cssi/SciSciGPT-SciSciNet huggingface dataset:
The A-kinase anchor protein MAP2B and cAMP-dependent protein kinase are associated with class C L-type calcium channels in neurons

Phosphorylation by cAMP-dependent protein kinase (PKA) increases the activity of class C L-type Ca2+ channels which are clustered at postsynaptic sites and are important regulators of neuronal functions. We investigated a possible mechanism that could ensure rapid and efficient phosphorylation of these channels by PKA upon stimulation of cAMP-mediated signaling pathways. A kinase anchor proteins (AKAPs) bind to the regulatory R subunits of PKA and target the holoenzyme to defined subcellular compartments and substrates. Class C channels isolated from rat brain extracts by immunoprecipitation contain an endogenous kinase that phosphorylates kemptide, a classic PKA substrate peptide, and also the main phosphorylation site for PKA in the pore-forming α1 subunit of the class C channel complex, serine 1928. The kinase activity is inhibited by the PKA inhibitory peptide PKI(5–24) and stimulated by cAMP. Physical association of the catalytic C subunit of PKA with the immunoisolated class C channel complex was confirmed by immunoblotting. A direct protein overlay binding assay performed with 32P-labeled RIIβ revealed a prominent AKAP with an M r of 280,000 in class C channel complexes. The protein was identified by immunoblotting as the microtubule-associated protein MAP2B, a well established AKAP. Class C channels did not contain tubulin and MAP2B association was not disrupted by dilution or addition of nocodazole, two treatments that cause dissociation of microtubules. In vitro experiments show that MAP2B can directly bind to the α1 subunit of the class C channel. Our findings indicate that PKA is an integral part of neuronal class C L-type Ca2+ channels and suggest that the AKAP MAP2B may mediate this interaction. Neither PKA nor MAP2B were detected in immunoprecipitates of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptors or class B N-type Ca2+ channels. Accordingly, MAP2B docked at class C Ca2+ channels may be important for recruiting PKA to postsynaptic sites.
Predicting turnover of employees from measured job attitudes

Abstract The study looks at the prediction of turnover by employee job attitudes and intent to remain with the company, among 911 salesmen. Intent to remain was highly correlated with actual turnover, both short term and long term. During the 18 months after attitudes were surveyed, turnover for men who stated they intended to remain was 9% versus 30% of those who were less committed. Employees' expressed intent was a better predictor of turnover than were other job attitudes. An examination of static and dynamic correlations showed that employees' intent to remain is most closely tied to feelings about the work itself and about the company as a place to work.
The Binding of Antibiotics in OmpF Porin.

The structure of OmpF porin in complex with three common antibiotics (zwitterionic ampicillin, anionic ertapenem, and di-anionic carbenicillin) was determined using X-ray crystallography. The three antibiotics are found to bind within the extracellular and periplasmic pore vestibules, away from the narrow OmpF constriction zone. Using the X-ray structures as a starting point, nonequilibrium molecular dynamics simulations with an applied membrane voltage show that ionic current through the OmpF channel is blocked with bound ampicillin, but not with bound carbenicillin. The susceptibility of Escherichia coli expressing OmpF mutants to ampicillin and carbenicillin was also experimentally characterized using microbiologic assays. These results show that general diffusion by OmpF porins allows for transfer of molecules with varied charged states and give insights into the design of more efficient antibiotics. A better understanding of this mechanism will shed light on nature's way of devising channels able to enhance the transport of molecules through membranes.
Absolute configuration of phorboxazole A C32C43 analogs by CD exciton-coupling of allylic 2-naphthoate esters

Abstract The configurations of phorboxazole model compounds 4a and 4b were assigned as (33 R ,35 S ,37 S ,38 S ) and (33 R ,35 S ,37 S ,38 R ), respectively, by analysis of exciton coupling in the corresponding 2-naphthoate esters. Spectroscopic comparisons with phorboxazoles A and B provides independent proof of the 38 R absolute configuration of these natural products .
A software systems management MBA option

In the past, software systems have often been viewed (at least by Business Schools) as simply tools for management. Thus, the majority of the attention paid to software systems has generally revolved around building systems that can be used more effectively by the user[1]. Other projects funded by the 1984 SIGBDP research program support this statement ("Human Computer Interaction for Management Tasks", "Information System Support for Group Decision Making", and "Critical Success Factors of Decision Support Systems"). This is a perfectly legitimate view of data processing. Much of the software system's worth is dependent on how effectively it can be used.
Five Position Synthesis of Spherical (6, 7) Linkages

