cssi/SciSciGPT-SciSciNet huggingface dataset:
A GABAergic, Strongly Inhibitory Projection to a Thalamic Nucleus in the Zebra Finch Song System

The anterior forebrain pathway (AFP) of the oscine song system is essential for song learning but not song production. Most cells recorded in this serially connected pathway show increased firing in response to song playback, suggesting largely excitatory connections among AFP nuclei. However, the neurons forming a key projection in this pathway, from area X to the medial nucleus of the dorsolateral thalamus (DLM), express glutamic acid decarboxylase in their somata and terminals, suggesting an inhibitory connection. To investigate the firing properties of DLM neurons and the functional influence of area X afferents in DLM, we made whole-cell recordings from DLM neurons in brain slices from adult male zebra finches. Most cells had intrinsic properties closely resembling those of mammalian thalamocortical cells, including a low-threshold Ca(2+) spike and time-dependent, hyperpolarization-activated inward rectification. Activation of afferents from area X evoked a strong, all-or-none IPSP whose amplitude and latency were unchanged by application of glutamate antagonists, consistent with a monosynaptic contact. The IPSP had a reversal potential near -70 mV and was blocked by the GABA(A) receptor antagonist bicuculline methiodide. Post-inhibitory rebound firing occurred in DLM neurons with a delay near 50 msec. Strong inhibition can combine with the intrinsic properties of DLM neurons to allow signaling on disinhibition. Our data are consistent with the hypothesis that the AFP corresponds to the mammalian corticobasal ganglia-thalamocortical loop. The similar functional properties of avian and mammalian thalamic neurons suggest conserved forebrain mechanisms of sensorimotor information processing across vertebrate taxa.
Integrating Physical Constraints in HW-SW Partitioning for Architectures With Partial Dynamic Reconfiguration

Partial dynamic reconfiguration is a key feature of modern reconfigurable architectures such as the Xilinx Virtex series of devices. However, this capability imposes strict placement constraints such that even exact system-level partitioning (and scheduling) formulations are not guaranteed to be physically realizable due to placement infeasibility. We first present an exact approach for hardware-software (HW-SW) partitioning that guarantees correctness of implementation by considering placement implications as an integral aspect of HW-SW partitioning. Our exact approach is based on integer linear programming (ILP) and considers key issues such as configuration prefetch for minimizing schedule length on the target single-context device. Next, we present a physically aware HW-SW partitioning heuristic that simultaneously partitions, schedules, and does linear placement of tasks on such devices. With the exact formulation, we confirm the necessity of physically-aware HW-SW partitioning for the target architecture. We demonstrate that our heuristic generates high-quality schedules by comparing the results with the exact formulation for small tests and with a popular, but placement-uanaware scheduling heuristic for a large set of over a hundred tests. Our final set of experiments is a case study of JPEG encoding-we demonstrate that our focus on physical considerations along with our consideration of multiple task implementation points enables our approach to be easily extended to handle heterogenous architectures (with specialized resources distributed between general purpose programmable logic columns). The execution time of our heuristic is very reasonable-task graphs with hundreds of nodes are processed (partitioned, scheduled, and placed) in a couple of minutes
Demography of Bell's Vireos in Missouri grassland-shrub habitats.

Abstract Numbers of Bell's Vireos (Vireo bellii) have declined throughout much of the breeding range in recent years, yet little information exists to determine factors that are causing these declines. We studied Bell's Vireos nesting in grassland-shrub habitats at two study areas in central Missouri to determine reproductive performance, survival, and population growth potential. Birds were color banded and observed during the breeding seasons of 1996, 1997, and 1998 to determine seasonal fecundity. We monitored 124 breeding pairs (127 pair years) and 213 nests. Density declined from 1.00 to 0.80 territories per 10 ha at the first site and increased from 1.11 to 1.33 at the second site during the study. Mean nesting success was 31 ± SE of 0.03% overall and ranged from 13 to 42% among years and study areas; 57% of the pairs fledged at least one young. Low annual production was a function of high rates of nest predation (41% of all nests observed, accounting for 44 to 78% of daily nest mortality annually) ...
CHESMIN: A Heuristic for State Reduction in Incompletely Specified Finite State Machines

A heuristic algorithm, chesmin (checking sequence based state minimization), is proposed for state reduction in incompletely specified finite state machines (ISFSMs). The algorithm is based on checking sequence generation and identification of sets of compatible states. We have obtained results as good as the best exact method in the literature but with significantly better run-times. In addition to finding a reduced FSM, our algorithm also generates an I/O sequence that can be used as test vectors to verify the FSM's implementation.
Biological manifestation of resistance to soybean cyst nematode development in ‘Hartwig’ soybean

