cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 5194: Development of a cytotoxic fusion protein targeting VEGF receptors with improved cytotoxicity, stability and pharmacokinetics

The serine protease granzyme B (GrB), a key effector in immune mediated cell killing is capable of inducing apoptosis through both caspase-dependent and caspase-independent multiple-cascade mechanisms. VEGF121 is a naturally-occurring isoform of the VEGF-A family and binds to VEGF receptors R-1 and R-2, which are over-expressed on tumor cells as well as the endothelium of tumor vasculature but not normal vasculature. We have previously reported the expression of a fusion protein composed of Granzyme B and VEGF121 (GrB/VEGF121) and its subsequent in vitro and in vivo characterization. We hypothesized that incorporation of an IgG heavy chain Fc-fragment, resulting in a relatively higher molecular weight (133 kDa vs 80 kDa), would improve in vivo circulation and efficacy. Accordingly, the VEGF inter-chain dimerization domains were mutated so that dimerization occurred only through the Fc domain. Transient expression of GrB-Fc-VEGF121 in HEK-293E cells under serum-free conditions, followed by purification by immobilized metal affinity chromatography, resulted in yields in the range of 20-25 mg/L. Comparison of GrB-Fc-VEGF121 with its expected molecular weight suggests significant glycosylation when produced in HEK293E cells. The enzymatic activity of GrB in GrB-Fc-VEGF121 was comparable to that of commercially available human GrB. Cytotoxicity studies against a panel of tumor and endothelial cells indicated improved cytotoxicity against cell lines expressing high levels of VEGFR-1 or VEGFR-2, unlike GrB/VEGF121, which targeted VEGFR-2+ cells more efficiently. Control (receptor-negative) cells demonstrated IC50 levels in the high micromolar range. Comparison of ex vivo stability of GrB-Fc-VEGF121 to GrB/VEGF121 over 96 hours indicated GrB/VEGF121 signal reduced by approximately 50% over the first 24 hours of incubation, but minimal loss of protein was observed thereafter for the duration of the study. On the other hand, the protein loss of GrB-Fc-VEGF121 was more gradual, while the overall loss of protein over 96 hours was similar to that of GrB/VEGF121. Thus, GrB-Fc-VEGF121 is very stable in mouse serum and further pharmacokinetic analysis is warranted to determine its stability in vivo. In vivo pharmacokinetics and efficacy against various tumor models are currently ongoing and will be presented. In summary, the GrB-Fc-VEGF121 produced in HEK293E cells is active and has significant potential as a targeted therapeutic. Research conducted, in part, by the Clayton Foundation for Research. Citation Format: Khalid A. Mohamedali, Lawrence H. Cheung, Ana A. Alvarez-Cienfuegos, Michael G. Rosenblum. Development of a cytotoxic fusion protein targeting VEGF receptors with improved cytotoxicity, stability and pharmacokinetics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5194.
Identification and characterization of genes found in Coccidioides spp. but absent in nonpathogenic Onygenales

Coccidioides spp. are dimorphic, pathogenic fungi that can cause severe human and animal disease. Like the other primary pathogens, infections of animals results in a morphologic transformation to a tissue phase, which in this case is known as a spherule. The sequencing and annotation of Coccidioides spp. and the genomes of several nonpathogenic Onygenales species allows comparisons of the genes that might provide clues about the pathogenic Coccidioides spp. genes. This analysis is a gene by gene orthology comparison. Although there were few differences in the size of genes families in the Coccidioides spp.-specific group compared to the genes shared by Coccidioides spp. and nonpathogenic Onygenales, there were some differences in the characterization of the two types of genes. Coccidioides spp.-specific genes contained many more orphan genes and more genes with up-regulated expression in spherules. Review of individual genes in the Coccidioides spp.-specific group identified two genes in the Velvet family, a histidine kinase, two thioredoxin genes, a calmodulin gene and ureidoglycolate hydrolase. Velvet genes have been found to be important for mycelium differention to yeast in Histoplasma capsulatum. Hopefully, identification of these genes will be useful for pursuing potential Coccidioides spp. virulence genes in the future.
Coordinated signaling of activating transcription factor 6α and inositol-requiring enzyme 1α regulates hepatic stellate cell-mediated fibrogenesis in mice

