Scaling up self-assembly: bottom-up approaches to macroscopic particle organization.

This review presents an overview of recent work in the field of non-Brownian particle self-assembly. Compared to nanoparticles that naturally self-assemble due to Brownian motion, larger, non-Brownian particles (d > 6 µm) are less prone to autonomously organize into crystalline arrays. The tendency for particle systems to experience immobilization and kinetic arrest grows with particle radius. In order to overcome this kinetic limitation, some type of external driver must be applied to act as an artificial "thermalizing force" upon non-Brownian particles, inducing particle motion and subsequent crystallization. Many groups have explored the use of various agitation methods to overcome the natural barriers preventing self-assembly to which non-Brownian particles are susceptible. The ability to create materials from a bottom-up approach with these characteristics would allow for precise control over their pore structure (size and distribution) and surface properties (topography, functionalization and area), resulting in improved regulation of key characteristics such as mechanical strength, diffusive properties, and possibly even photonic properties. This review will highlight these approaches, as well as discuss the potential impact of bottom-up macroscale particle assembly. The applications of such technology range from customizable and autonomously self-assembled niche microenvironments for drug delivery and tissue engineering to new acoustic dampening, battery, and filtration materials, among others. Additionally, crystals made from non-Brownian particles resemble naturally derived materials such as opals, zeolites, and biological tissue (i.e. bone, cartilage and lung), due to their high surface area, pore distribution, and tunable (multilevel) hierarchy.

Ambient hypoxia enhances the loss of muscle mass after extensive injury.

Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.

Serum apolipoprotein C-III is independently associated with chronic hepatitis C infection and advanced fibrosis.

BACKGROUND: The hepatitis C virus (HCV) is known to disrupt lipid metabolism, making serum lipoprotein levels good candidates to explore as markers of HCV disease progression. Assessment of the major apolipoproteins (Apo) and their relationship to hepatic fibrosis remain largely unexplored. METHODS: We compared the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and Apo A-I, -B, -C-III, and -E between patients with cleared versus active infection (n = 83), and between those chronically infected patients (n = 216) with advanced versus mild-moderate hepatic fibrosis (METAVIR stage F3-4 vs. F0-2) using multiple logistic regression. RESULTS: Apo C-III levels were 25% higher in subjects with cleared infection versus those with active infection (p = 0.009). Low levels of Apo C-III (p = 1.3 × 10(-5)), Apo A-I (p = 2.9 × 10(-5)), total cholesterol (p = 5.0 × 10(-4)), LDL-C (p = 0.005), and HDL-C (p = 2.0 × 10(-4)) were associated with advanced fibrosis in univariate analyses. Multivariable analysis revealed Apo C-III as the most significant factor associated with advanced fibrosis (p = 0.0004), followed by age (p = 0.013) and Apo A-I (p = 0.022). Inclusion of both Apo C-III and Apo A-I in a model to predict advanced fibrosis improved the area under the receiver operator curve only modestly. CONCLUSIONS: Relative to other lipoproteins, low serum Apo C-III levels are the most strongly associated with chronic versus cleared infection and decline with increasing severity of hepatic fibrosis. Apo C-III deserves further attention as a possible marker of HCV disease progression.

Granular mixing and segregation in zigzag chute flow.

Periodic flow inversions have been shown as an effective means to eliminate both density (D system) and size (S system) segregation. The frequency of these inversions, however, is the key to applying this technique and is directly related to the inverse of the characteristic time of segregation. In this work, we study size segregation (S system) and adapt a size segregation model to compliment existing work on density segregation and, ultimately, aid in determining the critical forcing frequency for S systems. We determine the impact on mixing and segregation of both the binary size ratio and the length of each leg of a "zigzag chute". Mixing is observed when L < U tS, where L, U, and t(S) denote the length of each leg of the zigzag chute, the average streamwise flow velocity of the particle, and the characteristic time of segregation, respectively.

Sex and age differences in lipid response to chronic infection with the hepatitis C virus in the United States National Health and Nutrition Examination Surveys.

