cssi/SciSciGPT-SciSciNet huggingface dataset:
Chemical insight from crystallographic disorder-structural studies of supramolecular photochemical systems. Part 2. The β-cyclodextrin–4,7-dimethylcoumarin inclusion complex: a new β-cyclodextrin dimer packing type, unanticipated photoproduct formation, and an examination of guest influence on β-CD dimer packing

As part of an ongoing structural study of supramolecular photochemical β-cyclodextrin(β-CD)–coumarin derivatives systems the crystal structure of the β-CD–4,7-dimethylcoumarin complex has been determined at 13 K and complemented with ab initio molecular orbital calculations on selected guest coumarin molecules. The 4,7-dimethylcoumarin molecules form a crystalline 2∶2 host–guest (H–G) complex with β-CD that is appropriately described as a “reaction nano-vessel” in which the inter-molecular interactions of import to the outcome of the reaction are confined to a single β-CD dimer host. Structure determination of the isolated photoproduct showed the product formed is the anti-HT photodimer. Production of this dimer is only possible with much rearrangement of the guests. This appears to occur because of a preferential spatial fit of this product to the β-CD dimer cavity. The crystal structure reveals a new β-CD dimer packing pattern, designated tetrad type, with reduced reaction tube intermolecular interactions among guest molecules. Tetrad packing is characterized in comparison with the previously reported β-CD dimer packing types. Guest influence on packing of β-CD dimers is examined in β-CD inclusion complexes with different derivatized coumarins. To probe basic molecular properties giving rise to inter-molecular interactions influencing crystal packing, ab initio molecular orbital calculations for the guest coumarin molecules were carried out to examine electrostatic interactions.
Analytical analyses of stress transfer in fibre-reinforced composites with bonded and debonded fibre ends

The elastic stress transfer from the matrix to the fibre is analysed analytically for fibre-reinforced composites when the loading direction is parallel to the fibre axis. The fibres with bonded lateral interfaces and (1) debonded and (2) bonded ends are considered in the present study. For the case of debonded ends, the present solutions contain refinements of the previously derived analytical solutions. For the case of bonded ends, unlike the numerical solutions derived previously, the present analytical solutions are ready to be used for further analyses. The results show that the stress transfer is more effective when the fibre has higher Young's modulus or longer length. Also, compared to the debonded ends case, the stress transfer is more effective and the stress distribution is more uniform when the ends are bonded to the matrix.
Clinical trials of health education for hypertensive outpatients: design and baseline data.

Abstract A research program was designed to proceed from a set of propositions about health education to a corresponding set of corollaries for evaluation of health education in hypertensive patients. The first step of the program consisted of a series of “diagnostic-baseline” studies to determine the educational needs of patients and health care staff and to analyze other barriers to patient compliance. Apart from a few widespread misconceptions about hypertension among patients and a tendency among staff to overestimate compliance, both patients and providers of health care in The Johns Hopkins clinics are better informed than expected on the basis of similar surveys conducted here nearly 2 yr earlier. Neither side effects nor costs of drugs were cited by patients as major reasons for noncompliance. Educational interventions are being designed on the basis of these findings to identify individual problems with compliance and to influence more deep-seated sources of resistance to change. If our educational diagnosis is correct, the proposed clinical trials of these interventions should yield more long-term compliance and blood pressure control than conventional patient education activities focused on more superficial knowledge, attitudes, and beliefs.
Fimbria/fornix lesions facilitate the learning of a nonspatial response task.

The spatial cognitive map theory of O’Keefe and Nadel (1978) predicts that lesions of the hippocampal system should impair learning on spatial tasks but not learning on nonspatial tasks. However, there is evidence that such lesions can facilitate learning on certain nonspatial tasks. Their theory does not predict such facilitation. Nevertheless, it is reasonable to expect that animals possessing a spatial cognitive map would have an inherent bias to engage a mapping strategy and thus be at a disadvantage on certain nonspatial tasks in comparison with animals without the mapping capacity and bias. In the present study, fimbria/fornix lesions impaired learning on a spatial task, but actually facilitated learning on a nonspatial task of equal difficulty. Thus, brain lesions that interfere with map functioning can facilitate learning on tasks for which a mapping strategy interferes with task solution. The results require a modification of the spatial cognitive map theory.
CW ultraviolet saturation spectroscopy of the 6p 3P0-9s 3S1 transition in mercury at 246.5 nm

Abstract We have measured the even isotope structure of the 6p 3 P 0 -9s 3 S 1 transition in mercury at 246.5 nm using saturated absorption spectroscopy with radiation produced as the sum frequency of a 363.8 nm argon ion laser and an LD700 ring dye laser in ADP. This is the first use of cw sum-frequency mixing in nonlinear laser spectroscopy in the ultraviolet. No previous cw Doppler-free measurements have been reported at wavelenghts below 294.5 nm
Mechanical Assist Devices

