cssi/SciSciGPT-SciSciNet huggingface dataset:
PERSPECTIVE A UNITS-OF-EVOLUTION PERSPECTIVE ON THE ENDOSYMBIONT THEORY OF THE ORIGIN OF THE MITOCHONDRION.

Discussions of mitochondria and their hosts often conceptualize this relationship in a more or less modern form, focusing on the metabolic benefits of mitochondria to the host cell or on the possibility of intragenomic conflict. A more inclusive units-of-evolution perspective recognizes that both costs and benefits must be viewed from the level of the cells that initiated this interaction, the protomitochondrion and the primitive host cell. From this perspective, ecological and physiological considerations become central to the characterization of initial and subsequent host-mitochondria associations. Foremost among these considerations is the generation of superoxide radicals by modern mitochondria and the deleterious effects of these endogenous oxidants on modern eukaryotic cells. Because of their photosynthetic and aerobic ecologies, protomitochondria likely were relatively tolerant of such oxidants; anaerobic, heterotrophic, primitive host cells, on the other hand, likely were not. In the initial association of host and symbiont, the latter may have manipulated the former's life history by means of both endogenous oxidants and a superabundance of ATP. A resolution of this units-of-evolution conflict was necessary to continue this association, and this resolution, in a ritualized form, may have shaped the evolution of many features of modern eukaryotic cells and mitochondria, for example, the messenger functions of calcium ions, the regulatory role of phosphorylation cascades in cell-division cycles, the absence from the mitochondrial genome of replication factors, transcription factors, and adenine nucleotide carrier genes. The initial host-mitochondria interaction may have further channeled the evolution of multicellular eukaryotes, particularly animals, resulting in the association of mitochondria and the germinal plasm and in the use of extracellular ATP and endogenous oxidants as developmental signals. Evolutionary explanations for "free-radical" theories of development and aging are thus suggested.
Metastatic choriocarcinoma in a middle-aged man presenting as a right thigh mass with venous thrombosis: a case report.

Choriocarcinoma is a highly aggressive β-subunit of human chorionic gonadotropin (βHCG)-producing germ cell tumor. In men, it is a rare neoplasm and can arise in the testes or in various extragonadal locations such as the retroperitoneum, mediastinum, and pineal body. We present a highly unusual case of a middle-aged man with primary metastatic βHCG-producing choriocarcinoma of the right thigh along with right lower-extremity venous thrombosis. We comment on prognostic variables as well as discuss several theories to account for the unusual location of his choriocarcinoma.
Phosphorylated pS1292 LRRK2 to Total LRRK2 Concentration Ratio in Urine Exosomes Distinguishes LRRK2-PD and Idiopathic PD (S7.002)

Objective: To measure total LRRK2 and phosphorylated pS1292-LRRK2 levels in urine exosomes of LRRK2 G2019S carriers with PD (LRRK2+/PD+), and non-carriers with (LRRK2-/PD+), and without PD (LRRK2-/PD-). Background: LRRK2 G2019S mutations may increase Parkinson’s disease (PD) risk through a gain of kinase function including autophosphorylation at the serine-1292 residue near the LRRK2 GTPase domain. Phosphorylated pS1292-LRRK2 may reflect LRRK2 kinase activity. Methods: 14 Male participants included LRRK2+/PD+ (n=7), LRRK2-/PD+ (n=4), and LRRK2-/PD- (n=3). Fresh urine was collected and frozen in a -80oC freezer. Urinary exosomes were purified from ~40 ml samples. Monoclonal anti-LRRK2/Dardarin clone acquired from NeuroMab were used to measure total LRRK2, and novel polyclonal antibodies generated in rabbits against pS1292-LRRK2 were used to quantify total-LRRK2 and pS1292-LRRK2 in Western blots. Total LRRK2, pS1292-LRRK2 and the ratio between total LRRK2 and pS1292-LRRK2 were compared between G2019S carriers with PD and non-carriers with and without PD. Results: All three groups were similar in age (mean=67.0; SD=7.5). The ratio of pS1292-LRRK2 to total LRRK2 was significantly different between LRRK2+/PD+ (mean=0.90; SD=0.28; range 0.60-1.46) and both LRRK2-/PD+ (mean=0.20; SD=0.03; range 0.16-0.24, p<0.001) and LRRK2-/PD- (mean=0.19; SD=0.09; range 0.10-0.29; p<0.001). The values did not overlap. Conclusion: A ratio of phosphorylated pS1292-LRRK2 to total LRRK2 in urine may distinguish between LRRK2+/PD+ and non-carriers with and without PD. Future studies are required to confirm that this ratio signifies LRRK2 autophosphorylation activity in the brain and to test if the elevated ratio is associated with disease characteristics in men and women. Disclosure: Dr. Alcalay has nothing to disclose. Dr. Fraser has nothing to disclose. Dr. West has nothing to disclose.
Solar irradiance observed at Summit, Greenland: Possible links to magnetic activity on short timescales