Low levels of serum lipids were reported in subjects chronically infected with the hepatitis C virus (HCV) and correlated with poorer clinical outcomes. Whether HCV 'hypo-lipidemia' is constant across age, sex and race has not been systematically explored. We therefore investigated the association between HCV infection and serum lipid levels in two independent National Health and Nutrition Examination Survey (NHANES) cohorts. HCV antibody status and serum lipid levels were obtained from 14 369 adults from NHANES 1999-2006 and 12 261 from NHANES III (enrolled in 1988-1994). In multivariable models, the prevalence of HCV-associated hypo-low density lipoprotein-cholesterol was highest among women >50 years of age in both NHANES 1999-2006 (OR: 10.51, 95% CI: 2.86, 38.62) and III (OR: 24.21, 95% CI: 6.17, 94.92), but among women <50 years of age, the odds ratios were 3.01 (95% CI: 1.00, 9.04) for NHANES 1999-2006 and 0.52 (95% CI: 0.14, 1.88) for III, respectively. HCV by age interaction among women was significant in both cohorts (P < 0.001 and P = 0.004, respectively). Among men, the odds ratios of HCV-associated hypo-LDL-cholesterol were 2.74 (95% CI: 1.55, 4.85) in NHANES 1999-2006 and 3.84 (95% CI: 1.66, 8.88) in III, respectively, with no significant age effects. Similar patterns were observed for total-cholesterol, but no significantly discernable patterns for high density lipoprotein-cholesterol and triglycerides. Results show that HCV infection is associated with lower total- and LDL-cholesterol in two US population-based cohorts, and this relationship varies significantly by age and sex, suggesting a possible influence of sex hormones on host lipid response to HCV infection.

Thermal expansion effects and heat conduction in granular materials.

In this paper, we report results and analysis on a simulation study of the effects of thermal expansion in granular systems. We show that these effects impact the force distribution inside a two-dimensional system of disks that are subject to thermal heating under two different boundary conditions. A significant increase in the average force is observed for steel particles confined within a box with fixed walls at temperature rises of 50 degrees C and 100 degrees C, respectively. As previously noted in the literature, thermal expansion also induces compaction. The results show that a systematic and controllable increase in granular packing can be induced by simply raising and then lowering the temperature, without the input of mechanical energy in agreement with previous experimental observations. We find that the evolution of the packing fraction is well described by a fractional relaxation model, which follows the Mittag-Leffler law.

Eliminating segregation in free-surface flows of particles.

By introducing periodic flow inversions, we show both experimentally and computationally that forcing with a value above a critical frequency can effectively eliminate both density and size segregation. The critical frequency is related to the inverse of the characteristic time of segregation and is shown to scale with the shear rate of the particle flow. This observation could lead to new designs for a vast array of particle processing applications and suggests a new way for researchers to think about segregation problems.

Recent Greenland ice mass loss by drainage system from satellite gravity observations.

Mass changes of the Greenland Ice Sheet resolved by drainage system regions were derived from a local mass concentration analysis of NASA-Deutsches Zentrum für Luftund Raumfahrt Gravity Recovery and Climate Experiment (GRACE mission) observations. From 2003 to 2005, the ice sheet lost 101 +/- 16 gigaton/year, with a gain of 54 gigaton/year above 2000 meters and a loss of 155 gigaton/year at lower elevations. The lower elevations show a large seasonal cycle, with mass losses during summer melting followed by gains from fall through spring. The overall rate of loss reflects a considerable change in trend (-113 +/- 17 gigaton/year) from a near balance during the 1990s but is smaller than some other recent estimates.

Phase diagrams for cohesive particle mixing and segregation.

By taking a discrete view of cohesion, we develop a particle-level model which can accurately predict the extent of particle mixing and segregation in cohesive (wet) granular systems. Our model is based on a discrete characterization tool and is used to generate phase diagrams of the predicted particle behavior. These phase diagrams exhibit both mixed and segregated phases where the boundary is determined by the mechanical and surface properties of the particles, such that manipulation of surface properties and/or size/density ratios provides a method to control cohesive particle mixing and segregation. A detailed description of the phase diagram development process as well as quantitative validation of the theoretical results are reported here.

Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes.

