cssi/SciSciGPT-SciSciNet huggingface dataset:
Apparent positive cooperative effects in cyclic AMP and corticosterone production by isolated adrenal cells in response to ACTH analogues.

Dose-response curves were con-structed for production of cAMP and corticosterone by isolated cells from rat adrenal cortex in response to ACTH1–24 and a number of ACTH analogues. A new method for fitting the parameters of an analogue of the Hill equation was developed, using a weighted iterative nonlinear least squares regres-sion capable of estimating both the response to zero dose (“control”), the response to “infinite dose” (“Vmax”), the ED50 or “Km”, and the “Hill coefficient.” This analysis indicates a mean Hill coefficient of 1.33 ± 0.04 for cAMP production and 1.41 ± 0.07 for corticosterone production. These results are suggestive of an apparent positive cooperative effect (possibly due to allosterism) at one or more steps in the mechanism of action of ACTH. These results are also compatible with a modified “quantal response” model of hormone action. These results appear inconsistent with simple “Michaelis-Menten” kinetics or with a mechanism involving two simple Michaelis-Menten type reactions in ...
Crystallographic and Biochemical Analysis of Rotavirus NSP2 with Nucleotides Reveals a Nucleoside Diphosphate Kinase-Like Activity

Rotavirus, the major pathogen of infantile gastroenteritis, carries a nonstructural protein, NSP2, essential for viroplasm formation and genome replication/packaging. In addition to RNA-binding and helix-destabilizing properties, NSP2 exhibits nucleoside triphosphatase activity. A conserved histidine (H225) functions as the catalytic residue for this enzymatic activity, and mutation of this residue abrogates genomic double-stranded RNA synthesis without affecting viroplasm formation. To understand the structural basis of the phosphatase activity of NSP2, we performed crystallographic analyses of native NSP2 and a functionally defective H225A mutant in the presence of nucleotides. These studies showed that nucleotides bind inside a cleft between the two domains of NSP2 in a region that exhibits structural similarity to ubiquitous cellular HIT (histidine triad) proteins. Only minor conformational alterations were observed in the cleft upon nucleotide binding and hydrolysis. This hydrolysis involved the formation of a stable phosphohistidine intermediate. These observations, reminiscent of cellular nucleoside diphosphate (NDP) kinases, prompted us to investigate whether NSP2 exhibits phosphoryl-transfer activity. Bioluminometric assay showed that NSP2 exhibits an NDP kinase-like activity that transfers the bound phosphate to NDPs. However, NSP2 is distinct from the highly conserved cellular NDP kinases in both its structure and catalytic mechanism, thus making NSP2 a potential target for antiviral drug design. With structural similarities to HIT proteins, which are not known to exhibit NDP kinase activity, NSP2 represents a unique example among structure-activity relationships. The newly observed phosphoryl-transfer activity of NSP2 may be utilized for homeostasis of nucleotide pools in viroplasms during genome replication.
Capturing deviation from ergodicity at different scales

Abstract We address here the issue of quantifying the extent to which a given dynamical system falls short of being ergodic and introduce a new multiscale technique which we call the “ergodicity defect”. Our approach is aimed at capturing both deviation from ergodicity and its dependence on scale. The method uses ergodic theory of dynamical systems and applies harmonic analysis, in particular the scaling analysis is motivated by wavelet theory. We base the definition of the ergodicity defect on the Birkhoff characterization. We systematically exploit the role of the observation function by using characteristic functions arising from a dyadic equipartition of the phase space. This allows us to view the dependence of the defect on scale. In order to build intuition, we consider the defect for specific examples with known dynamic properties and we are able to explicitly compute the defect for some of these simple examples. We focus on three distinctive cases of the dependence of the defect on scale: (1) a defect value that increases as the scale becomes finer, (2) a defect value decreasing with scale and (3) a defect value independent of scale, which occurs for instance when a map is ergodic. We explain the information contained in these three scenarios. We see more complicated behavior with an example which has invariant subsets at various scales.
Atypical soluble guanylyl cyclases in Drosophila as neutral oxygen sensors and their involvement in gestation

genome contains 5 genes that code for sGC subunits. Twoof these, Gycα-99B and Gycβ-100B form a conventionalsGC and the remaining 3 genes code for atypical subunitsGyc-88E, Gyc-89Da and Gyc-89Db. When expressed inheterologous cells, Gyc-88E forms active homodimers,whereas Gyc-89Da and Gyc-89Db are only active whenco-expressed with Gyc-88E. We cannot detect any bio-chemical differences between Gyc-89Da and Gyc-89Db.The atypical sGCs are only stimulated 2–4 fold by NOdonors, whereas Gyc α-99B/Gycβ-100B is stimulated up to100 fold. The atypical sGCs, by contrast, are potently acti-vated when incubated in an oxygen-free environment.This activation is graded over 0-21% oxygen and can bedetected within 1 minute when cells expressing the subu-nits are exposed to 100% nitrogen. The sGC inhibitorODQ inhibits the activation. These biochemical proper-ties are consistent with a role as molecular oxygen sensorsand are also supported by studies in
Detecting cervical microstructure via ultrasound and optical microscopy

A novel method for characterizing the microstructural integrity of the human cervix is under development. The cervix is composed of mostly aligned collagen and variations in acoustic backscattered power as a function of beam steering is an indicator of anisotropic scatterers. Results of experiments with phantoms and hysterectomy specimens suggest that this approach is a sensitive tool for describing the microstructure.
Misconceptions regarding spin 3/2.