Abstract Measurements of ground-level visible sunlight (400–600 nm) from Summit, Greenland over the period August 2004 through October 2014 define the attenuation provided by cloudiness, including its dependence on solar elevation and season. The long-term mean cloud-attenuation increases with increasing solar zenith angle, consistent with radiative transfer calculations which treat a cloud as a plane parallel layer with a strong bias toward forward scattering and an albedo for diffuse radiation near 0.1. The ratio of measured irradiance to clear-sky irradiance for solar zenith angles greater than 66° has a small, but statistically significant, positive correlation with the previous day's magnetic activity as measured by the daily Ap index, but no clear relationship exists between the irradiance ratio and daily changes in the ground-level neutron flux measured at Thule over the time frame considered. A high value of Ap on one day tends to be followed by a day whose ground-level solar irradiance is slightly greater than would occur otherwise. In an average sense, the visible irradiance following a day with Ap>16 exceeds that following a day with Ap≤16 by 1.2–1.3% with a 95% confidence range of approximately ±1.0%. The results are broadly compatible with small changes in atmospheric scattering following magnetic disturbances.
Ruses and Perfidy

Introduction Treaties addressing modern weapons aside, there is little that is new in the law of armed conflict (LOAC). Discussions of “new paradigms” in warfare usually illustrate the speaker's unawareness of history – allusions to the treachery of terrorists, for instance. In the twelth or thirteenth century b.c. , in the Trojan War, the Greeks employed the legendary Trojan horse to defeat Troy. In the seventh century, the Islamic Caliph Abu Bakr ordered his forces, “Let there be no perfidy, no falsehood in treaties with the enemy, be faithful to all things, proving yourselves upright and noble and maintaining your word and promises truly.” The Lieber Code holds that, “Military necessity…admits of deception, but disclaims acts of perfidy…,” yet perfidy persists. In 1882, near El Obeid Egypt, the Egyptian government had grown weary of Muhammad Ahmad, a young Muslim who proclaimed himself the Mahdi, the Awaited One. Ahmad initiated a surprisingly effective rebellion against the government, and Cairo finally sent an army to capture or kill the Mahdi. The force was led by a retired British Indian army officer, General William Hicks. “To Cairo's horrified astonishment, Hicks and most of his force was slaughtered at Shaykan…The Mahdi's sharpshooters had feigned retreat, luring inward Hick's army of 7,000 infantry, 1,000 cavalry, and 5,000 camels, together with its precious cannons and a horde of camp followers.” Does LOAC/IHL allow an armed force to “feign retreat” and then kill the pursuing enemy?
Engineered microenvironments for cancer study

Abstract While 2D models lack physiological relevance, animal models are highly complex and uncontrolled, and often do not mimic the human tumor microenvironment (TME). Therefore, more physiologically relevant engineered tumor models have begun to fill a unique niche in modeling the complex dynamics of the human TME. Advances in biomaterials and microfabrication techniques applied to soft materials have helped to drive a recent resurgence of this field, which has actually been around since spheroid culture models were first introduced decades ago. The varied geometries of microengineered tissues allow for hypotheses concerning a specific aspect of the TME to be efficiently addressed. To facilitate understanding of the importance of these varied 3D systems to cancer biology, we will provide an overview of the general composition and purpose for each of the more common as well as cutting-edge model platforms, including spheroids, microwell arrays, microfluidic tissues, and 3D printed tissues. To date, these models are rarely, if ever, created by two-photon polymerization, but the opportunity for use of two-photon polymerization, and more broadly dynamic manipulation with focused light, in important applications is clear.
Building a Sustainable Peace in Guatemala

Some conflicts are defined as ethnic from the start, while in others the ethnic dimensions are first latent and slowly emerge over time. In Guatemala, for example, the emergence of a Marxist guerrilla movement challenging the state led both sides to explain their actions in political and economic terms. The guerrillas stressed the injustice of Guatemala’s social inequality, while the government seeking American support explained the conflict in a Cold War framework emphasizing the danger of communism to the region.
Exploring metalorganic chemical vapor deposition of Si-alloyed Al 2 O 3 dielectrics using disilane

Abstract The alloying of Al2O3 films with Si is a promising route to improve gate dielectric properties in Si- and wide-bandgap- based MOS devices. Here we present a comprehensive investigation of alloyed film growth by metalorganic chemical vapor deposition (MOCVD) using trimethylaluminum, disilane, and oxygen precursors over a variety of temperature and flow conditions. Binary growth rates of Al2O3 and SiO2 were evaluated to explain the aggregate growth kinetics of Si-alloyed Al2O3 films, and refractive indices were used to monitor Si incorporation efficiencies. The temperature dependence of the reaction rate of disilane with oxygen was found to be similar to that of trimethylaluminum and oxygen, leading to well-behaved deposition behavior in the kinetic and mass-transport controlled growth regimes. Compositional predictability and stability was achieved over a wider growth space with disilane-based growths as compared to previous work, which used silane as the Si precursor instead. In situ (Al,Si)O/n-GaN MOS gate stacks were grown and showed increasing reduction of net positive fixed charges with higher Si composition.
Computational and Experimental Characterization of Patient Derived Mutations Reveal an Unusual Mode of Regulatory Spine Assembly and Drug Sensitivity in EGFR Kinase

