CHESS: The future direct geometry spectrometer at the second target station.

CHESS, chopper spectrometer examining small samples, is a planned direct geometry neutron chopper spectrometer designed to detect and analyze weak signals intrinsic to small cross sections (e.g., small mass, small magnetic moments, or neutron absorbing materials) in powders, liquids, and crystals. CHESS is optimized to enable transformative investigations of quantum materials, spin liquids, thermoelectrics, battery materials, and liquids. The broad dynamic range of the instrument is also well suited to study relaxation processes and excitations in soft and biological matter. The 15 Hz repetition rate of the Second Target Station at the Spallation Neutron Source enables the use of multiple incident energies within a single source pulse, greatly expanding the information gained in a single measurement. Furthermore, the high flux grants an enhanced capability for polarization analysis. This enables the separation of nuclear from magnetic scattering or coherent from incoherent scattering in hydrogenous materials over a large range of energy and momentum transfer. This paper presents optimizations and technical solutions to address the key requirements envisioned in the science case and the anticipated uses of this instrument.

A concept of a broadband inverted geometry spectrometer for the Second Target Station at the Spallation Neutron Source.

BWAVES is an acronym for Broadband Wide-Angle VElocity Selector spectrometer, indicating that a novel WAVES (Wide-Angle VElocity Selector) device will be used to select the velocity/wavelength of the detected neutrons after they are scattered by the sample. We describe a conceptual design of BWAVES, a time-of-flight broadband inverted-geometry neutron spectrometer for the Second Target Station at the Spallation Neutron Source operated by Oak Ridge National Laboratory. Being the first inverted geometry spectrometer where the energy of the detected neutrons can be chosen by a WAVES device mechanically, irrespective of the limitations imposed by the crystal analyzers or filters, BWAVES will feature a uniquely broad, continuous dynamic range of measurable energy transfers, spanning 4.5 decades. This will enable measurements of both vibrational and relaxational excitations within the same, continuous scattering spectra. Novel approaches that are necessary for the implementation of a WAVES device at the BWAVES spectrometer will result in a spectrometer with the design and characteristics much different from those displayed by the neutron spectrometers in existence today.

The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In-Situ Measurements in the Tropical Lower Stratosphere.

Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that may be intentionally enhanced in the future to offset greenhouse gases (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in maintaining background SAs has been debated for decades without in-situ measurements of SO2 at the tropical tropopause to inform this issue. Here we clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements to evaluate climate models and satellite retrievals. We then use the observed tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across the tropical tropopause. These analyses show that the tropopause background SO2 is about 5 times smaller than reported by the average satellite observations that have been used recently to test atmospheric models. This shifts the view of SO2 as a dominant source of SAs to a near-negligible one, possibly revealing a significant gap in the SA budget.

Acute effects of a beverage containing bitter melon extract (CARELA) on postprandial glycemia among prediabetic adults.

BACKGROUND: Acute ingestion of bitter melon (BM) has been shown to suppress the postprandial glycemic response in diabetics, but its impact on glucose regulation among individuals with impaired glucose tolerance is unclear. Moreover, one's glucose tolerance level may influence the effectiveness of BM. This study aimed to examine the acute effects of a beverage containing BM extract on blood glucose regulation during an oral glucose tolerance test (OGTT) among prediabetics. METHODS: Ten prediabetic adults completed two OGTTs-glucose only (D2) and glucose+BM (D3). Responders were identified as subjects whose area under the glucose curve (AUCglu) during D3 was lower than D2. To compare the acute effects of the beverage among individuals with varying glucose tolerance levels, subjects were grouped by their glucose response pattern-Fastpeak (peak glucose (Glupeak) at 30 min postglucose (30P)) and Slowpeak (Glupeak after 30P). RESULTS: During D3, responders (n=5) experienced a 13.2% reduction in AUCglu (95% confidence interval (CI): -18.1% to -8.3%), 12.2% reduction in mean glucose (95% CI: -17.3% to -7.0%) and 10.6% reduction in Glupeak (95% CI: -17.5% to -3.7%); plasma glucose was reduced by 9.1% at 30P (95% CI: -15.6% to -2.6%), -24.0% at 60P (95% CI: -36.8% to -11.2%) and -20.0% at 90P (95% CI: -35.8% to -4.2%) during D3. No between-trial differences were noted for Fastpeak or Slowpeak. CONCLUSIONS: Acute ingestion of BM prior to the second OGTT (D3) led to a reduced postprandial glucose response in 50% of the subjects but did not affect the insulin response. Furthermore, the effectiveness of the beverage was seemingly uninfluenced by the subjects' glucose tolerance level. Although BM has shown to aid blood glucose management in diabetics, it remains uncertain why only a portion of subjects responded positively to the BM extract in the current study.

