cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of varying inspiratory flow waveforms on pulmonary mechanics in critically ill patients.

Abstract Purpose: Ten mechanically ventilated patients were evaluated to determine the effect of three different inspiratory flow patterns on pulmonary mechanics. Materials and Methods: Ten consecutive mechanically ventilated critically ill patients with acute respiratory failure admitted to the intensive care unit were evaluated to assess the effects of decelerating, square, and sine waveforms on pulmonary mechanics. The variables measured were peak airway pressure (PaW), pleural pressure (Ppl), change in peak airway pressure (dPaW), inspiration time/total ventilation cycle time (Vi/Vtot), dynamic compliance (Cdyn), respiratory rate (RR), minute ventilation (Ve), and work of breathing (WOB). Results: The PaW, Ppl, and dPaW (cm H 2 O) were significantly lower using the decelerating inspiratory flow waveform ( P P P Conclusions: These results indicate that critically ill mechanically ventilated patients show improved respiratory mechanics with decelerating inspiratory waveform that may have beneficial clinical implication. Copyright © 2000 by W.B. Saunders Company
A multidimensional home-based care coordination intervention for elders with memory disorders: the Maximizing Independence at Home (MIND) Pilot Randomized Trial

Objectives To assess whether a dementia care coordination intervention delays time to transition from home and reduces unmet needs in elders with memory disorders. Design 18-month randomized controlled trial of 303 community-living elders. Setting 28 postal code areas of Baltimore, MD. Participants Age 70+ years, with a cognitive disorder, community-living, English-speaking, and having a study partner available. Intervention 18-month care coordination intervention to systematically identify and address dementia-related care needs through individualized care planning; referral and linkage to services; provision of dementia education and skill-building strategies; and care monitoring by an interdisciplinary team. Measurements Primary outcomes were time to transfer from home and total percent of unmet care needs at 18 months. Results Intervention participants had a significant delay in time to all-cause transition from home and the adjusted hazard of leaving the home was decreased by 37% (Hazard ratio: 0.63, 95% Confidence Interval: 0.42–0.94) compared with control participants. Although there was no significant group difference in reduction of total percent of unmet needs from baseline to 18 months, the intervention group had significant reductions in the proportion of unmet needs in safety and legal/advance care domains relative to controls. Intervention participants had a significant improvement in self-reported quality of life (QOL) relative to control participants. No group differences were found in proxy-rated QOL, neuropsychiatric symptoms, or depression. Conclusions A home-based dementia care coordination intervention delivered by non-clinical community workers trained and overseen by geriatric clinicians led to delays in transition from home, reduced unmet needs, and improved self-reported QOL.
OXIDATIVE PHOSPHORYLATION AND ULTRASTRUCTURAL TRANSFORMATION IN MITOCHONDRIA IN THE INTACT ASCITES TUMOR CELL

We have examined the ultrastructure of mitochondria as it relates to energy metabolism in the intact cell. Oxidative phosphorylation was induced in ultrastructurally intact Ehrlich ascites tumor cells by rapidly generating intracellular adenosine diphosphate from endogenous adenosine triphosphate by the addition of 2-deoxyglucose. The occurrence of oxidative phosphorylation was ascertained indirectly by continuous and synchronous monitoring of respiratory rate, fluorescence of pyridine nucleotide, and 90° light-scattering. Oxidative phosphorylation was confirmed by direct enzymatic analysis of intracellular adenine nucleotides and by determination of intracellular inorganic orthophosphate. Microsamples of cells rapidly fixed for electron microscopy revealed that, in addition to oxidative phosphorylation, an orthodox → condensed ultrastructural transformation occurred in the mitochondria of all cells in less than 6 sec after the generation of adenosine diphosphate by 2-deoxyglucose. A 90° light-scattering increase, which also occurs at this time, showed a t ½ of only 25 sec which agreed temporally with a slower orthodox → maximally condensed mitochondrial transformation. Neither oxidative phosphorylation nor ultrastructural transformation could be initiated in mitochondria in intact cells by the intracellular generation of adenosine diphosphate in the presence of uncouplers of oxidative phosphorylation. Partial and complete inhibition of oxidative phosphorylation by oligomycin resulted in a positive relationship to partial and complete inhibition of 2-deoxyglucose-induced ultrastructural transformation in the mitochondria in these cells. The data presented reveal that an orthodox → condensed ultrastructural transformation is linked to induced oxidative phosphorylation in mitochondria in the intact ascites tumor cell.
“Stay Out of the Way! My Kid is Video Blogging Through a Phone!”: A Lesson Learned from Math Tutoring Social Media for Children in Underserved Communities

The current trends in social network media, coupled with increasingly advanced and ubiquitous mobile technology point towards great potential for their use in learning support and an emerging possibility of â€œdeconstructing digital divide.â€ This paper explores a mobile video blogging model embedded in a learning support community as a means of addressing learning needs among underperforming students of low socioeconomic status. In this study, various mobile video recording approaches were analyzed and some blogging strategies were linked to higher learning outcomes. Although a few challenges and issues were identified, the mobile video blogging community was generally found to be a viable learning support model for children in underserved communities.
Sexual and food preference in apotemnophilia and anorexia: interactions between 'beliefs' and 'needs' regulated by two-way connections between body image and limbic structures.

