cssi/SciSciGPT-SciSciNet huggingface dataset:
Secure computation of hidden Markov models and secure floating-point arithmetic in the malicious model

Hidden Markov model (HMM) is a popular statistical tool with a large number of applications in pattern recognition. In some of these applications, such as speaker recognition, the computation involves personal data that can identify individuals and must be protected. We thus treat the problem of designing privacy-preserving techniques for HMM and companion Gaussian mixture model computation suitable for use in speaker recognition and other applications. We provide secure solutions for both two-party and multi-party computation models and both semi-honest and malicious settings. In the two-party setting, the server does not have access in the clear to either the user-based HMM or user input (i.e., current observations) and thus the computation is based on threshold homomorphic encryption, while the multi-party setting uses threshold linear secret sharing as the underlying data protection mechanism. All solutions use floating-point arithmetic, which allows us to achieve high accuracy and provable security guarantees, while maintaining reasonable performance. A substantial part of this work is dedicated to building secure protocols for floating-point operations in the two-party setting, which are of independent interest.
Characterization of PEGylated Factor VIII Molecules.

Patients with hemophilia A typically require frequent treatment with replacement Factor VIII (FVIII) products due to the relatively short circulating half-life of FVIII. Increasing the half-life of FVIII would profound impact the lives of patients with hemophilia A, especially children, by reducing the frequency of infusions. The addition of polyethylene glutamate (PEG) to therapeutic molecules or their carriers has been demonstrated to increase the survival of such molecules in the circulation. To create a longer circulating product, we have developed novel FVIII molecules using site specific PEGylation techniques. We present a characterization of these PEGylated FVIII molecules in terms of the site of PEGylation, the binding of von Willebrand Factor (vWF), and the effect of PEGylation on thrombin digestion, and we compare the one-stage and chromogenic potency test results. The site of PEGylation was determined using MALDI-mass spectrometry. A vWF binding assay was developed using surface plasmon resonance technology (Biacore). The effect of PEGylation on thrombin digestion of the novel constructs was evaluated using MALDI-mass spectrometry, thrombin activation, and potency decay curves following thrombin activation. All novel constructs were PEGylated on the expected target site based on the site of introduced mutation. PEGylation of FVIII appeared to have a slight reduction on vWF-binding capability. The site of PEGylation reduced the ability of thrombin to digest FVIII, as assayed by MALDI-mass spectrometry analysis and by thrombin digestion and decay curves. The size and position of the PEG molecule influenced the extent of FVIII thrombin sensitivity. The one-stage potency assay was more sensitive to the size and position of the attached PEG molecule than the chromogenic potency assay. We report that some PEGylated FVIII molecules are less sensitive to thrombin activation than unmodified FVIII, and that the size and position of the PEG molecule can significantly affect the potency of FVIII. The findings of this study suggest that site-directed PEGylation of FVIII may be a useful technique for the development of FVIII molecules with extended activity in circulation and that careful choice of size and position of the PEG molecule is critical.
Vulnerability and Cosusceptibility Determine the Size of Network Cascades.

Specific clusters within a network tend to fail consistently as part of large-scale network failures, such as those in electrical grids or airline transportation systems.
Abstract TMP35: Higher Predicted Aerobic Fitness is Related to Above Median Insulin-like Growth Factor 1 in Individuals With Acute Stroke

Background: In healthy individuals, higher circulating insulin-like growth factor-1 (IGF-1) is related to higher aerobic fitness, measured as peak VO2. IGF-1 has been shown to possess neuroprotecti...
Fluid-Model-Based Car Routing for Modern Ridesharing Systems

We consider a closed queueing network model of ridesharing systems such as Didi Chuxing, Lyft, and Uber. We focus on empty-car routing, a mechanism by which we control car flow in the network to optimize system-wide utility functions, e.g. the availability of empty cars when a passenger arrives. We establish both process-level and steady-state convergence of the queueing network to a fluid limit in a large market regime where demand for rides and supply of cars tend to infinity, and use this limit to study a fluid-based optimization problem. We prove that the optimal network utility obtained from the fluid-based optimization is an upper bound on the utility in the finite car system for any routing policy, both static and dynamic, under which the closed queueing network has a stationary distribution. This upper bound is achieved asymptotically under the fluid-based optimal routing policy. Simulation results with real-word data released by Didi Chuxing demonstrate that the utility under the fluid-based optimal routing policy converges to the upper bound with a rate of 1/√N, where N is the number of cars in the network.
Use of micro-photoluminescence as a contactless measure of the 2D electron density in a GaAs quantum well

