The anatomy of vocal divergence in North American Elk and European red deer.

Loud and frequent vocalizations play an important role in courtship behavior in Cervus species. European red deer (Cervus elaphus) produce low-pitched calls, whereas North American elk (Cervus canadensis) produce high-pitched calls, which is remarkable for one of the biggest land mammals. Both species engage their vocal organs in elaborate maneuvers but the precise mechanism is unknown.

Observation of time-reversal violation in the B0 meson system.

Although CP violation in the B meson system has been well established by the B factories, there has been no direct observation of time-reversal violation. The decays of entangled neutral B mesons into definite flavor states (B(0) or B(0)), and J/ψK(L)(0) or ccK(S)(0) final states (referred to as B(+) or B(-)), allow comparisons between the probabilities of four pairs of T-conjugated transitions, for example, B(0) → B(-) and B(-) → B(0), as a function of the time difference between the two B decays. Using 468 × 10(6) BB pairs produced in Υ(4S) decays collected by the BABAR detector at SLAC, we measure T-violating parameters in the time evolution of neutral B mesons, yielding ΔS(T)(+) = -1.

Precision measurement of the B → Xs γ photon energy spectrum, branching fraction, and direct CP asymmetry A(CP)((B → X(s+d)γ).

The photon spectrum in the inclusive electromagnetic radiative decays of the B meson, B → X(s)γ plus B → X(d)γ, is studied using a data sample of (382.8 ± 4.2) × 10(6)Υ(4S) → BB decays collected by the BABAR experiment at SLAC.

Evidence for an excess of B→D*τ(-)ν(τ) decays.

Based on the full BABAR data sample, we report improved measurements of the ratios R(D(*))=B(B[over ¯]→D(*)τ(-)ν[over ¯](τ))/B(B[over ¯]→D(*)ℓ(ℓ)(-)ν[over ¯](ℓ)), where ℓ is either e or μ. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D)=0.

Search for low-mass dark-sector Higgs bosons.

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb(-1) of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the standard model-dark-sector mixing angle and the dark-sector coupling constant.

Preclinical characterization of ABT-348, a kinase inhibitor targeting the aurora, vascular endothelial growth factor receptor/platelet-derived growth factor receptor, and Src kinase families.

ABT-348 [1-(4-(4-amino-7-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)thieno[3,2-c]pyridin-3-yl)phenyl)-3-(3-fluorophenyl)urea] is a novel ATP-competitive multitargeted kinase inhibitor with nanomolar potency (IC(50)) for inhibiting binding and cellular autophosphorylation of Aurora B (7 and 13 nM), C (1 and 13 nM), and A (120 and 189 nM). Cellular activity against Aurora B is reflected by inhibition of phosphorylation of histone H3, induction of polyploidy, and inhibition of proliferation of a variety of leukemia, lymphoma, and solid tumor cell lines (IC(50) = 0.3-21 nM).

How low can you go? Physical production mechanism of elephant infrasonic vocalizations.

Elephants can communicate using sounds below the range of human hearing ("infrasounds" below 20 hertz). It is commonly speculated that these vocalizations are produced in the larynx, either by neurally controlled muscle twitching (as in cat purring) or by flow-induced self-sustained vibrations of the vocal folds (as in human speech and song). We used direct high-speed video observations of an excised elephant larynx to demonstrate flow-induced self-sustained vocal fold vibration in the absence of any neural signals, thus excluding the need for any "purring" mechanism.

Morphological and functional features of the sex steroid-responsive posterodorsal medial amygdala of adult rats.

The rat posterodorsal medial amygdala (MePD) expresses receptors for gonadal hormones and integrates sex steroid-sensitive subcortical networks. Male-female differences are found in the morphology, connectivity, and local neuropil structure of MePD. For example, dendritic spine density is sexually-dimorphic and changes with the estrous cycle and following gonadal hormones manipulations.

Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET.

Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT(1A)) in the mode of action of antidepressant treatment.

Left ventricular systolic dysfunction associated with pulmonary hypertension riociguat trial (LEPHT): rationale and design.

Aims: Pulmonary hypertension (PH) due to systolic left ventricular dysfunction (PH-sLVD) frequently complicates heart failure (HF), and greatly worsens the prognosis of patients with sLVD, but as yet has no approved treatment. The LEPHT study aims to characterize the haemodynamic profile, safety, tolerability, and pharmacokinetic profile of riociguat (BAY 63-2521), an oral stimulator of soluble guanylate cyclase, in patients with PH-sLVD.

Methods And Results: This 16-week, phase IIb, randomized, placebo-controlled, double-blind study enrols patients with PH-sLVD, defined as left ventricular ejection fraction (LVEF) ≤40% and mean pulmonary arterial pressure (PAP(mean)) ≥25 mmHg at rest.

Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases.

In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly ip dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents.

Combining image-derived and venous input functions enables quantification of serotonin-1A receptors with [carbonyl-11C]WAY-100635 independent of arterial sampling.

