The Moderate-Resolution Imaging Spectroradiometer (MODIS) level-2 (L2) cloud product (earth science data set names MOD06 and MYD06 for Terra and Aqua MODIS, respectively) provides pixel-level ...retrievals of cloud top properties (day and night pressure, temperature, and height) and cloud optical properties (optical thickness, effective particle radius, and water path for both liquid water and ice cloud thermodynamic phases-daytime only). Collection 6 (C6) reprocessing of the product was completed in May 2014 and March 2015 for MODIS Aqua and Terra, respectively. Here we provide an overview of major C6 optical property algorithm changes relative to the previous Collection 5 (C5) product. Notable C6 optical and microphysical algorithm changes include: 1) new ice cloud optical property models and a more extensive cloud radiative transfer code lookup table (LUT) approach; 2) improvement in the skill of the shortwave-derived cloud thermodynamic phase; 3) separate cloud effective radius retrieval data sets for each spectral combination used in previous collections; 4) separate retrievals for partly cloudy pixels and those associated with cloud edges; 5) failure metrics that provide diagnostic information for pixels having observations that fall outside the LUT solution space; and 6) enhanced pixel-level retrieval uncertainty calculations. The C6 algorithm changes can collectively result in significant changes relative to C5, though the magnitude depends on the data set and the pixel's retrieval location in the cloud parameter space. Example L2 granule and level-3 gridded data set differences between the two collections are shown. While the emphasis is on the suite of cloud optical property data sets, other MODIS cloud data sets are discussed when relevant.
Orofacial clefts (OFCs) include a broad range of facial conditions that differ in cause and disease burden. In the published literature, there is substantial ambiguity in both terminology and ...classification of OFCs. This article discusses the terminology and classification of OFCs and the epidemiology of OFCs. Demographic, environmental, and genetic risk factors for OFCs are described, including suggestions for family counseling. This article enables clinicians to counsel families regarding the occurrence and recurrence of OFCs. Although much of the information is detailed, it is intended to be accessible to all health professionals for use in their clinical practices.
Photosynthetic organisms provide food and energy for nearly all life on Earth, yet half of their protein-coding genes remain uncharacterized
. Characterization of these genes could be greatly ...accelerated by new genetic resources for unicellular organisms. Here we generated a genome-wide, indexed library of mapped insertion mutants for the unicellular alga Chlamydomonas reinhardtii. The 62,389 mutants in the library, covering 83% of nuclear protein-coding genes, are available to the community. Each mutant contains unique DNA barcodes, allowing the collection to be screened as a pool. We performed a genome-wide survey of genes required for photosynthesis, which identified 303 candidate genes. Characterization of one of these genes, the conserved predicted phosphatase-encoding gene CPL3, showed that it is important for accumulation of multiple photosynthetic protein complexes. Notably, 21 of the 43 higher-confidence genes are novel, opening new opportunities for advances in understanding of this biogeochemically fundamental process. This library will accelerate the characterization of thousands of genes in algae, plants, and animals.
Background
Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010–2014.
...Methods
Data from 39 U.S. population‐based birth defects surveillance programs (16 active case‐finding, 10 passive case‐finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case‐finding approach. Fourteen active case‐finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time.
Results
The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case‐finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18.
Conclusion
National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.
Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient ...responses for patient-selection strategies. We established ∼1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 × 1 × 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Titanium (Ti) has been widely used as an implant material due to the excellent biocompatibility and corrosion resistance of its oxide surface. Biomaterials must be sterile before implantation, but ...the effects of sterilization on their surface properties have been less well studied. The effects of cleaning and sterilization on surface characteristics were bio-determined using contaminated and pure Ti substrata first manufactured to present two different surface structures: pretreated titanium (PT, Ra=0.4μm) (i.e. surfaces that were not modified by sandblasting and/or acid etching); (SLA, Ra=3.4μm). Previously cultured cells and associated extracellular matrix were removed from all bio-contaminated specimens by cleaning in a sonicator bath with a sequential acetone–isopropanol–ethanol–distilled water protocol. Cleaned specimens were sterilized with autoclave, gamma irradiation, oxygen plasma, or ultraviolet light. X-ray photoelectron spectroscopy (XPS), contact angle measurements, profilometry, and scanning electron microscopy were used to examine surface chemical components, hydrophilicity, roughness, and morphology, respectively. Small organic molecules present on contaminated Ti surfaces were removed with cleaning. XPS analysis confirmed that surface chemistry was altered by both cleaning and sterilization. Cleaning and sterilization affected hydrophobicity and roughness. These modified surface properties affected osteogenic differentiation of human MG63 osteoblast-like cells. Specifically, autoclaved SLA surfaces lost the characteristic increase in osteoblast differentiation seen on starting SLA surfaces, which was correlated with altered surface wettability and roughness. These data indicated that recleaned and resterilized Ti implant surfaces cannot be considered the same as the first surfaces in terms of surface properties and cell responses. Therefore, the reuse of Ti implants after resterilization may not result in the same tissue responses as found with never-before-implanted specimens.
The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic ...β-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD). However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients.
N=52 patients (n=16 NAFLD and n=36 Non-alcoholic steatohepatitis (NASH) patients) and n=50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration.
Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001). In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH.
Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
Increased delivery of bile acid salts (BA) to distal L‐cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after ...bariatric surgery. To further elucidate a potential role of BA in the secretion of GLP‐1 and PYY, we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospective, randomized 1‐year trial.
Design and Methods
Patients received a standard test meal and blood was collected before and after eating, prior to, and 1 week, 3 months, and 12 months after surgery.
Results
Pre‐surgery, basal BA concentrations were significantly lower in bariatric patients than in healthy controls. One year post‐surgery, bariatric patients expressed variably increased BA concentrations (gastric bypass patients ∼2 fold increase, P ≤ 0.05). However, whereas in both patient groups, marked increases in GLP‐1 and PYY and improved glycemic control was seen already 1 week and 3 months post‐surgery, changes in plasma BA followed a different pattern: basal and postprandial plasma BA concentrations increased much slower, more progressively with significant increases only 1‐year post‐surgery.
Conclusions
Based on these findings, BA do not appear to be key mediators of the early increase in GLP‐1 and PYY response in post‐bariatric patients.
Toxic metals including arsenic, cadmium, manganese, and lead are known human developmental toxicants that are able to cross the placental barrier from mother to fetus. In this population-based study, ...we assess the association between metal concentrations in private well water and birth defect prevalence in North Carolina.
A semi-ecologic study was conducted including 20,151 infants born between 2003 and 2008 with selected birth defects (cases) identified by the North Carolina Birth Defects Monitoring Program, and 668,381 non-malformed infants (controls). Maternal residences at delivery and over 10,000 well locations measured for metals by the North Carolina Division of Public Health were geocoded. The average level of each metal was calculated among wells sampled within North Carolina census tracts. Individual exposure was assigned as the average metal level of the census tract that contained the geocoded maternal residence. Prevalence ratios (PR) with 95% confidence intervals (CI) were calculated to estimate the association between the prevalence of birth defects in the highest category (≥90th percentile) of average census tract metal levels and compared to the lowest category (≤50th percentile).
Statewide, private well metal levels exceeded the EPA Maximum Contaminant Level (MCL) or secondary MCL for arsenic, cadmium, manganese, and lead in 2.4, 0.1, 20.5, and 3.1 percent of wells tested. Elevated manganese levels were statistically significantly associated with a higher prevalence of conotruncal heart defects (PR: 1.6 95% CI: 1.1-2.5).
These findings suggest an ecologic association between higher manganese concentrations in drinking water and the prevalence of conotruncal heart defects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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