cssi/SciSciGPT-SciSciNet huggingface dataset:
Recurrent Abnormalities in TGIF RNA Sequence in Blasts from Patients with Acute Myeloid Leukemia.

To identify genes with prognostic potential in acute myeloid leukemia (AML), we applied microarray analysis and real-time PCR to RNA from cryopreserved bone marrow or venous blood samples from 61 patients with newly diagnosed or relapsed AML, and the expression of one gene, TG-interacting factor ( TGIF ) was found to be highly predictive of relapse and survival. TGIF is a transcriptional repressor belonging to the TALE (three amino acid loop extension) class of homeobox proteins, and deletion or mutation of a single allele of TGIF is associated with the craniofacial genetic disorder holoprosencephaly (HPE). TGIF transcripts in blasts from patients with AML have now been analyzed for mutations using reverse transcriptase-based PCR followed by dideoxy fingerprinting and automated sequencing. Using this approach, we identified the identical, aberrantly spliced TGIF transcript in independent RNA samples from a subset of patients (10/48) with low TGIF expression and poor long-term survival. Sequencing of this novel product showed that it lacked part of exon 1, all of exon 2, and most of exon 3 and eliminated all of the known interacting domains of TGIF (DNA binding, SMAD2, and mSin3A interacting). In contrast, Southern blot analysis of DNA from these patients did not identify any gross abnormalities in TGIF gene structure. This in combination with the RNA results suggests the likelihood of aberrant splicing. In sum, these results identify a novel, recurrent genetic abnormality in AML. The presence of aberrant splicing in AML contrasts with HPE, which is associated with mono-allelic mutations or deletions. As the protein product of this transcript would not be expected to have any of the known functions of TGIF in the cell, reduced expression of functional protein product may have a role in relapse or progression of AML.
Delivery of foreign cytotoxic T lymphocyte epitopes to tumor tissues for effective antitumor immunotherapy against pre-established solid tumors in mice

Cytotoxic T lymphocyte (CTL) can have remarkable abilities to kill tumor cells. However, the establishment of successful CTL-based anticancer therapy has met with many challenges. Within tumor cells, there exist subpopulations with low or no expression of the targeted antigen (termed as antigen-loss variants). In addition, tumor cells can downregulate the levels of major histocompatibility complex class I (MHC-I) molecules on cell surface due to immune pressure. As a result, some tumor cells can escape the immune pressure bestowed by CTLs, resulting in treatment failure. To address these difficulties, a new approach is developed to deliver foreign high-affinity CTL epitopes to tumor tissues utilizing pH-responsive “smart” microparticles (MPs). These MPs could encapsulate CTL peptide epitope, release the peptide under acidic condition encountered in tumor tissues and enhance CTL activation. Mice bearing pre-established tumor as “antigen-loss variant” solid tumor models were administered intratumorally with MPs containing the CTL peptide, which showed 100% survival following the treatment. In contrast, all control mice died from tumor. Significant protection from tumor-induced death was also observed with systemic administration of CTL peptide-MPs. The therapeutic efficacy can be attributed to enhanced delivery of the epitope to tumor tissues, presentation of the epitope by tumor cells as well as tumor stromal cells and/or generation of epitope-specific CTLs by the peptide-containing MPs. These findings offer a promising new direction for treating established solid tumor using CTL therapy.
My Name is Great Among the Nations: A D’Var Torah on Parshat Toldot

This talk takes as its main text one of the most remarkable passages in the Hebrew Bible, at Malachi 1:11: “For, from where the sun rises to where it sets, My name is honored among the nations, and everywhere incense and pure oblation are offered to My name; for My name is honored among the nations – said Adonai Tzevaot.” The apparently universalistic message inscribed in these words provokes a host of questions in the theology of religious pluralism. The most obvious is whether nations and religious traditions “from where the sun rises to where it sets” are actually worshipping the “same God.” This talk argues, however, that the question of whether different faiths worship the “same God” is, at the end of the day, not particularly useful or interesting. More vital is whether we can see the God to whom we pray in the worship of others. Or, more to the point, whether we can learn about God from the differences we see in the worship of others. Appreciating other religions is not only important for the sake of mutual respect, though that is vital as well, but also and most deeply for the sake of our understanding of God – the God who yearns for relationship and is infinitely and mysteriously capable of finding it.
Polypoidal Choroidal Vasculopathy

Purpose of Review The goal of this paper is to review the recent literature of polypoidal choroidal vasculopathy (PCV) and provide an update on the epidemiology, pathophysiology, clinical findings, and management.
Recreational Sporting Activity Vehicle‐Related Deaths

