cssi/SciSciGPT-SciSciNet huggingface dataset:
Cluster formation and diagnostic significance in psychiatric symptom evaluation

The tremendous variability in symptom constellations associated with specific psychiatric diagnoses makes the use of statistical techniques a virtual necessity in the rigid formulation of any symptom-disease model. In addition, the large number of symptoms associated with psychiatric disorders suggest that an electronic computer can be used to considerable advantage in certain aspects of psychiatric diagnosis, e.g., in the correlation analysis between symptoms, in the determination of quantitative criteria for diagnosis, and in the evaluation of the reliability of symptom assignment by different personnel.This paper reports on the results obtained from the analysis of data on 199 subjects collected by the Childrens Unit of the Eastern Pennsylvania Psychiatric Institute. The types of information available, the method of collection, and the statistical methodology and techniques are all discussed along with the results obtained using the tools of correlation analysis and simultaneous multivariant analysis of variants.
Managing Negative Feedback Effects Associated With Brand Extensions: The Impact of Alternative Branding Strategies

This article investigates the relation between alternative brand extension strategies and negative feedback effects of such extensions. We examine situations in which extensions may dilute family brand beliefs and create negative affect and how a sub-branding strategy (a new brand name in conjunction with a family brand name) may mitigate these effects. We find negative feedback effects when (a) extensions are perceived as belonging to a product category dissimilar from those associated with the family brand and (b) extension attribute information is inconsistent with image beliefs associated with the family brand. Relative to a direct extension, a sub-branding strategy mitigated these negative feedback effects and improved consumer evaluations of extensions belonging to dissimilar product categories.
Probability fold change: A robust computational approach for identifying differentially expressed gene lists

Identifying genes that are differentially expressed under different experimental conditions is a fundamental task in microarray studies. However, different ranking methods generate very different gene lists, and this could profoundly impact follow-up analyses and biological interpretation. Therefore, developing improved ranking methods are critical in microarray data analysis. We developed a new algorithm, the probabilistic fold change (PFC), which ranks genes based on a confidence interval estimate of fold change. We performed extensive testing using multiple benchmark data sources including the MicroArray Quality Control (MAQC) data sets. We corroborated our observations with MAQC data sets using qRT-PCR data sets and Latin square spike-in data sets. Along with PFC, we tested six other popular ranking algorithms including Mean Fold Change (FC), SAM, t-statistic (T), Bayesian-t (BAYT), Intensity-Conditional Fold Change (CFC), and Rank Product (RP). PFC achieved reproducibility and accuracy that are consistently among the best of the seven ranking algorithms while other ranking algorithms would show weakness in some cases. Contrary to common belief, our results demonstrated that statistical accuracy will not translate to biological reproducibility and therefore both quality aspects need to be evaluated.
Long-range tunable diode laser

A novel, simple tuning mechanism for single-mode, pseudo-external-cavity diode lasers has been developed. The model calculations predict that the laser can be tuned continuously by as much as 300 GHz in the vicinity of the chosen frequency without locking it to an external cavity. Experimentally, the continuous tuning range is approximately 120 GHz at constant current and temperature for the 7-cm-long pseudo-external cavity; this is several times more than previously reported. A turning wedge inside the laser cavity is used as the tuning element. The laser is based on a commercial laser diode chip, and a diffraction grating is used for feedback. The total tuning range depends on the laser diode type and can be up to 20 nm.
Bilingual education for all: Latino dual language learners with language disabilities

There has been a growing concern about how best to address the needs of dual language learners with language impairments. Most dual language programmes have been evaluated with children with typical language development (TLD) and as a result, very little is known about the effect of these programmes on children with language disabilities. The Vocabulary, Oral Language and Academic Readiness (VOLAR) programme was designed specifically for preschool dual language learners with language impairment. In the last five years, we have completed several federally funded projects aimed at evaluating the feasibility and efficacy of VOLAR testing more than 300 children over time. In the current study, we examined the effect of VOLAR when implemented by teachers within the preschool curriculum. Participants were 40 children receiving the programme and 34 children receiving the ‘business as usual’ preschool curriculum (control group). The comparisons were based on spontaneous language measures obtained at baseline and ...
Self-organizing primitives for automated shape composition

Motivated by the ability of living cells to form into specific shapes and structures, we present a new approach to shape modeling based on self-organizing primitives whose behaviors are derived via genetic programming. The key concept of our approach is that local interactions between the primitives direct them to come together into a macroscopic shape. The interactions of the primitives, called morphogenic primitives (MP), are based on the chemotaxis-driven aggregation behaviors exhibited by actual living cells. Here, cells emit a chemical into their environment. Each cell responds to the stimulus by moving in the direction of the gradient of the cumulative chemical field detected at its surface. MPs, though, do not attempt to completely mimic the behavior of real cells. The chemical fields are explicitly defined as mathematical functions and are not necessarily physically accurate. The explicit mathematical form of the chemical field functions are derived via genetic programming (GP), an evolutionary computing process that evolves a population of functions. A fitness measure, based on the shape that emerges from the chemical-field-driven aggregation, determines which functions will be passed along to later generations. This paper describes the cell interactions of MPs and the GP-based method used to define the chemical field functions needed to produce user- specified shapes from simple aggregating primitives.
Spreadsheet risk analysis using simulation