Liver injury and the unfolded protein response (UPR) are tightly linked, but their relationship differs with cell type and injurious stimuli. UPR initiation promotes hepatic stellate cell (HSC) activation and fibrogenesis, but the underlying mechanisms are unclear. Despite the complexity and overlap downstream of UPR transducers inositol-requiring protein 1α (IRE1α), activating transcription factor 6α (ATF6α), and protein kinase RNA-like ER kinase (PERK), previous research in HSCs primarily focused on IRE1α. Here, we investigated the fibrogenic role of ATF6α or PERK in vitro and HSC-specific UPR signaling in vivo. Overexpression of ATF6α, but not the PERK effector activating transcription factor 4 (ATF4), promoted HSC activation and fibrogenic gene transcription in immortalized HSCs. Furthermore, ATF6α inhibition through Ceapin-A7, or Atf6a deletion, disrupted transforming growth factor β (TGFβ)-mediated activation of primary human hepatic stellate cells (hHSCs) or murine hepatic stellate cells (mHSCs), respectively. We investigated the fibrogenic role of ATF6α in vivo through conditional HSC-specific Atf6a deletion. Atf6aHSCΔ/Δ mice displayed reduced fibrosis and HSC activation following bile duct ligation (BDL) or carbon tetrachloride (CCl4)-induced injury. The Atf6aHSCΔ/Δ phenotype differed from HSC-specific Ire1a deletion, as Ire1aHSCΔ/Δ mice showed reduced fibrogenic gene transcription but no changes in fibrosis compared with Ire1afl/fl mice following BDL. Interestingly, ATF6α signaling increased in Ire1aΔ/Δ HSCs, whereas IRE1α signaling was upregulated in Atf6aΔ/Δ HSCs. Finally, we asked whether co-deletion of Atf6a and Ire1a additively limits fibrosis. Unexpectedly, fibrosis worsened in Atf6aHSCΔ/ΔIre1aHSCΔ/Δ mice following BDL, and Atf6aΔ/ΔIre1aΔ/Δ mHSCs showed increased fibrogenic gene transcription. ATF6α and IRE1α individually promote fibrogenic transcription in HSCs, and ATF6α drives fibrogenesis in vivo. Unexpectedly, disruption of both pathways sensitizes the liver to fibrogenesis, suggesting that fine-tuned UPR signaling is critical for regulating HSC activation and fibrogenesis.NEW & NOTEWORTHY ATF6α is a critical driver of hepatic stellate cell (HSC) activation in vitro. HSC-specific deletion of Atf6a limits fibrogenesis in vivo despite increased IRE1α signaling. Conditional deletion of Ire1α from HSCs limits fibrogenic gene transcription without impacting overall fibrosis. This could be due in part to observed upregulation of the ATF6α pathway. Dual loss of Atf6a and Ire1a from HSCs worsens fibrosis in vivo through enhanced HSC activation.
SYSTOLIC CLICKS AND THE LATE SYSTOLIC MURMUR; INTRACARDIAC PHONOCARDIOGRAPHIC EVIDENCE OF THEIR MITRAL VALVE ORIGIN.

Abstract The use of intracardiac phonocardiography has been employed as a method of documenting the origin of systolic clicks associated with an isolated late systolic murmur in a patient with hemodynamic evidence of mitral incompetence. Registration of both of these acoustical events within the left atrial chamber has not been hitherto described. Response of the clicks and murmur to the infusion of pressor amine and to the inhalation of amyl nitrite adds further weight to the concept of their origin at the mitral orifice. These observations confirm and extend previous information relating the late systolic murmur to organic mitral incompetence even if the murmur is accompanied by systolic clicks.
The NASA research program on propulsion for supersonic cruise aircraft

The objectives and status of the propulsion portion of a program aimed at advancing the technology and establishing a data base appropriate for the possible future development of supersonic cruise aircraft are reviewed. Research related to exhaust nozzles, combustors, and inlets that is covered by the noise, pollution, and dynamics programs is described.
Immunologic Approaches to the Therapy of Auto-Immune Salivary Gland Disease

A variety of immunologic mechanisms may theoretically give rise to disease in the salivary glands. Among them are abnormal antibody production, hyper-reactive T-lymphocytes, and mono- or oligoclonal expansions of B-lymphocytes. While it is not clear which, if any, of these mechanisms are of prime importance in the immunopathology of salivary gland disease, they provide a framework within which to discuss theoretical approaches to the treatment of auto-immune salivary gland disease. Among the techniques used to decrease antibody-induced damage are non-steroidal anti-inflammatory agents, plasmapheresis, and corticosteroids. Cyclosporin, monoclonal antibodies, and biologic response-modifiers may be used to modulate T-cell function, and anti-idiotype antibodies or immunosuppressive agents may be used to treat malignant expansions of B-cells. Although the generally benign nature of auto-immune salivary gland disease precludes the use of many of the potentially toxic treatment regimens discussed here, the appreciation of these approaches to immunomodulation provides a basis upon which to develop new and innovative therapeutic strategies.
CHEMICAL ASSAYS OF TEMPER AND CLAY: MODELLING POTTERY PRODUCTION AND EXCHANGE IN THE UPLANDS NORTH OF THE PHOENIX BASIN, ARIZONA, USA*

A lack of mineralogical variation characterizes the prehistoric pottery in the uplands of central Arizona. Virtually all of the ceramics in that region were tempered with phyllite, which has previously precluded provenance analyses and the investigation of pottery production and distribution in the upland zone. As shown with assays with an electron microprobe, however, both the clay fraction and the temper fragments are chemically diverse and geographically distinct, allowing many of the phyllite-tempered wares to be sourced, thereby leading to models about the organization of ceramic production and exchange in the upland zone north of the Phoenix Basin.
Lifetime Analysis of the ITER First Wall and Divertor Plates

