cssi/SciSciGPT-SciSciNet huggingface dataset:
SP0204 Barriers and Opportunities for Patient Organisations in Economically Disadvantaged European Countries

Background Southern European countries have been seriously attacked the last years by an economic crisis which has affected the life of their citizens in many ways. Among others financial crisis has seriously affected many aspects of life including the Health sector and has led to the severe degradation of health care system in these countries. Therefore issues like access to care, early diagnosis, appropriate rehabilitation and social support for people with rheumatic diseases are not considered as granted anymore and the access to these services is an issue for Southern European countries. Methods Validated surveys measure the effects and implications of crisis on the quality of life of people with RMSDs. Conclusions The current crisis despite the gloomy prospects maybe a starting point for reviewing practices of the past in health care system and a more equitable distribution of costs to the benefit of citizens. Equal attention should also be paid to the cooperation of all stakeholders inviting people with RMSDs to be involved in the decision making process related to health care services and in the design of a fair and more inclusive health care system. Disclosure of Interest None Declared
Why do some immobilized N-alkylated polyethylenimines far surpass others in inactivating influenza viruses?

A number of N-alkylated polyethylenimines (PEIs) were covalently attached to glass-slide surfaces, and their virucidal efficacies against three different strains of influenza viruses were examined quantitatively. The anti-influenza activities of the modified surfaces varied widely, with the most potent, immobilized N,N-hexyl,methyl-PEI and N,N-dodecyl,methyl-PEI, reducing the viral titer by over three logs (i.e., >99.9%). While the virucidal activities of the glass surfaces derivatized with N-alkylated PEIs displayed no discernible correlation with such surface properties as hydrophobicity, charge, protein affinity, roughness, adhesive interactions, and polymer-chain extension lengths, they exhibited a marginal correlation with the surface density of the quaternary ammonium group, as titrated by means of fluorescein binding. However, this correlation markedly improved (to the correlation coefficient of 0.97 with a two-tailed p value of 0.044) when the titration was instead carried out using a macromolecul...
The Physics of Solar Cells, by Jenny Nelson: Scope: monograph. Level: advanced undergraduate, scientist

The Physics of Solar Cells, by Jenny Nelson, Singapore, Imperial College Press, 2003, 384 pp., US$58/£38 (paperback), ISBN 978-1-86094-349-2. Scope: monograph. Level: advanced undergraduate, scient...
WE-DE-206-02: MRI Hardware - Magnet, Gradient, RF Coils

Magnetic resonance imaging (MRI) has become an essential part of clinical imaging due to its ability to render high soft tissue contrast. Instead of ionizing radiation, MRI use strong magnetic field, radio frequency waves and field gradients to create diagnostic useful images. It can be used to image the anatomy and also functional and physiological activities within the human body. Knowledge of the basic physical principles underlying MRI acquisition is vitally important to successful image production and proper image interpretation. This lecture will give an overview of the spin physics, imaging principle of MRI, the hardware of the MRI scanner, and various pulse sequences and their applications. It aims to provide a conceptual foundation to understand the image formation process of a clinical MRI scanner. Learning Objectives: 2. Understand the origin of the MR signal and contrast from the spin physics level. 3. Understand the main hardware components of a MRI scanner and their purposes 4. Understand steps for MR image formation including spatial encoding and image reconstruction 5. Understand the main kinds of MR pulse sequences and their characteristics.
Family of disulphide-linked dimers containing the ζ and η chains of the T-cell receptor and the γ chain of Fc receptors

Stimulation of T cells by antigen activates many signalling pathways. The capacity for this range of biochemical responses may reside in the complex structure of the seven-chain T-cell antigen receptor (TCR). In addition to the complexity shared by all TCRs, coexpression of zeta (zeta) and the distinct but related eta (eta) chains creates structural diversity among the TCR complexes expressed on a given cell. In most murine T cells that we have studied, about 90% of the heptameric receptor complexes contain a zeta zeta disulphide homodimer, whereas 10% contain a zeta eta disulphide heterodimer. Recent studies suggest that zeta has a critical role in allowing antigen to activate the cell, whereas eta expression has been correlated with the capacity for antigen-induced phosphoinositide turnover. A third zeta-related protein, the gamma (gamma) chain of the Fc epsilon and some Fc gamma receptors, exists as a disulphide homodimer in those complexes. The structural relatedness of zeta and gamma is emphasized by the recent demonstration of zeta zeta in association with CD16 in TCR-negative natural killer cells. Here we identify T cells lacking Fc receptors but coexpressing zeta, gamma, and eta, document the formation of novel heterodimers between zeta and gamma and between eta and gamma and show their association with the TCR. A greater range of homologous coupling structures than previously thought may be one way of achieving the variety of TCR-mediated (and possibly Fc receptor-mediated) biochemical responses and effector functions.
Femininity and fandom: the dual-stigmatisation of female comic book fans

