cssi/SciSciGPT-SciSciNet huggingface dataset:
Widespread Central Nervous System Gene Transfer and Silencing After Systemic Delivery of Novel AAV-AS Vector

Effective gene delivery to the central nervous system (CNS) is vital for development of novel gene therapies for neurological diseases. Adeno-associated virus (AAV) vectors have emerged as an effective platform for in vivo gene transfer, but overall neuronal transduction efficiency of vectors derived from naturally occurring AAV capsids after systemic administration is relatively low. Here, we investigated the possibility of improving CNS transduction of existing AAV capsids by genetically fusing peptides to the N-terminus of VP2 capsid protein. A novel vector AAV-AS, generated by the insertion of a poly-alanine peptide, is capable of extensive gene transfer throughout the CNS after systemic administration in adult mice. AAV-AS is 6- and 15-fold more efficient than AAV9 in spinal cord and cerebrum, respectively. The neuronal transduction profile varies across brain regions but is particularly high in the striatum where AAV-AS transduces 36% of striatal neurons. Widespread neuronal gene transfer was also documented in cat brain and spinal cord. A single intravenous injection of an AAV-AS vector encoding an artificial microRNA targeting huntingtin (Htt) resulted in 33-50% knockdown of Htt across multiple CNS structures in adult mice. This novel AAV-AS vector is a promising platform to develop new gene therapies for neurodegenerative disorders.
Abstract 12115: Phthalate Substitute Plasticizers Activate PXR and Induce Dyslipidemia in Mice

The pregnane X receptor (PXR) is a nuclear receptor activated by numerous drugs, xenobiotic and dietary chemicals. Many endocrine disrupting chemicals (EDCs) activate PXR, including organochlorine and organophosphate pesticides, alkylphenols, phthalates, polychlorinated biphenyls, bisphenol A and phthalate plasticizers. However, the role of PXR in mediating the pathophysiological effects of EDCs in humans and animals remains elusive. Mounting evidence implicates EDC exposure in the development of chronic human diseases, but the contribution of these EDCs to the etiology of cardiovascular disease (CVD) is poorly understood. In the present study, we identified several widely used phthalate substitute plasticizers used in food packaging materials, medical devices, cosmetics, and pharmaceutical drugs as agonists of PXR. Tributyl citrate (TBC), one of a large group of FDA-approved pharmaceutical plasticizers, is a potent and selective PXR agonist but does not activate other nuclear receptors. TBC can efficiently activate PXR and induce its target gene expression in vitro and in vivo. Short-term TBC exposure increased plasma total cholesterol and atherogenic LDL cholesterol levels in wild-type mice, but not in PXR-deficient mice. Interestingly, TBC is an intestine-specific PXR ligand but does not affect hepatic PXR activity. TBC-mediated PXR activation stimulated the expression of intestinal cholesterol transporter, Niemann Pick-C1 Like 1 (NPC1L1). Chromatin Immunoprecipitation experiments revealed that PXR can bind to the NPC1L1 promoter. Further, TBC treatment also significantly increased NPC1L1 expression and cholesterol uptake in human intestinal cells and murine primary enterocytes. These findings provide critical mechanistic insight for understanding the impact of EDC-mediated PXR activation on lipid homeostasis and demonstrate a potential role of PXR in mediating adverse effects of EDCs on CVD risk in humans.
International Rule of Law and the Market Economy

Law matters in economic development. The Rule of Law is an indispensable foundation for a market economy, which provides an essential environment for the creation and preservation of wealth, economic security, and well-being, and the improvement of the quality of life. The Rule of Law is part of the "software" of governmental regulation that is needed to operate the "hardware" of free markets. Its promotion can make a major contribution to economic growth, and an infrastructure that creates and promites legal rights is an essential platform for economic development. The cumulative costs of doing without the Rule of Law in a modern economy are enormous.Establishing a firmly rooted system of the Rule of Law is unfinished business in the countries participating in the Central American Free Trade Agreement ("CAFTA"). Building an effective Rule of Law is essencial to the promotion of a free market economic system that fosters transparency in business transactions and operations. The Rule of Law in the commercial sector promotes economic stability and growth, encourages investors to make investments, creates jobs, increases the standard of living, and promotes prosperity.The Rule of Law requirements for a market economy differ rather substantially from the Rule of Law requirements for other types of social needs. The purpose of this comment is to outline those Rule of Law features that are essential to the proper functioning of a free market economy and to call attention to the unique characteristics of these legal features. Part I introduces the role of the Rule of Law in a free market economy. Part II describes the major legal systems that the Rule of Law requires to support such an economy. Part III of this Comment concludes that the Rule of Law is an indispensable basis for a free market economy.
Constitutional Roulette: The Russian Parliament's Battles with the President Over Appointing a Prime Minister

Russia adopted a new constitution in December of 1993. This document created a separation of powers imbalance that granted the country's presidency great powers relative to those of its parliament. Most scholars believe this imbalance has allowed Russia’s president to dominate parliament, exacerbating a power imbalance between the branches that has hindered Russia’s democratic development. This article examines the specific constitutional powers of the Russian presidency and parliament over the nomination of the Russian prime minister and argues that the Russian president may not always be as strong as the conventional wisdom holds. While Russia’s constitution provides for a strong presidency, this is not the same as guaranteeing a strong president. To put it another way, there may be a difference between the powers granted to an office and how they are able to be used by its occupant. Numerous factors restrict a president from exercising his constitutional powers. The first has to do with the nature of the legislative majority that stands opposite him. If parliament is able to cobble a strong majority to stand in opposition to the president’s agenda, the president will function as if he has clipped wings. A second factor is institutional. Many constitutions contain clauses that restrict executive power during certain period of time. Yet a third external factor has to do with society. Even when presidents are inclined to stretch the limits of their powers, they can be held back by a nation's temperament. In September of 1998, as this article shows, the temperament of the Russian people sided with Russia’s parliament. It made parliament victorious in its negotiations with the president over the appointment of a prime minister, and it paved the way for a new, although ultimately brief, chapter in the history of executive-legislative relations in Russia.
Neuromonitoring in the Intensive Care Unit

This issue of Critical Care Nursing Clinics of North America is focused on neuromonitoring in the intensive care unit (ICU). Neuromonitoring is a broad umbrella term that elicits different concepts depending on a person’s role in the ICU. For instance, a trauma nurse may associate neuromonitoring with intracranial bolts, whereas an ultrasound technician may immediately think of transcranial Dopplers. A neuro ICU nurse may have visions of going to multiple scans or working with external ventricular drains. The term neuromonitoring includes all these concepts as well as more, which are discussed within this dedicated issue of Critical Care Nursing Clinics of North America. In designing this issue, we created three overriding themes of neuromonitoring that remained fairly broad. First, we thought of traditional methods of neuromonitoring that a nurse would expect to see in this issue. Robinson goes into depth on treating refractory increased intracranial pressures, while Heck discusses different modalities that are available for using invasive neuromonitoring for patients. Irick and Feil provide an extremely helpful overview of neuromonitoring in the operating room. Many ICU nurses are not familiar with neuromonitoring in the operating room, and the literature is resource-poor in this area. Therefore, the collaborative approach from Irick and Feil not only provides a better understanding of neuromonitoring but also gives nurses a glimpse into the role of the nurse anesthetist. The second approach we took on neuromonitoring was to explore novel concepts and products. Hylkema provides a look at one of the newest concepts of using optic sheath ultrasound as a method for assessing intracranial pressures noninvasively. The use of ultrasound has grown exponentially over the years due to its ease of use, low cost, and accessibility. Hylkema provides an overview of how it is being used for neurologic patients. Few centers have microdialysis, but the road on how to use it is being mapped by Kumar and Young in this issue. Even if your hospital setting does not use microdialysis, there is tremendous value in understanding brain metabolism. Wilson and Della Penna present evidenced-based research on the value of
Conscious and Unconscious Processes in Motivation

Recent research has provided evidence of the influence of both conscious and unconscious processes in motivation. Evidence in favour of the influence of phenomenal events on motivation is contained in Bandura’s studies of efficacy and in Carver and Scheier’s studies of the infuence of self directed attentional processes on behaviour. Among the research contributions that address the role of unconscious processes in motivation are Nisbett and Wilson’s (1977) discussion of the limitations of reports about psychological processes; research on the influence of stimuli that are allegedly prevented from entering consciousness by virtue of the use of masking or shadowing procedures reported by such investigators as Marcel, Fowler, Dawson, and Corteen and Wood; and research deriving from an explicitly psychoanalytic perspective reported by Silverman and his colleagues.
Measurement and modeling of the refilling plasmasphere during 2001

The Naval Research Laboratory SAMI3 (Sami3 is Also a Model of the Ionosphere) and the RAM-CPL (Ring current Atmosphere interaction Model-Cold PLasma) codes are used to model observed plasmasphere dynamics during 25 November 2001 to 1 December 2001 and 1–5 February 2001. Model results compare well to plasmasphere observations of electron and mass densities. Comparison of model results to refilling data and to each other shows good agreement, generally within a factor of 2. We find that SAMI3 plasmaspheric refilling rates and ion densities are sensitive to the composition and temperature of the thermosphere and exosphere, and to photoelectron heating. Furthermore, results also support our previous finding that the wind-driven dynamo significantly impacts both refilling rates and plasmasphere dynamics during quiet periods.
Structural and Photoelectrochemical Properties of GaP Nanowires Annealed in NH3

Nitrogen alloyed gallium phosphide (GaP1–xNx) nanowires have been prepared by annealing gallium phosphide (GaP) nanowires in flowing NH3(g) at 750 °C. X-ray diffraction patterns and electron micros...
Psychological and Pedagogical Factors Involved in Motor Skill Performance as Exemplified in Bowling

(1940). Psychological and Pedagogical Factors Involved in Motor Skill Performance as Exemplified in Bowling. Research Quarterly. American Association for Health, Physical Education and Recreation: Vol. 11, No. 4, pp. 42-52.
Adsorption characteristic of filtration reducer PAX.

Filtration reducer PAX is a novel binary polymer with temperature stability for water-base drill-ing fluid. With function groups of sulfonic acid group and amide group induced into its molecule structure,PAX has advantages such as remarkable fluid loss reduction, strong heat and salinity tolerance. To makefurther research on the filtration reduction mechanism of PAX, adsorption characteristic of it on clay parti-cles was studied in lab under conditions of different PAX concentration, different NaCl and CaCl 2 concen-trations, and different temperature, respectively. Results show that the time to reach adsorption equilibri-um is 0.5 h; and at the temperature of 25 ℃ ,the adsorption isotherm answers to Langmuir adsorption e-quation. As the temperature climb up, the absorbance increases, whereas with the same PAX concentra-tion, the higher the inorganic salt addition is, the less absorbance will take place.
Vaccinia virus as a subhelper for AAV replication and packaging

Adeno-associated virus (AAV) has been widely used as a gene therapy vector to treat a variety of disorders. While these vectors are increasingly popular and successful in the clinic, there is still much to learn about the viruses. Understanding the biology of these viruses is essential in engineering better vectors and generating vectors more efficiently for large-scale use. AAV requires a helper for production and replication making this aspect of the viral life cycle crucial. Vaccinia virus (VV) has been widely cited as a helper virus for AAV. However, to date, there are no detailed analyses of its helper function. Here, the helper role of VV was studied in detail. In contrast to common belief, we demonstrated that VV was not a sufficient helper virus for AAV replication. Vaccinia failed to produce rAAV and activate AAV promoters. While this virus could not support rAAV production, Vaccinia could initiate AAV replication and packaging when AAV promoter activation is not necessary. This activity is due to the ability of Vaccinia-driven Rep78 to transcribe in the cytoplasm and subsequently translate in the nucleus and undergo typical functions in the AAV life cycle. As such, VV is subhelper for AAV compared to complete helper functions of adenovirus.
Application of knowledge

The purpose of this chapter is to provide the reader with an opportunity to apply some of the biochemical and nutritional information presented in the preceding chapters. Due to limited space, the questions are few and arbitrary in nature and are not meant to be all-encompassing. The solutions require application of metabolic knowledge and principles. It is the hope of the authors that these exercises might serve as examples for an approach to future problem-solving.
Inertial shocks in surface waves and collapsing bubbles

There exists a class of analytic, free-surface flows which describes qualitatively the highly-accelerated re-entrant jets seen in bubble generation and collapse. In semi-Langrangian coordinates such a flow is given by $$ x + iy = ({F_1}\sin \omega - i{G_1}\cos {\rm{ }}\omega ) + {1 \over 2}({F_2}\sin 2\omega - i{\rm{ }}{G_2}{\rm{ }}\cos {\rm{ }}2\omega ) $$ where ? is a complex parameter, real at the free surface. The coefficients F 1, G 1, F 2 and G 2 are real functions of the time t only, related by a set of nonlinear, ordinary differential equations, so as to satisfy appropriate boundary conditions and conditions of regularity in the fluid. A wide variety of such flows exists, depending on the initial conditions. One remarkable feature of many of the flows is the occurrence of a sudden “inertial shock” at a critical time t = t o. This usually happens when the surface locally has the form of a rectangular hyperbola — as in the previously known “Dirichlet hyperbola”. The phenomenon is illustrated by the behaviour of the inwards acceleration y tt at the point ? = 0 on the free surface (the tip of the jet). The acceleration becomes infinite like (t — t o)−4/3, near the instant t o.
Minimally invasive management of colonoscopic perforation during polypectomy - a video vignette.

The incidence of perforation during diagnostic colonoscopy is about 0.4%, with an increase of up to 0.8% when polypectomy is undertaken.1 Perforation often requires an emergency laparotomy. Minimally invasive surgery is now routine for elective colorectal surgery, but its place in the emergency setting often depends on the preference of the individual surgeon and is not well defined.2,3 This article is protected by copyright. All rights reserved.
One-half century of hop research by the U.S. Department of Agriculture

U.S. government support for hop research started at Oregon State University in 1930 when most American hops were grown in that state. Research was aimed at finding genetic resistance to downy milde...
Guiding Elastic Rods With a Robot-Manipulated Magnet for Medical Applications

Magnet-tipped, elastic rods can be steered by an external magnetic field to perform surgical tasks. Such rods could be useful for a range of new medical applications because they do not require either pull wires or other bulky mechanisms that are problematic in small anatomical regions. However, current magnetic rod steering systems are large and expensive. Here, we describe a method to guide a rod using a robot-manipulated magnet located near a patient. We solve for rod deflections by combining permanent-magnet models with a Kirchhoff elastic rod model and use a resolved-rate approach to compute trajectories. Experiments show that three-dimensional trajectories can be executed accurately without feedback and that the system's redundancy can be exploited to avoid obstacles.
Surface retention of an inactivating lutropin receptor mutant in exoloop 3.

The heptahelical lutropin receptor (LHR) signals primarily via the Gs-adenylyl cyclase pathway and undergoes ligand-mediated receptor desensitization and internalization. A loss-of-function rat LHR mutant was recently described in which a single amino acid residue replacement in exoloop 3, K583E, had no effect on human choriogonadotropin (hCG) binding but essentially abolished signaling. This LHR mutant is a prime candidate for which to study hCG-mediated receptor internalization since it is highly unlikely that an amino acid residue in exoloop 3 , i.e. an extracellular portion of LHR connecting transmembrane helices 6 and 7, could have any direct interaction with Gαs, which is located on the cytoplasmic face of the plasma membrane. A method to study endocytosis was adapted that involves concanavalin A binding to the glycoproteins on the cell surface, thus facilitating separation of the plasma membrane fraction from other cellular membrane fractions by sucrose gradient centrifugation. Conditions were used such that a single round of endocytosis could be determined with [125I]hCG. Endocytic rate constants of 0.03 and 0 min-1 were obtained for LHR and the mutant, respectively, in transfected human embryonic kidney 293 cells; moreover, internalization of the mutant could not be restored by the addition of 8-Br-cAMP. Thus, the presence of the second messenger cAMP is not sufficient for internalization of ligand-occupied LHR. Rather, it appears that ligand-mediated activation and subsequent internalization of LHR results from an altered conformational state or a conformation-dependent post-ligand binding modification such as phosphorylation.
Normal fluoroscopic appearance status post-successful endoscopic Zenker diverticulotomy.

Objective Endoscopic Zenker diverticulotomy (EZD) is a primary treatment for Zenker diverticulum (ZD). During EZD, the diverticulum is not excised, and interpretation of postoperative videofluoroscopic swallow study (VFSS) is challenging. The purpose of this investigation was to describe normal VFSS findings status post-successful EZD. Methods The charts of all patients with ZD treated at our center between October 01, 2011, and May 30, 2014, were abstracted. Outcome measures included recidivistic diverticulum size, Eating Assessment Tool-10 (EAT-10), penetration aspiration scale, pharyngeal constriction ratio (PCR), and pharyngoesophageal segment (PES) opening. Results Twenty patients met inclusion criteria. The mean age was 70.5 (± 13) years. Seventy percent of the patients were male. Mean EAT-10 decreased 72.1% from 17.9 (± 8.2) to 5 (± 6.9) (P < 0.0001), and diverticulum size decreased 50.9% from 1.96 cm (± 0.68) to 0.96 cm (± 0.57) (P < 0.001). The PCR improved 33.6% from 0.17 (± 0.13) to 0.11 (± 0.11) (P < 0.001). Mean PES opening increased 61.6% from 0.53 cm (± 0.3544) to 0.86 cm (± 0.29) in lateral view and increased 40.0% from 1.00 cm (± 0.54) to 1.39 cm (± 0.46) in anteroposterior view (P < 0.001). Conclusion VFSS following successful EZD demonstrates an approximate 50% reduction in diverticulum size and significant improvement in PCR and PES opening. These data provide a framework for the expected fluoroscopic outcomes of successful diverticulotomy. Level of Evidence 4. Laryngoscope, 127:1762–1766, 2017
Segregated-Feed Membrane Reactor Design for Alkylpyridine N-Oxidation: Implications for Process Safety and Intensification

This manuscript provides theoretical analysis indicating the validity and promise of a continuous tube-in-tube membrane reactor for performing the industrially important yet potentially hazardous liquid phase, homogeneous catalytic N-oxidation of alkylpyridines in a more scalable and inherently safer fashion. The design facilitates controlled radial slip of hydrogen peroxide into cocurrent alkylpyridine flow driven by an applied trans-membrane pressure difference across the inner porous ceramic tube. Design rules in terms of relative permeation and reaction rates are established in terms of desired outlet alkylpyridine conversion and peroxide residue using a single isothermal tube-in-tube unit. Multiunit module design is then investigated to optimize productivity and module dimensions while balancing heat transfer capability to maintain isothermal operation in practice and preventing mass transfer across the unit boundary to ensure isolation.
Chicago and New Orleans: opposite ends of a great river

This paper considers the contrasting and deliberate efforts to reshape the Tluvial futures of two important American cities which essentially re-wrote their riparian heritages. Chicago’s aggressive extension of its commercial reach through its artiTicial connection with the Mississippi has become embodied in its environmental, political, and literary history. Conversely, New Orleans crafted a defensive local culture in its environmental history, politics, and literature. The contrasting investments in river-altering infrastructure and urban relationships with the one river expose the signiTicance of each city’s position within a watershed and in shaping its respective cultural history and its identity.
Microbiological Test Data—Assuring Data Integrity

Marketed drugs and devices possess specifications including critical microbiological quality attributes purposed to assure efficacy and patient safety. These attributes are legislated requirements intended to protect the recipient patient. Sampling, microbiological testing, interpretation of data for final products, raw materials and intermediates all contribute to a cohesive assessment in the assurance of finished product quality. Traditional culture-based microbiological methods possess inherent and unavoidable variability, recognized by the compendia and which might lead to erroneous conclusion pertaining to product quality. Such variability has been associated and intrinsically linked with data integrity issues; manufacturers have subsequently been encouraged by regulatory authorities to introduce multiple microbiologists or checks to prevent such issues. Understanding microbiological variability is essential such that genuine data integrity issues are identified. Furthermore, a range of meaningful preventative strategies are feasible beyond increasing the capacity of the quality control microbiological laboratory. This short review describes the legislative requirements, inherent microbiological variability and realistic actions and activities that genuinely assure patient safety.
Clinical Simulation Experiences of Newly Licensed Registered Nurses

Abstract Background The use of simulation for educating nurses has increased exponentially as it can augment or replace training in traditional clinical settings. Despite this increase, there is a lack of evidence about how to use simulation effectively to educate and prepare nurses for practice. Method For this descriptive exploratory study, 10 newly graduated registered nurses were interviewed about their simulation experiences. Results and Conclusion Data analysis yielded four themes and eight recommendations that can help inform simulation use in nursing programs and further research about using simulation to prepare newly graduated nurses for professional practice.
Quantifying Lateral Frontal Sinus Access: The Upper Blepharoplasty Approach.

Objective Despite advances in technology and instrumentation, access to the lateral frontal sinus remains a challenge for surgeons. We sought to quantify the reach and applicability of the upper blepharoplasty approach (UBA) to the frontal sinus. Methods Twelve cadaveric specimens were obtained for anatomic research and frontal sinuses divided into 3 zones. Zone 1 was defined as medial to the supraorbital neurovascular bundle (SON). The remaining orbit was then bisected to define zone 2 (centrally) and zone 3 (laterally). Twenty-four UBAs were performed followed by 12 modified endoscopic Lothrop procedures (MELP). The ability to instrument each wall of the frontal sinus was recorded for the MELP, UBA, and combined approach. Results The UBA provided excellent access to the lateral frontal sinus in zones 2 and 3 (89% and 100%). The MELP provided poorer access in zone 3 (67%) but improved access in zone 1 (83%-100%). Access for zone 1 through the UBA was limited. The combined approach yielded 100% access to each frontal sinus boundary. Conclusion The MELP in combination with the UBA/lateral trephination provides excellent access to each frontal sinus boundary. The UBA provides excellent access to the lateral frontal sinus but is limited medially by the SON.
Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous Cells

Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-) ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in native bone tissue, have been shown to promote osteogenic commitment of stem cells in vitro and in vivo. The intrinsic osteoconductivity and osteoinductivity of such biomaterials make them promising bone grafts for the treatment of bone defects. We thus aimed to evaluate the potential of mineralized biomaterials to induce bone repair of a critical-sized cranial defect in the absence of exogenous cells and growth factors. Our results demonstrate that the mineralized biomaterial alone can support complete bone formation within critical-sized bone defects through recruitment of endogenous cells and neo-bone tissue formation in mice. The newly formed bone tissue recapitulated many key characteristics of native bone such as formation of bone minerals reaching similar bone mineral density, presence of bone-forming osteoblasts and tartrate-resistant acid phosphatase-expressing osteoclasts, as well as vascular networks. Biomaterials that recruit endogenous cells and provide a tissue-specific microenvironment to modulate cellular behavior and support generation of functional tissues are a key step forward in moving bench-side tissue engineering approaches to the bedside. Such tissue engineering strategies could eventually pave the path toward readily available therapies that significantly reduce patient cost of care and improve overall clinical outcomes.
T-cell Dysfunction in Glioblastoma: Applying a New Framework

A functional, replete T-cell repertoire is an integral component to adequate immune surveillance and to the initiation and maintenance of productive antitumor immune responses. Glioblastoma (GBM), however, is particularly adept at sabotaging antitumor immunity, eliciting severe T-cell dysfunction that is both qualitative and quantitative. Understanding and countering such dysfunction are among the keys to harnessing the otherwise stark potential of anticancer immune-based therapies. Although T-cell dysfunction in GBM has been long described, newer immunologic frameworks now exist for reclassifying T-cell deficits in a manner that better permits their study and reversal. Herein, we divide and discuss the various T-cell deficits elicited by GBM within the context of the five relevant categories: senescence, tolerance, anergy, exhaustion, and ignorance. Categorization is appropriately made according to the molecular bases of dysfunction. Likewise, we review the mechanisms by which GBM elicits each mode of T-cell dysfunction and discuss the emerging immunotherapeutic strategies designed to overcome them. Clin Cancer Res; 24(16); 3792–802. ©2018 AACR.
Malignancies arising in oncocytic schneiderian papillomas: A report of 2 cases and review of the literature

c Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are rare, and, to our knowledge, only 14 such instances have been reported in the medical literature. We report 2 additional cases—a small cell carcinoma and a sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously with the benign neoplasm. The potential for malignant transformation in OSPs is small, but warrants that these papillomas be completely excised to exclude a coexisting carcinoma. (Arch Pathol Lab Med. 2001;125:1365‐1367)
From Bloch oscillations to many-body localization in clean interacting systems.

In this work we demonstrate that nonrandom mechanisms that lead to single-particle localization may also lead to many-body localization, even in the absence of disorder. In particular, we consider interacting spins and fermions in the presence of a linear potential. In the noninteracting limit, these models show the well-known Wannier–Stark localization. We analyze the fate of this localization in the presence of interactions. Remarkably, we find that beyond a critical value of the potential gradient these models exhibit nonergodic behavior as indicated by their spectral and dynamical properties. These models, therefore, constitute a class of generic nonrandom models that fail to thermalize. As such, they suggest new directions for experimentally exploring and understanding the phenomena of many-body localization. We supplement our work by showing that by using machine-learning techniques the level statistics of a system may be calculated without generating and diagonalizing the Hamiltonian, which allows a generation of large statistics.
Permanent Modular Construction: Construction Performance

Permanent modular construction (PMC) has been marketed as a more cost-effective, higher-quality, and faster-to-market solution than traditional stick-built construction. The added value of PMC, although conceptually strong, has yet to be significantly substantiated. The study quantifies the added value of PMC and evaluates the contextual factors by which PMC in building design and construction may be realized in North America and beyond. The data from the PMC projects was compared to benchmark projects developed by Cumming Corporation, a cost consultancy firm. It is important to note that most stakeholders reported PMC offers a greater control of cost compared to traditional build. This is attributed to the inherent ability to reduce the number of change orders in any given PMC project. The most significant benefit of PMC is its ability to be completed with reduction in schedule. Every survey respondent named meeting the substantial completion deadline as a success.
Reactivity of [Fe4S4] Clusters toward C1 Substrates: Mechanism, Implications, and Potential Applications.

ConspectusFeS proteins are metalloproteins prevalent in the metabolic pathways of most organisms, playing key roles in a wide range of essential cellular processes. A member of this protein family, the Fe protein of nitrogenase, is a homodimer that contains a redox-active [Fe4S4] cluster at the subunit interface and an ATP-binding site within each subunit. During catalysis, the Fe protein serves as the obligate electron donor for its catalytic partner, transferring electrons concomitant with ATP hydrolysis to the cofactor site of the catalytic component to enable substrate reduction. The effectiveness of Fe protein in electron transfer is reflected by the unique reactivity of nitrogenase toward small-molecule substrates. Most notably, nitrogenase is capable of catalyzing the ambient reduction of N2 and CO into NH4+ and hydrocarbons, respectively, in reactions that parallel the important industrial Haber–Bosch and Fischer–Tropsch processes. Other than participating in nitrogenase catalysis, the Fe protein ...
A Bayesian framework for materials knowledge systems

This prospective offers a new Bayesian framework that could guide the systematic application of the emerging toolsets of machine learning in the efforts to address two of the central bottlenecks encountered in materials innovation: (i) the capture of core materials knowledge in reduced-order forms that allow one to rapidly explore the vast materials design spaces, and (ii) objective guidance in the selection of experiments or simulations needed to identify the governing physics in the materials phenomena of interest. The framework builds on recent advances in the low-dimensional representation of the statistics describing the material’s hierarchical structure.
Heartbeat: telemedicine and outcomes in patients with an acute coronary syndrome

In patients with an acute coronary syndrome (ACS), prehospital transmission of the ECG offers the potential to reduce the time delay between symptom onset and initiation of treatment. However, the effect of this telemedicine intervention on clinical outcomes has not been well validated. In a systematic review and meta-analysis, Marcolino and colleagues1 identified 30 non-randomised controlled and 7 quasi-experimental studies of telemedicine for ACS that included a total of almost 17 000 patients. In these studies, prehospital ECG transmission (compared with usual care) was associated with a lower in-hospital mortality (relative risk (RR) 0.63 (95% CI 0.55 to 0.72)), door-to-balloon time (mean difference −28 min (95% CI −35 to –20)), 30-day and long-term mortality (RR 0.61 (95% CI 0.40 to 0.92)) (figure 1). However, there was moderate to large heterogeneity for all these findings suggesting that more rigorous evaluation of telemedicine strategies for improving outcome is needed. Figure 1 (A) Forest plot showing the risk of 30-day mortality in patients submitted to telemedicine strategies associated to usual care versus usual care. (B) Forest plot showing the risk of long-term mortality in patients submitted to telemedicine strategies associated to usual care versus usual care. LL, lower limit; RR, relative risk; UL, upper limit. In an editorial, Bosson2 points out that this meta-analysis focused on prehospital ECG transmission with or without teleconsultation. She goes on the discuss the untapped potential of telemedicine …
Pediatric Rhinosinusitis and Gastroesophageal Reflux