BACKGROUND: to date, only three groups have reported data from large scale genetic association studies of coronary heart disease using a case control design. METHODS AND RESULTS: to extend our initial report of 62 genes, we present data for 210 polymorphisms in 111 candidate genes genotyped in 352 white subjects with familial, premature coronary heart disease (onset age for men, 45; for women, 50) and a random sample of 418 population based whites. Multivariate logistic regression analysis was used to compare the distributions of genotypes between cases and the comparison group while controlling for age, sex, body mass, diabetes, and hypertension. Significant associations were found with polymorphisms in thrombospondin-4 (THBS4), thrombospondin-2 (THBS2) and plasminogen activator inhibitor-2 (PAI2), the strongest being with the A387P variant in THBS4 (p = 0.002). The THBS2 and THBS4 associations have since been replicated. We evaluated polymorphisms in 40 genes previously associated with coronary heart disease and found significant (p<0.05) associations with 10: ACE, APOE, F7, FGB, GP1BA, IL1RN, LRP1, MTHFR, SELP, and THPO. For five of these genes, the polymorphism associated in our study was different from that previously reported, suggesting linkage disequilibrium as an explanation for failure to replicate associations consistently across studies. We found strong linkage disequilibrium between polymorphisms within and between genes, especially on chromosome 1q22-q25, a region containing several candidate genes. CONCLUSIONS: despite known caveats of genetic association studies, they can be an effective means of hypothesis generation and complement classic linkage studies for understanding the genetic basis of coronary heart disease.

Controlling cohesive particle mixing and segregation.

We observe experimentally that particle systems that would otherwise mix can be made to segregate and vice versa simply by adding moisture. Using a newly developed theoretical approach, we generate phase diagrams that exhibit both mixed and segregated phases and show how the location of phase boundaries may be manipulated via modifying the mechanical and surface properties of the particles. These results have implications for industrial mixing/separation processes as well as novel particle production methods (e.g., engineered agglomerates with precisely prescribed compositions).

Personalized medicine: revolutionizing drug discovery and patient care.

Advances in human genome research are opening the door to a new paradigm for practising medicine that promises to transform healthcare. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual's molecular profile, will impact the way drugs are developed and medicine is practiced. Knowledge of the molecular basis of disease will lead to novel target identification, toxicogenomic markers to screen compounds and improved selection of clinical trial patients, which will fundamentally change the pharmaceutical industry. The traditional linear process of drug discovery and development will be replaced by an integrated and heuristic approach. In addition, patient care will be revolutionized through the use of novel molecular predisposition, screening, diagnostic, prognostic, pharmacogenomic and monitoring markers. Although numerous challenges will need to be met to make personalized medicine a reality, with time, this approach will replace the traditional trial-and-error practice of medicine.

Early radiographic differentiation of infantile tibia vara from physiologic bowing using the femoral-tibial ratio.

SUMMARY: The authors hypothesized that the ratio of the femoral to tibial metaphyseal-diaphyseal angles (femoral-tibial ratio [FTR]) more accurately differentiates physiologic bowing from infantile tibial vara than the tibial metaphyseal-diaphyseal angle (TMDA). The purpose of this study was threefold: to determine the false-negative and false-positive error rate of the FTR and TMDA; to determine to the effect of rotation on the FTR and TMDA; and to determine the reliability of the FTR and TMDA measurements. An FTR < 1 resulted in a false-negative error rate of 10% and a false-positive error rate of 7%, whereas a TMDA > 13 degrees resulted in a false-negative error rate of 23% and a false-positive error rate of 10%. The difference between internal and external rotation was not significant for the FTR, whereas it was for the TMDA. The FTR was found to have good interobserver and intraobserver reliability (0.78 and 0.98, respectively).

Hepatitis C in methadone maintenance patients: prevalence and public policy implications.

OBJECTIVE: This study measured the extent and examined implications of hepatitis C (HCV) infection in a methadone maintenance treatment (MMT) population. METHOD: Four hundred and sixty patients were tested for HCV-Ab, hepatic enzymes and bilirubin, HCV-RNA, and hepatitis B antibody. RESULTS: Overall, 87% of this population had evidence of HCV-Ab. Among drug injectors (IDU), 96% were HCV-Ab positive. Among a subset of Laotian opium-smoking patients prevalence was only 11%. Sixty-two percent of patients with HCV-Ab had detectable HCV-RNA. Only 41% had elevated hepatic enzymes, and 5% had elevated bilirubin levels. All age groups were equally infected. Systemic problems in screening and treating HCV in drug users were identified. CONCLUSION: HCV infection poses significant long-term health risks for this population. Harm reduction interventions aimed at reducing transmission of HCV and other needle-related infectious disease deserves more consideration.