Abstract ‘Hartwig’ soybean [ Glycine max (L.) Merr.] is the first cultivar reported to be resistant to all known races of soybean cyst nematode (SCN), Heterodera glycines Ichinohe; however, the nature of resistance in this cultivar is not known. Resistance to SCN in Hartwig and its donor parent, PI 437654, was studied from observations of the developmental stages of the nematode in the plant roots and compared with the development in susceptible ‘Essex’. Soybean seedlings (emerging roots) were exposed to a wild population of SCN for 8 h and transferred to hydroponics. Adult males and females were extracted and the number of immature juveniles in the roots was recorded from stained roots. A greater number of juveniles of SCN penetrated the roots of Hartwig than roots of PI 437654 or Essex. Several immature juveniles were observed in the roots of Hartwig and PI 437654; however, no mature females developed on either of these two lines. There were no immature juveniles in Essex. Many adult males developed in Hartwig and PI 437654. Complete resistance to female development operated in both Hartwig and PI 437654, whereas partial resistance to male development was observed in PI 437654. Hartwig soybean seems to attract more SCN juveniles, resulting in greater initial penetration than occurs in PI 437654 or Essex.
Assessment of novel anti-p185HER-2 monoclonal antibodies for internalization-dependent therapies.

Novel therapies that require internalization of effector domains may be improved by assessing the efficacy of postbinding receptor-mediated endocytosis. To achieve targeted gene therapy of immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal antibody (MAb) engineering have expanded the potential range of host cells that can be targeted for therapeutic intervention. However, relatively little is known about cellular responses after binding of a vector construct. We have tested the utility of four novel MAbs recognizing the extracellular domain of pl85HER-2, a membrane receptor protein, for use in internalization-dependent therapies. All four antibodies bound to pl85HER-2 in a number of immunoassays. Two antibodies recognized accessible epitopes of pl85HER-2 on viable cells. Radioimmunoassay demonstrated that antibody-membrane receptor complexes formed by two antibodies were internalized and trafficked through an endolysosomal degradative pathway. Two of the f...
Engaging Students in Autobiographical Critiqueas a Social Justice Tool: Narratives of Deconstructingand Reconstructing Meritocracy and PrivilegeWith Preservice Teachers

This self-study involves instructors of a Social Justice in Education course at a large university who engaged preservice teacher education students with assignments intended to solicit their critical self-reflection and to facilitate an awareness of themselves as sociocultural beings. Our work responds to the continued need to involve preservice teachers in experiences that foster critical consciousness and cognizance of their own socialization. For the assignments, students were first asked to describe key moments in their educational experience in the form of a multimedia submission and reflection. After a semester of critical discussions and readings, students were then asked to revisit their initial projects and critique those using course concepts. In addition, they were prompted to include plans for themselves as future social justice educators. In this article, we analyze those student submissions, and we find that many reached new conclusions about social justice topics such as race and gender, c...
Femtosecond Measurements Of Size-Dependent Spin Crossover In FeII(pyz)Pt(CN)4 Nanocrystals

We report a femtosecond time-resolved spectroscopic study of size-dependent dynamics in nanocrystals (NCs) of Fe(pyz)Pt(CN)4. We observe that smaller NCs (123 or 78 nm cross section and <25 nm thickness) exhibit signatures of spin crossover (SCO) with time constants of ∼5–10 ps whereas larger NCs with 375 nm cross section and 43 nm thickness exhibit a weaker SCO signature accompanied by strong spectral shifting on a ∼20 ps time scale. For the small NCs, the fast dynamics appear to result from thermal promotion of residual low-spin states to high-spin states following nonradiative decay, and the size dependence is postulated to arise from differing high-spin vs low-spin fractions in domains residing in strained surface regions. The SCO is less efficient in larger NCs owing to their larger size and hence lower residual LS/HS fractions. Our results suggest that size-dependent dynamics can be controlled by tuning surface energy in NCs with dimensions below ∼25 nm for use in energy harvesting, spin switching, ...
“Virtue and Knowledge Combined”: French Catholic Tradition within a Nineteenth-Century American School for Women

This article analyzes the rhetorical practices at a nineteenth-century Catholic school run by women religious for young women of all faiths. This school, St. Mary-of-the-Woods, embraced its motto “virtue and knowledge combined” to achieve its goal of establishing the French religious spirit in a country with anti-Catholic biases. Teaching lessons based on their French traditions, the sisters replaced lessons in religion with ones on morality and virtue. Thus the sisters promoted their French religious spirit without appearing to proselytize; even without converting students to Catholicism, the sisters succeeded in helping to establish the “French religious spirit” in Indiana.
Chapter 5 – Membrane Models

Before detailed structural information was available, much investigation led to the discovery of the important features of the structures of the membranes of cells and viruses. Key experiments in this exploration date back to the early part of the 20th century. The observation that one of the major components of biological membranes, membrane lipids, spontaneously form lipid bilayers was a formative step in building our current understanding of membrane structure. However, the conclusion that biological membranes also are built around a lipid bilayer is more recent, coming into its own in the 1960s and 1970s. Models from that time integrated developing knowledge of membrane proteins as well as membrane lipids to suggest the kind of structure seen in Fig. 5.2, the lipid bilayer in which are embedded membrane proteins. These advances laid the groundwork for a much more complete understanding of membrane structure and function, which is the focus of the remainder of this book.
A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein.