Apotemnophilia straddles the boundary between neurology and psychiatry. It is a condition in which individuals experience the strong and specific desire for amputation of a healthy limb. Research suggests this disorder may be of neurological origin, specifically that the body image centers of the brain lack a cortical representation for a particular limb. A curious aspect of this condition is that sufferers often report an attraction to amputees in addition to desiring their own limb be removed. We postulate that sexual ‘aesthetic preference’ for certain body morphology is dictated in all individuals in part by the cortical representation of one's body image.
The inhibition of thermomonospora by heat sterilized lactose broth

Heat sterilization of lactose solutions with phosphate buffers in alkaline conditions resulted in a browning reaction and in inhibition of growth of a Thermomonospora sp. Incubation at 55 ° increased both the browning reaction and the growth inhibition.
Food-Chains and the Food Cycle in Hawaiian Fish Ponds.–Part I. The Food and Feeding Habits of Mullet (Mugil Cephalus), Milkfish (Chanos Chanos), and the Ten-Pounder (Elops Machnata)

Abstract The food and feeding habits of the three most important market fish in Hawaiian ponds (Mugil cephalus, Chanos chanos, and Elops machnata) were analyzed to ascertain the position of these fish in the food-chains and the food cycle occurring within the ponds. Mullet (M. cephalus) subsist primarily on littoral diatoms and blue-green algae, the presence of a unique pharyngeal filtering device prohibiting them from swallowing larger forms. No variation in food because of season or size of fish was found. Milkfish (C. chanos) are also herbivores; juveniles consume unicellular and other minute algae while larger fish take an increasing amount of larger filamentous algae. Competition for food between mullet and milkfish is greater than hitherto supposed and cannot be diminished under present operational procedures. An increased food supply for both species probably could be achieved by the application of inorganic fertilizers together with the construction of additional shallow areas in the ponds. Ten-po...
Alcohol metabolism is not affected by sleeve gastrectomy

It has been published that patients who underwent gastric bypass surgery have impaired alcohol metabolism, predisposing them to higher rates of intoxication and DUI arrests. Yet the impact of laparoscopic sleeve gastrectomy (LSG) on alcohol metabolism and in particular the long-term effects are still unclear. We hypothesized that LSG does not alter alcohol metabolism. A prospective cohort study of patients undergoing LSG was evaluated. Blood alcohol concentration (BAC) was extrapolated using a Breathalyzer®. Alcohol metabolism was evaluated by determining BAC every 5 min after a single dose of alcohol (5 oz. glass of 14 % v/v Malbec wine), until BAC was equal to zero. Subjects were queried about alcohol intoxication symptoms. All parameters were obtained and analyzed preoperatively and at 3 and 12 months postoperatively. Our study consisted of 10 patients (9 female) with a mean age of 46.6 ± 2.2 years and BMI of 43.5 ± 2.2 kg/m2. The mean percentage excess weight loss was 39.5 ± 3.3 at 3 months and 55.6 ± 4.4 at 12 months. Peak BAC at 20 min was not different at 3 months (0.068 ± 0.007, p = 0.77) or at 12 months (0.047 ± 0.008, p = 0.19) when compared to the preoperative assessment (0.059 ± 0.014). In addition, the time to BAC equal to zero was not significantly different between baseline and the follow-up values (preoperative: 70 ± 9 min, 3 months: 95 ± 18 min, and 12 months: 57 ± 8 min, (p > 0.05). Symptoms of intoxication were not significantly different in patients before and after surgery. Our study suggests that LSG does not alter alcohol metabolism. Patients who undergo LSG do not have higher levels of intoxication following alcohol consumption and are therefore not prone to higher rates of DUI charges than the general public, in contrast to that previously reported following in patients who undergo gastric bypass surgery.
The new journalism and the image‐world: Two modes of organizing experience

This essay provides a cultural analysis of the New Journalism. Two modes of New Journalism are distinguished based on their ways of constructing the relationship of image to reality, observing to living, and storytelling to experience. The two modes, designated ethnographic realism and cultural phenomenology, reflect alternative ways of responding to cultural change and organizing the experience of reporting. These approaches to understanding social reality are related to the problem of creating meaning in contemporary society.
Converging Evidence for Underlying Phonological Representation in a Child Who Misarticulates

The liquid, fricative, and affricate sounds in the phonological system of a single misarticulating child were the focus of converging analyses. These analyses included structured measures of percep...
Altruism and skepticism in public attitudes toward food nanotechnologies