Sexual dimorphism in oxytocin responses to health perception and disgust, with implications for theories on pathogen detection.

In response to a recent hypothesis that the neuropeptide oxytocin might be involved in human pathogen avoidance mechanisms, we report the results of a study in which we investigate the effect of intranasal oxytocin on two behaviors serving as proxies for pathogen detection. Participants received either oxytocin or a placebo and were asked to evaluate (1) the health of Caucasian male computer-generated pictures that varied in facial redness (an indicator of hemoglobin perfusion) and (2) a series of pictures depicting disgusting scenarios. Men, but not women, evaluated all faces, regardless of color, as less healthy when given oxytocin compared to a placebo. Women, on the other hand, expressed decreased disgust when given oxytocin compared to a placebo. These results suggest that intranasal oxytocin administration does not facilitate pathogen detection based on visual cues, but instead reveal clear sex differences in the perception of health and sickness cues.

Early outcomes of staged bilateral reverse total shoulder arthroplasty: a case-control study.

Some surgeons are reluctant to perform a reverse total shoulder arthroplasty (RTSA) on both shoulders because of concerns regarding difficulty with activities of daily living post-operatively as a result of limited rotation of the shoulders. Nevertheless, we hypothesised that outcomes and patient satisfaction following bilateral RTSA would be comparable to those following unilateral RTSA. A single-surgeon RTSA registry was reviewed for patients who underwent bilateral staged RTSA with a minimum follow-up of two years. A unilateral RTSA matched control was selected for each shoulder in those patients undergoing bilateral procedures. The Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, Subjective Shoulder Values (SSV), visual analogue scale (VAS) for pain, range of movement and strength were measured pre- and post-operatively. The mean CMS, ASES, SSV, VAS scores, strength and active forward elevation were significantly improved (all p < 0.01) following each operation in those undergoing bilateral procedures. The mean active external rotation (p = 0.63 and p = 0.19) and internal rotation (p = 0.77 and p = 0.24) were not significantly improved. The improvement in the mean ASES score after the first RTSA was greater than the improvement in its control group (p = 0.0039). The improvement in the mean CMS, ASES scores and active forward elevation was significantly less after the second RTSA than in its control group (p = 0.0244, p = 0.0183, and p = 0.0280, respectively). Pain relief and function significantly improved after each RTSA in those undergoing a bilateral procedure. Bilateral RTSA is thus a reasonable form of treatment for patients with severe bilateral rotator cuff deficiency, although inferior results may be seen after the second procedure compared with the first.

Magnetic domain wall pumping by spin transfer torque.

We show that spin transfer torque from a direct spin-polarized current applied parallel to a magnetic domain wall (DW) induces DW motion in a direction independent of the current polarity. This unidirectional response of the DW to spin torque enables DW pumping--long-range DW displacement driven by an alternating current. Our numerical simulations reveal that DW pumping can be resonantly amplified through excitation of internal degrees of freedom of the DW by the current.

Rapid domain wall motion in permalloy nanowires excited by a spin-polarized current applied perpendicular to the nanowire.

We study domain wall dynamics in Permalloy nanowires excited by alternating spin-polarized current applied perpendicular to the nanowire. Spin torque ferromagnetic resonance measurements reveal that domain wall oscillations at a pinning site in the nanowire can be excited with velocities as high as 800 m/s at current densities below 10{7} A/cm{2}.

Resonant nonlinear damping of quantized spin waves in ferromagnetic nanowires: a spin torque ferromagnetic resonance study.

We use spin torque ferromagnetic resonance to measure the spectral properties of dipole-exchange spin waves in Permalloy nanowires. Our measurements reveal that geometric confinement has a profound effect on the damping of spin waves in the nanowire geometry. The damping parameter of the lowest-energy quantized spin-wave mode depends on applied magnetic field in a resonant way and exhibits a maximum at a field that increases with decreasing nanowire width. This enhancement of damping originates from a nonlinear resonant three-magnon confluence process allowed at a particular bias field value determined by quantization of the spin-wave spectrum in the nanowire geometry.

Origin of the inverse spin switch effect in superconducting spin valves.

Known as the spin switch effect (SSE), the resistance of a ferromagnet/superconductor/ferromagnet (F/S/F) spin valve near its superconducting transition temperature T c is different for parallel (R P) and antiparallel (R AP) configurations of the F layers. Here, we report the observation of the coexistence of the standard (RP>RAP) and inverse (RP

Prostate intraepithelial neoplasia in Noble rats, a potential intermediate endpoint for chemoprevention studies.