Media portrayals of comic book fandom routinely depict the comics community as a masculine space, one in which the female fan is an anomaly. Yet, women reportedly represent a growing number of comic book purchasers and convention attendees. If women are, in fact, such a large contingent of the comic book fan community, then why do these gendered stereotypes of female fans persist? Moreover, why do we continually see narratives about the ‘exotic’ female comics fan if women are such a large population within comics culture? I theorise that many female comic book fans render themselves invisible in the comics community out of fear of stigmatisation, from both non-comics fans as well as male members of comics fandom. Drawing on the work of Erving Goffman, I use semi-structured interviews to explore how female comics fans in the United States experience fandom as members of a culture that is coded as masculine.
Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency.

Glutamate chemical exchange saturation transfer (GluCEST) MRI was used to measure metabolic changes in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by mapping regional cerebral glutamate. The GluCEST contrast following MPTP treatment was correlated with 1 H-MR spectroscopy, motor function, and immunohistochemical measures. The GluCEST contrast was found to be significantly higher in the striatum and motor cortex of mice treated with MPTP than in controls (p < 0.001), which was confirmed by localized 1 H-MR spectroscopy. Elevated striatal GluCEST was positively associated with local astrogliosis measured by immunohistochemistry for glial fibrillary acidic protein. Additionally, a negative correlation was found between motor function, measured by the four-limb grip strength test, and GluCEST of the striatum (R = -0.705, p < 0.001) and the motor cortex (R = -0.617, p < 0.01), suggesting a role of elevated glutamate in the abnormal cerebral motor function regulation. The GluCEST contrast and glial fibrillary acidic protein immunostaining were unaltered in the thalamus indicating glutamate elevation was localized to the striatum and the motor cortex. These findings suggest that in addition to measuring spatial changes in glutamate, GluCEST may serve as an in vivo biomarker of metabolic and functional changes that may be applied to the assessment of a broad range of neuropathologies. Read the Editorial Highlight for this article on page 346.
Complications After In Vivo and Ex Vivo Autologous Bone Flap Storage for Cranioplasty: A Comparative Analysis of the Literature

Introduction The most common bone flap storage strategies after decompressive hemicraniectomy for malignant intracranial hypertension include freezer cryopreservation (CP) and subcutaneous abdominal implantation (AP). Numerous series have reported on patient outcomes after cranioplasty in terms of infection, cosmesis, and resorption. This meta-analysis compares published outcomes of bone flap CP and subcutaneous storage with respect to efficacy and complication risk in patients undergoing cranioplasty after hemicraniectomy. Methods A systematic review was performed using PubMed-searchable studies that included bone flap storage methods and outcome data for cranioplasties performed between 1975 and 2015. Results A total of 48 studies including 5346 patients were identified that met the inclusion criteria. Of these patients, 4096 underwent cranioplasty with an autologous flap. Mean bone flap storage times for CP and AP flaps were 69.9 and 69.7 days. Mean follow-up time for CP and AP flaps was 16.9 and 16.5 months. No statistically significant differences were found when comparing CP with subcutaneous storage of bone flaps with respect to percentage of patients developing infection (7.3% vs. 7.1%), percentage of patients needing revision surgery (15.9% vs. 7.6%), and percentage of patients experiencing resorption (9.7% vs. 7.7%). Conclusions This is the largest and most robust review comparing published outcomes of CP and subcutaneous storage of bone flaps in patients who have undergone decompressive hemicraniectomy. This review found no statistically significant differences in clinical outcomes (infection, resorption, reoperation) when comparing storage methods for bone flap preservation. This study suggests that both strategies may be used safely and successfully.
Female Offenders and the Inmate Subculture

This chapter will consider the pains of imprisonment for women and their methods of adaptation during incarceration, particularly the creation of play families. The mode of adaptation espoused by an offender in prison can negatively or positively impact rehabilitative and reintegrative success. The importance of embracing a new conventional role while incarcerated and obtaining support for that role, during incarceration and post-release, will be highlighted. HIV prison-based programming as a way to develop conventional roles and mitigate adherence to the inmate code is considered.
The perpetuation of the misconception that rats receive a 3-5 times lower lung tissue dose than humans at the same ozone concentration.

AbstractThis paper highlights the pervasive misconception concerning 1994 findings from Hatch et al. about ozone (O3) tissue dose in humans versus rats. That study exposed humans to 0.4 ppm and rats to 2 ppm 18O-labeled O3 and found comparable incorporation of 18O into bronchoalveolar lavage constituents. However, during O3 exposure humans were exercising, which increased their ventilation rate five-fold, while rats were at rest. This resulted in similar O3 tissue doses between the two species, and predominantly explained the comparable 18O incorporation at five-fold different concentrations. The five-times higher exercising human inhalation rate offset the five-times lower concentration, producing the same human dose expected at rest at 2 ppm (i.e. 0.4 ppm × 4686 L/2 hour ≈ 2 ppm × 998 L/2 hour). In 2013, Hatch et al. showed that resting humans and resting rats experienced fairly comparable 18O incorporation at the same O3 exposure concentration and activity state into BALF cells. Despite these findings,...
Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A Validation Cohort.