We compare micro-photoluminescence (μPL) as a measure of the electron density in a clean, two-dimensional (2D) system confined in a GaAs quantum well (QW) to the standard magneto-transport technique. Our study explores the PL shape evolution across a number of molecular beam epitaxy-grown samples with different QW widths and 2D electron densities and notes its correspondence with the density obtained in magneto-transport measurements on these samples. We also measure the 2D density in a top-gated quantum well sample using both PL and transport and find that the two techniques agree to within a few percent over a wide range of gate voltages. We find that the PL measurements are sensitive to gate-induced 2D density changes on the order of 109 electrons/cm2. The spatial resolution of the PL density measurement in our experiments is 40 μm, which is already substantially better than the millimeter-scale resolution now possible in spatial density mapping using magneto-transport. Our results establish that μPL c...
Automated dynamic symbology for visualization of high level fusion

Symbols play an important role in identifying informative objects and are widely used in geo-spatial decision support systems and applications. In high level fusion applications, however, simply placing symbols often lead to information overload problem; symbols quickly grow fast in many applications, such as the post disaster monitoring system we are interested in. This leads to cluttered and overlapped icons. With today’s advanced technologies, new visual effects can lead to better visualization systems where iconic overload may be perceived as a problem. Therefore, conventional method of storage-indexing-retrieval of large sets of prepared icon images is not flexible enough for the visualization of higher fusion levels. Instead, we propose a dynamic symbology, which automatically generates symbols from parameterized components in a three-dimensional space. The extension to tactical graphics can provide better situation awareness from simplified and abstract visualization. We also report on-going efforts on the prototype of a real-time immersive VR.
Attenuating the Agent: Reducing Opioid “Virulence”

One strategy in addressing the opioid epidemic is to decrease or attenuate the “virulence” of the agent, i.e., render opioids less “pathogenic.” Historic approaches to such attenuation have largely focused on altering existing and commercially available drugs by converting them to an extended-release form and equipping them with tamper-resistant and abuse-deterrent properties. While certainly not without merit, these approaches cannot prevent misuse or abuse by excessive consumption and do not alter the fundamental characteristics of the agent (e.g., propensity to cause euphoria, dependence and addiction, respiratory suppression). They can only affect the delivery of the agent. Novel modifications or alternative strategies using the endogenous opioid system, such as peripheral-only agonists, endogenous ligand protease inhibitors (e.g., dual enkephalinase inhibitors), heteromeric ligands with biased agonism, allosteric modifiers, and agents targeting glia, may provide safer analgesics and in effect reduce the population of virulent agents.
Fate of Salmonella enterica and Enterohemorrhagic Escherichia coli Cells Artificially Internalized into Vegetable Seeds during Germination.

ABSTRACT Vegetable seeds contaminated with bacterial pathogens have been linked to fresh-produce-associated outbreaks of gastrointestinal infections. This study was undertaken to observe the physiological behavior of Salmonella enterica and enterohemorrhagic Escherichia coli (EHEC) cells artificially internalized into vegetable seeds during the germination process. Surface-decontaminated seeds of alfalfa, fenugreek, lettuce, and tomato were vacuum-infiltrated with four individual strains of Salmonella or EHEC. Contaminated seeds were germinated at 25°C for 9 days, and different sprout/seedling tissues were microbiologically analyzed every other day. The internalization of Salmonella and EHEC cells into vegetable seeds was confirmed by the absence of pathogens in seed-rinsing water and the presence of pathogens in seed homogenates after postinternalization seed surface decontamination. Results show that 317 (62%) and 343 (67%) of the 512 collected sprout/seedling tissue samples were positive for Salmonella and EHEC, respectively. The average Salmonella populations were significantly larger (P IMPORTANCE The internalization of microorganisms into vegetable seeds could occur naturally and represents a possible pathway of vegetable seed contamination by human pathogens. The present study investigated the ability of two important bacterial pathogens, Salmonella and enterohemorrhagic Escherichia coli (EHEC), when artificially internalized into vegetable seeds, to grow and disseminate along vegetable sprouts/seedlings during germination. The data from the study revealed that the pathogen cells artificially internalized into vegetable seeds caused the contamination of different tissues of sprouts/seedlings and that pathogen growth on germinating seeds is bacterial species and vegetable seed-type dependent. These results further stress the necessity of using pathogen-free vegetable seeds for edible sprout production.
The pain of terror

Headaches and stress go hand in hand. Most individuals with a primary headache disorder perceive triggers for their attacks, and emotional stress is the trigger most commonly reported.1 Daily perceived stress correlates temporally with daily migraine activity.2 There may be a reciprocal relationship between migraines and stress whereby each influences the other over time.2 An association also occurs between perceived stress intensity and primary headache frequency.3 Even early childhood stressors such as trauma and neglect may predispose an individual to headaches later in life.4 Most studies that have analyzed the stress-headache relationship have done so by measuring prior or current stressors as reported by the patient with headaches. Rarely can the onset or worsening of headaches be attributed to a single life event.
Draft Genome Sequence of Bacillus velezensis OSY-S3, a Producer of Potent Antimicrobial Agents Active against Bacteria and Fungi.

