Miracle-dz/UniFAR-FTUs huggingface dataset:
Leucine Zipper Domain Targets cAMP-dependent Protein Kinase to Mammalian BK Channels*

Large conductance, calcium- and voltage-activated potassium (BK) channels control excitability in many tissues and are regulated by several protein kinases and phosphatases that remain associated with the channels in cell-free patches of membrane. Here, we report the identification of a highly conserved, non-canonical, leucine zipper (LZ1) in the C terminus of mammalian BK channels that is required for cAMP-dependent protein kinase (PKA) to associate with the channel and regulate its activity. A synthetic polypeptide encompassing the central d position leucine residues in LZ1 blocks the regulation of recombinant mouse BK channels by endogenous PKA in HEK293 cells. In contrast, neither an alanine-substituted LZ1 peptide nor a peptide corresponding to another, more C-terminal putative leucine zipper, LZ2, had any effect on regulation of the channels by endogenous PKA. Mutagenesis of the central two LZ1 d position leucines to alanine in the BK channel also eliminated regulation by endogenous PKA in HEK293 cells without altering the channel sensitivity to activation by voltage or by exogenous purified PKA. Inclusion of the STREX splice insert in the BK channel protein, which switches channel regulation by PKA from stimulation to inhibition, did not alter the requirement for an intact LZ1. Although PKA does not bind directly to the channel proteinin vitro, mutation of LZ1 abolished co-immunoprecipitation of PKA and the respective BK channel splice variant from HEK293 cells. Furthermore, a 127-amino acid fusion protein encompassing the functional LZ1 domain co-immunoprecipitates a PKA-signaling complex from rat brain. Thus LZ1 is required for the association and regulation of mammalian BK channels by PKA, and other putative leucine zippers in the BK channel protein may provide anchoring for other regulatory enzyme complexes.
Computational modeling of polyurea-coated composites subjected to blast loads

This manuscript presents computational modeling and simulation of woven E-glass fiber-reinforced vinyl-ester (EVE) composites and polyurea-coated EVE composites subjected to blast loading. The response of polyurea is idealized based on a temperature- and pressure-dependent visco-elastic constitutive model. The response of the EVE layers is modeled based on a multiscale computational damage model that includes adiabatic heating and rate-dependence in the constituent (i.e. matrix and fiber) behavior. Experimentally validated numerical simulations of EVE composite and polyurea-coated EVE composite specimens subjected to blast loading indicate that the proposed models are capable of accurately capturing the inelastic and failure characteristics of the specimens. The significant shock mitigation effect of polyurea coating is numerically demonstrated. Predictive simulations suggest better blast mitigation characteristics with increasing polyurea thickness and confining the perimeter of the polyurea layers.
Prolonged light exposure induces widespread phase shifting in the circadian clock and visual pigment gene expression of the Arvicanthis ansorgei retina

Purpose Prolonged periods of constant lighting are known to perturb circadian clock function at the molecular, physiological, and behavioral levels. However, the effects of ambient lighting regimes on clock gene expression and clock outputs in retinal photoreceptors—rods, cones and intrinsically photosensitive retinal ganglion cells—are only poorly understood. Methods Cone-rich diurnal rodents (Muridae: Arvicanthis ansorgei) were maintained under and entrained to a 12 h:12 h light-dark cycle (LD; light: ~300 lux). Three groups were then examined: control (continued maintenance on LD); animals exposed to a 36 h dark period before sampling over an additional 24 h period of darkness (DD); and animals exposed to a 36 h light period before sampling over an additional 24 h period of light (~300 lux, LL). Animals were killed every 3 or 4 h over 24 h, their retinas dissected, and RNA extracted. Oligonucleotide primers were designed for the Arvicanthis clock genes Per1, Per2, Cry1, Cry2, and Bmal1, and for transcripts specific for rods (rhodopsin), cones (short- and mid-wavelength sensitive cone opsin, cone arrestin, arylalkylamine N-acetyltransferase) and intrinsically photosensitive retinal ganglion cells (melanopsin). Gene expression was analyzed by real-time PCR. Results In LD, expression of all genes except cone arrestin was rhythmic and coordinated, with acrophases of most genes at or shortly following the time of lights on (defined as zeitgeber time 0). Arylalkylamine N-acetyltransferase showed maximal expression at zeitgeber time 20. In DD conditions the respective profiles showed similar phase profiles, but were mostly attenuated in amplitude, or in the case of melanopsin, did not retain rhythmic expression. In LL, however, the expression profiles of all clock genes and most putative output genes were greatly altered, with either abolition of daily variation (mid-wavelength cone opsin) or peak expression shifted by 4–10 h. Conclusions These data are the first to provide detailed measures of retinal clock gene and putative clock output gene expression in a diurnal mammal, and show the highly disruptive effects of inappropriate (nocturnal) lighting on circadian and photoreceptor gene regulation.
Sex-related differences in COPD in five Latin American cities: the PLATINO study