Study objective Previous studies have suggested that the initial emergency department (ED) lactate concentration may be an important prognostic indicator for inhospital mortality from acute drug poisoning. We conduct this cohort study to formally validate the prognostic utility of the initial lactate concentration in a larger, distinct patient population with acute drug overdose. Methods This observational, prospective, cohort study was conducted during 5 years at 2 urban teaching hospitals. Consecutive adult ED patients with acute drug overdose had serum lactate levels tested as part of clinical care. The primary outcome was inpatient fatality. Receiver operating characteristics were plotted to determine optimal cut points, test characteristics, area under the curve, odds ratios, and 95% confidence intervals (CIs). Results Of 3,739 patients screened, 1,406 were analyzed (56% women; mean age 43.1 years) and 24 died (1.7%). The difference in mean initial lactate concentration was 5.9 mmol/L (95% CI 3.4 to 8.1 mmol/L) higher in patients who died compared with survivors. The area under the curve for prediction of fatality was 0.85 (95% CI 0.73 to 0.95). The optimal lactate cut point for fatality was greater than or equal to 5.0 (odds ratio 34.2; 95% CI 13.7 to 84.2; 94.7% specificity). Drug classes for which lactate had the highest utility were salicylates, sympathomimetics, acetaminophen, and opioids (all area under the curve ≥0.97); lowest utility was for diuretics and angiotensin-converting enzyme inhibitors. Conclusion Initial lactate concentration is a useful biomarker for early clinical decisionmaking in ED patients with acute drug overdose. Studies of lactate-tailored management for these patient populations are warranted.
Assessing Medicare's Approach To Covering New Drugs In Bundled Payments For Oncology.

New oncology therapies can contribute to survival or quality of life, but payers and policy makers have raised concerns about the cost of these therapies. Similar concerns extend beyond cancer. In ...
Levels of Cu-Zn and Mn superoxide dismutases in rat liver during development

Superoxide dismutase is the main scavenger of superoxide radicals in the mammalian body. The liver has high levels of two types of superoxide dismutase enzymes, cytosolic Cu-Zn and mitochondrial Mn enzymes. The aim of the present study was to investigate the content of two distinct superoxide dismutases in liver during the perinatal transition from a hypoxic to a hyperoxic environment. Both isozymes were purified to homogeneity and used as immunogens in rabbits. Antisera raised were found to recognize only polypeptides of molecular weight 16,900 or 23,400, which correspond to Cu-Zn and Mn superoxide dismutases, respectively. It was found that the level of Cu-Zn superoxide dismutase enzymatic activity and protein as assessed by immunoquantitation increased 10-fold during the postnatal period, reaching adult levels by 3 weeks. In contrast, the amount of Mn superoxide dismutase content increased only twofold to adult levels during the first week of life. Neither of the superoxide dismutases showed an alteration in specific activity or apparent molecular weight in rat livers during ontogeny. These results show that the levels of two intracellular superoxide dismutases are differentially elevated during the perinatal period. It is suggested that each dismutase plays a different physiological role for superoxide scavenging in liver as a function of the hypoxic/hyperoxic environment at birth.
Plenary lecture 8: reconfigurable chip multiprocessors targeting performance and energy consumption

Heterogeneous chip multiprocessors form powerful computing platforms. For high-performance or realtime applications, their design should also rely on acceptable energy budgets. The inclusion of reconfigurable hardware can enhance these platforms even further. This talk first presents a very versatile family of reconfigurable chip multiprocessors that can support the run-time reconfiguration of resources in efforts to match target applications for better performance and/or lower energy consumption. This talk then introduces another family of reconfigurable chip multiprocessors where the hardware can be customized to speed up the execution of time-consuming application kernels. Hardware reconfiguration can then facilitate various customized kernels as execution proceeds. This approach greatly reduces the space and energy requirements, attributes that appeal to high-performance embedded designs. The kernel execution should be prudently scheduled considering the reconfiguration overheads. Suitable task scheduling and resource reconfiguration policies are presented for these families of chip multiprocessors and benchmarks are enlisted as well to showcase their success.
ECT and Anticoagulation

Electroconvulsive therapy (ECT) is an effective and safe treatment for depression. Anticoagulation therapy is used to reduce morbidity or mortality from stroke or recurrent pulmonary embolus in various cardiac and vascular conditions. We report in detail the successful ECT treatment of a patient suffering from major depression with psychotic features who continued warfarin (Coumadin) anticoagulant therapy.
The Hypertensive Heart: An Integrated Understanding Informed by Imaging

