Miracle-dz/UniFAR-FTUs huggingface dataset:
Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly

Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities. Abbreviations ADME - Absorption, distribution, metabolism and excretion, BBB - Blood brain barrier, CYP - Cytochrome P450, DENV - – Dengue virus, DHF - Dengue hemorrhagic fever, DSS - Dengue shock syndrome, GCMS - – Gas chromatography- Mass spectrometry, MOLCAD - Molecular Computer Aided Design, NS - Non structural, PDB - Protein data bank, PMF - Potential Mean Force.
Enhanced photoprotection pathways in symbiotic dinoflagellates of shallow-water corals and other cnidarians

Photoinhibition, exacerbated by elevated temperatures, underlies coral bleaching, but sensitivity to photosynthetic loss differs among various phylotypes of Symbiodinium, their dinoflagellate symbionts. Symbiodinium is a common symbiont in many cnidarian species including corals, jellyfish, anemones, and giant clams. Here, we provide evidence that most members of clade A Symbiodinium, but not clades B–D or F, exhibit enhanced capabilities for alternative photosynthetic electron-transport pathways including cyclic electron transport (CET). Unlike other clades, clade A Symbiodinium also undergo pronounced light-induced dissociation of antenna complexes from photosystem II (PSII) reaction centers. We propose these attributes promote survival of most cnidarians with clade A symbionts at high light intensities and confer resistance to bleaching conditions that conspicuously impact deeper dwelling corals that harbor non-clade A Symbiodinium.
Sensitivity of Surface Temperature to Oceanic Forcing via q-Flux Green’s Function Experiments. Part I: Linear Response Function

AbstractThis paper explores the use of the linear response function (LRF) to relate the mean sea surface temperature (SST) response to prescribed ocean heat convergence (q flux) forcings. Two methods for constructing the LRF based on the fluctuation–dissipation theorem (FDT) and Green’s function (GRF) are examined. A 900-yr preindustrial simulation by the Community Earth System Model coupled with a slab ocean model (CESM–SOM) is used to estimate the LRF using FDT. For GRF, 106 pairs of CESM–SOM simulations with warm and cold q-flux patches are performed. FDT is found to have some skill in estimating the SST response to a q-flux forcing when the local SST response is strong, but it fails in inverse estimation of the q-flux forcing for a given SST pattern. In contrast, GRF is shown to be reasonably accurate in estimating both SST response and q-flux forcing. Possible degradation in FDT may be attributed to insufficient data sampling, significant departure of the SST distribution from Gaussianity, and the no.
Expression of Hypoxia-inducible Factors in Human Renal Cancer : Relationship to Angiogenesis and to the von Hippel-Lindau Gene Mutation 1

The von Hippel-Lindau tumor suppressor protein acts as the substrate recognition component of a ubiquitin E3 ligase that targets hypoxiainducible factor (HIF)subunits for proteolysis. Stabilization of HIFsubunits has been described in VHL-defective cell lines, leading to HIF activation and up-regulation of hypoxia-inducible mRNAs. Mutations of the von Hippel-Lindau tumor suppressor protein are found in most clear cell renal cell carcinomas (CC-RCCs) but not other renal tumors, raising a question about the importance of activation of the HIF pathway in CC-RCC development. To address this question, we have examined the expression of HIFsubunits in 45 primary renal tumors and related this to tumor subtype, the presence of VHL mutations, and measures of angiogenesis. We show that HIFis up-regulated in the majority of CC-RCCs, and that the pattern of expression is biased toward the HIF-2 isoform. Expression of HIFproteins was associated significantly with up-regulation of VEGF mRNA and protein and increased microvessel density. Up-regulation of HIFin CC-RCC was found to involve increased mRNA as well as protein expression, suggesting that both VHLdependent and VHL-independent mechanisms are involved. These results suggest that activation of the HIF pathway is functionally important in CC-RCC development and might provide a new therapeutic target.
Surgeons’ early experience with the Acessa™ procedure: gaining proficiency with new technology