To better explore and understand the public's perceptions of and attitudes toward emerging technologies and food products, we conducted a US-based focus group study centered on nanotechnology, nano-food, and nano-food labeling. Seven focus groups were conducted in seven locations in two different US metropolitan areas from September 2010 to January 2011. In addition to revealing context-specific data on already established risk and public perception factors, our goal was to inductively identify other nano-food perception factors of significance for consideration when analyzing why and how perceptions and attitudes are formed to nanotechnology in food. Two such factors that emerged—altruism and skepticism—are particularly interesting in that they may be situated between different theoretical frameworks that have been used for explaining perception and attitude. We argue that they may represent a convergence point among theories that each help explain different aspects of both how food nanotechnologies are perceived and why those perceptions are formed. In this paper, we first review theoretical frameworks for evaluating risk perception and attitudes toward emerging technologies, then review previous work on public perception of nanotechnology and nano-food, describe our qualitative content analysis results for public perception toward nano-food—focusing especially on altruism and skepticism, and discuss implications of these findings in terms of how public attitudes toward nano-food could be formed and understood. Finally, we propose that paying attention to these two factors may guide more responsible development of nano-food in the future.
Free-Standing Silicon-on-Insulator Strip Waveguides for Submilliwatt Thermo-Optic Switches

A Mach-Zehnder interferometer thermo-optic switch using free-standing silicon-on-insulator strip waveguides is demonstrated. Measurements at 1550 nm result in a switching power of 540 microwatts, rise time of 141 microseconds, and extinction ratio of 25 dB.
Effect of learning to be submissive on status in the peck order of domestic fowl

Abstract The present study was designed to investigate the effects on rank in the peck order of encounters between experimental birds, which were taken from intact peck orders, and a despotic bird not involved in the peck orders. Four groups with 14 birds in a group were observed to determine the peck orders. A total of eight experimental birds was selected from these groups and each had a number of encounters with a despotic bird which was not a member of any of the groups. The peck orders were then redetermined to evaluate the effects of the encounters on the ranks of the experimental birds. Seven of the eight birds showed reductions in rank after the encounters, and the eighth showed an increase. The characteristics of the encounters were related to the changes in ranks of several of the experimental birds. Tranquilizers were found to have little effect on the behaviour of the despot or the experimental birds. The effects of the encounters are interpreted in terms of conditioning of submissive and avoidance responses which generalized to the home pens.
Formation of a ribonucleoprotein complex of mouse hepatitis virus involving heterogeneous nuclear ribonucleoprotein A1 and transcription-regulatory elements of viral RNA.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) specifically binds to two transcription-regulatory elements, i.e., the leader and intergenic sequence, of the negative-strand (template-strand) RNA of mouse hepatitis virus (MHV) and may play a role in viral RNA transcription. Previous studies based on the defective-interfering RNAs of MHV suggested that these two RNA elements may interact with each other during transcription, although they do not have complementary sequences. In this study, we showed by an in vitro reconstitution assay that hnRNP A1 could mediate the formation of an RNP complex involving these two RNA elements. Both the RNA-binding domains and protein-interacting domain of hnRNP A1 contributed to the efficient formation of the RNP complex; however, the presence of the two RNA-binding domains alone, without the protein-interacting domain, also resulted in some RNP formation. Omission of hnRNP A1 in the reconstitution reaction abolished the RNP formation, and mutations of the IG sequences significantly inhibited the RNP formation. These findings suggest that the two cis-acting transcription-regulatory sequences of MHV RNA can interact with each other through the formation of an RNP complex involving a cellular protein hnRNP A1. This RNP complex may participate in MHV RNA transcription.
Threats to Property Rights in Russia: From Private Coercion to State Aggression

This article explores a fundamental shift in threats to property rights in Russia. Whereas extortion rackets and other forms of physical intimidation once posed the gravest threat to property rights, state actors are now the primary aggressors. Based on in-depth interviews and an original survey of Russian firms, the article demonstrates a dramatic decline in threats related to private coercion, due partly to firms' increased reliance on formal legal institutions. By contrast, state threats to property rights have increased sharply. Key threats include seizing firms' assets, illegal corporate raiding, extortion, illicit fines, and unlawful arrests of businesspeople.
Solar Radiation Climatology of Alaska

There are only six locations in Alaska for which global radiation data of more than a year in duration are available. This is an extremely sparse coverage for a state which covers 1.5×10&6 km2 and stretches over at least three climatic zones. Cloud observations are, however, available from 18 stations. We used fractional cloud cover and cloud type data to model the global radiation and thus obtain a more complete radiation coverage for Alaska. This extended data set allowed an analysis of geographic and seasonal trends.
Phased array antenna model-in-the-loop radar waveform optimization