The performance of the ITER first wall and divertor plate is analyzed using a 1-D life-time code which includes the effects of radiation damage and surface erosion. The materials considered for the first wall are solution annealed and 20% cold-worked Type 316 stainless steel. The materials considered for the divertor plate are H-451 graphite bonded to a Cu-0.5 Be-2 Ni heat sink. The primary conclusion is that it is crucial to include radiation effects for obtaining realistic predictions of performance. 9 refs., 13 figs., 1 tab.
Electron microscopy in morphology and molecular biology

Electron microscopy, in scarcely more than two decades, has led to revolutionary new concepts of cell structure and the mechanism of basic life processes. In many instances biological systems have been observed at or near the molecular level. These advances become the more significant because of profound parallel discoveries in biochemistry, biophysics, and biophysical chemistry in about the same period. The fusion of these sciences into a single unified effort has already been begun, leading toward what may appropriately be called molecular biology, a term early employed by one of the pioneers in the field, W. T. Astbury.
Selection by parasites for clonal diversity and mixed mating

On theoretical grounds, coevolutionary interactions with parasites can select for cross-fertilization, even when there is a twofold advantage gained by reproducing through uniparental means. The suspected advantage of cross-fertilization stems from the production of genetically rare offspring, which are expected to be more likely to escape infection by coevolving enemies. In the present study, we consider the effects that parasites have on parthenogenetic mutants in obligately sexual, dioecious populations. Computer simulations show that repeated mutation to parthenogenesis can lead to the accumulation of clones with different resistance genotypes, and that a moderately diverse set of clones could competitively exclude the ancestral sexual subpopulation. The simulations also show that, when there are reasonable rates of deleterious mutation, Muller’s ratchet combined with coevolutionary interactions with parasites can lead to the evolutionary stability of cross-fertilization. In addition, we consider the effects that parasites can have on the evolution of uniparental reproduction in cosexual populations. Strategy models show that parasites and inbreeding depression could interact to select for evolutionarily stable reproductive strategies that involve mixtures of selfed and outcrossed progeny.
A 15-year follow-up of AJCC stage III malignant melanoma patients treated postsurgically with Newcastle disease virus (NDV) oncolysate and determination of alterations in the CD8 T cell repertoire.

The development of effective adjuvant therapies for the treatment of high-risk melanoma patients is critical for the prevention of metastatic disease and improvement of patient survival. Active specific immunotherapy has been tested as an adjuvant treatment in numerous clinical trials with overall limited, but occasionally promising, success rates. Newcastle disease virus (NDV) oncolysate has been utilized as an adjunctive immunotherapeutic agent in the postsurgical management of these patients. A phase II study initiated in 1975 using adjuvant vaccine therapy composed of allogeneic and autologous human melanoma cells infected with live NDV (NDV oncolysate) in patients with AJCC stage III melanoma following therapeutic lymph node dissection has shown >60% survival rate at 10 years with no adverse effects. Continued long-term analysis of trials with promising early results as well as assessment of immunologic responses generated in these patients may result in improved therapeutic decisions for clinical trials in the future. We analyzed the 15-year survival of patients treated postsurgically with NDV oncolysate in the phase II study described above. In an attempt to understand the immunological effects of this treatment, we have also carried out a comprehensive analysis of the peripheral blood T cell repertoire in these patients. The overall 15-year survival of this group of patients is 55%. Previous studies have suggested that improved outcome in patients undergoing immunotherapy is correlated with increased numbers of CD8+CD57+ cells. In surviving patients, we observed a striking oligoclonality in the CD8+ T cell population in peripheral blood, which reflects clonal expansions in the CD8+CD57+ subset. The data suggest that adjuvant vaccination with NDV oncolysates is associated with prolonged survival of patients with lymph node-positive malignant melanoma and that CD8+ T cells may be an important component of therapeutic efficacy.
Use of failure mode and effects analysis in improving the safety of i.v. drug administration

Purpose. Failure mode and effects analysis (FMEA) was used to identify dosing and administration errors associated with i.v. medications and evaluate the effectiveness of subsequent system improvements. Summary. A multidisciplinary medication safety team conducted an FMEA to identify and reduce common medication errors and selected wrong-dose errors for process improvement. In 2002, wrong-dose errors comprised 17% of all medication errors at the hospital (59 of 347 errors). The most common reason for administering the wrong dose was error in programming the i.v. infusion pump (41%). Potential errors (i.e., failures) identified were misinterpretation of the order, removing the wrong medication or wrong concentration of the correct medication, using the wrong diluent or drug to prepare the drip, and entering the wrong concentration or infusion rate on the pump. Errors in programming the i.v. infusion pump was the step in the medication-use process associated with the highest criticality index. Based on the results of the FMEA, two main interventions were performed. First, standard order sets were revised after streamlining the formulary and eliminating the use of unapproved abbreviations. Second, an i.v. pump with enhanced safety features was implemented. One-year follow-up data revealed that the number of medication errors related to dosing (wrong dose or incorrect infusion rate) had decreased slightly (from 59 in 2002 to 46 in 2003); however, a dramatic reduction was noted in the percentage of pump-related errors. In 2003, pump-related errors accounted for 22% of dosing errors, compared with 41% in 2002. Conclusion. Medication errors related to i.v. infusion pumps were reduced by conducting an FMEA and implementing the process changes needed.
The impact of ozone depleting substances on the circulation, temperature, and salinity of the Southern Ocean: An attribution study with CESM1(WACCM)

