cssi/SciSciGPT-SciSciNet huggingface dataset:
Whither Russia? Autocracy Is Here for Now, but Is It Here to Stay?

Judging from some of the titles of recent books on Russia—for example, Richard Sakwa's The Crisis of Russian Democracy, Gulnaz Sharafutdinova's Political Consequences of Crony Capitalism inside Russia, and Tom Remington's The Politics of Inequality in Russia—all is not well 20 years after the collapse of the Soviet Union. Corruption abounds, and state institutions are weak where they should be strong or strong where they should be weak. Under Vladimir Putin, democracy has deteriorated since the heady early days of the 1990s, and the negative externalities of Russia's rocky economic transition—especially privatization—have made it so that social inequality permeates postcommunist society.
Time dependent simulation of the plasma discharge in an electrothermal launcher

The authors have attempted to obtain information on the source plasma component of the electrothermal launcher by extending their previous model to include a momentum balance equation. A zero-dimensional time-dependent code and its application to simulation of the electrothermal launcher are given. The properties of the plasma are evaluated self-consistently with models for electrical resistivity, the ablation process, and ionization of the plasma for the plasma source component of electrothermal launchers. This is necessary in order to model the higher energies, larger source volumes, and pressure oscillations present in electrothermal chemical launchers. The code developed for this purpose is benchmarked against another theoretical analysis that is steady state in nature. A scaling law for the vapor shielding process is derived from the benchmark case, and is used for analysis of the desired time-dependent problem. The results are presented for two experimental cases of interest. >
Parallel auditory filtering by sustained and transient channels separates coarticulated vowels and consonants

A neural model of peripheral auditory processing is described and used to separate features of coarticulated vowels and consonants. After preprocessing of speech via a filterbank, the model splits into two parallel channels, a sustained channel and a transient channel. The sustained channel is sensitive to relatively stable parts of the speech waveform, notably synchronous properties of the vocalic portion of the stimulus. It extends the dynamic range of eighth nerve filters using coincidence detectors that combine operations of raising to a power, rectification, delay, multiplication, time averaging, and preemphasis. The transient channel is sensitive to critical features at the onsets and offsets of speech segments. It is built up from fast excitatory neurons that are modulated by slow inhibitory interneurons. These units are combined over high-frequency and low-frequency ranges using operations of rectification, normalization, multiplicative gating, and opponent processing. Detectors sensitive to frication and to onset or offset of stop consonants and vowels are described. Model properties are characterized by mathematical analysis and computer simulations. Neural analogs of model cells in the cochlear nucleus and inferior colliculus are noted, as are psychophysical data about perception of CV syllables that may be explained by the sustained-transient channel hypothesis. The proposed sustained and transient processing seems to be an auditory analog of the sustained and transient processing that is known to occur in vision.
Adaptive coordinated motion control of two manipulator arms

An adaptive controller is presented for the coordinated motion control of two manipulators handling an object of unknown mass. Global convergence in tracking of both position and internal force trajectories of the object is proved, assuming perfect models for both manipulators. The computational algorithm is similar to the Newton-Euler inverse dynamics algorithm with complexity linear in the number of links in the manipulators. A significant feature of the control method is that both manipulators use the identical computational algorithm. Thus, the concept of master/slave relationship between the two manipulators is avoided. Two simulations are presented. The first assumes an ideal model for each manipulator. As expected, the controller is stable and provides excellent tracking ability of the manipulator. The second simulation investigates the effects of modeling errors in the mass properties of each arm. The position trajectories track very close to their desired values; however, they never completely converge. >
When opportunity knocks The effect of a perceived unique opportunity on compliance

Four studies examined the effect of a perceived unique opportunity on compliance. In all four studies, participants who believed they had an opportunity available to few others were more likely to agree with a request than participants who believed the opportunity was widely available or participants who received no opportunity information. We attribute the effect to a widely held heuristic that one should take advantage of unique opportunities. Study results demonstrated that people respond to a perceived unique opportunity even when supplies are not limited and when the opportunity is the result of pure chance. The results of a mediation analysis supported the interpretation that the perceived uniqueness of the opportunity underlies the effect.
A high speed shift-invariant wavelet transform chip for video compression

Wavelet-based video compression can provide improved codec and bit rates. The shift-variance problem of the discrete wavelet transform on image sequences, however, may cause large errors in motion estimation in the wavelet domain and thus degrade its performance of video compression. To make the wavelet transform of an image shift-invariant, a large amount of additional computation is required. For this reason a high-speed hardware implementation is necessary. This paper is focused on the VLSI design and implementation of a highly parallel shift-invariant wavelet transform chip. The RTL design, synthesis, simulations, and layout have been completed, and OKI Semiconductor, Inc. is fabricating the chip.
The achromatic mechanism and mechanisms tuned to chromaticity and luminance in visual search