This paper presents a geometric synthesis procedure for spherical (6, 7) linkages, often known as spherical six-bar linkages, based on adding two spherical RR constraints to a spherical 3R serial chain. The design can use the spherical 3R chain to shape the movement of the linkage and identify a set of task positions that shape the trajectory of the end-effector. We use five task positions to completely specify the two RR chains that constrain the system to one degree-of-freedom. This procedure yields spherical versions of the various topologies for the planar Watt and Stephenson six-bar linkages. We find that for any design problem we obtain at a minimum of two design candidates for the Watt-type linkage, and as many as 185 different design for all of the topologies obtained by constraining the spherical 3R chain. Wampler’s method for the analysis of spherical loops is used to analyze these linkages. An example design is presented in detail.Copyright © 2008 by ASME
The effects of counterion composition on the rheological and conductive properties of mono- and diphosphonium ionic liquids

A series of monocationic and dicationic phosphonium ionic liquids was prepared and their thermal, rheological, and conductive properties were characterized. These phosphonium ionic liquids were paired with seven monoanionic counterions (chloride, hexafluorophosphate, hexafluoroantimonate, octanoate, perfluorooctanoate, dodecyl sulfate, dioctyl sulfosuccinate, and bis(trifluoromethane)sulfonimide) in order to examine the effects of the counterion size and chemical structure on bulk properties of the phosphonium ionic liquids. The length of the three alkyl chains surrounding the phosphorus atom was also varied from butyl, hexyl to octyl on the cation. All of the samples exhibited initial decomposition temperatures above 150 °C. The octanoate and its fluorinated analog possessed the lowest decomposition temperature and the dicationic hexyl sample bis(trifluoromethane)sulfonimide possessed the highest (>370 °C). The dicationic butyl and hexyl chloride samples displayed similar G′, G″ and viscosity curves, whereas the dicationic octyl chloride sample exhibited significantly lower values. The frequency sweeps of the monocationic phosphonium ionic liquids were all similar and showed minimal side chain dependence. The monocationic phosphonium ionic liquids have higher conductivity than their dicationic analogs at all measured temperatures.
On the identification of Preisach measures

The phenomenon of hysteresis is commonly encountered in the study of magnetic materials. The Preisach operator and its variants have been successfully used in the modeling of a physical system with hysteresis. In an application, one has to determine a density function for the Preisach operator using the input-output behavior of the system at hand. In this paper, we describe a method for numerically determining an approximation of the density function when there is not enough experimental data to uniquely solve for the density function. We also present numerical results where we estimate an approximate density function from data published in the literature for a magnetostrictive actuator and an electro-active polymer.
Design of low-loss 1-3 piezoelectric composites for high-power transducer applications

Lead zirconate titanate (PZT)/polymer 1-3 composites have improved electromechanical properties compared with monolithic counterparts, but possess a low mechanical quality factor, limiting their use in high-power transducer applications. The goal of this work was to improve the mechanical quality factor of 1-3 PZT/polymer composites by optimizing the polymer materials. Theoretical analysis and modeling were performed for optimum composite design and various polymers were prepared and characterized. 1-3 piezocomposites were constructed and their electromechanical properties were experimentally determined. The results demonstrated that the composites with high-thermal-conductivity polymers generally have degraded electromechanical properties with significantly decreased mechanical quality factors, whereas the composites filled with low-loss and low-moduli polymers were found to have higher mechanical quality factors with higher electromechanical coupling factors: Qm ~ 200 and kt ~ 0.68 for PZT4 composites; Qm ~ 400 and kt ~ 0.6 for PZT8 composites. The improved mechanical quality factor of 1-3 piezocomposites may offer improved performance and thermal stability of transducers under high-drive operation.
Implications of the asthma guidelines for the clinician.

JB is a 19-year-old sophomore at the local university. He is a member of the men’s tennis team and has been experiencing increasing shortness of breath requiring frequent use of his rescue inhaler since the beginning of the tennis season. Additionally, he uses his inhaler daily when walking up a steep hill to his classes and 2 or more times a week when he is awakened from sleep because of coughing. Further questioning reveals that he has received 3 bursts of oral corticosteroids in the past year for exacerbations. His previous physician, though, told him that he has only mild asthma and recommended that he be treated with albuterol on an as-needed basis only. At the time of the initial visit with JB, his spirometry revealed a prebronchodilator FEV1/forced vital capacity ratio of 75% of predicted value and an FEV1 of 76% of predicted value. His Asthma Control Test questionnaire score is 16. JB tells us that his goal is to be a competitive tennis player and not have symptoms that inhibit his performance. Additionally, he does not want his asthma to interfere with his regular activities, he wants to be able to sleep through the night without coughing, and he wants to not be dependent on his albuterol inhaler. What guidance does the new National Heart, Lung, and Blood Institute’s Expert Panel Report ‘‘Guidelines for the diagnosis and management of asthma’’ (Expert Panel Report 3) provide us about how to properly evaluate and treat him? The document states that the ultimate goal of treatment is to enable patients to live with few, if any, symptoms; no functional limitations; and no impairment in quality of life associated with asthma. Furthermore, there should be few, if any, adverse events from either the
Nanowire transistors: room for manoeuvre.

