cssi/SciSciGPT-SciSciNet huggingface dataset:
Increasing the length of poly-pyrimidine bulges broadens RNA conformational ensembles with minimal impact on stacking energetics.

Helical elements separated by bulges frequently undergo transitions between unstacked and coaxially stacked conformations during the folding and function of noncoding RNAs. Here, we examine the dynamic properties of poly-pyrimidine bulges of varying length (n = 1-4, 7) across a range of Mg2+ concentrations using HIV-1 TAR RNA as a model system and solution NMR spectroscopy. In the absence of Mg2+, helices linked by bulges with n ≥ 3 residues adopt predominantly unstacked conformations (stacked population 74%). In the presence of 3 mM Mg2+, the helices predominantly coaxially stack (stacked population >84%), regardless of bulge length, and the midpoint for the Mg2+-dependent stacking transition is within threefold regardless of bulge length. In the absence of Mg2+, the difference between free energy of interhelical coaxial stacking across the bulge variants is estimated to be ∼2.9 kcal/mol, based on an NMR chemical shift mapping with stacking being more energetically disfavored for the longer bulges. This difference decreases to ∼0.4 kcal/mol in the presence of Mg2+ NMR RDCs and resonance intensity data show increased dynamics in the stacked state with increasing bulge length in the presence of Mg2+ We propose that Mg2+ helps to neutralize the growing electrostatic repulsion in the stacked state with increasing bulge length thereby increasing the number of coaxial conformations that are sampled. Energetically compensated interhelical stacking dynamics may help to maximize the conformational adaptability of RNA and allow a wide range of conformations to be optimally stabilized by proteins and ligands.
Monaural edge pitch and models of pitch perception

Noise with a sharp spectral edge produces a definite, perceived pitch. The pitch of lowpass noise lies slightly below the edge and the pitch of highpass noise slightly above it. The pitch shifts away from the edge, expressed in semitones, increase with the decreasing edge frequency. A neural timing model based on positive peaks of the autocorrelation function accounts for the broad features of the shifts. So, does a place model based on the peak of an excitation pattern as enhanced by lateral inhibition. As the edge frequency decreases below 150 Hz, the pitch persists for a lowpass noise but disappears for highpass noise. This result is consistent with the timing model but not with the place model. For high edge frequencies, the pitch is stronger for highpass noise than for lowpass noise—consistent with both timing and place models. As the edge frequency approaches 5000 Hz, the pitch disappears for most listeners, but for some listeners, a pitch persists for edge frequencies beyond 8000 Hz. The latter res...
Commentary on Justin London’s MTO 0.2 article

OK, but I didn’t sense this. I.e. We start with no expectations, we hear a note, we ask “is it a downbeat or an upbeat?” We listen to confirm one or the other alternative. BUT for the last note A, we have heard quite a few pitches in a series, we come to expect the same, but hear silence instead, which thus accents the last note strongly. I seem to hear the A as stronger than the C, thus I arrange duples and triples to come up with A as downbeat. I end up getting either c alone as upbeat in duple meter (C DE FG A) or c and d as upbeats in triple meter (CD EFG A) (a possibility not mentioned by RP).
A Video-Based, Case-Control Study of Factors Associated With Intraosseous Catheterization During Pediatric Resuscitation.

Study objective Factors associated with intraosseous (IO) catheterization are not well described. Our objective is to identify factors associated with the attempt and timing of IO catheterization in a pediatric emergency department (ED) resuscitation setting. Methods We completed a video-based, case-control study (1:3 ratio) of children undergoing IO catheterization in the resuscitation area of a high-volume, academic, pediatric ED. We selected 8 independent factors a priori for analysis: younger than 2 years, Glasgow Coma Scale score less than 8, cardiopulmonary resuscitation (CPR), parent or caregiver presence, physician team leader with greater than 5 years of pediatric ED experience, 2 or more IO-catheterization-capable staff, ultrasonographically trained nurse vascular access team presence, and resuscitation occurring during the evening (4 pm to midnight) or overnight (midnight to 8 am) shift. We fit linear regression models to analyze for associations with IO access attempts and timing. Results One hundred fourteen patients were enrolled; 40 encounters involved IO catheterization (35.1%). Only CPR was associated with IO catheterization (odds ratio 39.0; 95% confidence interval 12.5 to 121.6). Mean time to IO attempt was shorter with CPR (3.2 versus 14.2 minutes) and longer with vascular access team presence (23.5 versus 3.4 minutes) or caregiver presence (10.5 versus 2.6 minutes). Of resuscitations that achieved peripheral intravenous access, only 1 (1.1%) did so in less than 90 seconds. Conclusion CPR was the only factor associated with IO access attempts, whereas providers may have been more hesitant to attempt IO catheterization with vascular access team or caregiver presence. Future studies should include a larger, multicenter sample and use qualitative methods to explore reasons for IO catheterization hesitancy, especially in the nonarrest scenario.
Ubiquitous Access for Local Water Management Through HCI Based App Development