Clinical sequelae of hypertension include heart failure, arrhythmias, and ischemic events, especially myocardial infarction and stroke. Recognizing the hypertensive heart has diagnostic as well as prognostic implications. Current imaging techniques offer noninvasive approaches to detecting myocardial fibrosis, ischemia, hypertrophy, and disordered metabolism that form the substrate for hypertensive heart disease. In addition, recognition of aortopathy and atrial myopathy as contributors to myocardial disease warrant incorporation of aortic and atrial functional measurements into a comprehensive understanding of the hypertensive heart.
Solving Polynomial Systems Using Numeric Gröbner Bases

Systems of polynomial or algebraic equations with finitely many solutions arise in many areas of applied mathematics. I will discuss the design and implementation of a hybrid symbolic-numeric method based on the endomorphism matrix approach pioneered by Stetter and others. It makes use of numeric Grobner bases and arbitrary-precision eigensystem computations. I will describe how to assess accuracy, find and remove parasite solutions in the case of fractional degrees in the system, handle multiplicity, as well as some of the other finer points not usually covered in the literature. This work is one of the methods used in the Wolfram Language NSolve function.
Scratch That (But Cache This): A Hybrid Register Cache/Scratchpad for GPUs

Graphics processing units (GPUs) are throughput-oriented architectures that implement massive multithreading. Large, power-hungry register files are required in GPUs to support the simultaneous execution of thousands of threads on the hardware. Prior work proposed reducing register access energy by adding a small register cache (RC) to the GPU. The cache stores recently referenced registers and services subsequent accesses to these registers, reducing accesses to the main register file. Later work obtained further energy savings by replacing this cache with a compiler-managed scratchpad. We note that registers are allocated to the cache dynamically and reactively whereas registers are allocated to the scratchpad statically and proactively. Our insight is that these allocation schemes are complimentary because the cache leverages runtime information unavailable to the compiler and the scratchpad leverages compile time information unavailable to the cache. Further, there exist register access patterns that are easily captured by one structure but for which the other structure is ineffective. Instead of implementing either an RC or scratchpad alone, we propose dividing temporary register storage capacity between a cache and a scratchpad in order to capture a broader range of register accesses. Given 12 KB of storage per streaming multiprocessor, our hybrid design reduces register energy to 38.7% of the baseline, compared to 47.9% for a RC and 47.1% for a register scratchpad.
Video-assisted thoracoscopic surgery versus robotic-assisted thoracoscopic surgery and postoperative opioid consumption

Even though the concept of thoracoscopy was first described in 1910s, video-assisted thoracoscopic surgery (VATS) was not used in the operating rooms until 1990’s (1). The use of VATS lobectomy procedures, compared to open approaches, increased from 10% in 2002 to 29% in 2007 (1,2). The reason for the popularization of VATS, as an alternative to thoracotomy, was the suggestion that VATS could reduce the surgery-related complications (1). A more recent and similarly less invasive alternative to VATS is robotic-assisted thoracoscopic surgery (RATS).
Consultant Corner: Bowel Obstruction

Bowel obstruction is a surgical disease and surgical consultation should occur early in management. The goals in treating bowel obstruction are to relieve intraluminal pressure by nasogastric decompression, resuscitate the patient, and intervene before ischemia, necrosis, and perforation occur. The complications of bowel obstruction are ischemia, perforation, sepsis, and death. Signs of bowel strangulation, ischemia, and perforation are all similar and include peritonitis, fever, tachycardia, leukocytosis, acidosis, and/or hemodynamic instability. Bariatric surgery patients, elderly and diabetic patients, and patients with obstruction due to malignancy require a higher degree of suspicion for complications and special considerations in management.
Adaptation to Provocative Motion

The question of adaptation is a key issue in dealing with motion sickness. It is generally accepted that most people should be capable of adapting to provocative motion. In that case, why do so many people suffer from chronic motion sickness? As I have said in the previous chapter, I believe that this is due to a psychological component based upon unpleasant motion responses in the past; perhaps as a result of individual motion experiences from a young age. Early and continued exposure to provocative motion may either sensitise a person or allow that person to adapt. This will depend upon the duration, character and frequency of exposure to whatever form of motion. In a sense it may be entirely fortuitous and depend on social and/or geographical circumstances. I shall return to this question later in Chap. 12, when discussing cognitive-behavioural training.
Experimental and numerical study on bond strength between conventional concrete and Ultra High-Performance Concrete (UHPC)

