Formation of an r8-Dominant Si Material.

The rhombohedral phase of Si (r8-Si), a promising semiconducting material, is formed by indentation together with the body-centered cubic phase (bc8-Si). Using a novel sample preparation method, x-ray diffraction is used to determine the relative volume of these phases in indented Si and allow observation of a distorted unit cell along the direction of indentation loading. Theoretical calculations together with these observations suggest the indent contains an intrinsic compression of ∼4 GPa that stabilizes the r8 phase.

Effects of acute exercise on inspiratory muscle strength and endurance in untrained women and men.

AIM: The purpose of this study was to determine if sex differences are present in exercise-induced inspiratory muscle function in untrained humans. METHODS: Eight young untrained women (23.8 ± 1.5 y, VO2max = 33.7 ± 4.0 mL/kg/min) and men (26.1 ± 2.0 y, VO2max = 36.7 ± 1.2 mL/kg/min) performed high-intensity cycling exercise (80% WRmax) to exhaustion. Inspiratory muscle strength and endurance were assessed pre- and post-exercise by measuring maximal inspiratory pressure (PImax) and time to task failure during a constant-load breathing test (CLBT), respectively. RESULTS: Relative intensity and time to exhaustion during high-intensity exercise was similar between women and men. Prior to exercise, PImax was similar between sexes. After exercise, women and men showed similar reductions in PImax (W: 140.4 ± 9.9 to 124.6 ± 6.7 cm H2O, P<0.05; M: 147.7 ± 10.2 to 128.1 ± 11.1 cm H2O, P<0.05). No sex difference was found in the magnitude change in PImax following exercise (W: 15.8 ± 7.9 vs. M: 19.6 ± 4.7 cm H2O). Time to task failure on the CLBT was reduced following exercise in women (360 ± 54 to 135 ± 29 s, P<0.05) and men (270 ± 36 to 150 ± 17 s, P<0.05). Women exhibited a greater reduction in time to task failure following exercise than men (W: 225 ± 55 vs. M: 120 ± 38 s, P=0.05). CONCLUSION: These data demonstrate that women exhibit a greater reduction in inspiratory muscle endurance following an acute bout of high-intensity exercise than men.

Reproducible improvement in endothelial function following two separate periods of high-intensity interval training in young men.

High-intensity interval training (HIIT) can improve vascular function, as assessed by brachial artery flow-mediated dilation (FMD). However, when separated by a period of detraining, the reproducibility of FMD responses to repeated periods of HIIT is unknown. The purpose of this study was to determine the group mean and intraindividual reproducibility of FMD responses to two 4-wk periods of HIIT, separated by 3 mo of detraining. Thirteen healthy, recreationally active men (21 ± 2 yr) completed the study. Each 4-wk HIIT period included 40 min of treadmill training four times/week. Each training session included four 7-min intervals: 4 min at 90%-95% heart rate maximum (HRmax) and 3 min at 70%-75% HRmax. Vascular (FMD) and cardiorespiratory fitness (maximal oxygen consumption [V̇o2max]) assessments were conducted before and following each 4-wk training period. Training resulted in significant improvements in V̇o2max (P < 0.001). Training also improved FMD (P < 0.001), with no differences between periods (P = 0.394), even after controlling for changes in baseline diameter and the shear rate stimulus. There was a significant, moderate relationship between the change in FMD in HIIT period 1 versus period 2 [R2 = 0.493, P = 0.011, intraclass correlation coefficient: 0.600, coefficient of variation: 17.3%]. Consecutive periods of HIIT separated by detraining resulted in similar improvements in FMD at the group level, and individual FMD changes in period 1 of HIIT predicted FMD changes in response to period 2. Considered alongside substantial between-participant variability in magnitude of FMD improvement, this suggests that there are reproducible, interindividual differences in the potential to improve vascular function with HIIT.NEW & NOTEWORTHY This is the first study examining endothelial function [flow-mediated dilation (FMD)] following repeated periods of high-intensity interval training (HIIT). Two periods of HIIT separated by detraining resulted in reproducible group-level improvements in FMD. Despite considerable between-subject variability in FMD adaptation, individual FMD changes with the first HIIT period predicted FMD changes in the second period. This indicates the existence of reproducible between-subject differences in susceptibility to FMD improvement with HIIT.

Relationship between adverse childhood experiences and perceived discrimination in adulthood.