The catalytic activation of protein kinases requires precise positioning of key conserved catalytic and regulatory motifs in the kinase core. The Regulatory Spine (RS) is one such structural motif that is dynamically assembled upon kinase activation. The RS is also a mutational hotspot in cancers; however, the mechanisms by which cancer mutations impact RS assembly and kinase activity are not fully understood. In this study, through mutational analysis of patient derived mutations in the RS of EGFR kinase, we identify an activating mutation, M766T, at the RS3 position. RS3 is located in the regulatory αC-helix, and a series of mutations at the RS3 position suggest a strong correlation between the amino acid type present at the RS3 position and ligand (EGF) independent EGFR activation. Small polar amino acids increase ligand independent activity, while large aromatic amino acids decrease kinase activity. M766T relies on the canonical asymmetric dimer for full activation. Molecular modeling and molecular dy...
Research Opportunities in Hydrology and Biology in Future Watershed Studies

The effects of timber harvesting practices on water resources are mostly known from paired watershed studies. The first paired watershed study in the United States was in Colorado and designed to assess the effects of timber harvesting on water yield (Bates and Henry 1928). Many of these studies were designed to have demonstrable effects on water resources, specifically the timber harvesting was large in comparison to the watershed area (up to 100%), streamside vegetation buffers were not used, all timber including non-merchantable materials were removed, or the forest regeneration was suppressed by herbicide applications. Although these experiments helped identify the hydrologic processes affected by timber harvesting, they do not necessarily represent the effects of normal forest operations. The scope of watershed studies was soon expanded beyond water quantity and the processes of the hydrologic cycle to include water quality. Measurements of inputs and outputs, as precipitation and streamflow, were used for chemical budgets. In the 1960s, 150 forested experimental watersheds were being studied; only 12 of these remain relatively active and half of those are long term ecological research sites (Ziemer and Ryan 2000). Many of the active research watersheds tend to focus on ecological processes in the watershed, rather than focus on hydrological processes as related to ecology. Nonetheless, several lessons learned from Alsea and other watershed studies (Stednick et al. 2004) are worth repeating. The original AlseaWatershed Study and the ongoing research have provided some very useful lessons in forest hydrology and the effects of timber harvesting on hydrological responses. Timber harvesting of a large area in a watershed (Needle Branch) resulted in increased annual water yield. These water yield increases are higher in wetter years and lower in wetter years. As vegetation grows and the hydrological processes of interception, transpiration, and storage
Real-Time Decision-Making to Serve the Unbanked Poor in the Developing World

The World Bank estimated in 2015 that 60% of the world's poor earning less than USD2.00 a day do not have a bank account or are unbanked. A major impediment to serve the unbanked poor is the high cost of the process of distributing small loans and collecting repayments from barely literate borrowers. This process requires loan officers to meet the poor at their door step, making it a people-intensive process requiring frequent face-to-face interaction. Real-time decision-making is a solution to address the key challenge experienced by banks when serving the unbanked poor in the developing word. Our poster is drawn from two case examples: Banco Azteca, a bank in Mexico, and Equitas Holdings Limited that makes small amounts of loans to unbanked poor in India. We focus on an Azteca's automated decision support system to serve low income people ignored by banks in Mexico, and a real-time performance dashboard custom-built by Equitas to improve the productivity of loan officers. Our analysis suggests that real-time decision making cannot enable banks to scale their operations for achieving significant social impact unless the following conditions are met: process, application of real time data, user friendly interfaces, and leadership by top management.
Meet Alfred Knobler

Alfred E. Knobler made several generous dona­ tions to Virginia Tech for the creation of Knobler scholarships and fellowships. These opportunities are for both undergraduate and graduate students in the Departments of Materials Science and Engineering and English. The purpose of these scholarships is to foster communication and exchange of ideas and skills between these two departments.
Punctate retinal hemorrhage and its relation to ocular and systemic disease in dogs: 83 cases

Objective To describe clinical aspects of dogs with punctate retinal hemorrhage (PRH). Animals studied 83 dogs (119 eyes) with PRH. Procedures Medical records of dogs evaluated by the Cornell University ophthalmology service with a clinical diagnosis of PRH between 2006 and 2015 were reviewed. For this study, PRH was defined as retinal hemorrhages ≤ 1 optic disk diameter in size and dogs with other posterior segment ocular diseases were excluded. Signalment and clinical features of the dogs were recorded, including concurrent ocular and systemic diseases. Results Punctate retinal hemorrhage was identified in 119 eyes of 83 dogs. The mean (±standard deviation) age of dogs was 10.0 (±3.8) years. Mixed-breed dogs, Golden Retrievers, Jack Russell Terriers, and English Springer Spaniels were statistically overrepresented relative to the ophthalmology service canine referral population during the same period. Hemorrhages were found in all retinal locations and varied in number. Concurrent ocular disease was present in 78 eyes (66%) including keratoconjunctivitis sicca, uveitis, and cataracts. Fifty dogs (60%) suffered from concurrent systemic disease and diabetes mellitus, multiple myeloma, and systemic hypertension were statistically overrepresented in the PRH population. Less frequently, other serious systemic diseases were present in dogs with PRH including immune-mediated thrombocytopenia, leptospirosis, metastatic neoplasia, and thromboembolic disease. Conclusions The risk of PRH in dogs may be increased by certain ocular and systemic diseases. As the presence of PRH can be associated with underlying systemic disease in dogs, it may prompt further clinical investigation and diagnostics.
Opening a Window into Reading Development: Eye Movements' Role Within a Broader Literacy Research Framework.