Purpose Successful adoption of a new surgical procedure varies among practicing surgeons, and skill acquisition depends on the surgeon’s innate ability, the complexity of the technique, and training. We report intraoperative and near-term postoperative outcomes from the Acessa procedure conducted by minimally invasive gynecologic surgeons new to Acessa, and report the surgeons’ experiences during the training period. Patients and methods The study was designed as a postmarket, prospective, single-arm, multicenter analysis of operative and early postoperative outcomes after proctored surgical training with the Acessa device and procedure (laparoscopic ultrasound-guided radiofrequency volumetric thermal ablation of symptomatic fibroids) in premenopausal, menstruating women as conducted in community and university hospitals in the USA and Canada. Surgeons completed evaluation forms once they felt they could safely and comfortably conduct the operations. Results Ten gynecologic surgeons without prior Acessa experience completed 40 Acessa procedures – all on an outpatient basis. Mean procedure time was 1.9±1.0 hours and was similar to that reported in the pivotal premarket study (2.1±1.0 hours). Two intraoperative complications occurred: a 1 cm uterine serosal laceration due to uterine manipulation and blood loss from both the probe insertion site and the lysis of uterine-omental adhesions. No postoperative complications or reinterventions for fibroid symptoms were reported. The surgeons completed the evaluation forms after two to five cases, and none found any factors affecting procedure efficiency to be inferior or needing improvement. Conclusion Minimally invasive gynecologic surgeons new to Acessa can perform the procedure and provide acceptable outcomes after two to five proctored cases.
Effect of protease inhibitor-containing regimens on lymphocyte multidrug resistance transporter expression.

BACKGROUND Increased expression of multidrug resistance transporters, such as P-glycoprotein (P-gp), has been suggested as a potential mechanism for decreased protease inhibitor (PI) availability at certain intracellular sites and tissue compartments. OBJECTIVES To investigate the effect of PIs on the surface lymphocyte expression of P-gp in vitro and in vivo. PATIENTS AND METHODS Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects (n = 15) and incubated (72 h) with 10 microM of each PI studied (saquinavir, ritonavir, nelfinavir, indinavir, amprenavir and lopinavir), or dimethyl sulphoxide (DMSO) control. PBMCs were also isolated from HIV-infected subjects (n = 50; viral load <50 copies/mL) on a PI- or a non-PI-containing combination antiretroviral regimen. P-gp expression was analysed by flow cytometry. RESULTS No differences in surface P-gp expression on lymphocytes, CD4+ or CD8+ lymphocyte subsets were observed following incubation with 10 microM saquinavir, ritonavir, indinavir, amprenavir or lopinavir in vitro. Nelfinavir, however, increased P-gp expression. In vivo, no difference in P-gp expression on total lymphocytes was observed between patients receiving a PI-containing regimen [saquinavir n = 9, ritonavir n = 6, nelfinavir n = 7, indinavir n = 7 and lopinavir/ritonavir n = 13, and two nucleoside reverse transcriptase inhibitors (NRTIs)] and patients receiving a control regimen of three NRTIs alone (n = 8). CONCLUSION This study suggests that, of the PIs, only nelfinavir increases P-gp expression in vitro, and in vivo the PI class of antiretrovirals do not increase P-gp expression on lymphocytes. It is clear that factors other than PI induction are important in the inter-individual variability in the lymphocyte expression of P-gp.
Amputation and ambulation in diabetic patients: Function is the goal

The role of amputation in limb salvage is often poorly defined because the surgeon and the patient often attempt to save all limbs at all costs. The difficulty lies in selecting limb salvage versus early amputation. For the sedentary patient, a poorly functional salvaged limb can provide him/her with a higher quality of life than he/she would have with an amputation. For the active patient, early major amputation may offer the best functional outcome. Our experience with diabetic limb salvage over the last 20 years was retrospectively reviewed and compared with the existing literature in an attempt to better understand the role of amputation versus limb salvage in patients with diabetes. In the process, surgical techniques that we believe optimize foot and leg amputations were reviewed. Utilizing a team approach, limb salvage can yield a 64% ambulation rate and an 80% 2‐year survival rate. Below‐knee amputation led to a similar ambulatory rate, but the 2‐year survival in these patients was 52%. With more severe rear‐foot ulcers and osteomyelitis, the ambulatory rate declined with each co‐morbity. However, those whose foot was saved had a higher chance of walking than those who underwent amputation. Function and quality of life are the outcomes of interest and may be maximized through either limb salvage or amputation. Our job as physicians is to match the correct solution to the patients' lifestyle and their medical, physical and psychological conditions so they can achieve their desired level of activity as quickly as possible. Level of evidence: IV. Copyright © 2012 John Wiley & Sons, Ltd.
Dietary methods and biomarkers of omega 3 fatty acids: a systematic review