ABSTRACT Bacillus velezensis OSY-S3 produces anti-Listeria, anti-Escherichia coli, and antifungal compounds. Additionally, fermentate of B. velezensis OSY-S3 culture removes Staphylococcus aureus biofilms effectively. The draft genome sequence of B. velezensis OSY-S3 reported here had a genome size of ~3.90 Mb and a G+C content of 46.5%.
Caffeine-catalyzed gels

Covalently cross-linked gels are utilized in a broad range of biomedical applications though their synthesis often compromises easy implementation. Cross-linking reactions commonly utilize catalysts or conditions that can damage biologics and sensitive compounds, producing materials that require extensive post processing to achieve acceptable biocompatibility. As an alternative, we report a batch synthesis platform to produce covalently cross-linked materials appropriate for direct biomedical application enabled by green chemistry and commonly available food grade ingredients. Using caffeine, a mild base, to catalyze anhydrous carboxylate ring-opening of diglycidyl-ether functionalized monomers with citric acid as a tri-functional crosslinking agent we introduce a novel poly(ester-ether) gel synthesis platform. We demonstrate that biocompatible Caffeine Catalyzed Gels (CCGs) exhibit dynamic physical, chemical, and mechanical properties, which can be tailored in shape, surface texture, solvent response, cargo release, shear and tensile strength, among other potential attributes. The demonstrated versatility, low cost and facile synthesis of these CCGs renders them appropriate for a broad range of customized engineering applications including drug delivery constructs, tissue engineering scaffolds, and medical devices.
Induction of smell through transethmoid electrical stimulation of the olfactory bulb.

Background Anosmia has an estimated prevalence of 5% of the general population. Outside of inflammatory causes, therapeutic options are limited despite research advances. Bypassing peripheral neuronal damage through central stimulation is a potential therapeutic option that has shown success in other sensory systems, most notably with hearing. We performed a pilot study to determine the feasibility of inducing smell through artificial electrical stimulation of the olfactory bulbs in humans. Methods Subjects with a history of sinus surgery, including total ethmoidectomy, with intact ability to smell were enrolled. The ability to smell was confirmed with a 40-item smell identification test. Awake subjects underwent nasal endoscopy and either a monopolar or bipolar electrode was positioned at 3 areas along the lateral lamella of the cribriform plate within the ethmoid sinus cavity. A graded stimulation current of 1-20 mA at 3.17 Hz was administered while cortical evoked potential (CEP) recordings were collected. Subjective responses of perceived smell along with reports of discomfort were recorded. Subjects with artificially induced smell underwent repeat stimulation after medically induced anosmia. Results Five subjects (age, 43-72 years) were enrolled. Three subjects reported smell perception smell with electrical stimulation. This was reproducible after inducing anosmia, but CEP recordings could not provide objective support. All subjects tolerated the study with minimal discomfort. Conclusion This is the first report of induced smell through transethmoid electrical stimulation of the olfactory bulb. These results provide a proof of concept for efforts in development of an olfactory implant system.
Utilization of a novel interactive mobile health platform to evaluate functional outcomes and pain following septoplasty and functional endoscopic sinus surgery

BACKGROUND Whether for research or quality improvement, assessment of postoperative quality of life outcomes faces a challenge in reliable data collection. Typical coordinator-led studies cite response rates from 35% to 70%. This study evaluates the utility of a digital patient engagement platform to track patient-reported outcome measures (PROMs) following septoplasty and functional endoscopic sinus surgery (FESS). METHODS A prospective cohort was recruited at a tertiary care center from January 2017 to March 2018. A mobile phone application relayed PROMs, including pain (assessed on a 0 to 10 visual analogue scale [VAS] every other day for 2 weeks, as well as the patient-reported outcome measure information system [PROMIS] pain interference short form 4a at baseline, 2 weeks, and 3 months) and timing of return to work. RESULTS Of 288 patients enrolled, 249 (86.5%) provided clinical data, including 208 who underwent septoplasty or FESS. Granular VAS scores, submitted by 195 patients, demonstrated 80% of these patients achieved minimal pain by postoperative day 8. A nonsignificant trend of increased days to pain relief by procedure emerged: septoplasty (mean ± standard deviation [SD], 3.60 ± 2.44), FESS (3.96 ± 3.25), FESS with septoplasty (4.40 ± 3.04), and FESS with drilling (4.86 ± 3.68). Across procedures, PROMIS pain interference increased at 2 weeks (9.17 ± 4.15) and decreased at 3 months (5.32 ± 2.61) compared with baseline (7.09 ± 4.63), with greater improvement noted in the FESS subgroup at 3 months. Patients returned to work at mean 7.1 days regardless of procedure. CONCLUSIONS With its high response rate, mobile digital patient engagement platforms may effectively track postoperative outcomes with the potential for reduced sample bias.
FACTOR ANALYSIS OF UPPER LIMB PROSTHETIC ACCEPTANCE FROM RETROSPECTIVE PROSTHETIC CLINICIAN SURVEY