Abstract A novel DNA sequence element termed the J element involved in the regulated expression of class II major histocompatibility complex genes was recently described. To study this element and its role in class II gene regulation further, a cDNA library was screened with oligonucleotide probes containing both the S element and the nearby J element of the human DPA gene. Several DNA clones were obtained by this procedure, one of which, clone 18, is reported and characterized here. It encodes a protein predicted to contain 688 amino acid residues, including 11 zinc finger motifs of the C2H2 type in the C-terminal region, that are Kruppel-like in the conservation of the H/C link sequence connecting them. The 160 N-terminal amino acids in the nonfinger region of clone 18 are highly homologous with similar regions of several other human, mouse, and Drosophila sequences, defining a subfamily of Kruppel-like zinc finger proteins termed TAB (tramtrack [ttk]-associated box) here. One of the Drosophila sequences, ttk, is a developmental control gene, while a second does not contain a zinc finger region but encodes a structure important in oocyte development. An acidic activation domain is located between the N-terminal conserved region of clone 18 and its zinc fingers. This protein appears to require both the S and J elements, which are separated by 10 bp for optimal binding. Antisense cDNA to clone 18 inhibited the expression of a reporter construct containing the DPA promoter, indicating its functional importance in the expression of this class II gene.
The structure of small, vapor-deposited particles: I. Experimental study of single crystals and particles with pentagonal profiles

Abstract The crystallographic structure of small gold particles vapor-deposited on NaCl substrates was investigated using high resolution,0 selected-zone dark field (SZDF), Bragg reflection imaging (BRI), moire fringe imaging, and strong beam and weak beam dark field (WBDF) transmission electron microscopy (TEM) imaging techniques. Those particles that exhibit uniform contrast in bright field (BF) and have a distinct triangular shape are perfect single crystals with a face-centered cubic (fcc) structure. The particles with pentagonal profile were determined to be regular decahedra composed of five identical tetrahedral building units of non-fcc structure. Each unit has a body-centered orthorhombic crystal symmetry, slightly distorted from the fcc structure. The experimental evidence for this new particle model and for the conclusion that the older model based on fcc tetrahedral building units does not apply includes (a) SZDF-BRI micrographs demonstrating the nonexistence of gaps between the tetrahedral units; (b) WBDF images showing thickness fringes that exclude nonuniform lattice strains that would result from an fcc model with closed gaps; and (c) micrographs exhibiting characteristics moire fringes in well-defined parts of the composite particles.
Effects of Freeze-Thawing Poultry Giblets on Amount and Composition of Fluid Released and Moisture and Fat Loss Due to Heating

Abstract Commercially processed broiler and turkey giblets (hearts, livers, and gizzards) were separated into four lots: unfrozen, or frozen for 4, 8, or 12 weeks at −10 C, then thawed. Thawing was accomplished at 2 C for 64 hr, and the volume of fluid released due to freeze-thawing was measured and analyzed for moisture and solids. All giblets were analyzed for percent moisture and the release of moisture and fat due to heating. Moisture content of the giblets was significantly related to species and whether giblets were unfrozen or frozen-thawed. Hearts showed the greatest loss in moisture due to freeze-thawing and also released more moisture and fat when heated than gizzards or livers. Frozen-thawed livers released significantly less moisture when heated than unfrozen livers. Livers lost practically no fat when heated. Frozen-thawed livers released significantly more fluid than did hearts, and hearts released more fluid than did gizzards. The fluid released from livers contained significantly more solids and less moisture than the fluid from hearts or gizzards.
Predicting Patterns of Grammatical Complexity Across Language Exam Task Types and Proficiency Levels

In the present article, we explore the extent to which previous research on register variation can be used to predict spoken/written task-type variation as well as differences across score levels in the context of a major standardized language exam (TOEFL iBT). Specifically, we carry out two sets of linguistic analyses based on a large corpus of TOEFL iBT responses: one investigating the use of 23 grammatical complexity features, and the second based on co-occurrence patterns among linguistic features, using Multi-Dimensional (MD) analysis. The first set of analyses confirms the predictions from research on register variation: there are systematic linguistic differences among spoken versus written and independent versus integrated task types. However, hypothesized developmental progressions in the use of these grammatical complexity features were generally not confirmed by score-level differences. In contrast, the MD analysis yielded more robust predictors of both task types and score-level differences, indicating that linguistic descriptions are more reliable and informative when they are based on dimensions of co-occurring lexico-grammatical features. In conclusion, we discuss the application of such dimensions as holistic complexity measures in language development/testing research.
Enhanced ultrasound for advanced diagnostics, ultrasound tomography for volume limb imaging and prosthetic fitting

