Distinction between the Poole-Frenkel and tunneling models of electric field-stimulated carrier emission from deep levels in semiconductors

The enhancement of the emission rate of charge carriers from deep-level defects in electric field is routinely used to determine the charge state of the defects. However, only a limited number of defects can be satisfactorily described by the Poole-Frenkel theory. An electric field dependence different from that expected from the Poole-Frenkel theory has been repeatedly reported in the literature, and no unambiguous identification of the charge state of the defect could be made. In this article, the electric field dependencies of emission of carriers from DX centers in AlxGa1-xAs:Te, Cu pairs in silicon, and Ge:Hg have been studied applying static and terahertz electric fields, and analyzed by using the models of Poole-Frenkel and phonon assisted tunneling. It is shown that phonon assisted tunneling and Poole-Frenkel emission are two competitive mechanisms of enhancement of emission of carriers, and their relative contribution is determined by the charge state of the defect and by the electric-field strength. At high-electric field strengths carrier emission is dominated by tunneling independently of the charge state of the impurity. For neutral impurities, where Poole-Frenkel lowering of the emission barrier does not occur, the phonon assisted tunneling model describes well the experimental data also in the low-field region. For charged impurities the transition from phonon assisted tunneling at high fields to Poole-Frenkel effect at low fields can be traced back. It is suggested that the Poole-Frenkel and tunneling models can be distinguished by plotting logarithm of the emission rate against the square root or against the square of the electric field, respectively. This analysis enables one to unambiguously determine the charge state of a deep-level defect

The age of Wolfe Creek meteorite crater (Kandimalal), Western Australia

Wolfe Creek crater lies in northwestern Australia at the edge of the Great Sandy Desert. Together with Meteor Crater, it is one of the two largest craters on Earth from which meteorite fragments have been recovered. The age of the impact is poorly constrained and unpublished data places the event at about 300,000 years ago. In comparison, Meteor Crater is well constrained by exposure dating. In this paper, we present new ages for Wolfe Creek Crater from exposure dating using the cosmogenic nuclides 10Be and 26Al, together with optically stimulated luminescence ages (OSL) on sand from a site created by the impact. We also present a new topographic survey of the crater using photogrammetry. The exposure ages range from ~86 to 128 ka. The OSL ages indicate that the age of the impact is most likely to be ~120 ka with a maximum age of 137 ka. Considering the geomorphic setting, the most likely age of the crater is 120 ± 9 ka. Last, we review the age of Meteor Crater in Arizona. Changes in production rates and scaling factors since the original dating work revise the impact age to 61.1 ± 4.8 ka, or ~20% older than previously reported

Attitudes towards fibromyalgia: A survey of Canadian chiropractic, naturopathic, physical therapy and occupational therapy students

<p>Abstract</p> <p>Background</p> <p>The frequent use of chiropractic, naturopathic, and physical and occupational therapy by patients with fibromyalgia has been emphasized repeatedly, but little is known about the attitudes of these therapists towards this challenging condition.</p> <p>Methods</p> <p>We administered a cross-sectional survey to 385 senior Canadian chiropractic, naturopathic, physical and occupational therapy students in their final year of studies, that inquired about attitudes towards the diagnosis and management of fibromyalgia.</p> <p>Results</p> <p>336 students completed the survey (response rate 87%). While they disagreed about the etiology (primarily psychological 28%, physiological 23%, psychological and physiological 15%, unsure 34%), the majority (58%) reported that fibromyalgia was difficult to manage. Respondants were also conflicted in whether treatment should prioritize symptom relief (65%) or functional gains (85%), with the majority (58%) wanting to do both. The majority of respondents (57%) agreed that there was effective treatment for fibromyalgia and that they possessed the required clinical skills to manage patients (55%).</p> <p>Chiropractic students were most skeptical in regards to fibromyalgia as a useful diagnostic entity, and most likely to endorse a psychological etiology. In our regression model, only training in naturopathic medicine (unstandardized regression coefficient = 0.33; 95% confidence interval = 0.11 to 0.56) and the belief that effective therapies existed (unstandardized regression coefficient = 0.42; 95% confidence interval = 0.30 to 0.54) were associated with greater confidence in managing patients with fibromyalgia.</p> <p>Conclusion</p> <p>The majority of senior Canadian chiropractic, naturopathic, physical and occupational therapy students, and in particular those with naturopathic training, believe that effective treatment for fibromyalgia exists and that they possess the clinical skillset to effectively manage this disorder. The majority place high priority on both symptom relief and functional gains when treating fibromyalgia.</p