Recent work involving virtual excitation of a spin (3/2) baryon resonance is seen to contain two distinct problems. The Feynman propagator for spin (3/2) from the Rarita-Schwinger formalism has often been mistaken for its on-mass-shell limit. In nonrelativistic work the direct channel exchange of a \ensuremath{\Delta} resonance is normally included, but with the exclusion of a term for the intermediate anti-\ensuremath{\Delta}. It is shown that both of these terms are of equal importance in the resonance region for the case of nucleon Compton scattering.
321: Correlation of Cylex ImmuKnow assay with lung allograft biopsy

PGD grade and ICU-days was seen in the extubated patients (r 0.14, p ns) in contrast to intubated patients (r 0.27, p 0.02). Intubated PGD grade 3 patients at T24 were associated with nitric oxide (40%), ECMO (33%) and differential-ventilation (13%) (nil in extubated patients). Thirty-day mortality in the extubated and intubated patients at T24 was 3% and 9%, respectively (p 0.04). Conclusions: The distribution and clinical impact of PGD grades in intubated and extubated patients are significantly different. Thus, it is recommended that extubated patients be automatically included as ‘grade 0-1’.
Adult survivors of childhood cancers' identity disclosures in the workplace.

Purpose Recent medical advances have resulted in unprecedented increases in the number and vitality of employed adult survivors. These survivors must make decisions about whether or not to disclose their identities to others. The purpose of this study was to examine the characteristics that are related to cancer survivorship disclosure in workplace settings (perceived organizational support, centrality of survivorship to one’s self-concept, and the degree to which family and friends know about one’s survivor status) and an important organizational consequence: intentions to leave one’s job.
Cognitive Correlates of Personality

Research examining associations between executive functioning (EF) and personality traits has demonstrated promising results; however, examination of associations between Big Five personality traits and EF using an established EF framework has yet to be demonstrated. The present study examines associations between three aspects of EF (i.e., Cognitive Flexibility, Inhibition, and Updating/Monitoring), based upon a well-established EF framework, and Big Five personality traits. Participants (N = 182) completed neuropsychological measures of Cognitive Flexibility, Inhibition, and Updating/Monitoring as well as a self-report measure of person- ality. Better Updating/Monitoring was associated with lower Neuroticism and higher Openness. Openness was also positively associated with Cognitive Flexibility. These findings suggest that there may be a common underlying cognitive characteristic (i.e., Updating/Mon- itoring) linked with Neuroticism and Openness. Additional implications of these findings are discussed.
Distinct Synaptic and Extrasynaptic NMDA Receptors in Developing Cerebellar Granule Neurons

In rat cerebellar granule neurons, mRNA and protein levels of the NR2A and NR2C subunits of the NMDA receptor increase during the second postnatal week. At this time, mRNA and protein levels of the NR2B subunit begin to fall. To investigate targeting of NMDA receptor subunits, we performed whole-cell recordings from rat cerebellar granule neurons at different times during development and investigated the pharmacological and biophysical properties of mossy fiber-evoked NMDA EPSCs. Isolated NMDA EPSCs from newly formed synapses in the first postnatal week exhibited partial block by the NR2B subunit-specific antagonist (1 S ,2 S )-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP 101,606). By the end of the second postnatal week, NMDA EPSCs were virtually unaffected by the NR2B antagonist. In parallel, NMDA EPSC decay times decreased over a similar developmental time course. We compared properties of synaptic NMDA receptors with extrasynaptic receptors that are present on the cell body with rapid application of glutamate to excised nucleated patches. Deactivation of patch responses accelerated with development and closely resembled evoked NMDA EPSCs in rats of the same age. However, patch responses were highly sensitive to CP 101,606 through the second postnatal week, and sensitivity was seen in some neurons up to the fourth postnatal week. Spermine potentiated peak NMDA patch responses from postnatal days 10–14 rats but had little effect on evoked NMDA EPSCs. Our data suggest selective targeting of a distinct NMDA receptor subtype to synaptic receptor populations in cerebellar granule neurons. Later in development, similar changes occur in the extrasynaptic receptor population.
Theory and implementation of a hybrid learning force control scheme