For many financial models implemented in electronic spreadsheets, input data values frequently are random variables because they are actually estimates of unknown quantities. As a result, the botto...
Targeted and Reversible Blood-Retinal Barrier Disruption via Focused Ultrasound and Microbubbles

The blood-retinal barrier (BRB) prevents most systemically-administered drugs from reaching the retina. This study investigated whether burst ultrasound applied with a circulating microbubble agent can disrupt the BRB, providing a noninvasive method for the targeted delivery of systemically administered drugs to the retina. To demonstrate the efficacy and reversibility of such a procedure, five overlapping targets around the optic nerve head were sonicated through the cornea and lens in 20 healthy male Sprague-Dawley rats using a 690 kHz focused ultrasound transducer. For BRB disruption, 10 ms bursts were applied at 1 Hz for 60 s with different peak rarefactional pressure amplitudes (0.81, 0.88 and 1.1 MPa). Each sonication was combined with an IV injection of a microbubble ultrasound contrast agent (Definity). To evaluate BRB disruption, an MRI contrast agent (Magnevist) was injected IV immediately after the last sonication, and serial T1-weighted MR images were acquired up to 30 minutes. MRI contrast enhancement into the vitreous humor near targeted area was observed for all tested pressure amplitudes, with more signal enhancement evident at the highest pressure amplitude. At 0.81 MPa, BRB disruption was not detected 3 h post sonication, after an additional MRI contrast injection. A day after sonication, the eyes were processed for histology of the retina. At the two lower exposure levels (0.81 and 0.88 MPa), most of the sonicated regions were indistinguishable from the control eyes, although a few tiny clusters of extravasated erythrocytes (petechaie) were observed. More severe retinal damage was observed at 1.1 MPa. These results demonstrate that focused ultrasound and microbubbles can offer a noninvasive and targeted means to transiently disrupt the BRB for ocular drug delivery.
On the convergence time of distributed quantized averaging algorithms

We come up with novel quantized averaging algorithms on synchronous and asynchronous communication networks with fixed, switching and random topologies. The implementation of these algorithms is subject to the realistic constraint that the communication rate, the memory capacities of agents and the computation precision are finite. The focus of this paper is on the study of the convergence time of the proposed quantized averaging algorithms. By appealing to random walks on graphs, we derive polynomial bounds on the expected convergence time of all the algorithms presented.
Optical Flow for Verification

Abstract Modern numerical weather prediction (NWP) models produce forecasts that are gridded spatial fields. Digital images can also be viewed as gridded spatial fields, and as such, techniques from image analysis can be employed to address the problem of verification of NWP forecasts. One technique for estimating how images change temporally is called optical flow, where it is assumed that temporal changes in images (e.g., in a video) can be represented as a fluid flowing in some manner. Multiple realizations of the general idea have already been employed in verification problems as well as in data assimilation. Here, a specific formulation of optical flow, called Lucas–Kanade, is reviewed and generalized as a tool for estimating three components of forecast error: intensity and two components of displacement, direction and distance. The method is illustrated first on simulated data, and then on a 418-day series of 24-h forecasts of sea level pressure from one member [the Global Forecast System (GFS)–fif...
Costs of elaborate weapons in a rhinoceros beetle: how difficult is it to fly with a big horn?

The giant horns of rhinoceros beetles exemplify the extreme morphologies that can result from sexual selection. Ornaments and weapons help males obtain mates but may also impose fitness costs. Intuitively, exaggerated sexually selected traits should impair locomotion, yet compensatory morphologies often make it difficult to detect locomotor costs. Here, we tested whether horns of the rhinoceros beetle Trypoxylus dichotomus impair flight and whether males compensate by developing larger wings or flight muscles. Contrary to our expectation that horns are costly for flight, males flew as fast as females, and among males, horn length was not correlated with flight speed or distance flown. We found some evidence for compensations in the male flight apparatus; males had relatively larger wings and flight muscles than females, and males with long horns for their body size had larger wings than males with relatively short horns. Flight muscle mass, however, was unaffected by horn length. We conclude that T. dichotomus horns may have been costly in the past and led to morphological compensations in wing and flight muscle size, but they do not currently impose significant flight costs. Fitness costs are a central tenet of sexual selection theory, and the large horns of rhinoceros beetles are expected to impose particularly strong costs on locomotion. Given our finding that T. dichotomus horns are surprisingly easy to carry, future work will be needed to identify the potential costs that have been important in shaping the evolution of elaborate horn morphologies. Key words: compensations, costs, flight, horns, rhinoceros beetles, sexual selection. [Behav Ecol]
Just Say No: How Are Visual Searches Terminated When There Is No Target Present?

How should a visual search task be terminated when no target is found? Such searches could end after a serial search through all items, but blank trials in many tasks are terminated too quickly for that to be plausible. This paper proposes a solution based on Wolfe's (1994) Guided Search model. The probability that each item is a target is computed in parallel based on items' differences from each other and their similarity to the desired target. This probability is expressed as an activation. Activations are examined in decreasing order until the target is found or until an activation threshold is reached. This threshold is set adaptively by the observer--more conservative following misses, more liberal following successful trials. In addition, observers guess on some trials. The probability of a guess increases as trial duration increases. The model successfully explains blank trial performance. Specific predictions are tested by experiments.
Adaptive perspectives: case-based reasoning with TYRO, the graphic designer's apprentice

The basic tool set for a constraint-based graphic designers assistant called TYRO has been expanded to include editors that allow a graphic designer to take a 'program by designing' approach to building a case library of basic design processes. Adaptation and augmentation of the case library takes place as trial layouts reveal failure conditions. Rule objects are formed as combinations of condition objects which trap the failure states and present cases that have been modified to avoid the problem state. The resulting layout is a network of constrained graphical objects capable of being reused in a range of similar contexts. The design environment is described. Building and editing cases are discussed. >
The Role of Novel Anticoagulants in the Management of Venous Thromboembolic Disease

The introduction of oral direct coagulation factor inhibitors is dramatically changing the landscape of anticoagulation delivery in patients experiencing or at risk for a thrombotic event. These novel anticoagulants can be particularly attractive for health care providers, as they deliver therapeutic anticoagulation at a fixed dose, require no routine coagulation monitoring, and have few drug interactions and no food restrictions. Herein, we will review the role of these novel anticoagulants for acute venous thromboembolism treatment, primary and secondary venous thromboembolism prevention, and management during the periprocedural period.
Stage IB or IIA-B carcinoma of the intact uterine cervix ≥ 6 cm in diameter: Is adjuvant extrafascial hysterectomy beneficial?

This is an analysis of 150 patients with Stage IB or IIA-B carcinoma of the intact uterine cervix greater than or equal to 6 cm in diameter treated with irradiation alone (75 patients) or irradiation followed by surgery (75 patients) at the University of Florida between October 1964 and June 1983. Minimum follow-up in this series was 5 years. There was no significant difference in the distribution of prognostic factors between the two treatment groups. The 5-year local control rate was 74% with irradiation alone and 76% with irradiation and surgery. The 5-year survival rates for irradiation alone versus irradiation plus surgery were as follows: cause specific, 62% and 55%, and absolute, 54% and 52%. The proportion of patients who developed treatment complications necessitating hospitalization or a second operation was 4/75 (5%) after irradiation alone and 12/75 (16%) after irradiation and surgery. The authors conclude that the routine use of adjuvant extrafascial hysterectomy is not warranted in this patient population.
Regulation of mammalian ciliary beating.

Recent advances in our understanding of the structure-function relationship of motile cilia with the 9 + 2 microtubular arrangement have helped explain some of the mechanisms of ciliary beat regulation by intracellular second messengers. These second messengers include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) as well as calcium and pH. cAMP activates protein kinase A (PKA), which is localized to the axoneme. The cAMP-dependent phosphorylation of PKA’s main target, originally described as p29 in Paramecium, seems to increase ciliary beat frequency (CBF) directly. The mechanism by which cGMP increases CBF is less well defined but involves protein kinase G and possibly PKA. Protein kinase C inhibits ciliary beating. The regulation mechanisms of CBF by calcium remain somewhat controversial, favoring an immediate, direct action of calcium on ciliary beating and a second cyclic nucleotide–dependent phase. Finally, intracellular pH likely affects CBF through direct influences on dynein arms.
Differential enhancement of Cry2A versus Cry11A yields in Bacillus thuringiensis by use of the cry3A STAB mRNA sequence.

Previously we demonstrated that the yield of Cry3A (70 kDa) can be increased as much as 10-fold when cry3A including its upstream STAB-SD mRNA stabilizing sequence is expressed in Bacillus thuringiensis under the control of cyt1A promoters. To determine whether the cyt1A promoters/STAB-SD combination (cyt1AP/STAB) has broader applicability, we used it to synthesize two other Cry endotoxins in the 70-kDa mass range, Cry2A and Cry11A. Combination of cyt1AP/STAB with orfs 2 and 3 of the cry2A operon yielded about 4.4-fold the amount of Cry2A obtained with the wild-type cry2A operon. The yield of Cry11A obtained with a construct that contained the cyt1AP/STAB, cry11A and the 20-kDa protein gene was 1.3-fold the amount obtained with a construct similar to the wild-type operon. These results demonstrate that the cyt1AP/STAB combination can enhance synthesis of different Cry proteins significantly, but that the level of enhancement varies with the specific protein synthesized.
PROSODY, SYNTAX AND PARSIN

