Dominant contribution of atmospheric nonlinearities to ENSO asymmetry and extreme El Niño events.

Extreme El Niño events have outsized impacts and strongly contribute to the El Niño Southern Oscillation (ENSO) warm/cold phase asymmetries. There is currently no consensus on the respective importance of oceanic and atmospheric nonlinearities for those asymmetries. Here, we use atmospheric and oceanic general circulation models that reproduce ENSO asymmetries well to quantify the atmospheric nonlinearities contribution.

A distinct and reproducible teleconnection pattern over North America during extreme El Niño events.

El Niño-Southern Oscillation (ENSO) teleconnections are an important predictability source for extratropical seasonal climate forecasts. Previous studies suggest that the ENSO teleconnection pattern depends on the ENSO phase (El Niño vs. La Niña) and/or Sea Surface Temperature (SST) pattern (central Pacific vs.

Preoperative Versus Perioperative Risk Factors for Delayed Pain and Opioid Cessation After Total Joint Arthroplasty: A Prospective Cohort Study.

Introduction: The evolution of pre- versus postoperative risk factors remains unknown in the development of persistent postoperative pain and opioid use. We identified preoperative versus comprehensive perioperative models of delayed pain and opioid cessation after total joint arthroplasty including time-varying postoperative changes in emotional distress. We hypothesized that time-varying longitudinal measures of postoperative psychological distress, as well as pre- and postoperative use of opioids would be the most significant risk factors for both outcomes.

A translational model-based approach to inform the choice of the dose in phase 1 oncology trials: the case study of erdafitinib.

Purpose: Erdafitinib (JNJ-42756493, BALVERSA) is a tyrosine kinase inhibitor indicated for the treatment of advanced urothelial carcinoma. In this work, a translational model-based approach to inform the choice of the doses in phase 1 trials is illustrated.

Methods: A pharmacokinetic (PK) model was developed to describe the time course of erdafitinib plasma concentrations in mice and rats.

Discovery of an Allosteric, Inactive Conformation-Selective Inhibitor of Full-Length HPK1 Utilizing a Kinase Cascade Assay.

Achieving selectivity across the human kinome is a major hurdle in kinase inhibitor drug discovery. Assays using active, phosphorylated protein kinases bias hits toward poorly selective inhibitors that bind within the highly conserved adenosine triphosphate (ATP) pocket. Targeting inactive ( active) kinase conformations offers advantages in achieving selectivity because of their more diversified structures.

Decadal climate variability in the tropical Pacific: Characteristics, causes, predictability, and prospects.

Climate variability in the tropical Pacific affects global climate on a wide range of time scales. On interannual time scales, the tropical Pacific is home to the El Niño–Southern Oscillation (ENSO). Decadal variations and changes in the tropical Pacific, referred to here collectively as tropical Pacific decadal variability (TPDV), also profoundly affect the climate system.

Impact of projected sea surface temperature biases on tropical cyclones projections in the South Pacific.

Climate model projections generally indicate fewer but more intense tropical cyclones (TCs) in response to increasing anthropogenic emissions. However these simulations suffer from long-standing biases in their Sea Surface Temperature (SST). While most studies investigating future changes in TC activity using high-resolution atmospheric models correct for the present-day SST bias, they do not consider the reliability of the projected SST changes from global climate models.

Contagious agalactia monitoring in caprine herds through regular bulk tank milk sampling.

Surveillance and control of Mycoplasma spp. responsible for contagious agalactia (CA) in caprine herds are important challenges in countries with a large small-ruminant dairy industry. In the absence of any clinical signs, being able to determine the potential circulation of mycoplasmas within a herd could help to prevent biosecurity issues during animal exchanges between farms and improve health management practices.

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects.

Author Correction: Tropical explosive volcanic eruptions can trigger El Niño by cooling tropical Africa.

The original version of this Article omitted a reference to previous work in 'Mann, M.E., Cane, M.

Publisher Correction: Tropical explosive volcanic eruptions can trigger El Niño by cooling tropical Africa.

A correction to this article has been published and is linked from the HTML version of this article.

Tropical explosive volcanic eruptions can trigger El Niño by cooling tropical Africa.

Stratospheric aerosols from large tropical explosive volcanic eruptions backscatter shortwave radiation and reduce the global mean surface temperature. Observations suggest that they also favour an El Niño within 2 years following the eruption. Modelling studies have, however, so far reached no consensus on either the sign or physical mechanism of El Niño response to volcanism.

Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor.