BACKGROUND: Adverse Childhood Experiences (ACEs) and perceived discrimination impact health overtime, however little is known about their association. METHODS: Data for 6,325 participants in the Midlife in the US (MIDUS) study were analyzed across three waves of data. ACEs included emotional or physical abuse, household dysfunction, or financial strain in childhood. Generalized Linear Models with Generalized Estimating Equation approach was used to test the unadjusted and adjusted associations for ACEs and perceived discrimination and perceived inequality. RESULTS: Individuals with ACEs reported significantly higher perceived inequality in work (ß=0.05, 95%CI 0.02-0.07), in home (ß=0.06, 95%CI 0.04-0.09), in family relationships (ß=0.09, 95%CI 0.06-0.11), perceived daily discrimination (ß=0.77, 95%CI 0.58-0.96), and perceived lifetime discrimination (ß=0.24, 95%CI 0.18-0.30). ACE types were significantly associated with more perceived inequality and perceived discrimination. . Abuse was independently associated with all outcomes after adjusting for household dysfunction, financial strain, age, sex, race/ethnicity, education, marital status, and income. LIMITATIONS: Findings cannot speak to the temporal relationship between ACEs and discrimination. It should not be assumed that ACEs cause perceived discrimination, but rather that there is an important association that warrants further investigation. CONCLUSIONS: These findings represent the first step in better understanding the relationship between ACEs and perceived discrimination. As both influence health across the lifespan, understanding the relationship, mechanisms, and pathways for intervening are of great importance from a population health perspective. Efforts to incorporate discussions on experiences with discrimination and inequality may be warranted as a part of treatment for ACEs to address psychosocial stressors across the lifespan.

Immunogenicity of synthetic peptides from circumsporozoite protein of Plasmodium falciparum.

In a study of recombinant proteins that might be useful in developing a vaccine against malaria, synthetic peptides from the circumsporozoite (CS) protein of Plasmodium falciparum were found to be immunogenic for mice and rabbits. Antibody to peptides from the repeating region of the CS protein recognized native CS protein and blocked sporozoite invasion of human hepatoma cells in vitro. Antibodies to peptides from regions I and II had no biologic activity, although antibody to region I recognized processed CS protein by Western blot analysis. These data support the feasibility of developing a vaccine against the sporozoite stage of the malaria parasite by using synthetic peptides of the repeating region of the CS protein conjugated to a carrier protein.

Achieving a narrow size distribution of Au particles at a precise depth in SiO2 by segregation of Au precipitates.

We propose a new method of confining Au nanoparticles of a narrow size distribution at a precise depth in an SiO2 matrix. The process involves the formation of nanocavities in silicon by hydrogen implantation and annealing (at 850 degrees C), followed by Au gettering to and precipitation in such cavities and a wet oxidation at 900 degrees C. Starting with a silicon-on-insulator wafer, Au precipitates can be segregated behind a growing Si/SiO2 interface during wet oxidation and ultimately trapped in SiO2 at the front interface of a buried oxide layer. The shape of the precipitates has been examined by transmission electron microscopy and found to be spherical. The average diameters of these precipitates before and after oxidation have been determined as around 15 nm and 30 nm, respectively.

Nanoindentation-induced phase transformations in silicon at elevated temperatures.

The nanoindentation-induced phase transformation behavior of silicon at elevated temperatures (25-150 degrees C) has been studied. Nucleation of Si-III/Si-XII on unloading is enhanced with increasing temperature and at the highest temperatures in an amorphous Si matrix, occurs in a continuous fashion without a pop-out event. Interestingly, for slow unloading at the highest temperatures, formation of Si-III/Si-XII in a crystalline Si matrix was not observed. Elevated temperatures enhance the nucleation of Si-III and Si-XII during unloading but the final composition of the phase transformed zone is also dependent on the thermal stability of the phases in their respective matrices.

Bent DNA functions as a replication enhancer in Saccharomyces cerevisiae.

Previous studies have demonstrated that bent DNA is a conserved property of Saccharomyces cerevisiae autonomously replicating sequences (ARSs). Here we showed that bending elements are contained within ARS subdomains identified by others as replication enhancers. To provide a direct test for the function of this unusual structure, we analyzed the ARS activity of plasmids that contained synthetic bent DNA substituted for the natural bending element in yeast ARS1. The results demonstrated that deletion of the natural bending locus impaired ARS activity which was restored to a near wild-type level with synthetic bent DNA. Since the only obvious common features of the natural and synthetic bending elements are the sequence patterns that give rise to DNA bending, the results suggest that the bent structure per se is crucial for ARS function.

Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia.