Radar systems are being held to ever more strenuous spectral compliance standards. To meet these expectations innovative approaches that compensate for spectral spreading or other effects from the physical hardware need to be developed. Specifically, when considering phased array radar systems, it is important to consider the distortions introduced by their antennas. Radar waveforms that are optimized comprehensively for an entire radar system, including these antenna effects need to be explored. Ongoing work is exploring the optimization of radar waveforms that include the physical effects from transmitters and antennas. Here radar waveform performance is optimized for a radar system that includes the effects of a slotted waveguide phased array antenna using Continuous Phase Modulations (CPM) implemented waveforms.
The relation between offence against the sine condition in the presence of spherical aberration and lateral aberration

Abstract We have already derived the sine condition in the presence of spherical aberration which coincides with that proposed by Marx. In this paper, a new relation between offence against the sine condition in the presence of spherical aberration and lateral aberration is derived and is examined by a numerical calculation of ray traces.
Denominator choice in the calculation of workplace fatality rates

The U.S. government currently publishes workplace fatality rates, using employment as the denominator. However, employment may not be a good proxy for worker exposure to risk if groups of workers differ in their hours worked. Using micro data from the Census of Fatal Occupational Injuries and Current Population Survey, this paper presents alternative fatality rates calculated using employment and hours worked. Rates are compared for worker groups defined by gender, age, occupation, and industry. In general, both measures identify the same groups of workers as facing especially high and low fatality risks. The rank correlation of the employment- and hours-based fatality rates for 222 detailed occupations is very high, with a value of 0.99. However, for a few groups, the hours- and employment-based rates may differ more than 10%. Most notably, workers below age 20 and above age 64 have rates that are 60% and 37% higher, respectively, when hours is used in the denominator. This suggests that hours—the conceptually preferable denominator—should be used when possible to calculate workplace fatality rates. Am. J. Ind. Med. 33:151–156, 1998. © 1998 Wiley-Liss, Inc.
Self-Control Predicts Later Symptoms of Posttraumatic Stress Disorder

Self-control, the ability to control one’s thoughts and actions, is perhaps one of the most important constructs in human psychology. Tangney, Baumeister, & Boone, (2004) found that greater levels of self-control were related to higher grade point averages, better relationships and interpersonal skills, secure attachment styles, greater optimal emotional responses to stressful situations, fewer reports of psychopathology, less binge eating and alcohol abuse, and greater self-esteem among college students. These findings highlight the many aspects of an individual’s environment that can be affected by self-control. Although self-control has been shown to be related to important outcomes, it has been rarely examined in clinical disorders, particularly with regards to PTSD. Self-control is arguably an essential skill for successful functioning in one’s environment. Freud (1930) contended that the ability to inhibit antisocial impulses and conform to social standards of society is the fundamental nature of civilized life. Freud
Extended Hückel MO calculations of the conformation of several amino acids

The conformation of the amino acid residues, glycine, alanine, proline, and phenylalanine have been predicted from molecular orbital calculations of appropriate model compounds. Using the current main chain rotation convention (Φ, ψ) the principle conformations were found to be glycine (0‡, 0‡), alanine (240‡, 240‡), proline (120‡, 330‡) and phenylalanine (30‡, 330‡). Several secondary conformations were also found for glycine. A comparison of the predicted conformations is in good agreement with experimental data on comparable residues or model compounds.
Sexualities, technologies, and the teaching of writing: A critical overview

Abstract In this introduction to a special issue of Computers and Composition, the authors critically review current literature on computer-assisted writing pedagogies that grapple with issues of sexuality. Although this body of work is small, it points to provocative ways to develop our students’ critical and rhetorical sensibilities about the constructions of sexuality in our culture. Further, such work innovatively addresses the place of networked communication technologies in the interrogation of such constructions. The authors conclude with both an introduction of the work in this special issue that addresses the intersection of sexuality studies and computer-assisted writing studies and with a call for additional work in this field.
Design of a mechanical-tunable filter spectrometer for noninvasive glucose measurement

The development of an accurate and reliable noninvasive near-infrared (NIR) glucose sensor hinges on the success in addressing the sensitivity and the specificity problems associated with the weak glucose signals and the overlapping NIR spectra. Spectroscopic hardware parameters most relevant to noninvasive blood glucose measurement are discussed, which include the optical throughput, integration time, spectral range, and the spectral resolution. We propose a unique spectroscopic system using a continuously rotating interference filter, which produces a signal-to-noise ratio of the order of 105 and is estimated to be the minimum required for successful in vivo glucose sensing. Using a classical least-squares algorithm and a spectral range between 2180 and 2312 nm, we extracted clinically relevant glucose concentrations in multicomponent solutions containing bovine serum albumin, triacetin, lactate, and urea.
Magnonlike Dispersion of Spin Resonance in Ni-doped BaFe2As2