The purpose of the study was to determine whether visual search can be mediated by an achromatic, or luminance, mechanism in which signals are independent of the chromaticity of the stimuli. Experiments were designed to determine whether variability in the chromaticity of distractor stimuli made it more difficult to search for a target that differed from the distractor stimuli in luminance. Variability in the chromaticity of the distractors had little or no effect on search times when the target stimulus was white. Variability in the chromaticity of the distractors increased search times when the target was a reddish or bluish chromaticity. Results obtained with white targets suggest that these searches are mediated by an achromatic mechanism in which the signals are independent of the chromaticity of the stimuli. Results obtained with reddish and bluish targets suggest that searches for those targets may be mediated by mechanisms tuned to both chromaticity and luminance. Further experiments in which observers searched for targets that differed from distractors in both chromaticity and luminance provided additional support for the second conclusion.
The Hedgehog pathway as targetable vulnerability with 5-azacytidine in myelodysplastic syndrome and acute myeloid leukemia

Therapy and outcome for elderly acute myeloid leukemia (AML) patients has not improved for many years. Similarly, there remains a clinical need to improve response rates in advanced myelodysplastic syndrome (MDS) patients treated with hypomethylating agents, and few combination regimens have shown clinical benefit. We conducted a 5-azacytidine (5-Aza) RNA-interference (RNAi) sensitizer screen to identify gene targets within the commonly deleted regions (CDRs) of chromosomes 5 and 7, whose silencing enhances the activity of 5-Aza. An RNAi silencing screen of 270 genes from the CDRs of chromosomes 5 and 7 was performed in combination with 5-Aza treatment in four AML cell lines (TF-1, THP-1, MDS-L, and HEL). Several genes within the hedgehog pathway (HhP), specifically SHH, SMO, and GLI3, were identified as 5-Aza sensitizing hits. The smoothened (SMO) inhibitors LDE225 (erismodegib) and GDC0449 (vismodegib) showed moderate single-agent activity in AML cell lines. Further studies with erismodegib in combination with 5-Aza demonstrated synergistic activity with combination index (CI) values of 0.48 to 0.71 in seven AML lines. Clonogenic growth of primary patient samples was inhibited to a greater extent in the combination than with single-agent erismodegib or 5-Aza in 55 % (6 of 11) primary patient samples examined. There was no association of the 5-Aza/erismodegib sensitization potential to clinical-cytogenetic features or common myeloid mutations. Activation of the HhP, as determined by greater expression of HhP-related genes, showed less responsiveness to single-agent SMO inhibition, while synergy between both agents was similar regardless of HhP gene expression. In vitro experiments suggested that concurrent dosing showed stronger synergy than sequential dosing. Inhibition of the HhP with SMO inhibitors in combination with the hypomethylating agent 5-Aza demonstrates synergy in vitro and inhibits long-term repopulation capacity ex vivo in AML and MDS. A clinical trial combining 5-Aza with LDE225 (erismodegib) in MDS and AML is ongoing based on these results as well as additional publications suggesting a role for HhP signaling in myeloid disease.
Design of broadband high-efficiency power amplifier using in-band Class-F −1 /F mode-transferring technique

A mode-transferring technique for designing high-frequency high-efficiency broadband power amplifiers is presented in this paper. It is demonstrated, for the first time, that by properly tuning the second and third harmonic impedances, a PA can operate between inverse Class-F and Class-F modes within a 1.5 ∶ 1 bandwidth. A broadband PA is designed by employing this technique with a commercial GaN transistor. The multi-mode PA operation and broadband matching are realized simultaneously using a three-stage, transmission-line-implemented, low-pass network. Simulation and experimental results show that Class-F−1 and Class-F PA modes are successfully performed at 1.8 and 2.8 GHz, respectively, with ≥ 80% measured efficiency. In addition, an overall bandwidth of 1.3–3.3 GHz is achieved by the implemented PA with > 10-dB gain, 60%–85% efficiency, and 10-W output power throughout this band.
Treatment for older men with fractures