Deaths occurring in the setting of nonprofessional, vehicle-related, recreational sporting activities occurring on land or in water during warm or winter months represent a diverse group of cases. These deaths tend to involve scenarios where the participants are purposefully attempting to enjoy themselves prior to experiencing sudden, catastrophic accidents resulting in lethal outcomes. Ultimately, many of the deaths are related to the high speed at which these vehicle-related activities normally occur. Three broad categories of factors may play contributory roles in death: human factors, vehicle factors, and environmental factors. A series of selected cases are presented, representing examples of varying activity types, involving motorized and nonmotorized vehicles, land and water activities, and warm weather and cold weather environments. For each case, the various human, vehicle and environmental factors believed to be contributory to the accident are considered, and strategies for prevention of these and similar deaths involving recreational sporting vehicles are presented.
Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) and Risk of Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Background The molecular mechanisms underlying cerebral vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) are incompletely understood. We hypothesized that circulating antiangiogenic factors, such as soluble Fms-like tyrosine kinase 1 (sFlt-1) and soluble transforming growth factor β coreceptor, soluble endoglin (sEng), are important markers of their pathophysiology. Methods We performed a prospective study in patients with aSAH and measured cerebrospinal fluid and serum levels of sFlt-1 and sEng on postbleed day 1 and 6 and correlated levels with incidence and severity of cerebral vasospasm and DCI. Results Twenty-seven patients with aSAH were enrolled in the study. Severe angiographic vasospasm was present in 14.8% of patients and DCI occurred in 33.3%. Serum sFlt1 levels were increased on postbleed day 6 in patients who developed vasospasm. However, on postbleed day 1, there were no differences in patients who developed vasospasm. Increased serum sFlt-1 levels on postbleed day 1 were found to predict the development of severe angiographic vasospasm with an area under the curve of 0.818 with an optimal cutoff value of 95 pg/mL. Alterations in sFlt1 were not associated with DCI. Serum and cerebrospinal fluid sEng levels did not correlate with vasospasm or DCI. Conclusions Serum levels of sFlt-1 are increased in patients with aSAH who are at risk for severe vasospasm. Further studies with larger sample sizes are needed to evaluate whether sFlt-1 levels may predict onset of severe vasospasm and DCI.
Circulating progenitor cells in patients with familial hypercholesterolemia.

Objective Familial hypercholesterolemia (FH) is a genetic disease with very high levels of circulating low density lipoprotein cholesterol (LDL-C) levels that leads to accelerated atherosclerosis. Lipoprotein apheresis is an effective treatment option for patients with FH and results in reduced cardiovascular morbidity and mortality. Circulating progenitor cells (CPCs) are markers of overall vascular health and diminished levels have been associated with decreased reparative potential and worse outcomes. We assessed the short-term change in CPC levels following a single lipoprotein apheresis session in FH patients who are already on stable lipoprotein apheresis therapy. We hypothesized that in addition to a reduction in atherogenic lipids, the cardiovascular benefit from lipoprotein apheresis therapy is mediated by enhanced vascular reparative capacity through mobilization of CPCs. Methods Eight FH patients (1 homozygous and 7 heterozygous) on stable lipoprotein apheresis therapy for at least three months had CPCs measured at baseline (prior to apheresis) and two hours after apheresis. Results were compared with data from age-matched hyperlipidemic (HLP) patients on statin therapy and healthy volunteers. Results FH patients had higher baseline circulating levels of CD34+/CD133+ and CD34+/CD133+/CXCR4+ cells compared to HLP and healthy subjects. There was no significant change in CPCs after apheresis in FH patients. Conclusions FH patients had higher CPC counts at baseline compared to age-matched HLP and healthy controls, suggesting activation of reparative mechanism in this high risk population. Larger studies are needed to better characterize differences in CPC counts between FH subjects and HLP patients over time.
Safe Collections and Stewardship on Cloud Kotta

The increasing collection and use of sensitive datasets in science, coupled with the need for inter-institutional collaboration, poses new challenges for infrastructure and administrative models. While enclaves, such as CLOUD KOTTA, provide for the secure management and analysis of data, they do not yet support the administrative models needed by today's researcher practices. Current approaches often rely on a single data administrator to be responsible for the research activities of multiple analysts. However, this approach is not scalable and is prone to errors. To address these challenges we introduce two new abstractions in CLOUD KOTTA: 'safe collections' and 'stewardship'. Safe-collections define a novel abstraction that refines the scope of a data-store and the policies tied to it. Stewards are a new class of privileged user who own and manage safe-collections. By introducing these abstractions, our aim is to relieve the tension between limiting access to, and promoting research on, sensitive data.
Core–Shell Microneedle Gel for Self-Regulated Insulin Delivery

A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core–shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and pr...
Are Radiographic and Direct Measures of Acetabular Polyethylene Wear Comparable

BACKGROUND All polyethylene acetabular liners wear over time, and numerous methods for calculating linear wear rates exist. The objective of this study was to compare 2-dimensional wear rates between direct, micrometer measurements and the computerized, edge-detection method using Hip Analysis Suite (HAS) 8.0.4.3. METHODS Two groups of retrieved acetabular liners from Harris-Galante Prosthesis I and Harris-Galante Prosthesis II implants in situ for more than 10 years were evaluated. Group 1 (n = 18) contained liners with both early postoperative (<6 months) and prerevision radiographs taken within 1 month of explantation. Group 2 (n = 55) included liners with only prerevision X-rays (ie, 1 radiograph for wear assessment). Average and maximum direct linear wear was calculated from thicknesses measured at 6 consistent, well-separated locations (3 in the worn and 3 in the unworn regions) using a calibrated, digital micrometer. HAS 8.0.4.3 was used to calculate 2-dimensional wear from anteroposterior pelvic radiographs. RESULTS Aggregate wear rates calculated by HAS were higher than those calculated by the average of direct measurements for group 1 (P = .020) and group 2 (P < .001). However, comparing the maximum direct micrometer measurements to HAS showed no difference for either group 1 (P = .351) or group 2 (P = .451). Linear regression analysis showed a strong correlation between HAS and both average and maximum direct wear measures for both groups, though the coefficient for the direct maximum measurement comparisons were closer to one, indicating a better one-to-one correspondence between HAS and direct maximum wear. CONCLUSION To our knowledge, this is the first study to compare and validate 2-dimensional wear rates in polyethylene acetabular liners between direct measurements from retrieved components and a radiographic computer-assisted technique (as opposed to comparison against a phantom component). Wear rates determined by direct measurements from retrievals were consistent with computer-assisted 2-dimensional methods when comparing maximum wear measurements. In addition, a single prerevision radiograph appears to be sufficient to assess 2-dimensional in vivo wear.
Designing for Student Interactions: The Role of Embodied Interactions in Mediating Collective Inquiry in an Immersive Simulation

Advances in mobile and wireless technologies provide new possibilities for supporting K-12 learning activities that can be spatially distributed in the classroom, for example in jointly investigating a scientific phenomenon. Such technologies have an impact on the ways in which students engage with one another, and with the quality of their engagement with the activity itself. This paper uses an embodied approach to understand the patterns of interactions between students (e.g., student-to-student, student-to-teacher) and with computational media within the environment (e.g., student-to-device, student-to-large display), in relation to students' real-time meaning making as they engage in collective inquiry in an immersive simulation environment. The design-based research study consists of two iterations tested in an authentic school setting. We found that increased student-to-student interactions was accompanied by improved observational accuracy and higher quality student explanations constructed. The design implications of the research findings are discussed.
Potential for Use of Electrical Conductivity Measurements for Refinement of Soil Survey Information

Precision agriculture (PA) is concerned with understanding and managing variability. PA is made possible by the merging of several technologies--GPS-Global Positioning Systems, GIS-Geographic Information Systems, yield monitors, remote sensing, digital soil maps and databases, and variable rate applicators. Operators may be involved in only one or all these technologies and still be considered involved in PA. The ultimate goal is to improve the management of agricultural land. To achieve this goal data on soils, crops, pests, weather, etc., that will help in determining the best management practices for a field are needed. However, these technologies are only tools to aid our understanding, analyses, and conservation of sustainable agricultural ecosystems.
Recent Developments in Kohn-Sham Theory for Orbital-Dependent Exchange-Correlation Energy Functionals

In the usual spin density Kohn-Sham[1,2] (KS) theory, the total ground state energy, E, of a system of electrons moving in an external potential, V(r), is the sum of the kinetic energy of non-interacting electrons with the same spin densities, nσ, the average energy due to the external potential, the Hartree energy, and the exchange-correlation energy, Exc, which is a universal functional of {nσ}. The KS single particle states, φiσ, are obtained by solving a system of Schrodinger-like equations in which the effective potential is the sum of V(r), the Hartree potential, and the exchange-correlation potential, which is the functional derivative of Exc with respect to the nσ(r). This procedure is in principle exact. However, one must make some approximations for the generally unknown Exc[{nσ}] in applying this method.
Measuring fish condition: an evaluation of new and old metrics for three species with contrasting life histories

Measuring fish condition should link ecosystem drivers with population dynamics, if the underlying physiological basis for variations in condition indices are understood. We evaluated traditional (...
Frequent premature ventricular beats in healthy children: when to ignore and when to treat?