Ultrasound imaging methods hold the potential to deliver low-cost, high-resolution, operator-independent and nonionizing imaging systems – such systems couple appropriate algorithms with imaging devices and techniques. The increasing demands on general practitioners motivate us to develop more usable and productive diagnostic imaging equipment. Ultrasound, specifically freehand ultrasound, is a low cost and safe medical imaging technique. It doesn't expose a patient to ionizing radiation. Its safety and versatility make it very well suited for the increasing demands on general practitioners, or for providing improved medical care in rural regions or the developing world. However it typically suffers from sonographer variability; we will discuss techniques to address user variability. We also discuss our work to combine cylindrical scanning systems with state of the art inversion algorithms to deliver ultrasound systems for imaging and quantifying limbs in 3-D in vivo. Such systems have the potential to track the progression of limb health at a low cost and without radiation exposure, as well as, improve prosthetic socket fitting. Current methods of prosthetic socket fabrication remain subjective and ineffective at creating an interface to the human body that is both comfortable and functional. Though there has been recent success using methods like magnetic resonance imaging and biomechanical modeling, a low-cost, streamlined, and quantitative process for prosthetic cup design and fabrication has not been fully demonstrated. Medical ultrasonography may inform the design process of prosthetic sockets in a more objective manner. This keynote talk presents the results of progress in this area.
Parturition in a Skunk, Mephitis mephitis hudsonica

A northern plains striped skunk that had for two years been a part of the skunk colony at the Vivarium, was in rut and on March 12, was bred to a northern plains striped male. From March 15 to 18, she was bred each day to the same male and on the 18th, was bred both morning and afternoon, but thereafter she was consistently antagonistic and attacked the male each time he was placed in her cage. Her copulatory period had extended over seven days. The following observations on parturition were made at close range, for the floor of the female's cage was approximately at shoulder level so that at no time were the observer's eyes more than one to three feet from her and yet she was not disturbed and seemed to pay no attention to his movements which consisted entirely of making notes. Since such close proximity of an observer during parturition of a skunk is unusual, these observations seemed worth recording. On the morning of May 18 (67 days after the first copulation and 61 days after the last) this skunk was discovered in parturition. She had already given birth to one kit, had practically completed the process of cleaning it, and the kit was slowly crawling about on the cage floor. This birth is believed to have occurred within the preceding half-hour, probably at about 9:15 am. The female was still in labor and frequently tensed her …
THE MAIN CONTROL FACTORS FOR DELTA SEDIMENTATION

Abstract The formation of a river delta is mainly due to the interaction of two different hy-drodynamics between a river,which carries much mud and sand,and a reservoir.Thereare many control factors to this process,but the main factors are the slope of river bed,the size of mud and sand,the geometry of river mouth,the annual volume of river loadand the hydrodynamics of reservoir.The simulation of depositional process for delta bycomputer is a new method for the research of sand-body formation。With this method,it is possible to observe quantitatively the effect of these significant control factors to thedistribution scale、the thickness and the heterogeneities of delta sediments.SUBJECT TERMS:delta sedimentation,numerical simulation
Connecting high school dropouts to employment and education: an impact study of the National Guard Youth ChalleNGe Program

This paper presents findings from the multi-year, random assignment study of the National Guard Youth ChalleNGe Program (NGYCP), an intensive residential program for high school dropouts. The “second chance” program gives youth an opportunity to earn a high school credential and prepare to enter the workforce or continue on to post-secondary education. The NGCYP study sample includes 1173 youth, ages 16–18, from ten program sites across the USA. Positive impacts on employment and educational outcomes were sustained 3 years after entering the study, with some evidence of older participants benefiting more than younger participants. Implications for research and practice are discussed. JEL codes: J1, I26
When To Hospitalize The Hypertensive Patient

The concept of “inappropriate” hypertension is a critical part of this article, which also examines the current status of management of the patient with malignant hypertension, outlines the criteria for surgical intervention in high-blood-pressure patients and discusses the role of arteriograhic and other radiologic techniques in making or confirming a definite diagnosis and guiding therapy.
Determinants of stillbirths in Ghana: does quality of antenatal care matter?

