cssi/SciSciGPT-SciSciNet huggingface dataset:
Biology of Bone

Bone is the main component of the skeleton, together with connecting tissues including cartilage, ligaments and tendons, providing mechanical and structural support for the remaining organs and systems in the body. This mechanical and structural support function is indispensable for life, both during the growth and development period as well as during adult life. However, bone also provides the unique architecture and microenvironment that preserve the niches which maintain immature stem cells. This niche aspect of bone is an inadequately recognized function, although an essential one, since stem cells are required for tissue repair and regeneration during adult life. In addition to providing mechanical support, bone contains and supports the main reservoir of cells needed to sustain tissue integrity and function throughout our lives. Thus, understanding how bone is made and maintained during life is central to developing adequate strategies to preserve a healthy skeleton as we age, so that proper mechanical support, structural integrity and tissue repair capacity are maintained.
Role of Human Xeroderma Pigmentosum Group D (XPD) Helicase in Various Cellular Pathways

Abstract Xeroderma pigmentosum group D helicase (XPD/ERCC2) is a member of the Rad3/XPD subfamily of ATP-dependent DNA helicases. It is an integral component of TFIIH, playing an essential role in transcription and nucleotide excision repair (NER). This chapter will primarily focus on studies showing that XPD associates with a functionally diverse class of proteins, including key factors involved in iron–sulfur (Fe-S) cluster assembly, cell-cycle regulation, chromosome segregation and mitochondrial function. The Fe-S cluster is crucial for XPD function. Our published data in 2012 and 2015, provide mechanistic insight into the pathways and factors required for the assembly of an Fe-S cluster on XPD. The importance of XPD’s Fe-S cluster in the context of NER and damage recognition will be discussed. Understanding different aspects of XPD biology in relation to the regulation of NER will be an essential aspect of cancer therapy as chemotherapy-resistant cells utilize their capacity to remove drug-induced DNA lesions.
Equilibrium Debt Financing

Building on Geanakoplos (2009), we study an equilibrium model of an asset market with cash-constrained optimists using their asset positions as collateral to raise debt financing. By using a general binomial setting with time-varying belief dispersion between agents, we highlight an asset's marketability as an important determinant of its collateral value. This is because the availability of secondary market trading allows creditors to sell seized collateral to other optimists with saved cash, which, in turn, not only boosts creditors' initial valuation of the collateral but also motivates optimists to save cash. Our model also establishes the maximum riskless short-term debt as the only debt contract used in the equilibrium and a risk-neutral representation of the equilibrium asset price and prices of debt contracts collateralized by the asset.
Stochastic Multi-Objective Optimization-Based Life Cycle Cost Analysis for New Construction Materials and Technologies

The sustainability of transportation infrastructure depends on the adoption of new construction materials and technologies that can potentially improve performance and productivity. However, most a...
Transform Analysis and Transient Response

Transform means change in form. For example, in finding the derivative of the product of two functions, we use the product rule and transform the problem into an easier one. Multiplication operation is more difficult than addition operation. By expressing the numbers in logarithmic form, we reduce the multiplication operation into an addition.
Successful Treatment of Disseminated Hepatocellular Carcinoma After Liver Transplantation With Nivolumab.

The use of immunotherapy in transplant recipients is considered a contraindication because of very high risks for graft loss. The graft loss is to be expected because cytotoxic T-lymphocyte–associated protein-4 and programmed death 1 pathways are implicated in graft tolerance. In this case report, we describe a woman with recurrent, disseminated hepatocellular carcinoma who was successfully treated with nivolumab, an immune checkpoint inhibitor.
CD3+ T cells are critical for the resolution of comorbid inflammatory pain and depression-like behavior.

Abstract Background Chronic pain and depression often co-occur. The mechanisms underlying this comorbidity are incompletely understood. Here, we investigated the role of CD3+ T cells in an inflammatory model of comorbid persistent mechanical allodynia, spontaneous pain, and depression-like behavior in mice. Methods C57Bl/6 wt and Rag2−/− mice were compared in their response to intraplantar administration of complete Freund’s adjuvant (CFA). Mechanical allodynia, spontaneous pain and depression-like behavior were assessed by von Frey, conditioned place preference and forced swim test respectively. Results Resolution of mechanical allodynia, spontaneous pain, and depression-like behavior was markedly delayed in Rag2−/− mice that are devoid of adaptive immune cells. Reconstitution of Rag2−/− mice with CD3+ T cells from WT mice before CFA injection normalized the resolution of indicators of pain and depression-like behavior. T cells did not contribute to onset or severity of indicators of pain and depression-like behavior. The lack of T cells did not affect cytokine expression in the paw, spinal cord and brain, indicating that the delayed resolution was not resulting from prolonged (neuro)inflammation. Conclusions Our findings show that T cells are critical for the natural resolution of mechanical allodynia, spontaneous pain, and depression-like behavior after an inflammatory challenge. Dysregulation of this T cell-mediated resolution pathway could contribute to the comorbidity of chronic pain and depression. Significance Chronic pain and depression are frequently associated with signs of inflammation. However, general immunosuppression is not sufficient to resolve comorbid pain and depression. Here we demonstrate that T cells are required for resolution of comorbid persistent mechanical allodynia, spontaneous pain, and depression in a model of peripheral inflammation, indicating the immune system can contribute to both onset and resolution of these comorbidities. Enhancing pro-resolution effects of T cells may have a major impact to treat patients with comorbid persistent pain and depression.
Early cytomegalovirus DNAemia and antiviral dose adjustment in high vs intermediate risk kidney transplant recipients.

