cssi/SciSciGPT-SciSciNet huggingface dataset:
Wind-driven mixing causes a reduction in the strength of the continental shelf carbon pump in the Chukchi Sea

[1] The Chukchi Sea is thought to be a globally important sink of atmospheric CO2 due to the summertime drawdown of surface pCO2 by phytoplankton and subsequent shelf-to-basin transport of CO2-enriched subsurface waters into the upper halocline of the Arctic Ocean. Here we show that annually occurring storm-induced mixing events during autumn months disrupt water column stratification and stir up remineralized carbon from subsurface waters to the surface, leading to CO2 outgassing to the atmosphere. Our analysis provides a new understanding of the dynamics of carbon cycling in the region and suggests that late season wind events are strong and frequent enough to significantly decrease the carbon sink strength of the Chukchi Sea on a scale of relevance to the global carbon cycle. These results highlight the importance of obtaining data with more complete seasonal and spatial coverage in order to accurately constrain regional to basin-scale carbon flux budgets.
Angiotensin stimulation of vasopressin release from the rat hypothalamo-neurohypophyseal system in organ culture.

Organ cultured hypothalamo-neurohypophyseal (HNS) explants from rats were maintained in vitro for up to 9 days. These explants contain the supraoptic nucleus with its vasopressin (AVP)- producing neurons, their axonal projections through the median eminence and axon terminals in the neurohypophysis. The presence of cells containing AVP was confirmed in 5 day cultured explants irnmunocytochemically. The rate of AVP release by the HNS explants remained constant over 9 days in culture. However, due to simultaneous degradation of AVP by enzymes released into the culture medium by the explant, it was necessary to develop a sampling protocol which allowed simultaneous estimation of AVP release and degradation. Utilizing this protocol, the rate of AVP release by the cultured HNS was 309 ± 32 pg\h\explant on day 3 in culture. This rate remained essentially unchanged during the subsequent 2 days in culture. This rate of hormone release corresponds closely with other in vivo and in vitro measures of AVP secretion. ...
Comparative Analysis of GPCR Crystal Structures

The phototransduction cascade is perhaps the best understood model system for G protein-coupled receptor (GPCR) signaling. Phototransduction links the absorption of a single photon of light to a decrease in cytosolic cGMP. Depletion of the cGMP pool induces closure of cGMP-gated cation channels resulting in the hyperpolarization of photoreceptor cells and consequently a neuronal response. Many biochemical and both low- and high-resolution structural approaches have been utilized to increase our understanding of rhodopsin, the key molecule of this signaling cascade. Rhodopsin, a member of the GPCR or seven-transmembrane spanning receptor superfamily, is composed of a chromophore, 11-cis-retinal that is covalently bound by a protonated Schiff base linkage to the apo-protein opsin at Lys(296) (in bovine opsin). Upon absorption of a photon, isomerization of the chromophore to an all-trans-retinylidene conformation induces changes in the rhodopsin structure, ultimately converting it from an inactive to an activated state. This state allows it to activate the heterotrimeric G protein, transducin, by triggering nucleotide exchange. To fully understand the structural and functional aspects of rhodopsin it is necessary to critically examine crystal structures of its different photointermediates. In this review we summarize recent progress on the structure and activation of rhodopsin in the context of other GPCR structures.
Stability boundary analysis of nonlinear dynamics subject to state limits

In the spirit of Morse-Smale systems, the paper analyzes the structure of stability boundary of a stable equilibrium point for nonlinear dynamics subject to state limits. Presence of state limits implies that the underlying dynamics does not satisfy the Lipschitz condition for solution existence/uniqueness. There does not exist a smooth flow for the dynamics thus complicating traditional analysis of stability boundary. By analyzing geometric properties of the solutions of the constrained dynamics, the paper establishes a characterization of the stability boundary under rather strong assumptions as a first step towards detailed boundary characterization.
The relative order of mKATP channels, free radicals and p38 MAPK in preconditioning's protective pathway in rat heart

Objectives: Ischemic preconditioning (PC) reduces myocardial infarction by a mechanism that involves opening of mitochondrial ATP-dependent potassium channels (mKATP), reactive oxygen species (ROS), and possibly activation of p38 mitogen-activated protein kinase (p38 MAPK). The actual order of these steps, however, is a matter of current debate. This study examined whether protection afforded by menadione, which protects by causing mitochondria to produce ROS, requires mKATP opening. In addition, we tested whether protection from anisomycin, a p38 MAPK activator, is dependent on ROS production. Methods and Results: Isolated, buffer-perfused rat hearts were pretreated with menadione, and infarction was assessed after 30 min of regional ischemia and 120 min of reperfusion. Menadione reduced infarction in a dose-dependent manner with an EC50 of 270 nM. Menadione's infarct-limiting effect was insensitive to 200 μM 5-hydroxydecanoate (5HD), an mKATP channel blocker, whereas protection by diazoxide and PC were blocked by 5HD. Anisomycin caused hearts to resist infarction and this protective effect was abrogated by SB203580, a p38 MAPK inhibitor, and 2-mercaptopropionylglycine (MPG), a free radical scavenger. Conclusions: These results indicate that mKATP opening occurs upstream of mitochondrial ROS generation in the protective pathway. Furthermore, protection afforded by anisomycin was p38 MAPK- and ROS-dependent.
Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen.