We describe the modification of a grammar to take advantage of prosodic information provided by a speech recognition system. This initial study is limited to the use of relative duration of phonetic segments in the assignment of syntactic structure, specifically in ruling out alternative parses in otherwise ambiguous sentences. Taking advantage of prosodic information in parsing can make a spoken language system more accurate and more efficient, if prosodic-syntactic mismatches, or unlikely matches, can be pruned. We know of no other work that has succeeded in automatically extracting speech information and using it in a parser to rule out extraneous parses.
Jewish Religiosity and Political Attitudes in the United States and Israel

Does religious commitment have a common political impact across national frontiers? To date, that question has been explored empirically only for Roman Catholics, who might be expected to behave similarly because of centralizing resources in their tradition. This article explores the extent of transnational political attitudes among Jews in the United States and Israel, two groups with less centralized authority structures and radically different religious situations. Parallel surveys of Jews in the United States and Israel, analyzed by OLS regression with the slope dummy approach, indicate that Jewish religiosity has a common influence on most political issues but often has much sharper effects in one society than the other. Given our expectation that Jews would exhibit lower levels of transnational similarity than Roman Catholics, the findings reinforce scholars who perceive religion as a potent transnational political factor.
Photosynthetic and growth responses of Zea mays L and four weed species following post‐emergence treatments with mesotrione and atrazine

We compared photosynthesis and growth of Zea mays L (corn) and four weed species, Setaria viridis (L) Beauv (green foxtail), Echinochloa crus-galli (L) Beauv (barnyardgrass), Abutilon theophrasti Medic (velvetleaf), and Amaranthus retroflexus L (redroot pigweed), following foliar applications with atrazine, mesotrione, or a combination of atrazine and mesotrione in two greenhouse experiments. Plant responses to the three herbicide treatments were compared with responses of untreated plants (control). Photosynthesis on day 14 and dry mass of Zm ayswas not reduced by any of the herbicide treatments. Photosynthesis and dry mass of E crus-galli, A retroflexus and A theophrasti were significantly reduced by mesotrione and atrazine alone and in combination. Photosynthesis on day 14 and dry mass of large S viridis plants were not suppressed by either herbicide applied alone. The mesotrione plus atrazine treatment was the most effective treatment for grass weed control because plants did not regain photosynthetic capacity and had significantly lower dry mass. Shoot dry mass of broadleaf weeds was significantly reduced by all three herbicide treatments, except for A retroflexus treated with mesotrione alone.  2004 Society of Chemical Industry
Social spaces, transnational immigrant communities, and the politics of incorporation

Transnational social spaces exist both `from above' and, in the case of contemporary immigrants, `from below'. This article is intended to offer conceptual clarity to current research agendas conce...
Active renin and angiotensinogen in cardiac interstitial fluid after myocardial infarction

The renin-angiotensin system promotes cardiac hypertrophy after myocardial infarction. The purpose of this study was to measure renin and angiotensinogen in plasma and myocardium 10 days after myoc...
A SPATIALLY EXPLICIT MODEL, DERIVED FROM DEMOGRAPHIC VARIABLES, TO PREDICT ATTITUDES TOWARD BLACK BEAR RESTORATION

Abstract Understanding human attitudes often is vital to the success of restoration projects, especially those involving controversial species such as carnivores. Support for restoration activities may differ depending on residence location of the respondent; thus, understanding the spatial distribution of attitudes is important when selecting suitable restoration sites. We used black bear (Ursus americanus) restoration as an example of how to calculate and use a spatially explicit model of human attitudes based on demographic variables to select restoration sites in Mississippi, USA. We sampled 2 populations (5,975 landowners adjacent to 10 public land areas and a random sample of 490 Mississippians) to determine human attitudes toward black bear reintroduction in Mississippi. We chose a series of reintroduction and demographic questions to develop 2 logistic regression models to predict support for reintroduction, and we validated the models. One model was developed on all demographic variables (how man...
Control under clock offsets and actuator saturation

This paper studies the stability analysis and the stabilization problem for systems with asynchronous sensors and controllers, and actuators subject to saturation. We consider systems with parameter uncertainties caused by clock offsets. By using a polytopic overapproximation, we investigate how large clock offsets affect stability. In addition, we employ a sector characterization approach to address actuator saturation. We see from a numerical study that the range of allowable clock offset bounds drops if the saturation limit becomes smaller than a certain value.
TRANSNATIONAL POLITICAL PROCESSES AND CONTENTION AGAINST THE GLOBAL ECONOMY

Research on transnational contention has largely overlooked how global economic negotiations and arrangements shape transnational dissent. In this article I examine how neoliberal economic arrangements structure transnational activism. I first describe neoliberalism as an important facet of economic globalization, and then suggest why neoliberal accords have become lightning rods for protest. I propose that transnational opposition to neoliberalism is supported by the growth of transnational mobilizing structures, as well as by the internationalization of political opportunities. For illustration, I draw upon qualitative research on the tactics of Canadian activists over more than fifteen years of sustained protest against trade and investment accords. I conclude by affirming that the link between international political processes and the rise of transnational social movement organizations and coalitions will mean significant transnational mobilizations in the future. I also caution against drawing premature conclusions about the long-term durability of these transnational alliances. Further research on recent anti-WTO and IMF protests will give a fuller picture of the roles played by these transnational alliances.
Pneumothorax following acupuncture.

