Impact of Radiatively Interactive Dust Aerosols in the NASA GEOS-5 Climate Model: Sensitivity to Dust Particle Shape and Refractive Index

We investigate the radiative effects of dust aerosols in the NASA GEOS-5 atmospheric general circulation model. GEOS-5 is improved with the inclusion of a sectional aerosol and cloud microphysics module, the Community Aerosol and Radiation Model for Atmospheres (CARMA). Into CARMA we introduce treatment of the dust and sea salt aerosol lifecycle, including sources, transport evolution, and sinks. The aerosols are radiatively coupled to GEOS-5, and we perform a series of multi-decade AMIP-style simulations in which dust optical properties (spectral refractive index and particle shape distribution) are varied. Optical properties assuming spherical dust particles are from Mie theory, while those for non-spherical shape distributions are drawn from a recently available database for tri-axial ellipsoids. The climatologies of the various simulations generally compare well to data from the MODIS, MISR, and CALIOP space-based sensors, the ground-based AERONET, and surface measurements of dust deposition and concentration. Focusing on the summertime Saharan dust cycle we show significant variability in our simulations resulting from different choices of dust optical properties. Atmospheric heating due to dust enhances surface winds over important Saharan dust sources, and we find a positive feedback where increased dust absorption leads to increased dust emissions. We further find that increased dust absorption leads to a strengthening of the summertime Hadley cell circulation, increasing dust lofting to higher altitudes and strengthening the African Easterly Jet. This leads to a longer atmospheric residence time, higher altitude, and generally more northward transport of dust in simulations with the most absorbing dust optical properties. We find that particle shape, although important for radiance simulations, is a minor effect compared to choices of refractive index, although total atmospheric forcing is enhanced by greater than 10 percent for simulations incorporating a spheroidal shape distribution versus ellipsoidal or spherical shapes

Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery

Chromosome 1 of Vibrio vulnificus tends to contain larger portion of essential or housekeeping genes on the basis of the genomic analysis and gene knockout experiments performed in this study, while its chromosome 2 seems to have originated and evolved from a plasmid.The genome-scale metabolic network model of V. vulnificus was reconstructed based on databases and literature, and was used to identify 193 essential metabolites.Five essential metabolites finally selected after the filtering process are 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine (AHHMP), D-glutamate (DGLU), 2,3-dihydrodipicolinate (DHDP), 1-deoxy-D-xylulose 5-phosphate (DX5P), and 4-aminobenzoate (PABA), which were predicted to be essential in V. vulnificus, absent in human, and are consumed by multiple reactions.Chemical analogs of the five essential metabolites were screened and a hit compound showing the minimal inhibitory concentration (MIC) of 2 μg/ml and the minimal bactericidal concentration (MBC) of 4 μg/ml against V. vulnificus was identified

A Prospective Study of Single-Dose Antibiotic Prophylaxis in Live Donor Nephrectomy

PURPOSE: To perform a prospective analysis of the clinical outcomes of prophylactic antibiotic treatment before the standard surgical modality of living donor nephrectomy (LDN) without postoperative antibiotic treatment. MATERIALS AND METHODS: From November 2005 to June 2010, a total of 470 patients underwent LDN at our medical institution, and 280 of these patients were injected with 1 g cephalosporin 30 minutes before the operation. The group receiving prophylactic antibiotics was compared with a control group composed of 190 patients who received injections of 2 g cephalosporin per day for 5 days after the operation. The presence of fever, incidence of blood transfusion, and period of drainage use were compared between the two groups. RESULTS: There were no significant differences in gender, age, body mass index, incidence of blood transfusion after the operation, fever over 38degrees C 3 days after the operation, or period of drain insertion between the single-dose group and the control group. The follow-up was conducted for 1 month after the operation, and 1 case of surgical site infection (SSI) was observed in each group (p=0.783). CONCLUSIONS: Of 280 patients in the single-dose group, 1 contracted SSI. In comparison with the control group, which was dosed with prophylactic antibiotics for 5 days after the operation, the single-dose group did not have a significantly different occurrence of SSI. We found that the incidence rate of SSI did not increase, even though prophylactic antibiotics were not used after standard and conventional open surgeries, such as video-assisted minilaparotomy surgery.ope

The pNNx Heart Rate Variability Statistics: An Application to Neuroautonomic Dysfunction of Clozapine-Treated Subjects

