cssi/SciSciGPT-SciSciNet huggingface dataset:
Integrated parallel reception, excitation, and shimming (iPRES) with multiple shim loops per radio‐frequency coil element for improved B0 shimming

Purpose Integrated parallel reception, excitation, and shimming (iPRES) coil arrays allow radio-frequency currents and direct currents to flow in the same coils, which enables excitation/reception and localized B0 shimming with a single coil array. The purpose of this work was to improve their shimming performance by adding the capability to shim higher-order local B0 inhomogeneities that are smaller than the radio-frequency coil elements. Methods A novel design was proposed in which each radio-frequency/shim coil element is divided into multiple direct current loops, each using an independent direct current current, to increase the number of magnetic fields available for shimming while maintaining the signal-to-noise ratio of the coil. This new design is termed iPRES(N), where N represents the number of direct current loops per radio-frequency coil element. Proof-of-concept phantom and human experiments were performed with an 8-channel body coil array to demonstrate its advantages over the original iPRES(1) design. Results The average B0 homogeneity in various organs before shimming and after shimming with the iPRES(1) or iPRES(3) coil arrays was 0.24, 0.11, and 0.05 ppm, respectively. iPRES(3) thus reduced the B0 inhomogeneity by 53% and further reduced distortions in echo-planar images of the abdomen when compared with iPRES(1). Conclusion iPRES(N) can correct for localized B0 inhomogeneities more effectively than iPRES(1) with no signal-to-noise ratio loss, resulting in a significant improvement in image quality. Magn Reson Med 77:2077–2086, 2017. © 2016 International Society for Magnetic Resonance in Medicine
GABA-Dependent Firing of Glutamate-Evoked Action Potentials at AMPA/Kainate Receptors in Developing Hypothalamic Neurons

Gao, Xiao-Bing, Gong Chen, and Anthony N. van den Pol. GABA-dependent firing of glutamate-evoked action potentials at AMPA/kainate receptors in developing hypothalamic neurons. J. Neurophysiol. 79:...
The Imperative and Missing Crux of Entrepreneurship Research

The Theory of Entrepreneurship: Creating and Sustaining Entrepreneurial Value posits that entrepreneurship is a crucial yet disorderly and complicated social process of value creation, and challenges researchers to expand and recast our research approaches and empirical tools to fully grasp this unruly and understudied process. We propose to intricately examine the interiors of this entrepreneurial process. At the same time, we offer a new unified and comprehensive entrepreneurship theory to afford empirical investigations as well as delineate a broader view of the entrepreneurial contextual milieu.
Are All Government Owners Viewed the Same? Evidence from Government Acquisitions of Publicly Traded Firms.

I study shareholder wealth effects associated with different types of government investors and varying levels of political interference in a sample of 2,118 government equity investments spanning 71 countries from 1987 to 2013. The results indicate that government investors are not viewed by the market as a homogeneous group. Investors differentiate their expectations of government investment targets based on the government investor’s implied level of political interference. Government investors that are most likely to have political motivations have negative value effects on target firms, while other government investors have positive effects, similar in size to other non-government investors. The negative effects are stronger for investments in domestic firms, in more regulated industries, by left-wing governments, and for large share purchases. Post-acquisition performance is weaker for targets of politically motivated government investors and is consistent with the pursuit of non-profit maximizing objectives by these investors.
Connectosomes for Direct Molecular Delivery to the Cellular Cytoplasm

Transport of biomolecules, drugs, and other reagents across the cell’s plasma membrane barrier is an inefficient and poorly controlled process, despite its fundamental importance to biotechnology, cell biology, and pharmaceutics. In particular, insufficient membrane permeability frequently limits the accumulation of drugs and reagents in the cytoplasm, undermining their efficacy. While encapsulating drugs in particles increases uptake by cells, inefficient release of drugs from these particles into the cytoplasm ultimately limits drug efficacy. In contrast, gap junctions provide a direct route to the cytoplasm that bypasses the plasma membrane. As transmembrane channels that physically connect the cytoplasm of adjacent cells, gap junctions permit transport of a diverse range of molecules, from ions and metabolites to siRNA, peptides, and chemotherapeutics. To utilize gap junctions for molecular delivery we have developed Connectosomes, cell-derived lipid vesicles that contain functional gap junction chann...
Questions for Copenhagen: EcoJustice Perspectives and Summary

More than 17 years ago, beginning with the Rio de Janeiro Earth Summit and the Kyoto Summit 13 years later, representatives from both industrialized countries and those with emerging economies began a dialogue centered around the reduction of carbon emissions that are believed to be responsible for the rise in average global temperatures. Economic concerns associated with costs versus benefits dominated the summit conversations. And in the plans to address the reduction in carbon emission, what became known as the Kyoto Protocol was never fully realized.
Studying Electrical Conductivity Using a 3D Printed Four-Point Probe Station

The design and fabrication of functional scientific instrumentation allows students to forge a link between commonly reported numbers and physical material properties. Here, a two-point and four-point probe station for measuring electrical properties of solid materials is fabricated via 3D printing utilizing an inexpensive benchtop fused-deposition modeling system and designed by standard computer-aided design software. Stainless steel tapestry needles serve as probes for contacting a sample; these are also electroplated in order to study their electrical performance, and provide a framework for discussion of electrical charge transport, contact resistance, and conductivity in materials. A microcontroller board is integrated into the probe and controlled using open-source software. Our robust and simple design provides an instrument that is easily fabricated by students and readily applied to a wide range of classroom settings focused on materials science, mechanical and electrical engineering, as well as...
Risk of substance abuse and dependence among young adult sexual minority groups using a multidimensional measure of sexual orientation.

Objective. We examined associations between two definitions of sexual minor ity status (SMS) and substance abuse and/or dependence among young adults in a national population. Methods. A total of 14,152 respondents (7,529 women and 6,623 men) interviewed during wave four of the National Longitudinal Study of Adolescent Health were included in the study (age range: 24–32 years). We used two definitions of SMS based on self-reported attraction, behavior, and identity: 1-indicator SMS (endorsing any dimension) and 3-indicator SMS (endorsing all dimensions). Outcomes included nicotine dependence as well as $3 signs of substance dependence, any sign of substance abuse, and lifetime diagnosis of abuse or dependence for alcohol, marijuana, and a composite measure of other drugs. Weighted logistic regression models were fit to estimate the odds of each outcome for each of the sexual minority groups (compared with the heterosexual majority), controlling for sociodemographic covariates. Results. SMS women were more likely than exclusively heterosexual women to experience substance abuse and dependence, regardless of substance or SMS definition. In adjusted models for women, 3-indicator SMS was most strongly associated with abuse/dependence (adjusted odds ratio [AOR] range: 2.74– 5.17) except for $3 signs of cannabis dependence, where 1-indicator SMS had the strongest association (AOR53.35). For men, the 1-indicator SMS group had higher odds of nicotine dependence (AOR=1.35) and the 3-indicator SMS group had higher odds of $3 signs of alcohol dependence (AOR51.64). Conclusions. Young adult female sexual minority groups, regardless of how defined, are at a higher risk than their heterosexual peers of developing alcohol, drug, or tobacco abuse and dependence.
Integrating remote sensing and species distribution modelling to predict benthic communities in a Great Lakes connecting channel

Species distribution models have become widespread in benthic ecology; however, they have mostly been applied to marine and lentic systems. In this study, we applied a maximum entropy model by using remote sensing-derived environmental variables to predict the distribution of 4 major benthic communities dominated by Tubificidae, Naididae, Echinogammarus ischnus, and Dreissena spp, respectively, in the lower Niagara River, NY, USA. The model showed very good accuracy for benthic communities with a narrow distribution range (Tubificidae and Naididae) indicated by the area under the curve test values of 0.906 and 0.987, respectively. In contrast, the model showed poor performance for E. ischnus and Dreissena indicated by the low area under the curve values of 0.615 and 0.618, respectively. Both communities are known to cope with a wide variety of environmental factors and habitats, making their accurate predictions difficult using presence-only data. Our results can further be used to locate important feeding grounds for higher trophic levels, to assess the potential spread of exotic species, and to identify areas for restoration.
Identification and Biosynthesis of 1-Mercaptoethanesulfonic Acid (1-MES), an Analogue of Coenzyme M, Found Widely in the Methanogenic Archaea.

Here I report on the identification of 1-mercaptoethanesulfonic acid (1-MES), an analogue of 2-mercaptoethanesulfonic acid (coenzyme M, HSCoM). 1-MES and HSCoM were both present in the growth media of eight different methanogens at concentrations ranging from ∼1 to 100 μM. In an effort to determine a chemical origin of 1-MES, several plausible chemical routes were examined each assuming that HSCoM was the precursor. In all examined routes, no 1-MES was formed. However, 1-MES was formed when a solution of vinylsulfonic acid and sulfide were exposed to ultraviolet light. On the basis of these results, I conclude 1-MES is formed enzymatically. This was confirmed by growing a culture of Methanococcus maripaludis S2 in the presence of [1,1′,2,2′-2H4]HSCoM and measuring the incorporation of deuterium into 1-MES. 1-MES incorporated three of the four deuteriums from the fed HSCoM. This result is consistent with the abstraction of a C-2 deuterium of the HSCoM, likely by a 5′-dAdoCH2• radical, followed by a radical...
Walking in Relation to Mortality in a Large Prospective Cohort of Older U.S. Adults.

Introduction Engaging in >150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity weekly is recommended for optimal health. The relationship between walking, the most common activity especially for older adults, and total mortality is not well documented. Methods Data from a large U.S. prospective cohort study including 62,178 men (mean age 70.7 years) and 77,077 women (mean age 68.9 years), among whom 24,688 men and 18,933 women died during 13 years of follow-up (1999–2012), were used to compute multivariable-adjusted hazard rate ratios and 95% CIs for walking as the sole form of activity or adjusted for other moderate- or vigorous-intensity physical activity in relation to total and cause-specific mortality (data analysis 2015–2016). Results Inactivity compared with walking only at less than recommended levels was associated with higher all-cause mortality (hazard rate ratio=1.26, 95% CI=1.21, 1.31). Meeting one to two times the recommendations through walking only was associated with lower all-cause mortality (hazard rate ratio=0.80, 95% CI=0.78, 0.83). Associations with walking adjusted for other moderate- or vigorous-intensity physical activity were similar to walking only. Walking was most strongly associated with respiratory disease mortality followed by cardiovascular disease mortality and then cancer mortality. Conclusions In older adults, walking below minimum recommended levels is associated with lower all-cause mortality compared with inactivity. Walking at or above physical activity recommendations is associated with even greater decreased risk. Walking is simple, free, and does not require any training, and thus is an ideal activity for most Americans, especially as they age.
Time crunch: increasing the efficiency of assessment of technical surgical skill via brief video clips.

Abstract Background Video review for assessment of surgical performance is gaining popularity but is time consuming for busy expert reviewers, making review delays inevitable. Decreasing review time and including nonexpert reviewers may facilitate more timely reviews. We hypothesized that a shorter duration video clip would not affect the quality of expert ratings compared with full-length review. A secondary aim was to examine the reliability between expert and novice raters and how it was affected by video clip duration. Methods Videos of laparoscopic suturing performed on a live porcine model by premedical students, surgery residents, and fully trained surgeons were edited into 3 different durations: full, part, and 30-second versions. Video clips (n = 36) were reviewed by experienced surgeons (n = 3) and novice volunteers (n = 4) using the validated Global Operative Assessment of Laparoscopic Skills (GOALS) assessment. Videos were assigned randomly during 3 review cycles held 1 week apart. Each cycle included 1 iteration of the 12 performance videos. We assessed the impact of the duration of the video on reviewer scores and inter-rater reliability. Results Variance in scores for 2 of 4 GOALS domains was dependent on the duration of the video clip (P Conclusion Our hypothesis was rejected as shorter video durations for surgical performance assessment led to inflated reviewer ratings both for expert and novice reviewers. Shortening duration of the video cannot be recommended for accurate performance assessment.
Factors Associated With Health-Related Quality of Life in Medically and Surgically Treated Patients With Glaucoma.

Importance Health-related quality of life (HRQOL) is often reduced with glaucoma, but associated factors are poorly understood. Objective To determine factors associated with reduced HRQOL in medically and surgically treated patients with glaucoma. Design, Setting, and Participants Prospective cohort study at a tertiary referral glaucoma practice, with 160 consecutive, prospectively enrolled medically or surgically treated adult patients with glaucoma. Main Outcome and Measures All patients completed 2 HRQOL questionnaires (the 25-item National Eye Institute Visual Function Questionnaire and the Adult Strabismus–20 questionnaire [AS-20]). Thirty-six patients had undergone glaucoma drainage device surgery, 51 underwent trabeculectomy, and 73 were medically treated. Factors considered for association with HRQOL in multiple regression analyses were age, sex, best-eye and worst-eye mean deviation on Humphrey visual fields, treatment modality, best-eye and worst-eye visual acuity, and diplopia. Results The mean (SD) age of participants was 69 (13) years, 63% were female, 97% were white, 93% were not Hispanic, and the mean deviation (SD) was −13 (10) dB. Reduced HRQOL was associated with worse diplopia (Diplopia Questionnaire score) on 6 subscales (range of partialr2[rp2], 0.207-0.069). Reduced HRQOL was associated with lower best-eye mean deviation on 5 of 6 subscales (rp2range, 0.379-0.027), lower worst-eye mean deviation on 4 of 6 (rp2 range, 0.242-0.046), treatment group on 3 of 6 (rp2range, 0.190-0.025), lower worst-eye visual acuity on 5 of 6 (rp2range, 0.063-0.025), lower best-eye visual acuity on 2 of 6 (rp2range, 0.032-0.017), and younger age on 2 of 6 (rp2range, 0.021-0.014). In adjusted analyses, glaucoma drainage device was associated with worse HRQOL in 3 AS-20 subscales compared with trabeculectomy and 2 AS-20 subscales compared with medical. Differences ranged from −14.7 to −7.4, with half the absolute magnitude of the full range of the 95% CI ranging from 9.2 to 5.7. Conclusions and Relevance Our findings support the assertion that reduced HRQOL is common in surgically and medically treated patients with glaucoma. Overall, poor HRQOL in patients with glaucoma is moderately associated with worse diplopia, lower mean deviation on visual field testing in either eye, poorer visual acuity in either eye, treatment type, and younger age. Previous glaucoma drainage device surgery was specifically associated with poorer HRQOL compared with trabeculectomy or medical treatment. Psychosocial effects of glaucoma drainage device should be considered when counseling patients with glaucoma.
Organizational Culture Mitigates Lower Ratings of Female Supervisors

The present study addresses a lack of literature examining contextual factors when investigating gender norms and leader effectiveness. Supervisor–subordinate dyads were assessed for gender dissimi...
Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014

In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines.
Wissensmanagement durch virtuelle Netzagenten

Wissen, Lernfahigkeit und Intelligenz sind keineswegs an das Nervensystem und Gehirn eines einzelnen Organismus gebunden. Tierpopulationen (z.B. Ameisen-und Termitenkolonien) entwickeln kollektive Problemlosungs-und Konstruktionsverfahren (z.B. Transportnetze und Termitenbauten), zu denen einzelne Tiere nicht fahig sind. Die Soziobiologie nennt daher solche Populationen Superorganismen. Auch im Gehirn denkt, plant und entscheidet nicht eine ausgezeichnete Nervenzelle, sondern ein Netz von neurochemisch kommunizierenden Neuronen. In einem Superorganismus kommunizieren alle Tiere uber chemische Diffusionsfelder und entwickeln funktionale Ordnungen mit Arbeits-, Transport-und Versorgungseinheiten ohne den Plan und das Kommando eines einzelnen Tieres.
New methodologies in heparin structure analysis and the generation of LMW heparins.

This chapter examines the methods used to prepare heparin, low molecular weight (LMW) heparins, and immobilized heparins. These heparins and heparin derivatives are polydisperse heterogeneous mixtures that require structural characterization. Analyses rely on integrated enzymatic, chemical, Chromatographic, electrophoretic and spectroscopic techniques. The goal is to establish the physical-chemical properties of a heparin preparation as well as the exact composition, distribution and sequence of the polysaccharide chains that are present. Ultrasensitive analytical techniques are also described for the analysis of heparin in tissues and biological fluids.
Epitaxial Film Growth of Tl0.78Bi0.22Sr1.6Ba0.4Ca2Cu3O9 on Rolling Assisted Biaxially Textured Nickel Substrates with YSZ And CeO2 Buffer Layers

Epitaxial film growth of Tl0.78Bi0.22Sr1.6Ba0.4Ca2Cu3O9 ((Tl,Bi)-1223) on rolling assisted biaxially textured substrates with YSZ and CeO2 buffer layers (RABiTS) has been successfully demonstrated by laser ablation and post-deposition annealing in flowing argon. X-ray diffraction (XRD) θ-2θ spectra showed that the films consisted mainly of c-axis aligned 1223 phase with some intergrown 1212 phase, while XRD Φ-scans of (102) pole figure revealed that the films are also a- and b-axes aligned, with an epitaxy of the «100» of (Tl,Bi)-1223 film on the «110» of the top YSZ buffer layer. Four-terminal electrical transport measurements showed that the zero-resistance transition temperature (Tc) was in the range of 106 - 110 K, and the critical current density (Jc) at 77 K and zero field was about 105 A/cm2 for the entire film width (3 mm) of a longer film (14 mm) which was processed differently from the shorter films (7 mm). For a shorter film (7 mm) that showed better ab-in-plane alignment, the magnetization Jc, at 77 K and extrapolated to zero field, calculated from Bean's model using the full film width (3.5 mm) as the appropriate lateral dimension, was 2 × 105 A/cm2.
A Critical Appraisal of the Placement of Xiphosura (Chelicerata) with Account of Known Sources of Phylogenetic Error

Horseshoe crabs (Xiphosura) are traditionally regarded as sister group to the clade of terrestrial chelicerates (Arachnida). This hypothesis has been challenged by recent phylogenomic analyses, but the non-monophyly of Arachnida has consistently been disregarded as artifactual. We re-evaluated the placement of Xiphosura among chelicerates using the most complete phylogenetic data set to date, expanding outgroup sampling, and including data from whole genome sequencing projects. In spite of uncertainty in the placement of some arachnid clades, all analyses show Xiphosura consistently nested within Arachnida as the sister group to Ricinulei (hooded tick spiders). It is apparent that the radiation of arachnids is an old one and occurred over a brief period of time, resulting in several consecutive short internodes, and thus is a potential case for the confounding effects of incomplete lineage sorting (ILS). We simulated coalescent gene trees to explore the effects of increasing levels of ILS on the placement of horseshoe crabs. In addition, common sources of systematic error were evaluated, as well as the effects of fast-evolving partitions and the dynamics of problematic long branch orders. Our results indicated that the placement of horseshoe crabs cannot be explained by missing data, compositional biases, saturation, or ILS. Interrogation of the phylogenetic signal showed that the majority of loci favor the derived placement of Xiphosura over a monophyletic Arachnida. Our analyses support the inference that horseshoe crabs represent a group of aquatic arachnids, comparable to aquatic mites, breaking a long-standing paradigm in chelicerate evolution and altering previous interpretations of the ancestral transition to the terrestrial habitat. Future studies testing chelicerate relationships should approach the task with a sampling strategy where the monophyly of Arachnida is not held as the premise.
Presbyphagia to Dysphagia: Multiple Perspectives and Strategies for Quality Care of Older Adults.

The aging population is rapidly growing, requiring speech–language pathologists to better manage a caseload that includes older adults who have a variety of needs. The purpose of this review is to summarize and discuss the current available evidence that will allow speech–language pathologists to make informed clinical decisions when working with older adults. To facilitate this, this article first establishes an understanding of both normal and disordered swallowing physiology in older adults, including how to differentiate between functional changes to swallowing (presbyphagia) and dysphagia. Other important factors to consider, such as caregiver burden, are also discussed so that clinicians can learn how to best support aging in place. Best practices for screening both community-dwelling older adults and residents of long-term care are identified as part of a framework introduced to guide decision making. The critical components of clinical swallow assessments are reviewed, including the adoption of an ethnographic approach and why nutritional status, urinary tract infections, and delirium are important considerations when working with older adults. Factors contributing to, and associated with, aspiration and aspiration pneumonia are also discussed so that clinicians better understand how to take a comprehensive approach to care, as well as consider the impact and influence of a temporary dysphagia versus a more chronic presentation. Finally, the evidence for management of dysphagia in this specialized population is reviewed, highlighting the importance of identifying physiological deficits, feedback, and taking a multidisciplinary approach to care.
Prevalence of beta-lactam drug-resistance genes in commensal Escherichia coli contaminating ready-to-eat lettuce

ABSTRACT The objective of this study was to evaluate the prevalence of antibiotic resistance and beta-lactam drug resistance genes in Escherichia coli isolated from ready-to-eat lettuce, obtained from local supermarkets in Northern California. Bags of lettuce were purchased from 4 chain supermarkets during three different periods—Oct 2018–Jan 2019, Feb 2019–Apr 2019 and May 2019–July 2019. From 91 packages of lettuce, we recovered 34 E. coli isolates from 22 (24%) lettuce samples. All E. coli isolates were genotyped by multilocus sequence typing (MLST), and we found 15 distinct sequence types (STs). Five of these genotypes (ST2819, ST4600, ST2432, ST1198 and ST5143) have been reported to cause infection in humans. Twenty (59%) E. coli isolates were found resistant to at least one of the antibacterial drugs. They included resistance to ampicillin (AMP, 85%) and ampicillin/sulbactam (SAM, 50%), cefoxitin (FOX, 40%) and cefuroxime (CXM, 35%). We found 8 (40%) of 20 beta-lactam resistant E. coli isolates to carry blaCTX-M; 5 (25%) tested positive for blaSHV, while only 4 (20%) tested positive for blaTEM. Additionally, we identified a class A broad-spectrum beta-lactamase SED-1 gene, blaSED, reported by others in Citrobacter sedlakii isolated from bile of a patient. This study found that a large proportion of fresh lettuce carry beta-lactam drug-resistant E. coli, which could serve as a reservoir for drug resistance genes that could potentially enter pathogens to cause human infections.
Enabling and Enforcing Social Distancing Measures using Smart City and ITS Infrastructures: A COVID-19 Use Case

Internet of Things is a revolutionary domain that has the caliber to impact our lives and bring significant changes to the world. Several IoT applications have been envisioned to facilitate data driven and smart application for the user. Smart City and Intelligent Transportation System (ITS) offer a futuristic vision of smart, secure and safe experience to the end user, and at the same time efficiently manage the sparse resources and optimize the efficiency of city operations. However, outbreaks and pandemics like COVID-19 have revealed limitations of the existing deployments, therefore, architecture, applications and technology systems need to be developed for swift and timely enforcement of guidelines, rules and government orders to contain such future outbreaks. This work outlines novel architecture, potential use-cases and some future directions in developing such applications using Smart City and ITS.
CFTR targeted therapies: recent advances in cystic fibrosis and possibilities in other diseases of the airways