Cardiac assist devices are the most complicated mechanical/electrical systems placed in human beings. They have fascinated heart specialists, the public, and the press for many years. On the positive side, they are awe-inspiring examples of sophisticated technology. They provide hope that with technology, determination, and money, the result can be similar to the quest to land men on the moon and return them safely. The journey to mechanical support has advanced a long way this decade. Today we routinely implant life-saving portable devices powered by small batteries that allow an acceptable quality of life for most patients and extend the life for many patients awaiting heart transplantation. Some patients even have recovery of their own heart function so that the device can be removed, and they may never need a transplant.
Extended Self: Spontaneous Activation of Medial Prefrontal Cortex by Objects that are “Mine”

The concept of extended self refers to the idea that people incorporate self-relevant others or objects into ones sense of self. Initial neural support for the notion of extended self was provided by fMRI evidence that medial prefrontal cortex (MPFC) showed greater activation while people imagined objects belonging to them compared with someone else (Kim & Johnson, 2012). This study investigated whether self-associated objects (i.e. �mine�) subsequently engage MPFC spontaneously when a task does not require explicit self-referential judgments. During fMRI scanning, participants detected �oddballs� (objects with a specific frame color) intermixed with objects participants had previously imagined belonging to them or to someone else and previously unseen non-oddball objects. There was greater activity in MPFC and posterior cingulate cortex for thoseself-ownedobjects that participants were more successful at imagining owning compared withother-ownedobjects. In addition, change in object preference following the ownership manipulation (a mere ownership effect) was predicted by activity in MPFC. Overall, these results provide neural evidence for the idea that personally relevant external stimuli may be incorporated into ones sense of self.
Evaluation and management of children with holoprosencephaly

Recent advances in genetics and neuroimaging have greatly contributed to our understanding of the spectrum of midline brain and craniofacial malformations known as holoprosencephaly. Neuroradiologic studies have provided detailed characteristics of four major types of holoprosencephaly: alobar, semilobar, lobar, and middle interhemispheric variant. Clinical studies in children with these types of holoprosencephaly have revealed a wide range of survival and neurologic outcomes. Motor and developmental dysfunctions correlate with the severity of the brain malformation in holoprosencephaly. These findings have implications in the management of medical problems associated with holoprosencephaly and overall prognostication.
Law and Power: The Sherman Antitrust Act and its Enforcement in the Petroleum Industry

An increasing number of sociologists agree that a society's legal norms tend to reflect its configuration of power. They differ on whether that power is pluralistically distributed among competing interest groups or concentrated in the hands of the corporate elite. This paper analyzes the struggle that led to the enactment of the Sherman Antitrust Act of 1890, and the attempts at antitrust enforcement in a key ogligopolistic industry-petroleum. Historical data show that passage of the act was indeed a defeat for the corporate elite; but elite interests ultimately prevailed through their domination of the enforcement process. My analysis of big oil's success in protecting its interests shows that private, profitoriented corporations enjoy fundamental structural advantages over both the enforcement bureaucracy and social movements pushing for change.
Three-dimensional structure of synapses in the brain and on the Web

The anatomical database that describes the neural networks of the brain will eventually contain sufficient detail to identify all neurons and the individual synapses between them. One approach to obtaining this level of detail is to reconstruct brain volumes from serial electron microscopic sections. Current techniques allow the creation of relatively small ultrastructural volumes, but these contain an enormous wealth of data. Many different kinds of data, including neuron membrane structure, synaptic connectivity, organelle distributions, etc., can be extracted from a single database using this representation. The ultimate size of the ultrastructural database of the brain depends on the advancement of techniques for data creation as well as the development of informatics tools for ultrastructural data mining.
Serologic survey for Toxoplasma gondii in lynx from interior Alaska.

Two hundred fifty-five lynx (Felis lynx) carcasses were collected from trappers in Interior Alaska (USA). Serosanguinous fluids were collected from the chest cavity of each carcass. These fluids were tested for evidence of exposure to Toxoplasma gondii by means of a modified agglutination test using formalin fixed tachyzoites and mercaptoethanol. Thirty-nine of the samples had titers greater than or equal to the threshold (≥25). Antibody prevalence differed between areas, and was directly related to age of the host.
Impending Challenges for the Use of Big Data.