The aims of the present study were to review the validity of dietary methods used to measure the usual long chain (LC) omega-3 polyunsaturated fatty acid (n-3 PUFA) intake of a population and to assess the usefulness of different biomarkers of n-3 PUFA in healthy humans. Two systematic literature searches were conducted until May 2011 to update previous systematic reviews. The first literature search aimed to find studies validating the methodology used for measuring the dietary intake of n-3 PUFA. The second search aimed to find human intervention studies in which n-3 PUFA status changed after 2 weeks of n-3 PUFA supplementation. Sixteen studies were identified for inclusion in the first review. Correlation coefficients between fatty acids in subcutaneous fat or blood lipids and dietary intake of n-3 PUFA from different questionnaires were similar. Subcutaneous fat has been reported as the best reference method for some authors, and these studies showed moderate correlation coefficients with no dietary intake method being superior to any other. As for the evaluation of biomarkers of docosahexaenoic acid (DHA, 22 : 6 n-3) and eicosapentaenoic acid (EPA, 20 : 5n-3) status in response to supplementation, the new search reaffirmed and reinforced the evidence supporting that plasma phospholipid DHA, erythrocyte DHA, and platelet DHA were all effective and robust biomarkers of DHA status. Our findings only confirmed earlier studies and did not provide evidence for reaching new conclusions.
Phosphorylation of Myristoylated Alanine‐Rich C Kinase Substrate (MARCKS) by Proline‐Directed Protein Kinases and Its Dephosphorylation

Abstract: We identified two major substrates for the proline‐directed protein kinases—cdc2 kinase and tau protein kinase II (TPKII)—in the cytosol fraction from rat brains. The molecular masses of the proteins were 80 and 46 kDa. Because the 80‐kDa protein was phosphorylated by protein kinase C and was heat stable, we examined the possibility that the protein might be myristoylated alanine‐rich C kinase substrate (MARCKS). On the basis of a comparison between the properties of the 80‐kDa protein and purified MARCKS, we concluded that the 80‐kDa protein is indeed MARCKS. The amounts of phosphate incorporated into MARCKS by protein kinase C, cdc2 kinase, and TPKII were 1.7, 1.4, and 0.6 mol/mol of the protein, respectively. Two‐dimensional tryptic peptide mapping indicated that phosphorylation sites by protein kinase C and proline‐directed protein kinases completely differed. Only the seryl residue was phosphorylated by protein kinase C, whereas both seryl and threonyl residues were phosphorylated by cdc2 kinase and TPKII. Phosphorylation of MARCKS by protein kinase C inhibited the binding to calmodulin, whereas phosphorylation by cdc2 kinase and TPKII significantly increased the binding to calmodulin. The holoenzyme of protein phosphatase 2A dephosphorylated MARCKS that had been phosphorylated by protein kinase C, cdc2 kinase, or TPKII, whereas calcineurin was unable to dephosphorylate it. These results suggest that cdc2 kinase and TPKII regulate the functions of MARCKS in different ways from protein kinase C.
Sonographic Visualization of the Fetal Upper Airway

Laryngeal obstruction is a life‐threatening condition which can sometimes be diagnosed by prenatal ultrasound examination. Dilatation of the fetal trachea is an important finding in these cases. Sonographic studies to evaluate the fetal upper airway were performed in 120 consecutive patients. The diameters of the trachea and pharynx were measured and our ability to visualize the trachea and the larynx was evaluated. The diameter of the trachea increased from a mean of 2.4 mm at 18 weeks to 4.6 mm at 38 weeks. The mean diameter of the pharynx increased from 4.4 mm at 18 weeks to 8.8 mm at 38 weeks. The fetal larynx was adequately visualized in 67%) of the cases, while the entire trachea was seen in 47% of the cases. Our success in visualizing the larynx and trachea was best between 20 and 30 weeks' gestation. This study shows that it is possible to obtain excellent views of the fetal airway in a high percentage of cases and reports the range of normal values for tracheal diameter. Early visualization of a diluted trachea may allow better management of a fetus with laryngeal obstruction. Copyright © 1994 International Society of Ultrasound in Obstetrics and Gynecology
Risk stratification of chronic heart failure patients by multiple biomarkers: implications of BNP, H-FABP, and PTX3.

BACKGROUND B-type natriuretic peptide (BNP), heart-type fatty acid-binding protein (H-FABP), and pentraxin 3 (PTX3) each predict adverse cardiac events in chronic heart failure (CHF) patients. For prognostic evaluation from different aspects, the utility of combined measurement of the 3 biomarkers in patients with CHF was examined in the present study. METHODS AND RESULTS Levels of BNP (associated with left ventricular dysfunction, positive if >200 pg/ml), H-FABP (marker of myocardial damage, positive if >4.1 ng/ml), and PTX3 (marker of inflammation, positive if >4.0 ng/ml) were measured in 164 consecutive CHF patients, and patients were prospectively followed with endpoints of cardiac death or rehospitalization. When patients were categorized on the basis of the number of elevated biomarkers, patients with 1, 2, and 3 elevated biomarkers had a 5.4-fold (not significant), 11.2-old (p<0.05), and 34.6-fold increase (p<0.01), respectively, in the risk of adverse cardiac events compared with those without elevated biomarkers. Kaplan-Meier analysis revealed that patients with 3 elevated biomarkers had a significantly higher cardiac event rate than patients with a lower number of elevated biomarkers. CONCLUSION The combination of these 3 biomarkers could reliably risk-stratify CHF patients for prediction of cardiac events.
Genetic analyses of DSM-IV nicotine withdrawal in adult twins