Climate conditions are uncertain, thus it is crucial to get advance information on parameters such as precipitation at various regions to plan sustainable living. It is useful to obtain this information anywhere and anytime to facilitate local water management. Accordingly, the main goal of our project is to develop a Hydro-climate Data App that estimates water related climactic parameters at given locations based on global predictive models in Earth and Environmental Science. We consider climate data for regions in New Jersey. Users are required to input a location and year for which the app displays the latitude and longitude, and predicts the output on precipitation, humidity and temperature. This app is interactive and user-friendly, deploying aspects of HCI (Human Computer Interaction), such that expert as well as non-expert users can easily access and interpret it. Challenges in this work include procurement and deployment of accurate prediction techniques. To address these, we research various scientific models, e.g. CCSM (Community Climate System Model) and embed suitable ones into the app using HCI aspects such as ethnographic studies. As evident from our evaluation, this app is beneficial to environmental scientists, students and local residents. It is useful for research on climate change and sustainability. This work fits the scope of SDGs (Sustainable Development Goals) of the United Nations, mapping to at least 3 of its 17 goals. It addresses the theme of IoT (Internet of Things) that entails providing Internet based information in everyday devices for ubiquitous access.
Nusinersen in adult patients with spinal muscular atrophy: Observations from a single center

Objective To report our experience with adult patients with spinal muscular atrophy (SMA), some of whom were treated with nusinersen. Methods We reviewed charts of adult patients with SMA seen in our neuromuscular clinic between 2017 and 2019 and noted their demographics, clinical characteristics, treatment, and side effects. Results Twenty-two patients were included. Nine had type 2 and 13 type 3 SMA. Median age was 36 years (range 20–71). Most could not walk unassisted. Ten patients had significant respiratory impairment necessitating ventilation and 2 had tracheostomy. Seventeen had severe scoliosis. Ten patients were treated with nusinersen for 6–24 months (median 12 months), 3 of whom required bone laminectomy for intrathecal access. One developed bowel and bladder incontinence following the procedure. In the treated group, on average, % Medical Research Council change was 2.5% at 12 months and 3.9% at 24 months. Most untreated patients remained stable; 3 had slightly declined. Five treated patients reported subjective improvement. Treatment side effects included post lumbar puncture headache in 5 patients, 2 of whom needed blood patch, and 1 bacterial meningitis requiring inpatient treatment. Three patients stopped treatment after 12–24 months due to lack of improvement, recurrent pneumonia, or proteinuria. Conclusion Side effects of nusinersen can be serious. Whereas half of treated patients reported modest improvement in function, there were no significant objective changes, which may point largely to a placebo effect. Classification of evidence This study provides Class IV evidence that for some adult patients with SMA, nusinersen improves subjective function and causes serious adverse effects.
Attending to Ancient Voices

This chapter explores the power of the voice as an entryway into the mysteries. The sound-based trance work of composer Wendalyn Bartley and experimental Inuit throat singer Tanya Tagaq are introduced. These artists demonstrate how a practice of working with the body as a vocal chamber resonating with ancient voices can awaken and attune us to the self, the other and the cosmos simultaneously. A sounding/listening practice is shared at the close of the chapter.
Health implications of maltreated children exposed to domestic violence

Domestic violence affects thousands of children in the United States every year. We aimed to obtain an association between caregiver suffrage of domestic violence and adverse health outcomes among maltreated children in the United States. Data from the National Child Abuse and Neglect Data System, a total sample of 3,459,625, was analyzed. Descriptive, bivariate, and logistic regression analysis was conducted to estimate the effect of domestic violence on maltreated children’s health outcomes such as children’s alcohol and drug use, mental developmental delay, emotional disturbances, visual or hearing impairment, learning, and physical disabilities, behavioral problems, and other medical conditions. Exposure to caregiver domestic violence was reported in 13% of cases (n = 276,770). Domestic violence was associated with gender, child’s age, race, ethnicity, and living arrangement (p = 0.001 for all). Adjusted logistic regression showed higher odds of children’s alcohol use (1.62, 95%CI 1.44–1.82), mental developmental delay (1.26 95%CI 1.11–1.42), emotional disturbances (1.13, 95%CI 1.05–1.22), learning disability (1.13, 95%CI 1.04–1.22), and behavioral problems (1.18, 95%CI 1.12–1.24) among those children whose caregivers were exposed to domestic violence. Domestic violence is a fundamental problem in the US that can lead to detrimental health and developmental issues in children.
Africana Studies, 21st Century Black Student Activism, and High Impact Educational Practices: A Biographical Sketch of David C. Turner, III:

This article examines the relationship between academia and activism. It explores the undergraduate experience of veteran 21st century Black student activist, David C. Turner, III, revealing the fo...
Path Following with Stable and Unstable Modes Subject to Time-Varying Dwell-Time Conditions

Abstract Systems are often tasked with operating in modes where state feedback is available intermittently. The analysis of such systems involves analyzing the behavior of individual subsystems and the time that each subsystem is active, i.e., dwell-time conditions. Often, these dwell-time conditions are conservative, potentially limiting the performance of the overall system. In an effort to reduce conservativeness of the dwell-time condition, an adaptive data-driven extremum seeking (ESC) method is used to develop a time-varying dwell-time condition. Specifically, the ESC drives the evolution of the dwell-time condition to a less conservative dwell-time condition while simultaneously ensuring stability of the overall system. Simulations demonstrate a nearly threefold increase in a maximum dwell-time that results in significant changes to the behavior of an agent tasked with following a path outside a feedback region.
Tegaserod for Irritable Bowel Syndrome With Constipation in Women Younger Than 65 Years Without Cardiovascular Disease: Pooled Analyses of 4 Controlled Trials.

