Critical temperature in feedback-controlled electromigration of gold nanostructures.

This paper presents several experiments demonstrating the need for a more nuanced picture of electromigration (EM) than that of a fixed critical junction temperature at which EM onset occurs. Our data suggests that even for a fixed cross-sectional geometry the critical junction temperature for EM, T c , varies with environmental temperature, thermal resistance of adjacent regions, and even the direction of the current flow in asymmetric structures. We have performed feedback-controlled EM on nanowires at environmental temperatures between 75 and 260 K and fit the EM onset points with a constant junction power model. We find that average fit critical power is monotonically increasing with decreasing temperature, but is decidedly nonlinear at lower temperatures. We extract and compare the corresponding T c values using several different thermal models which utilize measured values of nanowire thermal conductivity for our devices: these models all agree on a moderately increasing T c with decreasing environmental temperature. This is tentatively explained by enhanced current-driven annealing on the voltage ramp prior to EM onset which decreases structural scattering, thereby increasing the critical temperature at which wind-force-driven hopping events will achieve a critical atomic flux. We also obtain fit critical power for a series of bowtie structures of identical constriction but varying adjacent thermal resistance (R th ), and estimate that T c in the constriction varies with R th for higher resistance structures. Critical power measurements on a second series of asymmetric bowties further suggests that T c also depends on the alignment of the electron flow with the temperature gradient at the constriction.

Analysis of yeast protein kinases using protein chips.

We have developed a novel protein chip technology that allows the high-throughput analysis of biochemical activities, and used this approach to analyse nearly all of the protein kinases from Saccharomyces cerevisiae. Protein chips are disposable arrays of microwells in silicone elastomer sheets placed on top of microscope slides. The high density and small size of the wells allows for high-throughput batch processing and simultaneous analysis of many individual samples. Only small amounts of protein are required. Of 122 known and predicted yeast protein kinases, 119 were overexpressed and analysed using 17 different substrates and protein chips. We found many novel activities and that a large number of protein kinases are capable of phosphorylating tyrosine. The tyrosine phosphorylating enzymes often share common amino acid residues that lie near the catalytic region. Thus, our study identified a number of novel features of protein kinases and demonstrates that protein chip technology is useful for high-throughput screening of protein biochemical activity.

Neutrophils and secondary infections in COVID-19 induced acute respiratory distress syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is the cause of the current global pandemic and has affected more than 188 countries worldwide. Infection by the virus can have diverse clinical manifestations, with one of the most severe clinical manifestation being respiratory failure and the development of acute respiratory distress syndrome. Clinical manifestations of acute respiratory distress syndrome secondary to SARS-CoV-2 are also diverse with a lack of diagnostic tools to distinguish between primary viral infection and secondary bacterial infections. This was a single-centre, retrospective case-control study of bronchoalveolar lavage fluid cell counts, flow cytometry and culture results from mechanically ventilated patients with SARS-CoV-2 (COVID-19) pneumonia and acute respiratory distress syndrome. Neutrophils were the predominant cell type in bronchoalveolar fluid samples up to 2 weeks into mechanical ventilation. There also was a strong correlation between positive respiratory cultures and significant elevation in bronchoalveolar fluid neutrophil counts/percentages and serum C-reactive protein levels. Absolute levels of T cell subtypes correlated with reduced lung compliance measurements. Patients with SARS-CoV-2 and severe respiratory disease are at risk for secondary infections. In some COVID-19 patients, serum C-reactive protein and bronchoalveolar fluid neutrophils may be correlated with a secondary infection.

Infants' discrimination of the duration of a rapid spectrum change in nonspeech signals.

Two-month-old infants discriminated complex sinusoidal patterns that varied in the duration of their initial frequency transitions. Discrimination of these nonspeech sinusoidal patterns was a function of both the duration of the transitions and the total duration of the stimulus pattern. This contextual effect was observed even though the information specifying stimulus duration occurred after the transitional information. These findings parallel those observed with infants for perception of synthetic speech stimuli. Specialized speech processing capacities are thus not required to account for infants' sensitivity to contextual effects in acoustic signals, whether speech or nonspeech.

Transport spectroscopy of single Pt impurities in silicon using Schottky barrier MOSFETs.

