cssi/SciSciGPT-SciSciNet huggingface dataset:
Atomic broadcast in heterogeneous distributed systems

Communication services have long been recognized as possessing a dominant effect on both performance and robustness of distributed systems. Distributed applications rely on a multitude of protocols for the support of these services. Of crucial importance are multicast protocols. Reliable multicast protocols enhance the efficiency and robustness of distributed systems. Numerous reliable multicast protocols have been proposed, each differing in the set of assumptions adopted, especially for the communication network. These assumptions make each protocol suitable for a specific environment. The presence of different distributed applications that run on different LANs and single distributed applications that span different LANs mandate interaction between protocols on these LANs. This interaction is driven by the necessity of cooperation between individual applications. The state of the art in reliable multicast protocols renders itself inadequate for multicasting in interconnected LANs. The progress in development methodology for efficient and robust LAN software has not been matched by similar advances for WANs. A high-latency, a lower bandwidth, a higher probability of partitions, and a frequent loss of messages are the main restrictive barriers. In our work, we propose a global standard protocol that orchestrates cooperation between the different reliable broadcast protocols that run on different LANs. Our objective is to support a reliable ordered delivery service for inter-LAN messages and achieve the utmost utilization of the underlying local communication services. Our protocol suite accommodates the existence of LANs managed by autonomous authorities. To uphold this autonomy (as a defacto condition), LANs under different authorities must be able to adopt different ordering criteria for group multicasting. The developed suite assumes an environment in which multicasting groups can have members that belong to different LANs; each group can adopt either total or causal order for message delivery to its members. We also recognize the need for interaction between different reliable multicasting protocols. This interaction is a necessity in an autonomous environment in which each local authority selects a protocol that is suitable to its individual needs. Our protocols are capable of interacting with any reliable protocol that achieves a causal order as well as with all timestamp-based total-order protocols. Our protocols can also be used as a medium for interaction between existing reliable multicasting protocols. This feature opens new avenues in interactability between reliable multicasting protocols. Finally, our protocol suite enjoys a communication structure that can be aligned with the actual routing topology, which largely minimizes the necessary protocol messages.
Rigorously Collecting Commonsense Judgments for Complex Question-Answer Content

Community Question Answering (CQA) websites are a popular tool for internet users to fulfill diverse information needs. Posted questions can be multiple sentences long and span diverse domains. They go beyond factoid questions and can be conversational, opinion-seeking and experiential questions, that might have multiple, potentially conflicting, useful answers from different users. In this paper, we describe a large-scale formative study to collect commonsense properties of questions and answers from 18 diverse communities from stackexchange.com. We collected 50,000 human judgments on 500 question-answer pairs. Commonsense properties are features that humans can extract and characterize reliably by using their commonsense knowledge and native language skills, and no special domain expertise is assumed. We report results and suggestions for designing human computation tasks for collecting commonsense semantic judgments.
Referral to infertility counseling in cancer patients undergoing chemotherapy.

220Background: Reproductive concerns in survivorship are associated with distress, depression and anxiety. Patients who receive pretreatment fertility counseling report a better quality of life aft...
Semiparametric Mixed Models for Medical Monitoring Data: An Overview

The potential to characterize nonlinear progression over time is now possible in many health conditions due to advancements in medical monitoring and more frequent data collection. It is often of interest to investigate differences between experimental groups in a study or identify the onset of rapid changes in the response of interest using medical monitoring data; however, analytic challenges emerge. We review semiparametric mixed-modeling extensions that accommodate medical monitoring data. Throughout the review, we illustrate these extensions to the semiparametric mixed-model framework with an application to prospective clinical data obtained from 24-hour ambulatory blood pressure monitoring, where it is of interest to compare blood pressure patterns from children with obstructive sleep apnea to those arising from healthy controls.
Mexican illegality, black citizenship, and white power: immigrant perceptions of the U.S. socioracial hierarchy

While some scholars contend that immigrant integration is predicated on a strategic distancing from Blacks and closeness to Whites, others argue that highly racialised immigrants share more commona...
Micro-pillar density modulation in semi-packed MEMS column

For gas chromatography, the separation column is the most important component in influencing performance of a gas chromatography system. The semi-packed MEMS column design has been widely used because it enhances the separation efficiency and provides higher sample capacity. However, a limitation of this type of column is the large pressure drop that occurs across its column length. This paper reports a new semi-packed design that utilizes density modulation of the micro-pillars to improve the pressure drop and increase the separation efficiency for high speed separations.
Optomechanical coupling to ultra-high Q-factor phononic resonators on-chip at cryogenic temperatures