Theory and implementation of a repetitive learning control algorithm for hybrid position and force control of a robotic manipulator are presented. The complete control system will involve learning position control for translational motion tangent to an unknown surface, learning force control normal to the surface, and learning orientation control using torque feedback to maintain tangential motion relative to the surface. An IBM 7545 robot equipped with a wrist force/torque sensor was used to evaluate the performance of the proposed controller. It was found that the repetitive learning algorithm outperformed a compatible proportional-integral-derivative (PID) controller by a significant margin in terms of the tracking accuracy. This implementation also demonstrates the great flexibility and wide range of application of this control scheme, as well as its robustness to nonperiodic disturbances. >
A Gridded Reconstruction of Warm Season Precipitation for Asia Spanning the Past Half Millennium

The authors reconstructed May‐September precipitation over the Asian continent (58‐558N, 608‐1358E) back to AD 1470 on the basis of tree-ring data, historical documentary records, ice core records, and the few long-term instrumental data series available in the region. They employed the method of Regularized Expectation Maximization (RegEM) and applied it to 44 subregions within the continent. Verification exercises demonstrate that the reconstruction is skillful over most of the study domain, with eastern China, India, and other regions of humid climate displaying the greatest skill. Lower reconstruction skill is observed in semiarid andaridregions,whichwasattributableatleastinparttothescarcityofobservationsavailableforcalibration/ validation. The precipitation reconstructions agree well with previous reconstructions, where they are available. The explanatory value of the reconstruction is illustrated using five historically documented severe droughts in north-central China during the past half millennium. The reconstructions both validate and provide a larger-scale context for understanding these past climate events and their relationship with the Asian summer monsoons.
From theory to practice: utilizing integrative seminars as bookends to the Master of Public Administration program of study

Integrative seminar style courses are most often used as an application-oriented capstone in place of a thesis or comprehensive exam requirement in Master of Public Administration (MPA) degree prog...
Adsorption and dissociation of water on the (0001) surface of double hexagonal close packed americium

Ab initio total energy calculations within the framework of density functional theory have been performed for water molecule adsorption on the (0001) surface of double hexagonal packed americium using a full-potential all-electron linearized augmented plane wave plus local orbitals method (FP-L/APW + lo). Subsequent partial dissociation (OH + H) and complete dissociation (H + O + H) of the water molecule have been examined. The completely dissociated H + O + H configuration exhibit the strongest binding with the surface (3.35 eV), followed by partially dissociated species OH + H (2.23 eV), with all molecular H2O configurations showing weak physisorption (0.366 eV). For molecular adsorptions, the flat lying orientation of the water molecule if found to be more favorable for majority of the cases. In the case of partial dissociation (OH + H), the vertical orientation of OH molecule with O facing the surface adsorbed at a h3 adsorption site and the H atom adsorbed at another neighboring h3 site is found to be the most favorable. For complete dissociation (H + O + H), the dissociated species occupy three different neighboring h3 adsorption sites. The changes in work functions and net magnetic moments are presented for all the cases studied. The adsorbate-substrate interactions have been analyzed in detail using difference charge density distributions and the local density of states. The effects of adsorption on the Am 5f electron localization-delocalization characteristics have been discussed. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Patterns and Prognostic Value of Total and Differential Leukocyte Count in Chronic Kidney Disease

Summary Background and objectives The purpose of this study was to evaluate the levels and patterns of total and differential leukocyte counts and their prognostic importance in a cohort of people with and without chronic kidney disease (CKD). Design, setting, participants, & measurements Among 153 veterans without CKD and 267 with, blood leukocyte count was measured at baseline and then repeatedly over a decade. The patterns of change in leukocyte count between the two groups were compared. In the CKD cohort, the spikes in leukocyte counts were compared to the combined endpoint of ESRD and death. Results Patients with CKD had more granulocytes and eosinophils and fewer lymphocytes. Over time, granulocytes increased and lymphocytes decreased in those with and without CKD. In addition, in those with CKD, over time eosinophils fell and monocytes increased. Compared with their non-CKD counterparts, patients with CKD had between 1.5- and 3.0-fold more spikes in leukocyte counts. Independent risk factors for the combined endpoint were associated with spikes in the leukocyte counts of absolute and percent eosinophil count, percent granulocyte, and percent monocyte counts. In a multivariate adjusted joint model, both granulocyte and monocyte spikes were independently associated with ESRD and death (hazard ratio 1.67 and 1.52 respectively, P 0.05). Conclusions Compared with those without CKD, patients with CKD have more eosinophils and granulocytes and fewer lymphocytes. Greater variation in leukocytes is seen. Spikes in granulocyte and monocyte percentages among patients with CKD are of independent prognostic importance. Clin J Am Soc Nephrol 6: ●●● –●●● , 2011. doi: 10.2215/CJN.10521110
LOW VERSUS STANDARD DOSE CORONARY ARTERY CALCIUM SCANNING

Radiation exposure associated with coronary artery calcium scanning (CACS) may contribute to its delayed acceptance despite inclusion in guidelines. This study was designed to assess the accuracy of CACS acquired at radiation doses lower than mammography (0.7 mSv) and low dose lung scanning (0.65
Knowledge and Skill Measures of Emergency Medical Technicians