Inelastic neutron scattering measurements on Ba(Fe0.963Ni0.037)2As2 manifest a neutron spin resonance in the superconducting state with anisotropic dispersion within the Fe layer. Whereas the resonance is sharply peaked at the antiferromagnetic (AFM) wave vector Q(AFM) along the orthorhombic a axis, the resonance disperses upwards away from Q(AFM) along the b axis. In contrast to the downward dispersing resonance and hourglass shape of the spin excitations in superconducting cuprates, the resonance in electron-doped BaFe2As2 compounds possesses a magnonlike upwards dispersion.
532nm-Pumped Continuous-Wave Singly Resonant Optical Parametric Oscillator Based On Periodically-Poled Lithium Niobate

We report a continuous-wave 532-nm-pumped singly resonant optical parametric oscillator based on bulk periodically-poled lithium niobate (PPLN). Thermal focusing at 532nm in PPLN is reduced by chopping the pump. Less than one watt threshold and 64% quantum efficiency are achieved.
Survival ofEscherichia coli in great salt lake water

Survival ofEscherichia coli was studied in water from the Great Salt Lake, a highly saline lake with an ionic composition much like sea water. Samples used were from the most concentrated north arm (343.1 g l−1 solids) and the less concentrated south arm (about 113 g l−1 solids). At temperatures from 20°C to 9°C the bacterial death rate (k) for the north arm was −0.17 log day−1 and the south arm and 1:3 dilution −0.28 log day−1. Above 9°C the rate of death increased approximately exponentially and at 19°C the rate of death increased approximately exponentially and at 19°C the death rate was −1.31 log day−1 in the north arm and −0.98 log day−1 in the lower salinity water. These rates fall within those reported for sea water and are much higher than fresh water. Possible causes of death are discussed with the most likely being the high concentrations of minor elements or osmotic stress. The survival characteristics ofE. coli in waters with a sea water-like composition should require the same health concern as sea water regardless of the actual concentration of salt. High salt water of other ionic composition may behave differently, however.
Repaired coarctation of the aorta imaged by 64-detector computed tomography.

![Figure][1] A 35-year-old man with a history of aortic coarctation (CoA) repair during childhood presented with the complaint of atypical chest pain. During childhood, he had undergone CoA repair with the placement of a conduit from the aortic arch just distal to the left subclavian artery (
Characteristics and Coping Patterns of Families with Infants on Home Apnea Monitoring

The purposes of this study were to: (a) describe the characteristics of families with children who require apnea monitors in the home setting; (b) describe the family functioning characteristics and coping patterns of families with children on apnea monitors; and (c) describe the relationship between family functioning and coping patterns in these families. This descriptive study focused on families of 22 children ranging in age from 8 to 64 months who required home apnea monitoring. Interview results indicate that these families are high in adaptability and average in cohesion. Results also describe families who perceive themselves as coping adequately. Analysis of the data reveals significant correlations among family functioning scores and coping pattern subscale scores. Findings from this study support the importance of understanding the role of family functioning and coping patterns of families with children on home apnea monitoring. Information from this study can assist nurses in planning comprehen...
Targeting the vasculature of solid tumors

Abstract Targeting cytotoxic agents or other effectors to vascular endothelial cells in solid tumours is an attractive new concept in cancer therapy. Killing these cells should initiate platelet aggregation and blood coagulation locally within the tumour vasculature, leading to tumour cell killing through starvation of oxygen and nutrients. In the present article, we review our progress in the development of this concept, from its validation in a mouse tumour model, to the identification of markers that might permit the selective attack of tumour vasculature in man.
Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum

A water-soluble tetra-S-glycosylated porphyrin (P-Glu4) is absorbed by MDA-MB-231 human breast cancer cells whereupon irradiation with visible light causes necrosis or apoptosis depending on the concentration of the porphyrin and the power of the light. With the same amount of light irradiation power (9.4 W m−2), at 10–20 μM concentrations necrosis is predominantly observed, while at <10 μM concentrations, apoptosis is the principal cause of cell death. Of the various possible pathways for the induction of apoptosis, experiments demonstrate that calcium is released from the endoplasmic reticulum, cytochrome c is liberated from the mitochondria to the cytosol, pro-caspase-3 is activated, poly-(ADP-ribose) polymerase is cleaved, and the chromatin is condensed subsequent to photodynamic treatment of these cells. Confocal microscopy indicates a substantial portion of the P-Glu4 is located in the endoplasmic reticulum at <10 μM. These data indicate that the photodynamic treatment of MDA-MB-231 cells using low concentrations of the P-Glu4 porphyrin and low light induces apoptosis mostly initiated from stress produced to the endoplasmic reticulum.
Investigation of Wave Propagation in a Dielectric Rod Array: Toward the Understanding of HF/VHF Propagation in a Forest