Objective The percentage Of Successive normal cardiac interbeat intervals greater than 50 msec (pNN50) is a widely used heart rate variability measure, which is useful in identifying the neuroautonomic dysfunction of psychiatric disorders. However, pNN50 is only one member of a larger family of pNNx statistics, where x is greater than 0 msec. The potential application of the general pNNx statistics has not yet been explored in the psychiatric field. The authors examined the pNNx statistics in clozapine-treated subjects and normal controls to evaluate the usefulness of the general pNNx statistics. Methods Sixty-one schizophrenic patients treated with clozapine and fifty-nine normal controls were evaluated. probability values for the differences between the groups at each pNN value (range: pNN1-pNN100) were calculated using data obtained from a 30-minute electrocardiogram. Results The conventional pNN50 and pNNx values with x<50 msec were all significantly lower in the patient group (p<0.05). The distinction between the two groups was more prominent at pNN values less than 50 msec than that observed at pNN50. The maximum separation between groups occurred at pNN5 (68.2 +/- 19.1 vs 22.5 +/- 20.5, p<10(-22)). Conclusion The pNNx with x<50 msec provided more robust discrimination between the groups than the conventional pNN50, suggesting the importance of analyzing very small variations of interbeat interval in discriminating normal and pathological heart rate patterns. The results also Suggest that the general pNNx statistics may be applied and useful in evaluating the neuroautonomic dysfunction in patients treated with clozapine, complementing the traditionally Computed pNN50 value. Psychiatry Invest 2009;6:294-298This study was supported in part by the Brain Korea 21 project for Medicine, Dentistry, and Pharmacy (Seoul National University) and by Grant No. 04-2006-0540 from Seoul National University Hospital.Duschek S, 2009, HYPERTENS RES, V32, P938, DOI 10.1038/hr.2009.115Lollgen D, 2009, MUSCLE NERVE, V39, P536, DOI 10.1002/mus.21242Siepmann M, 2008, APPL PSYCHOPHYS BIOF, V33, P195, DOI 10.1007/s10484-008-9064-zBar KB, 2008, J CLIN PSYCHOPHARM, V28, P694, DOI 10.1097/JCP.0b013e31818a6d25Bar KJ, 2008, PSYCHIAT RES, V157, P255, DOI 10.1016/j.psychres.2007.04.021Bar KJ, 2007, CLIN NEUROPHYSIOL, V118, P2009, DOI 10.1016/j.clinph.2007.06.012Bar KJ, 2007, SCHIZOPHR RES, V95, P115, DOI 10.1016/j.schres.2007.05.034Kim JH, 2006, EUR NEUROPSYCHOPHARM, V16, P459, DOI 10.1016/j.euroneuro.2005.11.003Mujica-Parodi LR, 2005, NEUROPSYCHOBIOLOGY, V51, P10, DOI 10.1159/000082850KIM W, 2005, J KOREAN NEUROPSYCHI, V44, P176Tank J, 2004, HYPERTENSION, V43, P1035, DOI 10.1161/01.HYP.0000125729.90521.94Kim JH, 2004, PROG NEURO-PSYCHOPH, V28, P371, DOI 10.1016/j.pnpbp.2003.11.007Mueck-Weymann M, 2004, CLIN AUTON RES, V14, P15, DOI 10.1007/s10286-004-0123-0Yeragani VK, 2003, PSYCHIAT RES, V121, P185, DOI 10.1016/S0165-1781(03)00235-XAgelink MW, 2003, PHARMACOPSYCHIATRY, V36, P166Mietus JE, 2002, HEART, V88, P378Yeragani VK, 2002, BIOL PSYCHIAT, V52, P418Eschweiler GW, 2002, PHARMACOPSYCHIATRY, V35, P96Goldberger AL, 2002, P NATL ACAD SCI USA, V99, P2466, DOI 10.1073/pnas.012579499Ansakorpi H, 2002, J NEUROL NEUROSUR PS, V72, P26MALASPINA D, 2002, CNS SPECTRUMS, V7, P53Mueck-Weymann M, 2002, DEPRESS ANXIETY, V16, P93, DOI 10.1002/da.10037Cohen H, 2001, BRIT J PSYCHIAT, V179, P167Haapaniemi TH, 2001, J NEUROL NEUROSUR PS, V70, P305Cohen H, 2001, CLIN NEUROPHARMACOL, V24, P106Agelink MW, 2001, J CLIN PSYCHOPHARM, V21, P8Toichi M, 1999, INT J PSYCHOPHYSIOL, V31, P147Malaspina D, 1997, BIOL PSYCHIAT, V41, P612Korpelainen JT, 1996, STROKE, V27, P2059HALL RCW, 1995, PSYCHOSOMATICS, V36, P267RECHLIN T, 1994, BIOL PSYCHIAT, V35, P888*AM PSYCH ASS, 1994, DIAGN STAT MAN MENT, P273HUIKURI HV, 1990, AM J CARDIOL, V65, P391BIGGER JT, 1988, AM J CARDIOL, V61, P208KAY SR, 1987, SCHIZOPHRENIA BULL, V13, P261EWING DJ, 1984, BRIT HEART J, V52, P396GUY W, 1976, ECDEU ASSESSMENT PSY

Methylsulfonylmethane Suppresses Breast Cancer Growth by Down-Regulating STAT3 and STAT5b Pathways

Breast cancer is the most aggressive form of all cancers, with high incidence and mortality rates. The purpose of the present study was to investigate the molecular mechanism by which methylsulfonylmethane (MSM) inhibits breast cancer growth in mice xenografts. MSM is an organic sulfur-containing natural compound without any toxicity. In this study, we demonstrated that MSM substantially decreased the viability of human breast cancer cells in a dose-dependent manner. MSM also suppressed the phosphorylation of STAT3, STAT5b, expression of IGF-1R, HIF-1α, VEGF, BrK, and p-IGF-1R and inhibited triple-negative receptor expression in receptor-positive cell lines. Moreover, MSM decreased the DNA-binding activities of STAT5b and STAT3, to the target gene promoters in MDA-MB 231 or co-transfected COS-7 cells. We confirmed that MSM significantly decreased the relative luciferase activities indicating crosstalk between STAT5b/IGF-1R, STAT5b/HSP90α, and STAT3/VEGF. To confirm these findings in vivo, xenografts were established in Balb/c athymic nude mice with MDA-MB 231 cells and MSM was administered for 30 days. Concurring to our in vitro analysis, these xenografts showed decreased expression of STAT3, STAT5b, IGF-1R and VEGF. Through in vitro and in vivo analysis, we confirmed that MSM can effectively regulate multiple targets including STAT3/VEGF and STAT5b/IGF-1R. These are the major molecules involved in tumor development, progression, and metastasis. Thus, we strongly recommend the use of MSM as a trial drug for treating all types of breast cancers including triple-negative cancers

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie