cssi/SciSciGPT-SciSciNet huggingface dataset:
Adenylate-Cyclase-Coupled β- Adrenergic Receptors

A wide variety of hormones initiate their effects on target cells by binding to specific cell surface receptors. In numerous systems, this interaction leads to the generation of the second messenger, cAMP, which initiates a cascade of events responsible for the ultimate response to that particular hormone. Catecholamines such as epinephrine and norepinephrine and various polypeptide hormones such as ACTH, glucagon, LH, and FSH are examples of hormones that stimulate responsive cells by binding to their specific receptors and by increasing the concentration of cAMP within the cells. However, prolonged exposure of target tissues to hormones results in a rapid rise followed by a decline in intracellular levels of cAMP. This phenomenon, termed “desensitization,” “refractoriness,” or “tachyphylaxis,” appears to be quite a general mechanism for regulation of cellular sensitivity to hormonal stimulation (for review see Lefkowitz et al., 1980; Perkins, 1983; Harden, 1983).
The Mechanisms of the Liquid Scintillation Process

Publisher Summary This chapter discusses various mechanisms that comprise the liquid scintillation process. The liquid scintillation process is based upon the conversion of a part of the kinetic energy of an ionizing particle into photons. In all liquid scintillation counting with homogeneous distribution of the radionuclide, there is always a fraction of radionuclides near the walls of the container. A part of these radiations can reach the wall before losing all of their energy. Thus, the response produced is less than that produced by a particle of the same energy which releases all of its energy to the liquid scintillation medium. This is often called the wall effect. The wall effect has a slight effect on counting in a wide open counting channel, but can markedly alter the relative counts in narrow counting channels. In liquid scintillator solutions, the primary excitations occur in the solvent part of the solution. The final response is directly proportional to the number of excited solvent molecules produced in this initial step. Quenching is a term commonly used to denote some process that causes a decrease in the photon yield of a liquid scintillator solution relative to no quenching. These quenching mechanisms can be divided into four main categories: energy absorption, dilution-concentration, impurity (sometimes called chemical), and color.
Nitrogen Surface Catalyzed Recombination Efficiency from Two-Photon Laser Induced Fluorescence Measurements

Measurements of temperature and species gradients in the thermal boundary layer adjacent to different surfaces exposed to nitrogen plasma are made to characterize surface-catalyzed recombination. L...
Progressive Retinal Thinning in Sickle Cell Retinopathy.

Purpose To determine the rate of retinal thinning on spectral-domain (SD) OCT in patients with sickle cell compared with controls. Design Retrospective, longitudinal study. Participants Patients with sickle cell and age-similar control patients with SD-OCT macula volume scans at least 10 months apart were reviewed. Methods Automated segmentation of the SD-OCT macula volume scans was performed using the Iowa Reference Algorithms to divide the retina into 3 combined retina layers: superficial (retinal nerve fiber layer and ganglion cell layer), middle (inner plexiform layer and inner nuclear layer), and outer (outer plexiform layer to retinal pigment epithelium). The mean retinal thickness in each Early Treatment Diabetic Retinopathy Study (ETDRS) subfield was recorded. The rate of retinal thickness change was calculated using a multilevel mixed-effects model. Main Outcome Measures The rate of retinal thickness change in the superficial, middle, and outer retina. Results Thirty-eight eyes of 24 patients with sickle cell (age: mean 40 years, range 18–67 years; genotype: 12 hemoglobin SS, 11 hemoglobin SC, 1 not available) and 30 eyes of 30 control patients were followed on average for 25.5 months. The mean initial retinal thickness was thinner in the sickle cell group compared with the control group (superficial: 69.95 vs. 72.22 μm; middle: 65.24 vs. 71.22 μm; outer: 171.37 vs. 175.55 μm). The mean rate of retinal thinning was greater for the sickle cell group than the control group (superficial: −0.89 vs. −0.41 μm/year; middle: −0.45 vs. +0.18 μm/year; outer: −0.50 vs. −0.02 μm/year). The rate of thinning in patients with sickle cell was statistically significant (P Conclusions Patients with sickle cell exhibit a progressive retinal thinning predominantly affecting the superficial and middle retina that may represent chronic microvascular insult.
The Faith Frame: Or, Belief is Easy, Faith is Hard

This paper argues for thinking about religious commitments as different in kind from everyday ordinary understandings of the world. It argues against the straightforward assertion from the cognitive science of religion that belief in the supernatural is easy. That is, there is a way in which intuitions of invisible presence come very easily to people. Yet to sustain that belief commitment is hard, especially when the invisible other is omnipotent and benevolent. Here I suggest that it makes more sense to understand faith commitments as a kind of frame that coexists with everyday commitments. The approach shares much with Neil van Leeuwen’s understanding of religious commitments and factual commitments as being held with different kinds of cognitive attitudes. Here I suggest that people engage the faith frame the way engage play and fiction—except that in the case of faith, the commitment is a serious claim about the world.
A Comparison of the Central versus Peripheral Gastrointestinal Prokinetic Activity of Two Novel Ghrelin Mimetics.

