the Cardiovascular Health Study. Methods and Results—A total of 808 black and 4441 white participants (mean age, 73 years) were genotyped for the Arg16Gly and Gln27Glu polymorphisms of the &bgr;2-adrenergic receptor. There were 702 incident coronary events, 438 ischemic strokes, and 1136 combined cardiovascular events during 7 to 10 years of follow-up. Allele frequencies differed by race but not by age or hypertension status. Glu27 carriers had a lower risk of coronary events than Gln27 homozygotes (hazard ratio, 0.82; 95% CI, 0.70 to 0.95), and there was a suggestion of decreased risk among Gly16 carriers compared with Arg16 homozygotes (hazard ratio, 0.88; 95% CI, 0.72 to 1.07). There was no association of &bgr;2-adrenergic receptor genotype with ischemic stroke or combined cardiovascular events. Conclusions—The Glu27 allele of the &bgr;2-adrenergic receptor was associated with a lower risk of incident coronary events in this elderly population.