Abstract Ultra High-Performance Concrete (UHPC) has made progress in the bridge and building industry owing to its high strength, ductility, and durability. UHPC is a relatively expensive material and is mostly used in conjunction with conventional concrete. Such composite structures should be designed considering the interaction of different concrete layers. Generally, the simplest interaction model to simulate the complex behavior at the interface is ‘tie’ model, but simulation results may lead to an overestimation of load capacity. This study investigates a more realistic numerical approach comparing to tie interaction model, and its capability to predict the load capacity of structures where substrate concrete is joined to or repaired with an overlay concrete. This modeling technique uses an interface plane between the concrete layers. By calibrating the interface properties, designers can make a reliable prediction about the behavior of the composite structures. The numerical concept is evaluated when UHPC is employed as an overlay and normal strength concrete as substrate section. First, an experimental test program is performed on a series of composite specimens to characterize the bond performance between conventional concrete layers as well as regular concrete and UHPC. To validate the model, third-point loading beam, direct shear, and slant shear tests were performed. The numerical model is then used to evaluate the mechanism of force transfer at the interface between two materials. The results indicate that employing this modeling approach has the capability to provide a better estimation of the failure loads when compared to the tied model.
On the Impact of Ground Sound.

Rigid-body impact sound synthesis methods often omit the ground sound. In this paper we analyze an idealized ground-sound model based on an elastodynamic halfspace, and use it to identify scenarios wherein ground sound is perceptually relevant versus when it is masked by the impacting object's modal sound or transient acceleration noise. Our analytical model gives a smooth, closed-form expression for ground surface acceleration, which we can then use in the Rayleigh integral or in an "acoustic shader" for a finite-difference time-domain wave simulation. We find that when modal sound is inaudible, ground sound is audible in scenarios where a dense object impacts a soft ground and scenarios where the impact point has a low elevation angle to the listening point.
Childhood in Germany

My paternal ancestry is already fairly well documented in the biography of my father, Max Wertheimer, published by Transaction Publishers of Rutgers University Press in 2005, and in other places, so I needn’t elaborate on it too much here.
Impact of Water Ingress on Molybdenum Thin Films and Its Effect on Cu(In,Ga)Se 2 Solar Cells

Solar cell degradation can occur through many pathways and at the different stages of the fabrication process, notably because of the water condensation. In the case of Cu(In,Ga)Se2 (CIGS) solar cells, the impact of water ingress on Mo back contact can be substantial for not only the film itself but also the device performance and reliability. Microstructural modification, change in film morphology, loss in reflectance, and increased resistivity because of the moisture ingress were observed via X-ray diffraction, transmission electron microscopy, spectroscopic ellipsometry, and four-point probe measurements, respectively. Secondary ion mass spectrometry measurements revealed drastic changes in the alkali (Na, K) profiles in both the CIGS and Mo layers, likely because of the modification of their diffusion coefficient through Mo. This, in turn, negatively impacts the solar cell efficiency by decreasing both fill factor and open-circuit voltage. Additional experiments, modifying the substrate and utilizing a NaF postdeposition treatment, highlight the mechanisms of degradation as being due to both a modification of the Mo/CIGS interface and the lack of alkali diffusion after water ingress.
Novel Home-Based Devices for Male Infertility Screening

Laboratory-based conventional semen analysis is the primary diagnostic test to assess the male fertility potential. The semen analysis evaluates standard semen parameters such as volume, pH, concentration, motility, viability, and morphology as per World Health Organization (WHO 2010) guidelines. However, the method of producing a semen sample in a laboratory setting tends to be a stressful and difficult task for many men. Furthermore, lack/inadequate access to andrology services in developing countries portends a challenge for couples and may result in unnecessary investigations and infertility treatment for the female partner. A greater understanding of these barriers has led to the development of novel, commercially available, and affordable at-home-based semen analysis screening tests.
Simulating Bacterial Growth, Competition, and Resistance with Agent-Based Models and Laboratory Experiments

In this chapter, we will introduce the concepts of growth, competition, and adaptation using bacteria. We will use both simulation and laboratory-based exercises and provide practice with critical skills to assess your understanding throughout the chapter. The chapter ends by focusing on the capacious and global problem of antibiotic resistance, considered to be one of the most important public health threats of the twenty-first century. We will review the basic biological concepts underlying the phenomenon, and introduce the mathematical content necessary to begin to create agent-based models in order to simulate and analyze antibiotic resistance and its effect on the planet. we will present a selection of research projects throughout the later portion of the chapter for you to further explore antibiotic resistance and other contexts of bacteria.
Brazilian Peppertree Thrips Pseudophilothrips ichini (Hood) (Insecta: Thysanoptera: Phlaeothripidae)