Radiowave propagation inside a forested environment in the HF/VHF frequency ranges has long been of interest for communication and sensing. We report on the measurement of an array of water-filled straws as a simplified, scaled model of a forest. A periodic array is first constructed in the laboratory based on an approximate 1:50 scaling with respect to a typical forest. Transmission loss inside this structure versus frequency and distance is measured. The data are then processed to extract the dominant propagation mechanisms in the structure. The results are compared to the full-wave numerical simulation for an array of infinite rods. To provide physical interpretations for the wave propagation inside the array, an effective medium theory is also applied to calculate the effective permittivity and permeability of the structure. It is found that: (i) Passband/stopband behaviors exist in the measurement and approximately agree with the full-wave simulation for infinite rods. (ii) The water straw array can be described as a -negative (ENG) medium within a certain frequency band in the long wavelength limit. (iii) The extracted propagation constants from measurement, simulation and effective medium theory show good agreement. The positions and heights of the water rods are next perturbed to study the effect of randomization. Finally, the predictions from the dielectric rod array are correlated with the measurement data collected in a real forest in Bastrop, Texas.
Learning the sequence determinants of alternative splicing from millions of random sequences.

Most human transcripts are alternatively spliced, and many disease-causing mutations affect RNA splicing. Toward better modeling the sequence determinants of alternative splicing, we measured the splicing patterns of over two million (M) synthetic mini-genes, which include degenerate subsequences totaling over 100 M bases of variation. The massive size of these training data allowed us to improve upon current models of splicing, as well as to gain new mechanistic insights. Our results show that the vast majority of hexamer sequence motifs measurably influence splice site selection when positioned within alternative exons, with multiple motifs acting additively rather than cooperatively. Intriguingly, motifs that enhance (suppress) exon inclusion in alternative 5' splicing also enhance (suppress) exon inclusion in alternative 3' or cassette exon splicing, suggesting a universal mechanism for alternative exon recognition. Finally, our empirically trained models are highly predictive of the effects of naturally occurring variants on alternative splicing in vivo.
Characterization of Synthetic Hydroxyproline-Rich Proteoglycans with Arabinogalactan Protein and Extensin Motifs in Arabidopsis

A series of gene constructs encoding synthetic glycomodule peptides with N-terminal signal sequences and C-terminal green fluorescent proteins were expressed in transgenic Arabidopsis (Arabidopsis thaliana) under the control of the 35S promoter. The synthetic glycomodule peptides were composed of repetitive proline-containing motifs that have been previously found to be substrates for prolyl hydroxylases and subsequent O-glycosylation of the hydroxyproline residues. All of the constructs were secreted in aerial tissues, but not in roots. The amount of hydroxylation and glycosylation of the various constructs varied depending on the tissue. Also, accumulation of the proteins exhibited a high degree of cell-type specificity within various tissues due to posttranscriptional effects. The observations reveal a high level of complexity in the synthesis, secretion, and turnover of the glycoproteins.
High Salinity Tolerance in the stl2 Mutation of Ceratopteris richardii is Associated with Enhanced K+ Influx and Loss

The roles of K + uptake and loss in the salinity response of the wild type and the salt-tolerant mutant stl2 of Ceratopteris richardii were studied by measuring Rb + influx and loss and the effects of Na + , Mg 2+ , Ca 2+ and K + -transport inhibitors. In addition, electrophysiological responses were measured for both K + and Rb + and for the effects of Na + and NH 4 + on subsequent K + -induced depolarizations. stl2 had a 26-40% higher uptake rate for Rb + than the wild type at 0.5-10 mol m -3 RbCl. Similarly, membrane depolarizations induced by both RbCl and KCl were consistently greater in stl2. In the presence of 0-180 mol m -3 NaCl, stl2 maintained a consistently greater Rb + influx than the wild type. stl2 retained a greater capacity for subsequent KCl-induced depolarization following exposure to NaCl. Five mol m -3 Mg 2+ decreased Rb + uptake in stl2 ; however, additional Mg 2+ up to 40 mol m -3 did not affect Rb + uptake further. Ca 2+ supplementation resulted in a very minor decrease of Rb + uptake that was similar in the two genotypes. Tetraethylammonium chloride and CsCl gave similar inhibition of Rb + uptake in both genotypes, but NH 4 Cl gave substantially greater inhibition in the wild type than in stl2. NH 4 Cl resulted in a greater membrane depolarization in the wild type and the capacity for subsequent depolarization by KCl was markedly reduced. stl2 exhibited a higher K + -dependent loss of Rb + than the wild type, but, in the absence of external K + , loss of Rb + was equivalent in the two genotypes. Since constitutive K + contents are nearly identical, we conclude that high K + influx and loss exact a metabolic cost that is reflected in the inhibition of gametophytic growth. Growth inhibition can be alleviated by reduced supplemental K + or by treatments that slightly reduce K + influx, such as moderate concentrations of Na + or Mg 2+ . We propose that high throughput of K + allows maintenance of cytosolic K + under salt stress and that a high uptake rate for K + results in a reduced capacity for the entrance and accumulation of alternative cations such as Na + in the cytosol.
Programmed Necrosis, Not Apoptosis, in the Heart