The cumulative body of eye movement research provides significant insight into how readers process text. The heart of this work spans roughly 40 years reflecting the maturity of both the topics und...
Oxidation and hot corrosion behavior of some land based gas turbine superalloys in steam environment

The high temperature behavior of nickel based superalloys IN738, IN617, and CMSX-4 in pure steam and impure steam was investigated. Two kinds of experiment were carried out in this study. The first focused on the performance of superalloys IN738, IN617, and CMSX4 in high temperature pure steam at 845, 875, 900, and 950 C. The results of this study were used to investigate the high temperature oxidation behavior of the superalloys induced by pure steam compared to those in air. The second dealt with the performance of these alloys in contaminated steam. In this case, two streams of steam carrying the salt impurities NaCl and Na{sub 2}SO{sub 4}, passed through the internal bore of hollow cylindrical specimens of superalloys IN738, and IN617 housed in a furnace whose temperature was controlled at 875 C. One stream of steam was produced from water containing 5 ppm each of Na{sub 2}SO{sub 4} and NaCl salts while the second was from that containing 1 ppm of each salt. The temperature of steam in the internal passages of the tested specimens was estimated at about 225 C. This study was used to investigate the hot corrosion behavior of the tested superalloys induced by impure steam more » cooling. Thus in this paper, the performance of the superalloys in pure steam and impure steam at high temperature is examined, the mechanisms of the oxidation and corrosion of the superalloys induced by steam are briefly discussed, and suggestions are provided with regard to the application of steam cooling in land based gas turbine systems for power generation. « less
A sweet alternative: maintaining M2 macrophage polarization

Glycolytic metabolism functions as a backup mechanism for M2 macrophage polarization when oxidative phosphorylation is disrupted.
Predicting Dysphoria and Hostility Using the Diathesis-Stress Model of Sociotropy and Autonomy in a Contextualized Stress Setting

We examined the diathesis-stress model of sociotropy and autonomy in the prediction of dysphoria and self-reported hostility. Participants were 39 women who had recently relocated to the United States. Because participants relocated at approximately the same time and for the same reasons (husband enrolled in a university program), we were able to measure multiple stressors that occurred in the same context (relocation). We measured stress comprehensively using semistructured interviews and coded each negative stressor into interpersonal and achievement categories. The match between sociotropy and interpersonal stressors predicted dysphoria, whereas the match between autonomy and achievement stressors predicted hostility. Implications for the diathesis-stress model of sociotropy–autonomy are discussed.
Effects of 63 MeV proton-irradiation on the dark-current in III-V-based, unipolar barrier infrared detectors

Abstract Recent investigations demonstrated that III-V-based nBn infrared detectors typically experience relatively significant performance degradation under 63 MeV proton irradiation due to displacement damage, limiting their viability for certain space-based applications. Additionally, the investigations suggested, based on simplified expressions, that the nBn’s diffusion-limited dark-current would transition from a linear-dependence on proton fluence to a square-root-dependence as the minority carrier recombination lifetime decreased and the subsequently decreasing diffusion length became less than the thickness of the detector’s quasi-neutral absorbing region. Here, a closer examination of this expected behavior is reported on. Evidence from multiple nBn detector rad-tolerance experiments and simple numerical simulations indicated the behavior of the nBn’s diffusion-current under proton irradiation can be more complicated than was previously suggested. For example, in some nBn detectors proton irradiation was observed to increase the doping density of the absorber sufficient to impact the diffusion-current and lessen its power-law-dependence on the proton fluence. This increase was confirmed by analysis of in situ capacitance–voltage measurements on an irradiated nBn detector, which found an n-type carrier addition rate ∼ 140 cm−1. Simulations showed this level of carrier addition can lead to a ∼ 75 % reduction in the expected diffusion-current density for an equivalent dose of 100 krad(Si). Simulations also showed the nBn diffusion-current’s instantaneous power law-dependence on proton fluence peaked well below unity and then began approaching −.5 rather than.5, which was suggested by those previous investigation. A high native defect density prior to irradiation and finite surface recombination velocity were both found to reduce the initial power-law dependence and shift its peak position.
Understanding Symptoms of Muscle Tightness, Weakness, and Rigidity From a Nursing Perspective.