Fibroblast growth factor (FGF) signaling plays critical roles in key biological processes ranging from embryogenesis to wound healing and has strong links to several hallmarks of cancer. Genetic alterations in FGF receptor () family members are associated with increased tumor growth, metastasis, angiogenesis, and decreased survival. JNJ-42756493, erdafitinib, is an orally active small molecule with potent tyrosine kinase inhibitory activity against all four FGFR family members and selectivity versus other highly related kinases.

Tankyrase inhibition impairs directional migration and invasion of lung cancer cells by affecting microtubule dynamics and polarity signals.

Background: Tankyrases are poly(adenosine diphosphate)-ribose polymerases that contribute to biological processes as diverse as modulation of Wnt signaling, telomere maintenance, vesicle trafficking, and microtubule-dependent spindle pole assembly during mitosis. At interphase, polarized reshaping of the microtubule network fosters oriented cell migration. This is attained by association of adenomatous polyposis coli with the plus end of microtubules at the cortex of cell membrane protrusions and microtubule-based centrosome reorientation towards the migrating front.

Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in ∼20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions.

Upregulation of MAPK Negative Feedback Regulators and RET in Mutant ALK Neuroblastoma: Implications for Targeted Treatment.

Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies.

Activation of RAS family members confers resistance to ROS1 targeting drugs.

The ROS1 tyrosine kinase is activated in lung cancer as a consequence of chromosomal rearrangement. Although high response rates and disease control have been observed in lung cancer patients bearing rearranged ROS1 tumors (ROS1+) treated with the kinase inhibitor crizotinib, many of these patients eventually relapse.To identify mechanisms of resistance to ROS1 inhibitors we generated resistant cells from HCC78 lung cancer cells bearing the SLC34A2-ROS1 rearrangement.

Serosurvey of Schmallenberg Virus Infection in the Highest Goat-Specialized Region of France.

The monitoring of both the spread and clinical impact of Schmallenberg virus (SBV) infection within its full host range is important for the control of the epidemic and potential new outbreaks. In France, a national surveillance plan based on voluntary notifications of congenital malformations in newborn ruminants revealed that goats were the less affected host species. However, seroprevalence studies only targeted sheep and cattle, preventing accurate estimations of the real impact of SBV infection in goats.

Occurrence of bacteriuria in 18 catheterised cats with obstructive lower urinary tract disease: a pilot study.

The incidence of catheter-associated urinary tract infections in cats catheterised for an obstructive lower urinary tract disease (LUTD) has not previously been evaluated. The objective of this study was to evaluate the frequency of significant bacteriuria in cats with obstructive LUTD managed for 48 h with a closed urine collection system. Eighteen male cats admitted for a non-infectious obstructive LUTD were evaluated.

[Utilization of Essure® micro-insert for hydrosalpynx occlusion in infertile women].

Objective: To assess the feasibility and the results on fertility of tubal hysteroscopic proximal occlusion with Essure(®) micro-insert in women with hydrosalpinges.

Patients And Methods: Thirteen infertile women with hydrosalpinges, who underwent hysteroscopic tubal exclusion by Essure(®) prior to IVF procedure.

Results: The placement of micro-insert was feasible and easy in every patient, with no intra-operative complication.

Effect of an inactivated paratuberculosis vaccine on the intradermal testing of goats for tuberculosis.

The effect of an inactivated paratuberculosis vaccine on the diagnosis of tuberculosis (TB) in goats was investigated in a herd with a history of clinical paratuberculosis but which was free of TB. Cohorts of animals in 2006, 2008 and 2009, were vaccinated once at 1 month of age, and 50% of the 2006 cohort served as unvaccinated controls. The goats were aged 8 months, 20 months and 3.

Programming in vitro fertilization retrievals during working days after a gonadotropin-releasing hormone antagonist protocol with estrogen pretreatment: does the length of exposure to estradiol impact on controlled ovarian hyperstimulation outcomes?

Objective: To verify whether a variable number of days beyond the menses of estrogen (E) pretreatment may impact on controlled ovarian hyperstimulation (COH) outcomes and birth rate using a GnRH antagonist protocol.

Design: Single center, prospective, nonrandomized study.

Setting: Nonacademic fertility unit.

[Influence duration of the use of estrogens beyond the menses in estradiol IVF antagonist programming cycles].

Objective: To evaluate by the birth rate the impact of the number of days of estrogens continued beyond the menses in a four days estradiol IVF antagonist programming cycles.

Patients And Methods: Retrospective study from September 2004 to January 2009 among women of age ranging between 25 and 38 years. Four milligrams of provames is prescribed 3 to 5 days before the theorical menses and continued until the beginning day of stimulation, which is distributed equitably between Thursday and Sunday.