Purpose of review Premature ventricular beats (PVCs) are frequently identified in healthy children with structurally normal hearts and generally have a benign clinical course often disappearing spontaneously. However, a small percentage of children may develop a cardiomyopathy. The purpose of this review is to understand which children may be at risk of development of left ventricular (LV) dysfunction with idiopathic PVCs. Recent findings There is increasing evidence that a ventricular ectopic burden more than 24% in adults may lead to LV dysfunction. Most of the pediatric studies to date are retrospective, small case series from single institutions and have conflicting results regarding a direct correlation of the PVC burden to LV dysfunction. Development of a cardiomyopathy from frequent PVCs in children is likely multifactorial relating to the burden itself, presence of higher levels of ectopy (couplets and runs of ventricular tachycardia) as well as the duration of ventricular ectopy. Understanding the duration of ectopy is often unknown as patients are asymptomatic and the irregular heart beat was identified at a well-child examination. Summary Asymptomatic children with normal ventricular function and a low ectopy burden can be followed without any intervention and generally reassured. Children with an ectopy burden more than 30% are at some risk of developing LV dysfunction and should be more closely followed with noninvasive imaging. Development of symptoms attributed to the ectopy or signs of increasing LV dimensions or LV dysfunction should be treated with medication or catheter ablation.
Split graphs

The main topics of this article are split graphs, their degree sequences, and the place of these "split partitions" at the top of the partially ordered set of graphic partitions. One application is that threshold covered partitions are unigraphic.
Preserving privacy of drone videos using proxy re-encryption technique: poster

Unmanned Aerial Vehicles (UAVs) also known as drones are being used in many applications where they can record or stream video. One of such applications is the Intelligent Transportation Systems (ITS) where drones may need to record videos and send a control center to be shared by various clients such as law enforcement or emergency personnel. In such cases, the recording might include faces of civilians or other sensitive information that might pose privacy concerns. While the video can be encrypted and stored in the cloud that way, it can still be accessed once the keys are exposed to third parties. To prevent such cases, in this paper, we propose a proxy re-encryption technique that will provide a key to third parties that can be used only once to access the videos. The key management is handled by a trusted control center. The implementation results indicate that there is almost no additional overhead with the approach while it can still preserve the privacy.
Education: A Perfect Partner for Project-based Fundraising

Education programs are increasingly appealing to all types of funders and should not be overlooked in a museum's fundraising efforts. The economy and the rise of private family and corporate foundations make funders more and more interested in the enhanced and lasting impact museums can make in their communities.
Forgiveness and psychosocial reactions to disability a pilot study to examine change in persons with spinal cord injury

Spinal cord injuries (SCI) are among the most traumatic onset of disabilities to date. Due to the nature of spinal cord injury and how it affects the person’s life and psychosocial adjustment, there are a multitude of feelings, changes, persons, situations, and transgressions that need to be resolved and forgiven. In an effort to help persons with SCI do that, two interventions - Enright’s Forgiveness is a Choice intervention and Kennedy and Duff’s (2001) Coping Effectively with Spinal Cord Injury training – were facilitated on-line as part of a self-study treatment format among persons with spinal cord injury. The interventions were examined to determine their ability to aid in the increase of forgiveness and changes in psychosocial reactions to disability. Findings from this study found that both interventions are applicable and helpful in assisting persons with SCI in forgiving and experiencing changes in psychosocial reactions to disability, but differences were found in long-term change.
2738 Comparing Postoperative Pain with Laparoscopic Versus Robotic Sacrocolpopexy

Study Objective To compare postoperative pain and pain-related outcomes following laparoscopic (LS-MISC) versus robotic minimally invasive sacrocolpopexy (R-MISC). Design Secondary analysis of placebo-controlled RCT examining preoperative IV acetaminophen on postoperative pain following MISC. Setting Planned secondary analysis of multicenter RCT. Patients or Participants Women undergoing MISC. Interventions Primary outcome was total narcotics within 24 hours in morphine mg equivalents (MME) comparing LS-MISC and R-MISC. Measurements and Main Results We included 90 subjects undergoing MISC: 65 LS-MISC and 25 R-MISC. Most were Caucasian (97.8%) and postmenopausal (88.9%) with mean age 61.2±7.2 years and BMI 27.6±4.4 kg/m2. IV acetaminophen did not impact pain in the original study and was similar between LS-MISC and R-MISC. Baseline POP-Q stage was similar between groups. Concomitant hysterectomy was performed in 67% with LS-MISC, 60% with R-MISC (p=0.49). LS-MISC underwent more concomitant perineorrhaphies (15.4% vs 0%, p=0.04) and posterior repairs (18.5% vs 0%, p=0.02). Operative time was longer with LS-MISC (208.5±57.3 vs 143.6±21.0 minutes, p= Conclusion L-MISC showed increased length of stay and drowsiness. Most other outcomes showed either no difference or differences disappeared once adjusting for confounders as with primary outcome. Overall, MME narcotic use and VAS pain scales were low as were narcotic medication side effects.
FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster.