INTRODUCTION Tegaserod was the first US Food and Drug Administration-approved drug for irritable bowel syndrome with constipation (IBS-C) in women and was recently reapproved for use. Recognizing that clinical trials were performed almost 20 years ago, we performed an integrated analysis on patient-reported outcomes relevant to current practice including previously unpublished data. METHODS Data from 4 12-week, randomized, placebo-controlled trials evaluating tegaserod 6 mg b.i.d. in patients with IBS-C were pooled. We analyzed 2 groups: all women (overall population) and women younger than 65 years without a history of cardiovascular ischemic events (indicated population). The primary end point was subjective global assessment of IBS-C symptom relief. Responders rated themselves as "considerably" or "completely" relieved ≥50% of the time or at least "somewhat relieved" 100% of the time over the last 4 weeks. RESULTS The overall and indicated populations included 2,939 (tegaserod [n = 1,478]; placebo [n = 1,461]) and 2,752 (tegaserod [n = 1,386]; placebo [n = 1,366]) participants, respectively. The pooled odds ratios (95% confidence interval) for clinical response during the last 4 weeks in the overall and indicated populations with tegaserod were 1.37 (1.18, 1.59; P < 0.001) and 1.38 (1.18, 1.61; P < 0.001). In the overall and indicated populations, clinical response rates for tegaserod during the last 4 weeks were 43.3% and 44.1% versus 35.9% and 36.5% with placebo (P < 0.001). Adverse events were similar between groups. No significant cardiovascular events related to tegaserod were observed in patients with ≤1 cardiac risk factor. DISCUSSION Tegaserod 6 mg b.i.d. reduced IBS-C symptoms in overall and US Food and Drug Administration-indicated populations (women aged <65 years with no history of cardiovascular ischemic events).
App Usage Associated With Full Redemption of WIC Food Benefits: A Propensity Score Approach.

Abstract Objective To examine the relationship between WICShopper application (app) usage and full redemption of Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food benefits. Design A cross-sectional study. Setting West Virginia WIC program. Participants A total of 23,050 West Virginia WIC households in 2019. Main Outcome Measures Full redemptions were defined as the redemption rate of ≥ 90% for a given food benefit. Analysis App/non-app users were defined as households with someone using/not using the WICShopper app. Multivariate logistic regressions were applied. To address the potential self-selection bias in app usage, the propensity score (PS) of app usage was estimated. The regressions were rerun with the balanced sample by matching the PS. Results With PS matching, the prevalence of full redemption at the household level was 7.2% for app users vs 4.7% for nonapp users (odds ratio, 1.64; 95% confidence interval, 1.40–1.92; P Conclusions and Implications Use of the WICShopper app was associated with a higher prevalence of full redemptions in most food benefits after controlling the self-selection bias.
Software-Defined Architecture for Infrastructure-less Mobile Ad Hoc Networks

Most existing Software-Defined Networking (SDN) architectures for ad hoc networks impose one or more of the following constraints: infrastructure support, out-of-band single-hop (direct) links, location tracking, or preexisting IP connectivity. These limitations make the existing architectures inadequate for managing infrastructure-less Mobile Ad Hoc Networks (MANET) having limited bandwidth, unreliable connectivity, and susceptibility to high interference, packet collisions, and losses. In our dissertation, we design an architecture for Software-Defined Mobile Ad Hoc Networks (SD-MANET) that does not have any of the above constraints. We present three centralized communication protocols catering to MANET’s need for proactive, reactive, and hierarchical routing strategies. We also develop two decentralized zero-control-packet routing protocols for MANETs characterized by ultra-low data rates. We present theoretical analyses of our protocols and perform simulation experiments addressing a wide range of scenarios: network scalability, density, traffic load, node mobility, and data rate. The results indicate that our solutions provide better performance than state-of-the-art approaches in most scenarios and address the inherent MANET challenges.
Visits for Possible COVID-19 in a Pediatric Primary Care Practice Early in the Pandemic