Gastroesophageal reflux disease is a common occurrence in the pediatric age group and tends to improve with age. A relationship between pediatric chronic rhinosinusitis and gastroesophageal reflux has been speculated, though a true cause-and-effect relationship has yet to be solidified. Available evidence linking gastroesophageal reflux disease to pediatric rhinosinusitis will be reviewed in this chapter. Similarly, the impact of reflux therapy on the progress of rhinosinusitis in children will be summarized. Based on the current literature, there appears to be some correlation between the two entities, but the evidence does not seem to justify routine empiric treatment of reflux in children with chronic rhinosinusitis in the absence of overt gastroesophageal reflux disease symptoms.
7 – Thermal Radiation

Publisher Summary This chapter explores the phenomena of thermal radiation. Radiation is a mechanism that may take place in the absence of matter. At high temperatures, radiation is often the dominant mechanism of heat transfer and thus, it is important that one is able to accurately calculate radiant energy transport rates if he/she is to design high temperature processes with confidence. While radiation and high temperatures usually go hand-in-hand, one must not dismiss the mechanism at low temperatures, for any competent mountaineer negotiating the higher altitudes will always sleep under the “shade” of a tree or rock rather than participate in the esthetically pleasing but often bone-chilling experience of a night out under the stars. All bodies are capable of emitting electromagnetic radiation. At room temperature, most bodies emit radiation in the infrared region at such low rates that the radiant energy emitted can often be neglected in heat transfer calculations.
Anionic Lipids Impact RAS-Binding Site Accessibility and Membrane Binding Affinity of CRAF RBD-CRD

CRAF activation requires binding to membrane-anchored and active GTP-bound RAS. Whereas its RAS-binding domain (RBD) contains the main binding interface to the RAS G domain, its cysteine-rich domain (CRD) is responsible for association to anionic lipid-rich membranes. Both RAF domains are connected by a short linker, and it remains unclear if the two domains act independently or if one domain can impact the function of the other. Here, we used a combination of coarse-grained and all-atom molecular dynamics simulations of a CRAF RBD-CRD construct to investigate the dynamics of the RBD when it is tethered to CRD that is anchored to a POPC:POPS model membrane. First, we show that the RBD positioning is very dynamic with a preferential localization near the membrane surface. Next, we show that membrane-localized RBD has its RAS-binding interface mostly inaccessible because of its proximity to the membrane. Several positively charged residues in this interface were identified from simulations as important for driving RBD association to the membrane. Surface plasmon resonance (SPR) measurements confirmed that mutations of these RBD residues reduced the liposome partitioning of RBD-CRD. Last, simulations indicated that the presence of RBD near the membrane led to a local enrichment of anionic lipids that could potentially enhance the membrane affinity of the entire RBD-CRD construct. This was supported by SPR measurements that showed stronger liposome partitioning of RBD-CRD relative to CRD alone. These findings thus suggest that the RBD and CRD have synergistic effects on their membrane dynamics, with CRD bringing RBD closer to the membrane that impacts its accessibility to RAS and with RBD causing local anionic lipid enrichment that enhances the overall affinity between the membrane and RBD-CRD. These mechanisms have potential implications on the order of events of the interactions between RAS and CRAF at the membrane.
Stretched-Pulse Soliton Kerr Resonators

Kerr resonators support novel nonlinear wave phenomena including technologically important optical solitons. Fiber Kerr resonator solitons enable wavelength and repetition-rate versatile femtosecond-pulse and frequency-comb generation. However, key performance parameters, such as pulse duration, lag behind those from traditional mode-locked laser-based sources. Here we present new pulse generation in dispersion-managed Kerr resonators based on stretched-pulse solitons, which support the shortest pulses to date from a fiber Kerr resonator. In contrast to established Kerr resonator solitons, stretched-pulse solitons feature Gaussian temporal profiles that stretch and compress each round trip. Experimental results are in excellent agreement with numerical simulations. The dependence on dispersion and drive power are detailed theoretically and experimentally and design guidelines are presented for optimizing performance. Kerr resonator stretched-pulse solitons represent a new stable nonlinear waveform and a promising technique for femtosecond pulse generation.
Students’ perceptions and evaluations of plagiarism: Effects of text and context

As they navigate academic life, students must decide whether the acts of copying they encounter constitute plagiarism, and whether those acts are wrong. The present study investigated students’ per...
Analysis and Investigation of Small Flaws

Stress analysis of a single-edge-cracked specimen under uniaxial tension is performed by employing a Williams stress function and the boundary point collocation method. Full-field and singular stress fields are analyzed for small and large cracks, and it is shown that the inclusion of the nonsingular stresses in the description of the state of stress in the vicinity of the crack tip becomes significantly more important as the crack length decreases.
A cannabinoid type 2 (CB2) receptor agonist augments NOS-dependent responses of cerebral arterioles during type 1 diabetes.