The gastrointestinal (GI) prokinetic effects of ghrelin occur through direct peripheral effects on ghrelin receptors within the enteric nervous system and via the ghrelin receptor on the vagus nerve, which activate a centrally mediated mechanism. However, the relative contribution of peripheral versus central effects to the overall prokinetic effect of ghrelin agonists requires further investigation. Here, we investigated the central versus peripheral prokinetic effect of ghrelin by using two novel ghrelin agonists: HM01 (N′-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-methyl-N-[1,3,3-trimethyl-(4R)-piperidyl]-urea HCL) with high brain penetration compared with HM02 (N′-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-hydroxy-N-(1-methyl-4-piperidinyl)-urea), a more peripherally acting ghrelin agonist. The pharmacokinetic profiles of both ghrelin agonists were evaluated after intravenous and oral administration in rats. The efficacy of HM01 and HM02 was assessed in a rat model of postoperative ileus (POI) induced by abdominal surgery and in a rodent defecation assay. Pharmacokinetic results in our models confirmed that HM01, but not HM02, was a brain-penetrant ghrelin agonist. Administration of either HM01 or HM02 reversed the delayed upper and lower gastrointestinal transit induced by abdominal surgery to levels resembling the non-POI controls. In the defecation test, HM01, but not HM02, significantly increased the weight of fecal pellets. Our findings suggest that, in a rodent model of POI, synthetic ghrelin agonists stimulate GI transit through a peripheral site of action. However, in the defecation assay, our data suggest that a ghrelin-mediated mechanism is located at a central site. Taken together, a ghrelin agonist with both central and peripheral prokinetic activity may show therapeutic potential to treat delayed GI transit disorders.
The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness

Mitogen-activated protein kinase 6 (MAPK6) represents an atypical MAPK also known as extracellular signal-regulated kinase 3 (ERK3), which has been shown to play roles in cell motility and metastasis. ERK3 promotes migration and invasion of lung cancer cells and head and neck cancer cells by regulating the expression and/or activity of proteins involved in cancer progression. For instance, ERK3 upregulates matrix metallopeptidases and thereby promotes cancer cell invasiveness, and it phosphorylates tyrosyl-DNA phosphodiesterase 2, thereby enhancing chemoresistance in lung cancer. Here we discovered that ERK3 plays a converse role in melanoma. We observed that BRAF, an oncogenic Ser/Thr kinase, upregulates ERK3 expression levels by increasing both ERK3 messenger RNA levels and protein stability. Interestingly, although BRAF's kinase activity was required for upregulating ERK3 gene transcription, BRAF stabilized ERK3 protein in a kinase-independent fashion. We further demonstrate that ERK3 inhibits the migration, proliferation and colony formation of melanoma cells. In line with this, high level of ERK3 predicted increased survival among patients with melanomas. Taken together, these results indicate that ERK3 acts as a potent suppressor of melanoma cell growth and invasiveness.
Cardiac Event Rate in Hypertrophic Cardiomyopathy Patients

Background: ICD implantation can prevent sudden cardiac death (SCD) in high risk hypertrophic cardiomyopathy (HCM) patient. However, selecting patient to receive an ICD for primary prevention is challenging. ICD implantation also carries some risks. Aim: The aims of this study: (1) To evaluate the incidence of VT, VF in HCM patients. (2) To evaluate the mean time duration to the first appropriate shock. (3) To evaluate the incidence of inappropriate shock. Method: Retrospective analysis from the registry of ICD implantations for 51 HCM patients over the past 10 years in IJN with 35 primary preventions (group 1) and 16 secondary prevention (group 2). Results: Mean follow up duration time in group 1: 44±33.6 mths, 6 patients developed VT with appropriate shock (17%), mean duration time to first shock: 34.7±21.9 mths, 2 patients developed electrical storm (5.7%). In group 2 with follow up duration: 38.40+28.8 months, 9 patients developed VT with appropriate shock (56%), mean duration time to first shock: 5.76+6.24 months, 5 patients developed electrical storm (31%). No patient developed VF. Conclusion: Although the number of patient is rather small but with good follow up duration, the study demonstrated high incidence of VT in primary group. Secondary group had higher incedence and shorter duration time to develop event.
Cyberbullying: Playground Politics (and Worse) in Cyberspace

Cyberbullying is the act of using electronic means (e.g., e-mail, instant messaging, chat rooms, websites, gaming sites, cellular phones) to threaten, humiliate, insult, exclude, or intimidate others. However, given unique aspects of virtual communication (e.g., lack of vocal intonation, facial expression, body language) it is sometimes difficult to identify cyberbullying. Further, the three central features of traditional bullying (e.g., bullying not using electronic means), repetition, power imbalance, and intent to harm are complicated by the nuances of cyberbullying. This chapter discusses the definition of cyberbullying as well as defining the roles in the cyberbullying dynamic and explaining the different methods (e.g., exclusion, flaming) and means (e.g., text messaging, e-mail) used to cyberbully. The devastating consequences of cyberbullying on cybervictims, cyberbullies, and cyberbully-victims are discussed as well as the commonalties between cyberbullying and traditional bullying.
Wearable Technology to Quantify the Nutritional Intake of Adults: Validation Study