INTRODUCTION Upper limb prosthetic acceptance seems to be relatively unchanged from 1958 where it was measured to be 75% for transradial, 61% for transhumeral, and 35% for shoulder disarticulation levels. A practitioner survey from 2013 by the author found this to be largely unchanged at 79.6%, 57.8%, and 32.8% respectively. An upper limb meta-analysis showed that the most significant factors affecting prosthetic rejection using a median rating were function, comfort, ease of use, weight, heat, lack of sensory feedback, inconvenience, lifestyle, dissatisfaction with technology, irritation, and availability of services. An earlier survey by the author condensed these factors of rejection to amputation level, functional advantage, and comfort, and included confidence of the prosthetist, availability of therapy, and support of the patient context. Also it was speculated that the value of factors influencing rejection of prostheses may not be simply the converse of those accepting the prosthesis but different scales. Abstract PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/32045/24459 How to cite: Stark G E. FACTOR ANALYSIS OF UPPER LIMB PROSTHETIC ACCEPTANCE FROM RETROSPECTIVE PROSTHETIC CLINICIAN SURVEY. CANADIAN PROSTHETICS & ORTHOTICS JOURNAL, VOLUME 1, ISSUE 2, 2018; ABSTRACT, ORAL PRESENTATION AT THE AOPA’S 101ST NATIONAL ASSEMBLY, SEPT. 26-29, VANCOUVER, CANADA, 2018. DOI: https://doi.org/10.33137/cpoj.v1i2.32045 Abstracts were Peer-reviewed by the American Orthotic Prosthetic Association (AOPA) 101st National Assembly Scientific Committee. http://www.aopanet.org/
Factors affecting pathogenicity of the turfgrass dollar spot pathogen in natural and model hosts

Abstract Clarireedia sp. (formerly called Sclerotinia homoeocarpa), the fungal pathogen that causes dollar spot of turfgrasses, produces oxalic acid but the role of this toxin in Clarireedia sp. pathogenesis is unknown. In the current study, whole plant inoculation assays were used to evaluate pathogenesis of Clarireedia sp. in various model hosts and investigate the role of oxalic acid in dollar spot disease. These assays revealed that both host endogenous oxalate content and pathogen-produced oxalic acid influence the timing and magnitude of symptom development. In time-course expression analysis, oxalate oxidase and related defense-associated germin-like protein genes in creeping bentgrass showed strong up-regulation starting at 48-72 hpi, indicating that germin-like protein genes are most likely involved in defense following initial contact with the pathogen and demonstrating the importance of oxalic acid in Clarireedia sp. pathogenesis. Overall, the results of these studies suggest that oxalic acid and host endogenous oxalate content are important for pathogenesis by Clarireedia sp. and may be associated with the transition from biotrophy to necrotrophy during host infection.
An Examination of the Association Between Relationship Mindfulness and Psychological and Relational Well‐being in Committed Couples

Relationship mindfulness is the degree to which individuals tend to be mindful during interactions with romantic partners. In this study, we examined both the intrapersonal and interpersonal links between relationship mindfulness and psychological and relationship functioning in a sample of 219 couples who had been in their relationship for at least 1 year. Even when accounting for the general tendency to be mindful, relationship mindfulness was linked with markers of relationship well-being and psychological functioning, both intrapersonally and interpersonally. The findings bring to light the importance of considering relationship mindfulness in clinical work with couples that focuses on addressing deficiencies in relationship or psychological well-being.
Evolving to recognize high-dimensional relationships in data: GA operators and representation designed expressly for community detection

We present a new algorithm for network clustering based upon genetic algorithm methods to optimize modularity. The algorithm proposes an innovative, more abstract representation, along with newly designed domain-specific genetic operators. We then analyze the performance of the algorithm using popular real-world data sets taken from multiple domains. The analysis demonstrates that our algorithm consistently finds high quality or even optimal solutions without any a priori knowledge of the network or the desired number of clusters. Furthermore, we compare our results with five previously published methods and yield the highest quality for the largest of the benchmark datasets.
Cognitive assumptions and long-term distress in survivors of childhood abuse, parental alcoholism, and dysfunctional family environments

Covariance structure modeling was used to test unique contributions of childhood abuse, parental alcoholism, and dysfunctional family environment to symptom distress and to cognitive assumptions regarding a worthy self, benevolent world, meaningful world, and spiritual world in college students (N = 651). Abuse history was related to adult symptom distress, while a dysfunctional family environment was related to negative assumptions concerning the self and the benevolence of the world. When included in the model with abuse history, family environment, gender, and other characteristics of the family of origin, parental alcoholism did not appear to be causally related to symptom distress or to cognitive assumptions. Cognitive assumptions were initially presumed to be mediators of symptom distress. Sequential refinement of the model through specification procedures suggested that more negative self assumptions may be a result, rather than a mediator, of symptom distress. Other assumptions were not related to symptom distress in the model.
How interprofessional collaborative practice can help dismantle systemic racism.