Acupuncture is an alternative medicine procedure that in recent years has achieved immense popularity with the public.1,2 Several authors have voiced concerns, however, about the lack of regulations for acupuncture and the possibility of serious complications following the procedure.3-6 We hereby report a case of unilateral pneumothorax occurring as a complication of acupuncture treatment.
The role of evolved predispositions in cultural evolution: Or, Human Sociobiology meets Pascal's Wager

Abstract Much human behavior affected by culturally transmitted ideas—e.g., religious sentiments— does not appear to make adaptive sense. Whether sound sociobiological explanations can or cannot be given to such behavior is at the heart of debates between human sociobiologists and their critics. We argue that the debate has been miscast as a clash between mutually exclusive hypotheses, when in theory and probably in fact there are many cases that mix elements of both. When culture, using Darwinian methods, is modeled as a system of inheritance that coevolves with genes, it exhibits both adaptive properties and a series processes that give rise to maladaptive variation. On the one hand, there is every reason to expect that cultural evolution is substantially shaped by evolved, genetically transmitted predispositions and that these predispositions often result in highly adaptive behavior. However, some kinds of beliefs are weakly affected by evolved predispositions and can have strong effects on behavior. For example, religious sentiments are carefully constructed to be difficult to challenge on the basis of empirical experience. Beliefs in rewards or punishments in an afterlife can substantially affect the behavior of people with quite utilitarian evolved goals. Once beliefs arise that are difficult to judge using evolved predispositions, processes such as group selection on cultural variation can be relatively strong. Patterns of behavior that could not be predicted without taking account of the evolutionary properties of culture can arise as a result of such "nonsociobiological" forces. Four coevolutionary scenarios capture much of the rich behavior that is possible when genetic and cultural evolution interact: 1) Culture may be kept on a "leash" by evolved predispositions, as classical sociobiological arguments would have it; 2) the tables may be turned, and genes may be leashed by the evolution of cultural norms that affect mate choice (we present a simple model of this process); 3) harmful cultural elements with an ability to attract imitators may arise, leading to a host-pathogen type of coevolution between genes and culture; and 4) genes and culture may evolve like a system of obligate mutualists. We speculate that the last scenario is the most generally important, but that the others are common. We view the application of population genetical methodology to cultural evolution as a friendly amendment to human sociobiology, but one that is essential to a complete Darwinian theory of human behavior.
On the Viability of Galilean Relationalism

ABSTRACTI explore the viability of a Galilean relational theory of space-time—a theory that includes a three-place collinearity relation among its stock of basic relations. Two formal results are e...
Report of two paediatric cases of central line infections caused by species of the genus Kocuria

Introduction: Species of the genus Kocuria are Gram-positive cocci of the family Micrococcacceae that are ubiquitous in the environment and part of the normal skin and oral flora in humans. A paucity of cases have been reported of Kocuria as human pathogens and there are currently no evidence-based guidelines for managing these uncommon infections. Case presentation: We present two paediatric cases of central line infections with species of the genus Kocuria that required line removal despite antimicrobial therapy. Conclusion: Species of the genus Kocuria are uncommon human pathogens that have rarely been reported to cause opportunistic infections in both adult and paediatric populations. The cases presented here add to the growing body of literature documenting the pathogenicity of these organisms and the possible need for line removal to achieve clinical cure in central line-associated bacteraemia caused by species of the genus Kocuria.
Antiestrogenic action of high-dose clomiphene in primates pituitary augmentation but with ovarian attenuation.

Since the dominant follicle is selected by days 5 to 7 of the menstrual cycle, we assessed the differential effects of high-dose clomiphene (25mg daily) by giving 5-day courses either before (days 1 to 5), during (days 5 to 9), or after (days 9 to 13) emergence of the selected dominant follicle in monkeys. Peripheral sera were obtained daily and assayed for follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 β −estradiol (E 2 ), and progesterone (P); serial laparoscopics were performed. Rather than enhancement of gonadotropin-dependent folliculogenesis during clomiphine treatment cycles, ovulation was delayed in 18 of 18 treatment cycles. Interestingly, the interval from treatment to next ovulation lengthened when clomiphene was given in the late follicular phase. Consistently, the clomiphene treatment cycles were characterized by a marked decline of the serum E 2 during the 5 days of therapy, despite concurrent elevations of pituitary gonadotropins in circulation, especially FSH. These data suggest that a direct antiestrogenic effect of clomiphene imparted ovarian refractoriness to the prevailing, even enhanced, gonadotropin levels. The vulnerability of follicular maturation to these attenuating effects of clomiphene was greatest in the late follicular phase, well after the dominant follicle had been selected. Even after this clomiphene-induced ovarian hiatus and eventual resumption of new follicle growth, the initial apparent ovulation led to latent, severe corpus luteum insufficiency.
Stretch and Laceration Nerve Injuries