The role of the ambulance attendant in the emergency medical care delivery system has changed considerably over the past ten years. The major emphasis has changed from transportation to on-scene an...
Lazy Pipelines: Enhancing quality in approximate computing

Approximate computing techniques based on Voltage Over-Scaling (VOS) can provide quadratic improvements in power efficiency. However, voltage scaling is limited by the inherent fault-tolerance of an application, thus preventing VOS schemes from realizing their full potential. To gain further power efficiency a reduction of the error rate experienced in a given voltage level is required. We propose Lazy Pipelines, a micro-architectural technique that utilizes vacant cycles in a VOS functional unit to extend execution and reduce the error rate.
Fault-tolerant real-time analytics with distributed Oracle Database In-memory

Modern data management systems are required to address new breeds of OLTAP applications. These applications demand real time analytical insights over massive data volumes not only on dedicated data warehouses but also on live mainstream production environments where data gets continuously ingested and modified. Oracle introduced the Database In-memory Option (DBIM) in 2014 as a unique dual row and column format architecture aimed to address the emerging space of mixed OLTAP applications along with traditional OLAP workloads. The architecture allows both the row format and the column format to be maintained simultaneously with strict transactional consistency. While the row format is persisted in underlying storage, the column format is maintained purely in-memory without incurring additional logging overheads in OLTP. Maintenance of columnar data purely in memory creates the need for distributed data management architectures. Performance of analytics incurs severe regressions in single server architectures during server failures as it takes non-trivial time to recover and rebuild terabytes of in-memory columnar format. A distributed and distribution aware architecture therefore becomes necessary to provide real time high availability of the columnar format for glitch-free in-memory analytic query execution across server failures and additions, besides providing scale out of capacity and compute to address real time throughput requirements over large volumes of in-memory data. In this paper, we will present the high availability aspects of the distributed architecture of Oracle DBIM that includes extremely scaled out application transparent column format duplication mechanism, distributed query execution on duplicated in-memory columnar format, and several scenarios of fault tolerant analytic query execution across the in-memory column format at various stages of redistribution of columnar data during cluster topology changes.
Soluble TGF-β Type III Receptor Suppresses Malignant Progression of Human Cancer Cells

There is abundant evidence in cell and animal models that increased expression and/or activation of TGF-β can act as an autocrine as well as a paracrine factor to promote tumor progression. Elevated levels of TGF-β in tumor tissues and in plasma have been shown to be associated with poor patient outcome and to even predict early metastatic recurrence. Therefore. TGF-β antagonists that can sequester excessive TGF-β ligands and limits its tumor promoting effects in progressive cancers may have novel cancer therapeutic potentials. TGF-β type III receptor (RIII). also known as betaglycan (BG), is a proteoglycan that can present TGF-β to the type II signaling receptor, has two TGF-β binding domains and binds all three mammalian TGF-β isoforms (TGF-β1 β2, and β3) with high affinity. While the membrane-bound RIII enhances TGF-β effects. the soluble form of the receptor (sRIII or sBG), a naturally occurring protein generated by ectodomain shedding, is a potent TGF-β neutralizing agent. In this article, we analyze the effects of sRIII expression in cancer cells and the results of systemic treatment with a recombinant sRIII (rsRIII) in animal models of human breast, colon and prostate cancer. The results indicate that both ectopic expression of sRIII in cancer cells and systemic treatment with the recombinant protein in tumor bearing mice can suppress tumor growth in breast, colon, and prostate cancer xenograft models at least in part by inhibiting angiogenesis and promoting intratumoral apoptosis. Administration of rsRIII also significantly reduces lung and bone metastasis in human breast cancer models. Thus, blockade of TGF-β by rsRIII may have therapeutic potential in a wide variety of progressive cancer.
From Existential to Social Understandings of Risk: Examining Gender Differences in Nonreligion:

Across many social contexts, women are found to be more religious than men. Risk preference theory proposes that women are less likely than men to accept the existential risks associated with nonbelief. Building on previous critiques of this theory, we argue that the idea of risk is relevant to understanding the relationship between gender and religiosity if risk is understood not as existential, but as social. The research on existential risk focuses on religious identification as solely a matter of belief; as part of the movement away from this cognitivist bias, we develop the concept of social risk to theorize the ways that social location and differential levels of power and privilege influence women’s nonreligious choices. We show that women’s nonreligious preferences in many ways mirror those of other marginalized groups, including nonwhites and the less educated. We argue that nonreligion is socially risky, that atheism is more socially risky than other forms of nonreligion, and that women and memb...
Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.