Through engineerable optomechanical coupling to bulk acoustic modes of plano-convex resonators fabricated on-chip, we demonstrate ultra-high acoustic Q-factors of 28 million (6.6 million) for phonons at high frequencies of 12.7 GHz (37.8 GHz) in quartz (silicon) at cryogenic temperatures.
NEUROMUSCULAR DISEASE | Inherited Myopathies

Neuromuscular disorders include a diverse group of diseases with different etiologies. Respiratory failure, presenting both in the acute as well as in the chronic forms, is one of the leading causes of death in most of these diseases. The pathological characteristics of this group of disorders can be classified into five major categories that include muscular dystrophies, congenital and metabolic myopathies, disorders of the neuromuscular junction, peripheral neuropathies, and anterior horn cell disease (spinal muscular atrophies). Symptoms vary according to the type of disease and with the severity and age of onset, but usually include feeding and respiratory difficulties as well as skeletal and muscular abnormalities like scoliosis and kyphosis. Intercurrent illnesses may prompt sudden deterioration of the muscular weakness and lead to respiratory failure. The diagnosis is usually made during the first decade of life and in most cases a muscle biopsy is necessary to establish the diagnosis. However, since most of these disorders are genetically determined, gene testing is available or will soon become available. Interventional measures should involve a multidisciplinary team and are currently restricted to primarily supportive therapy including respiratory muscle training and noninvasive ventilation.
Urodynamics for Postprostatectomy Incontinence: When Are They Helpful and How Do We Use Them?

Urodynamics is indicated for the evaluation of postprostatectomy incontinence unless an artificial urinary sphincter placement is the preferred option, as in cases of severe incontinence, prior radiation, or previous male sling or artificial urinary sphincter placement--when male sling is unlikely to achieve efficacy. Urodynamics should be performed only when there is a question it can answer that would affect treatment choice or outcome. Urodynamic findings of detrusor underactivity, overactivity, and reduced compliance are important considerations in deciding how best to treat postprostatectomy incontinence.
Recent Results in Scanning Tunneling Microscopy

We review two of our recent developments in scanning tunneling microscopy (STM). The first is our use of a unique low-temperature STM to perform spectroscopic measurements of the new oxide superconductors. A second recent development is the direct writing of nanometer features with the STM.
Inside Arbitration: How an Arbitrator Decides Labor and Employment Cases

This book helps both lawyer and non-lawyer advocates better understand the arbitration process from a seasoned arbitrator’s viewpoint, and to improve their skills in using that process. This book offers answers to questions submitted by practicing advocates, based on both the author’s extensive arbitration experience and the experiences of his fellow arbitrators. These insights will benefit arbitrators in reviewing their own practices.
Effects of bioengineered scaffold loaded with neurotrophins and locomotor training in restoring H-reflex responses after spinal cord injury

The combinational effects of a bioengineered scaffold loaded with neurotrophins and rehabilitation training on spasticity observed after spinal cord injury (SCI) has not been studied. We used an animal model of moderate contusion injury at T9/T10 that received bioengineered scaffold poly N-isopropylacrylamide-g-poly ethylene glycol (PNIPAAm-g-PEG) loaded with BDNF/NT3 followed by body weight supported treadmill training (BWSTT) and assessed the efficacy of the combinational bioengineered approaches in treating spasticity. Five animal groups were included: Group 1: Sham, Group 2: Injury (SCI), Group 3: SCI + BWSTT (BWSTT), Group 4: SCI + PNIPAAm-g-PEG loaded with BDNF/NT3 (Transplant), and Group 5: SCI + PNIPAAm-g-PEG loaded with BDNF/NT3 + BWSTT (Combinational). Results indicate no significant changes in the BBB scores of animals among various groups, however, a significant restoration in the rate depression property of H-reflex was observed in both BWSTT and Combinational animals. Transplant group reported no improvement in the rate depression property of H-reflex and were similar to SCI only group. Histological findings report restoration of the chloride cotransporter (KCC2) labeling in both BWSTT and Combinational animals and down-regulation of KCC2 in both SCI and Transplant only animals. Findings from this study confirm that rehabilitation training is critical in restoring H-reflex responses and transplantation therapies alone cannot restore these responses after SCI. Also, although no significant difference was observed between the BWSTT and Combinational animals, comparable improvements in the two groups does open new pathways to exploring unique tissue-engineering approaches with promising clinical application for individuals with SCI.
Two-Stage Revision Total Hip Arthroplasty With a Specific Articulating Antibiotic Spacer Design: Reliable Periprosthetic Joint Infection Eradication and Functional Improvement