Abstract Stretch and laceration injuries of the peripheral nerves represent the most common modalities of nerve injury in trauma. These injuries feature unique biomechanical pathophysiology that stems from the microanatomy of the peripheral nerve. These biomechanical properties determine the treatment and outcomes of stretch and laceration injury. The surgical treatment of these injuries is predicated on the modality of injury. Lacerations require surgical repair in the acute or subacute phase. Stretch injuries represent lesions in continuity that may recover spontaneously or require surgical intervention.
The Structure of the Relaxed Thick Filaments from Lethocerus Asynchronous Flight Muscle

The structure of relaxed muscle thick filaments is a key element for understanding muscle physiology and the effect of mutations on muscle function. Previous thick filament structures by 3D-EM resolved individual myosin heads and revealed an interacting head motif (IHM) first identified in smooth muscle myosin. A later model based on X-ray fiber diffraction of Lethocerus flight muscle showed a different, intermolecular, interaction between myosin heads. Almost nothing is known about the structure of the long α-helical coiled-coil myosin rod in thick filaments. Here we show the relaxed structure of Lethocerus thick filaments by cryoEM at sufficient resolution to reveal the relative placement of individual myosin heads at ∼20 A resolution, as well as the myosin rod α-helices which can be traced from the head-rod junction all the way to their C-termini at a resolution of 5.5A. In contrast to the model suggested by X-ray diffraction, we find an IHM somewhat different from IHMs of other relaxed thick filaments. The myosin rod follows a tortuous path from the outside of the thick filament to the inside across a region we call the myosin rod annulus. The pitch of the rod coiled-coil is variable with long pitch regions in the approximate location of skip residues. Surprisingly, threading their way among the forest of myosin rods are four copies, matching the 4-fold symmetry of the filament, of four polypeptide chains. Their presence in this location could modulate the mechanical properties of the myosin backbone. Our results demonstrate the ubiquity of the IHM in relaxed myosin filaments but with a variation that might shed light on the mechanism of stretch activation and shortening deactivation. Supported by NIH and AHA.
In Vivo Imaging of Autoimmune Disease in Model Systems

Autoimmune diseases are characterized by infiltration of the target tissue with specific immune cells that ultimately leads to the destruction of normal tissue and the associated disease. There is a need for imaging tools that allow the monitoring of ongoing inflammatory disease as well as the response to therapy. We discuss new magnetic resonance imaging-based technologies that have been used to monitor inflammation and disease progression in animal models of type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. Therapeutic strategies for these diseases include the transfer of immune cells, such as dendritic cells, with the aim of preventing or halting the disease course. We discuss several new MRI labeling techniques developed to allow tracking of immune cells in vivo. These include direct ex vivo labeling techniques as well as the genetic modification of cells to allow them to produce their own contrast agents. This is an area of intense recent research and can be expanded to other conditions such as cancer.
Combined Inhibition of CDK and PI3K/Akt Pathways Induces Apoptosis of Mantle Cell Lymphoma.

Abstract Mantle cell lymphoma (MCL) arises from the neoplastic transformation of naive B cells in the mantle zone of the B cell follicle. It is an aggressive and incurable B cell neoplasm. It accounts for 5% to 8% of non-Hodgkin's lymphomas. Patients with MCL respond initially to chemotherapy but ultimately relapse. Mean survival time is only three to four years. Thus, the need for new treatments that effectively combat MCL is obvious and imperative. Defects in cell cycle regulation and apoptosis are primary events in MCL. It is characterized by the presence of a chromosomal translocation t (11:14)(q13:q32), which results in deregulated cyclin D1 expression. Cyclin D1 overexpression in MCL is thought to play a major role in lymphomagenesis, although the precise mechanisms by which tumor formation and progression occur are not fully understood. Constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis and survival of MCL. Activated AKT was found in cultured MCLs as well as in 100% of aggressive-blastoid variants of MCL tumors, compared to 30% of typical MCLs. Towards the search for novel therapies for MCLs, we examined the potential of roscovitine (rosc) or flavopiridol (flav), inhibitors of cyclin dependent kinase (CDK), as a single agent or in combination with LY294002 (LY), a PI3K/Akt inhibitor, in inducing apoptosis of various MCL lines as well as in MCL patient samples. CDK inhibitors modestly increased the percentage of apoptotic cells (∼30%), whereas LY had no effect. However, when added in combination, rosc/LY or flav/LY induced apoptosis in more than 70% of cells. In an effort to understand the mechanism of apoptosis, we identified three targets: cyclin D1, the anti-apoptotic proteins myeloid cell leukemia-1 (Mcl-1) and X-linked Inhibitor of Apoptosis (XIAP). CDK inhibitors eliminated Mcl-1 expression, slightly reduced XIAP abundance and had very little effect on abundance of cyclin D1. Conversely, LY reduced cyclin D1 expression and slightly reduced the abundance of Mcl-1 and XIAP. A larger decrease in XIAP abundance is seen in cultures treated with a combination of rosc/LY or flav/LY. On the basis of these findings, we suggest that agents that target Mcl-1, XIAP and cyclin D1 will be most effective in inducing apoptosis of human MCLs.
Endoscopic Spine Surgery: Distance Patients Will Travel for Minimally Invasive Spine Surgery.

