Role of Shape in the Self-Assembly of Anisotropic Colloids.

Self-assembly is the process of spontaneous organization of a set of interacting components. We examine how particle shape drives the self-assembly of colloids in three different systems. When particles interact only via their shape, entropic crystallization can occur; we discuss a design strategy using the Voronoi tesslelation to create “Voronoi particles,” (VP) which are hard particles in the shape of Voronoi cells of their target structure. Although VP stabilize their target structure in the limit of infinite pressure, the self-assembly of the same structure at moderate pressure is not guaranteed. We find that more symmetric crystals are often preferred due to entropic contributions of several kBT from configurational degeneracies. We characterize the assembly of VP in terms of their symmetries and the complexities of the target structure and demonstrate how controlling the degeneracies through modifying shape and field-directed assembly can improve the assembly propensity. With the addition of non-adsorbing, polymers, hard colloids experience an attraction dependent on polymer concentration, the form of which is dictated by the colloid shape; we study a system of oblate, spheroidal colloids that self-assemble thread-like clusters. In both simulation and experiment the colloids condense into disordered droplets at low polymer concentrations; at higher concentrations we observe kinetic arrest into primarily linear clusters of aligned colloids. We show that the mechanical stabilty of these low-valence structures results from the anisotropic particle shape. Particle surfaces can be patterned with metal coatings, introducing enthalpic attraction between particles; we study a system of prolate spheroidal colloids, half-coated in gold. We show with experiments and computer simulations that Janus ellipsoids can self-assemble into self-limiting one-dimensional fibers with shape-memory properties, and that the fibrillar assemblies can be actuated on application of an external alternating-current electric field. Actuation of the fibers occurs through a sliding mechanism (allowed by the curved ellipsoidal surface) that permits the reversible elongation of the Janus-ellipsoid chains by ~36%. In each case, we find shape plays a critical role. By understanding and isolating its impact, we enhance shape's utility as a parameter for the design of self-assembling colloids.PhDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111630/1/baschult_1.pd

Recombinant human activated protein C in the treatment of acute respiratory distress syndrome

Rationale: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome. Methods: A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria. Intervention: A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38). Outcomes: The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others. Results: Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or noninvasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market. Conclusion: There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering. Trial Registration: Nederlands Trial Registe

Targeting the HSP60/10 chaperonin systems of Trypanosoma brucei as a strategy for treating African sleeping sickness

Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis—HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival. We recently discovered several hundred inhibitors of the prototypical HSP60/10 chaperonin system from Escherichia coli, termed GroEL/ES. One of the most potent GroEL/ES inhibitors we discovered was compound 1. While examining the PubChem database, we found that a related analog, 2e-p, exhibited cytotoxicity to Leishmania major promastigotes, which are trypanosomatids highly related to Trypanosoma brucei. Through initial counter-screening, we found that compounds 1 and 2e-p were also cytotoxic to Trypanosoma brucei parasites (EC50 = 7.9 and 3.1 μM, respectively). These encouraging initial results prompted us to develop a library of inhibitor analogs and examine their anti-parasitic potential in vitro. Of the 49 new chaperonin inhibitors developed, 39% exhibit greater cytotoxicity to T. brucei parasites than parent compound 1. While many analogs exhibit moderate cytotoxicity to human liver and kidney cells, we identified molecular substructures to pursue for further medicinal chemistry optimization to increase the therapeutic windows of this novel class of chaperonin-targeting anti-parasitic candidates. An intriguing finding from this study is that suramin, the first-line drug for treating early stage T. brucei infections, is also a potent inhibitor of GroEL/ES and HSP60/10 chaperonin systems

Great Expectations: A Review of the Colorado River Basin Pilot Project—The Nation’s Most Expensive Randomized Orographic Cloud-Seeding Experiment

The Colorado River Basin Pilot Project (CRBPP), conducted in southwest Colorado during the winters of 1970/71–1974/75, was the largest and most expensive randomized orographic cloud-seeding experiment ever conducted in the United States. Its goal was to reproduce the 50%–200% increases in snowfall reported in the Climax I experiment and in preliminary reports in two other cloud-seeding experiments. However, the CRBPP failed to demonstrate increased snowfall for four primary reasons. First, Type I statistical errors (i.e., false positives on seeded days) occurred in two of the three previous experiments, whereas the third was impacted by errors that created a seeding success. Thus, there were no successes for the CRBPP to replicate. Second, a purported close correspondence between 500-hPa and cloud-top temperatures gave the prior experiments a credible, but false, microphysical foundation. Third, a preliminary report suggesting low concentrations of ice particles in clouds with cloud-top temperatures ≥ −20°C made the clouds look ripe for seeding potential but failed to be confirmed by later airborne and ground-based measurements of much higher concentrations. Fourth, near-surface stable air masses meant that the seeding agent released from ground-based seeding equipment did not reach the clouds on many wintertime days. This review also describes the lessons learned from the CRBPP and how cloud-seeding projects have been influenced by the CRBPP: a hiatus in randomized cloud-seeding experiments in wintertime orographic clouds following the CRBPP led to the realization of the need to improve the understanding of the structure and evolution of winter storms in the mountainous western United States.Significance StatementPutting silver iodide particles into orographic clouds with cloud-top temperatures higher than −23°C was thought to have increased snowfall, a process called cloud seeding. Cloud-seeding experimenters in the Rocky Mountains in the 1960s claimed 50%–200% increases in snowfall from wintertime seeded clouds. In the early 1970s, the Colorado River Basin Pilot Project was conducted to test those cloud-seeding results in the most expensive U.S. orographic cloud-seeding experiment. Our review found four primary reasons why the project failed to confirm these increases. Nevertheless, we found that the project was not a total failure, as meteorologists learned about the complexity of orographic clouds and precipitation formation that challenged oversimplified conceptual models, as well as critical lessons for planning later cloud-seeding experiments.<br/

Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

НАПРАВЛЕНИЯ СОВЕРШЕНСТВОВАНИЯ ОБРУДОВАНИЯ ДЛЯ ФЛОТАЦИОННОГО ОБОГАЩЕНИЯ ТОНКОДИСПЕРСНыХ МАТЕРИАЛОВ

Проблема и ее связь с научными и практическими задачами. В связи с тем, что в поступающем на обогатительные фабрики сырье содержится до 30% ма-териала крупностью менее 1 мм, роль процесса флотации существенно возрас-тает. Этому способствует и возможность создания достаточно простых замкну-тых водно-шламовых схем, включающих флотацию в качестве основного эле-мента очистки оборотных вод. Многими исследованиями, которые проводились ранее и продолжают выполняться и в настоящее время, установлены направле-ния совершенствования этого достаточно сложного физико-химического про-цесс