Less than 10% of men receive osteoporosis treatment, even after a fracture. A study of 17,683 men revealed that older men, those with spinal fractures, and those taking steroids or antidepressants are more likely to receive treatment after a fracture. Seeing a primary care physician also increases osteoporosis treatment rates. In 2000, the FDA approved bisphosphonates for the treatment of osteoporosis in men. The purpose of this study is to estimate the frequency of bisphosphonate therapy within 12 months following a fracture and describe patient/physician factors associated with treatment. Health insurance claims for 17,683 men ≥65 years of age, who had a claim for an incident fracture from 2000 to 2005, were followed for at least 6 months post-fracture for the initiation of treatment with a bisphosphonate. Patient characteristics, diagnostic procedures, therapies, co-morbidities, and provider characteristics were compared for men who received treatment with those who did not. Eight percent of men (n = 1,434) received bisphosphonate therapy. Overall treatment increased from 7% in 2001 to 9% in 2005 (p < 0.001). Treatment for hip fractures remained at 7% (p = 0.747). Treatment increased with age: 6% in men aged 65–69 compared to 11.6% in men aged 85–89 (p < 0.001). Factors associated with treatment included: diagnosis of osteoporosis (OR = 8.8; 95% CI, 7.7, 10.4), glucocorticoid therapy (OR = 3.2; 95% CI, 2.4, 4.3), bone mineral density measurement (OR = 3.4; 95% CI, 2.9, 4.0), and antidepressant therapy with tricyclics (OR = 2.0; 95% CI, 1.2, 3.5) or selective serotonin reuptake inhibitors (OR = 1.7; 95% CI, 1.3, 2.4). Men with vertebral fractures (OR = 2.2; 95% CI, 1.8, 2.6) and men seen by primary physicians (OR = 2.6; 95% CI, 2.3, 3.1) were more likely to receive treatment. Less than 10% of men received bisphosphonate therapy following a low-impact fracture. Men with a primary physician were more likely to receive bisphosphonate therapy; however, <25% of men were seen by a primary physician.
The rhetoric of nostalgia: postcolonial Alexandria between uncanny memories and global geographies

Memory, nostalgia and place are subjects of increasing scholarly interest. While invoked by cultural geographers as a ‘productive force’ moulding urban landscape, nostalgia often remains an unexamined, a priori concept. Through the exploration of different reactions to the spatialized history of postcolonial Alexandria, I consider nostalgia as a fluid, multifaceted, and performative force operating at different scales and levels: on one hand, an unconscious phenomenon in the years following Egyptian nationalization, intertwining with the uncanny and bringing to surface ‘unwanted’ memories; on the other, a powerful device increasingly exploited by urban developers and the state for the construction of a ‘cosmopolitan memory’. While the former kind of nostalgia presents itself as an effective counterpart to the colonial ‘cartographic gaze’, the latter responds to the logics of cultural consumption, and constitutes a strategy adopted in an increasing number of former cosmopolitan cities seeking to negotiate ...
Common features of microRNA target prediction tools

The human genome encodes for over 1800 microRNAs, which are short noncoding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one microRNA to target multiple gene transcripts, microRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of microRNA targets is a critical initial step in identifying microRNA:mRNA target interactions for experimental validation. The available tools for microRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to microRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all microRNA target prediction tools, four main aspects of the microRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MicroRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.
Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as Signaling Intermediates in the α6β4 Integrin-Dependent Activation of Phosphoinositide 3-OH Kinase and Promotion of Invasion

Expression of the alpha6beta4 integrin increases the invasive potential of carcinoma cells by a mechanism that involves activation of phosphoinositide 3-OH kinase (PI3K). In the present study, we investigated the signaling pathway by which the alpha6beta4 integrin activates PI3K. Neither the alpha6 nor the beta4 cytoplasmic domain contains the consensus binding motif for PI3K, pYMXM, indicating that additional proteins are likely to be involved in the activation of this lipid kinase by the alpha6beta4 integrin. We identified insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the activation of PI3K by the alpha6beta4 integrin. IRS-1 and IRS-2 are cytoplasmic adapter proteins that do not contain intrinsic kinase activity but rather function by recruiting proteins to surface receptors, where they organize signaling complexes. Ligation of the alpha6beta4 receptor promotes tyrosine phosphorylation of IRS-1 and IRS-2 and increases their association with PI3K, as determined by coimmunoprecipitation. Moreover, we identified a tyrosine residue in the cytoplasmic domain of the beta4 subunit, Y1494, that is required for alpha6beta4-dependent phosphorylation of IRS-2 and activation of PI3K in response to receptor ligation. Most importantly, Y1494 is essential for the ability of the alpha6beta4 integrin to promote carcinoma invasion. Taken together, these results imply a key role for the IRS proteins in the alpha6beta4-dependent promotion of carcinoma invasion.
Making the Maker

In this article, we present a new direction for the role of Making for children. Beyond the use of Making to teach specific STEM concepts as is common in prior work, we propose that Making activities should be designed with the focus of instilling a Maker mindset in children. Our target is elementary-school-level children aged 8 to 11. We present an approach that conceptualizes Making as a 'Means-to-an-Ends' to nurture a Maker mindset and identity in children. The approach was embodied in a carefully-designed storytelling Making kit called the Maker Theater, and two Maker workshops for children in the target age range. Our analysis goal in this article was to investigate how the potential for a Maker mindset/identity formation may be manifested in children's attitudes and behaviors. Guided by a theoretical framework of three key determinants of the Maker mindset (self-efficacy, motivation and interest), we analyzed workshop data using qualitative coding methods to derive thematic indicators. We discuss our contributions and the value of our findings for the child-computer interaction community.
The Sherman Act v. Labor

M R. JUSTICE STONE'S opinion in the Apex case' has not been very instructive. He has made it dear that the Sherman Act was designed to prevent restraints on free competition in national markets, and was not devised to set the federal courts up as policing agencies to prevent those interferences with interstate transportation which local authorities should punish. But he does not say precisely what he means by protection of competition in interstate markets from the restraining activities of labor unions. His attempt to interpret and to reconcile earlier labor decisions of the Court under the Sherman Act, to correlate these with the business decisions and thereby to explain the Court's position in the Apex case is confusing. But lawyers are anxious to understand the Court's attitude toward labor union activities under the act; and this speculation is an endeavor to determine what that position may be. I
p53 mutations are associated with histologic transformation of follicular lymphoma

The majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.
The Revised Listening Concepts Inventory (LCI-R): Assessing Individual and Situational Differences in the Conceptualization of Listening

Although research at the crossroads of communication and social cognition recognizes the importance of thought to the message reception process, none to date has systematically tested how “thinking for listening” might influence the listening process. One reason for this lacuna is the lack of a valid scale capable of measuring the many conceptualizations people have about listening. Consequently, this article sets out to develop and provide validity evidence for a measure to assess individual conceptualizations of listening. In Studies 1 through 3, evidence is gathered for the construct and nomological validity of the Revised Listening Concepts Inventory (LCI-R), whereas Study 4 provides evidence that listening conceptualizations vary across four listening situations. The general discussion argues for the importance of studying message reception processes as they occur in interaction and the role the LCI-R can play in helping to advance the theory building and practice of listening.
The Nest Defense Behavior of Eastern Screech-Owls: Effects of Nest Stage, Sex, Nest Type and Predator Location

The responses of male and female Eastern Screech-Owls (Otus asio) to a human approaching the nest were examined. Intensity of nest defense as measured by distance of approach, number of flights and dives, and number of vocalizations was more pronounced during the nestling stage than during the incubation stage. These results generally support both the age-investment and positive-reinforcement hypotheses. In addition, male owls defended nestlings more vigorously than did females. As in many other owls, male screechowls are smaller than females (reversed sexual dimorphism), and the increased maneuverability of the smaller males may have contributed to this difference. Other factors (e.g., the use of a relatively large predator), however, could also be involved. Males also responded with greater intensity as the human intruder moved closer to the nest, supporting the hypothesis that "well-armed" parents hould respond vigorously as a predator gets close to a nest. Such a response informs the potential predator of the direction it must move to reduce the likelihood of injury.
Reliability of late positive component activity (P3) in healthy elderly adults.

Auditory oddball paradigms (20% targets) were used to elicit components of the event-related brain potential in healthy, late middle-aged and elderly adults (N = 32) in two separate sessions approximately 4.5 months apart. Within each session data were acquired under two conditions: (a) 250 Hz standard, 500 Hz target; and, (b) 1000 Hz standard, 2000 Hz target. Measures of P3 latency and amplitude showed moderate to high reliability (.55 to .89) over the 4.5-month interval under both stimulus conditions using data acquired from the midline frontal (Fz), central (Cz), and parietal (Pz) sites. In the second session, latencies were prolonged in the 500 Hz target tone condition, and amplitudes tended to be reduced in the 2000 Hz target tone condition. These results suggest that P3 measures in studies of older adults are reliable over time, and the findings are discussed in conjunction with prior P3 reliability studies of younger adults.
A Study on Construction of Professional Training System for Teachers of Physical Education

The importance of the development of teachers' resource is recognized internationally for educational reform and reflects the critical rules of modern education.The establishment and perfection of socialist market economy in China and the further reformation of education require placing the development of teachers in a very important position and creating favorable conditions for the development of teachers.The professional development of teachers is an important trend for the reform of teachers and education in China and will become a major topic of teachers' educational practice.Therefore,establishing a reasonable and professional training system for teachers of physical education is an important aspect of reformation in institutions of physical education.This study mainly concerns the construction of a professional training system for teachers of physical education,which includes the three phases of pre-vocational training,post-vocational training and on-the-job training,for the purpose of making contributions for a systematic study of the professional training for teachers of physical education.
Establishment and Application of DNA Fingerprint Testing System on Rice Varieties

A set of DNA fingerprint testing system on rice varieties has been established on the basis of previous researches.The major contents included selecting DNA marker type,screening SSR markers,testing methods,assaying alleles of different SSR markers,making reference ladders of different SSR markers and recording alleles of rice varieties.A total of 442 rice varieties in the national regional trials of southern China from 2005 to 2006 were assayed with established DNA fingerprint testing system.8 new alleles were found and a DNA fingerprint database containing genotypic data of the 442 rice varieties at 12 preferred SSR marker loci was constructed.Based on the database,an excellent application effect has been achieved on the assay of different varieties in distinctness and in consistency assay of the same varieties in different years.The related judging standards on distinctness and consistency were also discussed.
SY22PERSISTENT EPIGENETIC MARKS-DNA METHYLATION: WHY THIS MATTERS IN ALCOHOLISMSY22-1TRANSGENERATIONAL EPIGENETIC INHERITANCE IN ALCOHOLISM

It is now recognized that both paternal preconceptions alcohol abuse as well as maternal conception alcohol affects behaviors and health outcomes in offspring. We and others have shown that maternal conception alcohol use increases incidence of later life adult-onset diseases in children including central nervous system dysfunction, depression, anxiety, hyperactivity, inability to deal with …
Shallow Intracellular O2 Gradients and Absence of Perimitochondrial O2 “Wells” in Heavily Working Red Muscle

It is generally believed that the principal site of resistance to O2 mass transport resides within the tissue cells.1,2 In this view the ΔPO2 from sarcolemma to cell interior greatly exceeds the ΔPO2 from red cell to interstitium. Precisely the reverse is suggested by recent mathematical models of O2 release from capillaries,3,4,5,6 and by measurements on suspensions of cardiac myocytes in vitro.7 This paper reports the first measurements with sufficient spatial resolution to map intracellular O2 gradients in vivo. We find that the large-scale O2 gradient from sarcolemma to cell interior is indeed shallow, and is not significantly perturbed by small-scale gradients around individual mitochondria.
Iontophoretic Transdermal Drug Delivery

Publisher Summary This chapter details the concepts, principles, and applications of iontophoresis and explores its current standing and potential in the increasingly growing transdermal drug delivery segment. Transdermal drug delivery systems (TDDS) constitute patches that deliver low-molecular-weight molecules such as fentanyl, clonidine, nicotine, scopolamine, and various hormones such as testosterone, estradiol, and the birth control combinations of norelgestromin/ethinyl estradiol. Various penetration enhancement techniques have been investigated over the years to extend the application of transdermal delivery to agents that target other therapeutic areas. These techniques, broadly classified as chemical and physical enhancement techniques, are reversible methods that alter the skin barrier to increase the permeation of compounds through the skin and achieve therapeutically effective concentrations in the underlying tissues. Fentanyl iontophoretic transdermal system, Hybresis iontophoresis drug delivery system, and gluco watch G2 biographer for monitoring of glucose are some iontophoretic devices that are commercially available or nearing commercialization. Iontophoresis has also demonstrated great value for the delivery of macromolecules such as proteins and peptides, as it enhances their transdermal permeation while protecting them from the harsh proteolytic environments encountered with oral delivery. In addition to transdermal delivery, iontophoresis has shown great potential in other fields and is being increasingly researched for its application in the treatment of hyperhidrosis, ocular drug delivery, and for delivery through the nail for the treatment of fungal nail infections
Demyelinating Diseases of the Peripheral Nerves

Abstract Demyelinating neuropathies can be acute, subacute, or chronic. They are characterized by depressed reflexes, weakness, discriminative sensory loss, and slowed nerve conduction velocities. Etiologies include autoimmune processes, inheritance, toxins, and infection. Cerebrospinal fluid studies that demonstrate an elevated protein without a cellular response are characteristic of acute demyelinating polyradiculoneuropathy and chronic demyelinating polyradiculoneuropathy. Advances in immunology and genetics have made more precise diagnosis possible. The autoimmune neuropathies are treated with immune modulating therapies. This may include steroids, intravenous immunoglobulins, plasma exchange, and immunosuppressive medications. There are no curative therapies for the hereditary neuropathies yet. The infectious etiologies for demyelinating neuropathies, such as diphtheria and leprosy, are now less common. Toxin exposure is still an important consideration in the diagnosis of demyelinating neuropathies. Advances in the medical care have greatly improved the mortality and morbidity of patients with Guillain-Barre syndrome.
Punctuated chromatin states regulate Plasmodium falciparum antigenic variation at the intron and 2 kb upstream regions