Background Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation. Methods We reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3-year period at a high-volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis. Results Despite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100 days after transplantation. For high risk patients, median time to DNAemia was 75 days after transplantation, and the majority of patients had experienced dose-reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64 days (P = .029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group. Conclusions Guidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation.
A Spatial Correlation-Based Anomaly Detection Method for Subsurface Modeling

Spatial data analytics provides new opportunities for automated detection of anomalous data for data quality control and subsurface segmentation to reduce uncertainty in spatial models. Solely data-driven anomaly detection methods do not fully integrate spatial concepts such as spatial continuity and data sparsity. Also, data-driven anomaly detection methods are challenged in integrating critical geoscience and engineering expertise knowledge. The proposed spatial anomaly detection method is based on the semivariogram spatial continuity model derived from sparsely sampled well data and geological interpretations. The method calculates the lag joint cumulative probability for each matched pair of spatial data, given their lag vector and the semivariogram under the assumption of bivariate Gaussian distribution. For each combination of paired spatial data, the associated head and tail Gaussian standardized values of a pair of spatial data are mapped to the joint probability density function informed from the lag vector and semivariogram. The paired data are classified as anomalous if the associated head and tail Gaussian standardized values fall within a low probability zone. The anomaly decision threshold can be decided based on a loss function quantifying the cost of overestimation or underestimation. The proposed spatial correlation anomaly detection method is able to integrate domain expertise knowledge through trend and correlogram models with sparse spatial data to identify anomalous samples, region, segmentation boundaries, or facies transition zones. This is a useful automation tool for identifying samples in big spatial data on which to focus professional attention.
Financial strain among unpaid family caregivers of frail elders in community

In the United States, 8 out of 10 elders, 65 or older, have at least one chronic disease. Their care likely falls mostly to family members; many experience financial strain associated with providin...
'Testimony Submitted to the U.S. House of Representatives Committee on Natural Resources, Subcommittee on Federal Lands, on Title XV of the 'Sportsmen’s Heritage and Recreational Enhancement Act' or Share Act, Pertaining to Hearing Protection'

Existing federal law allows civilians to purchase gun silencers, also referred to as “suppressors” (noting that eight states restrict such purchases). Hearing protection, amply available, serves the purpose of protecting gun operators from harmful firearm noise. So why tamper with a law that, with the rarest exceptions, has successfully kept silencers out of the hands of criminals for over eight decades? This paper examines the history, regulation, and arguments regarding such devices.
An Empirical Study of Americans’ Attitudes

I next investigate a possible reason that environmentalists (or at least U.S. environmentalists) currently lack interest in the increasing size of the human population and its impact on nature. Specifically, I explore whether, at the present time, Americans generally exhibit little or no sensitivity to the effect that population growth has on the ecosystem of the planet. If this is the case, environmentalists will simply be manifesting the attitudes of the public as a whole. A study that used data gathered in 1969 from a nationwide sample of U.S. adults found that attitudes toward the environment were no more than modestly related to attitudes toward population increase.
Robust RF shimming and small-tip-angle multispoke pulse design with finite-difference regularization.

PURPOSE A new regularizer is proposed for the magnitude least-squares optimization algorithm, to ensure robust parallel transmit RF shimming and small-tip-angle multispoke pulse designs for ultrahigh-field MRI. METHODS A finite-difference regularization term is activated as an additional regularizer in the iterative magnitude-least-squares based pulse design algorithm when an unwanted flip angle null distribution is detected. Both simulated and experimental B1+ maps from different transmit arrays and different human subjects at 7 T were used to evaluate the proposed algorithm. The algorithm was further demonstrated in experiment with dynamic multislice RF shimming for a single-shot gradient-echo EPI for human functional MRI at 7 T. RESULTS The proposed finite-difference regularizer effectively prevented excitation null to be formed for RF shimming and small-tip-angle multispoke pulses, and improved the latter with a monotonic trade-off relationship between flip angle error and RF power. The proposed algorithm was demonstrated to be effective with several head-array geometries by simulation and with a commercial head array with 12 healthy human subjects by experiment. During a functional MRI scan at 7 T with dynamic RF shimming, the proposed algorithm ensured high image SNR throughout the human brain, compared with near-complete local signal loss by the conventional magnitude-least-squares algorithm. CONCLUSION Using finite-difference regularization to avoid unwanted solutions, the robustness of RF shimming and small-tip-angle multispoke pulse design algorithms are improved, with better flip angle homogeneity and a monotonic trade-off relationship between flip angle error and RF power.
Efficient Methods for Online Multiclass Logistic Regression.