Abstract Background Two-stage revision utilizing spacers loaded with high-dose antibiotic cement prior to reimplantation remains the gold standard for treatment of periprosthetic joint infections (PJI) in total hip arthroplasty (THA) in North America, but there is a paucity of data on mid-term outcomes. We sought to analyze the survivorship free of infection, clinical outcomes, and complications of a specific articulating spacer utilized during 2-stage revision. Methods One hundred thirty-five hips (131 patients) undergoing a 2-stage revision THA for PJI with a specific articulating antibiotic spacer design from 2005 to 2013 were retrospectively reviewed. Infections were classified according to the Musculoskeletal Infection Society criteria. Mean age at resection was 65 years and mean follow-up was 5 years (rang, 2-10). Results Survivorship free of any infection after reimplantation was 92% and 88% at 2 and 5 years, respectively. Patients with a host-extremity grade of C3 compared to all patients with a host grade of A [hazard ratio (HR) 4.1, P = .05] were significant risk factors for poorer infection-free survivorship after reimplantation. Harris hip scores improved from a mean of 58 to a mean of 71 in the spacer phase (P = .002) and a mean of 81 post-reimplantation (P = .001). Fourteen (10%) patients dislocated after reimplantation, 9 (7%) of which required re-revision. Trochanteric deficiency (HR 19, P Conclusion Insertion of an articulating antibiotic spacer during a 2-stage revision THA for PJI demonstrates reliable infection eradication and improvement in clinical function, including the spacer phase. Patients with trochanteric deficiency and an articulating spacer dislocation are at high risk of post-reimplantation dislocation; judicial use of a dual-mobility or constrained device should be considered in these patients.
Calibration using power transformation

AbstractEstimation of the population mean or population total is considered. A new calibration estimator with a new likelihood function is proposed. The resultant estimator derives from the two-ste...
Fos activation patterns related to acute ethanol and conditioned taste aversion in adolescent and adult rats.

Abstract Studies in rats have revealed marked age differences in sensitivity to the aversive properties of ethanol, with a developmental insensitivity to ethanol aversion that is most pronounced during pre- and early adolescence, declining thereafter to reach the enhanced aversive sensitivity of adults. The adolescent brain undergoes significant transitions throughout adolescence, including in regions linked with drug reward and aversion; however, it is unknown how ontogenetic changes within this reward/aversion circuitry contribute to developmental differences in aversive sensitivity. The current study examined early adolescent (postnatal day [P]28–30) and adult (P72–74) Sprague–Dawley male rats for conditioned taste aversion (CTA) after doses of 0, 1.0, or 2.5 g/kg ethanol, and patterns of neuronal activation in response to ethanol using Fos-like immunohistochemistry (Fos+) to uncover regions where age differences in activation are associated with ethanol aversion. An adolescent-specific ethanol-induced increase in Fos+ staining was seen within the nucleus accumbens shell and core. An age difference was also noted within the Edinger-Westphal nucleus (EW) following administration of the lower dose of ethanol, with 1 g/kg ethanol producing CTA in adults but not in adolescents and inducing a greater EW Fos response in adults than adolescents. Regression analysis revealed that greater numbers of Fos+ neurons within the EW and insula (Ins) were related to lower consumption of the conditioned stimulus (CS) on test day (reflecting greater CTA). Some regionally specific age differences in Fos+ were noted under baseline conditions, with adolescents displaying fewer Fos+ neurons than adults within the prelimbic (PrL) cortex, but more than adults in the bed nucleus of the stria terminalis (BNST). In the BNST (but not PrL), ethanol-induced increases in Fos-immunoreactivity (IR) were evident at both ages. Increased ethanol-induced activity within critical appetitive brain regions (NAc core and shell) supports a role for greater reward-related activation during adolescence, possibly along with attenuated responsiveness to ethanol in EW and Ins in the age-typical resistance of adolescents to the aversive properties of ethanol.
High-Resolution Structural Studies Elucidate Antiatherogenic and Anti-Inflammatory Properties of Peptides Designed to Mimic Amphipathic α-Helical Domains of Apolipoprotein A-I.

Peptides designed to mimic the antiatherogenic and anti-inflammatory properties of apolipoprotein A-I show that although lipid association is required, not all lipid-associating peptides exhibit th...
A machine learning approach to predicting short-term mortality risk for patients starting chemotherapy.

6538Background: Patients who die soon after starting chemotherapy incur symptoms and financial costs without survival benefit. Prognostic uncertainty may contribute to increasing chemotherapy use n...
Guerra, biopolítica e inadaptación: los yerbales paraguayos de Rafael Barrett