Kinked nanowire transistors that can be manipulated in three dimensions can be used to record the intracellular electrical signals of targeted cells.
An Error-Correcting Map for Quartets Can Improve the Signals for Phylogenetic Trees

From the DNA sequences for N taxa, the (generally unknown) phylogenetic tree T that gave rise to them is to be reconstructed. Various methods give rise, for each quartet J consisting of exactly four taxa, to a predicted tree L(J) based only on the sequences in J, and these are then used to reconstruct T. The author defines an "error-correcting map" (Ec), which replaces each L(J) with a new tree, Ec(L)(J), which has been corrected using other trees, L(K), in the list L. The "quartet distance" between two trees is defined as the number of quartets J on which the two trees differ, and two distinct trees are shown to always have quartet distance of at least N - 3. If L has quartet distance at most (N - 4)/2 from T, then Ec(L) will coincide with the correct list for T; and this result cannot be improved. In general, Ec can correct many more errors in L. Iteration of the map Ec may produce still more accurate lists. Simulations are reported which often show improvement even when the quartet distance considerably exceeds (N - 4)/2. Moreover, the Buneman tree for Ec(L) is shown to refine the Buneman tree for L, so that strongly supported edges for L remain strongly supported for Ec(L). Simulations show that if methods such as the C-tree or hypercleaning are applied to Ec(L), the resulting trees often have more resolution than when the methods are applied only to L.
Urethral Sphincter Morphology and Function With and Without Stress Incontinence

Purpose: Using magnetic resonance images we analyzed the relationship between urethral sphincter anatomy, urethral function and pelvic floor function.Materials and Methods: A total of 103 women with stress incontinence and 108 asymptomatic continent controls underwent urethral profilometry, urethral axis measurement with a cotton swab, vaginal closure force measurement with an instrumented speculum and magnetic resonance imaging. Striated urogenital sphincter length was determined and its thickness was measured in the proximal sphincter, where its circular shape enables estimation of striated urogenital sphincter area. A length-area index was calculated as a proxy for volume.Results: The striated urogenital sphincter in women with stress incontinence was 12.5% smaller than that in asymptomatic continent women (mean ± SD length-area index 766.4 ± 294.3 vs 876.2 ± 407.3 mm3, p = 0.04). The groups did not differ significantly in striated urogenital sphincter length (13.2 ± 3.4 vs 13.7 ± 3.9 mm, p = 0.40), th...
Age, origin, and thermal histories of some plutonic rocks from the Salinian block of California

U-Pb isotopic measurements on zircons from some granitic rocks of the Salinian block indicate emplacement and crystallization of these rocks about 104 m.y. ago (mid-Cretaceous). The relatively radiogenic nature of initial Sr and common Pb in these rocks, and the presence of an inherited component of zircon in some of them strongly suggest the involvement of continental crust in the genesis of the magmas. Possibly the magmas were generated in a zone of melting that overlapped the boundary between the mantle and the continental crust. U-Pb measurements on sphene, apatite, and feldspar from the plutons, along with previously published K-Ar and fission-track ages shed light on the post-emplacement thermal histories of the plutons. Most of the samples from the northern part of the Salinian block (Bodega Head, Point Reyes) show relatively simple thermal histories. Evidently these plutons were emplaced at moderate levels in the crust, crystallized, and cooled to moderate temperatures over an interval of about 10–15 m.y. Plutons from the central Salinian block (Santa Lucia Range) show more complex and prolonged thermal histories. These plutons evidently were emplaced at greater depths in the crust than were the plutons from the northern Salinian block. They remained at elevated temperatures for ca. 25 m.y., then cooled fairly rapidly, probably as a result of rapid uplift and erosion. One sample from the northern Salinian block shows an even longer span of time between emplacement and cooling. The thermal evolution of the Salinian plutonic rocks predates major offset along the San Andreas fault zone and thus reflects the thermal evolution of the undisrupted source terrane of the Salinian block. Isotopic measurements of the type reported here might therefore prove valuable in correlations across the San Andreas fault zone. Moreover, detailed study of thermal evolution within the Salinian block could shed light on major offsets within the block.
Modeling and Performance Assessment of the HyTAQ, a Hybrid Terrestrial/Aerial Quadrotor

This paper analytically and experimentally evaluates the performance of the hybrid terrestrial and aerial quadrotor (HyTAQ) robot. The HyTAQ is composed of a quadrotor hinged at the center of a cylindrical cage. This configuration gives the robot an increased range compared with aerial-only quadrotors and negates any obstacle avoidance issues that are commonly associated with terrestrial-only robots. An accurate dynamical model of the robot is derived, which helps with an in-depth analysis of the system's energy consumption. The analysis quantifies the energy savings during terrestrial locomotion as compared with aerial locomotion. Experimental results validate the analysis and indicate that, depending on the surface, the robot's terrestrial range can be 11 times greater and operational time ten times greater than the aerial range/operation time at equivalent speeds.
From boys to men: predicting adult adaptation from middle childhood sociometric status.