Multiclass logistic regression is a fundamental task in machine learning with applications in classification and boosting. Previous work (Foster et al., 2018) has highlighted the importance of improper predictors for achieving "fast rates" in the online multiclass logistic regression problem without suffering exponentially from secondary problem parameters, such as the norm of the predictors in the comparison class. While Foster et al. (2018) introduced a statistically optimal algorithm, it is in practice computationally intractable due to its run-time complexity being a large polynomial in the time horizon and dimension of input feature vectors. In this paper, we develop a new algorithm, FOLKLORE, for the problem which runs significantly faster than the algorithm of Foster et al.(2018) -- the running time per iteration scales quadratically in the dimension -- at the cost of a linear dependence on the norm of the predictors in the regret bound. This yields the first practical algorithm for online multiclass logistic regression, resolving an open problem of Foster et al.(2018). Furthermore, we show that our algorithm can be applied to online bandit multiclass prediction and online multiclass boosting, yielding more practical algorithms for both problems compared to the ones in Foster et al.(2018) with similar performance guarantees. Finally, we also provide an online-to-batch conversion result for our algorithm.
Understanding Health Facility Needs for Human Trafficking Response in Michigan.

Objectives Human trafficking is a public health issue that has substantial health consequences. However, research on the preparedness of health facilities to serve people who have experienced or are experiencing human trafficking is limited. We examined health facility preparedness related to human trafficking in Michigan. Methods We used a cross-sectional design to explore health facility preparedness related to human trafficking in Michigan. We sampled 10 prosperity regions according to health facility type (Federally Qualified Health Centers, health departments, and hospitals). An email invitation was sent to identified health facility personnel (eg, administrators, physicians, nurses) from May to June 2019 with a link to a 26-item survey with items about current policies, protocols, and areas for improvement related to human trafficking. Results Forty-two Federally Qualified Health Centers, health departments, and hospitals responded to the survey. Most health facilities had screening policies and response protocols related to child maltreatment (screening: 32/41 [78.0%]; response: 38/40 [95.0%]) and intimate partner violence (screening: 33/41 [80.5%]; response: 37/40 [92.5%]). However, fewer facilities had a screening policy (16/41 [39.0%]) and response protocol (25/40 [62.5%]) for human trafficking; more of these facilities focused on sex trafficking than on labor trafficking. The top needs related to human trafficking were (1) individual-level health care provider training, (2) health facility-level screening policies and response protocols, (3) community-level resources, and (4) societal-level awareness, funding allocation, and data. Conclusions Facility-level resources are needed to ensure that health care providers have adequate training and support to address human trafficking in the health care system.
Dynamic (Effortful) Touch

Dynamic or effortful touch is a subsystem of the haptic perceptual system (Gibson 1966). It is the most common form of touch, hardly noticed as such, and rarely studied (until recently).
Poling: SMT Aided Linearizability Proofs

Proofs of linearizability of concurrent data structures generally rely on identifying linearization points to establish a simulation argument between the implementation and the specification. However, for many linearizable data structure operations, the linearization points may not correspond to their internal static code locations; for example, they might reside in the code of another concurrent operation. To overcome this limitation, we identify important program patterns that expose such instances, and describe a tool (Poling) that automatically verifies the linearizability of implementations that conform to these patterns. Open image in new window
Red Giant Masers

Basic concepts in the theory of astronomical masers which are necessary for the discussion of red giant masers are introduced. Maser radiation from late type stars is then discussed in detail with special emphasis on SiO masers as probes of the stellar atmosphere and OH masers as a tool for studying the mass loss process and the circumstellar shell.
Mapping haptic exploratory procedures to multiple shape representations

Research in human haptics has revealed a number of exploratory procedures (EPs) that are used in determining attributes on an object, particularly shape. This research has been used as a paradigm for building an intelligent robotic system that can perform shape recognition from touch sensing. In particular, a number of mappings between EPs and shape modeling primitives have been found. The choice of shape primitive for each EP is discussed, and results from experiments with a Utah-MIT dextrous hand system are presented. A vision algorithm to complement active touch sensing for the task of autonomous shape recovery is also presented. >
Functional Groups in the Protozoa: Roles in Differing Ecosystems1,2