Advances in data storage and data analysis materialized also in health care data. In recent years, we have seen an emphasis on using the full potential (1, 2) of these data to answer questions such as: who were the patients that received radiation therapy as primary treatment? Who among such patients experienced radiation therapyerelated complications? Given everything you know about my case, what is the chance that if I choose radiation therapy, I will experience incontinence in the next year? Factors contributing to this trend include more rapid data querying technologies, cheaper data storage, addition of genomic data to traditional clinical data sets, “meaningful use incentives” for increasing the adoption of electronic health records, and recent emergence of precision medicine (3). In this perspective paper, we discuss several challenges ahead for big data, some that are being addressed now and others that will need to be addressed in the near future. The list of challenges presented here is not meant to be an exhaustive list but is rather driven by our big data experience. For each challenge, we provide comments on current approaches to address the challenge.
Opportunistic Content-Based Dissemination in Disconnected Mobile Ad Hoc Networks

Content-based networking fosters a new kind of communication in which information flows towards interested hosts rather than towards specifically set destinations. Supporting this kind of communication in mobile ad hoc networks is still a challenge, though, especially in partially or intermittently connected networks. This paper addresses this problem by combining the concept of content-based communication with that of opportunistic networking. The protocol it describes exploits transient contacts between mobile hosts that exchange messages according to their respective interest profiles. A message thus disseminates in the network by being stored, carried, and forwarded by those hosts that show some interest for this message. Experimental results as well as simulations confirm that this approach makes it possible to disseminate information efficiently, while minimising the resources implied in this dissemination.
Neural Network Mapping and Clustering of Elastic Behavior From Tactile and Range Imaging for Virtualized Reality Applications

To fully reach its potential, virtualized reality needs to go beyond the modeling of rigid bodies and introduce accurate representations of deformable objects. This paper explores neural networks and vision-based and tactile measurement strategies to investigate the intricate processes of acquisition and mapping of properties characterizing deformable objects. An original composite neural network framework is applied to guide the tactile probing by clustering measurements representing uniform elasticity regions and, therefore, direct sensors toward areas of elasticity transitions where higher sampling density is required. The network characterizes the relationship between surface deformation and forces that are exemplified in nonrigid bodies. Beyond serving as a planner for the acquisition of measurements, the proposed composite neural architecture allows the encoding of the complex force/deformation relationship without the need for sophisticated mathematical modeling tools. Experimental results prove the validity and the feasibility of the proposed approach.
The FIELD Debugger

The process of programming centers around the edit-compile-debug cycle. Central to this cycle is debugging, i.e. executing the user’s program in a controlled fashion. Debuggers let one set breakpoints, single-step the program, examine and set variables, and view the execution stack. Their user interface lets the programmer work in terms of the source while actually manipulating values and code at the machine level.
Examining DCSP coordination tradeoffs

Distributed Constraint Satisfaction Problems (DCSPs) provide a model to capture a broad range of cooperative multiagent problem solving settings. Researchers have generally proposed two different sets of approaches for solving DCSPs, backtracking based approaches, such as Asynchronous Backtracking (ABT), and mediation based approaches, such as Asynchronous Partial Overlay (APO). These sets of approaches differ in the levels of coordination employed during conflict resolution. While the computational and communication complexity of the backtracking based approaches is well understood, the tradeoffs in complexity involved in moving toward mediation based approaches are not. In this paper we comprehensively reexamine the space of mediation based approaches for DCSP and fill gaps in existing frameworks with new strategies. We present different mediation session selection rules, including a rule that favors smaller mediation sessions, and different mediation strategies, including a decentralized hybrid strategy based on ABT. We present empirical results on solvable 3-coloring and random binary DCSP problems, that accurately capture the computational and communication tradeoffs between ABT and various mediation based approaches. Our results confirm that under some circumstances the newly presented strategies dominate previously proposed techniques.
NADH-Linked Electron Transfer Induces Cd2+ Movement in Corn Root Plasma Membrane Vesicles

The rate of electron transfer from NADH to ferricyanide associated with corn root plasma membrane vesicles was not significantly affected by the presence of Ca 2+, Cd2+, Zn2+, or Co2+. However, unlike Ca2+, other tested divalent cations induced an electron transfer-dependent increase in light scattering by the vesicles. The efficacy in inducing the light scattering increase followed the order of Cd 2+>Zn2+>Co2+. The extent of the light scattering change increased as the concentration of added Cd2+ increased. Using phase contrast microscopy, the increase in light scattering was related to an expansion of the vesicles. Accompanying the volume increase, a decrease of Cd 2+ concentration in the external space was observed by the use of Arsenazo III, a metallochromophore specific for divalent cations. Under a specified electron transfer condition, a similar percentage of decrease over a wide range of initial Cd2+ concentration was detected. The presence of A23187 decreased the rate and extent of light scattering increase and its associated Cd2+ concentration change. However, A23187 had no effect on scattering changes already established by the electron transfer and Cd2+. These results suggest that the NADH linked electron transfer reaction may induce a Cd2+ uptake by the vesicles of corn root plasma membrane with inside-out orientation.
Forest Tree Reproduction: Influence of Air Pollutants