La Guerra de la Triple Alianza (1864-1870) fue un acontecimiento catastrofico que devasto a gran parte de la poblacion paraguaya y dejo al pais sumido en una profunda crisis economica. El presente trabajo explora las secuelas de este conflicto en el proceso de consolidacion de los enclaves destinados a la explotacion de la yerba mate durante el largo periodo de reconstruccion nacional en Paraguay. Para ello, se enfoca en la cronica “Lo que son los yerbales” del escritor hispano-paraguayo Rafael Barrett (1876-1910), y en otros escritos suyos que rodean y amplian el sentido del texto. La escritura de Barrett ahonda criticamente en el significado del enclave yerbatero como un nuevo espacio liberal donde la guerra continua por otros medios, y donde la economia de mercado actualiza la cesura entre vidas valiosas y vidas prescindibles analizada por la tradicion del pensamiento biopolitico que inaugura el trabajo de Michel Foucault. Excediendo este marco, el ensayo propone considerar la nocion de inadaptacion en la doctrina libertaria de Barrett como una intervencion afirmativa opuesta a la biopolitizacion de la vida operante en los yerbales y, por extension, en el proyecto de reconstruccion nacional en el Paraguay de posguerra.
Commentary: Reducing adolescent suicide: a global imperative – a reflection on Glenn et al. (2020)

Glenn and colleagues have examined rates of adolescent suicide across 45 countries and explored the role of sex, age, rurality and availability of guns and railways on suicide rates. Higher rates of adolescent suicide in New Zealand may be explained by the very high rate of adolescent suicide in young Maoris. Future work could be enhanced by reporting on national trends in suicide, reporting on rates broken down by race and ethnicity, and through the development of international psychological autopsy studies that could shed light on cross-country differences. While this article found that income inequality was correlated with the male-to-female ratio of adolescent suicide across countries, the opposite trend has been reported in the United States. However, as noted by this article, the effects of poverty matter. The Move To Opportunity study found that when youth under the age of 13 were moved from a high poverty to a low poverty neighbourhood, there were enduring effects, including lower levels of depression and anxiety. While adolescent suicide is a global concern, reduction in the suicide rate may have local solutions, including those that address the pernicious effects of poverty and poor neighbourhoods on youth.
An Introduction to CRISPR-Mediated Genome Editing in Fungi†

Central dogma, transformation, and genome editing are key biological concepts for which junior scientists must gain experience during training. Here we present an exercise that introduces these concepts in a single practical laboratory exercise. Our exercise utilizes CRISPR/Cas9 genome editing to introduce a stop codon into Saccharomyces cerevisiae ADE2. This edit leads to the buildup of an adenine precursor that dyes the edited cells red. As the repair template, guide RNA, and Cas9 are all encoded in our vector, transformation can be performed in 2 hours. Furthermore, since all components of the Cas9/CRISPR system are encoded by the vector, specialized equipment and reagents, such as a PCR machine or oligonucleotides, are not required to perform the experiments as designed. As such, these exercises provide an efficient cost-effective introduction to a wide variety of key molecular biology concepts and lay the foundation for more rigorous investigations in upper-level classes and independent research projects.
JISAP: Joint Inference for Surgeon Attributes Prediction during Robot-Assisted Surgery

In Robot-Assisted Surgery, predicting surgeon attributes such as task workload, operation performance, and expertise levels is important in providing tailored assistance. This paper proposes Joint Inference for Surgeon Attributes Prediction (JISAP), a computational framework to jointly infer surgeon attributes (i.e., task workload, operation performance, and expertise level) from multimodal physiological signals (heart rate variability, wrist motion, electrodermal, electromyography, and electroencephalogram activity). JISAP was evaluated with a dataset of twelve surgeons operating on the da Vinci Skills Simulator. It was found that JISAP can simultaneously predict surgeon attributes with a percentage error of 11.05%. Additionally, joint inference was found to outperform isolated inference with a boost of 10%.
An Approach to Biomarker Discovery of Cannabis Use Utilizing Proteomic, Metabolomic, and Lipidomic Analyses.

Introduction: Relatively little is known about the molecular pathways influenced by cannabis use in humans. We used a multi-omics approach to examine protein, metabolomic, and lipid markers in plas...
Neurosurgical Options for Control of Chronic and Malignant Abdominal Pain

Neurosurgical treatment for chronic abdominal pain ranges from destructive spinal cord lesioning to ablate the ascending pain pathways to nondestructive therapies with the use of opioid pumps and electrical stimulation. Existence of unwanted side effects, socioeconomic factors, and the cost of long-term treatment, sometimes make opioid and neurostimulation therapies not feasible for the management of such pain. Consequently, destructive neurosurgical interventions may become the best option to manage chronic and malignant abdominal pain refractory to other treatment modalities. Although destruction of the thalamic nuclei was frequently performed decades ago for treatment of intractable pain, this approach is rarely used today, mainly due to advancements made in the surgeon’s ability to create targeted lesions within the spinal cord. The targets of such therapy are the spinothalamic tracts in the ventral spinal cord as well as another ascending pain pathway located in the center and dorsal midline of the spinal cord. Both of these locations are easily accessible and extremely amenable to procedures such as anterolateral cordotomy, commissurotomy, and midline myelotomy. While considered the last resort for the management of intractable abdominal pain, neuroablative procedures provide permanent pain relief with minimal side effects and low morbidity to those patients who have otherwise run out of treatment options.
A 1D Gaussian Function for Efficient Generation of Plane Waves in 1D, 2D, and 3D FDTD