The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML

Acute myeloid leukemia (AML) is currently treated with aggressive chemotherapy that is not well tolerated in many elderly patients, hence the unmet medical need for effective therapies with less toxicity and better tolerability. Inhibitors of FMS-like tyrosine kinase 3 (FLT3), JAK2 and histone deacetylase inhibitors (HDACi) have been tested in clinical studies, but showed only moderate single-agent activity. High efficacy of the HDACi pracinostat treating AML and synergy with the JAK2/FLT3 inhibitor pacritinib is demonstrated. Both compounds inhibit JAK-signal transducer and activator of transcription (STAT) signaling in AML cells with JAK2V617F mutations, but also diminish FLT3 signaling, particularly in FLT3-ITD (internal tandem duplication) cell lines. In vitro, this combination led to decreased cell proliferation and increased apoptosis. The synergy translated in vivo in two different AML models, the SET-2 megakaryoblastic AML mouse model carrying a JAK2V617F mutation, and the MOLM-13 model of FLT3-ITD-driven AML. Pracinostat and pacritinib in combination showed synergy on tumor growth, reduction of metastases and synergistically decreased JAK2 or FLT signaling, depending on the cellular context. In addition, several plasma cytokines/growth factors/chemokines triggered by the tumor growth were normalized, providing a rationale for combination therapy with an HDACi and a JAK2/FLT3 inhibitor for the treatment of AML patients, particularly those with FLT3 or JAK2 mutations

Organometallic palladium reagents for cysteine bioconjugation

Reactions based on transition metals have found wide use in organic synthesis, in particular for the functionalization of small molecules. However, there are very few reports of using transition-metal-based reactions to modify complex biomolecules, which is due to the need for stringent reaction conditions (for example, aqueous media, low temperature and mild pH) and the existence of multiple reactive functional groups found in biomolecules. Here we report that palladium(II) complexes can be used for efficient and highly selective cysteine conjugation (bioconjugation) reactions that are rapid and robust under a range of bio-compatible reaction conditions. The straightforward synthesis of the palladium reagents from diverse and easily accessible aryl halide and trifluoromethanesulfonate precursors makes the method highly practical, providing access to a large structural space for protein modification. The resulting aryl bioconjugates are stable towards acids, bases, oxidants and external thiol nucleophiles. The broad utility of the bioconjugation platform was further corroborated by the synthesis of new classes of stapled peptides and antibody–drug conjugates. These palladium complexes show potential as benchtop reagents for diverse bioconjugation applications.National Institutes of Health (U.S.) (GM-58160)National Institutes of Health (U.S.) (GM-101762)MIT Faculty Start-up FundDamon Runyon Cancer Research FoundationSontag Foundation (Distinguished Scientist Award)Massachusetts Institute of Technology. Dept. of Chemistry (George Buchi Research Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Fellowship in Cancer Research

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. SUBJECTS/METHODS: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. CONCLUSIONS: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting

Copper-catalysed selective hydroamination reactions of alkynes

The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of ​rivastigmine and the formal synthesis of several other pharmaceutical agents, including ​duloxetine, ​atomoxetine, ​fluoxetine and ​tolterodine.National Institutes of Health (U.S.) (GM58160

Genetic Dissection of the Function of Hindbrain Axonal Commissures

The Robo3 receptor controls midline crossing by axons. Deleting Robo3 in specific commissural neurons with a conditional knockout reveals their contribution to sensory and motor integration, and models human neurological conditions

Meteorites on Mars observed with the Mars Exploration Rovers

Reduced weathering rates due to the lack of liquid water and significantly greater typical surface ages should result in a higher density of meteorites on the surface of Mars compared to Earth. Several meteorites were identified among the rocks investigated during Opportunity&rsquo;s traverse across the sandy Meridiani plains. Heat Shield Rock is a IAB iron meteorite and has been officially recognized as &lsquo;&lsquo;Meridiani Planum.&rsquo;&rsquo; Barberton is olivine-rich and contains metallic Fe in the form of kamacite, suggesting a meteoritic origin. It is chemically most consistent with a mesosiderite silicate clast. Santa Catarina is a brecciated rock with a chemical and mineralogical composition similar to Barberton. Barberton, Santa Catarina, and cobbles adjacent to Santa Catarina may be part of a strewn field. Spirit observed two probable iron meteorites from its Winter Haven location in the Columbia Hills in Gusev Crater. Chondrites have not been identified to date, which may be a result of their lower strengths and probability to survive impact at current atmospheric pressures. Impact craters directly associated with Heat Shield Rock, Barberton, or Santa Catarina have not been observed, but such craters could have been erased by eolian-driven erosion.Additional co-authors: DW Ming, RV Morris, PA de Souza Jr, SW Squyres, C Weitz, AS Yen, J Zipfel, T Economo