Sexual reproduction of forest trees is critically important for maintenance of genetic flexibility and the persistence of most species in natural forest communities. Reproductive strategies, however, are typically beset by a variety of “weak points,” and reproductive growth of many forest trees is, at best, irregular and quite unpredictable. Generally there is a very good correlation between tree vigor and the capacity for flowering and fruiting (Kozlowski, 1971). A variety of environmental constraints may reduce tree vigor and, in view of the fact that numerous potential points of interaction have been identified between air pollutants and reproductive elements (Figure 8-1), it has been hypothesized that air contaminants may impact forest ecosystems by influencing reproductive processes.
ENERGY FUNCTIONS FOR POLYGONAL KNOTS

We define a scale-invariant energy function for polygonal knots in ℜ3 based on the minimum distances between segments. The energy is bounded below by 2π. (minimum crossing number of the knot type). For each knot type, there exists an ideal number of segments, from which can be made an ideal conformation of the knot having minimum energy among all polygons realizing that knot type. Results leading to this include the following: The energy of an n-segment polygon is greater than n; if energy is bounded then ratios of edge lengths and angles are bounded away from zero; changing knot type requires passing an infinite energy barrier. We implement an algorithm, with the feature that preserving knot-type is guaranteed, to discover local energy-minimizing conformations for a given number of segments, and present some of these examples.
Signaling and expression for mitochondrial membrane proteins during left ventricular remodeling and contractile failure after myocardial infarction.

Abstract OBJECTIVES This study was conducted to test hypotheses stating that: 1) altered signaling for mitochondrial membrane proteins occurs during postinfarction remodeling, and 2) successful myocardial adaptation relates to promotion of specific mitochondrial membrane components. BACKGROUND Abnormalities in high-energy phosphate content and limitations in adenosine 5′-triphosphate (ATP) synthesis rate occur during the transition to contractile failure from compensatory remodeling after left ventricular infarction. The adenine nucleotide translocator (ANT) and F1-ATPase respectively regulate mitochondrial adenosine 5′-diphosphate (ADP)/ATP exchange and ADP-phosphorylation, which are key components of high-energy phosphate metabolism. METHODS Steady-state mRNA and protein expression for ANT isoform1 and the beta subunit of the F1-ATPase (betaF1) were analyzed in myocardium remote from the infarction zone eight weeks after left circumflex coronary artery ligation in pigs, demonstrating either successful left ventricular remodeling (LVR, n = 8) or congestive heart failure (CHF, n = 4) as determined by clinical and contractile performance parameters. RESULTS Substantial reductions in steady-state mRNA expression for ANT1 and betaF1 relative to normal (n = 8) occur in CHF, p CONCLUSIONS Maintained signaling for major mitochondrial membrane proteins occurs in association with successful remodeling and adaptation after infarction. Reduced expression of these proteins relates to limited ATP synthesis capacity and high energy phosphate kinetic abnormalities previously demonstrated in CHF. These findings imply that mitochondrial processes participate in myocardial remodeling after infarction.
The Origins of Strategic Practice: Product Diversification in the American Mutual Fund Industry

Although strategy research has systematically investigated the organizational antecedents and consequences of diversification behavior, little attention has been paid to the role of larger institutional forces. Institutional researchers have aptly demonstrated how broader cognitive, normative and regulative structures affect organizational practices, but have not focused a great deal on how institutional forces shape strategic action. Building on recent efforts to develop more sociological perspectives on strategy, we show how institutional changes driven by the professionalization project of money managers in the mutual fund industry facilitated the widespread use of product diversification as a routinely used organizational strategy. Implications for strategic management research are discussed.
On graceful degradation of microprocessors in presence of faults via resource banking

Reliability and manufacturability have emerged as dominant concerns for today's multi-billion transistor chips. In this paper, we investigate how to degrade a chip multiprocessor (CMP) gracefully in presence of faults, by keeping its architected functionality intact at the expense of some loss of performance. The proposed solution involves banking resources and functional units that allow partial shutdown to isolate faulty regions. Within a processor chip, resources can be classified into three broad classes, namely the large memory structures such as caches, TLB, register file, the small memory structures namely the reorder buffer, issue queue, load-store buffer etc. and the datapath and control logic. The large arrays are usually well protected by ECC. Recent research has suggested that large datapath units such as FPU and integer division units are good candidates for execution outsourcing to other working cores in CMP. In this paper, we focus on relatively small but critically important integer ALU unit and small array structures. Outsourcing ALU operations incur large performance penalty and small arrays are critical for control operations. The proposed solution is based on banking of array structures and execution units as well as reducing instruction fetch, issue and retire widths that allow individual bank(s) to be disabled for operation. Reduction in resource size diminishes performance but retains functionality. In this paper we present performance degradation data for shutting down one or more banks for various small array structures and ALU units. Simulation confirms gradual degradation with diminishing resource sizes. On average over all considered structures, performance loss of just 6% was observed for single bank failures.
Demonstrating Mediation (Ob’S Forgotten Topic) Through the Use of Role Playing:

Mediation is rapidly catching on in the United States as a technique for dispute resolution.However, the typical organizational behavior course includes, at most, only a brief introduction to the topic. This article provides a role-playing exercise that can be used to demonstrate mediation and supplement assigned reading on the subject. The situation presented involves a dispute between coworkers that has become violent. The students and/or professor play the roles of mediator and disputants in an attempt to resolve the conflict.
A module selection algorithm for high-level synthesis

A heuristic approach to the module selection problem in high-level synthesis is presented. In contrast to the common assumption made by most high-level synthesis systems, which consider one available resource for each type of operation, the authors assume that several resources with different delays and areas are available in a functional-block library. The proposed algorithm solves the scheduling, resource sharing, and module selection problems at the same time to achieve a circuit structure with near minimal area under a given overall latency constraint. Following the presentation of the algorithm, experimental results are reported. >
Are mitochondrial reactive oxygen species required for autophagy

Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H(2)O(2) was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient ρ° HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.
SOLID-STATE LIGHTING TECHNOLOGY PERSPECTIVE

Solid-State Lighting (SSL) uses inorganic light-emitting diodes (LEDs) and organic light-emitting diodes (OLEDs) to convert electricity into light for illumination. SSL has the potential for enormous energy savings and accompanying environmental benefits if its promise of 50% (or greater) energy efficiencies can be achieved. This report provides a broad summary of the technologies that underlie SSL. The applications for SSL and potential impact on U.S. and world-wide energy consumption, and impact on the human visual experience are discussed. The properties of visible light and different technical metrics to characterize its properties are summarized. The many factors contributing to the capital and operating costs for SSL and traditional lighting sources (incandescent, fluorescent, and high-intensity discharge lamps) are discussed, with extrapolations for future SSL goals. The technologies underlying LEDs and OLEDs are also described, including current and possible alternative future technologies and some of the present limitations.
Characterization of the Cardiac Overexpression of HSPB2 Reveals Mitochondrial and Myogenic Roles Supported by a Cardiac HspB2 Interactome.

Small Heat Shock Proteins (sHSPs) are molecular chaperones that transiently interact with other proteins, thereby assisting with quality control of proper protein folding and/or degradation. They are also recruited to protect cells from a variety of stresses in response to extreme heat, heavy metals, and oxidative-reductive stress. Although ten human sHSPs have been identified, their likely diverse biological functions remain an enigma in health and disease, and much less is known about non-redundant roles in selective cells and tissues. Herein, we set out to comprehensively characterize the cardiac-restricted Heat Shock Protein B-2 (HspB2), which exhibited ischemic cardioprotection in transgenic overexpressing mice including reduced infarct size and maintenance of ATP levels. Global yeast two-hybrid analysis using HspB2 (bait) and a human cardiac library (prey) coupled with co-immunoprecipitation studies for mitochondrial target validation revealed the first HspB2 “cardiac interactome” to contain many myofibril and mitochondrial-binding partners consistent with the overexpression phenotype. This interactome has been submitted to the Biological General Repository for Interaction Datasets (BioGRID). A related sHSP chaperone HspB5 had only partially overlapping binding partners, supporting specificity of the interactome as well as non-redundant roles reported for these sHSPs. Evidence that the cardiac yeast two-hybrid HspB2 interactome targets resident mitochondrial client proteins is consistent with the role of HspB2 in maintaining ATP levels and suggests new chaperone-dependent functions for metabolic homeostasis. One of the HspB2 targets, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), has reported roles in HspB2 associated phenotypes including cardiac ATP production, mitochondrial function, and apoptosis, and was validated as a potential client protein of HspB2 through chaperone assays. From the clientele and phenotypes identified herein, it is tempting to speculate that small molecule activators of HspB2 might be deployed to mitigate mitochondrial related diseases such as cardiomyopathy and neurodegenerative disease.
Mechanically stacked and monolithically integrated perovskite/silicon tandems and the challenges for high efficiency

With the advent of high-bandgap perovskites, the opportunity now exists to make tandems with perovskites on top of silicon. We have prototyped a mechanically stacked tandem, achieving 17.9% certified efficiency using a perovskite cell with a silver nanowire mesh electrode. We have also prototyped a monolithically integrated tandem on silicon, with the two subcells electronically connected by band-to-band tunneling in the silicon. The primary challenges to propelling perovskite/silicon tandems into a high-efficiency (>25%) regime are spiro-OMeTAD parasitic absorption, perovskite crystal quality, stability of a perovskite with a 1.8 eV bandgap, perovskite environmental stability, and transparent electrode quality and stability.
Stiff Person Syndrome in Childhood: SPS-C Recognition and Review (P6.017)

