Enhanced Thermoelectric Properties in Bulk Nanowire Heterostructure-Based Nanocomposites through Minority Carrier Blocking

To design superior thermoelectric materials the minority carrier blocking effect in which the unwanted bipolar transport is prevented by the interfacial energy barriers in the heterogeneous nanostructures has been theoretically proposed recently. The theory predicts an enhanced power factor and a reduced bipolar thermal conductivity for materials with a relatively low doping level, which could lead to an improvement in the thermoelectric figure of merit (ZT). Here we show the first experimental demonstration of the minority carrier blocking in lead telluride–silver telluride (PbTe–Ag_2Te) nanowire heterostructure-based nanocomposites. The nanocomposites are made by sintering PbTe–Ag_2Te nanowire heterostructures produced in a highly scalable solution-phase synthesis. Compared with Ag_2Te nanowire-based nanocomposite produced in similar method, the PbTe–Ag_2Te nanocomposite containing ∼5 atomic % PbTe exhibits enhanced Seebeck coefficient, reduced thermal conductivity, and ∼40% improved ZT, which can be well explained by the theoretical modeling based on the Boltzmann transport equations when energy barriers for both electrons and holes at the heterostructure interfaces are considered in the calculations. For this p-type PbTe–Ag_2Te nanocomposite, the barriers for electrons, that is, minority carriers, are primarily responsible for the ZT enhancement. By extending this approach to other nanostructured systems, it represents a key step toward low-cost solution-processable nanomaterials without heavy doping level for high-performance thermoelectric energy harvesting

Composition Modulation of Ag_2Te Nanowires for Tunable Electrical and Thermal Properties

In this article, we demonstrated that composition modulation of Ag_2Te nanowires can be achieved during the self-templated transformation of Te nanowires into Ag_2Te nanowires during solution phase synthesis, which provides a mean to tune the carrier density of the Ag_2Te nanowires. Both nearly stoichiometric and Ag-rich nanowires have been synthesized, which give rise to p-type and n-type Ag_2Te nanocomposites after hot press, respectively. The electrical and thermal properties of the two kinds of samples have been measured. Theoretical modeling based on the near-equilibrium Boltzmann transport equations has been used to understand the experimental results. We found that ZT of the heavily doped n-type sample reaches 0.55 at 400 K, which is the highest ZT value reported for Ag_2Te at the same temperature mainly due to the reduced thermal conductivity by the nanostructures. Theoretical analysis on the carrier transport shows that the power factor is also very well optimized in the doped Ag_2Te sample considering the reduced carrier mobility by the nanostructures

Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda

Background: Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due to social desirability and recall bias. The aim of this study was to compare self-reported alcohol consumption to phosphatidylethanol (PEth), a biomarker of alcohol consumption, and to estimate the correlation between multiple measures of self-reported alcohol consumption with PEth. Methods: The Uganda AIDS Rural Treatment Outcomes (UARTO) cohort is located in southwestern Uganda and follows patients on ART to measure treatment outcomes. Patients complete standardized questionnaires quarterly including questions on demographics, health status and alcohol consumption. Baseline dried blood spots (DBS) were collected and retrieved to measure PEth. Results: One hundred fifty samples were tested, and 56 (37.3%) were PEth positive (≥8 ng/mL). Of those, 51.7% did not report alcohol use in the past month. Men were more likely to under-report compared to women, OR 2.9, 95% CI = 1.26, 6.65) and those in the higher economic asset categories were less likely to under-report compared to those in the lowest category (OR = 0.41 95% CI: 0.17, 0.94). Among self-reported drinkers (n = 31), PEth was highly correlated with the total number of drinking days in the last 30 (Spearman R = 0.73, p<0.001). Conclusions: Approximately half of HIV infected patients initiating ART and consuming alcohol under-report their use of alcohol. Given the high prevalence, clinicians should assess all patients for alcohol use with more attention to males and those in lower economic asset categories who deny alcohol use. Among those reporting current drinking, self-reported drinking days is a useful quantitative measure

Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Two Stellar Components in the Halo of the Milky Way

The halo of the Milky Way provides unique elemental abundance and kinematic information on the first objects to form in the Universe, which can be used to tightly constrain models of galaxy formation and evolution. Although the halo was once considered a single component, evidence for its dichotomy has slowly emerged in recent years from inspection of small samples of halo objects. Here we show that the halo is indeed clearly divisible into two broadly overlapping structural components -- an inner and an outer halo -- that exhibit different spatial density profiles, stellar orbits and stellar metallicities (abundances of elements heavier than helium). The inner halo has a modest net prograde rotation, whereas the outer halo exhibits a net retrograde rotation and a peak metallicity one-third that of the inner halo. These properties indicate that the individual halo components probably formed in fundamentally different ways, through successive dissipational (inner) and dissipationless (outer) mergers and tidal disruption of proto-Galactic clumps.Comment: Two stand-alone files in manuscript, concatenated together. The first is for the main paper, the second for supplementary information. The version is consistent with the version published in Natur

Monoclonal antibodies for copper-64 PET dosimetry and radioimmunotherapy

BACKGROUND: We previously described a two-antibody model of (64)Cu radioimmunotherapy to evaluate low-dose, solid-tumor response. This model was designed to test the hypothesis that cellular internalization is critical in causing tumor cell death by mechanisms in addition to radiation damage. The purpose of the present study was to estimate radiation dosimetry for both antibodies (mAbs) using positron emission tomography (PET) imaging and evaluate the effect of internalization on tumor growth. RESULTS: Dosimetry was similar between therapy groups. Median time to tumor progression to 1 g ranged from 7–12 days for control groups and was 32 days for both treatment groups (p < 0.0001). No statistically significant difference existed between any control group or between the treatment groups. MATERIAL AND METHODS: In female nude mice bearing LS174T colon carcinoma xenografts, tumor dosimetry was calculated using serial PET images of three mice in each group of either internalizing (64)Cu-labeled DOTA-cBR96 (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or non-internalizing (64)Cu-labeled DOTA-cT84.66 from 3 to 48 h. For the therapy study, controls (n = 10) received saline, DOTA-cBR96 or DOTA-cT84.66. Treatment animals (n = 9) received 0.890 mCi of (64)Cu-labeled DOTA-cBR96 or 0.710 mCi of (64)Cu-labeled DOTA-cT84.66. Tumors were measured daily. CONCLUSIONS: PET imaging allows the use of (64)Cu for pre-therapy calculation of tumor dosimetry. In spite of highly similar tumor dosimetry, an internalizing antibody did not improve the outcome of (64)Cu radioimmunotherapy. Radio-resistance of this tumor cell line and copper efflux may have confounded the study. Further investigations of the therapeutic efficacy of (64)Cu-labeled mAbs will focus on interaction between (64)Cu and tumor suppressor genes and copper chaperones

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al