In general, fabrication of well-defined organic nanowires or nanobelts with controllable size and morphology is not as advanced as for their inorganic counterparts. Whereas inorganic nanowires are ...widely exploited in optoelectronic nanodevices, there remains considerable untapped potential in the one-dimensional (1D) organic materials. This Account describes our recent progress and discoveries in the field of 1D self-assembly of planar π-conjugated molecules and their application in various nanodevices including the optical and electrical sensors. The Account is aimed at providing new insights into how to combine elements of molecular design and engineering with materials fabrication to achieve properties and functions that are desirable for nanoscale optoelectronic applications. The goal of our research program is to advance the knowledge and develop a deeper understanding in the frontier area of 1D organic nanomaterials, for which several basic questions will be addressed: (1) How can one control and optimize the molecular arrangement by modifying the molecular structure? (2) What processing factors affect self-assembly and the final morphology of the fabricated nanomaterials; how can these factors be controlled to achieve the desired 1D nanomaterials, for example, nanowires or nanobelts? (3) How do the optoelectronic properties (e.g., emission, exciton migration, and charge transport) of the assembled materials depend on the molecular arrangement and the intermolecular interactions? (4) How can the inherent optoelectronic properties of the nanomaterials be correlated with applications in sensing, switching, and other types of optoelectronic devices? The results presented demonstrate the feasibility of controlling the morphology and molecular organization of 1D organic nanomaterials. Two types of molecules have been employed to explore the 1D self-assembly and the application in optoelectronic sensing: one is perylene tetracarboxylic diimide (PTCDI, n-type) and the other is arylene ethynylene macrocycle (AEM, p-type). The materials described in this project are uniquely multifunctional, combining the properties of nanoporosity, efficient exciton migration and charge transport, and strong interfacial interaction with the guest (target) molecules. We see this combination as enabling a range of important technological applications that demand tightly coupled interaction between matter, photons, and charge. Such applications may include optical sensing, electrical sensing, and polarized emission. Particularly, the well-defined nanowires fabricated in this study represent unique systems for investigating the dimensional confinement of the optoelectronic properties of organic semiconductors, such as linearly polarized emission, dimensionally confined exciton migration, and optimal π-electronic coupling (favorable for charge transport). Combination of these properties will make the 1D self-assembly ideal for many orientation-sensitive applications, such as polarized light-emitting diodes and flat panel displays.
RNA sensing pathways are key elements in a host immune response to viral pathogens, but little is known of their importance during bacterial infections. We found that
(
) actively releases RNA into ...the macrophage cytosol using the mycobacterial SecA2 and ESX-1 secretion systems. The cytosolic
RNA induces IFN-β production through the host RIG-I/MAVS/IRF7 RNA sensing pathway. The inducible expression of IRF7 within infected cells requires an autocrine signaling through IFN-β and its receptor, and this early IFN-β production is dependent on STING and IRF3 activation.
infection studies using
mice support a role for RNA sensors in regulating IFN-β production and bacterial replication in vivo. Together, our data indicate that
RNA is actively released during an infection and promotes IFN-β production through a regulatory mechanism involving cross-talk between DNA and RNA sensor pathways, and our data support the hypothesis that bacterial RNA can drive a host immune response.
Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening complication of heparin exposure. Here, we review the pathogenesis, incidence, diagnosis, and management of HIT. The first step ...in thwarting devastating complications from this entity is to maintain a high index of clinical suspicion, followed by an accurate clinical scoring assessment using the 4Ts. Next, appropriate stepwise laboratory testing must be undertaken in order to rule out HIT or establish the diagnosis. In the interim, all heparin must be stopped immediately, and the patient administered alternative anticoagulation. Here we review alternative anticoagulation choice, therapy alternatives in the difficult-to-manage patient with HIT, and the problem of overdiagnosis.
Offering a comprehensive treatment of adhesive particle flows, this book adopts a particle-level approach oriented toward directly simulating the various fluid, electric field, collision, and ...adhesion forces and torques acting on the particles, within the framework of a discrete-element model. It is ideal for professionals and graduate students working in engineering and atmospheric and condensed matter physics, materials science, environmental science, and other disciplines where particulate flows have a significant role. The presentation is applicable to a wide range of flow fields, including aerosols, colloids, fluidized beds, and granular flows. It describes both physical models of the various forces and torques on the particles as well as practical aspects necessary for efficient implementation of these models in a computational framework.
The discovery of the obese gene and the demonstration that its encoded protein leptin can reverse obesity due to genetic deficiency of the hormone were landmark discoveries in endocrinology and ...metabolism. Regarding leptin's role in physiology, it is now established that falling leptin levels are a key signal of the starved state in mice and humans. Repleting leptin reverses the starvation signal both in physiologic starvation and in obesity resulting from genetic leptin deficiency. Since its discovery, it has also been hypothesized that rising leptin levels caused by overfeeding provide a physiologic signal that orchestrates resistance to obesity. Although still widely believed, and possibly true in some circumstances, this aspect of leptin physiology has not been experimentally demonstrated. It will be important to determine whether leptin or as yet undiscovered factors are responsible for the well-documented capacity for physiologic resistance to overfeeding.