BACKGROUND: Children with COVID-19 usually present with mild symptoms. We characterize visits with respect to symptoms and testing in the outpatient setting. METHODS: A retrospective chart review of sick visits in a pediatric academic primary care clinic April-August 2020. We included possible COVID-19 cases, or "persons under investigation" (PUIs), recording symptoms, positive contacts, and COVID-19 testing. Descriptive statistics and Chi-square or Fisher's exact tests for comparisons were used. RESULTS: 32% (476/1,474) of sick visits were PUIs;20% were telehealth. Symptoms most commonly reported were fever, congestion/rhinorrhea and cough. 76% of PUIs were tested for COVID-19. Only presence of COVID-19 contacts and loss of taste/smell were significantly associated with positive tests (p<0.001). CONCLUSION: Nearly a third of sick visits in an academic pediatric practice were seen for possible COVID-19 symptoms and most were tested. The majority with and without COVID-19 had fever, congestion and/or cough. Our findings suggest low thresholds for testing in children.
Hypothalamic actions and interactions of alcohol and IGF-1 on the expression of glial receptor protein tyrosine phosphatase-β during female pubertal development.

Background: Hypothalamic glial–neuronal communications are important for the activation of luteinizing hormone releasing hormone (LHRH) secretion at the time of puberty. As we have shown that alcohol (ALC) diminishes prepubertal LHRH secretion and delays puberty, we first assessed the effects of short-term ALC administration on the basal expression of a specific gene family involved in glial–neuronal communications. Second, as insulin-like growth factor-1 (IGF-1) is a critical regulator of LHRH secretion and the pubertal process, we then assessed whether IGF-1 could induce the expression of these signaling genes and determine whether ALC can block this affect. Methods: Immature female rats were fed a liquid diet containing ALC for 6 days beginning when 27 days old. Control animals received either the companion isocaloric liquid diet or rat chow and water. Animals were decapitated on day 33, in the late juvenile stage of development. Medial basal hypothalamic (MBH) tissues were obtained for gene and protein analyses of glial receptor protein tyrosine phosphatase-β (RPTPβ) and the 2 neuronal components, contactin and contactin-associated protein 1 (Caspr1). In the second experiment, IGF-1 was administered into the third ventricle (3V) and the MBH removed 6 hours after peptide delivery, and the above-mentioned 3 genes were analyzed by real-time PCR. To determine whether this action was affected by ALC, immature female rats were administered either ALC (3 g/kg) or water via gastric gavage at 0900 hours. At 1030 hours, the ALC and control groups were subdivided such that half of the animals were injected into the 3V with IGF-1 and the other half with an equal volume of saline. Rats were killed 6 hours after the IGF-1 injection and MBHs collected. Results: Real-time PCR showed that when compared with control animals, ALC caused a marked decrease (p < 0.001) in the basal expression of the RPTPβ gene, but did not affect the expression of either contactin or Caspr1. Likewise, analysis by Western blotting demonstrated that ALC caused suppressed (p < 0.001) levels of the RPTPβ protein, with the expressions of both contactin and Caspr1 proteins being unaltered. In the second experiment, results showed that only the RPTPβ gene was stimulated (p < 0.05) by IGF-1 in the MBH 6 hours after peptide delivery. Assessments revealed that the IGF-1 induced increase (p < 0.01) in the expression of the RPTPβ gene was blocked by the presence of ALC. Conclusions: Prepubertal ALC exposure is capable of interfering with hypothalamic glial–neuronal communications by suppressing the synthesis of the glial product, RPTPβ, which is required for binding to the contactin–Caspr1 complex on LHRH neuronal terminals, thus suggesting that this action of ALC contributes to its detrimental effects on the pubertal process.
The Early Evolution of the Hominoid Face

In phylogenetic analyses of hominoid primates, the face as an anatomical unit has often been considered to be of secondary importance in comparison with dental and postcranial evidence (e.g., Andrews and Martin, 1987), related both to the abundance of teeth in the fossil record and to the predominance of postcranial characteristics in diagnoses of the superfamily (e.g., Harrison, 1987). Recent fossil discoveries and the adoption of more rigorous phylogenetic methods, however, provide an opportunity to document more fully the evolution of the hominoid facial skeleton and to decipher the phylogenetic signal contained within this important anatomical region.*
Nuclear Fusion of Signaling Pathways

There is often crosstalk between signal transduction pathways activated by different cytokines. In this issue, Nakashima and colleagues report on one way in which signaling pathways communicate. They show that the signaling pathways for two cytokines (LIF and BMP2), which are necessary for astrocyte differentiation, can interact synergistically through the binding of their transcription factor targets (STAT3 and Smad1, respectively) to a common transcriptional coactivator molecule called p300. Janknecht and Hunter comment on these findings in a Perspective and discuss ways in which the STAT3-Smad1-p300 complex brings about transcription of target genes.
Does peak inspiratory flow contribute to setting VO2max? A test of symmorphosis.