The Brazilian peppertree thrips, Pseudophilothrips ichini (Hood) (Thysanoptera: Phlaeothripidae), is an insect native to Brazil (Figure 1). This species has been studied for the last 20+ years as a potential biological control agent of Brazilian peppertree, Schinus terebinthifolia Raddi (Sapindales: Anacardiaceae), in Florida (Cuda et al. 2008; Cuda et al. 2008; Manrique at al. 2014; Wheeler et al. 2016a, b). Host specificity experiments demonstrated that Pseudophilothrips ichini has a limited host range (Cuda et al. 2008; Cuda et al. 2009; Wheeler et al. 2017) and can cause a severe reduction of Brazilian peppertree biomass (Manrique at al. 2014).https://edis.ifas.ufl.edu/in1270
Mechanobiology in Tendon, Ligament, and Skeletal Muscle Tissue Engineering

Tendon, ligament, and skeletal muscle are highly-organized tissues that largely rely on a hierarchical collagenous matrix to withstand high tensile loads experienced in activities of daily life. This critical biomechanical role predisposes these tissues to injury, and current treatments fail to recapitulate the biomechanical function of native tissue. This has prompted researchers to pursue engineering functional tissue replacements, or dysfunction/disease/development models, by emulating in vivo stimuli within in vitro tissue engineering platforms; specifically mechanical stimulation, as well as active contraction in skeletal muscle. Mechanical loading is critical for matrix production and organization in the development, maturation, and maintenance of native tendon, ligament, and skeletal muscle, as well as their interfaces. Tissue engineers seek to harness these mechanobiological benefits using bioreactors to apply both static and dynamic mechanical stimulation to tissue constructs, and induce active contraction in engineered skeletal muscle. The vast majority of engineering approaches in these tissues are scaffold-based, providing interim structure and support to engineered constructs, and sufficient integrity to withstand mechanical loading. Alternatively, some recent studies have employed developmentally-inspired scaffold-free techniques, relying on cellular self-assembly and matrix production to form tissue constructs. Whether utilizing a scaffold or not, incorporation of mechanobiological stimuli has been shown to improve the composition, structure, and biomechanical function of engineered tendon, ligament, and skeletal muscle. Together, these findings highlight the importance of mechanobiology and suggest how it can be leveraged to engineer these tissues and their interfaces, and to create functional multi-tissue constructs.
Automatic Differentiation in MetaPhysicL and Its Applications in MOOSE

Efficient solution via Newton’s method of nonlinear systems of equations requires an accurate representation of the Jacobian, corresponding to the derivatives of the component residual equations wi...
Molecular and cell biological analysis of SwrB in Bacillus subtilis

Swarming motility is flagellar-mediated movement over a solid surface and Bacillus subtilis cells require an increase in flagellar density to swarm. SwrB is a protein of unknown function required for swarming that is necessary to increase the number of flagellar hooks but not basal bodies. Previous work suggested that SwrB activates flagellar type III secretion but the mechanism by which it might perform this function is unknown. Here we show that SwrB likely acts sub-stoichiometrically as it localizes as puncta at the membrane in numbers fewer than that of flagellar basal bodies. Moreover the action of SwrB is likely transient as puncta of SwrB were not dependent on the presence of the basal bodies and rarely co-localized with flagellar hooks. Random mutagenesis of the SwrB sequence found that a histidine within the transmembrane segment was conditionally required for activity and punctate localization. Finally, three hydrophobic residues that precede a cytoplasmic domain of poor conservation abolished SwrB activity when mutated and caused aberrant migration during electrophoresis. Our data are consistent with a model in which SwrB interacts with the flagellum, changes conformation to activate type III secretion, and departs. IMPORTANCEType III secretion systems (T3SS) are elaborate nanomachines that form the core of the bacterial flagellum and injectisome of pathogens. The machines not only secrete proteins like virulence factors but also secrete the structural components for their own assembly. Moroever, proper construction requires complex regulation to ensure that the parts are roughly secreted in the order in which they are assembled. Here we explore a poorly understood activator the flagellar T3SS activation in Bacillus subtilis called SwrB. To aid mechanistic understanding, we determine the rules for subcellular punctate localization, the topology with respect to the membrane, and critical residues required for SwrB function.
Using deep learning to predict brain age from brain magnetic resonance images and cognitive tests reveals that anatomical and functional brain aging are phenotypically and genetically distinct