The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.
Reducing Risks to Women Linked to Shift Work, Long Work Hours, and Related Workplace Sleep and Fatigue Issues

In the United States, an estimated 12% to 28% of working women are on shift work schedules, and 12% work more than 48 hours per week. Shift work and long work hours are associated with many health and safety risks, including obesity, injuries, and negative reproductive outcomes. Over time, the worker is at risk for developing a wide range of chronic diseases. These work schedules can also strain personal relationships, owing to fatigue and poor mood from sleep deprivation and reduced quality time to spend with family and friends. Worker errors from fatigue can lead to reduced quality of goods and services, negatively impacting the employer. In addition, mistakes by fatigued workers can have far-reaching negative effects on the community, ranging from medical care errors to motor vehicle crashes and industrial disasters that endanger others. To reduce the many risks that are linked to these demanding work hours, the National Institute for Occupational Safety and Health (NIOSH) conducts research, develops guidance and authoritative recommendations, and translates and disseminates scientific information to protect workers, their families, employers, and the community. The key message to reduce these risks is making sleep a priority in the employer's systems for organizing work and in the worker's personal life. The NIOSH website has freely available online training programs with suggestions for workers and their managers to help them better cope with this workplace hazard.
Sol-gel synthesis of high-quality heavy-metal fluoride glasses

Fluoride glasses are excellent laser hosts and are very well suited for a broad spectrum of optical applications. However, current fluoride glass synthesis is expensive. The sol-gel method is an affordable alternative for producing high-performance, optical-quality heavy-metal fluoride glasses. The method involves forming a hydrous oxide gel of the constituent metal alkoxides and salts, polymerizing the solution to form a gel, fluorinating the gel with anhydrous HF, melting the amorphous material in an oxidizing atmosphere of SF[sub 6], and casting the melt into desired shapes. ZBLA (57ZrF[sub 4] [times] 36BaF[sub 2] [times] 4LaF[sub 3] [times] 3AlF[sub 3], in mol%) and Nd-doped (0.3 mol%) ZBLA glass rods were prepared by this process and their properties were measured. The sol-gel-based glasses had thermal and optical properties similar to those found in the literature for conventionally prepared fluorides.
The task of the referee

Computer researchers have a professional obligation to referee the work of others. This article tells you how to evaluate a paper and write a report using common standards and procedures. It focuses on research papers in applied areas of computer science and engineering, such as systems architecture, hardware, communications, and performance evaluation, but most of the discussion is generally applicable; separate sections consider research proposals and survey and tutorial papers. >
Readout electronics and data acquisition system of the MicroBooNE experiment

MicroBooNE is a proposed Liquid Argon Time Projection Chamber (TPC) detector that will observe interactions of neutrinos from the on-axis Booster Neutrino Beam and off-axis NuMI Beam at Fermi National Accelerator Laboratory.
Automatically Scalable Computation

As our computational infrastructure races gracefully forward into increasingly parallel multi-core and clustered systems, our ability to easily produce software that can successfully exploit such systems continues to stumble. For years, we've fantasized about the world in which we'd write simple, sequential programs, add magic sauce, and suddenly have scalable, parallel executions. We're not there. We're not even close. I'll present a radical, potentially crazy approach to automatic scalability, combining learning, prediction, and speculation. To date, we've achieved surprisingly good speedup in limited domains, but the potential is tantalizingly enormous.
Residual Gas Phase Contamination of Al-Cu Alloy Films and its Effect on Electromigration Behavior

The major sources of impurities in sputtered Al alloy films for interconnects, prepared by physical vapor deposition include those originating from the target material, residual gases present in the vacuum system, and those introduced through the gas delivery system. In this study, we report the effect of impurities incorporated from residual gases present in vacuum systems on the electromigration performance of 0.6 μm wide Al-l%Cu lines. Controlled leaks of isotope gases H2O18, N215, O218, and C13H4, in 10−6 - 10−9 Torr range, were introduced into a PVD tool during the sputtering process. Using these isotope gases, the impurities originating from residual gases were distinguished from those originating from other sources of impurities. The sputtering target was found to be the major source of Η and Ο impurities in the film, whereas Ν atoms are introduced in the film mainly through the gas phase. Furthermore, Ν atoms in the film were found to affect its electromigration behaviour to a larger extent than Ο and H.
Effects of Fat on Blood Viscosity in Dogs