Feeding habits of freshwater protozoa were used to group species into functional, trophic groups. Community structure in differing ecosystems was examined in relation to the number of species occumng in the functional group categories. Six wetland ecosystems and a large river ecosystem were studied. Changes in community structure during the colonization of artificial substrates were also examined. Changes during colonization were studied in a mesotrophic lake, in low-order streams, and in laboratory micro- ecosystems. In the latter case, the response of colonizing communities to a heavy metal toxicant was studied. All communities studied were dominated by bactivorous-detritivorous species and, to a lesser extent, by photosynthetic species. The chief functional role of substrate-associated protozoans appears to be the processing of dead organic matter and its associated bacterial flora. Functional groups utilizing resources other than detntal or mineral nutrients (saprotrophs, algivores, omnivores, and predators) were always minor community components. Colonizing communities were often dominated by photosynthetic species during early colonization stages but were again dominated by bactivorous-detntivorous species at species equilibrium. Low levels of toxicant (Cd) reduced numbers of both photosynthetic and bactivorous-detritivorous species. Higher toxicant levels virtually eliminated photosynthetic species and reduced bacterial detritivores by over one-half. Roles of protozoan species in ecosystems are closely tied to the processing of detritus and the recycling of mineral nutrients. Enumeration of individuals in functional categories is proposed as a simplified method for studying the abundance and activity of protozoa in ecosystems. Examination of changes in functional group composition and the relationship of functional group abundances to rates of carbon processing are suggested for studies of the importance of protozoa to the flow of energy and materials in ecosystems. OST ecosystems are not fragile, random associations of M species but are composed of species associations with multiple redundancies that act to maintain system function even when a few or many component parts may be changing or miss- ing. Species patterns in aquatic ecosystems often appear ran- dom, and the probability of collecting a given taxon at a given site is frequently not great. Understanding large species arrays
Frequency-Dependent Climate Signal in Upper and Lower Forest Border Tree Rings in the Mountains of the Great Basin

We examine the relationships, over the past millennium, between tree-ring chronologies from long-lived pines at their upper and lower limits in four mountain ranges in and near to the semi-arid Great Basin. We confirm LaMarche's (1974a) finding, based on a single mountain range in this same region, and a much shorter period of comparison, that climate responses are frequency dependent. In particular, upper and lower forest border chronologies in each mountain range are strongly coherent at decadal periods and less, with particular strength in the 3–7 year band. Thisvariability is significantly correlated with precipitation. Conversely, we find no significant correlation between the low frequency fluctuations (60 years and longer) of upper and lower forest border chronologies. There are, however, significant correlations between the low-frequency components of the upper forest border chronologies in the different ranges, consistent with their containing a growing season temperature signal on decadal time scales. The four upper forest border chronologies all show an anomalous increase in growth since the late 19th century, and an apparent change in climate control of ring growth.
Diagnosis and Treatment of Patients With "Frontal Lobe" Syndromes

Nine case descriptions illustrate the three major prefrontal syndromes seen in clinical practice: disorganized type, disinhibited type, and apathetic type. A mixture of symptoms from each subtype is usually seen, but dysfunction in one prefrontal system often dominates. A careful history and examination are essential for accurate diagnosis. A complete history can rarely be elicited from the patient alone. Structural brain imaging, especially MRI, and neuropsychological testing are key to the diagnostic workup. EEG, video-EEG, and functional brain imaging can be valuable in the evaluation of possible partial complex seizures of frontal lobe origin and other atypical frontal lobe disorders. Effective treatment requires educating the patient and the family about the illness and modulating environmental factors that influence the patient's behavior. Judicious use of psychoactive medication may be helpful, but adverse effects are common.
Medication Errors in the LDRP

Medication errors are perhaps the most common type of error occurring in health care settings; the effects of these types of errors span the gamut from no harm to death. It's widely held today that the majority of errors result from latent errors within a complex health care system, rather than from individual clinician performances. Open discussion of a medication error leads to a better understanding of the causes and contributing factors associated with the events, as well as provides essential elements required for the prevention of future medication errors. Here's a look at the most common medication errors in the labor, delivery, recovery and postpartum areas.
Evacuation Times of Radio Transmitters Consumed by Largemouth Bass