Observations show robust changes in the circulation, temperature, and salinity of the Southern Ocean in recent decades. To what extent these changes are related to the formation of the ozone hole in the late twentieth century is an open question. Using a comprehensive chemistry-climate Earth system model, we contrast model runs with varying and with fixed surface concentrations of ozone depleting substances (ODS) from 1955 to 2005. In our model, ODS cause the majority of the summertime changes in surface wind stress which, in turn, induce a clear poleward shift of the ocean's meridional overturning circulation. In addition, more than 30% of the model changes in the temperature and salinity of the Southern Ocean are caused by ODS. These findings offer unambiguous evidence that increased concentrations of ODS in the late twentieth century are likely to have been been an important driver of changes in the Southern Ocean.
Accuracy of Depth Information from Cepstrum-Disparities of a Sequence of 2-D Projections

ABSTRACT One of the traditional techniques for extracting depth information is to find the disparities of corresponding points in stereo images following a biological model of three-dimensional vision. A normal binocular stereo system uses two images to determine which point in one image corresponds to a given point in the other, i.e., to find the correspondence between two images. If the distance between two cameras, i.e. the baseline, is small, no detail matching can be made. Conversely, for a large baseline, some points visible in one image will not be seen in the other thus making it difficult and sometimes even impossible to find the corresponding points.A sequence of a number of images can solve such problems in the stereo vision system. The algorithm developed here chooses the center image of a sequence of images as the reference and finds the corresponding points of its left and right halves from the images taken from its left and right, respectively. A recently developed two-dimensional power cepstrum technique to detect the translational difference , between the extracted features of sequential and complex images has been proven to be very accurate and noise tolerant. The two-dimensional power cepstrum technique can be applied to any two images to determine the translational difference, i.e. disparity, between them. The resolution of the disparity depends on the baseline used. High resolution in disparity is achieved by increasing the baseline and decreasing the window size. This technique matches the corresponding points in two images with several intermediate images to reduce the error in matching from widely different perspectives. Therefore the depth information extracted from a sequence of images by the cepstrum technique is more accurate than the existing matching techniques for the stereo vision model.
Placemaking and disaster recovery: targeting place for recovery in post-Katrina New Orleans

One of the central strategies employed by the City of New Orleans to address the challenge of disaster recovery after Hurricane Katrina was a place-based strategy of targeted investments. This strategy sought to address the twin challenges of the punctuated disaster from Katrina and the slow-motion disaster of economic decline that pre-dated the storm. We analyze the key components of the geographic targeting program in New Orleans through a case study of a particular target in the Gentilly planning district of the city. The goal of the process was to utilize reinvigorated places to both encourage community reinvestment and deal with the underlying challenge of rebuilding in a more resilient manner. Target-area resources were never fully translated into dedicated resources for project implementation. We find that weak implementation and management capacity significantly limited the effectiveness of the targeting program in meeting place-based goals.
An Early Design Stage UML-Based Safety Analysis Approach for High Assurrance Software Systems

High-assurance computer systems fulfill security, safety, fault-tolerant, and real-time properties. Analysis of these properties is typically performed in isolation. An integrated analysis of all the properties is a challenge that can be addressed by expressing these properties in a common integrated framework. The Unified Modeling Language is a standard modeling language which exhibits such a capability. In this paper we focus on using the Unified Modeling Language to analyze the safety properties of high-assurance systems. In particular we are interested in the study of software faults propagation and their functional level effects. In previous work we have developed the Failure Propagation and Simulation Approach to study whether a particular fault will propagate through the design and cause system-level functional failures. Mapping between different Unified Modeling Language diagrams is the central concept behind the approach. This paper briefly introduces the Failure Propagation and Simulation Approach and presents in detail the executable models developed to automate the simulation process. These executable models are built using the notations of the Event Sequence Diagram, one of the established reliability and safety analysis techniques for sequence progression.
Predator Evasion by White-tailed Deer Fawns

Despite their importance for understanding predator–prey interactions, factors that affect predator evasion behaviours of offspring of large ungulates are poorly understood. Our objective was to characterize the influence of selection and availability of escape cover and maternal presence on predator evasion by white-tailed deer, Odocoileus virginianus, fawns in the northern Great Plains, U.S.A. We observed 45 coyote, Canis latrans, chases of fawns, and we participated in 83 human chases of fawns during 2007–2009, of which, 19 and 42 chases, respectively, ended with capture of the fawn. Evasive techniques used by fawns were similar for human and coyote chases. Likelihood of a white-tailed deer fawn escaping capture, however, was influenced by deer group size and a number of antipredator behaviours, including aggressive defence by females, initial habitat and selection of escape cover, all of which were modified by the presence of parturient females. At the initiation of a chase, fawns in grasslands were more likely to escape, whereas fawns in forested cover, cultivated land or wheat were more likely to be captured by a coyote or human. Fawns fleeing to wetlands and grasslands also were less likely to be captured compared with those choosing forested cover, wheat and cultivated land. Increased probability of capture was associated with greater distance to wetland and grassland habitats and decreased distance to wheat. Use of wetland habitat as a successful antipredator strategy highlights the need for a greater understanding of the importance of habitat complexity in predator avoidance.
Activation of the dentate gyrus by pentylenetetrazol evoked seizures induces mossy fiber synaptic reorganization