Background: Wearable and mobile sensor technologies can be useful tools in precision nutrition research and practice, but few are reliable for obtaining accurate and precise measurements of diet and nutrition. Objective: This study aimed to assess the ability of wearable technology to monitor the nutritional intake of adult participants. This paper describes the development of a reference method to validate the wristband’s estimation of daily nutritional intake of 25 free-living study participants and to evaluate the accuracy (kcal/day) and practical utility of the technology. Methods: Participants were asked to use a nutrition tracking wristband and an accompanying mobile app consistently for two 14-day test periods. A reference method was developed to validate the estimation of daily nutritional intake of participants by the wristband. The research team collaborated with a university dining facility to prepare and serve calibrated study meals and record the energy and macronutrient intake of each participant. A continuous glucose monitoring system was used to measure adherence with dietary reporting protocols, but these findings are not reported. Bland-Altman tests were used to compare the reference and test method outputs (kcal/day). Results: A total of 304 input cases were collected of daily dietary intake of participants (kcal/day) measured by both reference and test methods. The Bland-Altman analysis had a mean bias of −105 kcal/day (SD 660), with 95% limits of agreement between −1400 and 1189. The regression equation of the plot was Y=−0.3401X+1963, which was significant (P<.001), indicating a tendency for the wristband to overestimate for lower calorie intake and underestimate for higher intake. Researchers observed transient signal loss from the sensor technology of the wristband to be a major source of error in computing dietary intake among participants. Conclusions: This study documents high variability in the accuracy and utility of a wristband sensor to track nutritional intake, highlighting the need for reliable, effective measurement tools to facilitate accurate, precision-based technologies for personal dietary guidance and intervention.
Dynamics of the Stool Virome in Very Early-Onset Inflammatory Bowel Disease.

Background and Aims Dysbiosis of the gut microbiota is a well-known correlate of the pathogenesis of inflammatory bowel disease [IBD]. However, few studies have examined the microbiome in very early-onset [VEO] IBD, which is defined as onset of IBD before 6 years of age. Here we focus on the viral portion of the microbiome—the virome—to assess possible viral associations with disease processes, reasoning that any viruses potentially associated with IBD might grow more robustly in younger subjects, and so be more detectable. Methods Virus-like particles [VLPs] were purified from stool samples collected from patients with VEO-IBD [n = 54] and healthy controls [n = 23], and characterized by DNA and RNA sequencing and VLP particle counts. Results The total number of VLPs was not significantly different between VEO-IBD and healthy controls. For bacterial viruses, the VEO-IBD subjects were found to have a higher ratio of Caudovirales vs to Microviridae compared to healthy controls. An increase in Caudovirales was also associated with immunosuppressive therapy. For viruses infecting human cells, Anelloviridae showed higher prevalence in VEO-IBD compared to healthy controls. Within the VEO-IBD group, higher levels of Anelloviridae DNA were also positively associated with immunosuppressive treatment. To search for new viruses, short sequences enriched in VEO-IBD samples were identified, and some could be validated in an independent cohort, although none was clearly viral; this provides sequence tags to interrogate in future studies. Conclusions These data thus document perturbations to normal viral populations associated with VEO-IBD, and provide a biomarker—Anelloviridae DNA levels—potentially useful for reporting the effectiveness of immunosuppression.
Weddell Sea Phytoplankton Blooms Modulated by Sea Ice Variability and Polynya Formation

Author(s): VonBerg, Lauren; Prend, Channing J; Campbell, Ethan C; Mazloff, Matthew R; Talley, Lynne D; Gille, Sarah T
College Graduation and Wealth Accumulation: Blacks' Diminished Returns.

Background: Based on the Minorities’ Diminished Returns (MDRs) framework, indicators of high S ocioeconomic S tatus (SES), such as high maternal educational attainment, show weaker protective effects on various developmental, behavioral, and health outcomes for Black than White families. As a result of these MDRs, families and individuals with high educational attainment still report high levels of depression, smoking, obesity, and chronic disease. Limited knowledge exists on MDRs of maternal education on indicators of wealth such as home ownership and home value. Aims: Built on the MDRs framework, we tested the hypothesis of whether the effects of maternal educational attainment at birth on home ownership and home value, as proxies of wealth, vary between Black and White families. We hypothesized that: 1) high maternal education would be associated with more wealth 15 years later, and 2) compared to Whites, Blacks would be less likely to accumulate wealth (own a house) across all educational levels, given a weaker boosting effect of maternal educational attainment on wealth for Black than White families. Methods: The Fragile Families and Child Well-being Study, is a 15-year follow up study of a random sample of births in cities larger than 200,000 population in the US. A total number of 2004 White or Black youth were included and were followed from birth to the age of 15. The predictor of interest was maternal educational attainment at birth, treated as a categorical variable (college graduation). The outcomes were home ownership and home value (worth - owed) 15 years later, as proxies of wealth. Logistic and linear regression were used for data analysis. Results: High maternal education at birth was associated with home ownership and higher value of owned home at age 15. We also found that maternal educational attainment at birth and race interact with each other, suggesting that the effects of high maternal educational attainment at birth on home ownership/value at age 15 were weaker for Black than White families. Conclusions: Diminished returns of maternal educational attainment at birth on wealth accumulation in Black families may be a mechanism that contributes to racial health disparities in high socioeconomic status and also poor outcomes of high SES Black families. That is, a smaller effect of maternal educational attainment on changing the real lives of Black than White youth may be one of the mechanisms by which health remains worse than expected in high SES Black families. Not all of the health, behavioral, and developmental disparities are due to the racial gap in SES but also diminishing returns of socioeconomic status indicators such as maternal educational attainment for racial minorities. Research should study how social stratification, discriminatory mortgage and banking, residential segregation, family formation, employment, and occupational prestige reduce Black families’ ability to mobilize their human capital and secure tangible economic and non-economic outcomes.
Neurothrombectomy for Acute Ischemic Stroke Across Clinical Trial Design and Technique: A Single Center Pooled Analysis