This report examines the predictive validity of sociometric status at age 9‐10 to young adult ~age 23‐24! antisocial behavior, work and school engagement, and arrests using Oregon Youth Study males ~N 5 206!. A variety of analytic strategies included ~a! multivariate analyses to examine the variation in adult adaptation as a function of sociometric classification at age 9‐10, ~b! regression analyses to evaluate the relative contribution of “liked most” and “liked least” peer nominations, and ~c! structural equation modeling to predict the young adult outcome constructs from social preference at age 9‐10. Contrary to expectation, when controlling for early antisocial behavior and academic skills, boys’ social preference scores still predicted young adult outcomes. Longitudinal findings are discussed with respect to the salience of male peer rejection in middle childhood and the social developmental processes that may account for the predictive validity of peer rejection.
Semivirtual simulations for the evaluation of vision-based ADAS

The design and development process of advanced driver assistance systems (ADAS) is divided into different phases, where the algorithms are implemented as a model, then as software and finally as hardware. Since it is unfeasable to simulate all possible driving situations for environmental perception and interpretation algorithms, there is still a need for expensive and time-consuming real test drives of thousands of kilometers. Therefore we present a novel approach for testing and evaluation of vision-based ADAS, where reliable simulations are fused with recorded data from test drives to provide a task-specific reference model. This approach provides ground truth with much higher reliability and reproducability than real test drives and authenticity than using pure simulations and can be applied already in early steps of the design process. We illustrate the effectiveness of our approach by testing a vision-based collision mitigation system on recordings of a german highway.
Agents Unchained: The Determinants of Takeover Defenses in IPO Firms

Many companies continue to go public with takeover defenses even though institutional investors zealously oppose defenses in public companies. In this Article, I analyze the determinants of takeover defenses at IPO firms using an empirical analysis of 259 IPOs from 2008-12, interviews with numerous practitioners, and a survey of the corporate governance policies of significant investors. I find that the type of an issuer’s legal counsel’s M&A experience and the identity of pre-IPO shareholders explain much of the variation in takeover defenses at IPO firms. Companies advised by law firms with more target-side M&A experience adopt more defenses, while companies advised by law firms with more acquirer-side M&A experience adopt fewer defenses. Companies backed by venture capital funds are significantly more likely to adopt more takeover defenses. However, private equity backing has no effect on the pre-IPO adoption of staggered boards. Even though mutual funds and public pension funds are some of the most ardent opponents of takeover defenses in public companies, I find that issuers that they had invested in prior to the IPO almost always go public with robust takeover defenses in place. A comparison of issuers backed by Silicon Valley law firm Wilson Sonsini and New York law firm Simpson Thacher is particularly telling: Wilson Sonsini, a firm well known for its ties to the venture capital industry and its representation of targets, installed staggered boards in all of its IPO clients while Simpson Thacher, known for its private equity practice and acquirer representation, installed staggered boards in only 50% of its IPO clients. The lack of a consensus regarding the efficiency of defenses among the most experienced participants in the IPO market leads me to reject the idea that takeover defenses are generally optimal for pre-IPO shareholders.
An end-user demonstration approach to support aspect-oriented modeling

Aspect-oriented modeling (AOM) is a technique to separate concerns that crosscut the modularity boundaries of a modeling hierarchy. AOM is traditionally supported by manual editing or writing model transformation rules that refine a base model. However, traditional model weaving approaches present challenges to those who are unfamiliar with a model transformation language or metamodel definitions. This poster describes an approach to weave aspect models by recording and analyzing demonstrated operations by end-users.
Eva's Story One Woman's Life Viewed Through the Interpretive Lens of Gilligan's Theory

This work is an interpretive reading of one Mexican American woman's story as told to an Anglo researcher. It demonstrates the methodological meaningfulness of reading for conflict and voice in the narratives of women who have experienced abuse and, perhaps more important, brings others into relationship with Eva and her story. The story is read through the interpretive lens of women's moral development as described by Carol Gilligan. The article begins with a review of Gilligan's theory of moral development, followed by a detailed interpretation of the reading of Eva's story. The method used for the analysis is an adaptation of the method developed by Gilligan and several of her colleagues. This method of analysis explicates experiences described as creating moral conflict, the narrator's sense of self, and the voices of psychological distress and resilience in her story.
On the invariance of accounting principles to business models: a discussion of the Singleton-Green and Page articles

Let me first begin by saying that I agree in general with Brian’s proposition that the theory of the firm provides insights into requisite financial reporting systems. I also agree with Mike’s characterization of business models as diverse, subjective, and mostly aspirational and if I may add, essentially vacuous. I disagree with the notion that financial reporting and recognition and measurement principles should be tailored to business models. Rather, I shall make the argument that recognition and measurement principles should be invariant to diverse business models. Indeed, the theory of the firm would suggest universal recognition and measurement principles that apply independently of the business models. The role of business models, I contend, is to facilitate proper quantifications—the required output of applying the universal recognition and measurement principles.
Invariant manifolds in singular perturbation problems for ordinary differential equations