Intravenous fat injections cause significant increases in blood viscosity. Nonemulsified or poorly emulsified oil produces pulmonary and other embolization. Plasma is lost rapidly and in alarming degree. The hematocrit increases rapidly and is accompanied by a nearly parallel increase in blood viscosity. Oil in stable emulsion in blood plasma or lymph can be injected in greater doses. Slow, but significant increases in the blood viscosity develop to maximum in 10 to 24 hours. Varying degrees of paralysis follow. The loss of plasma is not so marked, and increase in hematocrit is not sufficient to account for increase in viscosity.
Use of dietary supplements containing 1,3 dimethylamylamine by military personnel

Dietary supplement (DS) manufacturers have incorporated sympathomimetic ingredients, including 1,3 dimethylamylamine (DMAA), into body building and weight-loss DS products. Bodybuilding DS are cons...
Diffusion of flexible and semirigid polymers confined to the pore spaces in porous glass

The dynamics of polymer chains in solution within the pore spaces of controlled pore glasses has been studied experimentally by using dynamic light scattering and theoretically by computer simulation. For flexible chains, we have explored the dependence of diffusion on the degree of confinement (i.e. on molecular weight or on R h/R p where R h is the polymer hydrodynamic radius in free solution and R p is the glass pore radius), molecular architecture, and time or distance scale of the diffusion measurement. Flexible chain diffusion over macroscopic distances may be understood in terms of hydrodynamic interactions with the pore wall at low and intermediate confinement, and in terms of an entropic barrier model at strong confinement. At intermediate scattering wavevector (q R p≅1) the apparent diffusion coefficient is time-dependent, and exhibits a crossover from the free-solution value at short times to a smaller macroscopic (hindered) diffusion coefficient value at later times. Semirigid chains experience much stronger hindrance than flexible chains. We have developed a model of the dynamics based on reptation theory. The mean squared displacement of a sufficiently long chain is expected to display a power law time dependence; the exponent depends on the time, changing from approximately 1/4 at short times t o1 at long times. Diffusion measurements of a series of poly(hexylisocyanate) polymers in porous silica display a definite crossover to much slower hindered diffusion at higher molecular weight.
Ethical Considerations in Providing Mental Health Services Over Videoteleconferencing

As technology and the modes of service in mental health change, so do the ethical challenges. The innovations have great potential to help patients struggling with mental health concerns, but they also bring new professional responsibilities in balancing complex benefits and risks. In this chapter, the authors will address the general principles guiding the telemental health ethics discussion that encompass privacy, the altered relationship of the client and professional, access to care, and other issues unique to this setting. A telemental health case example will also be used to illustrate how to translate key ethical principles to the videoteleconferencing (VTC) setting. The authors emphasize that the safety of the client remains paramount across existing and emerging VTC technologies.
Could gut microbiota be the culprit

Pulmonary complications are among the most common causes of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HCT). Although there are several established post-HCT pulmonary complications, little is known about the factors predisposing HCT patients to developing lung pathology. Harris and colleagues set out to investigate the relationship between the bacterial composition of the gut and the development of post-HCT pulmonary complications by conducting an observational study of HCT patients at a single transplant center. The investigators recruited 94 HCT patients previously enrolled in a study involving the genetic sequencing of the gut microbiota and reviewed data for 40 months post-HCT looking for pulmonary complications. The study group defined “pulmonary complications” as any new pulmonary infiltrate on chest imaging in the setting of respiratory complaints or abnormal vital signs. In total, 112 post-HCT pulmonary events were documented in 66 (70.2%) of the 94 HCT patients recruited. Analysis of the gut microbiota data revealed that individuals with a gut microbiota that was dominated by γ-Proteobacteria were more likely to develop post-HCT pulmonary complications and showed a trend towards significance for mortality. Based on these results, the investigators concluded that a relationship exists between the gut microbiota and post-HCT pulmonary complications. The limitations of this study include the fact that the gut microbiome was analyzed after admission for the transplant but prior to the development of the pulmonary pathology, thus making the link between the gut microbiome and lung pathology less convincing. Also, the broad definition used to identify cases with post-HCT pulmonary complications potentially biased the study’s conclusions. In addition, the study group consisted of a relatively small sample of individuals from a single institution, limiting the generalizability of the data. B. Harris et al. , Gut microbiota predict pulmonary infiltrates after allogeneic hematopoietic cell transplantation. Am. J. Respir. Crit. Care Med. 10.1164/rccm.201507-1491OC (2016). [[Abstract]][1] [1]: http://www.atsjournals.org/doi/abs/10.1164/rccm.201507-1491OC#.Vs3hO2_2Zjo
Securing Big Data in our Future Intelligent Cities