AbstractReduction in transmitter size used in telemetry studies have allowed researchers to tag and track fish that are much smaller than could have been tagged previously. Researchers seek information on juvenile or small fish movement, behavior, and survival to better understand recruitment processes. Juvenile or small-bodied fish that have been tagged have an increased risk of predation, which results in transmitters being consumed. Knowledge about radio transmitter accumulation in a predator's gut and evacuation times are critical for interpreting locations of radio-tagged fish and their predators. Our objective was to determine what factors influenced the evacuation time of transmitters (0.3 g), implanted in juvenile Largemouth Bass Micropterus salmoides through the digestive system of adult Largemouth Bass that had preyed upon those tagged juveniles. All transmitters ingested by the predators were evacuated within 84 h. A Poisson regression model showed that transit time decreased significantly with...
Neurons and networks with activity-dependent conductances

Cultured lobster stomatogastric ganglion (STG) neurons appear to regulate their intrinsic properties in an attempt to maintain stable activity patterns. Previous theoretical descriptions of activity-dependent regulation resulted in highly restricted sets of maximal conductances that involved a number of free parameters. We first explore a single-compartment model with a conductance regulation scheme that is guided by calcium-dependent feedback pathways that span multiple time scales. The exploration of maximal conductance parameters in the model is completely unrestricted and the number of parameters is greatly reduced. We then explore the interplay between network interactions and single cell regulation in a network model of simple cells each having a single calcium feedback mechanism. It is shown that when the cells are properly coupled such a network is able to produce an oscillatory pattern that requires interaction between the elements, but that when the cells are uncoupled, they become capable of oscillating independently.
Airway Management in Trauma: Defining Expertise

Prompt attention to airway management is a fundamental component of the approach to trauma anesthesiology. While anesthesiologists manage the greatest number of airways in their training and practice, a variety of medical providers perform airway management in the trauma population (i.e., paramedics, emergency physicians, anesthesiologists, respiratory therapists). Rates of successful intubation can vary widely between groups; therefore, a definition of expertise is required to develop training plans, as well as standards for maintenance of proficiency. While competency is challenging to define in any field, the data suggest that individuals with the greatest experience achieve the highest level of success. Given that anesthesiologists manage several thousand airway encounters throughout their training and careers, their leadership as subject matter experts is essential to development of training curricula in airway management of all varieties. Consensus on training of less experienced providers, as well as tasking of the most difficult cases to the most experienced provider, is imperative for successful airway management in trauma.
Editorial: predicting response to a low FODMAP diet in children--authors' reply.

Sirs, We thank Drs. Hill and Gibson for their insightful editorial1 on our double-blind randomised, crossover study evaluating the low FODMAP dietary intervention in children with irritable bowel syndrome (IBS).2 Childhood IBS has been known to occur for several decades, in part based on studies in adults reporting symptoms beginning in childhood.3 Our study was undertaken prior to the publication of the Halmos et al. study4 and, as we noted in our discussion, we agree that we probably would have seen a larger effect size between the low FODMAP and typical American childhood diet with a longer (i.e. 7 day) intervention. Both our previously published pilot 1-week open label study of the low FODMAP diet in children with IBS5 and our current study identified a cohort of Responders (those who had a ≥50% reduction in abdominal pain frequency from baseline), suggesting that the low FODMAP diet may work better for certain children with IBS. We agree that additional studies are required to evaluate the predictors of success and nutritional adequacy of the low FODMAP diet. Additionally, only certain components (e.g. fructans) may be responsible for symptoms in a particular patient with IBS. With long-term trials, evaluation of gut microbiome composition and, perhaps more importantly the microbiome’s metabolic byproducts, may help further elucidate the mechanism of the low FODMAP diet and its potential biological implications. We also agree that having biomarkers of low FODMAP and other dietary intervention efficacy is important. As our study suggests, this may include baseline (prior to starting the dietary intervention) faecal microbiota composition and metabolic potential and help lead to personalised interventions for those with IBS.
Life table tests of evolutionary theories of senescence

The phenomenon of senescence requires both evolutionary and prox- imate explanations. The most widely accepted evolutionary explanation for senes- cence is that it never gets exposed to natural selection because environmental hazards kill all individuals before the age at which senescence causes decreased fitness. If this explanation is sufficient, wild populations should not demonstrate senescence, and their mortality rates should therefore remain constant during adult life, except when environmental causes of mortality have recently decreased. The alternative explanation for the persistence of the genes that cause senescence is that they have been selected for because they have pleiotropic effects that are beneficial early in life when the force of selection is strongest. Where this is the case, mortality rates should increase with age in wild populations. A method is described for using life table data to calculate an estimate of the intensity of selection acting on senes- cence in wild populations. This method is applied to a variety of life tables. The results suggest that pleiotropic genes may be important causes of senescence in some populations, but not in others. This has implications for research on the proximate mechanisms of senescence.
Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling.