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40–1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56– -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.
Chapter 6: Effects of Paternal Involvement on Fathers and Mothers

In the last two decades, average levels of paternal involvement in childcare have increased significantly (Lamb, Pleck, Charnov, & Levine, in press), albeit more slowly than many in the media would have us believe. Most professional discussions of these secular changes have focuscd on the effects of increased paternal involvement on children. In this brief chapter, we discuss the likely effects of increased paternal involvement on mothers and fathers.
Snowboarding Mums Carve Out Fresh Tracks: Resisting traditional motherhood discourse?

Abstract The purpose of this research was to explore the experiences of mothers who snowboard. Snowboarding was selected because the discourses surrounding the sport typically embody freedom, hedonism, and irresponsibility (Humphreys, 1996). These characteristics are at odds with traditional notions of motherhood (Miller & Brown, 2005). A feminist post‐structural approach was adopted, utilising Foucault's concepts of power, knowledge, truth, and resistance to investigate how the mothers shaped their identities and social relations. Five snowboarders were interviewed. It is argued that these snowboarding mothers resisted the social expectations created by the ‘ideology of motherhood’ by redefining what it means to be a ‘good mother’ and by creating practices to achieve their own happiness. Support from partners and other family members was integral to this.
What is Autism

Autism is conceptualized as a behavioural syndrome of multiple neurological injuries associated with a wide variety of medical conditions. The possibility that the brain dysfunction might underlie a specific lack of a theory of mind is discussed. Autism is seen as possibly existing on a spectrum of disorders including both Kanner autism and Asperger Syndrome. Epidemiological, biological, psychological and follow-up findings are briefly reviewed.
Utilization of Psychopharmacological Treatment Among Patients With Newly Diagnosed Bipolar Disorder From 2001 to 2010

Objective The aim of the study was to examine utilization and patterns of psychopharmacological treatment during a 1-year follow-up period among patients with newly diagnosed bipolar disorder from 2001 to 2010. Methods Patients with newly diagnosed bipolar disorder from 2001 to 2010 were identified from the National Health Insurance Research Database in Taiwan. We assessed prescription records related to 4 kinds of psychopharmacological medication, including antipsychotics (APs), antidepressants, mood stabilizers, and benzodiazepines, as well as health care utilization in a 1-year follow-up period among the study subjects. In addition, logistic regressions were applied to test the trends for utilization of psychopharmacological treatment during the 10-year study period. Results A total of 2703 patients newly diagnosed with bipolar disorder were enrolled. The ratio of good adherence, defined as medications possession ratio greater than 0.8, for use of the examined psychopharmacological medication was relatively low during the study period. The use of first-generation APs, selective serotonin reuptake inhibitors, tricyclic antidepressants, lithium, carbamazepine, and benzodiazepines has declined; however, the use of second-generation APs, serotonin and norepinephrine reuptake inhibitors, lamotrigine, and valproate has risen markedly during the 10-year period. Conclusions This study presents patterns of pharmacological treatment in patients with newly diagnosed bipolar disorder in Taiwan for a 10-year study period. It would be of importance to further investigate causes and outcomes for polytherapy and nonadherence to psychotropic medications among patients with bipolar disorder.
Efficient Representation and Analysis of Power Grids

Modern deep sub-micron ULSI designs with hundreds of millions of devices require huge grids for power distribution. Such grids, operating with increasingly low-power voltages, are a design limiting factor and accurate analysis of their behavior is of paramount importance as any voltage drops can seriously impact performance or functionality. As power grid models have millions of unknowns, highly optimized special purpose simulation tools are required to handle the time and memory complexity of solving for their dynamic behavior. In this work, we propose a hierarchical matrix representation of the power grid model that is both space and time efficient. With this representation, reduced storage matrix factors are efficiently computed and applied in the analysis at every time-step of the simulation. Results show an almost linear complexity growth, namely O(n loga (n)), for some small constant a, in both space and time, when using this matrix representation. Comparisons of our academic implementation with production-quality code proves this method to be very efficient when dealing with the simulation of large power grid models.
B-89Comparison of Driving Performance, Cognition, and Physical Symptoms in Individuals with Multiple Sclerosis and Healthy Controls