Each year, over two million babies die before they are born. Like maternal deaths, the great majority of these stillbirths occur in developing countries, with about a third of all cases worldwide in sub-Saharan Africa (SSA). Few studies have, however, examined the determinants of stillbirths in SSA. In addition, the emphases on promoting deliveries by skilled birth attendants and/or in health facilities to prevent maternal deaths, though important, may have undermined efforts to provide good quality antenatal care (ANC), which may have an additional role in preventing stillbirths. This study examines the factors associated with stillbirths in Ghana, focusing on the role of ANC quality.
Clinical applications of MR imaging in hand and wrist surgery

MR imaging is emerging as an invaluable tool in the diagnosis of hand and wrist disorders. It is extremely accurate in the diagnosis of stage 1 Kienbock's disease when plain radiographs are equivocal and in evaluating bone and soft-tissue tumors of the hand and wrist. MR imaging is replacing arthrography as the imaging modality of choice for disruptions of the TFCC. With refined technology and improved resolution, abnormalities involving the intercarpal ligaments ultimately will be able to be detected with a high degree of precision.
“We Are All Serafina’s Children”: Racial Landscapes in Rudolfo Anaya

Anaya’s literary corpus is a sustained celebration of hybridity and convergence, as well as a deconstruction of racial/cultural essentialism. Anaya is fully aware of the tragic destiny of the American Indian after the arrival of the European, and he recounts that tragedy once again in his writings, especially the fate of the Pueblos in the Southwest, for the past cannot be denied, much less forgotten. However, Anaya is very conscious of the fact that the past cannot be changed, and also of the fact that we can all learn from it. And I think that is precisely one of the overarching themes that unify Anaya’s fiction, the desire to draw lessons from the past that can help us understand, and change the present. In the closing lines of Serafina’s Stories, Anaya writes, “Perhaps by studying and understanding the history surrounding the 1680 Pueblo Indian Revolt we learn not to place blame, but how we can live together in mutual respect. As a wise man said, we cannot change history, but we can learn from it” (202).
Neurophysiological Effects of Insecticides

Publisher Summary This chapter describes several electrophysiological targets of pesticides, including the voltage-gated sodium channel, acetylcholine receptors, and the GABAA receptors, covering the neurophysiological mechanisms of action of various insecticides. The understanding of these interactions between several classes of pesticides, including the pyrethroids and organophosphate and carbamate insecticides, and these biological systems allows for the determination of the most sensitive biological component (e.g., ionic channel) but also the development of preventive strategies. Applications of molecular biology and genetics techniques have made it possible to identify the molecular species that are responsible for the toxic action of insecticides, particularly those related to the target resistance of insects to insecticides. Most insecticides are neuropoisons, but their target sites are rather limited. Voltage-gated sodium channels are the major target of pyrethroids and DDT; GABAA receptors are attacked by cyclodienes, hexachlorocyclohexane (HCH), and fipronil; neuronal nicotinic acetylcholine (nnACh) receptors are the target of nicotine, and nitromethylene and nitroimine hete-rocycles (e.g., imidacloprid). Organophosphate and carbamate insecticides inhibit acetylcholinesterase.
Deep Neural Networks for Identifying Cough Sounds

In this paper, we consider two different approaches of using deep neural networks for cough detection. The cough detection task is cast as a visual recognition problem and as a sequence-to-sequence labeling problem. A convolutional neural network and a recurrent neural network are implemented to address these problems, respectively. We evaluate the performance of the two networks and compare them to other conventional approaches for identifying cough sounds. In addition, we also explore the effect of the network size parameters and the impact of long-term signal dependencies in cough classifier performance. Experimental results show both network architectures outperform traditional methods. Between the two, our convolutional network yields a higher specificity 92.7% whereas the recurrent attains a higher sensitivity of 87.7%.
The effects of communication load and mode on perceived decision quality and satisfaction

This study examined the extent to which communication load (underload, normal load, or overload) and communication mode (oral or written) affect individuals’ perceptions of the quality of their decisions and of their satisfaction with those decisions. Data were collected from one group of university student subjects and one group of volunteers from a local organization. Results on communication load indicated that perceived quality of and perceived satisfaction with decisions were higher in underload than overload. However, university subjects perceived greater satisfaction in underload conditions while organization subjects did so for normal load conditions. All subjects perceived greater satisfaction for decisions made using the oral mode of communication, but they perceived higher quality for decisions made using the written mode. Implications of these results and questions for future study were discussed. Clearly, individuals’ perceptions of both quality and satisfaction were affected by the different...
Trenched gamma-ray detector

3-D detectors were first introduced by S. Parker et al. as radiation-hard detectors. We present 3-D detectors for use as thick gamma-ray detectors. Current room-temperature gamma-ray detectors are built in planar device architecture. We use micro-machining techniques to introduce vertical electrodes, which allow lateral charge collection, decoupling thickness and charge collection properties. The ultimate goal is the ability to form cm thick room-temperature gamma-ray detectors. The vertical electrodes are micro-machined trenches with depth up to 1.7 mm in silicon. We present the basic detector structure, SILVACO simulations, and first radiation measurements. An energy resolution of 2.3 keV FWHM at 59.5 keV was obtained. This is evidence of excellent charge collection from the trenches.
PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide

// Laurence Booth 1 , Jane L. Roberts 1 , Andrew Poklepovic 2 , Sarah Gordon 2 , Paul Dent 1 1 Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298-0035, USA 2 Department of Medicine, Virginia Commonwealth University, Richmond, VA 23298-0035, USA Correspondence to: Paul Dent, email: pdent@vcu.edu Keywords: sildenafil, autophagy, pemetrexed, chaperone, lung cancer Received: October 04, 2016 Accepted: November 15, 2016 Published: November 26, 2016 ABSTRACT Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. PDE5 inhibitors enhanced the anti-NSCLC cell effects of the NSCLC therapeutic pemetrexed. [Pemetrexed + sildenafil] activated an eIF2α – ATF4 – CHOP – Beclin1 pathway causing formation of toxic autophagosomes; activated a protective IRE1 – XBP-1 – chaperone induction pathway; and activated a toxic eIF2α – CHOP – DR4 / DR5 / CD95 induction pathway. [Pemetrexed + sildenafil] reduced the expression of c-FLIP-s, MCL-1 and BCL-XL that was blocked in a cell-type -dependent fashion by either over-expression of HSP90 / GRP78 / HSP70 / HSP27 or by blockade of eIF2α-CHOP signaling. Knock down of PKGI/II abolished the ability of sildenafil to enhance pemetrexed toxicity whereas pan-inhibition of NOS using L-NAME or knock down of [iNOS + eNOS] only partially reduced the lethal drug interaction. Pemetrexed reduced the ATPase activities of HSP90 and HSP70 in an ATM-AMPK-dependent fashion that was enhanced by sildenafil signaling via PKGI/II. The drug combination activated an ATM-AMPK-TSC2 pathway that was associated with reduced mTOR S2448 and ULK-1 S757 phosphorylation and increased ULK-1 S317 and ATG13 S318 phosphorylation. These effects were prevented by chaperone over-expression or by expression of an activated form of mTOR that prevented autophagosome formation and reduced cell killing. In two models of NSCLC, sildenafil enhanced the ability of pemetrexed to suppress tumor growth. Collectively we argue that the combination of [pemetrexed + PDE5 inhibitor] should be explored in a new NSCLC phase I trial.
Effects of selection for ethanol preference on gene expression in the nucleus accumbens of HS-CC mice

Previous studies on changes in murine brain gene expression associated with the selection for ethanol preference have used F2 intercross or heterogeneous stock (HS) founders, derived from standard laboratory strains. However, these populations represent only a small proportion of the genetic variance available in Mus musculus. To investigate a wider range of genetic diversity, we selected mice for ethanol preference using an HS derived from the eight strains of the collaborative cross. These HS mice were selectively bred (four generations) for high and low ethanol preference. The nucleus accumbens shell of naive S4 mice was interrogated using RNA sequencing (RNA-Seq). Gene networks were constructed using the weighted gene coexpression network analysis assessing both coexpression and cosplicing. Selection targeted one of the network coexpression modules (greenyellow) that was significantly enriched in genes associated with receptor signaling activity including Chrna7, Grin2a, Htr2a and Oprd1. Connectivity in the module as measured by changes in the hub nodes was significantly reduced in the low preference line. Of particular interest was the observation that selection had marked effects on a large number of cell adhesion molecules, including cadherins and protocadherins. In addition, the coexpression data showed that selection had marked effects on long non-coding RNA hub nodes. Analysis of the cosplicing network data showed a significant effect of selection on a large cluster of Ras GTPase-binding genes including Cdkl5, Cyfip1, Ndrg1, Sod1 and Stxbp5. These data in part support the earlier observation that preference is linked to Ras/Mapk pathways.
Epidemiology of Gastrointestinal Disease

The elderly represent a unique cohort of the US population—and their numbers are on the rise. Among the medical community, being 65 years or older represents an age associated with multiple comorbid conditions and a point in life at which practitioners are typically less likely to advise aggressive diagnostic, medical, and surgical interventions for common medical conditions. It is increasingly recognized that a subset of older individuals live longer and healthier lives without major disease entities or limitations in functional status. Although aging is associated with declines in the cardiovascular, metabolic, renal, endocrine, musculoskeletal, immunologic, and neurologic systems, the gastrointestinal (GI) tract differs in its greater reserves and ability to maintain relatively normal digestive and absorptive function. Nonetheless, certain gastrointestinal disorders are more common and cause greater morbidity and mortality in the aged. Additionally, parallel diminished reserves in other systems may cause profound gastrointestinal effects and the contributing roles of depression, cognitive decline, lack of social support, and polypharmacy may further incite deleterious gastrointestinal consequences. Aging is also associated with the accumulation of genetic mutations and chromosomal instability, reflected in the higher incidence and mortality of GI cancers in the old.
An Intuitive Approach for Predicting Potential Human Health Risk with the Tox21 10k Library