Based on Fenichel's geometric idea, invariant manifold theory is applied to singular perturbation problems. This approach clarifies the nature of outer and inner solutions. A specific condition is given to ensure the existence of heteroclinic connections between normally hyperbolic invariant manifolds. A method to approximate the connections is also presented.
SECTOR-STRUCTURED INTERPLANETARY MAGNETIC FIELD ASSOCIATED WITH THE FAST PLASMA STREAMS IN 1985-1996

An analysis of 373 well-defined high-speed solar-wind streams observed at 1 AU during the years 1985 –1996 is outlined. The distribution of the occurrence of these streams as a function of Bartels rotation days using the dominant polarity of the interplanetary magnetic field (IMF) associated with the referred fast streams shows that a four-sector pattern for the positive IMF polarity and a two-sector pattern for the negative IMF polarity are the dominant features in the investigated period. The high-speed streams seem to occur at preferred Bartels days: positive polarity streams are most frequent near Bartels days 5 and 18, while negative polarity streams are most frequent in days 14 and 23. Moreover, the corotating streams with positive IMF polarity prefer to occur in days 5 and 18 of the Bartels rotation period, whereas flare-generated streams with negative IMF polarity occur in days 14 and 23. The observed distribution of Bartels days is probably related to the distribution of the solar sources of high-speed solar wind streams as the solar wind carries with it the photospheric magnetic polarity of the solar source region. In addition, the distribution of the streams reveals a similar behaviour during the ascending and the declining phase of the last solar cycle (22nd) in contrast to the previous one where it has an opposite appearance. Determined differences in the characteristics of the sector structured IMF associated with the fast streams of the last cycle with the previous one (21st) and some similarities with the alternate solar cycle (20th) seem to be attributed to the 22-year magnetic cycle and to the polarity reversals of the polar magnetic field of the Sun. As the magnetic sectors are due to multiple crossings of the solar equatorial plane by a large-scale, warped heliospheric current sheet, it is suggested that the two-sector pattern arises from a tilted solar magnetic dipole component and the more commonly observed four-sector pattern from a quadrupole component of the solar interplanetary magnetic field.
Cumulative Spine Loading and Clinically Meaningful Declines in Low-Back Function:

Objective:The objective was to assess the role of cumulative spine loading measures in the development of a clinically meaningful decline in low-back function.Background:Cumulative spine loading has been a suspected risk factor for low-back pain for many years, yet the measures that characterize risk have not been well delineated.Methods:A total of 56 cumulative exposure measures were collected in a prospective field study of distribution center workers. An individual’s risk for a clinically meaningful decline in low-back function (true cases) was explored with daily, weekly, and job tenure cumulative exposure measures using univariate and multivariate statistical modeling techniques. True noncases were individuals with no decline in low-back function.Results:An individual’s risk for a clinically meaningful decline in low-back function (true cases) was predicted well versus true noncases (sensitivity/specificity = 72%/73%) using initial low-back function (p(n)), cumulative rest time, cumulative load expos...
FORMATION OF SINGLE-DOMAIN MAGNETITE BY A THERMOPHILIC BACTERIUM

Magnetite is a common product of bacterial iron reduction and may serve as a potential physical indicator of biological activity in geological settings. Here the authors report the formation of single-domain magnetite under laboratory conditions by a thermophilic fermentative bacterial strain TOR-39 that was isolated from the deep subsurface. Time-course analyses were performed at 65 C to study the effect of bacterial activity on solution chemistry and magnetite formation during the growth of TOR-39. Run products were examined by transmission electron microscopy. Magnetite particles formed exclusively outside of bacterial cells and exhibited octahedral shapes having relatively equal length and width (<15% difference). Tiny magnetite particles (<12 nm) nucleated between 10 and 11 h of incubation and increased to average lengths of 55.4 {+-} 26.8 nm after 24 h of incubation. Between 24 h and 22 d of incubation, magnetite particles maintained average lengths of 56.2 {+-} 24.8 nm. Based on size constraints, greater than 85% of the particles observed fell within the magnetic single domain. Little to no magnetite was detected in abiotic controls at 65 or 95 C, or in TOR-39 cultures whose activity was suppressed. Unlike mesophilic iron-reducing bacteria (e.g., GS-15), TOR-39 produced crystals having shapes and sizesmore » similar to some particles produced intracellularly by magnetotactic bacteria. Thus the single-domain magnetite produced by thermophiles such as TOR-39 may represent a heretofore unrecognized biological contribution to natural remanent magnetization in sedimentary basins and other geothermal environments.« less
Developing and Assessing Intercoder Reliability in Studies of Group Interaction