OBJECTIVE: Stiff person syndrome is especially rare in childhood,recognition of the disorder is difficult since it mimics other disorders with less incidence of other co-morbid conditions such as type 1 diabetes mellitus, thyroiditis, or paraneoplastic associations. We report the the features and review of SPS-C. BACKGOUND:Stiff person syndome has immunologic abnormalities. Antiglutamic acid decarboxylase antibodies ( antiGAD) are detected in 60-80% of patients ins serum or csf.Gabaergic pathways act as an inhibitory pathway in spinal interneurons coordinating motor function by inhibition of spontaneous discharges from spinal neurons. Impairment of gabaergic function leads to continuous firing of spinal motor neurons with stiffness and spasms. Antibodies to GABAA receptor associated protein (GABARAP) inhibit the GABAA receptor expression leading to receptor instability. DESIGN/METHODS: An 8 year old healthy female presented with 1 1/2 years of bilateral hamstring tightness,contractures, decreased truncal flexion and extension,scoliosis;evaluated by pediatric orthopedics and physical medicine with prior botulinum toxin injections plus stretching unsucessfully.Stiffness limited physical activity including ballet dancing.Family history negative for FSP.Exam revealed tight hamstrings,bilateral psoas limitation mild scoliosis as above. RESULTS:CBC Chem 20,CK,Carnitine, Acylcarnitine, pyruvate,lactate nl. Anti Gad 65 Antibodies Elevated in Serum; NCS; nl sensory,nl motor conduction;F,H nl;EMG:Increased Firing Units in Iliopsoas. MRI: nl.IVIG 2gm/kg instituted monthly x 2 courses: improvement in measurable degrees of flexion and extension noted.(Video) CONCLUSIONS: Childhood stiff person syndrome presents with uncommon/common orthopedic and physical findings.Differential diagnosis in childhood may be misleading or under recognized.Review of world literature demonstrates few cases; treatment with immunomodulatory therapy with/without benodiazepines demonstrates efficacy Disclosure: Dr. Lavenstein has nothing to disclose. Dr. Evans has nothing to disclose. Dr. Morozova has nothing to disclose.
Mechanism of Activation-Induced Downregulation of Mitofusin 2 in Human Peripheral Blood T Cells

Mitofusin 2 (Mfn2), a mitochondrial protein, was shown to have antiproliferative properties when overexpressed. In this article, we show that activation of resting human peripheral blood T cells caused downregulation of Mfn2 levels. This downregulation of Mfn2 was blocked by different inhibitors (mTOR inhibitor rapamycin, PI3K inhibitor LY294002, and Akt inhibitor A443654), producing cells that were arrested in the G0/G1 stage of the cell cycle. Furthermore, the activation-induced downregulation of Mfn2 preceded the entry of the cells into the cell cycle, suggesting that Mfn2 downregulation is a prerequisite for activated T cell entry into the cell cycle. Accordingly, small interfering RNA-mediated knockdown of Mfn2 resulted in increased T cell proliferation. Overexpression of constitutively active AKT resulted in the downregulation of Mfn2, which can be blocked by a proteasome inhibitor. Akt-mediated downregulation of Mfn2 was via the mTORC1 pathway because this downregulation was blocked by rapamycin, and overexpression of wild-type, but not kinase-dead mTOR, caused Mfn2 downregulation. Our data suggested that activation-induced reactive oxygen species production plays an important role in the downregulation of Mfn2. Collectively, our data suggest that the PI3K-AKT-mTOR pathway plays an important role in activation-induced downregulation of Mfn2 and subsequent proliferation of resting human T cells.
Discouraged by Peer Excellence Exposure to Exemplary Peer Performance Causes Quitting

People are exposed to exemplary peer performances often (and sometimes by design in interventions). In two studies, we showed that exposure to exemplary peer performances can undermine motivation and success by causing people to perceive that they cannot attain their peers’ high levels of performance. It also causes de-identification with the relevant domain. We examined such discouragement by peer excellence by exploiting the incidental exposure to peers’ abilities that occurs when students are asked to assess each other’s work. Study 1 was a natural experiment in a massive open online course that employed peer assessment (N = 5,740). Exposure to exemplary peer performances caused a large proportion of students to quit the course. Study 2 explored underlying psychological mechanisms in an online replication (N = 361). Discouragement by peer excellence has theoretical implications for work on social judgment, social comparison, and reference bias and has practical implications for interventions that induce social comparisons.
Electrophysiological Studies of Genetic Differences in Alcohol Action

Electrophysiological studies have demonstrated that ethanol has a wide variety of effects on the central nervous system (see Deitrich et al., 1989, for review). Even when these are examined at the cellular level (e.g., effects on ion channels), there are multiple substrates for ethanol action, many of which may have only marginal relevance to the behavioral effects of ethanol. To put many of these electrophysiological studies in perspective, it is important to have ways to distinguish functionally important responses from those that do not lead directly to changes in behavior and to relate specific electrophysiological responses to particular kinds of physiological and behavioral responses to ethanol.
Focal Presentations of Facioscapulohumeral Dystrophy (P04.082)