The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P 3] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P 3. These enzymes terminate the signal to release Ca2+ from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P 4]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories.
Whole transcriptome responses among females of the filariasis and arbovirus vector mosquito Culex pipiens implicate TGF-β signaling and chromatin modification as key drivers of diapause induction

Culex pipiens mosquitoes are important disease vectors inhabiting temperate zones, worldwide. The seasonal reduction in temperature and photoperiod accompanying late summer and early fall prompts female mosquitoes to enter diapause, a stage of developmental arrest and physiological conditioning that enhances survival during the winter months. To investigate the molecular mechanisms underlying diapause induction, we used custom whole transcriptome microarrays to identify differences in gene expression following exposure to nondiapause (long days, 25 °C) and diapause-inducing (short days, 18 °C) environmental conditions. Using a two-way ANOVA, we identified 1130 genes that were differentially expressed. We used the expression of these genes across three time points to construct a gene co-expression network comprising five modules. Genes in modules 1, 2, and 3 were largely up-regulated, while genes in modules 4 and 5 were down-regulated when compared to nondiapause conditions. Pathway enrichment analysis of the network modules revealed some potential regulatory mechanisms driving diapause induction. Module 1 was enriched for genes in the TGF-s and Wnt signaling pathways; module 2 was enriched for genes involved in insect hormone biosynthesis, specifically, ecdysone synthesis; module 3 was enriched for genes involved in chromatin modification; and module 5 was enriched for genes in the circadian rhythm pathway. Our results suggest that TGF-β signaling and chromatin modification are key drivers for the integration of environmental signals into the diapause induction phase in C. pipiens mosquitoes.
An in silico ensemble method for lead discovery: decision forest.

Recent progress in combinatorial chemistry and parallel synthesis has radically changed the approach to drug discovery in the pharmaceutical industry. At present, thousands of compounds can be made in a short period, creating a need for fast and effective in silico methods to select the most promising lead candidates. Decision forest is a novel pattern recognition method, which combines the results of multiple distinct but comparable decision tree models to reach a consensus prediction. In this article, a decision forest model was developed using a structurally diverse training data set containing 232 compounds whose estrogen receptor binding activity was tested at the U.S. Food and Drug Administration (FDA)'s National Center for Toxicological Research (NCTR). The model was subsequently validated using a test data set of 463 compounds selected from the literature, and then applied to a large data set with 57,145 compounds as a screening example. The results show that the decision forest method is a fast, ...
Microfabricated implantable flow sensor for medical applications

A RF wireless capacitive flow sensor is developed. The sensor has integrated inductor with the flow sensitive capacitors as LC circuit. The resonant frequency of the sensor changes as the capacitance changes with applied flow. The sensor uses LPCVD silicon nitride as sensitive membrane and the residual stress of the membrane has been measure as 139 MPa. The sensor has size of 10 mm × 4 mm × 0.5 μm. The sensor integrated two pressure sensors together and designed related to flow 5-20ml/hour. The deflection of different shape of membranes and the parameters of flow sensor sensitivity are discussed. The deflection of square membrane is 130% to circular membrane under same applied pressure.
Determinacy of equilibrium in stationary economies with both finite and infinite lived consumers

Abstract We consider the determinacy of perfect foresight equilibrium near steady-state equilibria of stationary infinite-horizon economies. The work of T. J. Kehoe and D. K. Levine (Econometrica 53 (1985) , 433–453) is generalized by the inclusion of both infinite lived agents and overlapping generations of finite lived agents, and the inclusion of production and non-depreciating pure rents. We show that indeterminacy is possible in robust examples, and that the dimension of the indeterminacy can be as large as the number of goods per period. We also discuss extreme cases in which determinacy is guaranteed.
Wnt Signaling Selectively Inhibits Sodium Channels in Cardiac Myocytes