Purpose This study examined the nature of muscle tightness from nurses' perspectives and explored how the symptoms of muscle tightness are communicated, managed, and differentiated from other conditions, such as muscle rigidity and muscle weakness. Design An exploratory, descriptive qualitative design was used. Methods Eight rehabilitation nurses described lexicons, care strategies, and communication for muscle tightness, weakness, and rigidity. Findings Nurses used conflicting terms to describe muscle tightness, weakness, and rigidity. They identified medications and range of motion as the best strategies to manage muscle conditions. Nurses approach care holistically and do not differentiate care strategies that are based only on a symptoms lens. Conclusions Nurses were unable to clearly differentiate between muscle tightness and rigidity. Clinical relevance Nurses influence patients' choice of vocabulary; therefore, they must use simple but precise terminologies to educate their patients. Miscommunication between nurses and patients can lead to errors, which can have negative consequences.
Robust Chemical and Chemical-Resistant Material Detection Using Hyper-Spectral Imager and a New Bend Interpolation and Local Scaling HSI Sharpening Method

We present new results from our ongoing research activity for chemical threat detection using hyper-spectral imager (HSI) detection techniques by detecting nontraditional threat spectral signatures of agent usage, such as protective equipment, coatings, paints, spills, and stains that are worn by human or on trucks or other objects. We have applied several current state-of-the-art HSI target detection methods such as Matched Filter (MF), Adaptive Coherence Estimator (ACE), Constrained Energy Minimization (CEM), and Spectral Angle Mapper (SAM). We are interested in detecting several chemical related materials: (a) Tyvek clothing is chemical resistance and Tyvek coveralls are one-piece garments for protecting human body from harmful chemicals, and (b) ammonium salts from background could be representative of spills from scrubbers or related to other chemical activities. The HSI dataset that we used for detection covers a chemical test field with more than 50 different kinds of chemicals, protective materials, coatings, and paints. Among them, there are four different kinds of Tyvek material, three types of ammonium salts, and one yellow jugs. The imagery cube data were collected by a HSI sensor with a spectral range of 400–2,500nm. Preliminary testing results are promising, and very high probability of detection (Pd) and low probability of false detection are achieved with the usage of full spectral range (400– 2,500nm). In the second part of this paper, we present our newly developed HSI sharpening technique. A new Band Interpolation and Local Scaling (BILS) method has been developed to improve HSI spatial resolution by 4-16 times with a low-cost high-resolution pen-chromatic camera and a RGB camera. Preliminary results indicate that this new technique is promising.
Physiology of Aging

Our population is aging at an astonishing rate. According to the US census, the US population totaled about 321 million in 2015, and 14.9% were over the age of 65. By the year 2050, this percentage is expected to grow to 22.1% (He et al. An aging world: 2015 [Internet]. Washington D.C: U.S. Government Publishing Office; 2016). You will likely care for older adults in whatever specialty you choose to practice and will need to be able to distinguish between the changes expected with normal aging and changes that indicate underlying pathology. Toward that goal, this chapter reviews the physiology of aging by organ system.
Spatial Wage Gaps in Frictional Labor Markets

We develop a job ladder model with labor reallocation across firms and regions, and estimate it on matched employer-employee data to study the large and persistent real wage gap between East and West Germany. We find that the wage gap is mostly due to firms paying higher wages per efficiency unit in West Germany and quantify a rich set of frictions preventing worker reallocation across space and across firms. We find that three spatial barriers impede East Germans' ability to migrate West: migration costs, their preference to live in the East, and fewer job opportunities received from the West. The estimated model highlights that the spatial barriers needed to generate the large wage gap between East and West are small relative to the frictions preventing the reallocation of labor across firms. Therefore, policies that directly promote regional integration lead to smaller aggregate benefits than equally costly hiring subsidies within region.
Thermal decomposition of methyl linoleate and methyl linolenate hydroperoxides analyzed by capillary gas chromatography.

Much work has been reported on the volatile oxidation products of unsaturated fats because they cause rancidity in foods and cellular damage in the body. Decomposition of fatty ester hydroperoxides creates a wide range of carbonyl compounds, hydrocarbons, furans, and other materials that contribute to flavor deterioration of foods and that are implicated in biological oxidation. Interaction of some of these degradation products with DNA, proteins, and enzymes may be involved in cell-damaging reactions.2–4 Although fatty acid hydroperoxides are the recognized precursors of volatile secondary products, relatively little information is available on the mechanism of their decorposition. New information on the volatile lipid oxidation products is needed to better evaluate precursors of oxidative deterioration in lipid-containing foods and to understand the biological significance of lipid peroxidation.
Stable AC-DC Source for Josephson and Impedance Measurement Systems

The paper describes a digital low-frequency ac voltage source with amplitude stability better than 10−6 V/V per hour. It was developed to be used as a transfer standard for calibrations with ac Josephson systems and fast synchronous ac-dc transfer measurements. Its low-distortion and superb phase adjustment resolution makes it suitable for impedance measurements as well.
Numerical investigation of biomechanically coupled growth in cortical folding