We investigate low temperature electron transport in silicon Schottky barrier metal-oxide-semiconductor field-effect transistors (MOSFETs), which consist of PtSi metallic source/drain electrodes. Measurements are made on approximately 23 inversion layers and resonances attributed to single impurities close to the metal/semiconductor interface are observed. We ascribe these impurities to Pt atoms that have diffused into the semiconductor channel from the contacts.

Rapid modulation of lipogenesis by clofibrate in rat and monkey hepatocytes.

Previous studies have proposed various possible mechanisms for the hypolipidemic actions of clofibrate. In the present study, isolated liver cells freshly prepared from rats and squirrel monkeys were used to investigate the acute effects of sodium clofibrate (sodium chlorophenoxyisobutyrate) on hepatic lipogenesis. Incubation of liver cells with levels of the drug (1 mM) known to lower plasma lipid level in vivo produced a rapid inhibition of [14C]acetate incorporation into cellular lipids. The degree of inhibition caused by the drug was not diminished by preincubation with an excess of unlabeled acetate. Conversion of [14C]acetate to 14CO2 was not significantly altered by sodium clofibrate at 1--3 mM levels, but was decreased at 5--10 mM levels. Incorporation of [14C]acetate into all lipid classes was suppressed by this agent, but inhibition of sterol synthesis was more pronounced than that of fatty acids. Sodium clofibrate (1 mM) reduced the synthesis of sterols from either labeled acetate or labeled mevalonate to a similar degree, but the decline was augmented in each case by a 30-min preincubation of the cells with sodium clofibrate. Addition of fatty acids to cell incubations stimulated sterol generation from [14C] acetate or from [3H] mevalonate, but did not reverse the inhibitory effects of the drug. These results suggest (a) the sodium clofibrate rapidly interferes with hepatic fatty acid and sterol synthesis by direct or indirect actions at diverse loci; (b) that these effects probably occur after acetyl-CoA formation and do not stem from precursor pool dilution; (c) that sodium clofibrate diminishes sterol production at post-mevalonic and perhaps also at pre-mevalonic sites; (d) that a similar pattern of inhibition occurs with sodium clofibrate in the presence of added fatty acids; and (e) that rat and primate livers demonstrate similar metabolic responses to the drug.

Potent inhibitory ligands of the GRB2 SH2 domain from recombinant peptide libraries.

We cloned and expressed the SH2 domain of human GRB2 as glutathione S-transferase and maltose binding protein fusion proteins. We screened three phagemid-based fd pVIII-protein phage display libraries against SH2 domain fusion proteins. Sequence analysis of the peptide extensions yielded a variety of related peptides. By examining the ability of the phage clones to bind other SH2 domains, we demonstrated that the phage were specific for the SH2 domain of GRB2. Based on the sequence motif identified in the "random" library screening experiment, we also built and screened a phage display library based on a Tyr-X-Asn motif (X5-Tyr-X-Asn-X8). To examine the affinity of the phage derived peptides for GRB2, we set up a radioligand competition binding assay based on immobilized GRB2 and radiolabelled autophosphorylated EGFR ICD as the radioligand. Results obtained with peptide competitors derived from the phage sequences demonstrated that nonphosphotyrosine-containing peptides identified with the phage display technology had an affinity for the receptor similar to tyrosine-phosphorylated peptides derived from the EGFR natural substrate. Interestingly, when the phage display peptides were then phosphorylated on tyrosine, their affinity for GRB2 increased dramatically. We also demonstrated the ability of the peptides to block the binding of the GRB2 SH2 domain to EGFR in a mammalian cell-based binding assay.

Mechanism of electron conduction in self-assembled alkanethiol monolayer devices.

Electron tunneling through self-assembled monolayers (SAMs) of alkanethiols was investigated using nanometer scale devices that allow temperature-dependent current-voltage, I(V, T), measurements. The I(V, T) measurement results show, for the first time, temperature-independent electron transport characteristics, proving direct tunneling as the transport mechanism in alkanethiol SAMs. The measured tunneling currents can be fitted with theoretical calculations using the modified rectangular barrier model of direct tunneling with a barrier height Phi(B) = 1.42 +/- 0.04 eV and a non-ideal barrier factor alpha = 0.65 +/- 0.01 (that may correspond to effective mass of 0.42 m). From the length-dependent conduction measurement on different alkanethiols of various lengths, the tunneling current exhibits exponential dependence on the molecular length, d, as I proportional, variant exp(-betad), where beta is a decay coefficient that was found to be bias-dependent and agrees with the existing theory of direct tunneling. A zero field decay coefficient beta(0) of 0.79 +/- 0.01 A(-1) was obtained.