Screening for primary hyperaldosteronism (PHA) is often indicated in individuals with resistant hypertension or hypokalaemia. However, in the far larger subset of the hypertensive population who do not fit into these criteria, the evidence for screening is conflicting and dependent on the disease prevalence. The purpose of this study was to examine the prevalence of PHA in a large population with mild to moderate hypertension and without hypokalaemia using a carefully controlled study protocol including a normotensive control population. Hypertensive subjects underwent medication washout and both hypertensive and normotensive subjects placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study specific cutoff values were based on results from the normotensive population studied under identical conditions. A screening test (serum aldosterone/PRA ratio [ARR]>25 with a serum aldosterone level >8 ng/dl) was followed by a confirmatory test (urine aldosterone excretion rate [AER] >17 microg/24 h) to demonstrate evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER, consistent with evidence of PHA. Individuals with PHA had higher blood pressure and lower serum potassium levels while on a high-sodium diet. Sodium restriction neutralized these differences between PHA and essential hypertensives. The prevalence of PHA in this mild to moderate hypertensive population without hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives with random screening in comparable populations. Hyperaldosteronism, when present, is responsive to sodium restriction.

Neoplasms in young dogs after perinatal irradiation.

For a study of the life-time effects of irradiation during development, 1,680 beagles were given single, whole-body exposures to 60Co gamma-radiation at one of three prenatal (preimplantation, embryonic, and fetal) or at one of three postnatal (neonatal, juvenile, and young adult) ages. Mean doses were 0, 0.16, or 0.83 Gy. For comparison with data on childhood cancer after prenatal irradiation, examination was made of tumors occurring in young dogs in this life-span experiment. Up to 4 years of age, 18 dogs had neoplasms diagnosed, 2 of these being in controls. Four dogs that were irradiated in the perinatal (late fetal or neonatal) period died of cancers prior to 2 years of age. This risk was of significant increase compared to the risks for other experimental groups and for the canine population in general. Overall, 71% (5 of 7) of all cancers and 56% (10 of 18) of all benign and malignant neoplasms seen in the first 4 years of life occurred in 29% (480 of 1,680) of the dogs irradiated in the perinatal period. These data suggest an increased risk for neoplasia after perinatal irradiation in dogs.

Cold temperature resistance, chromosomal polymorphism and interpopulation heterosis in Drosophila pseudoobscura.

Descendants of two Colorado, U.S.A., populations of D. pseudoobscura, Boulder and La Foret, were exposed to +2 degrees and -2 degrees . In third instar larvae from Boulder AR and PP third chromosome gene arrangements survived better than TL and others, while the reverse situation occurred for La Foret. Deleterious dominant effects were observed for AR from La Foret. In adults from Boulder there was a trend towards greater survival for AR and PP than for other gene arrangements, while AR from La Foret showed relatively poor cold resistance. Survival of Boulder and La Foret flies, and their interpopulation hybrid, was determined after exposure to -2 degrees at two humidities. Order of survival of developmental stages was: adults >> third instar larvae > mixture of first and second instar larvae. Adults survived better at low humidity, while larvae survived better at high humidity. Boulder adults and larvae survived better than those from La Foret. Advantage in survival of hybrids over the midparent ranged from 23% to 138%. Hybrid advantage over the higher parent ranged from 5% to 111%. Order of expression of heterosis was: mixture of first and second instar larvae > third instar larvae > adults. Relation of all results to the chromosomal polymorphisms at Boulder (seasonally constant) and La Foret (seasonally cyclic) is discussed.

Response to Selection for Mating Speed and Changes in Gene Arrangement Frequencies in Descendants from a Single Population of DROSOPHILA PSEUDOOBSCURA.

Heritability estimates, based on 19 generations of selection for fast and slow mating speed, were not significantly different from zero at the 0.05 level in any replicate of selected lines in a population of flies descended from the Mather population in California. Only the combined heritability estimate of approximately 2% was significant. This indicated that very little additive genetic variance was present in the base population and that strong directional selection for rapid mating may have occurred in the previous history of the local population at Mather and/or during its many generations of laboratory propagation. Frequencies of third chromosome gene arrangements were monitored during the course of selection. Balancing selection, unrelated to that imposed for mating speed, and genetic drift appeared to be the major factors causing changes in chromosome frequencies. Present differences in adaptive value of third chromosome variants in nature may be associated with nonadditive effects on mating speed, as well as effects on other components of fitness.

Influence of dietary sodium on the renin-angiotensin-aldosterone system and prevalence of left ventricular hypertrophy by EKG criteria.