Cortical folding-the process of forming the characteristic gyri (hills) and sulci (valleys) of the cortex-is a highly dynamic process that results from the interaction between gene expression, cellular mechanisms, and mechanical forces. Like many other cells, neurons are sensitive to their mechanical environment. Because of this, cortical growth may not happen uniformly throughout gyri and sulci after the onset of cortical folding, which is accompanied by patterns of tension and compression in the surrounding tissue. Here, as an extension of our previous work, we introduce a biomechanically coupled growth model to investigate the importance of interaction between biological growth and mechanical cues during brain development. Our earlier simulations of cortical growth consisted of a homogeneous growing cortex attached to an elastic subcortex. Here, we let the evolution of cortical growth depend on a geometrical quantity-the mean curvature of the cortex-to achieve preferential growth in either gyri or sulci. As opposed to the popular pre-patterning hypothesis, our model treats inhomogeneous cortical growth as the result of folding rather than the cause. The model is implemented numerically in a commercial finite element software Abaqus/Explicit in Abaqus reference manuals, Dassault Systemes Simulia, Providence (2019) by writing user-defined material subroutine (VUMAT). Our simulations show that gyral-sulcal thickness variations are a phenomenon particular to low stiffness ratios. In comparison with cortical thickness measurements of [Formula: see text] human brains via a consistent sampling scheme, our simulations with similar cortical and subcortical stiffnesses suggest that cortical growth is higher in gyri than in sulci.
Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Children in a Large Regional US Health System During the Coronavirus Disease 2019 Pandemic.

BACKGROUND: The objective was to evaluate patterns of pediatric coronavirus disease 2019 testing in a large health system throughout the pandemic, before and after school reopening. METHODS: This was a cross-sectional time-series study of clinical virology results from children tested for severe acute respiratory syndrome coronavirus 2 in Southern Connecticut and areas of New York and Rhode Island. Data collected include demographics, hospital admission, changes in percent positive tests over time, detection intervals in persistently positive children and cycle threshold values. The setting was the Yale New Haven Health System has 6 hospitals at 4 Connecticut locations, 1 hospital in Rhode Island and ambulatory locations in Connecticut, Rhode Island and New York. Participants included twenty-three-thousand one-hundred thirty-seven children ≤ 18 years of age, tested for coronavirus disease 2019 at an ambulatory testing site, the emergency department or on an inpatient unit within the Yale New Haven Health System. RESULTS: Among all tests, 3.2% were positive. Older children consistently made up the larger portion of positive pediatric cases, regardless of community prevalence. Increased pediatric cases later in the pandemic when prevalence in adults was relatively low correlates with a higher number of tests performed in children and not with an increased positivity rate. No significant changes in trends of positivity were detected after the reopening of schools. Symptomatic and asymptomatic children had similar cycle threshold values regardless of age, and a subset of children demonstrated persistent viral detection, some for as long as 6 weeks. CONCLUSION: An increase in pediatric cases documented in the late summer was predominately due to increased access to testing for children. The percent positivity in children did not change in the first 3 weeks after school opened. A subset of children has detectable severe acute respiratory syndrome coronavirus 2 RNA in the upper respiratory tract for weeks after the initial infection.
Visualizing defect energetics.

Defect energetics impact most thermal, electrical and ionic transport phenomena in crystalline compounds. The key to chemically controlling these properties through defect engineering is understanding the stability of (a) the defect and (b) the compound itself relative to competing phases at other compositions in the system. The stability of a compound is already widely understood in the community using intuitive diagrams of formation enthalpy (ΔHf) vs. composition, in which the stable phases form the ‘convex-hull’. In this work, we re-write the expression of defect formation enthalpy (ΔHdef) in terms of the ΔHf of the compound and its defective structure. We show that ΔHdef for a point defect can be simply visualized as intercepts in a two-dimensional convex-hull plot regardless of the number of components in the system and choice of chemical conditions. By plotting ΔHf of the compound and its defects all together, this visualization scheme directly links defect energetics to the compositional phase stability of the compound. Hence, we simplify application level defect thermodynamics within a widely used visual tool understandable from basic materials science knowledge. Our work will be beneficial to a wide community of experimental chemists seeking to build an intuition for appropriate choice of chemical conditions for defect engineering.
Periodontal Disease and Incident CKD in US Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

Rationale & Objective Recent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented. Study Design Observational cohort. Setting & Participants We analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline. Predictors Predictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition ( Outcomes Outcomes were incident low estimated glomerular filtration rate (eGFR) (eGFR Analytic Approach Poisson and linear regression. Results For the sample (n = 7.732), baseline mean age was 41.5 years, 45.2% were male, 11.7% had ≥30% of sites with clinical attachment loss ≥3 mm, 5.1% had ≥30% of sites with probing depth ≥4 mm, 30.7% had ≥50% of sites with bleeding on probing, and 16.2% had absent functional dentition. During a median follow-up of 5.9 years, 149 patients developed low eGFR and 415 patients developed albuminuria. On multivariable analysis, presence versus absence of ≥30% of sites with probing depth ≥4 mm and absence of functional dentition were each associated with increased risk for incident low eGFR (incident density ratio, 2.31; 95% CI, 1.14-4.65 and 1.65, 95% CI, 1.01-2.70, respectively). None of the other predictors were associated with outcomes. Limitations Only a single kidney function follow-up measure. Conclusions In this cohort of US Hispanics/Latinos, we found that select measures of periodontal disease were associated with incident low eGFR. Future work is needed to assess whether the treatment of periodontal disease may prevent CKD.
Description and management of retinopathy of prematurity reactivation after intravitreal antivascular endothelial growth factor therapy.