Introduction: The practice of endovascular therapy has evolved dramatically over the last 10 years with randomized clinical trials investigating the benefit of thrombectomy in select patient populations based on time of presentation, imaging criteria, and procedural technique. We sought to understand the benefit of thrombectomy in patients treated within the context of a clinical trial at a single academic center. Methods: Patient-level data recorded in case forms and core-lab adjudicated data were analyzed from patients enrolled in RCTs investigating the benefit of endovascular thrombectomy over medical management (IMSIII, MR RESCUE, ESCAPE, SWIFT PRIME, and DAWN) between 2007 and 2017 at a single academic referral center. Results: A total of 134 patients (intervention group, n = 81; medical group, n = 53) were identified across five clinical trials (IMSIII, n = 46; MR RESCUE, n = 4; ESCAPE, n = 24; SWIFT PRIME, n = 14; DAWN, n = 46). There were no significant differences between the treatment arm and control arm in terms of age, gender, baseline NIHSS, ASPECTS, and site of occlusion. Rates of good outcome were superior in the intervention group with early neurological recovery (NIHSS of 0-1 or increase NIHSS of 8 points at 24 h) at a higher rate of 49% vs. 17% (p = <0.001) and higher rates of functional independence (90 day mRS 0-2 of 53% vs. 26%, p = 0.002). In multivariate logistic regression analysis, lower NIHSS and younger age were predictors of good outcome. There were comparable rates of good outcome irrespective of clinical trial, imaging selection criteria (CTP vs. MRI), early vs. late time window (0-6 h vs. 6-24 h) and procedural technique (Merci vs. Solitaire/Trevo device). There were no differences in rates of sICH, PH-2 or mortality in the intervention group vs. medical group. Conclusions: At a large academic center, the benefit of endovascular therapy over medical therapy is observed irrespective of clinical trial design, patient selection or procedural technique.
Landfall After the Perfect Storm: Cohort Differences in the Relationship Between Debt and Risk of Heart Attack

Analyses of the Health and Retirement Study (HRS) between 1992 and 2014 compare the relationship between different levels and forms of debt and heart attack risk trajectories across four cohorts. Although all cohorts experienced growing household debt, including the increase of both secured and unsecured debt, they nevertheless encountered different economic opportunity structures and crises at sensitive times in their life courses, with implications for heart attack risk trajectories. Results from frailty hazards models reveal that unsecured debt is associated with increased risk of heart attack across all cohorts. Higher levels of housing debt, however, predict higher rates of heart attack among only the earlier cohorts. Heart attack risk trajectories for Baby Boomers with high levels of housing debt are lower than those of same-aged peers with no housing debt. Thus, the relationship between debt and heart attack varies by level and form of debt across cohorts but distinguishes Baby Boomer cohorts based on their diverse exposures to volatile housing market conditions over the sensitive household formation period of the life course.
Practice patterns and results of tumor and germline genetic evaluation of women with endometrial cancer in south Louisiana.

Abstract The objectives were to describe rates of MMRd or MSI-H EC tumors, the prevalence of LS, the practice patterns of EC genetic evaluation and adherence to NCCN guidelines, and to identify disparities in the genetic evaluation of women with EC. A retrospective cohort study was performed on women with EC from 1/2013 to 12/2019, and information collected included demographics, personal and family history, EC diagnosis and treatment, and details of genetic evaluation. Statistical analysis included a multivariable logistic regression to adjust for all covariate effects simultaneously and Fisher exact tests of independence and Wilcoxon rank-sum tests to compare categorical and continuous covariates, respectively. Of the 286 women with EC, 80 EC tumors were tested, and 27.5% were MMRd or MSI-H. Of the 21 women who had germline testing, no cases of LS were identified. Before the NCCN recommended universal tumor testing, 17.6% of women had tumor testing performed compared to 60.0% after February of 2017 (OR = 2.51, 95% CI 1.89–3.32). Advanced cancer stage was nearly associated with an increased likelihood of tumor testing (OR = 1.40, 95% CI 1.00–1.97). No disparities were identified. We described patterns of genetic evaluation and tumor testing results for women with EC in south Louisiana and found similar rates of MMRd or MSI-H EC tumors as previously reported in other populations. Rates of tumor testing increased after the NCCN recommendation for universal tumor testing, but it is critical to identify weaknesses in this process and develop an algorithm to improve care for women with EC.
Predicting muscular strength using demographics, skeletal dimensions, and body composition measures