Symmorphosis predicts that animal design is optimized in such a way that structure 'statisfies but does not exceed' functional requirements. To provide one test of this hypothesis, we examined peak inspiratory flow and its relation to maximum oxygen uptake in humans. We measured maximal forced (peak) inspiratory flow (VImax) and maximum oxygen uptake (VO2max) via cycle ergometry in well trained (VO2max > 65 ml O2.kg-1.min-1) and untrained (VO2max < 45 ml O2.kg-1.min-1) male subjects. Tests of VImax and peak oxygen uptake (VO2peak) were made while the subjects were breathing through inspiratory orifices differing in area. VImax varied as an identical function of orifice diameter in both groups of subjects. However, VO2peak was more sensitive to decreasing orifice diameter in trained endurance athletes than it was in untrained individuals. The diameter of the largest orifice that caused a reduction in oxygen uptake was over two times larger for trained than for untrained subjects, corresponding to about a four-fold difference in resistance at any flow rate. These results suggest that the structures setting VImax (airway resistance and inspiratory muscle strength) are not matched to oxygen demand (VO2max) in humans. While these structures seem to be 'over-built' and hence do not likely contribute to setting the limits to aerobic performance in most humans, they may be among the primary limiting factors in the most elite endurance athletes.
How retinal microcircuits scale for ganglion cells of different size

Ganglion cell receptive field centers are small in central retina and larger toward periphery. Accompanying this expansion, the distribution of sensitivity across the centers remain Gaussian, but peak sensitivities decline. To identify circuitry that might explain this physiology, we measured the density of bipolar cell synapses on the dendritic membrane of beta (X) and alpha (Y) ganglion cells and the distribution of dendritic membrane across their dendritic fields. Both central and peripheral beta cells receive bipolar cell synapses at a density of approximately 28/100 microns2 of dendritic membrane; central and peripheral alpha cells receive approximately 13/100 microns2. The distribution of dendritic membrane across the dendritic field is dome- like; therefore, the distribution of bipolar cell synapses is also dome- like. As the dendritic field enlarges, total postsynaptic membrane increases with field radius, but only linearly. Consequently, density of postsynaptic membrane in the dendritic field declines, and so does density of synapses within the field. The results suggest a simple model in which the receptive field center9s Gaussian profile and peak sensitivity are both set by the density of bipolar cell synapses across the dendritic field.
A high performance 3.0 mm /spl times/3.0 mm /spl times/1.1 mm FBAR full band Tx filter for U.S. PCS handsets

A stringent demand has been placed on the transmit and receive bands of the 1900 MHz U.S. PCS communication standard which requires that the bands be separated by a 20 MHz (1 %) guardband. This narrow guardband poses a challenge to RF filter designers who want to produce a transmit (Tx) filter with low insertion-loss and with sufficient receive band (Rx) rejection required to prevent Tx signal power from being splattered into the Rx signal path. The transition region (from pass to stop band) would have to be a fraction of the 20 MHz guardband. The unused portion of the guardband would have to be allotted to account for random and systematic variations in the center frequency of the transition due to filter manufacturing variations and operating temperature variations respectively. The difficulty in designing a Tx filter with a sufficiently narrow transition region has caused handset manufacturers to employ a dual filter scheme in which each filter operates over half of the Tx band and can be switched into or out of the transmit path. In this scheme the guardband for each filter is increased to 50 MHz, thus greatly relaxing the filter design constraints. The downside of this scheme is that each handset must employ a control line, two filters, two switches, and miscellaneous discrete circuit elements to select which filter is active. Thus the handset's complexity and cost are increased. In this work a single standalone filter that meets the stringent handset requirements and which resides in a 3.0 mm /spl times/3.0 mm /spl times/1.1 mm ceramic package was fabricated using a suspended membrane thin film bulk acoustic resonator (FBAR) technology. The filter has a minimum insertion loss of /spl sim/1 dB, is guaranteed to have a 60 MHz bandwidth (1850-1910 MHz), and typically exhibits 35 dB of rejection in the Rx band (1930-1990 MHz). Enabled by high-Q FBAR resonators, the filter has a 10 MHz rolloff so that the transition can occur within the 20 MHz guardband while accounting for both manufacturing and temperature drift variations (-30 C to +85 C). In addition to meeting these requirements, the filter topology and wire bond scheme are chosen to allow the filter to achieve 30 dB of rejection at the second harmonic (3860-3980 MHz) and typically 15 dB of rejection at the third harmonic (5790-5970 MHz). The filter requires neither external components nor a control line thus reducing the size, complexity, and cost of PCS handsets. This is the first manufacturable standalone transmit filter of which we are aware that can meet all of the major handset manufacturers' technical requirements.
Nanoparticles for Cancer Detection and Therapy

The administration of nanovectors, nanoparticles or other systems having nanoscale components, that direct active agents to concentrate preferentially into their target lesion sites, has emerged as a striking treatment option which can improve therapeutic index and or enhance the imaging contrast. The challenge in achieving desired pharmacokinetic, pharmacodynamic and toxicological profiles, is decoupled from the specific in vitro recognition of a biological target, but is directly related to the presence of numerous biobarriers which all molecular agents or nanovectors should surpass to efficiently reach their destination. For more than a decade, oncology has been occupying the foremost position in nanomedicine, being the area of medicine for which numerous ‘nanodrugs’ are routinely used in the clinical situation. This chapter starts with an introduction to tumor physiology and medicaments currently used in oncology. Later, therapeutic and imaging delivery vectors from a ‘nano-toolbox’, in clinical use and under various stages of development, are presented. The ‘pros’ and ‘cons’ of these systems for the design of specific, personalized and targeted medications are then critically discussed. The advantages of the nanovectors' rational design to efficiently negotiate biobarriers and various aspects of a preclinical characterization for the nanoscale systems are further argued. The chapter concludes with an outlook on the unresolved issues and opportunities in cancer nanomedicine. Keywords: nanovectors; nanoparticles; cancer; biobarriers; angiogenic vasculature; chemotherapy; liposomes; drug targeting; rational design
Pediatric Endocrinology and Diabetes