In vitro–in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited. This study represents the first report applying IVIVE approaches and exposure comparisons using the entirety of the Tox21 federal collaboration chemical screening data, incorporating assay response efficacy and quality of concentration–response fits, and providing quantitative anchoring to first address the likelihood of human in vivo interactions with Tox21 compounds. This likelihood was assessed using a maximum blood concentration to in vitro response ratio approach (Cmax/AC50), analogous to decision-making methods for clinical drug–drug interactions. Fraction unbound in plasma (fup) and intrinsic hepatic clearance (CLint) parameters were estimated in silico and incorporated in a three-compartment toxicokinetic (TK) model to first predict Cmax for in vivo corroboration using therapeutic scenarios. Toward lower exposure scenarios, 36 compounds of 3925 unique chemicals wit...
Just transitions: A humble approach to global energy futures

Abstract Persistent mismatches between problems, policy framings, and solutions point to unsettled ethical conundrums in the ways that the energy transition is being imagined at the centers of global power. First, development is too often seen as the means to achieve more sustainable futures, even though experience points to complex and uncertain relationships between prosperity and sustainability. Second, while technological change is seen as essential to the transition, less attention is paid to the fact that disparities within societies demand differentiated solutions. Third, there are few principles in place for how to effect an energy transition with due attention to social justice in an unequal world. This article reflects on all three points.
Cezanne/OTUD7B is a cell cycle‐regulated deubiquitinase that antagonizes the degradation of APC/C substrates

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and key regulator of cell cycle progression. Since APC/C promotes the degradation of mitotic cyclins, it controls cell cycle-dependent oscillations in cyclin-dependent kinase (CDK) activity. Both CDKs and APC/C control a large number of substrates and are regulated by analogous mechanisms, including cofactor-dependent activation. However, whereas substrate dephosphorylation is known to counteract CDK, it remains largely unknown whether deubiquitinating enzymes (DUBs) antagonize APC/C substrate ubiquitination during mitosis. Here, we demonstrate that Cezanne/OTUD7B is a cell cycle-regulated DUB that opposes the ubiquitination of APC/C targets. Cezanne is remarkably specific for K11-linked ubiquitin chains, which are formed by APC/C in mitosis. Accordingly, Cezanne binds established APC/C substrates and reverses their APC/C-mediated ubiquitination. Cezanne depletion accelerates APC/C substrate degradation and causes errors in mitotic progression and formation of micronuclei. These data highlight the importance of tempered APC/C substrate destruction in maintaining chromosome stability. Furthermore, Cezanne is recurrently amplified and overexpressed in numerous malignancies, suggesting a potential role in genome maintenance and cancer cell proliferation.
Iterative image coding using hybrid wavelet-based triangulation

This paper presents a novel hierarchical subdivision scheme for generating triangular meshes to represent intensity images. The resulting representation is well suited to content-based management of images and videos, including storage and retrieval for multimedia applications. Mesh node locations are selected using multiresolution wavelet-based analysis, and this leads to a piecewise-linear approximation of image intensity values. Interpretation of wavelet coefficients at successively finer levels leads to fast, efficient triangular mesh construction in which the number of approximating elements depends on the image content and on user-specified maximum error. By combining Delaunay and data-dependent triangulation approaches, the result is an efficient multiresolution coding scheme that approximates the image to a desired level of detail, while retaining information related to image content under user-specified triangulation regularity. We demonstrate the utility of this approach for such multimedia applications such as selective compression, segmentation, and eye detection in images of human faces.
BIOMECHANICAL ANALYSIS OF POROUS TITANIUM AND LTI CARBON HIP PROSTHESES

Publisher Summary This chapter discusses the stress state and presents the remodeling changes associated with porous coated titanium and Pyrolite carbon hip hemiarthroplasties, with special attention given to the effects of Implant-bone interface conditions. A two dimensional finite element model was constructed to represent the proximal femur and device. The isotropic moduli for the cancellous and cortical bone were taken as the average of the respective orthotropic moduli. Six different materials were assumed for cancellous bone and were distributed according to trabecular density. The strain energy densities around each device were normalized by dividing by the strain energies of the corresponding elements of a natural femur model, giving the relative change in the strain associated with each device. Four cases were studied using a finite element model corresponding to full bone growth into the porous coating, complete bone opposition to low temperature isotropic carbon, and each device with an Interposed fibrous tissue layer. The good correlation between computer analysis and the experimental model indicated that the condition of the bone-implant interface may be determined not exclusively by the appearance of a radiolucent line, but also by assessing the global and trabecular remodeling pattern.
Anesthesia for Redo Cardiac Surgery

In recent years, an increasing proportion of elderly patients have been referred for repeat cardiac surgery despite the higher morbidity and mortality associated with redo procedures. This patient population requires additional considerations when planning their anesthetic and perioperative care, based on the higher incidence of preexisting conditions in elderly patients as well as the greater surgical risk associated with sternal reentry.
Feminism, Labour and Digital Media: The Digital Housewife

Kylie Jarrett’s book Feminism, labour and digital media: The digital housewife (2015) examines digital, free, consumer labour as gendered, at the same time as revealing how the seemingly mutually e...
Where do we stand? Recent AEA member views on professionalization.

