Highly Enantioselective Catalytic Alkynylation of Quinolones: Substrate Scope, Mechanistic Studies, and Applications in the Syntheses of Chiral -Heterocyclic Alkaloids and Diamines.

The alkynylation of 4-siloxyquinolinium triflates has been achieved under the influence of copper bis(oxazoline) catalysis. The identification of the optimal bis(oxazoline) ligand was informed through a computational approach that enabled the dihydroquinoline products to be produced with up to 96% enantiomeric excess. The conversions of the dihydroquinoline products to biologically relevant and diverse targets are reported.

Bark beetle impacts on forest evapotranspiration and its partitioning.

Insect outbreaks affect forest structure and function and represent a major category of forest disturbance globally. However, the resulting impacts on evapotranspiration (ET), and especially hydrological partitioning between the abiotic (evaporation) and biotic (transpiration) components of total ET, are not well constrained. As a result, we combined remote sensing, eddy covariance, and hydrological modeling approaches to determine the effects of bark beetle outbreak on ET and its partitioning at multiple scales throughout the Southern Rocky Mountain Ecoregion (SRME), USA.

Geographically targeted chronic infection screening: lessons from a hepatitis B pilot study in the UK.

Chronic hepatitis B (CHB) most commonly occurs following infection in early childhood. Prevalence varies markedly around the globe. Country of birth is therefore a strong predictor of CHB risk in adults.

No evidence of canopy-scale leaf thermoregulation to cool leaves below air temperature across a range of forest ecosystems.

Understanding and predicting the relationship between leaf temperature () and air temperature () is essential for projecting responses to a warming climate, as studies suggest that many forests are near thermal thresholds for carbon uptake. Based on leaf measurements, the limited leaf homeothermy hypothesis argues that daytime is maintained near photosynthetic temperature optima and below damaging temperature thresholds. Specifically, leaves should cool below at higher temperatures (i.

MEDLINE search retrieval issues: A longitudinal query analysis of five vendor platforms.

This study compared the results of data collected from a longitudinal query analysis of the MEDLINE database hosted on multiple platforms that include PubMed, EBSCOHost, Ovid, ProQuest, and Web of Science. The goal was to identify variations among the search results on the platforms after controlling for search query syntax. We devised twenty-nine cases of search queries comprised of five semantically equivalent queries per case to search against the five MEDLINE database platforms.

Montane forest productivity across a semiarid climatic gradient.

High-elevation montane forests are disproportionately important to carbon sequestration in semiarid climates where low elevations are dry and characterized by low carbon density ecosystems. However, these ecosystems are increasingly threatened by climate change with seasonal implications for photosynthesis and forest growth. As a result, we leveraged eddy covariance data from six evergreen conifer forest sites in the semiarid western United States to extrapolate the status of carbon sequestration within a framework of projected warming and drying.

Mechanistic evidence for tracking the seasonality of photosynthesis with solar-induced fluorescence.

Northern hemisphere evergreen forests assimilate a significant fraction of global atmospheric CO but monitoring large-scale changes in gross primary production (GPP) in these systems is challenging. Recent advances in remote sensing allow the detection of solar-induced chlorophyll fluorescence (SIF) emission from vegetation, which has been empirically linked to GPP at large spatial scales. This is particularly important in evergreen forests, where traditional remote-sensing techniques and terrestrial biosphere models fail to reproduce the seasonality of GPP.

PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial.

Purpose: Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth . Presurgical window studies allow rapid assessment of antitumor activity.

Assessing the interplay between canopy energy balance and photosynthesis with cellulose δO: large-scale patterns and independent ground-truthing.

There are few whole-canopy or ecosystem scale assessments of the interplay between canopy temperature and photosynthesis across both spatial and temporal scales. The stable oxygen isotope ratio (δO) of plant cellulose can be used to resolve a photosynthesis-weighted estimate of canopy temperature, but the method requires independent confirmation. We compare isotope-resolved canopy temperatures derived from multi-year homogenization of tree cellulose δO to canopy-air temperatures weighted by gross primary productivity (GPP) at multiple sites, ranging from warm temperate to boreal and subalpine forests.

Measuring spatiotemporal variation in snow optical grain size under a subalpine forest canopy using contact spectroscopy.

The distribution of forest cover exerts strong controls on the spatiotemporal distribution of snow accumulation and snowmelt. The physical processes that govern these controls are poorly understood given a lack of detailed measurements of snow states. In this study, we address one of many measurement gaps by using contact spectroscopy to measure snow optical grain size at high spatial resolution in trenches dug between tree boles in a subalpine forest.

Inhibition of DYRK1A Stimulates Human β-Cell Proliferation.

Restoring functional β-cell mass is an important therapeutic goal for both type 1 and type 2 diabetes (1). While proliferation of existing β-cells is the primary means of β-cell replacement in rodents (2), it is unclear whether a similar principle applies to humans, as human β-cells are remarkably resistant to stimulation of division (3,4). Here, we show that 5-iodotubercidin (5-IT), an annotated adenosine kinase inhibitor previously reported to increase proliferation in rodent and porcine islets (5), strongly and selectively increases human β-cell proliferation in vitro and in vivo.