Background Transforaminal lumbar endoscopic discectomy is a minimally invasive spine surgery procedure performed principally for the treatment of lumbar herniated discs. Endoscopic spine surgeons around the world have noted how far patients will travel to undergo this minimally invasive spine surgery, but the actual distance patients travel has never been investigated. Objective We present here our analysis of how far patients will travel for endoscopic spine surgery by studying the referral patterns of patients to 3 centers in 3 different countries. Study design Retrospective chart review of de-identified patient data was performed to analyze the distance patients travel for spine surgery. Methods Patient demographic data was analyzed for patients undergoing transforaminal lumbar endoscopic discectomy procedures over the same 8 month period in 2015 at centers in the United States (U.S.), Netherlands, and Germany. Results Travel distances for patients were determined for 327 patients. The average distance traveled for the U.S. center was 91 miles, the Dutch center was 287 miles, and the German center was 103 miles. For the U.S. center 16% of patients traveled out of state for surgery and for the European centers combined, 4% of patients traveled out of the country for surgery. Limitations The period of data analyzed was less than one year and the data collected was analyzed retrospectively. Conclusions Quality metrics in health care tend to be focused on how health care is delivered. Another health care metric that focuses more on what patients desire is presented here: how far patients will travel for innovative spine care.Key words: Endoscopic spine surgery, transforaminal, minimally invasive, travel, lumbar disc herniation.
Core Labour Standards and Globalisation

The ILO Declaration on Fundamental Principles and Rights at Work and its follow-up (henceforth the Declaration) was adopted by the ILO Conference in 1998.
Determinants of gait stability while walking on a treadmill: A machine learning approach

Abstract Dynamic balance in human locomotion can be assessed through the local dynamic stability (LDS) method. Whereas gait LDS has been used successfully in many settings and applications, little is known about its sensitivity to individual characteristics of healthy adults. Therefore, we reanalyzed a large dataset of accelerometric data measured for 100 healthy adults from 20 to 70 years of age performing 10 min treadmill walking. We sought to assess the extent to which the variations of age, body mass and height, sex, and preferred walking speed (PWS) could influence gait LDS. The random forest (RF) and multiple adaptive regression splines (MARS) algorithms were selected for their good bias-variance tradeoff and their capabilities to handle nonlinear associations. First, through variable importance measure (VIM), we used RF to evaluate which individual characteristics had the highest influence on gait LDS. Second, we used MARS to detect potential interactions among individual characteristics that may influence LDS. The VIM and MARS results indicated that PWS and age correlated with LDS, whereas no associations were found for sex, body height, and body mass. Further, the MARS model detected an age by PWS interaction: on one hand, at high PWS, gait stability is constant across age while, on the other hand, at low PWS, gait instability increases substantially with age. We conclude that it is advisable to consider the participants’ age as well as their PWS to avoid potential biases in evaluating dynamic balance through LDS.
Reducing tobacco-related harm: FDA’s proposed product standard for smokeless tobacco

This Special Communication discusses the Food and Drug Administration9s (FDA9s) proposed rule that would limit N -nitrosonornicotine (NNN) levels in smokeless tobacco products. It argues that finalising and implementing this first 9product standard9 would mark a significant step forward in the FDA9s efforts to reduce tobacco-related harms.
Centella asiatica Attenuates Mitochondrial Dysfunction and Oxidative Stress in Aβ-Exposed Hippocampal Neurons

Centella asiatica has been used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) protects against the deleterious effects of amyloid-β (Aβ) in neuroblastoma cells and attenuates Aβ-induced cognitive deficits in mice. Yet, the neuroprotective mechanism of CAW has yet to be thoroughly explored in neurons from these animals. This study investigates the effects of CAW on neuronal metabolism and oxidative stress in isolated Aβ-expressing neurons. Hippocampal neurons from amyloid precursor protein overexpressing Tg2576 mice and wild-type (WT) littermates were treated with CAW. In both genotypes, CAW increased the expression of antioxidant response genes which attenuated the Aβ-induced elevations in reactive oxygen species (ROS) and lipid peroxidation in Tg2576 neurons. CAW also improved mitochondrial function in both genotypes and increased the expression of electron transport chain enzymes and mitochondrial labeling, suggesting an increase in mitochondrial content. These data show that CAW protects against mitochondrial dysfunction and oxidative stress in Aβ-exposed hippocampal neurons which could contribute to the beneficial effects of the extract observed in vivo. Since CAW also improved mitochondrial function in the absence of Aβ, these results suggest a broader utility for other conditions where neuronal mitochondrial dysfunction occurs.
Chirurgie der Aortenklappe