Kindled seizures evoked by electrical stimulation of limbic pathways in the rat induce sprouting and synaptic reorganization of the mossy fiber pathway in the dentate gyrus (DG). To investigate whether seizures evoked by different methods also induce reorganization of this pathway, the distribution of mossy fiber terminals in the DG was examined with Timm histochemistry after systemic administration of pentylenetetrazol, a chemoconvulsant that reduces Cl- mediated GABAergic inhibition. Myoclonic seizures evoked by subconvulsant doses of pentylenetetrazol (24 mg/kg i.p.) were not accompanied by electrographic seizures in the DG, and did not induce mossy fiber sprouting. Generalized tonic-clonic seizures evoked by repeated administration of PTZ (24 mg/kg i.p.) were consistently accompanied by electrographic seizure activity in the DG, and induced sprouting and synaptic reorganization of the mossy fiber pathway. The results demonstrated that repeated generalized tonic-clonic seizures evoked by pentylenetetrazol induced mossy fiber synaptic reorganization when ictal electrographic discharges activated the circuitry of the DG.
Androgen modulation of luteinizing hormone secretion by female rat gonadotropes.

In the female, androgens can have negative and positive actions in the regulation of LH, but it is not clear how they may function during the reproductive cycle. Toward resolving these potentially conflicting roles for androgen, we used an in vitro model of preovulatory gonadotropes to examine the effect of proestrous levels of testosterone (1.7 nm) or dihydrotestosterone (DHT; 0.7 nm) on LH secretion in response to pulsatile GnRH (1 nm) or elevated extracellular K+ (54 mm). For female rat pituitary cells cultured in 17β-estradiol (E2)-containing medium, androgen treatment for 16 h, but not for 4 h, inhibited the LH secretory response to a pulse of either GnRH or K+ by about 60% and suppressed the acute augmentation action of 20 nm progesterone on GnRH- or K+-induced LH secretion. In the absence of E2, DHT also decreased LH secretion induced by a pulse of GnRH. DHT’s suppressive effect on progesterone could be partially overcome with increased progesterone (200 nm) or by removal of DHT during progesterone...
Automatic tools for testing expert systems

In the last several years, validating and verifying (VV is the system knowledge adequate? Domain validation ensures accuracy and completeness of the knowledge base while procedural validation establishes the accuracy and reliability of system output [3]. Verification, on the other hand, establishes structural correctness and process effectiveness by testing the logic of the knowledge base while testing executes a piece of software with the goal of finding errors; structural testing exercises a set of test cases on as many paths as possible, although it does not guarantee that each path is tested while functional testing validates problem specifications by comparing system output with known results. Both functional and structural testing are necessary to build reliable systems[1]. Current tools and techniques for testing expert systems include test case generation, face validation, Turing test, field tests, subsystem validation, and sensitivity analysis. Since there is no one single test technique that captures all errors, developers must try a combination of different methods [2]. Of these techniques, test case generation continues to be the most popular technique. Some limitations of manual test case generation can be overcome by automatic test case generators: software that automatically identifies a set of input-output pairs, where the input identifies the path(s), conditions, and condition values to be tested while the output identifies the results associated with the input. Other approaches and tools to automating the testing process include Expert Systems Validation Associate (EVA) [4], dependency charts, decision tables, graphs or Petri nets, and exploration of dynamic and temporal relationship between rules [8, 9].
On the cool flames of methane

ABSTRACT Methane is an attractive alternate fuel. It bums cleanly and is resistant to “knock.” For many years methane was believed not to give rise to the phenomenon of cool flame, a process basic to the problem of “knock” in internal combustion engine. This paper shows that methane exhibits the same combustion events as those observed in higher hydrocarbons: slow combustion; production of hydrogen peroxide; multistage, low temperature ignition; single and multiple cool flames; regions of negative temperature coefficient; and high temperature ignition. The ignition diagrams are normal, but the cool-flames regions are found at higher temperatures and are much narrower than for higher hydrocarbons. This is the reason why the methane cool flames escaped experimental observation for such a long time. These findings give a rationale for the high, but not absolute, resistance of methane to “knock.”
Exfoliated graphite nanoplatelets–V2O5 nanotube composite electrodes for supercapacitors

Abstract Exfoliated graphite nanoplatelet (xGnP) and V2O5 nanotube (VNT) composite electrodes were fabricated and tested as electrodes for supercapacitors. Enhancement of the electrochemical performance of the composite over its component materials was demonstrated using cyclic voltammetry (CV), constant current charge/discharge testing and electrochemical impedance spectroscopy in aqueous and organic electrolytes. The calculated specific capacitance of the composite was 35 F g−1 in the aqueous electrolyte and 226 F g−1 in the organic electrolyte at a scan rate of 10 mV s−1 using a three-electrode system. Asymmetric coin cell devices were fabricated using activated carbon cloth as the positive electrode and xGnP–VNT composite as the negative electrode. The energy and power densities in 1 M LiTFSI were 28 Wh kg−1 and 303 W kg−1, respectively, at a discharge current density of 250 mA g−1.
Update on Epilepsy in Pediatric Patients