Although group interaction is a rich source of data, it offers many challenges for analysis. We discuss how pretesting can solve many coding and reliability issues before the actual data collection...
Social Workers' Suggestions for Effective Rural Practice

Two focus groups of participants at a national rural social work conference answered the research question, “What are your suggestions for engaging in effective social worker practice in rural areas?” The participants offered specific recommendations for social work practice with rural people and communities. They supported these recommendations with illustrations from their experiences as social work practitioners in rural settings. Text data drawn from transcribed audiotapes of the focus groups were coded into open, axial, and selective data themes. While generalizability is limited, this small sample of social workers offered a glimpse of their views of rural practice. They offered practical, down-to-earth advice for rural social work practitioners within main data themes of community, connections, generalist practice, and diversity.
The Molecular Perspective: Microtubules and the Taxanes

interlocking protein filaments. A beautiful star of microtubules, the largest of these filaments, radiates outward from the center of the cell to the cell surface. This “aster” of microtubules is the railway system of the cell. Many types of cargo are carried along these rails. The endoplasmic reticulum is pulled by molecular motor proteins along microtubules, spreading it evenly throughout the cell. Vesicles are delivered to their destinations along microtubules. And, when cells divide, the most valuable cargo of the cell is carried by microtubules. Paired copies of each of the chromosomes are attached to the ends of a doubled microtubule aster and carefully separated into the two daughter cells. The cytoskeleton, in contrast to our articulated skeleton of bones, is a dynamic structure. It is continually constructed and demolished according to the shifting needs of the cell. A typical microtubule lasts for only 10 minutes before it is disassembled and the parts used to build a new one. Microtubules are nucleated in the “microtubule-organizing center,” at the center of the cell, and then extended one piece at a time into the cytoplasm. Growth proceeds in fits and starts in a process known as “dynamic instability.” Tubules grow slowly and steadily, but are punctuated by periods of rapid disassembly, when large regions peel away from the ends. A small portion of the microtubule may break up, or the fragmentation may extend all the way back to the start, completely destroying the tubule. In special cases, such as the microtubules that support the long axons and dendrites of nerve cells, auxiliary proteins stabilize the microtubule for longer periods of time. But the dynamic structure of microtubules is essential for their everyday function in transport and cell division. Essential functions make excellent targets for toxins and for cancer chemotherapy. The central role of microtubules in cell division makes them particularly attractive. Many organisms have developed toxins that block the dynamic instability of microtubules, thus blocking the ability of the cell to divide. Two types of natural plant toxins are widely used in medicine. They have the identical result of blocking division, but achieve it in exactly opposite ways. The vinca alkaloids, such as vinblastine, vincristine, and vinorelbine, bind to the end of growing microtubules, blocking the addition of more tubulin dimers. The tubule cannot grow, but it can still disassemble, so the microtubules ultimately break down into nothing. Alternatively, the taxanes, The Molecular Perspective: Microtubules and the Taxanes
Worm genomes hold the smoking guns of intron gain.

Spliceosomal introns are prevalent in our genomes and also in our minds as unsolved evolutionary mysteries. Are introns primordial features of eukaryotic genes? Or have they been acquired during eukaryotic evolution? These questions are central to a still-simmering debate among biologists. To describe the phylogenetic pattern of introns across eukaryotes, two general models have emerged: the introns-late view claims that all introns have been gained into preformed genes, with their current-day distributions explained by processes of both gain and loss; whereas introns-early proponents posit that most introns can be explained by frequent loss from intron-rich ancestral genes that predate eukaryotic cells (1–4). But the key questions remain unanswered. Both views agree that intron loss does occur, but the main disagreement concerns what fraction of present-day introns have been gained, and how. Spliceosomal introns are dominant features of most eukaryotic genes and genomes, yet we have little knowledge about their mechanisms of acquisition (1). By using evolutionary comparisons between nematode genes, Coghlan and Wolfe (5), in this issue of PNAS, make major strides in understanding spliceosomal intron gain and provide us with a clearer picture of intron evolution in eukaryotic genomes. They not only demonstrate that 122 introns have been gained recently in Caenorhabditis genes, but also provide solid evidence that 28 of them are actually derived from “donor” introns present in the same genome. Indeed, a few of these new introns apparently derive from other introns in the same gene! Previous phylogenetic interpretations of introns indicate that many, if not most, introns have been gained once without subsequent loss (1, 6). These inferences are powerful when considering the pattern of the vast number of introns known to take residence in eukaryotic genes, but they have been impotent in illuminating the underlying molecular mechanism(s) of intron insertion. Scant …
Formal semantics for logics of cryptographic protocols

A logic and associated formal semantics specifically designed to represent and analyze cryptographic protocols are presented. A language is given with distinct means to represent knowledge of an individual word (e.g., the ability to recognize or produce a decryption key) and propositional knowledge. A sample analysis of a protocol is given to demonstrate the potential usefulness of the system. >
Responsiveness of the PedsQL to Pain-Related Changes in Health-Related Quality of Life in Pediatric Sickle Cell Disease