Background: Wnt signaling plays crucial roles in heart development but is normally suppressed postnatally. In arrhythmogenic conditions, such as cardiac hypertrophy and heart failure, Wnt signaling is reactivated. We explored the potential role of Wnt signaling in arrhythmogenic electrical remodeling by examining ion channel changes in postnatal cardiomyocytes with activated Wnt signaling.Methods: Neonatal rat ventricular myocytes (NRVMs) were treated with either recombinant Wnt3a protein (0.1-1.0 μg/ml) or CHIR-99021 (CH, 3 μM, a glycogen synthase kinase-3β inhibitor) to activate canonical Wnt signaling. Gene expression was assayed by real-time RT-PCR. Western blot and immunocytostaining were used to investigate protein changes. Ionic currents were recorded using whole-cell patch-clamp.Results: Treatment of NRVMs with either Wnt3a or CH caused a dose-dependent increase in Wnt target gene expression (Axin2 and Lef1), indicating activation of the Wnt/β-catenin pathway. Cardiac Na+ current (INa) density was reduced (p 10) by Wnt3a (−20±4 vs. control −59±7 pA/pF, at −30 mV) or CH (−22±5 pA/pF), without changes in steady-state inactivation or repriming kinetics. Wnt3a and CH also produced dose-dependent reductions in the mRNA level of Scn5a (the cardiac Na+ channel α subunit gene), as well as a 60% reduction in Nav1.5 protein level. Consistent with INa reduction, action potentials in Wnt3a-treated NRVMs had lower (p<0.01, n=5) upstroke amplitude (91±3 vs. control 137±2 mV) and decreased maximum upstroke velocity (70±10 vs. control 163±15 V/s). In contrast, inward rectifier K+ current and L-type Ca2+ current were not affected by Wnt3a treatment (n=8).Conclusions: The Wnt/β-catenin pathway selectively suppresses INa expression in postnatal cardiomyocytes and may contribute to arrhythmogenic remodeling in heart failure. Thus, the Wnt/β-catenin pathway may be a novel therapeutic target for heart failure and cardiac arrhythmias.
EFFECT OF DELAY BETWEEN GROUP HOUSING AND TESTING ON REDUCTION OF EMOTIONALITY

Rats subject to delay between group housing and testing did not show the reduction in emotionality commonly found. The effect dissipated linearly with time between group housing and open-field testing.
Differential transcriptional activation of matrix metalloproteinase-2 and membrane type-1 matrix metalloproteinase by experimental deep venous thrombosis and thrombin.

Objective Resolution of deep venous thrombosis (DVT) is involved in the pathogenesis of postthrombotic syndrome. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are critical in angiogenesis and tissue remodeling. We hypothesized that MMP-2 and its membrane-bound activator membrane type-1 matrix metalloproteinase (MT1-MMP) expression would be expressed and activated during the resolution of DVT. Methods DVT was generated by caval ligation in wild-type and MMP-2 transgenic reporter mice. Ligated and sham-operated (control) cavae were analyzed for MMP-2 transcription (β–galactosidase activity in MMP-2 reporter mice) and MT1-MMP mRNA by real-time polymerase chain reaction. MMP-2 activity was determined by zymography, and immunohistochemical staining for β–galactosidase and MT1-MMP protein was used to localize expression. Human umbilical vascular endothelial cells (HUVEC) were treated with 10 U/mL thrombin and MMP-2 and MT1-MMP mRNA levels and MMP-2 activity was determined. Results MMP-2 activity increased 71% (n = 5, P P P P P P P P Conclusions Resolution of DVT is associated with increased MMP-2 transcription and activity as well as MT1-MMP expression. Thrombin may mediate the increase in MT1-MMP noted in DVT. This is the first article studying MMP-2 and MT1-MMP transcription in DVT. These findings add DVT resolution to the class of inflammatory and fibrotic disorders in which transcriptional activation of the MT1-MMP/MMP-2 genes occurs and identify a potential therapeutic target to modulate this clinically relevant process. Clinical Relevance Postthrombotic syndrome remains a significant clinical problem after deep venous thrombosis (DVT), but the cellular and molecular mechanisms involved in thrombus resolution and vein wall fibrosis remain undefined. Matrix metalloproteinase (MMP) enzymes are critical to cell migration and matrix breakdown. We identify gene transcription and activity of two MMP isoforms, MMP-2 and MMP-14 (membrane type MMP 1, MT1-MMP) in the resolution phase of experimental DVT and in thrombin-treated endothelial cells. These studies define new proteases potentially important to resolution of DVT and development of postthrombotic syndrome.
Assay Procedure Optimization of a Rapid, Reusable Protein C Immunosensor for Physiological Samples

A fiber-optic immunosensor for quantifying the protein C (PC) amount in a plasma sample is being developed to provide accurate, fast, cost-effective diagnosis of heterozygous PC deficiency (0.5–2.5 μgml−1). As a progress report on the sensor development, this paper focuses on optimizations of various assay steps. These include: (1) the primary antibody concentration; (2) the effect of the primary antibody leaching on the sensitivity; (3) the fluorophore to secondary antibody ratio; and (4) the sample and secondary antibody incubation times. The optimal primary antibody concentration for the PC sensor was determined to be 65 μgml−1; its leaching was minor, stabilized within 3 days, and the sensor sensitivity change after 30 days of storage was minor; sample and secondary antibody incubation times were reduced from 10 to 5 and from 5 to 3 min, respectively, while maintaining a reasonable signal-to-noise level. The immunosensor was also tested with (5) human serum albumin and human plasma and (6) with and without convective flow. High viscosity of human plasma decreased signal intensity, but clear signal discrimination was possible in the concentration range of interest. (7) Application of convective flow increased the signal intensity by increasing PC mass transport rate to the sensor surface. The optimized PC immunosensor provides a smaller (100 μl sample chamber) and faster (10–15 min) tool for PC detection in human plasma. © 2002 Biomedical Engineering Society. PAC02: 8780-y, 8714Ee
Cerebral metabolism and sleep homeostasis: A comment on Vyazovskiy et al.