With the world population aging, the prevalence of age-related brain diseases such as Alzheimers, Parkinsons, Lou Gehrigs, and cerebrovascular diseases. In the following, we built brain age predictors by leveraging 46,000 brain magnetic resonance images [MRIs] and cognitive tests from UK Biobank participants. We predicted age with a R-Squared [R2] of 76.4{+/-}1.0% and a root mean squared error of 3.58{+/-}0.05 years and identified the features driving the prediction using attention maps. We defined accelerated brain aging as the difference between brain age (predicted age) and age. Accelerated brain aging is partially heritable (h_g2=35.9{+/-}2.6%), and is associated with 219 single nucleotide polymorphisms [SNPs] in 25 genes (e.g CRHR1, involved in the hypothalamic-pituitary-adrenal pathway). Similarly, it is associated with biomarkers (e.g blood pressure), clinical phenotypes (e.g general health), diseases (e.g diabetes), environmental (e.g smoking) and socioeconomic variables (e.g income and education). We performed the same analysis, this time distinguishing between anatomical (MRI-based) and functional (cognitive tests-based) brain aging. We found the two accelerated aging phenotypes to be phenotypically .112{+/-}.006 correlated and genetically uncorrelated, with distinct SNPs and non-genetic factors associated with each. In conclusion, anatomical and functional brain aging are two distinct, complex phenotypes, which also differ in their genetic and non-genetic factors. Our brain predictors could be used to monitor the effects of emerging rejuvenating therapies on the brain.
Promise of metformin for preventing age-related cognitive dysfunction.

The expanded lifespan of people, while a positive advance, has also amplified the prevalence of age-related disorders, which include mild cognitive impairment, dementia, and Alzheimer’s disease. Therefore, competent therapies that could improve the healthspan of people have great significance. Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age. Metformin, a drug widely used for treating diabetes, is one such candidate that could alleviate age-related cognitive dysfunction. However, the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies. While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer’s disease in aged diabetic people, its efficacy in the nondiabetic population is still unclear. Moreover, a previous animal model study implied that metformin could adversely affect cognitive function in the aged. However, a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age. The study also revealed that cognition-enhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase, diminished neuroinflammation, inhibition of the mammalian target of rapamycin signaling, and augmented autophagy in the hippocampus. The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function. Nonetheless, additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.
High Intensity Focused Ultrasound for the Treatment of Prostate Cancer: Assessing Location of Failure after Focal Therapy in Prostate Cancer and Review of Histological Characteristics and Clinicopathologic Correlates after Treatment: A 5-Year Experience.

Abstract Background High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. Histological changes in post-treatment biopsies are reviewed to better understand HIFU failures. Design Between 2016 and 2021, 50 patients with localized prostate cancer were enrolled and treated in this study. Of these, 10 patients underwent salvage therapy following radiation failure and 7 did not have post-treatment biopsies available for review and were excluded. Inclusion criteria included pathologically confirmed prostate cancer and clinical stage T1/T2 disease. We describe the histological changes in post-treatment biopsies as part of routine follow-up. Biopsies were examined for presence, distribution and extent of residual adenocarcinoma, Gleason score, and ablative tissue changes. Results A total of 33 patients underwent HIFU hemi-ablation treatment of localized prostate cancer as primary treatment with post-treatment biopsies available for review. The average mean age of the patients was 64 years (range 52-81 years). The average PSA level of the patients was 6.3 ng/mL (range 2.4-14.7 ng/mL). The Gleason score in pre-treatment prostate needle biopsies are as follows: 3+3: 1 (3%), 3+4: 21 (64%), 4+3: 9 (27%), 4+4: 1 (3%). In post-treatment prostate needle biopsies, 33 cases (100%) showed variable degree of fibrosis ranging from mild to moderate. 24/33 cases (73%) showed necrosis usually associated with acute and/or chronic inflammation. Histological examination of benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. 8 cases (24%) had residual prostatic adenocarcinoma after treatment, of which 4 cases were Gleason score: ≥3+4. In cases with residual adenocarcinoma, 8 cases (100%) showed nuclear enlargement, 5 cases (63%), cytoplasmic vacuolization and 1 case (13%) showed nuclear pyknosis, otherwise no discernable effects of treatment were seen. Conclusions Morphological alterations included a spectrum of changes ranging from extensive coagulative stromal necrosis secondary to thermal injury to atrophic changes in benign prostatic tissue after HIFU treatment. Our findings also support the hypothesis that HIFU failure results from inadequate targeting rather than failure within a treated zone.
KSRP and Roquin-2: Mediators of PTH-Induced Npt2a mRNA Destabilization?

Parathyroid hormone (PTH) potently induces phosphaturia through the downregulation of the type IIa sodium-phosphate cotransporter (Npt2a), at the protein and the mRNA level. We previously identifie...
Modification of pepsinogen with pyridoxal phosphate.