It is well known that apoptosis is an actively mediated cell suicide process. In contrast, necrosis, a morphologically distinct form of cell death, has traditionally been regarded as passive and unregulated. Over the past decade, however, experiments in Caenorhabditis elegans and mammalian cells have revealed that a significant proportion of necrotic death is, in fact, actively mediated by the doomed cell. Although a comprehensive understanding of necrosis is still lacking, some key molecular events have come into focus. Cardiac myocyte apoptosis and necrosis are prominent features of the major cardiac syndromes. Accordingly, the recognition of necrosis as a regulated process mandates a reexamination of cell death in the heart. This review discusses pathways that mediate programmed necrosis, how they intersect with apoptotic pathways, roles of necrosis in heart disease, and new therapeutic opportunities that the regulated nature of necrosis presents.
Endothelial cell protein C receptor opposes mesothelioma growth driven by tissue factor

The pro-coagulant protein Tissue Factor (TF, F3) is a powerful growth promoter in many tumors but its mechanism of action is not well understood. More generally, it is unknown whether hemostatic factors expressed on tumor cells influence TF-mediated effects on cancer progression. In this study, we investigated the influence of TF, endothelial cell protein C receptor (EPCR, PROCR) and protease activated receptor-1 (PAR1, F2R) on the growth of malignant pleural mesothelioma (MPM), using human MPM cells that lack or express TF, EPCR or PAR1 and an orthotopic nude mouse model of MPM. Intrapleural administration of MPM cells expressing TF and PAR1 but lacking EPCR and PAR2 (F2RL1) generated large tumors in the pleural cavity. Suppression of TF or PAR1 expression in these cells markedly reduced tumor growth. In contrast, TF overexpression in non-aggressive MPM cells that expressed EPCR and PAR1 with minimal levels of TF did not increase their limited tumorigenicity. More importantly, ectopic expression of EPCR in aggressive MPM cells attenuated their growth potential, whereas EPCR silencing in non-aggressive MPM cells engineered to overexpress TF increased their tumorigenicity. Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced tumor cell proliferation and enhanced apoptosis. Overall, our results enlighten the mechanism by which TF promotes tumor growth through PAR1, and they show how EPCR can attenuate the growth of TF-expressing tumor cells.
Cellular signaling with nitric oxide and cyclic GMP

During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.
Clinical presentations, diagnosis, and prognostic factors of bacterial meningitis.

Abstract The clinical presentations of children and adults with bacterial meningitis have not changed over the past several decades, and a high index of suspicion remains critical for timely identification of infected patients. With the virtual disappearance of H. influenzae type B meningitis (Hib) in areas of the world where Hib conjugate vaccine is administered routinely, the utility of commercially available tests for rapid detection of bacterial polysaccharides has diminished. Detection of gene products of meningeal pathogens in cerebrospinal fluid or blood is still experimental. The prognostic findings of recent studies are not different from those previously described, despite advances in the supportive care of critically ill patients.
Multi-scale data-driven modeling and observation of calcium puffs.

signaling Puff termination a b s t r a c t The spatiotemporal dynamics of elementary Ca 2+ release events, such as “blips” and “puffs” shapes the hierarchal Ca2+ signaling in many cell types. Despite being the building blocks of Ca2+ patterning, the mechanism responsible for the observed properties of puffs, especially their termination is incompletely understood. In this paper, we employ a data-driven approach to gain insights into the complex dynamics of blips and puffs. We use a model of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) derived directly from single channel patch clamp data taken at 10 M concentration of IP3 to simulate calcium puffs. We first reproduce recent observations regarding puffs and blips and then investigate the mechanism of puff termination. Our model suggests that during a puff, IP3R s proceed around a loop through kinetic states from “rest” to “open” to “inhibited” and back to “rest”. A puff terminates because of self-inhibition. Based on our simulations, we rule out the endoplasmic reticulum (ER) Ca 2+ depletion as a possible cause for puff termination. The data-driven approach also enables us to estimate the current through a single IP3R and the peak Ca 2+ concentration near the channel pore.
A Nongenomic Action of Estradiol as the Mechanism Underlying the Acute Suppression of Secretion of Luteinizing Hormone in Ovariectomized Ewes

The objective of the present study was to determine how rapidly estradiol (E2) was able to suppress the secretion of LH in ovariectomized (OVX) ewes and to evaluate the ability of conjugated forms of E2 (E2 conjugated to BSA [1,3,5(10)-estratrien-3,17beta-diol-6-one-6-carboxymethyloxime:BSA [E2-BSA] and a novel conjugate, E2 conjugated to a small peptide [E2-PEP]) to mimic the actions of E2 on secretion of LH and FSH. Animals (n = 5-6 per group) were given infusions for 4 h of 50 microg of E2 or equimolar concentrations of E2-BSA or E2-PEP. Treatments with E2, E2-BSA, and E2-PEP each induced an acute suppression of LH secretion (<20 min, P < 0.01). In contrast, E2, but not E2-BSA or E2-PEP, induced the characteristic preovulatory-like surge of LH (at 10 h after priming treatment) and decreased secretion of FSH (at 4 h after priming treatment). In conclusion, the acute inhibition of LH secretion induced by E2 in OVX ewes supports the concept of a nongenomic action as the mechanism underlying the sudden suppression in secretion of LH. In addition, the fact that conjugated forms of E2 mimicked only the acute suppression of secretion of LH, without inducing the putative genomic actions on secretion of LH or FSH (i.e., a preovulatory-like surge), suggests that the acute effect of E2 may be mediated via the plasma membrane.
Fat-Tailed Uncertainty in the Economics of Catastrophic Climate Change