OBJECTIVE: This study compared driving using a virtual reality driving simulator (VRDS), cognitive functioning, and fatigue in Multiple Sclerosis (MS) individuals with age and education-matched healthy controls (HC). METHOD: 26 MS (mean age = 47.46), and 21 HC (Mean age = 42.09) were administered the Fatigue Severity Scale, Trails B, Paced Auditory Serial Addition Test-2 second condition, Timed Walking Test, and 9-hole Peg Test. All the participants drove a standardized route in the VRDS. Center lane (CL) and speed deviations were examined for a simple straight lane segment, with and without distractions. RESULTS: Paired samples t-test revealed differences in driving performance only for the HC group. Specifically, HC's driving speed varied more during the undistracted (M = 2.50, SD = 1.46) vs. distracted (M = 1.75, SD = 0.99) driving segment, t(20) = -2.314, p = 0.03. However, driving speed was not associated with any cognitive or physical measures. MS participants' CL deviations were associated with fine motor movement during undistracted (r = 0.45, p = 0.05) and distracted driving (r = 0.49, p = 0.03). In contrast, HC's CL deviations were associated with working memory during undistracted (r = 0.50, p = 0.03) and distracted (r = 0.63, p = 0.004) driving. Fatigue severity (r = 0.56, p = 0.03) was associated with undistracted driving in the MS group. CONCLUSION(S): Driving performance of MS individuals was affected by physical symptoms and cognitive symptoms played a more important role for HC. In MS individuals, fatigue may be the moderating factor between driving and cognition. Keywords: Driver distraction; Language: en
The Synonym Lookaside Buffer: A Solution to the Synonym Problem in Virtual Caches

To support dynamic address translation in today's microprocessors, the first-level cache is accessed in parallel with a translation lookaside buffer (TLB). However, this current approach faces mounting problems. This paper introduces new ideas to enable the use of virtual addresses in the cache hierarchy. The major idea is the replacement of the on-chip TLB by a synonym lookaside buffer (SLB). The SLB translates synonyms into a primary virtual address, which is a unique identifier resolving all ambiguities due to synonyms in the memory system. We introduce various system configurations with SLBs and discuss all functional issues associated with them. An SLB is much more scalable than a regular TLB. It scales with memory data set sizes, physical memory sizes and number of cores in a multiprocessor. Moreover SLB entry flushes and shootdowns due to physical memory management are eliminated. We show performance data resulting from the simulation of several applications as diverse as scientific computing, database, and JAVA virtual machines. These evaluations target SLB miss rates and flushes as well as the impact of the SLB on cache miss rates. They show that small SLBs of 8-16 entries are sufficient to solve the synonym problem in virtual caches and that their performance overhead is negligible.
An Efficient MPI Message Queue Mechanism for Large-scale Jobs

The Message Passing Interface (MPI) message queues have been shown to grow proportionately to the job size for many applications. With such a behaviour and knowing that message queues are used very frequently, ensuring fast queue operations at large scales is of paramount importance in the current and the upcoming exascale computing eras. Scalability, however, is two-fold. With the growing processor core density per node, and the expected smaller memory density per core at larger scales, a queue mechanism that is blind on memory requirements poses another scalability issue even if it solves the speed of operation problem. In this work we propose a multidimensional queue traversal mechanism whose operation time and memory overhead grow sub-linearly with the job size. We compare our proposal with a linked list-based approach which is not scalable in terms of speed of operation, and with an array-based method which is not scalable in terms of memory consumption. Our proposed multidimensional approach yields queue operation time speedups that translate to up to 4-fold execution time improvement over the linked list design for the applications studied in this work. It also shows a consistent lower memory footprint compared to the array-based design.
Nystagmus inhibition as an effect of eye-closure.

In the present investigation the nystagmus response during rotation with open eyes in darkness was compared with the response recorded during eye-closure. Eye-closure reduced the induced nystagmus response and in 20 out of 30 subjects the response decreased to such an extent that it was impossible to record by electronystagmography. A relation was found between vertical eyeball deviation during eye-closure and the degree of nystagmus inhibition. From the present investigation it appears that examinations of the peripheral vestibular function carried out while the subjects' eyes are closed often give misleading recordings which may result in incorrect conclusions. The best way of recording vestibular induced nystagmus, therefore, is to test the subjects with eyes open in total darkness.
Faster Clustering via Preprocessing

We examine the efficiency of clustering a set of points, when the encompassing metric space may be preprocessed in advance. In computational problems of this genre, there is a first stage of preprocessing, whose input is a collection of points M; the next stage receives as input a query set Q ⊂ M, and should report a clustering of Q according to some objective, such as 1-median, in which case the answer is a point a ∈ M minimizing P q2Q dM(a,q). We design fast algorithms that approximately solve such problems under standard clustering objectives like p-center and p-median, when the metric M has low doubling dimension. By leveraging the preprocessing stage, our algorithms achieve query time that is near-linear in the query size n = |Q|, and is (almost) independent of the total number of points m = |M|.
A Prediction Model for Depression Risk