Dear colleagues, In May 2015, the world learned that the National Aeronautics and Space Administration (NASA) believes that Antarctica’s Larsen B Ice Shelf will disappear by 2020. This Ice Shelf is estimated to have existed for over 10,000 years. As recently as 1995, it was 4445 square miles; by February 2002, it was only 2573 square miles. Then, after another major disintegration a month later, Larsen B was down to 1337 square miles. Currently, it is thought to be about 618 square miles. This Antarctic Ice Shelf is expected to be gone by the year 2020 (http://www.cnn.com/2015/05/16/us/antarcticalarsen-b-ice-shelf-to-disappear/index.html). This news is distressing for sure, but, you might be wondering, what does it have to do with an issue on pediatric endocrine disorders? Well, actually, quite a lot. Please note that half of the articles in this fascinating and extremely well-written issue deal with diabetes. There are several reasons for this focus. One reason represents a “good thing”: there have been many advances in our understanding of the causes and treatments of diabetes. Another reason is neither a “good thing” nor a “bad thing”—but is glacierlike. Like glaciers, diabetes has been recognized as a disorder of mankind for thousands of years. In fact, even the term “diabetes” was used by the Greeks over two thousand years ago (http://www.diabetescausestreatments.com/history-of-diabetes.html). In 1936, the two types of diabetes were recognized. Since that time, until recently, diabetes type II has been described as very rare in children. The third reason is a “bad thing”: this long-recognized disorder has been increasing dramatically among children and adults in recent years. Since the year 2000, accompanying the greatly increased rate of obesity among children around the globe, the rate of diabetes mellitus type II has also been increasing dramatically. Diabetes mellitus II is expected to exceed 5% of the global population within the next decade; it already afflicts an estimated 4% of the population. It is expected that by 2050, diabetes may
OBLIGATED CLINICAN SELF-DISCLOSURE: JONE THERAPITS'S INTERVENTIONS FOLLOWING A FAMILY MEMBERS'S PUBLICIZED MURDER*

This article describes a family therapist's management of the sudden collision between profesional and personal boundaries following the publicized murder of her spouse. Reasons are offered to explain why it is becoming difficult for all clinicians to control the process of self-disclosure in therapy. Strategies used to meet the demands of affirming professional distance while maintaining therapeutic effectiveness are described. Brief recommendations are proposed for therapists in group, medical, rural, inpatient, and underserved settings. It is hoped that this case study will generate further discussion and assist health care providers who may face this challenge in the future.
Stress to indicator species as assessment endpoints

Abstract The use of indicator species as assessment endpoints for ecological risk assessment provides a basis for a scientifically valid extrapolation from measurements to those impacts which are of primary importance to environmental decision makers and managers. Assessment endpoints should be chosen on the basis of ecological significance, economic importance, or regulatory significance. Indicator species, to be useful as assessment endpoints, must perform an ecologically significant function as well as being sensitive to chemical induced stresses to the ecosystem. In this paper, we will examine how indicator species can be utilized as assessment endpoints within an integrated logical framework for ecological risk assessment.
Influence of Shimada Seamount on sediment composition in the eastern tropical North Pacific

Abstract Shimada Seamount is a large, young volcanic edifice in the east-central Pacific that is not associated with any active spreading center or known hot spot. The sediments on the abyssal plain surrounding Shimada Seamount consist of pelagic clay with ferromanganese micronodules and zeolites. The pelagic clay is mostly barren of microfossils except for a few occurrences of highly corroded specimens of Radiolaria and diatoms. Eolian terrigenous material is the dominant component of the pelagic clay to a depth of at least 8 m below sea floor, with minor contributions from volcanic debris and hydrothermal and hydrogenous sources. The average amount of basaltic debris is only 0.25%, but concentrations are as high as 10% in some samples. The average hydrothermal component (metalliferous sediment) is 8.8% with a maximum of about 13% at 7.5 m below sea floor in one core. The hydrogenous component, mostly as ferromanganese micronodules, averages 4.1% with a maximum of 5.6%. There is no calcareous biogenic debris and essentially no siliceous biogenic debris. In the past, a decrease in hydrothermal components through time may have been the result of a decrease in relative importance of hydrothermal influences, or an increase in the flux of terrigenous debris transported by the northeast trade winds. Because volcanic activity is still active on Shimada Seamount, or has been in the recent past, the observed increase in relative abundance of terrigenous components probably was the result of increased wind transport and not decreased hydrothermal activity. Shimada Seamount may be an important local source of metalliferous sediment in the eastern equatorial North Pacific, and may have been an even more important source in the past.
Let's Have a Conversation