In the early 2000s, the Institute of Medicine in the United States issued two landmark reports. The first, To Err is Human (Institute of Medicine, 2000), shed light on the scale and cost of medical...
Integrative technologies to make supply chains lean, agile and green: a review

This research paper aims to qualitatively review the novel concept of lean, agile and green (LAG) supply chains through technology integration. Excessive carbon-footprint of supply chains in this era of globalisation, customised consumer needs and cost efficiency requires lean, agile and green supply chains. Therefore, this study reviews the impact of integrative technologies on LAG supply chain drivers through systematic literature review and content analysis. Findings of this study suggests that integrative technologies foster lean, agile and green key performance drivers. Managerial implications of this study are significant from technology adoption perspective as supply chain managers justify the integration of highlighted technologies for lean, green and agile supply chains. The future work as proposed by this study can motivate supply chain firms to further investigate the cost-benefit analysis for integrative technologies adoption and the empirical impact on LAG supply chain drivers.
A Simple Extreme Learning Machine Model for Detecting Heart Arrhythmia in The Electrocardiography Signal

Electrocardiogram (ECG) or (EKG) is the common mechanism of recording the electrical signals of the heart to detect heart impairment functionality. In this paper, we proposed a novel Extreme Learning Machine based model for heart arrhythmia detection in the ECG signal (ELM-D). Empirically, the proposed ELM-D model exceeds the state-of-the-art model in the detection accuracy over the ECG arrhythmia benchmarks. In addition, it is quite simple to implement using a small implementation budget. Moreover, it could be implemented on an FPGA or any small hardware device.
The lack of) fluency and perceptions of decision making

Research consistently finds that fluent stimuli in marketing communications are better liked and more trusted than more difficult to process stimuli. This paper describes four studies showing that ...
Quantification of CO2 Mineralization at the Wallula Basalt Pilot Project.

In 2013, Pacific Northwest National Laboratory led a geologic carbon sequestration field demonstration where ~1000 tonnes of CO2 were injected into several deep Columbia River Basalt zones near Wal...
The Kappa Opioid Receptor is required for some intermittent alcohol drinking induced changes in stress and threat responding in male C57BL/6J mice

The dynorphin/kappa opioid receptor (KOR) system in the brain regulates both stressful experiences and negative, aversive states during withdrawal from drugs of abuse. We explored the role of this system during acute withdrawal from long-term alcohol drinking. Male C57BL/6J mice were subjected to repeated forced swim tests, home cage exposure to a predator odor, and a visual threat after intermittent access to alcohol or water. Systemic injection of KOR antagonist norBNI reversed alcohol-related differences in immobility time during the second swim test and reduced burying behavior in response to predator odor, but did not affect behavioral response to visual threat.
Cost evaluation of adjunctive osimertinib use in resected epidermal growth factor receptor-positive non-small cell lung cancer.

8525Background: About 30% of patients with epidermal growth factor receptor positive (EGFR+) non small cell lung cancer (NSCLC) are eligible for surgical resection. Osimertinib, a first line therap...
High-Q optical design for a laser-diode-based packaged ring laser gyroscope

We discuss using a basic design with a high-Q optical system that is capable of reducing random drift to enhance sensor accuracy in a laser-diode-based packaged ring laser gyroscope. We show that adding optical cavities to the packaged optical loop could potentially compensate for optical losses in certain specific straight-line segments of the loop (optical paths and mirror systems) by increasing the overall Q of the system. We present model results for symmetric triangular optical designs with path lengths of 50, 100, 150, and 200 mm. The optical design developed in this paper yielded performance that was nearly an order of magnitude better: Our design with a path length of 100 mm had a Q factor of 5.8×1014 and a random drift of 8×10−4deg/h1/2, which conforms to Class 1 accuracy standards for inertial gyroscopes. Increasing the Q factor for the optical design expanded the coverage range of the gyroscope package scale factor. The results of this study were used to develop a prototype laser-diode-based packaged ring laser gyroscope.
Achieving performance portability in Gaussian basis set density functional theory on accelerator based architectures in NWChemEx

Abstract The numerical integration of the exchange–correlation (XC) potential is one of the primary computational bottlenecks in Gaussian basis set Kohn–Sham density functional theory (KS-DFT). To achieve optimal performance and accuracy, care must be taken in this numerical integration to preserve local sparsity as to allow for near linear weak scaling with system size. This leads to an integration scheme with several performance critical kernels which must be hand optimized for each architecture of interest. As the set of available accelerator hardware goes more diverse, a key challenge for developers of KS-DFT software is to maintain performance portability across a wide range of computational architectures. In this work, we examine a modular software design pattern which decouples the implementation details of performance critical kernels from the expression of high-level algorithmic workflows in a device-agnostic language such as C++; thus allowing for developers to target existing and emerging accelerator hardware within a single code base. We consider the efficacy of such a design pattern in the numerical integration of the XC potential by demonstrating its ability to achieve performance portability across a set of accelerator architectures which are representative of those on current and future U.S. Department of Energy Leadership Computing Facilities.
WS06.2 R117H-CFTR has a defect in channel gating activity that can be potentiated by ivacaftor