Die Chirurgie der Aortenklappe betrifft alle Altersgruppen; sie umspannt ein breites Spektrum der pathologischen Anatomie und chirurgischen Technik. In diesem Kapitel stellen wir die Valvotomie und den Ersatz der Aortenklappe dar; auserdem besprechen wir kurz die chirurgische Behandlung anderer Obstruktionsformen der linksventrikularen Ausflusbahn.
Weight discrimination in the american workplace: Ethical issues and analysis

Research providing consistent evidence of pervasive discrimination against overweight job applicants and employees in the American workplace raises important questions for organizational stakeholders. To what extent is the disparate treatment of job applicants or employees based on their weight ethically justified? Are there aspects of weight discrimination that make it more acceptable than discrimination based on other characteristics, such as race or gender? What operational steps can employers take to address concerns regarding the ethical treatment of overweight individuals in the workplace? This article investigates these and related questions. Its purpose is to provide information and analysis that will assist organizations in formulating ethical responses to a widespread phenomenon: weight discrimination in the workplace. Although its focus is the American workplace, the proposed employer ethical obligations and the practical guidance that is provided are viewed as generalizing across countries and cultures.
Neuromodulatory Transmitters in Sensory Processing and Plasticity in the Primary Visual Cortex

In this chapter we discuss the roles of four neurotransmitter systems, noradrenaline (NA), acetylcholine (ACh), serotonin (5-HT) and dopamine (DA) in processing at the level of the primary visual cortex (V1), and review their participation in experience-dependent plasticity paradigms. For each of these neuromodulators, two parts are presented: First we discuss the anatomical distribution of neuromodulatory fibers and terminals, and post-synaptic receptors in V1. Second, we review the effects of altering neuromodulatory transmission to receptive field (RF) properties, sensory processing and experience-dependent plasticity, with an emphasis on plasticity of ocular dominance column paradigms. Postsynaptic receptor subtypes determine which of several modulatory signal transduction systems will be activated, thus influencing how a given transmitter will act: with excitatory effects, inhibitory effects, or both. As discussed below, neuromodulatory transmitters may contribute to plasticity by increasing the signal-to-noise ratio of cell populations, changing the threshold for activity-dependent synaptic modifications, and gating behavioral states. Receptor classes and even receptor subtypes generally show distinct laminar distributions within the visual cortex that vary across species. The distribution patterns and densities of afferent inputs also differ across cortical layers, and in a species-specific manner. Whenever possible, and wherever relevant to the issues discussed, we outline inter-species differences in both fiber and receptor distributions. Knowledge of the anatomical-functional organization of these neurotransmitter systems allows for a more complete understanding of visual
Understanding the Origins of Campaign Strategies

Just as theories of American voting behavior were largely developed with indifference to campaigns, research on campaign strategy has often failed to fully incorporate voters. In this paper, I develop a more nuanced understanding of campaigns that accounts for the way in which candidates learn from previous elections when crafting their strategies. Using campaign advertising data from the 2000 presidential election, I demonstrate that candidates' decisions to target African Americans, Hispanics, the elderly, union households, and members of the religious right are based on the influence those groups had exerted in determining recent statewide outcomes in the 2000 presidential election. I conclude by discussing the important role that candidate learning plays in the development of campaign strategies by producing an interdependency between candidates and voters that serves to represent the interests of some groups while leaving other voters absent from the campaign.
On the Origin of High Couplings Two-Dimensional Modes of Vibration in Aluminum Nitride Plates

This work discusses, for the first time through the Lamb-Wave theory, the origin of the recently reported high electromechanical coupling coefficient values $(k_{t}^{2})$ in two-dimensional modes of vibration excited in Aluminum Nitride (AIN) plates. In particular, we investigate the operation of the recently demonstrated Two-Dimensional Mode Resonators (2DMRs) and Cross-Sectional Lame Mode Resonators (CLMRs). Precisely, we show how 2DMRs consist of dispersive $\mathbf{s}_{1}$ -mode resonators. In contrast, we demonstrate that CLMRs consist of multi-modal resonators relying on both the $\mathbf{S}_{0^{-}}$ and $\mathbf{S}_{1}$ -modes of vibration by operating at higher resonance frequencies, for the $\mathbf{S}_{0}$ -mode, than the dilatational frequency relative to the $\mathbf{S}_{1}$ -mode.