Objective To determine if caregiver report of the Pediatric Quality of Life Inventory (PedsQL) is responsive to changes in health-related quality of life (HRQL) associated with pain episodes in pediatric sickle cell disease (SCD). Methods 81 caregivers of children ages 2–19 years with SCD completed the PedsQL as part of routine psychosocial screenings at 2 time points, ranging from 6 to 18 months apart. Frequency of SCD-related pain episodes between time points was assessed using medical chart review. Results The frequency of pain episodes between time points was a significant predictor of decreases in physical, psychosocial, and total HRQL, even after controlling for time interval, demographic, and medical variables. Conclusions The caregiver report of the PedsQL appears to be a useful tool for capturing changes in HRQL over time associated with pain episodes in SCD.
Low calcium-phosphate intakes modulate the low-protein diet-related effect on peak bone mass acquisition: a hormonal and bone strength determinants study in female growing rats

Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous(P)arealsokeynutrientsforskeletalhealth,andinadequateintakesreducebonemassaccrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementationonbonemassinprepubertalchildrenappearstobeinfluencedbyproteinintake.Tofurther exploretheinteractionofdietaryproteinandCa-Pintakeonbonegrowth,1-month-oldfemalerats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-proteindiet-induceddecreaseinbonemassandstrength.However,thiswasassociatedwithlower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal growth. (Endocrinology 155: 4305–4315, 2014)
Tectonics, Marine Geology, and Bathymetry of the Celebes Sea-Sulu Sea Region

Contoured bathymetric charts of the Celebes Sea-Sulu Sea region form the primary basis for a geologic interpretation of the region. The large ridges and basins show abundant evidence of active tectonism in the form of scarps, recent troughs, warping, large vertical displacements, and volcanoes. Terraces below the 1000-fathom depth in the basins of both seas are an enigma. Turbidity-current deposition has flattened the floors of the basins, while Pleistocene lowering of sea level caused the cutting of wide marine shelves on the ridges. Deep channels were cut in the shelves by intensive marine currents. Deep erosional features are evidence of local and regional subsidence. Published evidence regarding tectonism and geologic history combined with the marine data reveal that: (1) the left-lateral strike-slip Philippine fault extends south of the Talaud Islands and may have at least 110 km of horizontal displacement; (2) no land existed prior to Cretaceous time; (3) much spilitic lava was extruded in late Cretaceous and early Tertiary time; (4) a major orogeny occurred in late Miocene time and that another, still active, began in late Pliocene and Quaternary time.
Food Restriction Reduces Aflatoxin B1 (AFB1)-DNA Adduct Formation, AFB1-Glutathione Conjugation, and DNA Damage in AFB1-Treated Male F344 Rats and B6C3F1 Mice

The objective of this study was to examine effects of food restriction (FR) on the metabolic activation of aflatoxin B1 (AFB1) in rats and mice, which are AFB1-sensitive and -resistant rodent species, respectively. Forty percent FR [60% of ad libitum (AL) food consumption] reduced the metabolic activation of AFB1 in both rats and mice, causing formation of hepatic AFB1-DNA adducts to be 43% and 31% lower, respectively. The AFB1-DNA adduct 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) was predominantly formed in rat liver DNA; the formation of the ring-open analogue of AFB1-N7-Gua, AFB1-formamidopyrimidine (AFB1-FAP), was predominantly found in mouse liver DNA. In contrast to the in vivo results, the in vitro AFB1-DNA adduct formation mediated by the microsomes of liver, kidney or lung from FR-mice was greater than the formation of AFB1-DNA adducts mediated by the tissue microsomes from the AL-mice. Food restriction induced hepatic glutathione S-transferase (GST) activity, as measured by the formation of AFB1-glutathione conjugates (AFB1-SG), in both rats and mice; AFB1-SG was also formed in mouse kidney. Food restriction-induced GST activity assayed in an in vitro system, using [3H]AFB1-8,9-epoxide and glutathione (GSH) as substrates, was also found when mouse kidney and lung cytosolic fractions were used. Food restriction inhibited the AFB1-induced DNA double strand breaks in mouse kidney. The reduction of levels of AFB1-DNA adduct formation in mouse kidney was comparable to the degree of AFB1-induced DNA strand breakages. The results of this study indicate that the metabolic activation of AFB1 can be modulated by FR through the alteration of the formation of AFB1-DNA adducts and AFB1-SG conjugation. However, species and tissue specificities exist regarding the metabolic activation of AFB1.
Cutaneous manipulation of vascular growth factors leads to alterations in immunocytes, blood vessels and nerves: Evidence for a cutaneous neurovascular unit

Background Skin cells produce soluble factors which influence keratinocyte proliferation, angiogenesis, nerve innervation and immunocyte response.
Magnetic Resonance Imaging Detection of Microbleeds Before Thrombolysis An Emerging Application