Abstract The professionalization of evaluation continues to be debated at numerous conferences in the U.S. and abroad. At this time, AEA member views on the potential benefits and negative side effects of professionalization are essential as the discussion evolves. This study provides recent views on major topics in professionalization, including potential benefits, negative side effects, processes, competencies, and procedures. Results from in-depth interviews and an online survey demonstrate that AEA members view potential benefits of professionalization to be stakeholder trust, evaluator reputation and identity, while concerns about a potential negative side effect known as the “narrowing effect” (i.e., some evaluators will be alienated based on their background, competencies, etc.) were expressed by participants. These recent findings can inform the ongoing discussion of professionalization, and suggest new directions for future research on evaluation.
Do racial and ethnic disparities in health care use vary with health

Objective To determine the relationship between health status and the magnitude of black-white and Hispanic-white disparities in the likelihood of having any office-based or hospital outpatient department visits, as well as number of visits. Data source 2010-2014 Medical Expenditure Panel Survey. Study design The probability of having a visit is modeled using a Probit model, and the number of visits using a negative binomial model. We use a nonlinear rank-and-replace method to adjust minority health status to be comparable to that of whites, and predict utilization at different levels of health by fixing an indicator of health status. We compare estimated differences in predicted utilization across racial/ethnic groups for each level of health status to map out the relationship between the racial/ethnic disparity and health status, also stratifying by health insurance coverage. Extraction methods We subset to nonelderly adults. Principal findings We find that Hispanic-white differences in the probability of having an office-based or hospital outpatient department were widest among adults in excellent health (27 percentage points, 95% CI: [23, 31]) and narrowest when reporting poor or fair health (15 p.p. [13, 17]). Black-white and Hispanic-white differences in the number of visits were wider for adults who report poor or fair health (5.3 visits [4.0, 6.6] and 5.7 [4.3, 7.0], respectively) compared to excellent health (1.7 [1.2, 2.1] and 1.5 [1.1, 2.0], respectively) among adults who are full-year privately insured. Conclusions The magnitudes of racial/ethnic disparities vary with level of health.
Exploring Tropical Variability and Extremes Impacts on Population Vulnerability in Piura, Peru: The Case of the 1997–98 El Niño

Abstract Tropical variability and extremes contribute to significant societal and public health impacts in the northwestern coast of South America. In this chapter, the complexity of hydrometeorological risk and population vulnerability in Piura, Peru, an El Nino hot spot, is explored by examining the interactions of climate, environment, and society components during the extreme event of 1997–98. Using a cross-disciplinary framework, grounded in “climate affairs,” the analysis shows that El Nino vulnerability is not only a matter of physical climate risk but also one of the preexisting social and health conditions, which set the stage for unsafe environments. Beyond the economic costs of damages to the built environment, public services, industries, and in general livelihoods, is an excess burden of disease morbidity (i.e., ecosyndemics), in addition to loss of life, along with gender inequalities, all of which exacerbate tropical climate risk. Thus, in conceiving public policy for adaptation and resilience to increasing hydrometeorological risk and the quasiperiodic threats of El Nino, decision makers must take into account the potential intersections of various vulnerabilities that coexist in their respective constituent communities and affect the public's health and well-being. In doing so, policy-makers can appropriately address root causes of hydrometeorological risk, build up existing resilience capacities, and move toward disaster risk reduction that is part and parcel of El Nino “readiness” and sustainable development.
Callibora Cognato (Coleoptera: Curculionidae: Scolytinae: Xyleborini), a New Genus of Xyleborine Ambrosia Beetle from Ecuador

The Ecuadorian Amazonian canopy has revealed a new genus, Callibora Cognato (type species Callibora sarahsmithae Cognato, new species). This new genus represents a presumably endemic species related to a Neotropical radiation of xyleborines belonging to the Dryocoetoides Hopkins/ Sampsonius Eggers/ Dinoxyleborus Smith species clade. A truncated elytral declivity and inflated protibae distinguish it from other Neotropical xyleborine genera.
The Tocqueville Paradox: When Does Reform Provoke Rebellion?

We develop a model of reform and rebellion to explore Alexis de Tocqueville's conjecture that reform provokes political unrest. Our theory emphasizes that reform often must be implemented by local actors with a stake in the status quo. In this setting, the promise of reform represents an implicit contract against which subsequent implementation is measured: when implementation falls short of the promise, citizens are aggrieved and more likely to rebel. In equilibrium, when reform is predominantly under local control, a more ambitious reform encourages greater implementation; nonetheless, the equilibrium probability of rebellion also increases. We illustrate our argument with a discussion of Russia's Emancipation Reform of 1861.