Terrestrial carbon balance in a drier world: the effects of water availability in southwestern North America.

Global modeling efforts indicate semiarid regions dominate the increasing trend and interannual variation of net CO2 exchange with the atmosphere, mainly driven by water availability. Many semiarid regions are expected to undergo climatic drying, but the impacts on net CO2 exchange are poorly understood due to limited semiarid flux observations. Here we evaluated 121 site-years of annual eddy covariance measurements of net and gross CO2 exchange (photosynthesis and respiration), precipitation, and evapotranspiration (ET) in 21 semiarid North American ecosystems with an observed range of 100 - 1000 mm in annual precipitation and records of 4-9 years each.

Epidemiology and patterns of musculoskeletal motorcycle injuries in the USA.

Introduction: Motorcycles have become an increasingly popular mode of transportation despite their association with a greater risk for injury compared with automobiles. Whereas the recent incidence of annual passenger vehicle fatalities in the United States of America (USA) has progressively declined, motorcycle fatalities have steadily increased in the past 11 years. Although motorcycle injuries (MIs) have been studied, to the author's knowledge there are no published reports on MIs in the USA during this 11-year period.

Greenness indices from digital cameras predict the timing and seasonal dynamics of canopy-scale photosynthesis.

The proliferation of digital cameras co-located with eddy covariance instrumentation provides new opportunities to better understand the relationship between canopy phenology and the seasonality of canopy photosynthesis. In this paper we analyze the abilities and limitations of canopy color metrics measured by digital repeat photography to track seasonal canopy development and photosynthesis, determine phenological transition dates, and estimate intra-annual and interannual variability in canopy photosynthesis. We used 59 site-years of camera imagery and net ecosystem exchange measurements from 17 towers spanning three plant functional types (deciduous broadleaf forest, evergreen needleleaf forest, and grassland/crops) to derive color indices and estimate gross primary productivity (GPP).

The relationship between manuscript title structure and success: editorial decisions and citation performance for an ecological journal.

A poorly chosen article title may make a paper difficult to discover or discourage readership when discovered, reducing an article's impact. Yet, it is unclear how the structure of a manuscript's title influences readership and impact. We used manuscript tracking data for all manuscripts submitted to the journal Functional Ecology from 2004 to 2013 and citation data for papers published in this journal from 1987 to 2011 to examine how title features changed and whether a manuscript's title structure was predictive of success during the manuscript review process and/or impact (citation) after publication.

Kinase-Independent Small-Molecule Inhibition of JAK-STAT Signaling.

Phenotypic cell-based screening is a powerful approach to small-molecule discovery, but a major challenge of this strategy lies in determining the intracellular target and mechanism of action (MoA) for validated hits. Here, we show that the small-molecule BRD0476, a novel suppressor of pancreatic β-cell apoptosis, inhibits interferon-gamma (IFN-γ)-induced Janus kinase 2 (JAK2) and signal transducer and activation of transcription 1 (STAT1) signaling to promote β-cell survival. However, unlike common JAK-STAT pathway inhibitors, BRD0476 inhibits JAK-STAT signaling without suppressing the kinase activity of any JAK.

Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.

High-throughput luminescent reporter of insulin secretion for discovering regulators of pancreatic Beta-cell function.

Defects in insulin secretion play a central role in the pathogenesis of type 2 diabetes, yet the mechanisms driving beta-cell dysfunction remain poorly understood, and therapies to preserve glucose-dependent insulin release are inadequate. We report a luminescent insulin secretion assay that enables large-scale investigations of beta-cell function, created by inserting Gaussia luciferase into the C-peptide portion of proinsulin. Beta-cell lines expressing this construct cosecrete luciferase and insulin in close correlation, under both standard conditions or when stressed by cytokines, fatty acids, or ER toxins.

Targeting the pancreatic β-cell to treat diabetes.

Diabetes is a leading cause of morbidity and mortality worldwide, and predicted to affect over 500 million people by 2030. However, this growing burden of disease has not been met with a comparable expansion in therapeutic options. The appreciation of the pancreatic β-cell as a central player in the pathogenesis of both type 1 and type 2 diabetes has renewed focus on ways to improve glucose homeostasis by preserving, expanding and improving the function of this key cell type.

Finding a job in an overcrowded market: getting what you want.

As the number of fellowship-trained orthopaedic trauma surgeons entering the workforce increases, so does the competition for available practice opportunities. The process of finding employment has seemingly become more involved as the relative availability of positions has declined over recent years. To manage this new environment, new graduates need to become much more proactive in the process of seeking and obtaining orthopaedic trauma positions.

Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes during acquisition of typical fluoroscopic views of the hip and pelvis.

Background: Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward.

Methods: Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views.