Purpose of review To review the literature regarding reactivation of retinopathy of prematurity (ROP) after treatment with antivascular endothelial growth factor (anti-VEGF) agents. Recent findings Reactivation can occur after anti-VEGF or laser. Risk factors for reactivation include patient and disease-related factors. Various studies are evaluating the use of different anti-VEGF agents and reactivation rates. However, the definition of reactivation varies between studies. Summary The literature has varied definitions of reactivation, which is often used interchangeably with recurrence. It is important to recognize features of reactivation of ROP to appropriately manage patients and conduct clinical trials. The International Classification of ROP 3rd edition has established a consensus guideline regarding terminology describing reactivation.
Experience using dupilumab for pediatric atopic dermatitis at a tertiary care c enter: Inadequate response and adverse events

Background/objective Dupilumab is highly effective in treating atopic dermatitis (AD). However, some patients experience difficulties with dupilumab therapy, such as inadequate clinical response, failure to achieve long-term disease control, or adverse events (AEs). Our objective is to assess inadequate response and AEs occurring in children on dupilumab therapy for AD. Methods This is a retrospective cohort study of children on dupilumab for AD. Collected variables included patient demographics, medical histories, and dupilumab therapy characteristics. Response analysis was conducted in those with ≥3 months of dupilumab therapy: primary poor responders were defined as those whose EASI scores did not decrease by >50%, and secondary poor responders were those who initially responded but had significant AD flares while on therapy. Results We included 200 patients on dupilumab for AD in our cohort; 192 received ≥3 months of therapy and were included in our response analysis. Twelve children experienced inadequate primary response, and 4 were secondary poor responders. Four of these 16 children discontinued therapy due to inadequate response. The most common dupilumab-associated AEs were facial erythema (n = 24, 12.0%) and injection-site reactions (n = 24, 12.0%). Female sex was significantly associated with experiencing injection-site reactions, and prior hospitalization was significantly associated with HSV infection on dupilumab. Eight patients discontinued therapy due to an AE. Conclusion A small but significant number of patients experienced treatment difficulties while on dupilumab. The risk of inadequate response to dupilumab and dupilumab-associated AEs should be discussed thoroughly with patients and their families prior to initiation.
P163. Reduction of excitability in the left inferior frontal gyrus by cathodal tDCS facilitates emotion recognition

Facial emotion recognition (ER) is a prerequisite of successful social cognition and interaction (Haxby et al. 2002). The left inferior frontal gyrus (IFG) is critically involved in the neuronal network subserving ER (Dal Monte et al. 2014). Transcranial direct current stimulation (tDCS) can be used to modulate cortical excitability and associated behavioral functions in a polarity-specific and activity-dependent manner (Dayan et al. 2013; Wolkenstein et al. 2014; Wolkenstein and Plewnia 2013; Zwissler et al. 2014). The aim of this study was to show the facilitation of tDCS on ER. In a sham-controlled crossover design, excitability enhancing anodal and excitability decreasing cathodal tDCS of 1 mA (Exp. I) and 2 mA (Exp. II) were applied to the left IFG in 84 healthy subjects performing the ‘Reading the Mind in the Eyes’ (RME) test. The RME is widely used to measure ER in healthy subjects and psychiatric disorders (Baron-Cohen et al. 2001). In Exp. II, prior to the two (verum/sham) stimulation session, near infrared spectroscopy (NIRS) was applied to measure brain activity in the IFG during RME performance (Ehlis et al. 2014). With tDCS of 1 mA (Exp. I) no effects on RME performance were found. In Exp. II NIRS indicated a deactivation in the IFG during emotion recognition that was associated with faster responses. Consistently, cathodal, inhibitory tDCS of 2 mA clearly accelerated ER in the RME. Moreover, the change in response correctness induced by cathodal tDCS was positively correlated with the emotion-specific IFG activity measured with NIRS during RME performance. This is first evidence for a beneficial, state dependent effect of excitability-decreasing cathodal tDCS on ER. The correlation with individual imaging data supports the concept of a focusing effect of cathodal tDCS that reduces neuronal noise facilitating signal detection (Antal et al. 2004; Dockery et al. 2009; Miniussi et al. 2013).
Circadian variation in gene expression in the medulla of DOCA/salt hypertensive rats (1126.14)

Salt intake has been linked to changes in HSD2 expression in the medulla. Hypocretin (HCRT), neuropeptide FF(NPFF), and brain-derived neurotrophic factor (BDNF) have also been implicated in feeding...
Mutations within the proteolytic cleavage site of the Rous sarcoma virus glycoprotein define a requirement for dibasic residues for intracellular cleavage.