AbstractIn this article, I revisit some basic issues concerning structural uncertainty and catastrophic climate change. My target audience here are general economists, so this article could also be...
Undermining the Zeigarnik effect: Another hidden cost of reward

Forty college students participated in a study ostensibly designed to obtain measures of the hemispheric activity while they worked on a spatial reasoning task. In fact, our true interest was in determining whether subjects would return to the spatial reasoning task once the hemispheric recordings were completed. Subjects would normally be expected to return to the task by virtue of the Zeigarnik effect because no subject completed the task during the “hemispheric recording” phase. The manipulation involved telling one group of subjects that they would be paid $1.50 for participating in the study (expected reward group). The remainder of the subjects were not led to expect the reward (unexpected reward group). The result was that 86% of the unexpected reward subjects but only 58% of the expected reward subjects (p < .05) manifested the Zeigarnik effect. This differential tendency to return to the task was further reflected in time differences. The average unexpected reward subject spent 3 min 48 sec of a five-minute free-choice period at the task, whereas the average expected reward subject spent only 2 min 20 sec (p < .05). Reward expectancy, therefore, led to an undermining of the Zeigarnik effect. This observation supports Condry's prediction that rewarding performance at a task can lead to premature task disengagement.
Considering testability at behavioral level: use of transformations for partial scan cost minimization under timing and area constraints

We address the problem of transforming a behavioral specification so that synthesis of a testable implementation from the new specification requires significantly less area and partial scan cost than synthesis from the original specification. The proposed approach has three components: a library of relevant transformation mechanisms, an objective function, and an optimization algorithm. The most effective transformations for testability optimization are identified by analyzing the fundamental relationship between transformational mechanisms and topological and functional properties of the computations that affect testability. A dynamic, two-stage objective function that estimates the area and testability of the final implementation, and also captures enabling and disabling effects of the transformations, is developed. Optimization is done using a new randomized branch and bound steepest descent algorithm. Application of the transformation algorithm on several benchmark examples demonstrates significant simultaneous improvement in both area and testability of the final implementations. >
Advances in prenatal diagnosis. Social-psychological and policy issues.

Chorionic villus sampling (CVS), a new technique for prenatally diagnosing chromosomal and genetic disorders, may soon replace amniocentesis. This procedure, performed by inserting a catheter through the pregnant woman's cervix or through the abdomen and removing cells from the placenta, has the advantages of being available earlier in the pregnancy than amniocentesis (at 9 to 11 weeks gestational age) and of yielding results in a shorter time. Although the medical aspects of the procedure are being investigated, its psychosocial and policy implications have not been studied systematically. These issues include the subjective assessment of risk that prompts women to choose or to reject CVS, the implications of earlier diagnosis for feelings about abortion, the potential of negative findings (i.e., the absence of the designated disorder) for well-being during the remainder of the pregnancy, the ramifications of first trimester identification of fetal sex, equity of access to prenatal diagnosis, and the possible over-utilization of these procedures. Drawing on previous research regarding amniocentesis and more recent research concerning CVS, this article discusses the potential implications of CVS.
Neural Correlates of Preparatory and Regulatory Control Over Positive and Negative Emotion

This study used functional magnetic resonance imaging to investigate brain activation during preparatory and regulatory control while participants (N = 24) were instructed either to simply view or decrease their emotional response to, pleasant, neutral or unpleasant pictures. A main effect of emotional valence on brain activity was found in the right precentral gyrus, with greater activation during positive than negative emotion regulation. A main effect of regulation phase was evident in the bilateral anterior prefrontal cortex (PFC), precuneus, posterior cingulate cortex, right putamen and temporal and occipital lobes, with greater activity in these regions during preparatory than regulatory control. A valence X regulation interaction was evident in regions of ventromedial PFC and anterior cingulate cortex, reflecting greater activation while regulating negative than positive emotion, but only during active emotion regulation (not preparation). Conjunction analyses revealed common brain regions involved in differing types of emotion regulation including selected areas of left lateral PFC, inferior parietal lobe, temporal lobe, right cerebellum and bilateral dorsomedial PFC. The right lateral PFC was additionally activated during the modulation of both positive and negative valence. Findings demonstrate significant modulation of brain activity during both preparation for, and active regulation of positive and negative emotional states.