Background The R117H mutation is associated with residual chloride transport and a delayed onset of CF symptoms. Although generally called a conductance mutation, R117H-CFTR exhibits defective channel gating. This study aimed to more fully explore the mechanistic defect of R117H-CFTR and to evaluate the effect of ivacaftor, a CFTR potentiator, on R117H-CFTR. Methods and Results In single-channel, patch-clamp studies, the channel open probability (gating activity) of R117H-CFTR was 22% of normal, whereas the channel conductance was 88% of normal. The channel gating activity of R117H-CFTR was characterized by frequent but brief openings of the channel compared with normal CFTR. The brief openings are consistent with a low channel open probability due in part to destabilization of the channel open state by R117H. The addition of ivacaftor increased the channel open probability of R117H-CFTR from 22% to 42% of normal. The increase in open probability was due to an increase in the frequency of channel opening and a decreased closed duration. Channel open duration and conductance were not increased. In Ussing chamber studies using R117H-5T/F508del-human bronchial epithelial cells from two donor bronchi, chloride transport was 23% of normal, which is consistent with residual chloride transport. Ivacaftor treatment for 18–24 hours increased chloride transport to 36% of normal. Conclusion These data confirm that R117H is a residual function CFTR mutation that causes a predominant defect in channel gating activity that is potentiated by ivacaftor. Based on these in vitro data, ivacaftor would be expected to enhance CFTR activity in people with the R117H mutation.
Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea

Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea. Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9. MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression. Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.
I. Nonextensive Statistical Mechanics and Thermodynamics: Historical Background and Present Status

The domain of validity of standard thermodynamics and Boltzmann-Gibbs statistical mechanics is focused on along a historical perspective. It is then formally enlarged in order to hopefully cover a variety of anomalous systems. The generalization concerns nonextensive systems, where nonextensivity is understood in the thermodynamical sense. This generalization was first proposed in 1988 inspired by the probabilistic description of multifractal geometry, and has been intensively studied during this decade. In the present effort, we describe the formalism, discuss the main ideas, and then exhibit the present status in what concerns theoretical, experimental and computational evidences and connections, as well as some perspectives for the future. The whole review can be considered as an attempt to clarify our current understanding of the foundations of statistical mechanics and its thermodynamical implications.
A graphical aid for sensitivity analysis of estimated regression coefficients

A problem often arising in applied linear regression modeling is determining the appropriate weight to attach to each observation. In the extreme, the problem extends to the deletion of observations from a data base. Since the choice of weights, fitting criteria, and estimation procedure depend on the specific objectives of the modeling, universally applicable guidelines are virtually nonexistent. However, the sensitivity of analytic conclusions to weights assigned to “suspect” observations can be conveniently assessed using a graphical display. This report develops such a display based on a modeling of outliers which leads naturally to estimators based on a weighted least-squares criterion, and a data-analytic method for determining how much downweighting to impose on a specific subset of observations. This technique is illustrated with several examples, including one relating air pollution to human mortality.
Eating Disorders in Childhood and Adolescence (4th ed.)

The 4th edition of Bryan Lask and Rachel Bryant-Waugh's edited volume, Eating Disorders in Childhood and Adolescence continues their well-established history of providing significantly updated chap...
Quantitation of glycolysis and skeletal muscle glycogen synthesis in humans.

We measured the net rates of skeletal muscle glycogen synthesis and glycolysis (conversion of [3-3H]glucose to 3H2O) in healthy overnight-fasted volunteers. Two studies were performed. In study 1, ...
A dihydropyridine conjugate which generates high and sustained levels of the corresponding pyridinium salt in the brain does not exhibit neurotoxicity in cynomolgus monkeys.

Abstract Many drugs can be selectively delivered to the brain by using a dihydropyridine ⥂ pyridinium salt chemical delivery system (CDS). The interaction of these systems with central dopaminergic function was examined in this communication. Castrate female Sprague-Dawley rats when treated with a CDS for estradiol (i.e. 3-hydroxy-17β-{[(1-methyl-1,4-dihydropyridin-3-yl)carbonyl]oxy}estra-1,3,5(10)-triene or E 2 CDS) exhibit sustained and profound suppression of serum levels of luteinizing hormone (LH). Treatment of rats with pargyline (80 mg/kg) prior to E 2 CDS (2 mg/kg) did not mitigate the biological effectiveness of this estrogen indicating at least indirectly that monoamine oxidate (MAO) was not involved in the CDS activation. In a more direct examination, cynomolgus monkeys treated with various repeated doses of E 2 CDS (cumulative doses of 0.2–40.0 mg/kg) demonstrated neither impaired motor function nor depleted striatal dopamine concentrations. The latter parameter was measured using liquid chromatographic-electrochemical analysis. These experiments support the contention that the CDS is not neurotoxic and further strengthens the strict structure-activity requirements for MPTP-induced neurotoxicity.
EFFECT OF DIETARY PROTEIN QUALITY AND QUANTITY ON GLUCOSE UTILIZATION IN RAT MAMMARY GLANDS DURING LACTATION