Future Intelligent Cities, or Smart Cities, represent an opportunity to enable growth, prosperity, employment, education and greater social welfare through a combination of careful planning, connected communities, educated citizens and clever technology. In the creation of an intelligent city we also create vast amounts of data, but collecting Big Data poses security risks which if left unaddressed will leave everyone exposed to potential cyber crime or misuse of data. This paper looks at how we might secure this data from cyber criminals or malicious attack and how we can balance that data security with the open access required to enable a truly Smart City.
PALEOECOLOGICAL SUCCESSION OF NORIAN (LATE TRIASSIC) BENTHIC FAUNA IN EASTERN PANTHALASSA (LUNING AND GABBS FORMATIONS, WEST-CENTRAL NEVADA)

The Norian Stage of the Late Triassic represents a long interval from which the benthic faunal succession is poorly understood, particularly from eastern Panthalassa. Fossiliferous bulk samples of shallow marine carbonates were collected from the Luning and Gabbs formations in west-central Nevada to evaluate the changes in faunal composition and paleoecological structure during the Norian Stage. Stationary epifauna dominated the early Norian faunal assemblages but gradually became less common by the late Norian, with the exception of cementing bivalves, which were common in the middle and late Norian. After the early Norian, mobile infauna also became increasingly abundant and diverse. These paleoecological trends are similar to those observed in Tethyan level-bottom carbonate deposits from the Lombardian Basin in northern Italy. Reclining epifauna remained uncommon in the local area until the Early Jurassic, and this Mesozoic decline in recliners preceded the end-Triassic mass extinction in Nevada.
The clinical observation to extraction of impacted maxillary teeth on palate side after artificial eruption

Objective To explore the easy way of extraction for impacted maxillary teeth on palate side.Methods Ten impacted maxillary teeth are extracted after surgical-orthodontic treatment on palate side.Results Ten impacted maxillary teeth were extracted successfully.The time for orthodontics was 3.5months.The time for extraction was 27.1min.There was no untoward reaction after extraction.Conclusion The way is easy and advisable to apply surgical-orthodontic extraction for impacted maxillary teeth on palate side.
Research on Design Methods of Products Based on ADSM

With the constant progress of technology,the updating of products expedites year by year,causes the recycle of waste products catching more and more attention. A main factor that restricts the recycle of products is the low efficiency and high costs in disassembling the waste products. One of solutions is active disassembly using smart materials (ADSM). The elements and characteristics of ADSM are introduced,and the design methods of products based on ADSM and the design rules of active disassembly devices and active disassembly products are put forward. Based on these design methods and rules,some remote controls are redesigned. The active disassembly experiments of redesigned remotes show that the disassembly efficiency is obviously enhanced,which proves the feasibility and advantage of design methods based on ADSM.
Abstract A20: Increasing information-seeking about HPV and HPV vaccine among Hispanics in the Lower Rio Grande Valley

The purpose of the Vivir Sin Cancer study is to develop and test materials to increase calls to the Cancer Information Service (CIS) about the HPV vaccine and cervical cancer among Hispanics. In depth interviews were conducted with CIS community partners and focus groups were conducted with Hispanic parents and young women 18–26 to determine factors influencing HPV vaccine acceptability as well as factors related to information seeking about HPV and HPV vaccine. The formative assessment also explored the cultural relevance of test messages and images. Findings for parents showed a lack of knowledge of HPV, the HPV vaccine and cervical cancer, negative attitudes about HPV vaccine, and lack of perceived risk for cervical cancer and HPV (for daughter). Results from the groups conducted with young women indicated lack of awareness of HPV, the HPV vaccine and cervical cancer, lack of perceived risk for cervical cancer and HPV, and perceived barriers to the HPV vaccine including a concern about vaccine affecting future fertility. In general both parents and young women were not familiar with the CIS. Those who were did not think the information provided by CIS would be relevant to them since they were not cancer patients. Findings from the formative phase were used to develop the program materials that were delivered in communities through lay health workers and in clinics. Materials included: (1) PowerPoint fotonovela (photo stills and video embedded), (2) fotonovela booklet, (3) questions cards and (4) a video for Hispanic parents and young women. Preliminary study findings indicate that after 6 months of program implementation, calls to CIS increased by 63% in the intervention community (Lower Rio Grande Valley) and decreased (by 41%) in the comparison community (El Paso). Calls among Hispanics also increased in the LRGV. Final study findings will be presented.
Particle morphology, composition and associated ice chemistry of tephra layers in the Byrd ice core: evidence for hydrovolcanic eruptions

In 1968 an ice core 2164 m long was recovered from Byrd station in West Antarctica. About 2000 tephra layers were observed in the core and have been differentiated into ash and dust bands according to the grain size and concentration of particles in the layers. Mount Takahe, a local volcano in Marie Byrd Land, Antarctica is the probable source. Detailed examinations of the particle morphology, composition and ice chemistry associated with some of the tephra layers have led to the conclusion that the eruptions which produced the layers were probably hydrovolcanic. Melted glacier ice is considered the most likely source of the water involved in the eruptions. Processes associated with hydrovolcanism such as particle aggregation (causing premature deposition of fine particles), rapid conversion of sulfur dioxide to sulfuric acid (in the presence of abundant moisture) and scavenging of acid droplets by the fine dust particles are inferred to have taken place. Such processes would greatly reduce the atmospheric residence time of the eruptive products and thus their atmospheric and climatic impact.
Conversion of Furfural to 1,5-Pentanediol: Process Synthesis and Analysis