Epilepsy is a common condition that affects 0.5 to 1% of all children. Although most children with epilepsy have well-controlled seizures with use of one antiepileptic drug (AED), some children have medically refractory seizures. This situation can be the result of inaccurate classification of the paroxysmal event, use of an inappropriate AED, of a truly medically refractory seizure disorder. Paramount to the initial assessment of a child with presumed epilepsy is the appropriate classification of the paroxysmal event. Several nonepileptic conditions, such as motor tics or breath-holding spells, can cause paroxysmal abnormalities in children, which can be confused with epilepsy. The common pediatric epileptic and nonepileptic conditions are reviewed, and the standard and new AEDs and their side effects are discussed. When a child's seizure disorder is intractable despite adequate trials of AEDs, surgical treatment is increasingly becoming an effective option. Such procedures should ideally be performed at centers with extensive experience in this area and with a multidisciplinary team approach. With improved magnetic resonance imaging technology, increasing numbers of children with medically intractable localization-related epilepsy are being found to have underlying focal cortical dysplasia, tumors, or hippocampal atrophy. These abnormalities can often be surgically resected with excellent results. A generalized epilepsy may also be remediable with surgical treatment. Specifically, preliminary data suggest that infantile spasms, when triggered by an underlying focal cortical dysplasia, may be effectively treated by surgical resection. Patients with certain catastrophic seizure disorders, such as Sturge-Weber syndrome or hemimegalencephaly, require prompt intervention with hemispherectomy. The presurgical evaluation relies heavily on the magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography scan data as well as the electroencephalogram in identifying the area of epileptogenic abnormality.
The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP

Mutations in the gene encoding NLRP3 cause a spectrum of autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS). NLRP3 is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine interleukin-1β (IL-1β) by activating caspase-1. Although several models for inflammasome activation, such as K(+) efflux, generation of reactive oxygen species and lysosomal destabilization, have been proposed, the precise molecular mechanism of NLRP3 inflammasome activation, as well as the mechanism by which CAPS-associated mutations activate NLRP3, remain to be elucidated. Here we show that the murine calcium-sensing receptor (CASR) activates the NLRP3 inflammasome, mediated by increased intracellular Ca(2+) and decreased cellular cyclic AMP (cAMP). Ca(2+) or other CASR agonists activate the NLRP3 inflammasome in the absence of exogenous ATP, whereas knockdown of CASR reduces inflammasome activation in response to known NLRP3 activators. CASR activates the NLRP3 inflammasome through phospholipase C, which catalyses inositol-1,4,5-trisphosphate production and thereby induces release of Ca(2+) from endoplasmic reticulum stores. The increased cytoplasmic Ca(2+) promotes the assembly of inflammasome components, and intracellular Ca(2+) is required for spontaneous inflammasome activity in cells from patients with CAPS. CASR stimulation also results in reduced intracellular cAMP, which independently activates the NLRP3 inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and the uncontrolled mature IL-1β production from CAPS patients' peripheral blood mononuclear cells is attenuated by increasing cAMP. Taken together, these findings indicate that Ca(2+) and cAMP are two key molecular regulators of the NLRP3 inflammasome that have critical roles in the molecular pathogenesis of CAPS.
Behavioral sensitization to cocaine in rats: Evidence for temporal differences in dopamine D3 and D2 receptor sensitivity

Cocaine-induced changes in D2 receptors have been implicated in the expression of sensitized behavioral responses and addiction-like behaviors; however, the influence of D3 receptors is less clear. To characterize the effects of repeated cocaine administration on the sensitivity of rats to D2- and D3-mediated behaviors, as well as the binding properties of ventral striatal D2-like and D3 receptors. Pramipexole was used to assess the sensitivity of rats to D3/D2 agonist-induced yawning, hypothermia, and locomotor activity, 24 h, 72 h, 10, 21, and 42 days after repeated cocaine or saline administration. The locomotor effects of cocaine (42 day) and the binding properties of ventral striatal D2-like and D3 receptors (24 h and 42 days) were also evaluated. Cocaine-treated rats displayed an enhanced locomotor response to cocaine, as well as a progressive and persistent leftward/upward shift of the ascending limb (72 h–42 day) and leftward shift of the descending limb (42 days) of the pramipexole-induced yawning dose–response curve. Cocaine treatment also decreased B max and K d for D2-like receptors and increased D3 receptor binding at 42 days. Cocaine treatment did not change pramipexole-induced hypothermia or locomotor activity or yawning induced by cholinergic or serotonergic agonists. These studies suggest that temporal differences exist in the development of cocaine-induced sensitization of D3 and D2 receptors, with enhancements of D3-mediated behavioral effects observed within 72 h and enhancements of D2-mediated behavioral effects apparent 42 days after cocaine. These findings highlight the need to consider changes in D3 receptor function when thinking about the behavioral plasticity that occurs during abstinence from cocaine use.
Quantitative studies of pinnule development in the ferns Adiantum raddianum and Cheilanthes viridis