Abstract The effects on glucose metabolism in the mammary gland of feeding diets deficient in protein quality or quantity from conception through day 4 of lactation were measured. Protein sources were 13% casein plus methionine (13CM), 13% wheat gluten (13WG) or 5% casein plus methionine (5CM). Dams were sacrificed on day 20 of gestation or day 4 of lactation. Mammary slices or isolated acini were incubated with 5 mM [U-14C] glucose in the presence and absence of insulin and recovery of 14C in CO2, lipid and lactose determined. In slices on day 4 of lactation, neither dietary protein quality or quantity significantly influenced incorporation of labeled glucose into CO2, lipid or lactose. Insulin significantly increased incorporation into CO2 and lipid 15% and 17%, respectively, and reduced incorporation into lactose 16%. In acini on day 4 of lactation, reduction in protein quality (13WG vs. 13CM) reduced lipogenesis and lactose synthesis per mg DNA, but no consistent effect of insulin was observed. In both slices and acini, incorporation rates were significantly higher on day 4 of lactation than on day 20 of gestation. The almost total failure of lactation previously observed in 13WG fed dams likely is related at least in part to a reduction in glucose utilization per secretory cell as well as to reductions in mammary gland size and content of DNA, RNA and protein previously observed.
The effect of timeout on performance on a variable-interval schedule of electric-shock presentation

Responding was maintained in squirrel monkeys under variable-interval schedules of electric shock presentation when a period of timeout followed each response-dependent shock. Response rate decreased when timeout duration was decreased, and responding ceased when timeout was eliminated. These results indicate that under certain conditions, a shock-free period following each response-produced shock is necessary to maintain responding.
Dislocation drag at the nanoscale.

Abstract The mobility of dislocations is shown to be a size-dependent phenomenon. When dislocations intersect free surfaces, the mobility decreases as the dislocation length decreases, suggesting that dislocation motion in small structures may be more difficult. This increased drag may be related to surface forces acting where the dislocation intersects the free surface or from altered dislocation–phonon interactions. Mobility, however, is not as dependent on the film thickness and converges rapidly to bulk values.
The effect of secondary phase on thermoelectric properties of Zn4Sb3 compound

Abstract Zn 4 Sb 3 is a promising thermoelectric material because of its high thermoelectric performance and the abundance of Zn and Sb in nature. Samples of Zn 4 Sb 3 with ZnSb or Zn as the minor phase were prepared to optimize the figure-of-merit ( ZT ). The effects of ZnSb or Zn secondary phase on the thermoelectric properties of Zn 4 Sb 3 were investigated. The highest peak ZT of about 1.2 was achieved at 400 °C in the sample with single Zn 4 Sb 3 phase, which has the lowest thermal conductivity. Transmission electron microscopy observations of the nanostructures suggest that the precipitated ZnSb, Zn-rich nanoparticles, and nanovoids, caused by volatile Zn diffusion, all contribute to the extraordinarily low thermal conductivity.
Evaluating an interdisciplinary undergraduate training program in health promotion research.

Background The University of California at Irvine Interdisciplinary Summer Undergraduate Research Experience (ID-SURE) program had three objectives: (1) designing an interdisciplinary health promotion training curriculum for undergraduate research fellows; (2) developing measures for evaluating and assessing program-related educational processes and products; and (3) comparing these educational process and product measures between groups of students who did or did not receive the training. Methods A total of 101 students participated in the ID-SURE program during 2005, 2006, and 2007. A longitudinal research design was employed whereby students' interdisciplinary attitudes and behaviors were assessed at the beginning and end of the training program. The interdisciplinary and intellectual qualities of students' academic and research products were assessed at the conclusion of the training activities. In addition, ID-SURE participants' interdisciplinary attitudes, behaviors, and research products were compared to those of 70 participants in another fellowship program that did not have an interdisciplinary training component. Results Exposing undergraduate research fellows to the interdisciplinary curriculum led to increased participation in, and positive attitudes about, interdisciplinary classroom and laboratory activities. Products, such as the integrative and interdisciplinary quality of student research projects, showed no differences when compared to those of undergraduates who were not exposed to the interdisciplinary curriculum. However, undergraduates exposed to the training engaged in more interdisciplinary behaviors at the end of the program than students who were not trained in interdisciplinary research techniques. Conclusions The findings from this study offer evidence for the efficacy of the ID-SURE program for training undergraduate students in transdisciplinary concepts, methods, and skills that are needed for effective scientific collaboration. Additionally, this study makes two important contributions to the development and evaluation of interdisciplinary health research training programs: (1) It presents and evaluates a novel curriculum for training undergraduate students in interdisciplinary theories, concepts, and methods of health promotion that can be replicated in other settings and contexts; (2) It provides and tests the reliability of new measures for evaluating interdisciplinary collaborative processes and develops objective criteria for rating the integrative and intellectual quality of students' research products.
Clinical Versus Reliable and Significant Change