Unlabelled: image- derived input functions (IDIFs) represent a promising technique for a simpler and less invasive quantification of PET studies as compared to arterial cannulation. However, a number of limitations complicate the routine use of IDIFs in clinical research protocols and the full substitution of manual arterial samples by venous ones has hardly been evaluated. This study aims for a direct validation of IDIFs and venous data for the quantification of serotonin-1A receptor binding (5-HT(1A)) with [carbonyl-(11)C]WAY-100635 before and after hormone treatment.

Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families.

In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations.

The ontogeny of acoustic individuality in the nasal calls of captive goitred gazelles, Gazella subgutturosa.

Individualistic voices are important for establishing personalized relationships among individuals. In young animals, individual vocal identity is affected by permanent changes of the acoustics due to the growth of their vocal apparatus. Different acoustic variables change uncoordinatedly, so vocal individuality should be repeatedly upgraded along development.

Vocal anatomy, tongue protrusion behaviour and the acoustics of rutting roars in free-ranging Iberian red deer stags (Cervus elaphus hispanicus).

Roaring in rutting Iberian red deer stags Cervus elaphus hispanicus is unusual compared to other subspecies of red deer, which radiated from the Iberian refugium after the last glacial maximum. In all red deer stags, the larynx occupies a permanent low mid-neck resting position and is momentarily retracted almost down to the rostral end of the sternum during the production of rutting calls. Simultaneous with the retraction of the larynx, male Iberian red deer pronouncedly protrude the tongue during most of their rutting roars.

Directional limits on persistent gravitational waves using LIGO S5 science data.

The gravitational-wave (GW) sky may include nearby pointlike sources as well as stochastic backgrounds. We perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. Finding no evidence to support the detection of GWs, we present 90% confidence level (C.

Actigraphic measurements in opioid detoxification with methadone or buprenorphine.

The objective of the present naturalistic study was to assess the differential effects of opioid detoxification with methadone or buprenorphine on activity, circadian rhythm, and sleep. Forty-two consecutive inpatients with opiate addiction were switched to either methadone or buprenorphine and gradually tapered down over the course of 2 to 3 weeks. There were no significant differences in comedication (lofexidine, quetiapine, and valproic acid) between the methadone and buprenorphine groups.

Search for hadronic decays of a light Higgs boson in the radiative decay Υ→γA0.

We search for hadronic decays of a light Higgs boson (A(0)) produced in radiative decays of an Υ(2S) or Υ(3S) meson, Υ→γA(0). The data have been recorded by the BABAR experiment at the Υ(3S) and Υ(2S) center-of-mass energies and include (121.3±1.

Pharmacokinetics of the soluble guanylate cyclase activator cinaciguat in individuals with hepatic impairment.

Cinaciguat is intended for use in patients with acute decompensated heart failure. The drug is eliminated predominantly via the liver and, therefore, the potential impact of hepatic impairment on cinaciguat pharmacokinetics needs to be determined. This nonrandomized, open-label, observational study investigated the pharmacokinetics of cinaciguat in individuals with mild (Child-Pugh A; n = 8) or moderate (Child-Pugh B; n = 8) hepatic impairment and matched healthy volunteers (n = 16).

Developmental changes of nasal and oral calls in the goitred gazelle Gazella subgutturosa, a nonhuman mammal with a sexually dimorphic and descended larynx.

In goitred gazelles (Gazella subgutturosa), sexual dimorphism of larynx size and position is reminiscent of the case in humans, suggesting shared features of vocal ontogenesis in both species. This study investigates the ontogeny of nasal and oral calls in 23 (10 male and 13 female) individually identified goitred gazelles from shortly after birth up to adolescence. The fundamental frequency (f0) and formants were measured as the acoustic correlates of the developing sexual dimorphism.

Iodobenzene catalysed synthesis of spirofurans and benzopyrans by oxidative cyclisation of vinylogous esters.

Vinylogous esters bearing para or meta methoxy benzyl groups undergo oxidative cyclisation with 5-20 mol% iodobenzene and m-CPBA to give spirofuran or benzopyran containing heterocycles. The reaction allows rapid generation of skeletal complexity in good to excellent yields via a novel oxidative cyclisation.

The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations.

Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations.

Functional PU.1 in macrophages has a pivotal role in NF-κB activation and neutrophilic lung inflammation during endotoxemia.

Although the role of ETS family transcriptional factor PU.1 is well established in macrophage maturation, its role in mature macrophages with reference to sepsis- related animal model has not been elucidated. Here, we report the in vivo function of PU.

Assessment of the effects of renal impairment on the pharmacokinetics of the soluble guanylate cyclase activator cinaciguat after a single intravenous dose.

This open-label, parallel-group, single-dose study assessed the safety and pharmacokinetics of cinaciguat, a novel soluble guanylate cyclase activator in clinical development for the treatment of acute decompensated heart failure, in individuals with mild, moderate, or severe renal impairment compared with individuals with normal renal function. Cinaciguat was administered as a 100 µg/h continuous infusion over 4 hours. Plasma concentrations were determined by high-performance liquid chromatography coupled with mass spectrometry.