In most prostate chemoprevention studies conducted with animal models, the incidence and multiplicity of tumours have been used as endpoints for efficacy. However, the latency of tumours is usually over 1 year, making these studies costly and time consuming. The main purpose of this study was to assess the utility of prostate intraepithelial neoplasia (PIN), induced in Noble rats by continuous testosterone + oestradiol (T + E) administration, as a potential intermediate endpoint biomarker of efficacy in chemoprevention studies. Noble rats at the age of 12 weeks were treated for 36 weeks with T + E given subcutaneously via Silastic capsules. The incidence and multiplicity of PIN were assessed in various prostate glands by serial sections generated at three separate tissue levels. The efficacy of dehydroepiandrosterone (DHEA) and DHEA 8354 (1000 and 2000 mg/kg diet), difluoromethylornithine (DFMO) (1000 and 2000 mg/kg diet) and oltipraz (125 and 250 mg/kg diet) to inhibit PIN was assessed in two independent sets of experiments. T + E induced multiple PIN in the dorsolateral prostate (DLP) of 80-100% of the animals. DHEA and DHEA 8354 did not affect the incidence but decreased the multiplicity of PIN in the DLP, from 3.2 +/- 1.0 in control group to 1.5 +/- 1.0 in the low-dose and to 1.6 +/- 0.6 in the high-dose group for DHEA (P<0.05 and P<0.02, respectively), and to 1.9 +/- 0.8 in the high-dose (P<0.05) DHEA 8354. Both agents did not affect PIN in anterior prostate, seminal vesicles or ventral prostate. In a second experiment, DFMO and oltipraz were found not effective in inhibiting PIN. In this study, we provide new evidence that PIN in Noble rats, induced by continuous T + E treatment, is a useful intermediate endpoint for determining the efficacy of DHEA and other potential chemopreventive agents. The hormonal pathogenesis, high multiplicity, short latency, preferential location in the DLP, similarity in morphology and biology to PIN of human prostate, and the sensitivity to agents that suppress prostate carcinogenesis, makes PIN in Noble rats a promising intermediate endpoint for chemoprevention studies.

Role of scaffolds in MAP kinase pathway specificity revealed by custom design of pathway-dedicated signaling proteins.

BACKGROUND: Signal transduction pathways with shared components must be insulated from each other to avoid the inappropriate activation of multiple pathways by a single stimulus. Scaffold proteins are thought to contribute to this specificity by binding select substrates. RESULTS: We have studied the ability of scaffold proteins to influence signaling by the yeast kinase Ste11, a MAPKKK molecule that participates in three distinct MAP kinase pathways: mating, filamentation, and HOG. We used protein fusions to force Ste11 to associate preferentially with a subset of its possible binding partners in vivo, including Ste5, Ste7, and Pbs2. Signaling became confined to a particular pathway when Ste11 was covalently attached to these scaffolds or substrates. This pathway bias was conferred upon both stimulus-activated and constitutively active forms of Ste11. We also used membrane-targeted derivatives of the mating pathway scaffold, Ste5, to show that stimulus-independent signaling initiated by this scaffold remained pathway specific. Finally, we demonstrate that loss of pathway insulation has a negative physiological consequence, as nonspecific activation of both the HOG and mating pathways interfered with proper execution of the mating pathway. CONCLUSIONS: The signaling properties of these kinase fusions support a model in which scaffold proteins dictate substrate choice and promote pathway specificity by presenting preferred substrates in high local concentration. Furthermore, insulation is inherent to scaffold-mediated signaling and does not require that signaling be initiated by pathway-specific stimuli or activator proteins. Our results give insight into the mechanisms and physiological importance of pathway insulation and provide a foundation for the design of customized signaling proteins.

Systematic genetic analysis with ordered arrays of yeast deletion mutants.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Dynamically coated capillaries improve the identification power of capillary zone electrophoresis for basic drugs in toxicological analysis.

In systematic toxicological analysis (STA), analytical methods should have a high identification power. This can be suitably expressed by parameters such as mean list length (MLL) or discriminating power (DP). The reproducibility of a method has a great impact on its identification power, and should be as high as possible. In this study, two separation methods based on capillary zone electrophoresis (CZE) were evaluated towards STA applications. Besides a normal phosphate buffer, the commercially available buffer CElixir was used, which is a double-layer dynamic coating system. The coating stabilizes the endoosmotic flow, is independent of the pH, and is claimed to be more reproducible and faster at low pH than with normal buffers. A test set of 73 basic pharmaceutical compounds was analyzed by the two CZE methods. The total analysis time, including rinsing steps, was 8 min when the coating was used and 18 min without the coating. Effective mobilities were calculated and the reproducibilities were a factor of 2 better when the coating was used (between-days SD 0.020 and 0.040 m2/V s with and without the coating, respectively). MLL and DP were calculated for the two CZE methods and for combinations with standardized liquid and gas chromatography systems. CZE with CElixir coating clearly has a high potential for STA applications, as it was shown to have a higher identification power and shorter analysis times than normal CZE.