A new process for the production of 1,5-pentanediol (1,5-PDO) from biomass-derived furfural is studied. In this process, furfural is converted to 1,5-PDO in a high overall yield (80%) over inexpensive catalysts via multiple steps involving hydrogenation, dehydration, hydration, and hydrogenation subsequently. To effectively recycle H2 as well as recover 1,5-PDO, detailed separation subsystems have been designed and integrated with reaction subsystems. Furthermore, a pioneer plant analysis is performed to estimate the risk on the cost growth and plant performance shortfalls. The integrated process leads to a minimum selling price of $1973 ton–1 for 1,5-PDO, which suggests that it could be a promising approach for converting biomass into oxygenated commodity chemicals, which are difficult to produce from petroleum-derived feedstocks. The sensitivity analysis also identifies that the most important economic parameters for the process include the furfural feedstock price and plant size.
Diagnosis and Screening for Pancreatic Malignancy

This chapter uses a case of painless jaundice resulting in the diagnosis of a pancreatic malignancy to discuss current evidence behind the most common presentation, diagnosis, and potential screening and management. Currently, surgical resection is the only treatment that improves the 5-year survival rate. Screening with CA 19-9 and CEA is not currently recommended, though they may be used to monitor tumor progression after diagnosis. The most appropriate imaging includes CT and EUS with FNA for tissue diagnosis. Without any current recommendations for preventative screening, pancreatic cancer remains difficult to detect early.
A Light-Field Journey to Virtual Reality

Producing ultra-high-quality content is the next grand challenge for the VR industry. Creating a virtual reality that even the human eye cannot distinguish from the real world will require light-field technology--3D imaging technology that captures the light rays people perceive from different locations and directions. When combined with computer vision and machine learning, light-field technology provides a viable path for producing low-cost, high-quality VR content.
A note on a theorem of Cadoret and Tamagawa

We prove Cadoret and Tamagawa’s open image theorem for curves defined over number fields using their arguments and the machinery of Ellenberg–Hall–Kowalski employed in their paper on expander graphs.
Designing cyber-physical systems from natural language descriptions

We present an approach to allow a non-programmer develop simple cyber-physical systems using natural language text to specify the system behavior. Users specify the relationship between sensor inputs and actuator outputs through a series of conditional sentences written in English. The relationships are used to generate code for an Arduino development platform and to produce a netlist connecting the Arduino UNO pins to sensors and actuators. Our current approach supports only combinational relationships between sensors and actuators, but we intend to extend the approach to sequential systems in the future.
Warriors or bulls: introducing retroactive gambling line simulation

Gambling lines provide a rich source of data for Monte Carlo simulations of sports seasons. Since data for complete seasons are available after the seasons are completed, we refer to such simulations as retroactive gambling line simulations. We use the motivating and expository example of comparing the performances of the 2015-16 Golden State Warriors (who won a record 73 games) and the 1995-96 Chicago Bulls (who held the previous record of 72 wins) and provide a detailed treatment of this application. The more general applicability of the approach is examined by describing the flexibility in building the models and relating this flexibility to a few specific examples. We hope this paper will seed further explorations of retroactive gambling line simulation (and settle the Warriors vs. Bulls comparison along the way).
The impact of posttraumatic stress symptoms on social support and social conflict during hematopoietic stem cell transplant.

Purpose/Objectives: Social support and its relationship to psychological distress are of interest in hematopoietic stem cell transplant (HSCT) as patients are dependent on caregivers pre-, during, ...
The Impact of Raw Materials Price Volatility on Cost of Goods Sold (COGS) for Product Manufacturing

The supply chain ecosystem has become increasingly volatile due to a host of different factors. In an unpredictable environment, the factors influencing decision-making fluctuate constantly over time, and the effect of volatility on supply chain parameters such as cost, revenue, and working capital must be evaluated periodically. This paper seeks to develop a set of mathematical programming models for exploring the impact of price fluctuation of raw materials on the cost of goods sold (COGS) of end products relative to targets in manufacturing companies. The mathematical programming problems proposed in this paper rationally minimize the COGS of end products while satisfying a set of constraints regarding forecasting and physical conditions. The optimal solutions of the proposed models provide guidelines on the optimal price at which to purchase all raw materials, leading to the minimum the overall COGS value for the enterprise. We also introduce a special type of sensitivity analysis, in which we explore the conditions where the optimal purchasing price of a raw material used to manufacture an end product changes within its feasibility range, and the relative effect on how much the minimum COGS of end products fluctuates. Finally, an empirical example presented in this paper illustrates the practicality and usefulness of the proposed approach in practice.
On the theory of drainage area for regular and non-regular points.