A 1D Gaussian expression is derived and used as the 1D E/H incident field in the TF/SF formulation to efficiently generate plane waves in 1D, 2D, and 3D FDTD simulations. The analytic expression is simple, and it eliminates the need for computational resources to store and compute the E/H-field incident arrays and their associated absorbing boundaries. FDTD simulation results at the magic time-step in 1D, 2D, and 3D FDTD show good correlation between plane waves generated by the 1D analytic Gaussian function vs. those generated by 1D FDTD incident arrays.
Observations of Velocity-Dependent Drag and Bearing Stress in Sand Penetration

Data from rapid penetration tests into granular media were analyzed using a two-step Poncelet equation to determine values for the Poncelet drag coefficient on a projectile. The data were from a spherical projectile launched into both densely and loosely packed Ottawa sand at transonic impact velocities of approximately 300 m/s. Velocity data were obtained and integrated over time to produce data for penetration depth. Three approaches were investigated: (1) Fitting the data with a constant drag coefficient, (2) fitting the data with a constant drag coefficient along with a constant velocity-independent term computed as the average of the quasi-static penetration resistance into the same target, and (3) by separating the data into two segments about a transition velocity, and using best fit values for the inertial drag and bearing stress terms. The latter approach produced superior fits compared to the other two procedures investigated. The result indicates a velocity dependence of both the inertial drag coefficient and bearing stress on a projectile during rapid penetration into granular media.
DeepLIIF: Deep Learning-Inferred Multiplex ImmunoFluorescence for IHC Quantification

Reporting biomarkers assessed by routine immunohistochemical (IHC) staining of tissue is broadly used in diagnostic pathology laboratories for patient care. To date, clinical reporting is predominantly qualitative or semi-quantitative. By creating a multitask deep learning framework referred to as DeepLIIF, we present a single-step solution to stain deconvolution/separation, cell segmentation, and quantitative single-cell IHC scoring. Leveraging a unique de novo dataset of co-registered IHC and multiplex immunofluorescence (mpIF) staining of the same slides, we segment and translate low-cost and prevalent IHC slides to more expensive-yet-informative mpIF images, while simultaneously providing the essential ground truth for the superimposed brightfield IHC channels. Moreover, a new nuclear envelop stain, LAP2beta, with high (>95%) cell coverage is introduced to improve cell delineation/segmentation and protein expression quantification on IHC slides. By simultaneously translating input IHC images to clean/separated mpIF channels and performing cell segmentation/classification, we show that our model trained on clean IHC Ki67 data can generalize to more noisy and artifact-ridden images as well as other nuclear and non-nuclear markers such as CD3, CD8, BCL2, BCL6, MYC, MUM1, CD10, and TP53. We thoroughly evaluate our method on publicly available benchmark datasets as well as against pathologists’ semi-quantitative scoring. The code, the pre-trained models along with easy-to-run containerized docker files as well as Google CoLab project are available at https://github.com/nadeemlab/deepliif.
Generative Adversarial Networks: A Survey Toward Private and Secure Applications

Generative Adversarial Networks (GANs) have promoted a variety of applications in computer vision and natural language processing, among others, due to its generative model’s compelling ability to generate realistic examples plausibly drawn from an existing distribution of samples. GAN not only provides impressive performance on data generation-based tasks but also stimulates fertilization for privacy and security oriented research because of its game theoretic optimization strategy. Unfortunately, there are no comprehensive surveys on GAN in privacy and security, which motivates this survey to summarize systematically. The existing works are classified into proper categories based on privacy and security functions, and this survey conducts a comprehensive analysis of their advantages and drawbacks. Considering that GAN in privacy and security is still at a very initial stage and has imposed unique challenges that are yet to be well addressed, this article also sheds light on some potential privacy and security applications with GAN and elaborates on some future research directions.
Chemical composition of dissolved organic matter draining permafrost soils