A protein interaction map for cell polarity development.

Many genes required for cell polarity development in budding yeast have been identified and arranged into a functional hierarchy. Core elements of the hierarchy are widely conserved, underlying cell polarity development in diverse eukaryotes. To enumerate more fully the protein-protein interactions that mediate cell polarity development, and to uncover novel mechanisms that coordinate the numerous events involved, we carried out a large-scale two-hybrid experiment. 68 Gal4 DNA binding domain fusions of yeast proteins associated with the actin cytoskeleton, septins, the secretory apparatus, and Rho-type GTPases were used to screen an array of yeast transformants that express approximately 90% of the predicted Saccharomyces cerevisiae open reading frames as Gal4 activation domain fusions. 191 protein-protein interactions were detected, of which 128 had not been described previously. 44 interactions implicated 20 previously uncharacterized proteins in cell polarity development. Further insights into possible roles of 13 of these proteins were revealed by their multiple two-hybrid interactions and by subcellular localization. Included in the interaction network were associations of Cdc42 and Rho1 pathways with proteins involved in exocytosis, septin organization, actin assembly, microtubule organization, autophagy, cytokinesis, and cell wall synthesis. Other interactions suggested direct connections between Rho1- and Cdc42-regulated pathways; the secretory apparatus and regulators of polarity establishment; actin assembly and the morphogenesis checkpoint; and the exocytic and endocytic machinery. In total, a network of interactions that provide an integrated response of signaling proteins, the cytoskeleton, and organelles to the spatial cues that direct polarity development was revealed.

Screening for the presence of drugs in serum and urine using different separation modes of capillary electrophoresis.

Capillary electrophoresis (CE) is a modern separation technique that has some distinct advantages for toxicological analysis, such as a high efficiency, fast analysis, flexibility, and complementary separation mechanisms to chromatographic methods. CE can be applied in various modes, which each have a different separation mechanism or selectivity. The most common mode is capillary zone electrophoresis (CZE), in which charged analytes migrate in a buffer under the influence of an electric field. In micellar electrokinetic chromatography (MEKC), micelles are added to the buffer which interact with the analytes. MEKC can also be used for the separation of neutral compounds. In non-aqueous CE (NACE), the aqueous buffer is replaced by a background of electrolytes in organic solvents. A sample that needs to be screened can easily be analyzed subsequently by these CE modes using the same instrumentation. The aim of the study was to develop procedures for the analysis of basic and acidic drugs in serum and urine using CZE, MEKC, and NACE. A test mixture that consisted of six basic and six acidic compounds was used to study the separation behavior of five CE methods. The results showed that three methods (based on CZE, MEKC, and NACE) were suitable for the analysis of basic compounds and three methods (based on CZE and MEKC) for the analysis of acidic compounds. For the extraction of analytes from serum and urine, a solid-phase extraction (SPE) and a liquid-liquid extraction (LLE) method were compared. Both SPE and LLE methods provided clean extracts after extraction of the basic compounds from serum and urine. The extracts of acidic compounds contained more matrix interferences, especially for urine. The SPE method had some advantages compared to LLE, as it lead to cleaner extracts and higher peaks, and as it elutes basic and acidic compounds in one fraction. The potentials and pitfalls of the various methods for screening purposes in analytical toxicology are discussed.

How curcumin works preferentially with water soluble antioxidants.

In this study we investigated physicochemical characteristics of the curcumin radical by pulse radiolysis and laser flash photolysis. Two methylated curcumin derivatives, methylcurcumin and trimethylcurcumin, were synthesized to explore the role of phenol hydroxy and beta-diketone moieties in the free radical chemistry of curcumin. Our results show that the initially generated beta-oxo-alkyl transforms rapidly, probably via an intramolecular H-atom shift, into the phenoxyl-type curcumin radical. This phenoxyl does not react with oxygen, k < 10(5) M(-1) s(-1), and can be repaired by any water-soluble antioxidant with appropriate redox potential, E(6) < 0.83 V, for example, with vitamin C, k = (6 +/- 1) x 10(6) M(-1) s(-1). A molecular mechanism of cancer chemoprevention by curcumin is proposed, with special emphasis on the synergism with water-soluble antioxidants.