Background. We examined whether there are genetic influences on nicotine withdrawal, and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Method. Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from young adult Australian twins reporting any cigarette use (3026 women, 2553 men; mean age 30 years). Results. Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26–43%), and similar in men and women. The exceptions were depressed mood upon withdrawal, which had stronger additive genetic influences in men (53%) compared to women (29%), and decreased heart rate, which had low heritability (9%). Although prevalence rates were substantially lower for DSM-IV nicotine withdrawal syndrome (15·9%), which requires impairment, than for the DSM-IV nicotine dependence withdrawal criterion (43·6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime (‘progression’), quantity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations=0·53–0·76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Conclusions. Our results suggest that at least some individuals become ‘hooked’ or progress in the smoking habit, in part, because of a vulnerability to nicotine withdrawal.
Cellular data meet vehicular traffic theory: location area updates and cell transitions for travel time estimation

Road traffic can be monitored by means of static sensors and derived from floating car data, i.e., reports from a sub-set of vehicles. These approaches suffer from a number of technical and economical limitations. Alternatively, we propose to leverage the mobile cellular network as a ubiquitous mobility sensor. We show how vehicle travel times and road congestion can be inferred from anonymized signaling data collected from a cellular mobile network. While other previous studies have considered data only from active devices, e.g., engaged in voice calls, our approach exploits also data from idle users resulting in an enormous gain in coverage and estimation accuracy. By validating our approach against four different traffic monitoring datasets collected on a sample highway over one month, we show that our method can detect congestions very accurately and in a timely manner.
Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites

The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga. DOI: http://dx.doi. org/10.7554/eLife.06974. 001
Urban greenhouse gas emissions as observed using a high-density sensor network

Author(s): Shusterman, Alexis | Advisor(s): Cohen, Ronald C | Abstract: More than 70% of anthropogenic carbon dioxide emissions originate from cities, and that fraction is expected to grow with the increasing urbanization of the world population. Monitoring, reporting, and verification (MRV) of emission mitigation initiatives are complicated in urban areas by the combination of spatio-temporally heterogeneous landscapes of CO2 sources and poorly constrained turbulent fluid dynamics near the rough and irregular surfaces of urban topography. In this dissertation, I present a novel approach to MRV of urban emissions using a distributed network of near-surface ambient CO2 monitors stationed at 2 km intervals across an urban dome. The study area is the San Francisco Bay Area, a location characterized by a high density of disparate emission sources, irregular topography, as well as strong municipal and state level commitments to emission reductions. First, I describe the design, implementation, and evaluation of this unprecedented monitoring approach, hereafter the BErkeley Atmospheric CO2 Observation Network (BEACO2N). I demonstrate how the use of lower cost sensor technologies enables a high volume of monitors to be deployed at a cost competitive with conventional, non-spatially resolved monitoring approaches and find the lower cost monitors to be of sufficient accuracy and precision to capture typical urban CO2 phenomena. Second, I leverage this validated framework to provide the first high-resolution characterization of the neighborhood-to-neighborhood variability in local CO2 concentrations across the San Francisco Bay Area. I find significant differences even between nearby pairs of monitoring sites, leading to the derivation of a relatively short spatial correlation length scale for the study area and demonstrating a high degree of sensitivity to the unique emission sources local to each site. I determine these sensitivities to be capable of detecting changes in emission processes of policy-relevant magnitudes, providing a viable new constraint on regulations concerning, for example, fuel efficiency and vehicle electrification. Finally, I compare the CO2 concentrations measured at nine BEACO2N sites to those predicted by an ensemble of atmospheric transport models. I find large disagreements between the observations and the simulations, only a small portion of which can be explained by known measurement errors or the spread in plausible transport and emissions scenarios, highlighting the utility of high-density observations for the validation and improvement of conventional modeling frameworks. Taken together, this body of work demonstrates the promise of atmospheric observation networks based on moderate quality sensor technologies as a practicable approach to the challenge of monitoring urban greenhouse gas emission patterns and trends.