Abstract Northern circumpolar permafrost soils contain roughly twice the amount of carbon stored in the atmosphere today, but the majority of this soil organic carbon is perennially frozen. Climate warming in the arctic is thawing permafrost soils and mobilizing previously frozen dissolved organic matter (DOM) from deeper soil layers to nearby surface waters. Previous studies have reported that ancient DOM draining deeper layers of permafrost soils was more susceptible to degradation by aquatic bacteria compared to modern DOM draining the shallow active layer of permafrost soils, and have suggested that DOM chemical composition may be an important control for the lability of DOM to bacterial degradation. However, the compositional features that distinguish DOM drained from different depths in permafrost soils are poorly characterized. Thus, the objective of this study was to characterize the chemical composition of DOM drained from different depths in permafrost soils, and relate these compositional differences to its susceptibility to biological degradation. DOM was leached from the shallow organic mat and the deeper permafrost layer of soils within the Imnavait Creek watershed on the North Slope of Alaska. DOM draining both soil layers was characterized in triplicate by coupling ultra-high resolution mass spectrometry, 13C solid-state NMR, and optical spectroscopy methods with multi-variate statistical analyses. Reproducibility of replicate mass spectra was high, and compositional differences resulting from interfering species or isolation effects were significantly smaller than differences between DOM drained from each soil layer. All analyses indicated that DOM leached from the shallower organic mat contained higher molecular weight, more oxidized, and more unsaturated aromatic species compared to DOM leached from the deeper permafrost layer. Bacterial production rates and bacterial efficiencies were significantly higher for permafrost compared to organic mat DOM; however, respiration rates were similar between DOM sources. Increased release of permafrost DOM from arctic soils to surface waters will change the chemical composition of DOM and its lability to bacteria, but this study suggests that these shifts in DOM composition and lability may not increase the carbon dioxide produced by bacterial respiration of permafrost DOM exported to arctic surface waters compared to DOM currently draining the shallow active layer.
Clinical pharmacokinetics and pharmacodynamics of selegiline. An update.

Selegiline is a selective inhibitor of monoamine oxidase-B (MAO-B) at a dose of 10 mg/day and is given to patients with Parkinson’s disease as an adjunct to levodopa therapy. By inhibiting MAO-B, selegiline increases the dopamine levels in the substantia nigra. Selegiline also blocks dopamine re-uptake from the synaptic cleft, thus increasing the dopamine concentrations in the brain. At a dose of 10 mg/day, selegiline is devoid of ‘cheese effect’. The pharmacokinetics of selegiline are highly variable. Following an oral dose of selegiline 10mg, it is rapidly absorbed and metabolised to desmethylselegiline, levoamphetamine and levomethamphetamine. The mean peak plasma concentration (Cmax) is approximately 2 µg/L and the time to reach the peak is under an hour. The absolute bioavailability of selegiline is approximately 10%. It has an apparent volume of distribution of 1854L. The oral clearance of selegiline (59 L/min) is many fold higher than the liver blood flow (1.5 L/min), indicating that extrahepatic processes are involved in the elimination of selegiline. The elimination half-life of selegiline is about 1.5 hours. Following multiple administration of selegiline 10 mg/day, the accumulation of both the parent compound and its metabolites have been reported. At least a 4-fold increase in the half-lives of selegiline and desmethylselegiline has been reported. There is at least a 3-fold increase in the Cmax and area under the concentration-time curve of selegiline with food. One of the metabolites of selegiline, desmethylselegiline, is believed to posses some MAO-B inhibitory property, though to a lesser extent than that of selegiline. Within 2 to 4 hours of an oral dose of selegiline 10mg, 86% of the platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO-B activity to return to the baseline values. Transdermal administration of selegiline resulted in an increase in the plasma concentrations of selegiline and a decrease in the formation of its metabolites, indicating that the extensive first-pass effect is avoided when selegiline is given transdermally.
The Dynamic Response of Porous Calcium Carbonate Minerals

A theoretical study of the shock-loaded response of calcium carbonate materials is presented in which both dry and water-saturated samples with porosities up to 50 percent are considered. Data are presented for the unloading response from 15.0 and 18.5 GPa, and calculations from a mixture model using a Mie-Gruneisen equation of state with volume-dependent parameters are compared to both the Hugoniot and the isentropic unloading response.
Abstract 12926: Transition Readiness Assessment in Adolescents and Young Adults With Heart Disease: Can We Improve the Outcome?

Objective: Transition is defined as “the process by which adolescents and young adults with chronic childhood illnesses are prepared to take charge of their lives and their health in adulthood”. We previously reported common knowledge deficits and lack of transition readiness (TR) in 13-25 year olds with congenital or acquired heart disease. The aims of this study were to re-evaluate TR in these patients at follow-up (F/U) and to examine the relationship between changes in TR and quality of life (QOL). Methods: Patients (n=106) completed the TR Assessment and Pediatric Quality of Life Inventory (PedsQL) utilizing an e-tablet, web-based format at a routine F/U clinic visit. Changes from initial to F/U scores were evaluated. Results: Median patient age was 18.7 yrs at a median F/U time of 1.02 yrs. Average perceived knowledge deficit score (% of items with no knowledge) at F/U was 18.0 ± 15.2%, decreased from 24.7 ± 16.5%, p Conclusion: While deficits in knowledge and self-management skills persist, TR assessment and recognition of deficits can improve transition readiness with improved psychosocial QOL. Routine TR assessment is important to identify transition needs. Further studies are needed to examine the relationship between TR and outcomes in young adults with heart disease.
1‐Methyl‐4‐phenylpridinium (MPP+)‐induced functional run‐down of GABAA receptor‐mediated currents in acutely dissociated dopaminergic neurons