Communicating inside a single program is trivial: one method calls another, the result comes back, and the calling method continues. If anything goes wrong, an exception is thrown. If the program aborts altogether, both caller and callee share the same fate, making the interaction an all-or-nothing affair. This kind of binary outcome is a welcome behavior in the predictive world of computer software, especially one that's based on 1s and 0s. In the land of loosely coupled distributed systems, things are a little more complicated. Using procedure call semantics for distributed systems is generally considered a bad idea, so systems should communicate in a more loosely coupled way - preferably by exchanging messages. Message-based communication results in a simple interaction model and, if used with message queues, temporal decoupling between sender and receiver: splitting the request-response interaction into two separate messages means that callers don't have to sit around waiting for response messages
Phase relations of a high-Mg basalt from the Aleutian Island Arc: Implications for primary island arc basalts and high-Al basalts

Many volcanic centers in the Aleutian Islands have erupted lavas that range in composition from high-Mg basalt (MgO>9 wt%) to more fractionated and voluminous high-Al basalts and basaltic andesites. The petrogenetic relationships between these rock types and the composition of primary magmas has been vigorously debated. The phase relations of a typical high-Mg basalt from the Makushin volcanic field on Unalaska Island provide important constraints on petrogenetic models. Results of one-atmosphere and moderate-to high-pressure (5–20 kb) anhydrous experiments are similar to results obtained from primitive MORB. At low pressures olivine is the liquidus phase joined by plagioclase and clinopyroxene at progressively lower temperatures. Clinopyroxene is the second phase to crystallize at pressures greater than 5 kb and replaces olivine on the liquidus at approximately 10 kb. Above 10 kb the liquidus pyroxene is aluminous augite and orthopyroxene is the second phase to crystallize. Glasses in equilibrium with olivine and clinopyroxene at intermediate-pressure (5 to 10 kb) are similar in composition to high-Al basalt. Plagioclase is not involved and most likely does not become a liquidus phase until the liquid has evolved significantly. Although our studies do not confirm the primary nature of high-Mg basalts they do support a model in which high-Al basalts are generated by moderate amounts of crystal fractionation from more primitive (high Mg/Mg+Fe, lower Al2O3) basaltic magmas near the arc crust-mantle boundary.
Measuring responses to simulated predation threat using behavioral and physiological metrics: the role of aquatic vegetation

An organism's daily activities are affected by predation and predation risk that have behavioral and physiological costs, which translate into long-term population and community consequences. We tested the hypothesis that the perception of predation risk from sand seatrout, Cynoscion arenarius, affects the behavior, and immediate and intermediate physiological responses of longnose killifish, Fundulus majalis. We further hypothesized that prey responses change if prey are buffered by artificial submerged aquatic vegetation (SAV), a potential refuge from predators. Experiments were conducted to quantitatively estimate the behavior, plasma cortisol (PC) concentration, mass-specific oxygen consumption, and short-term growth rate changes relative to full, partial, and no visual exposure to the predator. The partial visual exposure treatment involved the use of artificial SAV. Our results indicate that there are significant behavior and physiological responses of longnose killifish to predation threat. Longnose killifish in the full visual and partial exposure treatments displayed different behaviors than the control treatments by shifting towards the rear of the aquaria. In addition, longnose killifish in the full visual exposure compared to the partial exposure and the control treatments responded by exhibiting an elevation of PC and mass-specific oxygen consumption rate, and through decreased short-term growth. These responses were less intense in the partial exposure, when artificial SAV was present. The significance of this study is that it examines a suite of responses from cellular to the whole-organism level as they are affected by predation threat and modified by the presence or absence of artificial SAV.
Crossing the Industrial Divide: State, Society, and the Politics of Economic Transformation in Malaysia . By Alasdair Bowie. New York: Columbia University Press, 1991. xvi, 222 pp. $40.00.

Contrasting industrial development in late-industrializing third world countries with industrial change in advanced industrial societies, Bowie (politics, Catholic U.) shows how the structural characteristics of third world societies affect state policy choices in the industrial realm, and explores
The implications of liquidity and order flows for neoclassical finance

Abstract While liquidity and order flows are microstructure constructs, we show that they have profound implications for all of finance. In particular, liquidity is intimately connected with the fundamental building blocks of finance, namely, the pricing of risk, the powerful no-arbitrage theorems, and market efficiency. Large-sample studies of liquidity show that both liquidity and liquidity risk are priced in the cross-section of stock returns, the law of one price is more likely to hold in more liquid markets, and liquidity enhances market efficiency. Hence policies to enhance liquidity encourage efficiency and reduce costs of raising capital. Furthermore, order flows are powerful predictors of returns as well as the real economy.
Will direct thrombin inhibitors replace warfarin for preventing embolic events in atrial fibrillation