The drainage area is an important, non-local property of a landscape, which controls surface and subsurface hydrological fluxes. Its role in numerous ecohydrological and geomorphological applicatio...
The current state of GPCR‐based drug discovery to treat metabolic disease

One approach of modern drug discovery is to identify agents that enhance or diminish signal transduction cascades in various cell types and tissues by modulating the activity of GPCRs. This strategy has resulted in the development of new medicines to treat many conditions, including cardiovascular disease, psychiatric disorders, HIV/AIDS, certain forms of cancer and Type 2 diabetes mellitus (T2DM). These successes justify further pursuit of GPCRs as disease targets and provide key learning that should help guide identifying future therapeutic agents. This report reviews the current landscape of GPCR drug discovery with emphasis on efforts aimed at developing new molecules for treating T2DM and obesity. We analyse historical efforts to generate GPCR-based drugs to treat metabolic disease in terms of causal factors leading to success and failure in this endeavour. Linked articles This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
Electronic Pink Book — Business Case

The original Pink Book (1991) was produced in hard copy form and was intended to provide a communication link between the West Suffolk Hospitals NHS Trust and General Practioners. Unfortunatley it was not revised and became out of date.
Reducing Ambiguity: Tools to Define and Communicate Paraprofessional Roles and Responsibilities:

One-on-one and program-based special education paraprofessionals are often used to support students with disabilities across school settings. While paraprofessionals may have the best of intentions...
Marker-free monitoring of the grandstand structures and modal identification using computer vision methods:

In this study, a vision-based multi-point structural dynamic monitoring framework is proposed. This framework aims to solve issues in current vision-based structural health monitoring. Limitations ...
Privatization and Firm Performance: a Study of Indonesia’s State-owned Enterprises

This study aimed to examine the differences in the company’s performance before and after privatization. This study also examined the differences in performance before and after privatization on specific sub-samples of the data which is based on privatization method. Government policy of carrying out the privatization toward SOEs is still pro and contra. Various Privatization methods offer its weaknesses and strengths. There are different opinions on the best method for SOE privatization in Indonesia. The population is all companies which execute the privatization method. Secondary data were used namely financial statement which was taken from the Indonesia Stock Exchange, and the company’s website. Data were analyzed using normality test data. In addition, the paired t-test by using normally distributed data assumption was used to test the hypothesis. The results showed that Direct method privatization positive and significant changes in measuring Total Asset Turnover. Performance conducted Privatization through the capital markets showed different results. Test on the capital market method of data showed a similar effect with an analysis on the entire data (without separating the privatization method used) that occur significant performance degradation, especially in measuring Total Asset Turnover, Debt Ratio and Return On Equity. Conducted Management/ Employee Buy-Out (MBO) privatization implied a substantial reduction in measuring Debt Ratio and Return on Equity Performance.
Asymmetric clustering of centrosomes defines the early evolution of tetraploid cells

Tetraploidy has long been of interest to both cell and cancer biologists, partly because of its documented role in tumorigenesis. A common model proposes that the extra centrosomes that are typically acquired during tetraploidization are responsible for driving tumorigenesis. However, this model is inconsistent with the observation that tetraploid cells evolved in culture lack extra centrosomes. This observation raises questions about how tetraploid cells evolve and more specifically about the mechanisms(s) underlying centrosome loss. Here, using a combination of fixed cell analysis, live cell imaging, and mathematical modeling, we show that populations of newly formed tetraploid cells rapidly evolve in vitro to retain a near-tetraploid chromosome number while losing the extra centrosomes gained at the time of tetraploidization. This happens through a process of natural selection in which tetraploid cells that inherit a single centrosome during a bipolar division with asymmetric centrosome clustering are favored for long-term survival.
Abstract WP45: Subarachnoid Hemorrhage After Mechanical Thrombectomy With a Direct Aspiration First Pass Technique

Introduction: The incidence and clinical significance of subarachnoid hemorrhage post mechanical thrombectomy (MT) has been evaluated after stent retriever use in limited studies. The goal of this ...
Towards understanding pressure ulcer formation: Coupling an inflammation regulatory network to a tissue scale finite element model