Understanding the regulation mechanism of var gene expression is crucial for explaining antigenic variation in Plasmodium falciparum. Recent work observed that while all var genes produce transcripts, only a few var genes exhibit high expression levels. However, the global regulation of var expression and the relationship between epigenetic and genetic control remains to be established. We have systematically reanalyzed the existing genomic data including chromatin configurations and gene expressions; and for the first time used robust statistical methods to show that the intron and 2 kb upstream regions of each endogenous var gene always maintain high chromatin accessibility, with high potential to bind transcription factors (TFs). The levels of transcripts for different var gene family members are associated with this chromatin accessibility. Any given var gene thus shows punctuated chromatin states throughout the asexual life cycle. This is demonstrated by three independent transcript datasets. Chromatin accessibility in the var intron and 2 kb upstream regions are also positively correlated with their GC content, suggesting the level of var genes silencing might be encoded in their intron sequences. Interestingly, both var intron and 2 kb upstream regions exhibit higher chromatin accessibility when the genes have relatively lower transcription levels, suggesting a punctuated repressive function for these regulatory elements. By integrating and analyzing epigenomic, genomic and transcriptomic data, our work reveals a novel distal element in var control. We found dynamic modulations of specific epigenetic marks around the var intron and distal upstream regions are involved in the general var gene expression patterns in malarial antigenic variation.
Managing and Preventing Soft Tissue Complications

Minimally invasive surgery (MIS) techniques for lumbar fusion have been undergoing a development and evolution for the past two decades. As such, they are continuously being validated by clinical and radiological studies. Among various surgical methods, the approach to the anterior column of the lumbar spine with a lateral and transpsoas procedure was innovated and popularized by Pimenta in 2001, who described the procedure as an “extreme lateral interbody fusion” (XLIF) [1]. Whether it is called lateral lumbar interbody fusion (LLIF), direct lateral interbody fusion (DLIF), or XLIF, this surgical approach offers several advantages comparing to traditional methods for interbody fusion, including the avoidance of mobilization of great vessels, less operative time, and reduced blood. In addition, there is no requirement for retraction of the nerve roots or the need for an approach surgeon (such as with true anterior approaches). The application of such MIS techniques and its application as a more sophisticated procedure to treat adult deformity undoubtedly have been a powerful tool in the surgical armamentarium in the new millennium.
Paradoxes of Immunity and Immunosuppression in Salmonella Infection

There is continuing interest in mechanisms of immunity to systemic Salmonella infection, as concepts regarding the relative contributions of humoral and cellular immunity to host defense against these organisms form the theoretical basis for development of improved vaccines against typhoid fever (1,2). (Experimentally, investigations are carried out using a mouse model of systemic infection with Salmonella typhimurium as S. typhi is not virulent for mice.) Although the current typhoid vaccine, consisting of acetone-killed cells, has been shown to be protective in humans (3), it has an undesirable level of toxicity (1). Recent efforts have focused on live, attenuated strains of S. typhi which can be given orally, as an alternative vaccine strategy. A galE mutant, Ty21a, has been shown to have efficacy in a field trial in Egypt (4) although results have been less promising in field trials in Chile (5). One drawback of the Ty2la strain is that the exact nature of the genetic lesions which confer loss of virulence are not known (6). Stocker and colleagues have developed a series of mutants in various species of Salmonella which are blocked in aromatic synthesis due to transposon-mediated gene deletions or inversions (7,8). Based on high levels of protection induced in mouse models of typhoid fever using these aroAstrains of S. typhimurium Stocker has developed attenuated S. typhi with similar types of lesions for potential use in humans against typhoid fever (9). In addition, there is also considerable interest in using these aro-strains as vectors for cloned genes of other organisms such as E. coli enterotoxins (10,11).
Effect of Increased Tissue Factor Pathway Inhibitor (TFPI) Levels On Factor Xa Inhibition and Global Hemostasis in the Presence of TFPI-Antagonistic Aptamer BAX 499.