Summary Cellular iron homeostasis is dominated by FBXL5-mediated degradation of iron regulatory protein 2 (IRP2), which is dependent on both iron and oxygen. However, how the physical interaction between FBXL5 and IRP2 is regulated remains elusive. Here, we show that the C-terminal substrate-binding domain of FBXL5 harbors a [2Fe2S] cluster in the oxidized state. A cryoelectron microscopy (cryo-EM) structure of the IRP2-FBXL5-SKP1 complex reveals that the cluster organizes the FBXL5 C-terminal loop responsible for recruiting IRP2. Interestingly, IRP2 binding to FBXL5 hinges on the oxidized state of the [2Fe2S] cluster maintained by ambient oxygen, which could explain hypoxia-induced IRP2 stabilization. Steric incompatibility also allows FBXL5 to physically dislodge IRP2 from iron-responsive element RNA to facilitate its turnover. Taken together, our studies have identified an iron-sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.
Immunotherapy against Prion Disease

The term "prion disease" encompasses a group of neurodegenerative diseases affecting both humans and animals. Currently, there is no effective therapy and all forms of prion disease are invariably fatal. Because of (a) the outbreak of bovine spongiform encephalopathy in cattle and variant Creutzfeldt-Jakob disease in humans; (b) the heated debate about the prion hypothesis; and (c) the availability of a natural prion disease in rodents, the understanding of the pathogenic process in prion disease is much more advanced compared to that of other neurodegenerative disorders, which inspired many attempts to develop therapeutic strategies against these fatal diseases. In this review, we focus on immunotherapy against prion disease. We explain our rationale for immunotherapy as a plausible therapeutic choice, review previous trials using either active or passive immunization, and discuss potential strategies for overcoming the hurdles in developing a successful immunotherapy. We propose that immunotherapy is a plausible and practical therapeutic strategy and advocate more studies in this area to develop effective measures to control and treat these devastating disorders.
The Influences of Effective Inflow Layer Streamwise Vorticity and Storm-Relative Flow on Supercell Updraft Properties

AbstractThe relationship between storm-relative helicity (SRH) and streamwise vorticity (ωs) is frequently invoked to explain the often robust connections between effective inflow layer (EIL) SRH a...
The BRAIN Initiative and Neuroethics: Enabling and Enhancing Neuroscience Advances for Society.

As the Brain Research through Advancing Neurotechnologyies, better known as the BRAIN Initiative moves forward at a rapid pace increasing attention has focused on neuroethics. The National Institut...
Optimal integration between host physiology and functions of the gut microbiome

Host-associated microbial communities have profound impacts on animal physiological function, especially nutrition and metabolism. The hypothesis of ‘symmorphosis’, which posits that the physiologi...
Accelerated brain aging predicts impaired cognitive performance and greater disability in geriatric but not midlife adult depression.

Depression is associated with markers of accelerated aging, but it is unclear how this relationship changes across the lifespan. We examined whether a brain-based measure of accelerated aging differed between depressed and never-depressed subjects across the adult lifespan and whether it was related to cognitive performance and disability. We applied a machine-learning approach that estimated brain age from structural MRI data in two depressed cohorts, respectively 170 midlife adults and 154 older adults enrolled in studies with common entry criteria. Both cohorts completed broad cognitive batteries and the older subgroup completed a disability assessment. The machine-learning model estimated brain age from MRI data, which was compared to chronological age to determine the brain-age gap (BAG; estimated age-chronological age). BAG did not differ between midlife depressed and nondepressed adults. Older depressed adults exhibited significantly higher BAG than nondepressed elders (Wald χ2 = 8.84, p = 0.0029), indicating a higher estimated brain age than chronological age. BAG was not associated with midlife cognitive performance. In the older cohort, higher BAG was associated with poorer episodic memory performance (Wald χ2 = 4.10, p = 0.0430) and, in the older depressed group alone, slower processing speed (Wald χ2 = 4.43, p = 0.0354). We also observed a statistical interaction where greater depressive symptom severity in context of higher BAG was associated with poorer executive function (Wald χ2 = 5.89, p = 0.0152) and working memory performance (Wald χ2 = 4.47, p = 0.0346). Increased BAG was associated with greater disability (Wald χ2 = 6.00, p = 0.0143). Unlike midlife depression, geriatric depression exhibits accelerated brain aging, which in turn is associated with cognitive and functional deficits.
The electrostatic allostery could be the trigger for the changes in dynamics for the PDZ domain of PICK1