Pyridoxal-PO4 binds to pepsinogen in a reaction in which the stoichiometry is highly dependent on the conformation of the protein. When pepsinogen is in its native conformation, pyridoxal-PO4 forms Schiff bases with the α-NH2 group of Leu1 and the e-NH2 group of Lys358. When the protein is mildly denatured and assumes a more extended conformation, pyridoxal-PO4 can react with the e-NH2 groups of approximately 3 other lysine residues present in the NH2-terminal region of the pepsinogen molecule. Pepsinogen with pyridoxal-PO4 covalently attached at Leu1 and Lys358 by reduction of the protein-pyridoxal-PO4 Schiff bases can be activated to pepsin. This modified pepsin, which has a pyridoxal-PO4 molecule covalently attached to the e-NH2 group of its sole lysine residue, cannot be distinguished catalytically from the unmodified enzyme. As soon as 1 or 2 of the lysine residues in the NH2-terminal region of pepsinogen become modified with pyridoxal-PO4, the zymogen can no longer be activated, possibly because the protein cannot assume the proper conformation required for activation. No pattern to the sequence of pyridoxal-PO4 incorporation into pepsinogen was observed after the first 2 pyridoxal-PO4 molecules were incorporated. The lysine residues showing the greatest reactivity toward pyridoxal-PO4 other than Lys358 were found in regions of the NH2 terminus in which the density of basic amino acids was highest.
Trisomy 8 mosaicism syndrome.

Chromosome 8 is the largest autosome thus far found to be trisomic among liveborn infants. Trisomy 8 "mosaicism" syndrome (T8mS) consists primarily of individuals whose chromosome complement is mosaic for chromosome 8 (T8m), i.e., patients with a chromosomally normal cell line in addition to the trisomic 8 cell line, and a few known individuals with full trisomy 8 (T8), i.e., each cell observed contains an extra chromosome 8. Reported cases of both types share a number of common features and thus have helped to delineate a new syndrome. Common features of T8mS include mild-to-moderate mental retardation, strabismus, osseous and soft tissue abnormalities, lowset and/or malformed ears, broad bulbous nose, palate deformity, various types of congenital cardiovascular disorders, hydronephrosis, cryptorchidism, and characteristic dermatoglyphics. Since chromosomal mosaicism is often present in this syndrome it is not surprising that considerable phenotypic variation exists. The present report of one of the youngest individuals yet described with T8m adds two more physical findings (dense corneal clouding and a heretofore undescribed clavicular deformity) to the constellation of abnormalities associated with T8mS. On the basis of the phenotypic and cytogenetic findings in this and 17 similar patients previously reported it is proposed that T8mS is a distinct clinical entity.
Mixed-initiative activity planning for Mars rovers

One of the ground tools used to operate the Mars Exploration Rovers is a mixed-initiative planning system called MAPGEN. The role of the system is to assist operators building daily plans for each of the rovers, maximizing science return, while maintaining rover safety and abiding by science and engineering constraints. In this paper, we describe the MAPGEN system, focusing on the mixed-initiative planning aspect. We note important challenges, both in terms of human interaction and in terms of automated reasoning requirements. We then describe the approaches taken in MAPGEN, focusing on the novel methods developed by our team.
The incorporation of communicative language teaching into the elaboration of interactive software for esl/efl learning

This study investigated the extent to which ESL/EFL software programs currently available on the market develop language skills according to the principles of Communicative Teaching and an interactive approach to computer use for language learning. A software evaluation instrument was developed and validated. The validated instrument was used to evaluate fifteen ESL/EFL software programs currently available on the market for the technological, pedagogical and individualization features that would account for the incorporation of Communicative Language Teaching principles and an interactive approach to computer use in language teaching. Results indicated that only three programs incorporated more than seventy-five percent of the technological features, four programs incorporated more than seventy percent of the pedagogical features, and only one program contained more than seventy percent of the features that allow for individualization of instruction. Overall, only two programs incorporated more than seventy percent of the technological, pedagogical and individualizing features and created environments that developed language skills according to the principles of Communicative Language Teaching and an interactive approach to computer use for language learning. The use of the ESL/EFL software evaluation instrument for evaluating the programs provided evidence that the key differentiating factor in ESL software programs lies not only in their pedagogical orientation, but also in how and the extent to which they incorporate Communicative Language Teaching principles and an interactive language learning approach into their design. Although all programs claimed to incorporate communicative theories of language learning into their elaboration, they had to a lesser or greater degree difficulty in elaborating activities that would develop language skills according to this approach.
Fundamental studies of the sampling process in an inductively coupled plasma mass spectrometer-II: Ion kinetic energy measurements

Abstract Retarding-plate analysis was used to monitor kinetic energies of argon and analyte ions in the second and third stages of a three-stage ICP-MS instrument. In these studies, forces that influence ion movement (i.e. gas-kinetic or ion-ion interactions) and their relative strengths are deduced from retarding-potential curves. Coulombic interactions among ions have been found to be so strong in the mass spectrometer second stage that they can overpower influences on ion movement imparted by gas-kinetic forces. In contrast, ion movement in the third stage was found to be influenced less by these coulombic interactions than in the second stage. However, ion-ion interactions could be intentionally exaggerated in the third stage by increasing ion flux. Results from these experiments were useful not only in identifying the forces that influence ion movement but also in the development of a new qualitative ion-transport model for a three-stage ICP-MS instrument