Electrical characterization of metal-molecule-silicon junctions.

Direct assembly of molecules onto silicon surfaces is of particular interest for potential employment in hybrid organic-semiconductor devices. In the study we report here, aryl diazonium salts were used to assemble covalently bound molecular groups on a hydride-passivated, oxide-free n-type Si(111) surface. The reaction of 4-(trimethylsilylethynyl)benzenediazonium tetrafluoroborate generates a molecular layer of 4-(trimethylsilylethynyl)phenylene (TMS-EP) on the n++-Si(111) surface. The monolayer modifies the electrical properties of the interface and exhibits nonlinear current-voltage characteristics, as compared with the ohmic behavior observed from metal-n++-Si(111) junctions. The result of current-voltage measurements at variable temperatures (from 300 to 10 K) on samples made with the TMS-EP molecule does not show significant thermally-activated transport, indicating that tunneling is the dominant transport mechanism. The measured data is compared to a tunneling model.

Molecular wires, switches, and memories.

Design and measurements of molecular wires, switches, and memories offer an increased device capability with reduced elements. We report: Measurements on through-bond electronic transport properties of nanoscale metal-1,4-phenylene diisocyanide-metal junctions are reported, where nonohmic thermionic emission is the dominant process, with isocyanide-Pd showing the lowest thermionic barrier of 0.22 eV; robust and large reversible switching behavior in an electronic device that utilizes molecules containing redox centers as the active component, exhibiting negative differential resistance (NDR) and large on-off peak-to-valley ratio (PVR) are realized; erasable storage of higher conductivity states in these redox-center-containing molecular devices are observed; and a two-terminal electronically programmable and erasable molecular memory cell with long bit retention time is demonstrated.

Temperament and attention: orienting toward and away from positive and negative signals.

Two studies used a target detection task to examine temperament-related attentional biases toward and away from significant stimuli. Pretarget cues were used to orient attention to locations carrying a positive incentive value (where points could be gained) or a negative value (where points could be lost). Under both involuntary and voluntary conditions, extraverts were slow to shift attention away from positive locations, whereas introverts were slow to shift from negative locations. These biases were enhanced on trials following negative feedback and tended to be strongest in Ss high in Neuroticism. The findings support models proposing that Extraversion reflects the combined activity of positive (strongest in extraverts) and negative (strongest in introverts) incentive motivational processes. They further suggest that incentive processes regulate the ability to shift attention away from, rather than toward, significant stimuli.

Nursing consideration in acute spinal cord injury.

The nurse who cares for the SCI patient during the acute phase provides the assessment, implementation of routine care, and critical interventions necessary for survival. Although this group of patients requires the coordinated efforts of a multidisciplinary team for rehabilitation, it is the ICU nurse during the acute phase of care who lays the groundwork necessary for the patient to attain an optimal level of function. Care of the acutely ill SCI patient is a challenge that constantly demands innovative, individualized professional nursing care.

A method for cultivating morphologically undifferentiated embryonic stem cells from porcine blastocysts.

Variable conditions were tested to determine an in-vitro cultivation method for the formation of morphologically undifferentiated embryonic stem cells from the inner cell mass (ICM) derived outgrowth of porcine blastocysts. Although all 16 Day-9 embryos failed to form colonies, 14 such colonies were obtained from a total of 69 Day-10 embryos when they were co-cultivated with porcine uterine fibroblast (PUF) cells over a 6-day period. The best results were obtained in Dulbecco's modified Eagle medium (DMEM) with 10% fetal calf serum and 10% porcine serum supplemented with bovine insulin and beta-mercaptoethanol, in which six out of seven embryos formed adequate ICM-derived colonies. Since murine fibroblasts were not found to be suitable feeder cells in this procedure, an endocrine synergistic interaction, which promotes embryonic attachment and colony formation, between porcine blastocysts and PUF cells is hypothesized. Continued propagation of the ICM-derived cells was not dependent on these factors; a total of seven cell lines were obtained after three to five subsequent passages on murine feeder-layers that resembled morphologically undifferentiated embryonic cells.