Abstract The purpose of this study was to develop an equation to predict strength for seven common resistance training exercises using anthropometric and demographic measures. One-hundred forty-seven healthy adults (74 males, 73 females, 35 ± 12 yr, 174 ± 10 cm, 88 ± 19 kg) volunteered to participate. Body composition values (regional/total) and body dimensions were assessed using dual-energy x-ray absorptiometry (DEXA). Subjects underwent the following maximal strength assessments: Leg Press, Chest Press, Leg Curl, Lat Pulldown, Leg Extension, Triceps Pushdown, and Biceps Curl. Multiple linear regression with stepwise removal was used to determine the best model to predict maximal strength for each exercise. Independent predictor variables identified (p
10.3 A 100MHz-BW 68dB-SNDR Tuning-Free Hybrid-Loop DSM with an Interleaved Bandpass Noise-Shaping SAR Quantizer

Emerging communication and radar applications place enormous demands on ADC performance by requiring wide BW (100MHz) and high DR (70dB). Continuous-time delta-sigma modulators (CT-DSM) [1–2] are a mainstream solution as they deliver high amplifier efficiency, are easy to drive, and provide innate anti-aliasing. However, CTDSMs have some inherent drawbacks: 1) the loop filter is typically based on RC time-constants which are poorly defined and require digital tuning; 2) they do not scale with sampling frequency; and 3) they are very sensitive to DAC ISI and jitter [2]. Discrete-time (DT) DSMs, such as the emerging noise-shaping (NS) SAR architecture, avoid these problems, but cannot provide the essential benefits of CT-DSMs. We propose the new hybrid-loop (HL) DSM architecture, which combines the advantages of both CT and DT DSMs and eliminates the drawbacks. Moreover, a bandpass, time-interleaved noise-shaping (TINS) SAR quantizer [3] further boosts the new architecture’s performance. The prototype HL-DSM provides 68dB SNDR over a 100MHz BW for a quadrature input, without any calibration or tuning, while occupying only 0.09mm2 and consuming 13mW at 1.6GS/s. The resulting 166dB FoM S shows the potential of the HL-DSM as a more robust and practical alternative to CT-DSM.
Numerical investigation of the penetrating gas flow into particle clusters for circulating fluidized beds

Abstract Gas-solid circulating fluidized beds (CFBs) are widely used as reactors in industry with performances heavily relying on the interaction between gas and particles. In a CFB, some particles stay dispersed, while other particles aggregate to form dense and large clusters. As the gas-particle interaction is simple for dispersed particles, the prediction of reactor performances calls for a thorough analysis of the gas-cluster interaction. In the literature, cluster properties have been characterized extensively. However, how the gas interacts with clusters has not been quantified systematically yet. In this work, the gas-cluster interaction was quantified numerically by characterizing the penetrating gas flow into clusters. With 99 simulations, influences of the particle randomness, cluster solids holdup, cluster diameter, particle diameter, superficial gas velocity and fluid properties on the gas-cluster interaction were investigated systematically. Then, an empirical correlation was proposed to quantify the gas-cluster interaction, significantly contributing to the design and optimization of CFBs.
Psychometric properties of the PEDI-CAT for children and youth with spinal muscular atrophy.

Purpose The purpose of this study was to examine the psychometric properties of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) in children and youth with Spinal Muscular Atrophy (SMA). Methods In this prospective cross-sectional study, caregivers of children and youth with SMA completed the PEDI-CAT Daily Activities and Mobility domains. A subset of caregivers completed a questionnaire about the measure. Results Mean ranks of scaled scores for Daily Activities (n = 96) and Mobility (n = 95) domains were significantly different across the three SMA types and across the three motor classifications. Normative scores indicated that 85 participants (89.5%) had limitations in Mobility and 51 in Daily Activities (53.1%). Floor effects were observed in≤10.4%of the sample for Daily Activities and Mobility. On average, caregivers completed the Mobility domain in 5.4 minutes and the Daily Activities domain in 3.3 minutes. Most caregivers reported that they provided meaningful information (92.1%), were willing to use the PEDI-CAT format again (79%), and suggested adding content including power wheelchair mobility items. Conclusion Convergent validity was demonstrated for the Daily Activities and Mobility domains. Normative scores detected limitations in Mobility and Daily Activity performance for most participants with SMA. The PEDI-CATwas feasible to administer and caregivers expressed willingness to complete the PEDI-CAT in the future.
The multiscale nature of the brain and traumatic brain injury