Objective: To identify additional focal presentations of FSHD. Background Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant myopathy, classically presenting with facial and shoulder girdle weakness. Recently, monomelic lower limb presentations of genetically confirmed FSHD have been reported. Design/Methods: A retrospective review of our academic center medical record database of all FSHD cases seen from 1996 to 2011. Of 139 cases identified, 8 had DNA confirmation with a focal presentation. Demographic and clinical data was abstracted. Results: There were 8 cases (4 male) with mean age at onset 39 years (range 18-63) and age at diagnosis 45 years (range 20-74). Presenting symptoms were monomelic lower limb atrophy (3); unilateral shoulder atrophy (3); and axial weakness (2). Examination showed isolated focal weakness in five. CK was normal or mildly elevated. All had a single family member with “weakness”. Co-existent unusual symptoms included dyspnea (2), S1 radicular pain with calf atrophy (2), peripheral neuropathy (1) and post-traumatic onset (1). EMG showed myopathic changes in all, apart from one case with severe denervation later followed by myopathic changes. DNA analysis showed D4Z4 EcoRI fragment size ranging from 20 to 37 kilobases. Conclusions: The clinical phenotype of FSHD should be expanded to include focal atrophy with myopathic EMG findings; axial weakness; or dyspnea at presentation. These cases are challenging due to lack of typical FSHD signs and coexistent symptoms suggestive of an alternative diagnosis. Disclosure: Dr. Hassan has nothing to disclose. Dr. Jones has nothing to disclose. Dr. Milone has nothing to disclose. Dr. Kumar has nothing to disclose.
Home Range Shape and Activity in Peromyscus leucopus

Shape of the home range and the distribution of activity within the home range were analyzed for 15 female and seven male Peromyscus leucopus. Ten of the 22 home ranges were circular. In all of the home ranges, the frequency with which animals were recorded in any unit of area in the home range decreased normally away from the center of activity. During the last 20 years, investigators of home range behavior in small mam- mals have been increasingly concerned with the way activity is distributed within home ranges. The statistical analysis of home range activity, an ap-
Oncogenic epidermal growth factor receptor mutants with tandem duplication: gene structure and effects on receptor function.

A number of epidermal growth factor receptor (EGFR) deletion mutants have been identified in gliomas, in which the EGFR gene is frequently amplified and rearranged. We have previously characterized the structure of a gene in A-172 human glioma cells that encodes a 190-kDa EGFR mutant with tandem duplication of the tyrosine kinase (TK) and calcium-mediated internalization (CAIN) domains. Here we describe a 185-kDa tandem duplication mutant (TDM) that is expressed in KE and A-1235 glioma cells, along with certain functional characteristics of the mutants. The corresponding transcripts in KE and A-1235 cells contain 1053 additional nucleotides representing an in-frame duplication of exons 18 through 25 which encode the entire TK region and a portion of the CAIN domain. As with duplication of the entire TK/CAIN region (exons 18-26) in A-172 cells, duplication of exons 18-25 is associated with a specific genomic rearrangement between flanking introns. Involved introns contain homology to recombination signal sequence (RSS) heptamers present in the V(D)J region of the T lymphocyte receptor gene. In defined medium, both oncogenic TDM are constitutively autophosphorylated and inefficiently downregulated. High-affinity binding is reduced in EGFR.TDM/18-26, although the t1/2 of receptor internalization is not prolonged.
Exposure estimate for FD&C colour additives for the US population

Dietary exposures to the seven food, drug, and cosmetic (FD&C) colour additives that are approved for general use in food in the United States were estimated for the US population (aged 2 years and older), children (aged 2-5 years) and teenage boys (aged 13-18 years) based on analytical levels of the FD&C colour additives in foods. Approximately 600 foods were chosen for analysis, based on a survey of product labels, for the levels of FD&C colour additives. Dietary exposure was estimated using both 2-day food consumption data from the combined 2007-10 National Health and Nutrition Examination Survey (NHANES) and 10-14-day food consumption data from the 2007-10 NPD Group, Inc. National Eating Trends - Nutrient Intake Database (NPD NET-NID). Dietary exposure was estimated at the mean and 90th percentile using three different exposure scenarios: low exposure, average exposure and high exposure, to account for the range in the amount of each FD&C colour additive for a given food. For all populations and all exposure scenarios, the highest cumulative eaters-only exposures in food were determined for FD&C Red No. 40, FD&C Yellow No. 5 and FD&C Yellow No. 6. In addition, the eaters-only exposure was estimated for individual food categories in order to determine which food categories contributed the most to the exposure for each FD&C colour additive. Breakfast Cereal, Juice Drinks, Soft Drinks, and Frozen Dairy Desserts/Sherbet (also referred to as Ice Cream, Frozen Yogurt, Sherbet (including Bars, Sticks, Sandwiches)) were the major contributing food categories to exposure for multiple FD&C colour additives for all three populations.
Determination of content of tacrolimus in polyanhydride nanoparticles by RP-HPLC