Leptin, the product of the ob gene, effectively treats leptin-deficient obesity. Flier et al. discuss two distinct aspects of leptin physiology. Whereas reduced levels with starvation evoke key adaptations to starvation, a role for rising leptin with overfeeding in resistance to obesity has not been experimentally demonstrated.
Bacteria swim by rotating rigid helical flagella and periodically reorienting to follow environmental cues. Despite the crucial role of reorientations, their underlying mechanism has remained unknown ...for most uni-flagellated bacteria. Here, we report that uni-flagellated bacteria turn by exploiting a finely tuned buckling instability of their hook, the 100-nm-long structure at the base of their flagellar filament. Combining high-speed video microscopy and mechanical stability theory, we demonstrate that reorientations occur 10 ms after the onset of forward swimming, when the hook undergoes compression, and that the associated hydrodynamic load triggers the buckling of the hook. Reducing the load on the hook below the buckling threshold by decreasing the swimming speed results in the suppression of reorientations, consistent with the critical nature of buckling. The mechanism of turning by buckling represents one of the smallest examples in nature of a biological function stemming from controlled mechanical failure and reveals a new role for flexibility in biological materials, which may inspire new microrobotic solutions in medicine and engineering. PUBLICATION ABSTRACT
Hospitals use rates from the best quartile or decile as benchmarks for quality improvement aims, but to what extent these aims are achievable is uncertain.
To determine the proportion of neonatal ...intensive care units (NICUs) in 2014 that achieved rates for death and major morbidities as low as the shrunken adjusted rates from the best quartile and decile in 2005 and the time it took to achieve those rates.
A total of 408 164 infants with a birth weight of 501 to 1500 g born from January 1, 2005, to December 31, 2014, and cared for at 756 Vermont Oxford Network member NICUs in the United States were evaluated. Logistic regression models with empirical Bayes factors were used to estimate standardized morbidity ratios for each NICU. Each ratio was multiplied by the overall network rate to calculate the 10th, 25th, 50th, 75th, and 90th percentiles of the shrunken adjusted rates for each year. The proportion in 2014 that achieved the 10th and 25th percentile rates from 2005 and the number of years it took for 75% of NICUs to achieve the 2005 rates from the best quartile were estimated.
Death prior to hospital discharge, infection more than 3 days after birth, severe retinopathy of prematurity, severe intraventricular hemorrhage, necrotizing enterocolitis, and chronic lung disease among infants less than 33 weeks' gestational age at birth.
Of the 756 hospitals, 695 provided data for 2014. The mean unadjusted infant-level rate of death before hospital discharge decreased from 14.0% in 2005 to 10.9% in 2014. In 2014, 689 of 695 NICUs (99.1%; 95% CI, 97.4%-100.0%) achieved the 2005 shrunken adjusted rates from the best quartile for death prior to discharge, 678 of 695 (97.6%; 95% CI, 95.8%-99.6%) for late-onset infection, 558 of 681 (81.9%; 95% CI, 77.2%-86.6%) for severe retinopathy of prematurity, 611 of 693 (88.2%; 95% CI, 81.7%-97.0%) for severe intraventricular hemorrhage, 529 of 696 (76.0%; 95% CI, 71.8%-81.2%) for necrotizing enterocolitis, and 286 of 693 (41.3%; 95% CI, 36.1%-45.6%) for chronic lung disease. It took 3 years before 445 NICUs (75.0%) achieved the 2005 shrunken adjusted rate from the best quartile for death prior to discharge, 5 years to achieve the rate from the best quartile for late-onset infection, 6 years to achieve the rate from the best quartile for severe retinopathy of prematurity and severe intraventricular hemorrhage, and 8 years to achieve the rate from the best quartile for necrotizing enterocolitis.
From 2005 to 2014, rates of death prior to discharge and serious morbidities decreased among the NICUs in this study. Within 8 years, 75% of NICUs achieved rates of performance from the best quartile of the 2005 benchmark for all outcomes except chronic lung disease. These findings provide a novel way to quantify the magnitude and pace of improvement in neonatology.
Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. ...Often referred to as a "liquid biopsy," CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care.
Many are frustrated with the lack of translational progress in the pain field, in which huge gains in basic science knowledge obtained using animal models have not led to the development of many new ...clinically effective compounds. A careful re-examination of animal models of pain is therefore warranted. Pain researchers now have at their disposal a much wider range of mutant animals to study, assays that more closely resemble clinical pain states, and dependent measures beyond simple reflexive withdrawal. However, the complexity of the phenomenon of pain has made it difficult to assess the true value of these advances. In addition, pain studies are importantly affected by a wide range of modulatory factors, including sex, genotype and social communication, all of which must be taken into account when using an animal model.
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