ABSTRACTIntroduction: Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease.Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also dis...
Invasive Cancer of the Vulva

Vulvar cancer is an uncommon type of gynecologic cancer involving the external female genitalia. PET/MR imaging provides superior assessment for soft tissue, vaginal, and rectal invasion that allows for accurate local staging of vulvar cancer. Utilizing FDG in PET/MRI helps in detecting nodal involvement and distant metastasis as well as soft tissue delineation of local extension.
PEROXIDE SCAVENGING BY Cu(II) SULFATE AND Cu (II) (3 ,5-DIISOPROPYLSALICYLATE)2

The production of reactive oxygen species (ROS) in biological systems provides key mediators of physiological and pathological processes. Arguably the most important of this class are the partially reduced oxygen species, which include the superoxide anion radical (O2 ÷), hydrogen peroxide (H2O2), and the hydroxyl radical (•OH). These species have been proposed as mediators of both inflammation1–3 and in various stages in carcinogenesis3–5. One line of evidence supporting a role for ROS in these processes drives from the ability of exogenous scavengers for ROS to inhibit the process.
Addressing fake news: Open standards & easy identification

Fake news proliferation and distrust in news media has become an endemic problem in the American society and has aided in the corruption of civil political discourse. The formation of a standard and subsequent implementation using automated algorithmic processes will provide unbiased ratings and evaluations of online news media truthfulness in the form of easy-to-understand scores. This easily accessible information will aid in the reduction of fake news proliferation and help produce a more informed electorate.
Ultrahigh Frequency Nanomechanical Piezoresistive Amplifiers for Direct Channel-Selective Receiver Front-Ends.

Channel-selective filtering and amplification in ultrahigh frequency (UHF) receiver front-ends are crucial for realization of cognitive radio systems and the future of wireless communication. In the past decade, there have been significant advances in the performance of microscale electromechanical resonant devices. However, such devices have not yet been able to meet the requirements for direct channel selection at RF. They also occupy a relatively large area on the chip making implementation of large arrays to cover several frequency bands challenging. On the other hand, electromechanical piezoresistive resonant devices are active devices that have recently shown the possibility of simultaneous signal amplification and channel-select filtering at lower frequencies. It has been theoretically predicted that if scaled down into the nanoscale, they can operate in the UHF range with a very low power consumption. Here, for the first time nanomechanical piezoresistive amplifiers with active element dimensions ...
Recurrence of task-related electroencephalographic activity during post-training quiet rest and sleep.

Offline reactivation of task-related neural activity has been demonstrated in animals but is difficult to directly observe in humans. We sought to identify potential electroencephalographic (EEG) markers of offline memory processing in human subjects by identifying a set of characteristic EEG topographies (“microstates”) that occurred as subjects learned to navigate a virtual maze. We hypothesized that these task-related microstates would appear during post-task periods of rest and sleep. In agreement with this hypothesis, we found that one task-related microstate was increased in post-training rest and sleep compared to baseline rest, selectively for subjects who actively learned the maze, and not in subjects performing a non-learning control task. Source modeling showed that this microstate was produced by activity in temporal and parietal networks, which are known to be involved in spatial navigation. For subjects who napped after training, the increase in this task-related microstate predicted the magnitude of subsequent change in performance. Our findings demonstrate that task-related EEG patterns re-emerge during post-training rest and sleep.
Essentials of the macroscopic-microscopic folded-Yukawa approach and examples of its record in providing nuclear-structure data for simulations

The macroscopic-microscopic model based on the folded-Yukawa singleparticle potential and a “finite-range” macroscopic model is probably the approach that has provided the most reliable predictions of a large number of nuclear-structure properties for all nuclei between the proton and neutron drip lines. I will describe some basic features of the model and the development philosophy that may be the reason for its success. Examples of quantities modeled within the same model framework are, nuclear masses, ground-state level structure, including spins, ground-state shapes, fission barriers, heavy-ion fusion barriers, sub-barrier fusion cross sections, β -decay half-lives and delayed neutron emission probabilities, shape coexistence, and α -decay Qα energies to name a few. I will show how well it predicted various properties measured after published results. Rather than giving an incomplete model description here I will give a timeline of model development and provide references to typical applications and references that are sufficiently complete that several individuals have written computer codes based on these references, codes whose results have excellent agreement with ours.
In vivo and in vitro evidence for in situ activation and selective covalent binding of acetaminophen (APAP) in mouse kidney.

Acetaminophen (APAP, N-acetyl-p-aminophenol) is a widely used analgesic and antipyretic which, at high doses, causes acute hepatic centrilobular necrosis in man and a variety of laboratory animals (Proudfoot and Wright, 1970; Boyer and Rouff, 1971; Mitchell et al., 1973). In addition, acute renal proximal tubular necrosis following APAP has been reported in man (Kleinman et al., 1980; Cobden et al., 1982; Kher and Makker, 1987; Davenport and Finn, 1988). A similar lesion has been described in the Fischer rat (McMurtry et al., 1978; Newton et al., 1983) andthe CD-1 mouse (Placke et al, 1987) but the APAP metabolite responsible for the toxicity is different between species. In the rat, APAP is enzymatically deacetylated to paminophenol, a potent nephrotoxicant whose activation is independent of cytochrome P450 (Crowe et al., 1979; Calder et al., 1979; Newton et al., 1982; 1985a; 1985b). By contrast, enzymatic deacetylation of APAP is not required in the mouse but instead activation of intact APAP by cytochrome P450 appears to mediate nephrotoxicity (Bartolone et al, 1989; Emeigh Hart et al., 1989a; 1989b). Since hepatic metabolism of APAP is similarly dependent on cytochrome P450 (Mitchell et al, 1973), nephrotoxicity and renal adduct accumulation could arise from transport of a livergenerated metabolite or adduct to the kidney and not from in situ metabolism of APAP. The purpose of the present study was to determine, using renal proximal tubule (RPT) cell suspensions and immunohistochemistry, if the mouse kidney could generate such adducts in situ.
Clinical Psychology: Validity of Judgment