Abstract The complex multiscale nature of the brain’s structure requires that each length scale be considered to understand injuries to the brain. Experimentally, this includes a mix of in vivo, ex vivo, and in vitro tests. However, these experiments are not sufficient to identify, explain, and quantify injury mechanisms across the length scales, necessitating the use of computational methods. This chapter provides an overview of the brain’s multiscale structure to demonstrate the brain’s interconnected structural hierarchy. Additionally, an overview of the multiscale aspects of traumatic brain injury (TBI) is introduced, including types of injuries, examples of injuries, and potential neurobehavioral sequeulae. Finally, representative methods for experiment and simulation methods related to TBI are described.
The mitochondrial deubiquitinase USP30 regulates AKT/mTOR signaling

Mitophagy is an intracellular mechanism to maintain mitochondrial health by removing dysfunctional mitochondria. The E3 ligase Parkin ubiquitinates the membrane proteins on targeted mitochondria to initiate mitophagy, and USP30 antagonizes this Parkin-dependent mitophagy. AKT/mTOR signaling is a master regulator of cell proliferation, differentiation, survival, and growth. Although mounting evidence showed mitophagy and AKT/mTOR signaling interact with each other during mitophagy, the specific mechanisms between Parkin/USP30 and AKT/mTOR signaling have not been elucidated. This research artificially expressed Parkin and USP30 in Hela cells and compared AKT/mTOR and apoptosis signals between Hela cells, HeLa Parkin cells, and Hela Parkin USP30 cells during mitophagy. The study results suggest that Parkin promotes AKT degradation via ubiquitination, which induces cell apoptosis during mitochondrial stress. On the contrary, USP30 protects AKT via deubiquitination. These findings provide new insights into the roles of Parkin and USP30 in cell apoptosis and physiological and pathological functions of USP30 beyond mitophagy.
Real-time Wireless Transmitter Authorization: Adapting to Dynamic Authorized Sets with Information Retrieval.

As the Internet of Things (IoT) continues to grow, ensuring the security of systems that rely on wireless IoT devices has become critically important. Deep learning-based passive physical layer transmitter authorization systems have been introduced recently for this purpose, as they accommodate the limited computational and power budget of such devices. These systems have been shown to offer excellent outlier detection accuracies when trained and tested on a fixed authorized transmitter set. However in a real-life deployment, a need may arise for transmitters to be added and removed as the authorized set of transmitters changes. In such cases, the system could experience long down-times, as retraining the underlying deep learning model is often a time-consuming process. In this paper, we draw inspiration from information retrieval to address this problem: by utilizing feature vectors as RF fingerprints, we first demonstrate that training could be simplified to indexing those feature vectors into a database using locality sensitive hashing (LSH). Then we show that approximate nearest neighbor search could be performed on the database to perform transmitter authorization that matches the accuracy of deep learning models, while allowing for more than 100x faster retraining. Furthermore, dimensionality reduction techniques are used on the feature vectors to show that the authorization latency of our technique could be reduced to approach that of traditional deep learning-based systems.
Empirical identification and validation of tumor-targeting T cell receptors from circulation using autologous pancreatic tumor organoids.

Background Tumor-specific cytotoxic T cells and T cell receptors are effective tools for cancer immunotherapy. Most efforts to identify them rely on known antigens or lymphocytes that have infiltrated into the tumor bed. Approaches to empirically identify tumor-targeting T cells and T cell receptors by exploiting all antigens expressed on tumor cell surfaces are not well developed for most carcinomas, including pancreatic cancer. Methods Autologous tumor organoids were stimulated with T cells from the patients’ peripheral blood for 2 weeks to generate the organoid-primed T (opT) cells. opT cell phenotype was analyzed by monitoring changes in the expression levels of 28 cell surface and checkpoint proteins. Expression of ligands of the immune checkpoints was investigated by immunohistochemistry staining. T cells were labeled with carboxyfluorescein succinimidyl ester (CFSE) and assayed by flow cytometry to monitor tumor-induced T cell proliferation changes. opT cell-mediated killing of three-dimensional organoids was measured using an M30 ELISA kit. T cell receptors (TCRs) were identified by deep sequencing of gDNA isolated from T cells, and the TCR specificity was confirmed by transferring TCRs to the T cell line SKW-3 or donor T cells. Results The co-culture was effective in the generation of CD8 + or CD4+opT cells. The opT cells killed autologous tumors in a granzyme B or Fas-Fas ligand-dependent manner and expressed markers of tissue-resident memory phenotype. Each patient-derived opT cell culture displayed a unique complement of checkpoint proteins. Interestingly, only NKG2A blockade showed a potent increase in the interferon-γ production compared with blocking programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) or TIM3 or TIGIT or LAG3. Importantly, TCR sequencing demonstrated a dramatic clonal expansion of T cells with a restricted subset of TCRs. Cloning and transferring the TCRs to heterologous T cells was sufficient to confer tumor cell recognition and cytotoxic properties in a patient-specific manner. Conclusion We report a platform for expanding tumor-targeting T cells from the peripheral blood of patients with pancreatic cancer. We identify the NKG2A-HLA-E axis as a potentially important checkpoint for CD8 +T cells for pancreatic cancer. Lastly, we demonstrate empirical identification of tumor-targeting TCRs that can be used for TCR-therapeutics.
Eye movement-driven defense against iris print-attacks