Abstract While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D). Our goal was to test the hypothesis that administration of a CB2 agonist (JWH-133) would improve impaired endothelial (eNOS)- and neuronal (nNOS)-dependent dilation of cerebral arterioles during T1D. In vivo diameter of cerebral arterioles in nondiabetic and T1D rats was measured in response to an eNOS-dependent agonist (adenosine 5′-diphosphate; ADP), an nNOS-dependent agonist (N-methyl- d -aspartate; NMDA), and an NOS-independent agonist (nitroglycerin) before and 1 h following JWH-133 (1 mg/kg IP). Dilation of cerebral arterioles to ADP and NMDA was greater in nondiabetic than in T1D rats. Treatment with JWH-133 increased responses of cerebral arterioles to ADP and NMDA in both nondiabetic and T1D rats. Responses of cerebral arterioles to nitroglycerin were similar between nondiabetic and T1D rats, and JWH-133 did not influence responses to nitroglycerin in either group. The restoration in responses to the agonists by JWH-133 could be inhibited by treatment with a specific inhibitor of CB2 receptors (AM-630; 3 mg/kg IP). Thus, activation of CB2 receptors can potentiate reactivity of cerebral arterioles during physiologic and pathophysiologic states. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular diseases via a mechanism that can increase cerebral blood flow.
Towards a realistic type IIA T6/ℤ4 orientifold model with background fluxes, part 1. Moduli stabilization

We apply the methods of DeWolfe et al. (hep-th/0505160) to a T6/4 orientifold model. This is the first step in an attempt to build a phenomenologically interesting meta-stable de Sitter model with small cosmological constant and standard model gauge groups.
Large Vessel Occlusion with Low NIHSS: Approach and Strategy

Managing patients presenting with large vessel occlusion (LVO) and mild stroke symptoms has been a challenging clinical scenario. Acute stroke therapy is often withheld for these patients; however, their natural clinical outcomes may not be favorable. Identifying patients who do well without treatment is not straightforward. In the absence of randomized clinical trials evaluating this specific population, acute stroke therapy remains a clinical conundrum. Intravenous thrombolysis alone appears safe, but may not be efficacious for proximal large vessel occlusions based on prior scientific data. Mechanical thrombectomy (MT) has been shown to achieve good recanalization rates and clinical outcomes in LVO patients with moderate-to-severe strokes, but it has not been widely studied in patients with low National Institute of Health Stroke Scale (NIHSS) scores. In this chapter, we review current data looking at this unique cohort, and discuss natural history, management options, ongoing research, and future directions.
Addressing Violence Against Children Through Anti-racism Action

Racism is a system of structuring opportunity and assigning value based on the social interpretation of how one looks (which is what we call "race"). Racism unfairly disadvantages some individuals and communities, unfairly advantages other individuals and communities, and saps the strength of the whole society through the waste of human resources. There are 7 barriers to achieving health equity that are deeply embedded in US culture. These serve as values targets for anti-racism action. This article is an invitation to all who love children to become actively anti-racism.
Weighted Voting, Multicameral Representation, and Power

Abstract A simple game (P, W) can serve as a model of a voting system in which an alternative is pitted against the status quo. In what follows, we investigate the following three aspects of such games as they apply to four real-world examples of voting systems: a characterization of weighted voting systems in terms of the ways in which coalitions can gain or lose by trading players; the application of a graph-theoretic notion of dimension to simple games and voting systems; and the consideration of a way to measure the power of a player as an interval of real numbers. American Mathematical Society Classification Numbers: 90A28, 90D80, 05C65. Journal of Economic Literature Classification Number: C71.
Stabilization of Feedback Linearized Nonlinear Processes under Bounded Perturbations

In this paper, we consider the problem of designing a stabilizing linear controller for a feedback linearized nonlinear system under the influence of bounded perturbations. The feedback linearized (and perturbed) nonlinear system is equivalent to a Quasi Linear System. A sufficient condition using Lyapunov stability theory is presented to obtain a linear state feedback controller stabilizing the Quasi Linear System and the nonlinear system as well. A method is given to obtain th least conservative (smallest) stabilizing gains. The results are applied on a chemical reactor.
OrBEAGLE: integrating orthography into a holographic model of the lexicon

Many measures of human verbal behavior deal primarily with semantics (e.g., associative priming, semantic priming). Other measures are tied more closely to orthography (e.g., lexical decision time, visual word-form priming). Semantics and orthography are thus often studied and modeled separately. However, given that concepts must be built upon a foundation of percepts, it seems desirable that models of the human lexicon should mirror this structure. Using a holographic, distributed representation of visual word-forms in BEAGLE, a corpustrained model of semantics and word order, we show that free association data is better explained with the addition of orthographic information. However, we find that orthography plays a minor role in accounting for cue-target strengths in free association data. Thus, it seems that free association is primarily conceptual, relying more on semantic context and word order than word form information.