We investigated the interplay of dietary sodium and renin-angiotensin-aldosterone system (RAAS) activity with the prevalence of left ventricular hypertrophy (LVH) in essential hypertension. Electrocardiograms (EKG) were reviewed for the presence of LVH in 160 hypertensive patients. We then compared the rate of LVH to levels of plasma renin activity (PRA) and serum aldosterone under high and low sodium diet conditions. On high sodium diet, serum aldosterone was significantly higher (7.7+/-0.93 vs 5.7+/-0.35 ng/dl, P=0.02) in participants with LVH. With low sodium diet and upright posture, PRA was significantly lower in subjects with LVH vs those without (5.6+/-1.1 vs 7.6+/-0.56 ng/ml/h, P=0.026). Aldosterone levels on low sodium diet were not different between those with and those without LVH. PRA was then dichotomized at the lowest quartile under low sodium/upright posture conditions to define a 'low renin' group. In a multivariate logistic regression containing renin status (low renin vs normal/high renin), aldosterone on a high sodium diet, age, body mass index, gender, race, duration of hypertension, systolic and diastolic blood pressure and salt-sensitivity only low-renin status on a low sodium diet (P=0.019) and serum aldosterone on a high sodium diet (P=0.04) were significant predictors of LVH. Thus, reduced modulation of renin activity in response to sodium restriction and an increased aldosterone on a high sodium diet appear to identify characteristics of hypertensive patients predisposed to abnormal cardiac remodelling.

Purification and amino acid analysis of a human macrophage cytotoxicity-inducing factor (MCF).

Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, MCFs). Both MCF species were purified to apparent homogeneity, as assessed by two-dimensional (2D) gel electrophoresis, by a combination of dye ligand, ion exchange, and hydrophobic interaction chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Exhaustive treatment of P29 by endoglycosidase F, performic acid, and 40x molar excess 2-mercaptoethanol failed to generate P14.7 from P29. Antisera raised to P29 recognized only P29 in immunoblots of 2D gels of crude hybridoma supernatant. Amino acid composition analyses of both species are similar but not identical. These MCFs appear to be distinct but possibly related proteins important in the inflammatory response, whereas N-terminal analysis of P29 reveals it to be a previously undescribed cytokine.

The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control. Hyperaldosteronism and hyperparathyroidism represent pathophysiologic conditions that may contribute to or perpetuate each other; aldosterone regulates parathyroid hormone and associates with adverse skeletal complications, and parathyroid hormone regulates aldosterone and associates with adverse cardiovascular complications. As dysregulation in both systems is linked to poor cardiovascular and skeletal health, it is increasingly important to fully characterize how they interact to more precisely understand their impact on human health and potential therapies to modulate these interactions. This review describes the known clinical interactions between these two systems including observational and interventional studies. Specifically, we review studies describing the inhibition of renin activity by calcium and vitamin D, and a potentially bidirectional and stimulatory relationship between aldosterone and parathyroid hormone. Deciphering these relationships might clarify variability in outcomes research, inform the design of future intervention studies and provide insight into the results of prior and ongoing intervention studies. However, before these opportunities can be addressed, more effort must be placed on shifting observational data to the proof of concept phase. This will require reallocation of resources to conduct interventional studies and secure the necessary talent.

Experimental evidence of new tetragonal polymorphs of silicon formed through ultrafast laser-induced confined microexplosion.

Ordinary materials can transform into novel phases at extraordinary high pressure and temperature. The recently developed method of ultrashort laser-induced confined microexplosions initiates a non-equilibrium disordered plasma state. Ultra-high quenching rates overcome kinetic barriers to the formation of new metastable phases, which are preserved in the surrounding pristine crystal for subsequent exploitation. Here we demonstrate that confined microexplosions in silicon produce several metastable end phases. Comparison with an ab initio random structure search reveals six energetically competitive potential phases, four tetragonal and two monoclinic structures. We show the presence of bt8 and st12, which have been predicted theoretically previously, but have not been observed in nature or in laboratory experiments. In addition, the presence of the as yet unidentified silicon phase, Si-VIII and two of our other predicted tetragonal phases are highly likely within laser-affected zones. These findings may pave the way for new materials with novel and exotic properties.

Bacterial expression and characterization of the CREB bZip module: circular dichroism and 2D 1H-NMR studies.

In this paper we describe the expression and purification from bacteria of the recombinant basic leucine zipper (bZip) domain of the cAMP response element binding protein, CREB327. The bZip peptide, CREB259-327, purified to near homogeneity, maintains the sequence-specific CRE site recognition demonstrated by in vitro competition assays. Alkylation of the three cysteine residues of CREB259-327 was employed to prevent aggregation of the peptide due to cysteine oxidation. The Kd of the purified native and modified CREB259-327 for the CRE site was determined by gel retardation assays to be on the order of 10(-7) M. We employed CD spectroscopy to study the folding properties of the native and modified CREB259-327. The CD analyses of the native/modified CREB259-327 peptide demonstrated a 20% increase in the alpha-helical content upon binding to the cAMP response-element. Only a 5% increase in the alpha-helical content of CREB259-327 is observed upon binding to the AP-1 site. This observation contrasts with CREB from the GCN4 protein (Weiss, M.A., et al., 1990, Nature 347, 575-578). In addition, the two-dimensional (2D) 1H-NMR studies of the bZip CREB peptide further support the distinct features of the CREB protein, in comparison to GCN4. Analysis by CD and 2D NMR of the dimerization domain of CREB suggests that the distinct DNA binding characteristics of CREB reside in the basic portion of the bZip module.