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion transporter that regulates mucus hydration, viscosity and acidity of the airway epithelial surface. Genetic defects in CFTR impair regulation of mucus homeostasis, causing severe defects of mucociliary clearance as seen in cystic fibrosis. Recent work has established that CFTR dysfunction can be acquired in chronic obstructive pulmonary disease (COPD) and may also contribute to other diseases that share clinical features of cystic fibrosis, such as asthma, allergic bronchopulmonary aspergillosis and bronchiectasis. Protean causes of CFTR dysfunction have been identified including cigarette smoke exposure, toxic metals and downstream effects of neutrophil activation pathways. Recently, CFTR modulators, small molecule agents that potentiate CFTR or restore diminished protein levels at the cell surface, have been successfully developed for various CFTR gene defects, prompting interest in their use to treat diseases of acquired dysfunction. The spectrum of CFTR dysfunction, strategies for CFTR modulation, and candidate diseases for CFTR modulation beyond cystic fibrosis will be reviewed in this manuscript.
Manifestations of A Rare Italian Variant of Transthyretin Amyloidosis

Background Hereditary forms of amyloidosis are rare, but diagnosis will impact the treatment course of the patient and have lasting implications for other family members. Case 77 year old gentleman of Italian descent with a history of systolic heart failure (ejection fraction of 41%), hypertension, bilateral carpal tunnel syndrome, persistent atrial fibrillation (pulmonary vein isolation in 2013), history of mixed aortic valve disease status post 24 mm homograft presents with homograft degeneration. He subsequently underwent an aortic valve replacement with #23 CE valve and a 30 mm hemashield graft, mitral valve replacement and Left atrial appendage ligation. Left atrial appendage and mitral valve tissue were positive for amyloid on thioflavin S stain and immunohistochemical staining with strong reactivity to transthyretin. TTR genotyping confirmed an Italian variant c.252T>G; p.Phe84Leu (old nomenclature Phe64Leu). A technetium pyrophosphate (TcPYP) scan was not suggestive of cardiac amyloidosis (H/CL ratio G; p.Phe84Leu mutation. He has been referred to neuromuscular clinic for further evaluation and potential initiation of a medical therapy. Conclusion The two brothers highlight some of the difficulty associated with the diagnosis of amyloidosis given its variable clinical phenotype. Additionally, it is known that myocardial uptake in bone compound scintography scans can be falsely negative for unclear reasons in patients with c.252T>G; p.Phe84Leu mutations. Lastly, the isolated left atrial uptake on TcPYP scans should be further investigated as an early manifestation of cardiac amyloidosis.
Tocilizumab in the treatment of critical COVID-19 pneumonia: A retrospective cohort study of mechanically ventilated patients.

Abstract Objectives The purpose of this study is to evaluate clinical outcomes in patients with critical COVID-19 pneumonia requiring invasive mechanical ventilation who were treated with tocilizumab Design Single-center retrospective cohort study Setting Stony Brook University Hospital, a 600-bed academic tertiary medical center in Suffolk County, New York Participants Consecutive patients with COVID-19 confirmed by nasopharyngeal polymerase chain reaction (PCR) who were admitted to Stony Brook University Hospital between March 10 and April 2 2020 and required mechanical ventilation in any intensive care unit during their hospitalization Exposure Treatment with tocilizumab while intubated Main Outcome Overall mortality 30 days from the date of intubation Results Forty-five patients received tocilizumab compared to seventy controls. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and sequential organ failure assessment (SOFA) scores were similar between the two cohorts. Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 vs 3.0,P = 0.01) than controls. There was a trend towards younger mean age in the tocilizumab exposed group (56.2 vs 60.6; P = 0.09). In logistic regression analysis there was no reduction in mortality associated with receipt of tocilizumab (odds ratio (OR) 1.04; 95% CI, 0.27–3.75). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 vs 25.7; OR 1.17; 95% CI, 0.51–2.71). Conclusion When controlling for age, severity of illness, and co-morbidities, tocilizumab was not associated with reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine the role of tocilizumab in the treatment of COVID-19.
Investigating the Food and Drug Administration Biotherapeutics Review and Approval Process: Narrative Review.