The PDZ domain is a highly abundant protein-protein interaction domain that exists in many signaling proteins, such as PICK1. Despite the highly conserved structure of the PDZ family, the PDZ family has an extremely low sequence identity, making each PDZ domain unique. PICK1 is the only protein in the human genome that is comprised of a PDZ domain and a BAR domain. PICK1 regulates surface membrane proteins and has been identified as an integral player in drug addiction. Like many PDZ-containing proteins, PICK1 is positively regulated by its PDZ domain and has thus drawn attention to be a potential drug target to curb the effects of substance abuse. The goal of this study is to use all-atom molecular dynamics simulations and the electrostatic analysis program, DelPhi, to better understand the unique interactions and dynamic changes in the PICK1 PDZ domain upon complex formation. Our results demonstrated that the PICK1 PDZ domain shares similar canonical PDZ-ligand hydrogen bonding networks and fluctuations of the carboxylate-binding loop to other PDZ domains. Furthermore, our results are unique to the PICK1 PDZ domain as we reveal that the binding of ligand opens up the binding pocket and, at the same time, reduces the fluctuations of both the central part of the binding pocket and the short loop region between the A-helix and {beta}C-strand. More importantly, the binding of ligand resulted in charge redistribution at the binding pocket region as well as the N- and C-termini of the PDZ domain that are not a part of the binding pocket. These results suggest that the electrostatic allostery resulted from ligand binding could be the key factor leading to the changes in dynamics which may be associated with the activation of PICK1. Based on these results, an effective drug to target PDZ domain must not only stably bind to the PICK1 PDZ domain but also prevent the electrostatic allostery of the PDZ domain.
Bonus Plan Choices During an Economic Downturn

We use survey data to estimate the effect of the 2008–2009 recession on three fundamental bonus plan choices. We find robust evidence that the recession (i) reduced incentive strength, (ii) increased the relative incentive weight on financial performance measures, and (iii) increased the perceived difficulty of financial performance targets, not only in absolute terms but also relative to the perceived difficulty of nonfinancial targets. To assess the extent to which these findings can be explained by standard theoretical explanations, we review prior agency literature and discuss several channels through which an economic downturn can affect firms’ bonus plan choices. Our review highlights that contracting issues rarely examined in prior empirical work such as retention concerns and information asymmetry issues are likely to play an important role during an economic downturn.
A Systematic Review of Interventions to Increase Physical Activity Among American Indian and Alaska Native Older Adults.

Background and objectives Physical activity (PA) is a powerful protective factor known to reduce risk for chronic conditions across the lifespan. PA levels are lower among American Indians and Alaska Natives (AIANs) when compared with other racial/ethnic groups and decrease with age. This evidence justifies a synthesis of current intervention research to increase PA levels among AIANs. This systematic review examines completed interventions to increase PA among AIAN older adults and considers recommended practices for research with Indigenous communities. Research design and methods The systematic review was designed in accordance with the PRISMA statement for systematic review protocols and reporting guidelines. Electronic databases PubMed, Web of Science, and PsycINFO were searched for academic literature. Trials investigating interventions to increase PA among AIAN adults ages 50+ were eligible. The Quality Assessment Tool for Quantitative Studies was used to evaluate the quality of evidence. Results Three published trials were identified, including one group-level, clinic-based and two individual-level, home-based interventions. All were 6-weeks in duration, took place in urban areas, and used self-report PA measures. Findings indicated an overall increase in PA levels, improved PA-related outcomes, and improved psychosocial health among participants. None described a community-engaged or culture-centered research strategies. Discussion and implications The narrow yet promising evidence represents a need for expanded research and a call to action for using culture-centered strategies. An advanced understanding of cultural and contextual aspects of PA may produce more impactful interventions, supporting health and mobility across the lifespan.
Reality, from virtual to augmented

Abstract Virtual reality (VR) technology has existed for decades, and the promise for its groundbreaking applications to healthcare has been discussed for almost as long. Recent advances in computer technology and decreasing costs of VR hardware have now allowed this technology to become increasingly utilized in the medical and healthcare industries. Additionally, newer technologies such as augmented reality promise additional benefit to patients and clinicians. By creating immersive and realistic environments, these technologies can be used as medical education tools for clinicians and patients, visualization tools for surgical planning and intraoperative guidance, and therapeutic tools for a wide range of health problems.
Middle Meningeal Artery Embolization and the Treatment of a Chronic Subdural Hematoma.

Chronic subdural hematoma (cSDH) is a common pathology that typically affects the elderly. It is believed to occur due to injury to the dural border cells, which creates an inflammation/proliferation reaction. Ineffective repair leads to the formation of a new external layer of cells and fragile capillaries, which damage easily and can worsen the condition. Conventionally, asymptomatic cSDH is managed by observation, and symptomatic cases are treated by surgical evacuation. Unfortunately, recurrence rates of the SDH following surgical evacuation can be high. One treatment option for SDH involves embolization of the middle meningeal artery (MMA). The MMA provides blood supply to the dura mater and feeds the membrane capillaries covering the SDH. MMA embolization blocks the blood flow to this system and can promote hematoma resolution. In this paper, we review the existing literature on MMA embolization and discuss the underlying pathophysiology of cSDH.
The Global Emergence of Human Babesiosis.