Cloning of the canine interleukin-2-encoding cDNA.

Here we report the nucleotide sequence of the canine interleukin-2 (IL-2)-encoding cDNA. Cloning of the canine IL-2 cDNA was achieved by the polymerase chain reaction employing, as a template, a cDNA derived from mitogen-stimulated canine splenic lymphocyte mRNA. The deduced amino acid (aa) sequence of canine IL-2 consists of 155 aa and displays 84% sequence similarity to human IL-2.

N-methyl-D-aspartate evokes the release of somatostatin from striatal interneurons in primary culture.

Indirect immunocytochemistry of striatal neurons in primary culture, generated from the embryonic mouse brain, suggested that 2-4% of the neurons contained somatostatin-like immunoreactivity; the majority of these cells also contained neuropeptide Y immunoreactivity, characteristic of a subset of striatal interneurons. Although 10-15% of cultured striatal neurons showed moderate or intense immunoreactivity for calbindin-D28k, the majority of neurons with somatostatin-like immunoreactivity did not contain calbindin-D28k-like immunoreactivity; parvalbumin immunoreactivity was absent from the culture preparation. A highly sensitive radioimmunoassay was used to examine the actions of depolarizing agents and excitatory amino acids on the release of endogenous somatostatin-like immunoreactivity from striatal interneurons. During a 15 min incubation period, 47 +/- 10 fmol of somatostatin-like immunoreactivity were released from 14 days in vitro striatal neurons, cultured in 35 mm dishes. Depolarization with 56 mM KCl or 10 micrograms/ml veratrine resulted in an additional 105 +/- 9 and 56 +/- 5 fmol, respectively, of somatostatin-like immunoreactivity released; the release evoked by veratrine was blocked by 1 microM tetrodotoxin. In the presence of 100 microM N-methyl-D-aspartate, 112 +/- 21 fmol of somatostatin-like immunoreactivity (above basal) were released (+238%); the N-methyl-D-aspartate-evoked release was dose-dependent (EC50, 20 microM), attenuated in the absence of added Ca2+, potentiated in the absence of added Mg2+ and unaffected by the presence of 1 microM tetrodotoxin. The selective antagonists 2-amino-5-phosphonovalerate (100 microM) and MK-801 (1 microM) blocked the N-methyl-D-aspartate-evoked release of somatostatin-like immunoreactivity; KCl-evoked release was unaffected. Kainate was slightly more effective, yet five-fold less potent (EC50, 100 microM), than N-methyl-D-aspartate in evoking somatostatin-like immunoreactivity release; quisqualate was marginally effective. The results of this study suggest that N-methyl-D-aspartate and kainate receptors are present on striatal somatostatinergic interneurons in primary culture.

Receptor pharmacology of calcium entry blocking agents.

The mechanism of action of calcium channel modulators, a class of drugs that includes 3 chemical groups--1,4-dihydropyridines, phenylalkylamines and benzothiazepines--has been extensively reviewed. The best known representatives of these 3 groups are nifedipine, verapamil and diltiazem, respectively. These drugs bind reversibly, stereospecifically and with high affinity to both the membrane-bound and the purified receptor complex. Non-dihydropyridines allosterically regulate dihydropyridine binding. This has been shown by using (-) [3H]202-791 and (+) [3H]PN200-110 as labeled ligands. The purified receptor complex that possesses binding sites for all 3 chemical groups is likely to be related to the voltage-dependent calcium channel. As the result of a drug-receptor interaction, voltage-dependent calcium channels are either activated or inactivated. The drugs that activate channels act by promoting long-lasting channel openings. The drugs that inhibit calcium channels, the calcium entry-blocking agents, act by preventing channel openings upon membrane depolarization. A complex pharmacologic, electrophysiologic, biochemical, immunologic and molecular genetic approach is required to determine the molecular mechanism of action of calcium channel modulators. Clinically, calcium entry-blocking agents are recommended for the treatment of angina pectoris, hypertension, posthemorrhagic cerebral vasospasm, supraventricular tachycardia, migraine and asthma and the protection of the ischemic myocardium.