Abstract Abstract 2207 In a recent hemophilia clinical trial, patients' TFPI plasma levels substantially increased after intravenous or subcutaneous administration of TFPI-inhibitory aptamer BAX 499. To better understand the consequences of elevated plasma full-length (fl)-TFPI and the potency of BAX 499, the TFPI-inhibitory activity of a wide concentration range of BAX 499 was tested at levels up to 10 nM fl-TFPI in two model systems and in two global hemostatic coagulation assays. Factor Xa (FXa) inhibition assay measured the influence of BAX 499 on the interaction between TFPI and FXa. BAX 499 at 1000 nM efficiently inhibited fl-TFPI within the physiological concentration ( In thrombin generation assays with FVIII-inhibited plasma, a substantial excess of BAX 499 was required to compensate the anticoagulant activity of increasing fl-TFPI. Based on peak thrombin values, fl-TFPI levels that could be neutralized by a given BAX 499 concentration were determined. For example, a ∼50-fold excess of BAX 499 neutralized 0.2 nM TFPI added to FVIII-inhibited plasma, whereas a 140-fold excess was required for neutralization of 7.3 nM fl-TFPI added. An equivalent ROTEM experiment performed in FVIII-inhibited whole blood confirmed these findings. In summary, the data showed that even a high concentration of BAX 499 (1 μM) was not able to counteract the strong inhibitory effect of 10 nM fl-TFPI on FXa, on TF-FVIIa-catalyzed FX activation, on thrombin generation in plasma and clot formation in whole blood, due to the partially inhibitory properties of BAX 499. The current study offers an explanation for increased bleeding tendency in hemophilia patients associated with the ≥25-fold elevated fl-TFPI plasma levels after BAX 499 administration. BAX 499 does not appear to be able to compensate the anticoagulant activity of increased TFPI levels caused by partial inhibition in patients treated with BAX 499. Disclosures: No relevant conflicts of interest to declare.
Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Return in a 13-Day-Old Infant Presenting Acutely to the Emergency Department: A Case Report.

Abstract Background Total anomalous pulmonary venous return (TAPVR) is an uncommon congenital heart defect. Obstructed forms are more severe, and typically present earlier in life, usually in the immediate newborn period, with symptoms of severe cyanosis and respiratory failure. Case Report A 13-day-old boy presented to the emergency department (ED) with respiratory extremis. He appeared cyanotic and limp, and was found to have significant hypoxia with oxygen saturation of 40%. He had no improvement of oxygenation with bag-valve-mask ventilation despite a fraction of inspired oxygen near 100%. This gave clear indication that the hypoxia was caused by a shunt and not by hypoventilation, a ventilation/perfusion mismatch, or a barrier to diffusion. Next, the patient was intubated emergently. Broad spectrum antibiotics and fluid resuscitation with normal saline were initiated. A chest radiograph showed evidence of pulmonary edema vs. diffuse interstitial disease. Cardiology was consulted and evaluated the child with an echocardiogram, which revealed TAPVR with infradiaphragmatic obstructed veins. Once stabilized, he was transferred for definitive surgical repair. This is, to our knowledge, the first reported case of TAPVR with infradiaphragmatic obstruction presenting to the ED with hemodynamic and respiratory compromise beyond the first week of life. Why Should an Emergency Physician Be Aware of This? Despite improvements in antenatal and newborn screening, congenital heart disease often remains an elusive diagnosis. Some patients with these critical lesions are discharged home before the manifestation of their disease becomes apparent. Once symptomatic, these patients often present to the ED in extremis. We conclude that it is important to recognize this presentation to ensure proper evaluation and early diagnosis. If misdiagnosed, many of the usual therapies for other diseases could be detrimental.
Flipping a citrate switch on liver cancer cells

Energy homeostasis and oncogenic signaling are critical determinants of the growth of human liver cancer cells, providing a strong rationale to elucidate the regulatory mechanisms for these systems. A new study reports that loss of solute carrier family 13 member 5, which transports citrate across cell membranes, halts liver cancer cell growth by altering both energy production and mammalian target of rapamycin signaling in human liver cancer cell lines and in both an in vitro and in vivo model of liver tumors, suggesting a new target for liver cancer chemoprevention and/or chemotherapy.
Responses of inflammatory cytokines following moderate intensity walking exercise in overweight or obese individuals

This study investigated the effects of a 4-week moderate intensity walking exercise on the levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and adiponectin in overweight or obese individuals. Twenty-seven (13 men and 14 women) physically inactive, over-weight or obese (body mass index>25.0 kg/m2) individuals participated in the study. Each participant was randomly assigned to either exercise (EX; n=15) or control (CON; n=12) group. The EX group performed moderate intensity walking exercise on a treadmill for 60 min at 70% of maximal heart rate for 4 weeks (3 days/wk). Overnight fasting blood samples were collected before and after the study period (Pre and Post) to analyze the levels of pro-/anti-inflammatory cytokines such as CRP, TNF-α, and adiponectin. CRP and adiponectin as well as body weight and body composition were not significantly altered following the 4-week exercise intervention. However, there was a significant group×time interaction for TNF-α. The post hoc test revealed that the level of TNF-α significantly decreased only in EX (EX: mean±standard deviation, Pre 55.18±6.57 pg/mL, Post 50.31±6.22, P=0.018 vs. CON: Pre 55.5±5.88, Post 58.19±6.48, P=0.25). EX Post was also significantly lower as compared to CON Post (P=0.0074). Although there was no change in body weight or fat mass, the 4-week aerobic exercise training was long enough to decrease the level of TNF-α, indicating physical activity may improve level of inflammation independently from the change in fat mass. The current study also confirmed previous research suggesting that longer period of exercise training accompanied by weight loss may be required to induce significant changes in CRP and adiponectin.
A Comparison of Guernsey Sires: II. Based on the Average Mature Equivalent Fat Production of Daughters During the Month of Maximum Production