We have evaluated GABAA receptor function during treatment of 1-methyl-4-phenylpridinium (MPP+) using patch-clamp perforated whole-cell recording techniques in acutely dissociated dopaminergic (DAergic) neurons from rat substantia nigra compacta (SNc). γ-Aminobutyric acid (GABA), glutamate or glycine induced inward currents (IGABA, IGlu, IGly) at a holding potential (VH) of −45 mV. The IGABA was reversibly blocked by the GABAA receptor antagonist, bicuculline, suggesting that IGABA is mediated through the activation of GABAA receptors. During extracellular perfusion of MPP+ (1–10 μm), IGABA, but neither IGlu nor IGly, declined (termed run-down) with repetitive agonist applications, indicating that the MPP+-induced IGABA run-down occurred earlier than IGly or IGlu under our experimental conditions. The MPP+-induced IGABA run-down can be prevented by a DA transporter inhibitor, mazindol, and can be mimicked by a metabolic inhibitor, rotenone. Using conventional whole-cell recording with different concentrations of ATP in the pipette solution, IGABA run-down can be induced by decreasing intracellular ATP concentrations, or prevented by supplying intracellular ATP, indicating that IGABA run-down is dependent on intracellular ATP concentrations. A GABAA receptor positive modulator, pentobarbital (PB), potentiated the declined IGABA and eliminated IGABA run-down. Corresponding to these patch-clamp data, tyrosine hydroxylase (TH) immunohistochemical staining showed that TH-positive cell loss was protected by PB during MPP+ perfusion. It is concluded that extracellular perfusion of MPP+ induces a functional run-down of GABAA receptors, which may cause an imbalance of excitation and inhibition of DAergic neurons.
The histone deacetylase inhibitor, PXD101, potentiates bortezomib-induced anti-multiple myeloma effect by induction of oxidative stress and DNA damage

SummaryClinical trials have shown the high anti-myeloma activity of the proteasomeinhibitor bortezomib. The present study examined the activity of bortezomibcombined with PXD101, a histone deacetylase inhibitor, against multiplemyeloma (MM) and osteoclastogenesis. Treatment of myeloma cell lines withcombinations of bortezomib and PXD101 led to synergistic inhibition ofproliferation and induction of cell death. The combination signiﬁcantlydecreased the viability of primary human CD138 + myeloma cells but not ofbone marrow mononuclear cells. Further studies showed a dose-dependentactivation of caspases-3, -8 and -9 and nuclear fragmentation in myelomacells. Bortezomib/PXD101 treatment markedly triggered reactive oxygenspecies (ROS) generation that was accompanied by p53, H2A.X and p38–mitogen-activated protein kinase phosphorylation. ROS generation could beblocked by the free radical scavenger N-acetyl-l-cysteine. The combination ofbortezomib and PXD101 also resulted in synergistic inhibition of osteoclastformation. In conclusion, bortezomib and PXD101 have different moleculartargets. The combination induces cell death in myeloma cells via ROS-mediated DNA damage and also inhibits osteoclastogenesis. Therefore, thisstudy provides the rationale for the clinical evaluation of bortezomibcombined with PXD101 in patients with MM.Keywords: multiple myeloma, PXD101, oxidative stress, apoptosis, osteo-clastogenesis.
Anti‐nociception mediated by a κ opioid receptor agonist is blocked by a δ receptor agonist

Background and Purpose The opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception. Experimental Approach We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception. Key Results Etorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg−1), unmasked etorphine (3 mg·kg−1) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg−1) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg−1) and diazepam (1 mg·kg−1). Conclusions and Implications Systemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation. Linked Articles This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Using measurement error models to account for georeferencing error in species distribution models

Georeferencing error is prevalent in datasets used to model species distributions, inducing uncertainty in covariate values associated with species occurrences that result in biased probability of occurrence estimates. Traditionally, this error has been dealt with at the data-level by using only records with an acceptable level of error (filtering) or by summarizing covariates at sampling units by using measures of central tendency (averaging). Here we compare those previous approaches to a novel implementation of a Bayesian logistic regression with measurement error (ME), a seldom used method in species distribution modeling. We show that the ME model outperforms data-level approaches on 1) specialist species and 2) when either sample sizes are small, the georeferencing error is large or when all georeferenced occurrences have a fixed level of error. Thus, for certain types of species and datasets the ME model is an effective method to reduce biases in probability of occurrence estimates and account for the uncertainty generated by georeferencing error. Our approach may be expanded for its use with presence-only data as well as to include other sources of uncertainty in species distribution models.
Image Retrieval as Linguistic and Nonlinguistic Visual Model Matching.