We investigated the amino acid sequence requirements for intracellular cleavage of the Rous sarcoma virus glycoprotein precursor by introducing mutations into the region encoding the cleavage recognition site (Arg-Arg-Lys-Arg). In addition to mutants G1 (Arg-Arg-Glu-Arg) and Dr1 (deletion of all four codons) that we have reported on previously (L. G. Perez and E. Hunter, J. Virol. 61:1609-1614, 1987), we constructed two additional mutants, AR1 (Arg-Arg-Arg-Arg), in which the highly conserved lysine is replaced by an arginine, and S19 (Ser-Arg-Glu-Arg), in which no dibasic pairs remain. The results of these studies demonstrate that when the cleavage sequence is deleted (Dr1) or modified to contain unpaired basic residues (S19), intracellular cleavage of the glycoprotein precursor is completely blocked. This demonstrates that the cellular endopeptidase responsible for cleavage has a stringent requirement for the presence of a pair of basic residues (Arg-Arg or Lys-Arg). Furthermore, it implies that the cleavage enzyme is not trypsinlike, since it is unable to recognize arginine residues that are sensitive to trypsin action. Substitution of the mutated genes into a replication-competent avian retrovirus genome showed that cleavage of the glycoprotein precursor was not required for incorporation into virions but was necessary for infectivity. Treatment of BH-RCAN-S19-transfected turkey cells with low levels of trypsin resulted in the release of infectious virus, demonstrating that exogenous cleavage could generate a biologically active glycoprotein molecule. Images
Sequential Pareto-Optimal Decisions Made During Emergent Complex Systems of Systems: An Application to the FAA NextGen

This article addresses the challenges facing participants, including stakeholders, decision makers, systems engineers, and risk analysts in modeling and managing the development of on-going emergent complex systems of systems S-o-S, with a focus on the centrality of the state variables and the time frame. More specifically, this article addresses the critical role that shared common states and decisions, and the time frame play in modeling the interconnectedness and interdependencies among the subsystems that constitute emergent S-o-S. The theoretical and methodological concepts are harmonized through their relevance to the ongoing emergent Federal Aviation Administration's FAA's Next Generation NextGen complex S-o-S project. Appropriate parts of the Dynamic Roadmap for risk modeling, assessment, management, and communication and their companion principles and guidelines, are used to guide the analyses. Moreover, decisions made at time t for one subsystem will subsequently change the states of that subsystem as well as affect other interconnected and interdependent subsystems that share states. This phenomenon is profoundly important even when the time frame of the affected states is measured in months or years, as is the case in the application discussed in this article. The centrality of the time frame in decision making is even more important when the impact of current decisions on future options affect not only the intended subsystem, but can also inadvertently affect other subsystems in the future. A Flowchart relates the S-o-S-based theory and methodology to the FAA's NextGen complex S-o-S project.
Origins of Programmable Nucleases for Genome Engineering

Genome engineering with programmable nucleases depends on cellular responses to a targeted double-strand break (DSB). The first truly targetable reagents were the zinc finger nucleases (ZFNs) showing that arbitrary DNA sequences could be addressed for cleavage by protein engineering, ushering in the breakthrough in genome manipulation. ZFNs resulted from basic research on zinc finger proteins and the FokI restriction enzyme (which revealed a bipartite structure with a separable DNA-binding domain and a non-specific cleavage domain). Studies on the mechanism of cleavage by 3-finger ZFNs established that the preferred substrates were paired binding sites, which doubled the size of the target sequence recognition from 9 to 18bp, long enough to specify a unique genomic locus in plant and mammalian cells. Soon afterwards, a ZFN-induced DSB was shown to stimulate homologous recombination in cells. Transcription activator-like effector nucleases (TALENs) that are based on bacterial TALEs fused to the FokI cleavage domain expanded this capability. The fact that ZFNs and TALENs have been used for genome modification of more than 40 different organisms and cell types attests to the success of protein engineering. The most recent technology platform for delivering a targeted DSB to cellular genomes is that of the RNA-guided nucleases, which are based on the naturally occurring Type II prokaryotic CRISPR-Cas9 system. Unlike ZFNs and TALENs that use protein motifs for DNA sequence recognition, CRISPR-Cas9 depends on RNA-DNA recognition. The advantages of the CRISPR-Cas9 system-the ease of RNA design for new targets and the dependence on a single, constant Cas9 protein-have led to its wide adoption by research laboratories around the world. These technology platforms have equipped scientists with an unprecedented ability to modify cells and organisms almost at will, with wide-ranging implications across biology and medicine. However, these nucleases have also been shown to cut at off-target sites with mutagenic consequences. Therefore, issues such as efficacy, specificity and delivery are likely to drive selection of reagents for particular purposes. Human therapeutic applications of these technologies will ultimately depend on risk versus benefit analysis and informed consent.
Biosynthesis of branched-chain amino acids in yeast: regulation of leucine biosynthesis in prototrophic and leucine auxotrophic strains.

The first enzyme in the biosynthesis of leucine in yeast, α-isopropylmalate synthetase, is inhibited by l-leucine. In a mutant resistant to the analogue 5′,5′,5′-trifluoroleucine, the enzyme is markedly resistant to inhibition by l-leucine. Growth ing the presence of exogenous l-leucine results in repression of the second and third enzymes of the pathway. The first enzyme is not repressed unless both l-leucine and l-threonine are supplied in the medium. Comparison of levels of the remaining two enzymes in leucine auxotrophs grown under conditions of leucine excess and leucine limitation reveals deviations from the wild-type derepression pattern in some mutants. In some, repression of the synthetase by leucine alone was observed. In others, the repressibility of the dehydrogenase was lost. It is unlikely that these deviations were due to the same primary mutational event that caused leucine auxotrophy. No mutants were found in which an altered gene was recognized to be clearly responsible for the level of the leucine-forming enzymes.