Over 1,000 studies have been published on the validity of judgments made by mental health professionals. In this article, highlights of the research are described. In general, mental health professionals are able to make reliable and valid judgments for some tasks, but not for others. For example, they can reliably describe psychiatric symptoms, but results vary for describing personality traits, and reliability is poor for describing defense mechanisms. As another example, clinicians' diagnoses are reliable and moderately valid, but only when they attend to diagnostic criteria. When they do not attend to criteria, biases occur (including race bias and gender bias) and some mental disorders are overdiagnosed while others are underdiagnosed. Results are also described for the following tasks: case formulation, the prediction of behavior, and the formulation of treatment decisions.
PHOTOCHEMISTRY AND PHOTOBIOLOGY OF SPORE-FORMING BACTERIA

Ten years ago, Beukers et al. (1959) and Wacker et al. (1962) observed that the pyrimidine base,thymine,could form dimers when irradiated with ultraviolet light (UV) either in frozen solution or when the thymine had been incorporated into the DNA of living cells. Figure 1 shows such a dimer in one chain of the DNA helix. Dimerization occurs when the excited complex of two adjacent pyrimidines causes the formation of a stable cyclobutane ring. Fortunately, thymine can be labeled easily with radioactivity and the dimers may be quantiated by acid hydrolysis and chromatography. Using these and other photochemical and photobiological techniques, the Setlows (see Setlow, 1960, for review) showed that the dimers caused 50 to 90% of the lethal effect of UV in viruses and bacteria. This effect can be partially circumvented by two different types of enzymatic repair. Shortly before the discovery of cyclobutane dimers, Kelner (1951) found that certain bacteria exposed to a lethal dose of light of wavelengths around 260 nm could be reactivated by exposure to light in the region of 400 nm. Cook (1967) then showed that this photoreactivation occurred by the enzymatic monomerization of the dimerized pyrimidines back to the normal base in the presence of light. The second repair mechanism occurs in cells maintained in the dark and consists of the removal of a short segment of one strand of DNA containing the dimer and resynthesis of that segment using the complementary strand as template. Cells lacking this type of repair are very sensitive to UV as one might expect (Setlow and Carrier,1964; Boyce and Howard-Flanders, 1964).
Incorporation of 15N from glycine into uric acid in gout: a follow-up study.

The incorporation of 15N-glycine into uric acid was studied three times in one gouty patient in an interim of 19 years. The objective of repeated studies was to see the effects of long-term therapy, aging, and changing life style on the nature of the metabolic aberration of uric acid metabolism in gout using 15N-glycine.
The influence of housing satisfaction on job satisfaction, job performance and overall quality of life

This study examined the possible effects that housing satisfaction may have upon overall quality of life of university faculty. Responses to a questionnaire assessing quality of life and an interview schedule assessing housing satisfaction were obtained from 60 faculty members at a large midwestern land-grant university. Multiple regression analysis indicated that total housing satisfaction is a significant predictor of overall quality of life. Introduction Studies by Andrews and Withey (1976) and Rodgers and Converse (1975) have suggested that overall quality of life is dependent on several domains or components of a person's life. Research conducted by Andrews & Withey (1974) identified 12 specific life components that affect or contribute to overall quality of life. They were: yourself, family life, money, amount of fun, house/apartment, activities with family, time to do things, spare time, national government, goods and services, health, and occupation. Rodgers and Converse (1975) incorporated both subjective and objective indicators when they examined measures of overall quality of life.
Abstract 4186: Monensin is selectively cytotoxic to cancer cells in an EMT-like state