Babesiosis is an emerging tick-borne disease caused by intraerythrocytic protozoa that are primarily transmitted by hard-bodied (Ixodid) ticks and rarely through blood transfusion, perinatally, and organ transplantation. More than 100 Babesia species infect a wide spectrum of wild and domestic animals worldwide and six have been identified as human pathogens. Babesia microti is the predominant species that infects humans, is found throughout the world, and causes endemic disease in the United States and China. Babesia venatorum and Babesia crassa-like agent also cause endemic disease in China. Babesia divergens is the predominant species in Europe where fulminant cases have been reported sporadically. The number of B. microti infections has been increasing globally in recent decades. In the United States, more than 2000 cases are reported each year, although the actual number is thought to be much higher. In this review of the epidemiology of human babesiosis, we discuss epidemiologic tools used to monitor disease location and frequency; demographics and modes of transmission; the location of human babesiosis; the causative Babesia species in the Americas, Europe, Asia, Africa, and Australia; the primary clinical characteristics associated with each of these infections; and the increasing global health burden of this disease.
Auricular Flutter and Complete Heart Block: With Restoration of Sinus Rhythm and A-V Conduction

Excerpt Neither auricular flutter nor complete heart block are by themselves extraordinarily uncommon and it is safe to say that they would be even more familiar were the presumptive signs and symp...
Permeation of Glucose by Simple and Facilitated Diffusion by Novikoff Rat Hepatoma Cells in Suspension Culture and Its Relationship to Glucose Metabolism

Abstract The incorporation of 2-deoxy-d-[14C]glucose by cultured Novikoff rat hepatoma cells was investigated as a function of the deoxyglucose concentration in the medium. The intracellular radioactivity was mainly associated with deoxyglucose 6-phosphate, to a small extent with 6-phosphodeoxygluconate, and the remainder with free deoxyglucose. Below a concentration of 1 to 2 mm in the medium, the initial rate of deoxyglucose incorporation followed simple Michaelis-Menten kinetics at 22, 27, 32, and 37° with an apparent Km of about 2 mm. The Vmax values increased with a Q10 of about 2.5 with an increase in temperature. Between 2 and 10 mm, on the other hand, the initial rate of incorporation increased linearly with an increase in deoxyglucose concentration and the relative increase in incorporation rate with increase in deoxyglucose concentration was about the same at the temperatures tested. Treatment of the cells with 0.5 mm p-chloromercuribenzoate for 15 min or heat shock (48.5°, 5 min) abolished the saturable uptake component without affecting the nonsaturable component. When combined, the results indicate that at low concentrations, deoxyglucose is taken up mainly by carrier-mediated transport (probably facilitated diffusion), whereas at concentrations above 2 mm, simple diffusion becomes the principal mode of entry of deoxyglucose into the cells. Results from studies on d-glucose and 3-O-methyl-d-glucose incorporation support this conclusion and suggest that all three substrates are transported by a single system. Persantine competitively inhibited deoxyglucose uptake by whole cells and decreased the metabolism of glucose without affecting the phosphorylation of the substrates. Prior treatment with p-chloromercuribenzoate or heat shock also had no effect on the hexokinase activity of the cells. Little if any hexokinase activity was associated with the plasma membrane and the kinetic properties of the in vitro hexokinase reaction differed from that for glucose or deoxyglucose uptake by whole cells. These results indicate that transport of glucose into the cell is a reaction distinct from phosphorylation and is the rate-limiting step in the metabolism of glucose by the cells. Since the cells possess an excess of hexokinase, glucose is phosphorylated as rapidly as it enters the cells and thereby trapped. At low concentrations of glucose in the medium (5 to 50 µm), the glucose 6-phosphate formed was exclusively used by the cells for macromolecular synthesis and oxidative processes without net production of lactate. The rate of CO2 production and incorporation of glucose in macromolecules approached a maximum at about 1 mm glucose in the medium and the excess glucose 6-phosphate formed, particularly at higher concentrations of glucose in the medium, was converted to lactate.
Imaging of vertebral trauma

The imaging methods used to evaluate patients with suspected vertebral injuries have undergone radical changes in the past decade, the most significant being the ascendancy of computed tomography (CT) to become the primary investigative modality. Issues such as high radiation dose associated with CT studies and health care reform and cost containment also have a significant impact on clinical decision-making. This new edition of the classic landmark text for vertebral trauma imaging provides an in-depth discussion on the indications and methods of imaging the spine based on currently available clinical evidence. Every chapter has been extensively revised and the illustrations represent state-of-the-art imaging. A completely new chapter on pediatric injuries has been added. Imaging of Vertebral Trauma, third edition, is an invaluable and essential tool in the assessment of any patient with suspected vertebral or spinal cord injury.
Security analysis of a token ring using Ulysses