In this journal, Vyazovskiy et al. reported deoxyglucose data that they interpreted as supporting the Tononi and Cirelli hypothesis that cerebral metabolic rate (CMR) increases across waking. We summarize contradictory PET-deoxyglucose data that show CMR is the same in the morning and evening and that it decreases rather than increases after a night of sleep deprivation. We propose an alternative model of CMR-sleep homeostasis relations that points to novel experiments.
Growth response of Populus fremontii, Salix gooddingii, and Tamarix ramosissima seedlings under different nitrogen and phosphorus concentrations

Abstract Treated effluent can potentially be used to restore riparian ecosystems to the many stream reaches in the south-western United States that have been dewatered. We undertook this study to determine how elevated nutrient levels in effluent influence riparian tree seedling performance. Seedlings of Fremont cottonwood ( Populus fremontii ), Goodding willow ( Salix gooddingii ), and exotic saltcedar ( Tamarix ramosissima ) were grown in a greenhouse for 43 days to address how concentration increases of ammonium-N and nitrate-N (5·56, 55·6, 278 and 556 mmol m −3 ), and phosphate-P (3·23, 32·3, 162 and 323 mmolm −3 ) would influence height, leaf or stem number, and biomass production. Seedlings of all species grew significantly taller, produced more leaves or stems, and produced greater biomass at the two larger treatments than at the two smaller treatments. Populus fremontii grew significantly taller, and produced more leaves and biomass than S. gooddingii or T. ramosissima at all nutrient concentrations, whereas T. ramosissima produced significantly less biomass than either P. fremontii or S. gooddingii at all concentrations. Only T. ramosissima showed a significant increase in stem number, shoot biomass and total biomass from the third to highest treatment. All species increased their shoot: root biomass ratio as nutrient concentration increased. Concentrations above the third highest nutrient treatment may favor establishment of T. ramosissima seedlings, while concentrations below these levels may provide the greatest potential for reestablishment of cottonwood-willow riparian forests along streams of the south-western United States.
Effect of rate controlled sintering on microstructure and electrical properties of ZnO doped with bismuth and antimony oxides

Various rate controlled sintering (RCS) schedules were used on isostatically pressed particulate compacts of ZnO with Bi 2 O 3 and Sb 2 O 3 additives. For low additive content, smaller average grain sizes with more rapid RCS schedules were attributable to thermal schedules which minimized the time at elevated temperatures where grain growth could occur. β–Bi 2 O 3 , Zn 7 Sb 2 O 12 , and Zn 2 Sb 3 Bi 3 O 14 phases formed during/after sintering. Elevated heat-treatment temperatures favored the formation of Zn 7 Sb 2 O 12 and additional β–Bi 2 O 3 , while Zn 2 Sb 3 Bi 3 O 14 was dominant in sintered samples where the RCS schedule did not result in temperatures in excess of 1100 °C. Zn 2 Sb 3 Bi 3 O 14 precipitated during sintering, functioning as grain boundary pinning sites which impeded ZnO grain growth. Bismuth and antimony oxide-based liquid facilitated sintering at lower temperatures, which in turn resulted in decreased average grain size. Rapid RCS schedules for samples with low dopant content resulted in lower sintering temperatures, since time was not allowed for Zn 2 Sb 3 Bi 3 O 14 precipitation to deplete the liquid phase. For higher dopant contents, liquid phase was adequately plentiful, wherein longer RCS schedules resulted in lower sintering temperatures. Increasing concentration of second phase generally fostered decreased grain size and attenuated the effect of thermal schedule on the microstructure. Electrical resistance and breakdown voltage increased consistent with decreasing ZnO average grain size.
Othering across time and place in the suikoden video game series

As geographers begin investigating the imaginative geographies of media spaces, attention is drawn to the landscapes of interactive media. The virtual environments of video games continue to grow in complexity and use, and questions remain as to the experience of the users of the designed environments. Focusing specifically on messages and metaphors in written representations, this paper investigates the changing experience of gamers through time and place by examining the Suikoden fantasy series. Beginning with the adaptation of the Chinese classic Shui Hu Zhuan into Suikoden in 1996, continuing to the release of Suikoden V 10 years later, the virtual environments of the Suikoden series are embedded with mythological and cultural messages about Self and Other. This paper utilizes visual and textual analysis to examine these changing representations over time and place in terms of the experience of these ideological messages by the players of this series.