THISARTICLE REVIEWS RESEARCH ON HOW people use mental models of images in an information retrieval environment. An understanding of these cognitive processes can aid a researcher in designing new systems and help librarians select systems that best serve their patrons. There are traditionally two main approaches to image indexing: concept-based and content-based (Rasmussen, 1997). The concept-based approach is used in many production library systems, while the content-based approach is dominant in research and in some newer systems. In the past, contentbased indexing supported the identification of “low-level” features in an image. These features frequently do not require verbal labels. In many cases, current computer technology can create these indexes. Conceptbased indexing, on the other hand, is a primarily verbal and abstract identification of “high-level” concepts in an image. This type of indexing requires the recognition of meaning and is primarily performed by humans. Most production-level library systems rely on concept-based indexing using keywords. Manual keyword indexing is, however, expensive and introduces problems with consistency. Recent advances have made some content-based indexing practical. In addition, some researchers are working on machine vision and pattern recognition techniques that blur the line between concept-based and content-based indexing. It is now possible to produce computer systems that allow users to search simultaneously on aspects of both concept-based and content-based indexes. The intelli
Inverse Ablation Analysis and the Calibration Integral Equation Method

The calibration integral equation method has been demonstrated for resolving inverse heat conduction problems based on an invariant sample geometry. This paper proposes to extend its applicability to the investigation of ablation through an abstraction based on forming a fictive surface temperature poised at the nonrecessive origin. Resolving this time-dependent temperature history provides a boundary condition that can be used in a restricted space defined between the nonrecessive origin and an in-depth thermocouple. This fictive temperature (or heat flux) provides an equivalence-based formulation defined in the original spatial domain because the calibration integral equation method is based on conservation principles. The extraction of the fictive boundary condition does not require knowledge of the thermophysical properties or probe position(s) because it is based on calibration. The complexity of ablation requires a compromise between a fully calibrative technique and forward solving approaches. The ...
Control performance limitations: to achieve or not to achieve?

This tutorial is intended to provide a summary survey of the classical results and recent developments in control performance limitation studies. The topics of primary interest include such frequency-domain results as Bode and Poisson type integral relations, as well as time-domain developments on optimal tracking and regulation problems. The presentation focuses on multivariable systems and address a number of new, unique issues only found in multivariable systems.
Review: Asthma: Emerging Concepts and Potential Therapies

Asthma is a disease of the airways that results in reversible airflow obstruction. Recent investigations have suggested that airway inflammation is associated with increased airway responsiveness and worsening of asthmatic symptoms. The role that mast cell mediators might play in the production of asthma has been investigated by use of newer analytical techniques and by use of fiberoptic bronchoscopy with lavage to obtain lower respiratory tract fluid and cells. In addition, new investigational compounds that interfere with the synthesis or action of inflammatory mediators have been tested. Developing lines of investigation suggest that chronic activation of inflammatory cells may be important in the pathogenesis of asthma.
Secondary Bifurcations in a Lotka–Volterra Model for N Competitors with Applications to Action Selection and Compulsive Behaviors

A Lotka–Volterra model for an arbitrary number of competitors is studied for different ratios of self-inhibition versus cross-inhibition. It is shown that winner-takes-all fixed points (states of single surviving species) are the only stable fixed points of the model when cross-inhibition exceeds self-inhibition. Secondary bifurcations in terms of bifurcations between winner-takes-all fixed points induced by changes in the exponential growth rates of competitors are studied and the critical control parameters are identified. A selection principle is derived that states that evolution proceeds in such a way that exponential growth rates of surviving competitors are magnified in evolutionary bifurcation steps. The interacting competitor model is applied as an amplitude equation model for interacting patterns of self-organizing pattern formation systems with an eye on action selection and compulsive behaviors in humans. The possibility is discussed that human behavior is subjected to the selection principle of "faster growth rates".
Pitch detection algorithms modifications and implementations towards automated vocal analysis

Discriminating between deceit and truth is a significant security challenge in a variety of situations, including border crossings, job interviews, flight passenger screenings, and police interviews. Previous research indicates that some features of vocal speech, e.g., fundamental frequency, are related to human emotion and stress levels making them applicable deception detection. This paper focuses on voice and speech feature extraction using advanced signal processing methodology. These generated speech features are used to submit data mining algorithms for classifying deception. The result of this paper is expected to be directly applied to the deception detection system.
Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar.

Bioassay-guided fractionation of the cytotoxic leaf and flower extract of Casearia nigrescens led to the isolation of four new clerodane diterpenoids, designated caseanigrescens A−D (1−4). These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3. The structures of compounds 1−4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83−1.4 μM.