In vitro and in vivo development of bovine embryos from zygotes and 2-cell embryos microinjected with exogenous DNA.

The objectives of these experiments were: 1) to determine an effective culture method for production of transferable bovine embryos following exogenous DNA microinjection; 2) to determine the effect of these methods on the ability of the injected zygotes and 2-cell embryos to develop in vivo; and, 3) to compare development of embryos microinjected as zygotes or 2-cell embryos. DNA fragments encoding bovine growth hormone (bGH), bGH-10Delta6, and a bGH antagonist, bGH-M8 (5) were used. A total of 639 zygotes and 153 2-cell embryos were injected. Zygotes and 2-cell embryos microinjected with bGH-M8 were incubated for 6 days in oviducts of intermediate recipients (rabbits or sheep) or co-cultured in vitro with bovine oviduct epithelial cells. Zygotes and 2-cell embryos microinjected with bGH-10Delta6 were co-cultured in vitro only. The most effective method for the production of transferable bovine embryos following exogenous DNA microinjection was via in vitro co-culturing with bovine epithelial cells. For example, 32.3% of the bGH-M8 and 33.5% of the bGH-10Delta6 microinjected zygotes reached the morula/blastocyst stage while 48.4% and 63.0% of the 2-cell embryos injected with bGH-M8 and bGH-10Delta6, respectively, developed to the morula/blastocyst stage. The percentage of blastocysts obtained for control, non-injected zygotes and 2-cell embryos was 34.5% and 69.6%, respectively. The developmental rate to the morula/blastocyst stage was approximately 20% greater for embryos obtained from microinjected 2-cell embryos relative to microinjected zygotes. However, there was no significant difference in pregnancy rates following transfer of these blastocysts to cow uteri.

Observation of the linear stark effect in a single acceptor in Si.

The Stark splitting of a single fourfold degenerate impurity located within the built-in potential of a metal-semiconductor contact is investigated using low temperature transport measurements. A model is developed and used to analyze transport as a function of temperature, bias voltage, and magnetic field. Our data is consistent with a boron impurity. We report g factors of g_{1/2}=1.14 and g_{3/2}=1.72 and a linear Stark splitting 2Delta of 0.1 meV.

Speech perception and the discrimination of brief auditory cues in reading disabled children.

The processing of speech and nonspeech sounds by 23 reading disabled children and their age- and sex-matched controls was examined in a task requiring them to identify and report the order of pairs of stimuli. Reading disabled children were impaired in making judgments with very brief tones and with stop consonant syllables at short interstimulus intervals (ISI's). They had no unusual difficulty with vowel stimuli, vowel stimuli in a white noise background, or very brief visual figures. Poor performance on the tones and stop consonants appears to be due to specific difficulty in processing very brief auditory cues. The reading disabled children also showed deficits in the perception of naturally produced words, less sharply defined category boundaries, and a greater reliance on context in making phoneme identifications. The results suggest a perceptual deficit in some reading disabled children, which interferes with the processing of phonological information.

Evaluation of commercial imported fire ant extracts by crossed immunoelectrophoresis and radioallergosorbent test.

Imported fire ant whole-body extracts (IFAWBE) from three major U.S. commercial suppliers and a reference IFAWBE and imported fire ant venom (IFAV) preparation were compared by crossed immunoelectrophoresis and RAST-inhibition testing. Results of crossed immunoelectrophoretic studies showed major differences in antigen content between commercial preparations. IFAWBE and IFAV RAST-inhibition testing showed that no commercial extract had equivalent inhibitory activity to the reference IFAWBE. Reference IFAWBE reached 50% inhibition of IFAWBE and IFAV RAST at 52 and 492 micrograms/ml, respectively. IFAV gave 50% inhibition of IFAWBE and IFAV RAST at 5.9 and 58 micrograms/ml, respectively. Of the commercial extracts, only those from one supplier were able to reach 50% inhibition of the reference IFAWBE RAST, and no commercial extract from any supplier was able to reach 50% inhibition of IFAV RAST. Analysis of inhibition slopes and intercepts confirmed that there were both qualitative and quantitative differences among the commercial extracts and the reference IFAWBE and IFAV. Our findings suggest possible reasons why some individuals fail to respond to testing or immunotherapy with IFAWBE and show the urgent need for standardization of allergenic extracts for diagnosis and treatment of imported fire ant sensitivity.