Pinnule development was investigated in two fern species, Adiantum raddianum Presl cv. Decorum and Cheilanthes viridis (Forsk.) Swartz, by using clearings to facilitate the recording of mitotic divisions. Both species were found to possess a marginal meristem. This meristem consists of both a marginal row of large initials and a submarginal meristematic zone. The marginal meristem in these ferns is responsible for establishing the layers of the lamina, providing new cells which by enlargement will expand the pinnule, establishing general pinnule form, initiating the procambial stands, and forming the false indusia. The cells of the submarginal meristem were found to divide parallel to the pinnule margin more frequently if they were to become ground tissue, while dividing perpendicular to the margin more frequently if they were to become procambial. Details of vein dichotomies were also studied. Perimeter expansion was found to be associated with dichotomy of the veins, and venation pattern was found to be correlated with leaf form. The marginal meristem is active from the time of pinnule initiation until the pinnule reaches about 50% of its final length or width. Leaf development in leptosporangiate ferns resembles the traditional concept of development in angiosperms somewhat more than it does the more recent concepts. It is clear, though, that there is not a high degree
Growth and evaluation of lpe graded composition Al x Ga 1−x As layers for high efficiency graded bandgap solar cells

A melt-mixing LPE growth technique to obtain a graded composition AlxGa1−xAs layer is described. The graded bandgap AlGaAs/GaAs solar cell requires the Al fraction (x) in the AlxGa1−xAs surface layer to increase from the junction towards the surface. The graded composition AlxGa1−xAs layer creates a built-in electric field for minority carriers which improves the carrier collection process. This graded bandgap solar cell should enable one to realize the full potential of GaAs as a material for solar energy conversion. Quantitative evaluation of the composition profile for these graded layers is needed to develop the proper growth technique and to understand the resulting solar cell characteristics. Rutherford backscattering analysis technique is described which has been successfully used to profile such layers.
STARTERS AND CONTROLLERS FOR U. S. NAVY ALTERNATING CURRENT AUXILIARY MOTORS

Previously, in the November, 1925, issue of the JOURNAL, the author classified the starting and control equipment used in Naval vessels for d.c. motors. In the August, 1933, issue, following the introduction of alternating currrent wachinery, he described the types of motors suitable for shipboard use. He proceeds now to sort out the manifold functions performed by starters and controllers for a.c. motors. Safety and protective devices are included in the classification. Materials are described. The operating engineer is the principal beneficiary of this presentation. But the designing engineer will do well to have in mind a clear picture of the available control devices together with their applications.
Optimizing the use of anti-tumor necrosis factor in the management of patients with Crohn's disease.

Since the approval of the first anti-tumor necrosis factor (anti-TNF) therapy in late 1998, the treatment for Crohn’s disease (CD) has been revolutionized. Anti-TNF therapy has been consistently shown in numerous clinical trials to be effective for patients with more aggressive perianal, internal penetrating, and fistulizing CD. However, the loss of clinical remission is frequent and only one-third of patients remain in clinical remission at 1 year. The pharmacokinetics of anti-TNF is highly variable among patients and could be influenced by many factors including serum albumin, gender, body weight, systemic inflammation and route of administration. The main factor impacting anti-TNF pharmacokinetics and efficacy is the development of immunogenicity where antidrug antibodies accelerate anti-TNF drug clearance. In this review paper, we evaluate the role of combination therapy with anti-TNF drugs and immunomodulators, the role of therapeutic drug monitoring, and strategies to recapture loss of clinical response in order to improve both short- and long-term outcomes in CD patients.
Hall viscosity, orbital spin, and geometry: Paired superfluids and quantum Hall systems

The Hall viscosity, a nondissipative transport coefficient analogous to Hall conductivity, is considered for quantum fluids in gapped or topological phases. The relation of the Hall viscosity to the mean orbital spin per particle $\overline{s}$ (discovered in previous work) is elucidated with the help of examples and of the geometry of shear transformations and rotations. For noninteracting particles in a magnetic field, there are several ways to derive the result (even at nonzero temperature), including standard linear response theory. Arguments for the quantization, and the robustness of $\overline{s}$ to small changes in the Hamiltonian that preserve rotational invariance, are given. Numerical calculations of adiabatic transport are performed to check the predictions for quantum Hall systems, with excellent agreement for trial states. The coefficient of ${k}^{4}$ in the static structure factor is also considered and shown to be exactly related to the orbital spin and robust to perturbations in rotation invariant systems.
Substance abuse among Asian American youth: An ecological review of the literature

Abstract The purpose of this review is to understand the risk and protective factors that are associated with substance use among Asian American youth. Using the Bronfenbrenner's (1994) ecological systems theory, we examine how individual characteristics (age, gender, psychopathology, genetics, and ethnic differences), micro- (family and peers), meso-/exo- (relations between family and peers, cultural norms, and economic stress), macro- (academic achievement and cultural influences), and chrono-systems (acculturation) level factors influence or inhibit substance use among Asian American youth. In addition, this review highlights major implications for practice and policy to prevent substance misuse and to improve outcomes for substance abusing Asian American youth.
Detecting Razorback Suckers Using Passive Integrated Transponder Tag Antennas in the Green River, Utah