PURPOSE OF REVIEW Atrial fibrillation is the most frequently encountered tachyarrhythmia requiring therapy. Treatment issues include therapy for any reversible cause; the identification and treatment of any underlying structural disorder; control of the ventricular rate, both for symptom reduction and prevention of tachycardic-induced cardiomyopathy; restoration and maintenance of sinus rhythm when symptoms persist despite rhythm control; and anticoagulation in patients with high-risk markers for systemic embolization: age over 65 years, hypertension, diabetes, ventricular failure, rheumatic valvular disease, and prior stroke or other embolic event. In such patients, anticoagulation with warfarin is currently recommended. Warfarin therapy carries significant risks (especially bleeding), inconveniences (the cost of prothrombin time monitoring, the need for rigid dietary stability, the concerns of drug and herbal interactions), and other concerns (the issue of generic formulation substitution). RECENT FINDINGS Under development are oral thrombin inhibitors. The first to reach clinical approval will likely be ximelagatran. In clinical trials to date, ximelagatran has proven to be equal to or superior to warfarin in the prevention and treatment of thrombophlebitis. In atrial fibrillation patients, the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) trials completed so far appear to show a similar or better efficacy for ximelagatran versus warfarin as regards both prevention of embolic events and lower risks of major bleeding, with no serious adverse effects except for apparently reversible alterations in liver function tests in approximately 6% of subjects, all occurring early in therapy to date. If the remaining SPORTIF trial (SPORTIF V) is confirmatory (results to be available in late 2003), it is expected that this exciting new product will be submitted this winter to the Food and Drug Administration for approval. Recent findings also include the observations in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) and Rate Control Versus Electrical Cardioversion (RACE) trials that anticoagulation should not be discontinued despite the restoration and maintenance of sinus rhythm. SUMMARY Oral direct thrombin inhibitors, such as ximelagatran, appear likely to replace the use of warfarin in most patients in the near future, because of a better risk-benefit profile.
The complexity and the case method

Purpose – The purpose of this paper is to propose a framework that uses complexity as a means of better understanding the role that case studies can play in the classroom and in building bridges between research and practice. Design/methodology/approach – The paper synthesizes complexity theory and the practical classroom and case writing experiences of the author into a framework. Findings – A narrow view of the impact of case studies severely limits their widespread adoption. Rather than treating a case study as a document of very limited value to an academic career, the author needs to recognize their role in building relationships between research and practice. Through these relationships, opportunities for students and two-way flows of knowledge between academia and practice can be achieved. Research limitations/implications – The framework developed assumes that domain of study is complex – involving many interacting elements taking place in a context where an objectively “right” or “best” answer is...
High-accuracy 3D image-based registration of endoscopic video to C-arm cone-beam CT for image-guided skull base surgery

Registration of endoscopic video to preoperative CT facilitates high-precision surgery of the head, neck, and skull-base. Conventional video-CT registration is limited by the accuracy of the tracker and does not use the underlying video or CT image data. A new image-based video registration method has been developed to overcome the limitations of conventional tracker-based registration. This method adds to a navigation system based on intraoperative C-arm cone-beam CT (CBCT), in turn providing high-accuracy registration of video to the surgical scene. The resulting registration enables visualization of the CBCT and planning data within the endoscopic video. The system incorporates a mobile C-arm, integrated with an optical tracking system, video endoscopy, deformable registration of preoperative CT with intraoperative CBCT, and 3D visualization. Similarly to tracker-based approach, the image-based video-CBCT registration the endoscope is localized with optical tracking system followed by a direct 3D image-based registration of the video to the CBCT. In this way, the system achieves video-CBCT registration that is both fast and accurate. Application in skull-base surgery demonstrates overlay of critical structures (e.g., carotid arteries) and surgical targets with sub-mm accuracy. Phantom and cadaver experiments show consistent improvement of target registration error (TRE) in video overlay over conventional tracker-based registration-e.g., 0.92mm versus 1.82mm for image-based and tracker-based registration, respectively. The proposed method represents a two-fold advance-first, through registration of video to up-to-date intraoperative CBCT, and second, through direct 3D image-based video-CBCT registration, which together provide more confident visualization of target and normal tissues within up-to-date images.
Poe in the Marketplace

Thomas Woodson, ed. Twentieth Century Interpretations of “The Fall of the House of Usher”: A Collection of Critical Essays. Eric W. Carlson, ed. Edgar Allan Poe: “The Pall of the House of Usher.” William L. Howarth, ed. Twentieth Century Interpretations of Foe's Tales: A Collection of Critical Essays.
An Experimental Investigation of Subharmonic Currents

This investigation of the series circuit shown in figure 1, consisting of resistance, capacitance, and nonlinear inductance, was undertaken with a view of determining the behavior of the subharmonic current which may result when a sine-wave voltage of fundamental frequency is applied. The magnetization characteristic of the inductor is given in figure 2, and all results, therefore, are associated with this one particular inductor. All values of resistance are ohmic values.