Abstract Pressure ulcers (PUs) are a major clinical concern affecting more than 2.5 million adults annually in the US. Ischemia is recognized as one of the most important contributors to ulcer formation, triggering a sterile inflammatory cascade that culminates in necrosis of native skin cells and ulceration. While there is a general understanding of the biological elements involved in this process and their interdependence within the biological PU signaling network, this system’s spatio-temporal dynamics have not yet been studied in detail. Here we first present a 0D mathematical description of the PU regulatory network consisting of two cell types – keratinocytes and neutrophils- and six chemical species – TNFα, KC, ROS, DAMPs, O2 and XO. We extend this regulatory network from a set of ordinary differential equations to realistic spatial domains by coupling each species’ dynamic equations to reaction diffusion partial differential equations. Furthermore, we couple this model to mechanical deformation of the spatial domain by including a pressure-sensitive oxygen perfusion term. The total model provides solutions to the regulatory network dynamics at the tissue scale with spatio-temporal detail on the evolution of each species. Among other features, the model correctly predicts patterns of PU formation in response to moderate loads, as seen clinically and experimentally. In conclusion, this work extends our current PU modeling capabilities and improves our understanding of PUs by carefully analyzing the motifs of the regulatory network and by exploring the implications of coupling this system to a tissue scale model of skin mechanics and oxygen perfusion.
An Efficient and Affordable Web-based Prototyping and Testing Platform for Analog Sensors

In the Internet of Things (loT) era, technology offers the ability to collect and understand information collected from the nature and environment around us. As an essential component of reliable sensing, sensors play a vital role in any IoT system. The point of departure for our work is the anticipated potential of an efficient, low-cost prototyping and testing platform for analog sensors. In this paper, we explore the fundamental building blocks of such a system: an accurate, configurable analog front end, a light-weight communication component, and efficient data-centric middleware, and a user-friendly web portal.
The Use of Fresh Frozen Soft Tissue Allografts in Knee Ligament Surgery

The use of soft tissue allografts in knee ligament reconstruction has an important role in the surgical treatment of patients in the field of sports medicine. Currently, the most common uses for soft tissue allografts involve isolated anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction, revision ACL and PCL reconstruction, medial collateral ligament augmentation, lateral collateral ligament augmentation, and combined ligamentous injuries of the knee. This chapter will highlight the current basic science, clinical knowledge, and controversies regarding the use of fresh frozen allograft tissues. In addition, we report the results of our early clinical experience using fresh frozen shft tissue allografts in knee ligament reconstruction. We will be focussing our attention on fresh frozen allografts as this has been our preferred allograft of choice since 1985. The use of freeze-dried allografts will only be mentioned briefly in this chapter.
Muslim women and White femininity: reenactment and resistance

Haneen Shafeeq Ghabra’s book, Muslim Women and White Femininity: Reenactment and Resistance, serves to interrogate the internal performative tensions Muslim feminists must navigate in their pursuit...
Thermospheric Heating and Cooling Times During Geomagnetic Storms, Including Extreme Events

We present the first quantitative calculations of thermospheric heating and cooling times for geomagnetic storms of different intensity, including extreme events. We utilize the neutral mass density database of the CHAllenging Mini‐satellite Payload and Gravity Recovery And Climate Experiment missions to produce thermospheric global system response to geomagnetic storms caused by coronal mass ejections via superposed epoch analysis during May 2001 to December 2015. Storm events are grouped in five different categories based on the minimum value of the SYM‐H index. We calculate the time from storm onset for the thermosphere to reach maximum intensification (heating time) and the time from onset for the thermosphere to recover (cooling time). We find that heating and cooling times decrease as storm intensity increases and the effect is more pronounced for the cooling times. For extreme storms, the thermospheric heating time is 9.5 hr, while the cooling time is 22 hr.
Right in our Own Backyard

Abstract A 3-year-old male presented to the emergency department with two episodes of abdominal pain, 1 week apart. His evaluation was unrevealing, but he was admitted for continued bouts of severe, intermittent abdominal pain. Further history obtained the day after admission revealed the cause of his symptoms and the ultimate diagnosis.
A digital twin feasibility study (Part I): Non-deterministic predictions of fatigue life in aluminum alloy 7075-T651 using a microstructure-based multi-scale model

Abstract The Digital Twin (DT) concept has the potential to revolutionize the way systems and their components are designed, managed, maintained, and operated across a vast number of fields from engineering to healthcare. The focus of this work is the implementation of DT for the health management of fatigue critical structures. This paper is the first part of a two-part series. The second part focuses on the use of in-situ diagnostics to reduce uncertainty in fatigue life predictions once a life-limiting fatigue crack has reached the point where it is observable. In contrast, the focus of this work is to form a non-deterministic prediction of fatigue life prior to the accumulation of observable damage, a condition that often dominates the majority of a component or system’s lifetime. This predictive capability is enabled by a DT framework that simulates crack growth from initiation to failure using microstructure-based, multi-scale modeling. Two models are used in this work, one that incorporates microstructure explicitly and one that uses more traditional linear elastic fracture mechanics. The models are joined by a transition crack length between the micro- and macroscales, which facilitates both the coupling of fatigue life predictions and the transference of uncertainty across scales. The ability to predict fatigue life under uncertainty and across scales is demonstrated in the context of a geometrically complex, metallic test specimen subjected to uniaxial fatigue loading. Conclusions are drawn regarding the feasibility of the approach as a DT-based health management method.
Fibonacci numbers and Ford circles