Metastatic, drug-resistant cancer is lethal. Epithelial-to-mesenchymal transition (EMT) is a type of phenotypic plasticity that has been implicated in cancer metastasis and drug resistance. One potential therapeutic approach is to specifically target cancer cells in an EMT-like state. In this study, we have developed a cell-based high-throughput screening (HTS) protocol using the high content Operetta imaging platform to identify EMT cytotoxic compounds. This screen was performed on epithelial (PC-3E) and mesenchymal-like (TEM 4-18) cell lines, both isolated from the parental PC-3 prostate cancer cell line based on their differential ability to invade an endothelial monolayer. A library of 2,640 compounds was screened on co-cultured PC-3E GFP cells and TEM 4-18 mCherry cells. After 72h exposure to compounds, relative numbers of GFP- and mCherry-positive cells were quantitated. Dose-response curves were established for each compound exhibiting a greater toxicity against EMT-like cells. The mechanisms of action of one of the most potent and selective compound against EMT-like cells, monensin, were further evaluated. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. A closely related compound absent from the compound library, nigericin, was also evaluated and appeared to be the most potent of the three compounds tested. Monensin (10nM) induced apoptosis, cell cycle arrest, and an increase in ROS production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus, a previously known effect of monensin, in multiple cell lines most likely resulting in a blockage of intracellular protein trafficking and cell death. We then evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100nM. Supporting these findings, Gene Set Enrichment Analysis identified EMT as the top of the gene sets enriched in the sensitive group. Increased monensin sensitivity in EMT-like cells is associated with elevated uptake of H3-monensin compared to resistant cells. In conclusion, using a high-throughput screening approach, we identified monensin as a potent and specific inhibitor of cancer cells in an EMT-like state where it rapidly disrupts Golgi function. At least part of selectivity of monensin for EMT-like cells is due to increased uptake of this compound. Citation Format: Marion Vanneste, Huang Qin, Devon Moose, Mengshi Li, Michael Schultz, Meng Wu, Michael Henry. Monensin is selectively cytotoxic to cancer cells in an EMT-like state [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4186.
Locating Microgrids to Improve Smart City Resilience

Determining the best location and configuration of microgrids to support post-disaster critical infrastructure operation in smart cities is a significant issue for policymakers and electric system planners. In this paper, we propose a two-phase approach to locating microgrids to increase critical infrastructure resilience. In the first phase, we consider how to prioritize critical infrastructure components in smart cities using either a normalized combination of characteristics or a ranked list of lists method. Numerical results show that the two methods give similar results. In the second phase, we propose to combine prioritization information across multiple infrastructures geographically to identify potential locations for microgrids. A simple heuristic for location of a microgrid is proposed and compared with an optimization model that seeks to find the location that minimizes a weighted combination of prioritization information and cost.
Biomimetic sponges for regeneration of skeletal muscle following trauma

Skeletal muscle is inept in regenerating after traumatic injuries due to significant loss of basal lamina and the resident satellite cells. To improve regeneration of skeletal muscle, we have developed biomimetic sponges composed of collagen, gelatin, and laminin (LM)-111 that were crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). Collagen and LM-111 are crucial components of the muscle extracellular matrix and were chosen to impart bioactivity whereas gelatin and EDC were used to provide mechanical strength to the scaffold. Morphological and mechanical evaluation of the sponges showed porous structure, water-retention capacity and a compressive modulus of 590-808 kPa. The biomimetic sponges supported the infiltration and viability of C2 C12 myoblasts over 5 days of culture. The myoblasts produced higher levels of myokines such as VEGF, IL-6, and IGF-1 and showed higher expression of myogenic markers such as MyoD and myogenin on the biomimetic sponges. Biomimetic sponges implanted in a mouse model of volumetric muscle loss (VML) supported satellite, endothelial, and inflammatory cell infiltration but resulted in limited myofiber regeneration at 2 weeks post-injury. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 92-103, 2019.
Measuring Variability in Rest-Activity Rhythms from Actigraphy with Application to Characterizing Symptoms of Depression

The twenty-four hour sleep-wake pattern known as the rest-activity rhythm (RAR) is associated with many aspects of health and well-being. Researchers have utilized a number of interpretable, person-specific RAR measures that can be estimated from actigraphy. Actigraphs are wearable devices that dynamically record acceleration and provide indirect measures of physical activity over time. One class of useful RAR measures are those that quantify variability around a mean circadian pattern. However, current parametric and non-parametric RAR measures used by applied researchers can only quantify variability from a limited or undefined number of rhythmic sources. The primary goal of this article is to consider a new measure of RAR variability: the log-power spectrum of stochastic error around a circadian mean. This functional measure quantifies the relative contributions of variability about a circadian mean from all possibly frequencies, including weekly, daily, and high-frequency sources of variation. It can be estimated through a two-stage procedure that smooths the log-periodogram of residuals after estimating a circadian mean. The development of this measure was motivated by a study of depression in older adults and revealed that slow, rhythmic variations in activity from a circadian pattern are correlated with depression symptoms.
Carbonic anhydrase II in complex with carboxylic acid-based inhibitors.