This paper proposes a methodology for the utilization of eye movement cues for the task of iris print-attack detection. We investigate the fundamental distortions arising in the eye movement signal during an iris print-attack, due to the structural and functional discrepancies between a paper-printed iris and a natural eye iris. The performed experiments involve the execution of practical print-attacks against an eye-tracking device, and the collection of the resulting eye movement signals. The developed methodology for the detection of print-attack signal distortions is evaluated on a large database collected from 200 subjects, which contains both the real ('live') eye movement signals and the print-attack ('spoof') eye movement signals. The suggested methodology provides a sufficiently high detection performance, with a maximum average classification rate (ACR) of 96.5% and a minimum equal error rate (EER) of 3.4%. Due to the hardware similarities between eye tracking and iris capturing systems, we hypothesize that the proposed methodology can be adopted into the existing iris recognition systems with minimal cost. To further support this hypothesis we experimentally investigate the robustness of our scheme by simulating conditions of reduced sampling resolution (temporal and spatial), and of limited duration of the eye movement signals. Eye movement cues are used for iris print-attack detection.Feature extraction is based on statistical modeling of signal distortions.Print-attack detection performance reaches a top rate of 96.5%.Extended analysis regarding the signal recording conditions is performed.
Hyperlink-Aware Mining and Analysis of the Web

The approximately seven billion hyperlinks on the WWW, and the anchortext surronding them, represent a valuable collection of editorial information about web pages. We begin by discussing methods for incorporating this link information into web search. Next, we consider a follow-on question: is it possible to apply data mining techniques to the link structure of the web in order to discover all communities, including those that have only just formed and whose members may not yet be aware of one another. We also consider modeling and measurement of this hyperlink structure. A recent analysis of the web graph indicates that the macroscopic structure is considerably more intricate than suggested by earlier experiments. We describe these results, and go on to discuss some progress towards defining analytical models for graphs such as the web. The work described here is joint with Andrei Broder, Ravi Kumar, Farzin Maghoul, Prabhakar Raghavan, Raymie Stata, Sridhar Rajagopalan, Eli Upfal and Janet Wiener.
Coupling of dephosphorylation and nuclear export of smads in TGF-β signaling

In eukaryotes, regulation of signaling mediators/effectors in the nucleus is one of the principal mechanisms that govern duration and strength of signaling. Smads are a family of structurally related intracellular proteins that serve as signaling effectors for transforming growth factor beta (TGF-beta) and TGF-beta-related proteins. Accumulating evidence demonstrates that Smads possess intrinsic nucleocytoplasmic shuttling capacity, which enables them to transmit TGF-beta signals from cell membrane to nucleus. We recently identified two important steps in the termination of nuclear Smad signaling. The first step is initiated by a serine/threonine phosphatase PPM1A that dephosphorylates Smad2/3 in the nucleus, thereby shutting down signaling capacity of phosphorylated Smad2/3. The second step involves nuclear export of dephosphorylated Smad2/3 with the aid of nuclear protein RanBP3 to terminate Smad signaling. This chapter introduces methods for examining nuclear export of Smad2/3 in TGF-beta signaling.
Mitochondrial depolarization in glutamate-stimulated neurons : an early signal specific to excitotoxin exposure

A brief exposure to high concentrations of glutamate kills cultured forebrain neurons by an excitotoxic process that is dependent on Ca2+ influx through the NMDA receptor. In this study, we have measured striking changes in mitochondrial function during and immediately after intense glutamate receptor activation. Using indo-1 microfluorometry and a specific inhibitor of the mitochondrial Na+/Ca2+ exchanger, CGP-37157, we have demonstrated that mitochondria accumulate large quantities of Ca2+ during a toxic glutamate stimulus and further that Ca2+ efflux from mitochondria contributes to the prolonged [Ca2+]i elevation after glutamate removal. We then used JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine+ ++ iodide), a ratiometric indicator of mitochondrial membrane potential (delta psi), to show that Ca2+ accumulation within the organelle dissipates delta psi. The abrupt loss of delta psi after glutamate stimulation did not occur in the presence of MK801 or in the absence of extracellular Ca2+. The mitochondrial depolarization was also cyclosporin A-sensitive, indicating a probable role for the permeability transition pore. Hence mitochondrial Ca2+ accumulation and the subsequent permeability transition may be a critical early event specific to the NMDA receptor-mediated excitotoxic cascade.
Effect of water temperature on early life history of African sharp-tooth catfish, Clarias gariepinus (Burchell, 1822)