Background— Hemorrhagic transformation (HT) is a major complication of thrombolytic treatment for acute ischemic stroke. Although a history of prior intracerebral hemorrhage diagnosed by head CT is a contraindication to thrombolysis, there are no guidelines or data regarding evidence of prior asymptomatic microbleeds visualized with T2*-weighted magnetic resonance imaging (MRI). Methods— Pretreatment T2*-weighted MRI sequences were retrospectively analyzed in all patients receiving intra-arterial thrombolytic therapy and undergoing a pretreatment MRI at our institution. The frequency and location of prior microbleeds was determined and compared with the frequency and location of secondary HT after therapy. Results— Five of 41 patients undergoing MRI before receiving intra-arterial thrombolytic therapy demonstrated evidence of prior microbleeds on the pretreatment MRI studies. Major symptomatic hemorrhage occurred in 1 of 5 patients with microbleeds compared with 4 of 36 patients without. Only 1 patient in...
Chronic Fatigue Syndrome: A Biopsychosocial Perspective

This article reviews the current state of definitions, etiology, epidemiology, psychology, and prognosis for chronic fatigue syndrome (CFS). The evidence for understanding the pathophysiology of CFS including viral, neuroendocrine, central nervous system, and psychosocial explanations are reviewed. Research into the pathophysiology of CFS remains inconclusive but CFS is best understood as a biopsychosocial illness. Effective treatment strategies are outlined, emphasizing the importance of mind–body interactions.
Increased superoxide anion generation and altered vasoreactivity in rabbits on low-potassium diet

Potassium reduces blood pressure in populations at high risk of developing hypertension, which suggests that potassium depletion may increase vascular resistance. This study was designed to examine...
Hydrogen-bond dynamics of water at the interface with InP/GaP(001) and the implications for photoelectrochemistry.

We investigate the structure, topology, and dynamics of liquid water at the interface with natively hydroxylated (001) surfaces of InP and GaP photoelectrodes. Using ab initio molecular dynamics simulations, we show that contact with the semiconductor surface enhances the water hydrogen-bond strength at the interface. This leads to the formation of an ice-like structure, within which dynamically driven water dissociation and local proton hopping are amplified. Nevertheless, the structurally similar and isovalent InP and GaP surfaces generate qualitatively different interfacial water dynamics. This can be traced to slightly more covalent-like character in the binding of surface adsorbates to GaP, which results in a more rigid hydrogen-bond network that limits the explored topological phase space. As a consequence, local proton hopping can give rise to long-range surface proton transport on InP, whereas the process is kinetically limited on GaP. This allows for spatial separation of individual stages of hyd...
Medical student education: time for a radical change.

Dr Lindeque is from the Department of Orthopedics, University of Colorado-Denver, Aurora, Colorado. Dr Lindeque has no relevant fi nancial relationships to disclose. Correspondence should be addressed to: Bennie G.P. Lindeque, MD, Department of Orthopedics, Mail Stop F722, University of Colorado-Denver, 1635 N Aurora Ct, Aurora, CO 80045 (bennie.lindeque@ucdenver.edu). doi: 10.3928/01477447-20100924-01 I have had the opportunity to train medical students, fellows, residents, and attending physicians for 25 years. I have been exposed to and have worked with these groups on more than one continent, experiencing fi rsthand the good, the bad, and the ugly regarding medical student education. In the United States, we believe it is better to have medical students obtain a college degree fi rst so they mature and grow up in an academic world, gaining cognitive, academic, and emotional skills. We believe it will provide those who plan to attend medical school with the necessary skills to become a wellrounded physician. Let us look at the fi nancial cost of such a venture. Whether a student is privileged to receive bursaries or scholarships or whether their parents or some fi nancial institution pays for it, it does not really matter: the cost to society remains the same. What are the costs? In interviews with numerous medical students and residents over a long period, medical school costs are approximately $35,000 per year for a college degree, and by the end of medical school they are $250,000. No one, during residency, is able to signifi cantly reduce the capital debt that normally allows for living expenses. This signifi cant amount only accrues terrifying amounts of interest with big loans and the hefty task of paying back their loans at age 30 years or older (remember a fellowship also needs to be completed). Let us look at the merit of this unbelievably expensive education. Is there unequivocal proof that a medical student is too immature to start medical school directly after graduation from high school? The answer is no. Many European countries start medical students directly after high school. Most students complete a 5to 6-year medical school education and then enter a residency program. Asking medical students and residents their opinion, I have yet to meet one who thinks a 4-year college degree is essential. When asked about 4 years in medical school, they all agree that they waste time on a curriculum
Occurrence of Triscelophorus Monosporus in Upland Sites on Oahu, Hawaii

(1978). Occurrence of Triscelophorus Monosporus in Upland Sites on Oahu, Hawaii. Mycologia: Vol. 70, No. 1, pp. 188-189.