Carbonic anhydrases (CAs) are molecular targets in various diseases. While many sulfonamide-based drugs are in clinical use, CA inhibitor design is moving towards the incorporation of alternative zinc-binding groups, such as carboxylic acids, to promote CA isoform-specific inhibition. Here, X-ray crystal structures of CA II in complex with nicotinic acid and ferulic acid determined to 1.70 and 1.50 A resolution, respectively, are reported. Furthermore, the structures of these two compounds are superimposed with previously determined structures to compare the mechanisms of inhibition and the properties of carboxylic acid-based CA inhibitors. This study examines an important class of alternative, non-sulfonamide-based CA inhibitors and provides insight to facilitate the structure-guided design of CA isoform-specific inhibitors.
W!NCE: Unobtrusive Sensing of Upper Facial Action Units with EOG-based Eyewear

The ability to unobtrusively and continuously monitor one's facial expressions has implications for a variety of application domains ranging from affective computing to health-care and the entertainment industry. The standard Facial Action Coding System (FACS) along with camera based methods have been shown to provide objective indicators of facial expressions; however, these approaches can also be fairly limited for mobile applications due to privacy concerns and awkward positioning of the camera. To bridge this gap, W!NCE re-purposes a commercially available Electrooculography-based eyeglass (J!NS MEME) for continuously and unobtrusively sensing of upper facial action units with high fidelity. W!NCE detects facial gestures using a two-stage processing pipeline involving motion artifact removal and facial action detection. We validate our system's applicability through extensive evaluation on data from 17 users under stationary and ambulatory settings, a pilot study for continuous pain monitoring and several performance benchmarks. Our results are very encouraging, showing that we can detect five distinct facial action units with a mean F1 score of 0.88 in stationary and 0.82 in ambulatory settings, and that we can accurately detect facial gestures that due to pain.
Alcohol-induced IL-17A production in Paneth cells amplifies endoplasmic reticulum stress, apoptosis, and inflammasome-IL-18 activation in the proximal small intestine in mice

Gut microbial translocation contributes to alcoholic hepatitis. Using a mouse model of alcoholic hepatitis, we investigated the effects of chronic alcohol plus binge and found increased abundance of Paneth cells and IL-17A in the proximal small intestine (PSI). Alcohol increased IL-17A production and pro-apoptotic signaling evidenced by Bax, Bim, caspase-3, and caspase-8 increases via endoplasmic reticulum (ER) stress indicated by C/EBP homologous protein (CHOP) upregulation; this was prevented by the ER stress inhibitor, 4-PBA, in isolated crypts in vitro and in vivo. Mechanistically, IL-17 augmented alcohol-induced ER stress in isolated crypts. In vivo IL-17A blocking antibody administration in alcohol-treated mice attenuated ER stress-mediated apoptosis and IL-18 induction and prevented alcohol-induced impairment of tight junctions in the PSI and LPS translocation to the liver. Acute-on-chronic alcohol resulted in inflammasome activation, caspase-1 cleavage, and IL-18 production in the PSI. In vivo treatment with antibiotics or 4-PBA prevented CHOP upregulation and inflammasome activation. Our data suggest that alcohol upregulates innate immune mechanisms by increasing Paneth cell numbers and IL-17A release contributing to apoptosis amplification, inflammasome activation, and gut leakiness in the PSI. Binge alcohol-induced Paneth cell expansion, ER stress, and inflammasome activation in the PSI are modulated by the gut microbiome.
The elasticity of individual protocadherin 15 molecules implicates cadherins as the gating springs for hearing

Hair cells, the sensory receptors of the inner ear, respond to mechanical forces originating from sounds and accelerations1,2. An essential feature of each hair cell is an array of filamentous tip links, consisting of the proteins protocadherin 15 (PCDH15) and cadherin 23 (CDH23)3, whose tension is thought to directly gate the cell’s transduction channels4,5,6. These links are considered far too stiff to represent the gating springs that convert hair-bundle displacement into forces capable of opening the channels7,8, and no mechanism has been suggested through which tip-link stiffness could be varied to accommodate hair cells of distinct frequency sensitivity in different receptor organs and animals. As a consequence, the gating spring’s identity and mechanism of operation remain central questions in sensory neuroscience. Using a high-precision optical trap, we show that an individual monomer of PCDH15 acts as an entropic spring that is much softer than its enthalpic stiffness alone would suggest7,8. This low stiffness implies that the protein is a significant part of the gating spring that controls a hair cell’s transduction channels. The tip link’s entropic nature then allows for stiffness control through modulation of its tension. We find that a PCDH15 molecule is unstable under tension and exhibits a rich variety of reversible unfolding events that are augmented when the Ca2+ concentration is reduced to physiological levels. Tip-link tension and Ca2+ concentration are therefore likely parameters through which nature tunes a gating spring’s mechanical properties.
Two decades of progress in structural and dynamic studies of amyloids by solid-state NMR

In this perspective article I briefly highlight the rapid progress made over the past two decades in atomic level structural and dynamic studies of amyloids, which are representative of non-crystalline biomacromolecular assemblies, by magic-angle spinning solid-state NMR spectroscopy. Given new and continuing developments in solid-state NMR instrumentation and methodology, ongoing research in this area promises to contribute to an improved understanding of amyloid structure, polymorphism, interactions, assembly mechanisms, and biological function and toxicity.