Summary Early life history of Clarias gariepinus from egg fertilization to full yolk sac resorption was studied at 33 temperatures within the thermal range 17.4–35.6°C. The viable temperature range for embryonic development; temperature at which ontogeny is hypothetically arrested (15.4°C); viable temperature range for larval development; and the number of effective day-degrees for the embryonic and larval periods were determined. The early life history of C. gariepinus was found to be temperature-dependent in terms of the onset of key ontogenetic events, developmental rate, survival rate, and size of larvae. The length of the incubation period, hatching period, size of larvae at hatching, time to first intake of exogenous food, and time to full yolk sac resorption with and without exogenous feed supply, were inversely proportional to the temperature within the optimal temperature range. In terms of survival, the zone of thermal tolerance for early life history of C. gariepinus ranged from 18.9 to 33.2°C with the thermal optimum from 22.9 to 30.3°C, typical for thermophilous species. Temperature ranges of 20.6–22.9°C and 30.2–33.2°C were found to be suboptimal. Temperatures below 17.5 and above 35.1°C may be considered lethal during the embryonic period, and those below 18.9 and above 33.2°C are lethal during the larval period.
Muscles Get Dendrites into Shape

Sensory neurons interact with muscles in many contexts, but muscle-derived signals that pattern sensory dendrites have not been extensively characterized. In this issue of Developmental Cell, Liang et al. (2015) report a signaling system in which positional cues from muscle are transduced to hypodermal cells to direct sensory dendrite outgrowth.
A Review of “The Initial Psychotherapy Interview: A Gay Man Seeks Treatment.”

If a friend were to ask you “what kind of therapist should I be looking for?”, what might you say? If a gay friend were to ask you the same question, would your answer be the same? What are the hal...
A Phospholipase D-mediated Pathway for Generating Diacylglycerol in Nuclei from Madin-Darby Canine Kidney Cells *

Many receptors, in response to their specific ligands, trigger activation of phospholipase D (PLD), resulting in the production of phosphatidic acid which, in turn, is acted upon by a specific phosphatase, phosphatidate phosphohydrolase, to produce diacylglycerol. We report here that isolated nuclei from Madin-Darby canine kidneys (MDCK)-D1 cells exhibit a PLD activity that is enhanced by the presence of ATP. PLD activity was measured in the presence of ethanol, by quantitating the production of phosphatidylethanol. Non-phosphorylating ATP analogs were unable to substitute for ATP in activating PLD, indicating that ATP acts as a phosphoryl group donor in a kinase-mediated phosphorylation reaction. The protein kinase C inhibitors chelerythrine and calphostin completely suppressed the ATP-induced nuclear PLD, implicating protein kinase C as the kinase involved in ATP-dependent PLD activity in nuclei from MDCK-D1 cells. In the absence of ethanol, phosphatidic acid was detected in ATP-treated nuclei. Accumulation of phosphatidic acid preceded or closely paralleled that of diacylglycerol, suggesting a precursor-product relationship. Consistent with those results, we detected phosphatidate phosphohydrolase activity in MDCK-D1 cell nuclei. Measurements of phosphatidic acid and diacylglycerol levels at increasing amounts of ethanol demonstrated that PLD and phosphatidate phosphohydrolase are responsible for generating the majority of the diacylglycerol accumulating in MDCK-D1 cell nuclei. The ability of nuclei to generate diacylglycerol from the concerted action of those two enzymes provides a means to regulate nuclear lipid synthesis as well as protein kinase C activity.
Productivity responses of periphyton and phytoplankton to bleach-kraft mill effluent

Abstract Responses of periphyton and phytoplankton productivity in the lower Sulphur River (Texas-Arkansas) to bleach-kraft mill effluent (BKME) were monitored using in situ 14 C incubation. Periphyton productivity was not significantly decreased downstream of mill discharge nor were periphyton productivity efficiencies. The community structure of the periphyton community shifted toward heterotrophic population near the mill discharge but recovered to upstream characteristics at downstream stations. Phytoplankton primary productivity and productivity efficiency were significantly decreased downstream of the mill discharge. These decreases were associated with increased light attenuation downstream due to the mill effluent. Chlorophyll a concentrations of periphyton and phytoplankton were not significantly altered by the mill effluent; therefore, the effluent was not lethal to the algae. Significant inverse relationships found with increased light attenuation indicators (ϵ and selected water chemistry) indicated that light availability was associated with changes in 14 C rates.
Inelastic analysis of partially restrained unbraced steel frames

The development of a finite element for use in the inelastic ultimate load analysis of steel frames is presented. The element is capable of modelling partial plastification within the cross-section, residual stresses, shift in the elastic neutral axis with plastification and partially restrained connections. The incremental equations of equilibrium are written and the constant work implementation of the simple Euler stepping algorithm is used to trace the full nonlinear load-deformation response of several structural steel frames with partially restrained connections. The effect of connection stiffness on the load-deflection behaviour and spread of plastification throughout the frames is quantified and discussed.
Computation on abstract data types. The extensional approach, with an application to streams

Abstract In this paper we specialize the notion of abstract computational procedure previously introduced for intensionally presented structures to those which are extensionally given. This is provided by a form of generalized recursion theory which uses schemata for explicit definition, conditional definition and least fixed point (LFP) recursion in functional of type level ⩽ 2 over any appropriate structure. It is applied here to the case of potentially infinite (and more general partial) streams as an abstract data type.
Coulomb attraction between Bloch electrons

Abstract It is shown that an attractive interaction between electrons in solids exists, for states with antibonding character. It is proposed that this interaction is the origin of superconductivity in all superconducting materials.