Background: The development, review, and approval process of therapeutic biological products in the United States presents two primary challenges: time and cost. Advancing a biotherapeutic from concept to market may take an average of 12 years, with costs exceeding US $1 billion, and the product may still fail the US Food and Drug Administration (FDA) approval process. Despite the FDA’s practices to expedite the approval of new therapies, seeking FDA approval remains a long, costly, and risky process. Objective: The objective of this paper is to explore the factors and gaps related to the FDA review and approval process that contribute to process inefficiencies and complexities as well as proposed methods and solutions to address such gaps. This paper also aims to investigate the available modeling efforts for the FDA approval process of therapeutic biological products. Methods: A narrative review of literature was conducted to understand the scope of published knowledge about challenges, opportunities, and specific methods to address the factors and gaps related to the review and approval of new drugs, including therapeutic biological products. Relevant peer-reviewed journal articles, conference proceedings, book chapters, official reports from public policy professional centers, and official reports and guidelines from the FDA were reviewed. Results: Of the 23 articles identified in this narrative literature review, none modeled the current FDA review and approval process structure to address issues related to the robustness, reliability, and efficiency of its operations from an external point of view. Although several studies summarize the FDA approval process with clarity, in addition to bringing to light the problems and challenges faced by the regulatory agency, only a few attempts have been made to provide solutions for the problems and challenges identified. In addition, although several reform models have been discussed, these models lack the application of scientific methodologies and modeling techniques in understanding FDA as a complex sociotechnical system. Furthermore, tools and methods to assess the efficacy of the models before implementation are largely absent. Conclusions: The findings suggest the efficacy of model-based systems engineering approaches for identifying opportunities for significant improvements to the FDA review and approval process. Using this holistic approach will serve several investigative purposes: identify influential sources of variability that cause major delays, including individual, team, and organizational decision making; identify the human-system bottlenecks; identify areas of opportunity for design-driven improvements; study the effect of induced changes in the system; and assess the robustness of the structure of the FDA approval process in terms of enforcement and information symmetry. Trial Registration:
CALCIFIED AND CARTILAGINOUS TISSUE WOUND HEALING

SUMMARY The importance of understanding the intricacies of the wound-healing response in bone and cartilage cannot be overemphasized. Armed with knowledge of the various mechanical, biochemical, and environmental variables at the tissue level, the surgeon can predict and affect favorable healing more consistently.
Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance.

Abstract Aims To retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening. Materials and methods Patients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II–III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan–Meier and Cox proportional hazards models. Results In total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II–III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08–0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12–0.51; P Conclusions In the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II–III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.
Physical connection of sensible and ground heat flux

Abstract Characterizing physical relationships between the sensible, latent and ground heat flux at the Earth surface is of crucial importance in studying the global energy, water, and carbon cycles. Here we demonstrate an analogy between the daily mean turbulent heat transfer in the atmospheric surface layer and conductive-advective heat transfer in soil. This finding, in conjunction with temperature continuity at the land–atmosphere interface, uncovers a physical linkage between sensible and ground heat flux. The proposed relationship and its ramification for estimation of latent heat flux are validated based on daily averaged data from six AmeriFlux eddy covariance stations in North America over a wide range of land covers and climate regimes.
Fructan synthesis in starch-storing tissue expressing a bacillus SacB gene

Expressing microbial genes in transgenic plants represents an opportunity to produce renewable resources of novel carbohydrate polymers. Novel polymers may be use in place of starch in unique food and industrial applications. Altering carbohydrate metabolism in plants also provides information about native pathways and how they are regulated. Diverting carbohydrate from endogenous pathways by expressing a microbial gene may be used as a tool in determining how plants sense and react to altered sugar concentrations.
Strategies for developing effective neural network applications

Summary form only given, as follows. Although some authors have emphasized the "black box" nature of neural networks, effective applications require a clear theoretical understanding of networks and the fundamental issues involved in representation, learning and generalization. I will develop a general theory of neural networks, show how that theory can be applied in a number of specific cases and provide a number of "helpful hints" for the development of useful applications.
Alloy: A New Technology for Software Modelling

Alloy is a lightweight language for software modelling. It's designed to be flexible and expressive, and yet amenable to fully automatic simulation and checking. At its core, Alloy is a simple first order logic extended withrelational operators. A simple structuring mechanism allows Alloy to be used in a variety of idioms, and supports incremental construction of models. Alloy is analyzed by translation to SAT. The current version of the tool uses the Chaff and Berkmin solvers; these are powerful enoughto handle a searchspace of 2100 or more. Alloy has been applied to problems from very different domains, from checking the conventions of Microsoft COM to debugging the design of a name server. Most recently, we have used it to check distributed algorithms that are designed for arbitrary topologies. We are also investigating the use of Alloy to analyze object-oriented code.
Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism

Exercise offers several benefits for health, including increased lean body mass and heightened energy expenditure, which may be partially attributable to secretory factors known as myokines. Irisin, a recently identified myokine, was shown to increase metabolic rate and mitochondrial content in both myocytes and adipocytes; however, the mechanism(s) of action still remain largely unexplained. This work investigated if irisin functions by acting as an inflammatory myokine leading to cellular stress and energy expenditure. C2C12 myotubes were treated with various concentrations of irisin, TNFα, or IL6 for various durations. Glycolytic and oxidative metabolism, as well as mitochondrial uncoupling, were quantified by measurement of acidification and oxygen consumption, respectively. Metabolic gene and protein expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting, respectively. Mitochondrial content was assessed by fluorescent imaging. NFκB activity was assessed using an NFκB GFP-linked reporter system. Consistent with previous findings, irisin significantly increased expression of several genes including peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) leading to increased mitochondrial content and oxygen consumption. Despite some similarities between TNFα and irisin treatment, irisin failed to activate the NFκB pathway like TNFα, suggesting that irisin may not act as an inflammatory signal. Irisin has several effects on myotube metabolism which appear to be dependent on substrate availability; however, the precise mechanism(s) by which irisin functions in skeletal muscle remain unclear. Our observations support the hypothesis that irisin does not function through inflammatory NFκB activation like other myokines (such as TNFα).
sGD: software for estimating spatially explicit indices of genetic diversity

Anthropogenic landscape changes have greatly reduced the population size, range and migration rates of many terrestrial species. The small local effective population size of remnant populations favours loss of genetic diversity leading to reduced fitness and adaptive potential, and thus ultimately greater extinction risk. Accurately quantifying genetic diversity is therefore crucial to assessing the viability of small populations. Diversity indices are typically calculated from the multilocus genotypes of all individuals sampled within discretely defined habitat patches or larger regional extents. Importantly, discrete population approaches do not capture the clinal nature of populations genetically isolated by distance or landscape resistance. Here, we introduce spatial Genetic Diversity (sGD), a new spatially explicit tool to estimate genetic diversity based on grouping individuals into potentially overlapping genetic neighbourhoods that match the population structure, whether discrete or clinal. We compared the estimates and patterns of genetic diversity using patch or regional sampling and sGD on both simulated and empirical populations. When the population did not meet the assumptions of an island model, we found that patch and regional sampling generally overestimated local heterozygosity, inbreeding and allelic diversity. Moreover, sGD revealed fine-scale spatial heterogeneity in genetic diversity that was not evident with patch or regional sampling. These advantages should provide a more robust means to evaluate the potential for genetic factors to influence the viability of clinal populations and guide appropriate conservation plans.
Minimally invasive surgery in the management of rectal cancer.

Abstract Advances in minimally invasive colon surgery, shown to be safe and effective, facilitated its rapid spread throughout the world. Minimally invasive rectal surgery however, has been much slower to take hold due to technical difficulty and concerns for oncologic outcomes. To date, there has been enough data accumulated to show that its similarly safe in skilled hands and leads to better patient outcomes.
Eigenfunctions on a Stadium Associated with Avoided Crossings of Energy Levels

The authors examine graphical properties of eigenfunctions with stadium boundaries associated with avoided crossings of energy levels.
Model update for mesospheric/thermospheric nitric oxide

Abstract In reviewing the large deficit in model predictions of nitric oxide (NO) abundance near the mesosphere/lower thermosphere [NO] peak region, this paper shows that the deficit is now largely reduced using an updated model. Prior model/data comparison study (Swaminathan, 1998) which included comprehensive chemistry, contemporaneously measured solar soft x ray flux, and time-dependence of the suprathermal N( 4 S) atom source, pointed to a large net deficit based on current NO chemistry. Although the suprathermal source has been invoked for many decades, its importance has been recently disestablished (Balakrishnan 1998). The present update to the model has no suprathermal N( 4 S) source, a recently measured higher NO + recombination branching ratio and extended empirical solar x ray wavelength coverage based on combined YOHKOH and SNOE solar x ray flux data; and it is found that the large deficit is no longer present. The model predicts [NO] peak density within 30% of the data after accounting for the ever-present auroral transport contribution derived by Barth (1999) from recent SNOE measurements. This result dramatically impacts the thermospheric nitric oxide abundance problem that has existed for many decades. Further search for minor NO chemical sources is only appropriate while also quantifying the role of multidimensional atmospheric dynamics in detailed model/data comparisons.
Multiplicity distribution in πp, Kp, and pp collisions in an impact-parameter model

Abstract The fact that multiplicity distributions in high-energy π p and Kp collisions are less broad than those in pp collisions is related, in a model which considers the impact-parameter dependence of the multiplicity, to the fact that the ratio of σ e1 to σ tot is smaller for π p and Kp than for pp collisions.