Summary 1.Rather than to attempt a factorial analysis of the milk secreting function of the dairy cow, it is proposed that the characteristics of the lactation curve be studied in order to group together all factors which may affect certain parts and to study these characteristics from a genetic standpoint. 2.The two most important characteristics of the lactation curve of milk secretion are believed to be the height of production of milk and fat during the maximum month or other convenient unit of time, and the persistency of secretion or the rate of decline of production. 3.A study was made of Guernsey Advanced Registry records to determine the relative effect of the sire and dam on the daughters maximum fat production. 4.The results were expressed by the two following equations: \( 1 \) Daughter's maximum fat production = 0.20 × dam's maximum fatproduction + sire's potential transmittingability \( 2 \) Sire's potential transmitting ability = daughter's maximumfat production -0.20 × dam's maximum fatproduction 5.The cytological studies indicate that the sire and dam contribute the same number of chromosomes to the female. The male is the result of the usual number of chromosomes from the dam and one less from the sire. This is taken to indicate that the above results can not be explained by sex-linked inheritance. 6.The results are believed to be explained by assuming that the majority of the genes concerned in the inheritance of large fat secretion are dominant over small secretion. Such being the case, the only true test of an animal's transmitting ability is a test of the progeny as compared to a performance record.
Stress and Stress Management with the Elderly

The relationship of stress to psychological functioning and health has been examined for some time by both basic and applied researchers. Stress has been associated with the onset and/or course of a number of physical and psychological conditions. Consequently, stress reduction procedures have been increasingly utilized with children and adults in both primary and adjunctive treatment. Such procedures have been used successfully to treat a range of anxiety disorders such as phobias, obsessive-compulsive behavior, and generalized anxiety. They have also been used in the treatment of other psychological disorders in which anxiety plays an important role, such as somatic complaints, paranoid ideation, depression, and in the treatment of psychophysiological dysfunctions such as high blood pressure, lower-back pain, headache pain, and the aversive side effects of cancer treatment. Despite relatively high rates of both psychological disorders and psychophysiological conditions, the elderly have been systematically neglected in the stress management literature. These individuals face a number of potentially stressful situations that are unique to this age group and place them at risk for developing stress-related disorders. This chapter will focus upon the use of stress management procedures with the elderly First, there will be a brief examination of conceptual issues in stress research. This will be followed by a discussion of reported problems in generalizing stress management procedures to the elderly population.
Virtual Reality Interaction Techniques for Individuals with Autism Spectrum Disorder

Virtual reality (VR) systems are seeing growing use for training individuals with Autism Spectrum Disorder (ASD). Although these systems indicate effective use of VR for training, there is little work in the literature evaluating different VR interaction techniques for this audience. In this paper, different VR interaction techniques are explored in the Virtual Reality for Vocational Rehabilitation (VR4VR) system and additional data analysis on top of our previously published preliminary results [1] was performed via a user study with nine individuals with ASD and ten neurotypical individuals. The participants tried six vocational training modules of the VR4VR system. In these modules, tangible object manipulation, haptic device, touch and snap and touchscreen were tested for object selection and manipulation; real walking and walk-in-place were tested for locomotion; and head mounted display and curtain screen were tested for display. Touchscreen and tangible interaction methods were preferred by the individuals with ASD. The walk-in-place locomotion technique were found frustrating and difficult to perform by the individuals with ASD. Curtain display received higher preference scores from individuals with ASD although they accepted the HMD as well. The observations and findings of the study are expected to give insight into the poorly explored area of experience of individuals with ASD with various interaction techniques in VR.
Controlling workability in alkali-activated Class C fly ash

Abstract Alkali-activation of Class C fly ashes can produce Portland cement-free binders that take advantage of sodium aluminosilicate hydrate (N-A-S-H) and aluminum-substituted calcium silicate hydrate (C-A-S-H) phases for strength development. However, alkali-activated Class C fly ashes suffer from poor workability and rapid setting; traditional water-reducing admixtures are not effective. In this study, different methods to modify the workability of alkali-activated Class C fly ash mixtures were investigated. Retarders decreased the mixture stiffness and delayed setting, but strength development suffered. Increasing mixing intensity slightly improved workability without significantly impacting strength. Controlling silica modulus significantly improved workability, but the impact on strength was inconsistent.
Critique Of Session II

In hearing the four different perspectives on the Climate Change Action Plan, I think three very important themes emerge. The first is that there is a gap, a gap between the objectives of our efforts and current policies to address climate change. That’s true at both the international and the national level.