Objectives To establish an RP-HPLC method for the determination of tacrolimus in polyanhydride nanoparticles. Methods RP-HPLC method was adopted. Kromasil-ODS(250 mm×4.6 mm, 5 μm)column was used. The mobile phase consisted of acetonitrile-water(V:V=90:10). The flow rate was1.0 mL·min-1 and the detection wavelength was set at 216 nm. The column temperate was 60℃. The sample volume was 20 μL. The contents of tacrolimus in 3 batches polyanhydride nanoparticles were determined. Results Good linear correlation(r=0.999 9) between peak areas(A) and concentration(ρ) of tacrolimus ranging from 2.0 to 200.4 mg·L-1 was obtained, and the calibration curve was A=12 530 ρ-1 641.4. The lower limit of quantitation(LLOQ) for tacrolimus was 0.5 mg·L-1. The average recovery was 100.1%(n=9) and RSD was 1.18%. The contents of tacrolimus in 3 batches of polyanhydride nanoparticles were 866.3,876.3,878.3 mg·L-1, respectively. Conclusions RP-HPLC method established here was competent for the assay of tacrolimus in polyanhydride nanoparticles.
SLANTS: Sequential Adaptive Nonlinear Modeling of Time Series

We propose a method for adaptive nonlinear sequential modeling of time series data. Data are modeled as a nonlinear function of past values corrupted by noise, and the underlying nonlinear function is assumed to be approximately expandable in a spline basis. We cast the modeling of data as finding a good fit representation in the linear span of multidimensional spline basis, and use a variant of $l_1$ -penalty regularization in order to reduce the dimensionality of representation. Using adaptive filtering techniques, we design our online algorithm to automatically tune the underlying parameters based on the minimization of the regularized sequential prediction error. We demonstrate the generality and flexibility of the proposed approach on both synthetic and real-world datasets. Moreover, we analytically investigate the performance of our algorithm by obtaining both bounds on prediction errors and consistency in variable selection.
Cholecystokinin-induced satiety, a key gut servomechanism that is affected by the membrane microenvironment of this receptor

The gastrointestinal (GI) tract has a central role in nutritional homeostasis, as location for food ingestion, digestion and absorption, with the gut endocrine system responding to and regulating these events, as well as influencing appetite. One key GI hormone with the full spectrum of these activities is cholecystokinin (CCK), a peptide released from neuroendocrine I cells scattered through the proximal intestine in response to fat and protein, with effects to stimulate gall bladder contraction and pancreatic exocrine secretion, to regulate gastric emptying and intestinal transit, and to induce satiety. There has been interest in targeting the type 1 CCK receptor (CCK1R) for drug development to provide non-caloric satiation as an aid to dieting and weight loss; however, there have been concerns about CCK1R agonists related to side effects and potential trophic impact on the pancreas. A positive allosteric modulator (PAM) of CCK action at this receptor without intrinsic agonist activity could provide a safer and more effective approach to long-term administration. In addition, CCK1R stimulus-activity coupling has been shown to be negatively affected by excess membrane cholesterol, a condition described in the metabolic syndrome, thereby potentially interfering with an important servomechanism regulating appetite. A PAM targeting this receptor could also potentially correct the negative impact of cholesterol on CCK1R function. We will review the molecular basis for binding natural peptide agonist, binding and action of small molecules within the allosteric pocket, and the impact of cholesterol. Novel strategies for taking advantage of this receptor for the prevention and management of obesity will be reviewed.
Control of Normal and Pathologic Cognitive Functions through Neuromuscular Circuits

Everyday language is replete with a variety of mentalistic terms, such as dreams, hallucinations, ideas, images, thoughts, fears, anxieties, depressions, and emotions, that refer to functions of the “mind.” While these mentalistic (cognitive) terms vary, the subjective experiences to which they refer are all quite similar. The different terms merely indicate similar experiences that occur under various environmental and organismic conditions. For instance, night dreams, daydreams, and rational thought all differ, in part, because of the degree to which they are influenced by environmental input. During sleep, the images of our night dreams are chaotic since they are not directed by external reality. In contrast, problem-solving processes are more systematic and are directed to a greater extent by reference to cues in the external environment, such as in notes and calculations. While hallucinations are (mistakenly) ascribed to external factors, they are controlled by internal stimuli such as those generated by covert speech (McGuigan, 1966). Perceptual processes probably represent the extreme of cognitive events that are directly controlled by external stimuli. Even so, our awarenesses of what is happening in our immediate world constitute subjective experiences that themselves do not seem to differ from those of night dreams or hallucinations. They merely occur under different circumstances. It is not unusual, in fact, for us to confuse the content of night dreams with actual perceptions, not being sure whether something happened in our dreams or in our waking life.