Sheldrick, Kendall, and Heimberg have illustrated and compared the use of the reliable change index (RCI) and normative comparisons procedures for assessing the clinical meaningfulness of research findings. Their presentation illustrates how the method of normative comparisons, combined with a reliability of change index such as that offered by Jacobson and colleagues can be used to assess the clinical meaningfulness of treatments. Their comparisons of treatments that have been previously identified as empirically supported reveal that a definition of worth, based on statistical significance, fails to identify the power (or lack thereof) of the intervention. Reliable change and clinical meaningful change estimates add substantially to the interpretation of statistical significance. However, they are complementary, not equivalent methods. The RCI can only indicate whether the change noted exceeds what can be expected because of the unreliability of the instrument used. Although estimates of clinical utility should be routine in research reports of treatment effects wherever possible, there are still situations in which procedures for estimating clinical significance are lacking, and new methods are needed in these instances.
Characterization and Regulation of the Rat and Human Ghrelin Promoters

Ghrelin is a recently discovered stomach hormone and endogenous ligand for the GH secretagogue receptor. The aim of these studies is to elucidate molecular mechanisms underlying regulation of the ghrelin gene. Distal and proximal transcription initiation sites are present. A short transcript, a product of the proximal site, showed a more widespread distribution. Two sets of 5'-upstream segments of the rat and human ghrelin genes were cloned and sequenced. Rat promoter segments upstream of the distal site showed highest activity in kidney (COS-7) and stomach (AGS) cells, whereas human promoter segments upstream of the proximal site showed highest activity in AGS and pituitary (GH3) cells in transient transfection assays. For the human, the core promoter spanned -667 to -468 bp, including the noncoding exon 1 and a short 5' sequence of intron 1. For the rat, the core promoter spanned -581 to -469 bp, and inclusion of exon 1 and a short 5'-sequence of intron 1 reduced activity by 67%. Mutation of initiator-like elements in the rat lowered activity by 20-50%, whereas in the human, all activity was abolished. Overexpression of upstream stimulatory factors increased ghrelin core promoter activity. Fasting increases stomach ghrelin expression, glucagon-a fasting-induced hormone, increased ghrelin expression in vivo in rats, and promoter activity by approximately 25-50%. Together, these findings indicate that structural differences between the rat and human ghrelin core promoters may account in part for the differences in their transcriptional regulation. Nonetheless, upstream stimulatory factor and glucagon exert similar effects on regulation of rat and human ghrelin promoters.
A role for the HOXB7 homeodomain protein in DNA repair

Homeobox genes encode transcription factors which function in body axis patterning in the developing embryo. Recent evidence suggests that the maintenance of specific HOX expression patterns is necessary for regulating the homeostasis of adult tissues as well. In this study, HOXB7 transformed human mammary epithelial cells, MCF10A, to grow in minimally supplemented medium, to form colonies in Matrigel, and display resistance to ionizing radiation. Searching for protein partners of HOXB7 that might contribute to resistance to ionizing radiation, we identified four HOXB7-binding proteins by GST pull-down/affinity chromatography and confirmed their interactions by coimmunoprecipitation in vivo. Interestingly, all four HOXB7-binding proteins shared functions as genomic caretakers and included members of the DNA-dependent protein kinase holoenzyme (Ku70, Ku80, DNA-PK(cs)) responsible for DNA double-strand break repair by nonhomologous end joining pathway and poly(ADP) ribose polymerase. Exogenous and endogenous expression of HOXB7 enhanced nonhomologous end joining and DNA repair functions in vitro and in vivo, which were reversed by silencing HOXB7. This is the first mechanistic study providing definitive evidence for the involvement of any HOX protein in DNA double-strand break repair.
Absence of a redundant-signals effect in a reaction time task with divided attention.

In letter-identification reaction time experiments, a redundant-signals advantage was obtained when one location contained an irrelevant letter on single-target trials. It was not obtained when the position was blank. This confirms a prediction from a previous analysis in terms of variable criterion theory. The intercept of the linear function relating the growth of excitatory strength for redundant targets to that for the sum of single-target strengths is determined by the presence or absence of an irrelevant distractor. This confirms a second prediction. In this task, the redundant-signals advantage is due to distraction from an irrelevant stimulus occupying a relevant location. There is also evidence for a smaller distraction effect even from a redundant target. These findings are inconsistent with predictions of separate activation theory. Apparent differences be-tween these results and those of tachistoscopic recognition experiments are discussed.