The Ulysses security modeling environment and methodology is illustrated by using a secure token ring network as an example. It is shown that by using a flow analyzer and a library of preproved components, it is possible to decompose the functionality of a system and to determine which components have possible security flaws. The analysis also highlights the issue of tradeoffs between requirements on systems. It is often the case that in order to achieve a high degree of security for a system it is necessary to implement measures which decrease its performance. For this reason, it is important to be able to quickly determine the security flaws of a system at the level of design, as Ulysses does, so that the relative benefits and disadvantages of design decisions can be weighed before they are implemented. >
Glucosamine/chondroitin combined with exercise for the treatment of knee osteoarthritis: a preliminary study

Summary Objective This preliminary study sought to determine whether using 1500/1200mg of glucosamine hydrochloride and chondroitin sulfate (GH/CS) is effective, both separately and combined with exercise, compared to a placebo plus exercise program in improving physical function, pain, strength, balance, and mobility in older adults with knee osteoarthritis (OA). Methods This double-blind, placebo-controlled, randomized clinical trial lasted 12 months. Participants included 89 older adults (age≥50 years) with knee OA randomized to either GH/CS or placebo group. Phase I was a 6-month trial comparing the effects of assignment to either GH/CS or placebo. Phase II added 6 months of exercise for both groups. The primary outcome measure was Western Ontario and McMaster University Osteoarthritis Index (WOMAC) function, and secondary outcome measures included WOMAC pain, 6-min walk, balance, and knee strength. Results Of the 89 randomized participants, 72 (81%) completed the study. The median pill compliance was 94% and 95% in Phase I, and, in Phase II, 97% and 91% for the GH/CS and placebo groups, respectively. Median exercise compliance during Phase II was 77% for the GH/CS group and 78% for the placebo group. WOMAC function and pain did not differ significantly between the groups at 6- or 12-month follow-up. There were also no significant differences between the groups in 6-min walk or knee strength; however, balance was better in the placebo group with approximately a 10% difference compared to the GH/CS group. Conclusions The GH/CS group was not superior to the placebo group in function, pain, or mobility after both phases of the intervention (pill only and pill plus exercise).
Magnetic-field-dependent surface resistance and two-level critical-state model for granular superconductors.

We develop a two-level critical-state model for calculating the intergranular fluxon density of a granular superconductor as a function of the external magnetic field, and compare it to our measurements of magnetic-field hysteresis of the microwave surface resistance of ${\mathrm{YBa}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7}$ bulk samples and of Nb-Cu-Nb proximity-effect Josephson-junction arrays. Our model deals with the magnetic-flux profiles on both macroscopic and local levels, as the intergranular critical current density is significantly smaller than the intragranular critical current density. We first solve the simplified special case of an infinitely large flat-slab geometry with an ideal ordered superconducting lattice microstructure, where the resulting intergranular fluxon density leads to anomalous magnetic hysteresis as observed experimentally. Then we generalize to disordered samples by introducing a type of clusters of grains. In this case, fluxons move freely in and out of the sample through percolative paths between the clusters, forming a structure topologically identical to our simplified ordered structure. The sizes of clusters depend on the microstructure and the stiffness of flux-line lattices, and on whether the sample is cooled in zero magnetic field or in a magnetic field. These dependences are studied both theoretically and experimentally. Finally, we use the model to explain features observed in transport critical-current and flux-creep measurements.
Effects of large parasitic loops on alford-loop counterpoise radiation patterns

The effects of large parasitic loop elements on the radiation patterns of an Alford loop above a circular ground plane are discussed. It has been found that, on properly choosing the parasitic loop parameters, it is possible to reduce the ground-plane edge-diffraction effects considerably without appreciable deterioration of the overall pattern.
Hydrocarbon-derived carbonate buildups of the northern Gulf of Mexico continental slope: A review of submersible investigations

Hydrocarbon-derived and microbially mediated authigenic carbonates occur over the entire depth range of the northern Gulf of Mexico slope. These carbonates consist of nodules and incipient nodules in surface sediments, hardgrounds and isolated slabs, and moundlike buildups of up to 10–20 m relief above the surrounding seafloor. The authigenic carbonates are characterized byδ13C negative values in the range −18‰ to −55‰ (PDB) suggesting mixing of seawater carbon with13C-depleted carbon sources ranging from crude oil to biogenic methane. Near the shelf edge, carbonates are “diluted” with biogenic material produced by reefs—bioherms developed at low sea level stands. Fossil-poor carbonates over salt diapirs of the upper and middle slope formed in the shallow subsurface and have been exhumed by the combined processes of uplift and physical erosion. Middle and lower slope carbonates are generally rich in fossil shells of chemosynthetic organisms. Mg calcite pelloidal matrix and acicular to botryoidal aragonitic void-filling cements are common petrographic features of these hydrocarbonderived carbonates. At two sites carbonates are mixed with barite.
What Matters: The Formation of Attitudes Toward the Police

Public attitudes toward the police are often studied because of their relationship with citizens' support of the existing order. Much of the literature on the public's opinion of law enforcement pe...