An amusing connection between Ford circles, Fibonacci numbers, and golden ratio is shown. Namely, certain tangency points of Ford circles are concyclic and involve Fibonacci numbers. They form four circles that cut the x-axis at points related to the golden ratio.
EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer

EGFR inhibition is an effective treatment in the minority of non-small cell lung cancer (NSCLC) cases harboring EGFR-activating mutations, but not in EGFR wild type (EGFRwt) tumors. Here, we demonstrate that EGFR inhibition triggers an antiviral defense pathway in NSCLC. Inhibiting mutant EGFR triggers Type I IFN-I upregulation via a RIG-I-TBK1-IRF3 pathway. The ubiquitin ligase TRIM32 associates with TBK1 upon EGFR inhibition, and is required for K63-linked ubiquitination and TBK1 activation. Inhibiting EGFRwt upregulates interferons via an NF-κB-dependent pathway. Inhibition of IFN signaling enhances EGFR-TKI sensitivity in EGFR mutant NSCLC and renders EGFRwt/KRAS mutant NSCLC sensitive to EGFR inhibition in xenograft and immunocompetent mouse models. Furthermore, NSCLC tumors with decreased IFN-I expression are more responsive to EGFR TKI treatment. We propose that IFN-I signaling is a major determinant of EGFR-TKI sensitivity in NSCLC and that a combination of EGFR TKI plus IFN-neutralizing antibody could be useful in most NSCLC patients.
Abstract PO088: Sensitivity of cancer cells to oncolytic viruses is defined by IWS1 phosphorylation dependent epigenetic regulation of U2AF2 splicing and nucleocytoplasmic export of type I IFN transcripts

We have previously shown that loss of IWS1 phosphorylation promotes the alternative RNA splicing of U2 Associated-Factor 2 (U2AF2), resulting in transcripts lacking exon 2. This exon encodes part of the Serine-Rich (SR) domain of U2AF65, which is responsible for its binding with pre-mRNA Processing Factor 19 (Prp19). Here, we show that whereas both U2AF65 isoforms bind cytoplasmic accumulation response elements (CAR-E) of intronless mRNAs, the loading of Prp19 occurs only in exon 2-containing U2AF65, in cells expressing phosphorylated IWS1, promoting their nucleocytoplasmic export. Furthermore, this Prp19 loading is RNA Pol II dependent. Given that IFNA1 and IFNB1 are among the target genes, the expression of IFNα and IFNβ was decreased in cells deficient in IWS1 phosphorylation, and their sensitivity to the oncolytic VSV and Reovirus virus infection was increased accordingly. More importantly, treatment of the lung adenocarcinoma cells with the pan-AKT inhibitor, MK2206 phenocopied the loss of IWS1 phosphorylation and showed increased sensitivity to oncolytic viral infection. These data identify a novel mechanism by which the AKT/p-IWS1 axis, via the epigenetic regulation of alternative RNA splicing, contribute to the sensitivity to oncolytic viruses. Citation Format: Georgios I. Laliotis, Adam D. Kenney, Evangelia Chavdoula, Arturo Orlacchio, Vollter Anastas, Alessandro La Ferlita, Abdul Kaba, Lalit Sehgal, Vincenzo Coppola, Jacob S. Yount, Philip N. Tsichlis. Sensitivity of cancer cells to oncolytic viruses is defined by IWS1 phosphorylation dependent epigenetic regulation of U2AF2 splicing and nucleocytoplasmic export of type I IFN transcripts [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO088.
Democratic Disarray: Organizational Messaging Coherence and the Local Echoing Press During the 2020 Iowa Democratic Caucus:

The Iowa caucuses are the inaugural event of the American presidential nomination process. When the state Democratic Party failed to report the 2020 caucus results in a timely manner and manage the...
Atomistic modeling of peptide aggregation and β-sheet structuring in corn zein for viscoelasticity

The structure-function relationships of plant-based proteins that give rise to desirable texture attributes in order to mimic meat products are generally unknown. In particular, it is not clear how to engineer viscoelasticity to impart cohesiveness and proper mouthfeel; however, it is known that intermolecular β-sheet structures have the potential to enhance the viscoelastic property. Here, we investigated the propensity of selected peptide segments within common corn α-zein variants to maintain stable aggregates and β-sheet structures. Simulations on dimer systems showed that stability was influenced by the initial orientation and the presence of contiguous small hydrophobic residues. Simulations using eight-peptide β-sheet oligomers revealed that peptide sequences without proline had higher levels of β-sheet structuring. Additionally, we identified that sequences with a dimer hydrogen-bonding density of >22% tended to have a larger percent β-sheet conformation. These results contribute to understanding how the viscoelasticity of zein can be increased for use in plant-based meat analogues.