Abstract Bipolar disorder is a psychopathy characterized by manic and major depressive episodes. It is important todetermine the degree of depression when treating patients with bipolar disorder because 8 ˘ 10% of bipolarpatients commit suicide during the periods in which they experience major depressive episodes. The Hamil-ton depression rating scale is most commonly used to estimate the degree of depression in a patient. Thispaper proposes using the Hamilton depression rating scale to estimate the eﬀectiveness of patient treatmentbased on the linear mixed eﬀects model and the transition model. Study subjects were recruited from theSeoul National University Bundang Hospital who scored 8 points or above in the Hamilton depression ratingscale on their ﬁrst medical examination. The linear mixed eﬀects model and the transition model were ﬁttedusing the Hamilton depression rating scales measured at the baseline, six month, and twelve month follow-ups. Then, Hamilton depression rating scale at the twenty-four month follow-up was predicted using thesemodels. The prediction models were then evaluated by comparing the observed and predicted Hamiltondepression rating scales on the twenty-four month follow-up.Keywords: Prediction model, linear mixed eﬀects model, transition model, bipolar disorder, Hamilton de-pression rating scale.
Why idioms mean what they do

This reply to Kreuz and Graesser (1991) expands on some of the theoretical and empirical issues discussed in an article on idiom interpretation by Nayak and Gibbs (1990). Specifically addressed are (a) the generality of Nayak and Gibbs's earlier findings on emotion idioms to idioms representative of other conceptual categories, (b) Nayak and Gibbs's characterization of the dead metaphor theory of idiomaticity, (c) the need for a componential analysis of idioms, and (d) a problem in the design and interpretation of one of Nayak and Gibbs's experimental studies
Normal Cell Cycle and Checkpoint Responses in Mice and Cells Lacking Cdc25B and Cdc25C Protein Phosphatases

ABSTRACT The Cdc25 family of protein phosphatases positively regulates cell division by activating cyclin-dependent protein kinases (CDKs). In humans and rodents, there are three Cdc25 family members—denoted Cdc25A, Cdc25B, and Cdc25C—that can be distinguished based on their subcellular compartmentalizations, their abundances and/or activities throughout the cell cycle, the CDKs that they target for activation, and whether they are overexpressed in human cancers. In addition, murine forms of Cdc25 exhibit distinct patterns of expression throughout development and in adult tissues. These properties suggest that individual Cdc25 family members contribute distinct biological functions in embryonic and adult cell cycles of mammals. Interestingly, mice with Cdc25C disrupted are healthy, and cells derived from these mice exhibit normal cell cycles and checkpoint responses. Cdc25B− / − mice are also generally normal (although females are sterile), and cells derived from Cdc25B − / − mice have normal cell cycles. Here we report that mice lacking both Cdc25B and Cdc25C are obtained at the expected Mendelian ratios, indicating that Cdc25B and Cdc25C are not required for mouse development or mitotic entry. Furthermore, cell cycles, DNA damage responses, and Cdc25A regulation are normal in cells lacking Cdc25B and Cdc25C. These findings indicate that Cdc25A, or possibly other phosphatases, is able to functionally compensate for the loss of Cdc25B and Cdc25C in mice.
Developmental precise excision of Oxytricha trifallax telomere‐bearing elements and formation of circles closed by a copy of the flanking target duplication.

The 4.1 kbp TBE1 elements of Oxytricha fallax and Oxytricha trifallax are deduced to transpose into a centrisymmetric target, CAnTG, and to duplicate the central AnT. Despite conserved C(A4C4)2 telomeric repeats at their tips, free TBE1s found during macronuclear development are not linear but 4.1 kbp circles closed on one copy of the AnT target duplication. The macronucleus‐destined flanks are rejoined to regenerate the target, effecting efficient and precise somatic reversion of the germline transpositional mutation. A model is presented in which transposase catalyzes concerted precise rejoining of the flanks and cyclization of the excised element.
Context Specificity in Performance - The Defining Problem for Human Factors/Ergonomics

This report addresses what I believe represents the major unresolved problem confronting the field of human factors/ergonomics (HF/E): context—also termed design—specificity in human behavior and performance. Context specificity implies an intimate interaction, or coupling, between performance and design. The problem of context specificity in performance can be framed in terms of: (1) the difficulties it poses for basic and applied research in HF/E; (2) its relevance to social and organizational performance; (3) underlying neurobehavioral mechanisms; and (4) validity of models of human behavior and performance. Questions addressing these different problem areas are introduced, followed by a series of strategies and conclusions directed at problem resolution. The conceptual perspective adopted here for understanding context specificity is that of behavioral cybernetics, which assumes that task-specific variance in performance occurs as an inevitable consequence of dynamic spatiotemporal feedback interaction between sensory feedback (design) and sensory feedback control (motor behavior).