Abstract In order to increase detections of razorback suckers Xyrauchen texanus tagged with passive integrated transponders in the upper Colorado River basin, we deployed two passive instream flat-plate antennas (33 × 68 cm) at a razorback sucker spawning location in the Green River, Utah, during spring of 2012 and 2013. Over the course of 29 d in 2012 and 90 d in 2013, the antennas detected 569 razorback suckers, 19 Colorado pikeminnow Ptychocheilus lucius, 16 flannelmouth suckers Catostomus latipinnis, and 1 bluehead sucker Catostomus discobolus. Despite extensive sampling via boat electrofishing (rafts and hard-bottom boats) and netting (fyke, trammel, and gill) in wetlands that occurred from the 1990s to present in the upper Colorado River basin, a large number of tagged razorback suckers and Colorado pikeminnow, including a fish released in 1996, were detected for the first time by our antennas. Our data indicate that the detectability of razorback suckers, and precision and accuracy of survival and ...
Optimal Load Control via Frequency Measurement and Neighborhood Area Communication

We propose a decentralized optimal load control scheme that provides contingency reserve in the presence of sudden generation drop. The scheme takes advantage of flexibility of frequency responsive loads and neighborhood area communication to solve an optimal load control problem that balances load and generation while minimizing end-use disutility of participating in load control. Local frequency measurements enable individual loads to estimate the total mismatch between load and generation. Neighborhood area communication helps mitigate effects of inconsistencies in the local estimates due to frequency measurement noise. Case studies show that the proposed scheme can balance load with generation and restore the frequency within seconds of time after a generation drop, even when the loads use a highly simplified power system model in their algorithms. We also investigate tradeoffs between the amount of communication and the performance of the proposed scheme through simulation-based experiments.
Timed appearance of a calcium-binding protein containing γ-carboxyglutamic acid in developing chick bone☆

Abstract Bone contains a small protein, rich in the vitamin K-dependent calcium-binding amino acid γ-carboxyglutamate (Gla). This protein, named osteocalcin , is extractable by neutral EDTA demineralization and contains over 80% of the total peptide Gla found in bone. Osteocalcin binds Ca 2+ ions with moderate affinity (2 moles of Ca 2+ /6500 g of protein; K d = 0.83 mM). Osteocalcin appears in embryonic chick bones (mandible, calvaria, tibiotarsus, and femur) coincident with the first histologically observable deposition of bone mineral at 8 to 12 days after fertilization. The quantity of this protein increases dramatically during development with characteristic onset and kinetics for each type of bone. In the long bone diaphysis (midshaft), the fraction of noncollagen protein represented by osteocalcin increases 100- to 200-fold between the 8th and 20th day. Relative to total bone protein, the increase is about 35-fold. Osteocalcin may play a role in the development of mineralized tissues and may be a characteristic product of cells differentiated with respect to bone and/or cartilage formation.
Genomic organization and DNA sequences of two human phenol sulfotransferase genes (STP1 and STP2) on the short arm of chromosome 16.

Abstract A family of human phenol sulfotransferase genes has been suggested by the cloning of numerous cDNA isolates from different tissues. We have previously cloned and sequenced theSTMgene encoding the monoamine neurotransmitter-preferring sulfotransferase, M-PST, and a portion of theSTP1gene encoding the phenol-preferring isozyme, P-PST1 (BBRC205,1325–1332;Genomics18,440–443). Both genes were mapped to a small region on the short arm of chromosome 16 (BBRC205,482–489). Here we report on the sequencing and genomic organization of theSTP1andSTP2genes from a single cosmid clone obtained from chromosome 16p12.1-p11.2.STP1andSTP2are 95.9% identical at the amino acid sequence level, whereas theSTMgene is only 92.9% and 90.5% identical toSTP1andSTP2,respectively. Alignment of the genomic sequences indicated that all three genes have 7 coding exons and conserved intron-exon boundaries. These results facilitated the assignment of previously published cDNA isolates as “alleles” of the individualSTM, STP1,andSTP2loci on 16p, and provide to us a greater understanding of the complexity and roles of the phenol sulfotransferase gene family in the metabolism of endogenous and xenobiotic agents.
Stephen Decatur: American Naval Hero, 1779–1820 – By Robert J. Allison

Ignored by academic historians for almost seventy years, Stephen Decatur was the subject of two different but outstanding biographies in 2005. The first, Spencer Tucker's excellent Stephen Decatur:...
Superconformal Electrodeposition for 3-Dimensional Interconnects

Electrodeposition is a key fabrication process used in the state-of-the-art multilevel Cu metallization of microelectronic interconnects, from transistor to circuit board length scale. Recent electrochemical surface science and feature filling studies have provided mechanistic insight into the role of additives in superconformal film growth responsible for void-free filling of recessed surface features. These studies have shown that a physical model based on mass conservation of accelerating surfactant species during area change very effectively describes feature filling of Cu, Ag, and Au from different electrolytes. This paper presents a selective and cursory review of some relevant developments underway in our laboratory.