cssi/SciSciGPT-SciSciNet huggingface dataset:
Complications of surgery for gastroesophageal reflux.

In the course of approximately 350 operations for gastroesophageal reflux and 1,500 evaluations of patients previously operated on or being assessed for therapy, a number of complications and undesirable side effects of antireflux surgery have been encountered. This report describes unfavorable outcomes including postoperative dysphagia, “gas-bloat syndrome,” postoperative gastric dilatation, unplanned vagotomy, failure to relieve symptoms, persistence or recurrence of reflux or hiatal hernia, perforation of the esophagus or stomach, postoperative bleeding, unplanned splenectomy, and persistence of stricture, which have followed the antireflux repairs introduced by Belsey, Nissen, or Hill, the gastroplasty procedures described by Thal, and by Collis, intrathoracic fundoplication, and esophageal resection with gastrointestinal interposition.
The Myth and Reality of Reversal of Aging by Hormesis

Hormesis is an adaptive response to low doses of otherwise harmful agents by triggering a cascade of stress-specific resistance pathways. Evidence from protozoa, nematodes, flies, rodents, and primates indicate that stress-induced tolerance modulates survival and longevity. "Reality" is that hormesis can prolong the healthy life span. Genetic background provides the potential for longevity duration induced by stress. Senesence, or aging, is generally thought to be due to a different impact of selection for alleles positive for reproduction during early life but harmful in later life, a process called antagonistic pleiotropy (multiple phenotypic changes by a single gene). After reproduction, life span is "invisible" to selection. I propose the revision that mutations selected for survival until reproduction in early life may also extend later life (protagonistic pleiotropy). The protagonist candidate genes for extended life span are hormetic response genes, which activate the protective effect in both early and later life. My revision of the earlier evolutionary theory implies that natural selection of genes critical for early survival (life span until reproduction) can also be beneficial for extended longevity in old age, tipping the evolutionary balance in favor of a latent inducible life span extension unless excess stressor challenge exceeds the protection capacity. Mimetic triggers of the stress response promise the option of tricking the induction of metabolic pathways that confer resistance to environmental challenges, increased healthy life span, rejuvenation, and disease intervention without the danger of overwhelming damage by the stressor. Public policy should anticipate an increase in healthy life span.
Substrate binding and conformational changes of Clostridium glutamicum diaminopimelate dehydrogenase revealed by hydrogen/deuterium exchange and electrospray mass spectrometry

C. glutamicum meso-diaminopimelate dehydrogenase is an enzyme of the L-lysine biosynthetic pathway in bacteria. The binding of NADPH and diaminopimelate to the recombinant, overexpressed enzyme has been analyzed using hydrogen/deuterium exchange and electrospray ionization/mass spectrometry. NADPH binding reduces the extent of deuterium exchange, as does the binding of diaminopimelate. Pepsin digestion of the deuterated enzyme and enzyme-substrate complexes coupled with liquid chromatography/mass spectrometry have allowed the identification of eight peptides whose deuterium exchange slows considerably upon the binding of the substrates. These peptides represent regions known or thought to bind NADPH and diaminopimelate. One of these peptides is located at the interdomain hinge region and is proposed to be exchangeable in the "open," catalytically inactive, conformation but nonexchangeable in the "closed," catalytically active conformation formed after NADPH and diaminopimelate binding and domain closure. Furthermore, the dimerization region has been localized by this method, and this study provides an example of detecting protein-protein interface regions using hydrogen/deuterium exchange and electrospray ionization.
The Positive Impact of Creative Activity: Effects of Creative Task Engagement and Motivational Focus on College Students' Learning

This study assessed the effectiveness of engaging students in a creative activity on a topic as a means of encouraging an active cognitive set toward learning that topic area. This technique was examined in three motivational contexts. Before reading a short instructional passage, subjects completed either, a creative or a noncreative pretask and heard one of three sets of directions: task focused (emphasizing intrinsic involvement), test focused (emphasizing external evaluation), or task/test focused (previous two combined). After reading the passage, subjects answered questions assessing immediate retention, wrote a creative essay, and responded to a questionnaire assessing intrinsic and extrinsic motivation. Long-term retention was assessed 5 days later with a phone quiz. Creative task engagement was found to be an effective means of enhancing creativity (in the absence of evaluation expectation), intrinsic motivation, and long-term retention.
Mesh effects for Rossby waves

Abstract Dispersion relations are obtained for Rossby waves on Arakawa grids A-E. The discretization accuracy is compared for both inertia-gravity and Rossby waves in terms of "domains of accuracy" for a given level of percentage error. In particular, the B-grid appears to be superior to the C-grid for the case of both resolved and under-resolved Rossby radius. This is in contrast to the well-known situation for inertia-gravity waves where the B-grid is inferior for the case of resolved Rossby radius.
The Student Left in Puerto Rico1

Leftist students at the University of Puerto Rico are similar to New Left students in the United States in that they are likely to have liberal or leftist fathers, to be either non-religious or anti-religious, to be enrolled in the Schools of Social Sciences or Humanities, and to be intelligent. Since 1956 the University Federation for Independence (FUPI), a leftist student organization, has been active on the campus. In recent years, FUPI has grown in size and political prominence, mostly due to such external factors as the Vietnam War, the draft, controversy over the island's status problem, and the student and black movements in the U.S.
Simultaneous Master-Slave Omega Pairs

Master-slave sequence ordering of the OMEGA system is suggested as a method of improving the pair geometry for low-cost receiver user benefit. The sequence change will not affect present sophisticated processor users other than require new labels for some pair combinations, but may require worldwide transmitter operators to slightly alter their long-range synchronizing techniques.
Four Wing Flapping Micro Air Vehicles - Dragonies or X-Wings?

ve connected rigid bodies, a central body and four wings. The equations of motion are derived using D’Alembert’s Principle for Multiple Rigid Bodies. Each wing is given three separate degrees of freedom relative to the central body. Open loop simulations are presented using the full nonlinear equations of motion, which include the inertial eects of the wings on the central body. Simulations show that an ‘x-wing’ conguration and a ‘revised’ dragony conguration may provide better, inherent stability than a biomimetic vehicle modeled after a dragony. Simulations of the two congurations show better pitch stability than a biomimetic simulation and the ‘revised’ dragony exhibits outstanding stability and lift characteristics.
Ontogeny and phylogeny of language

How did language evolve? A popular approach points to the similarities between the ontogeny and phylogeny of language. Young children’s language and nonhuman primates’ signing both appear formulaic with limited syntactic combinations, thereby suggesting a degree of continuity in their cognitive abilities. To evaluate the validity of this approach, as well as to develop a quantitative benchmark to assess children’s language development, I propose a formal analysis that characterizes the statistical profile of grammatical rules. I show that very young children’s language is consistent with a productive grammar rather than memorization of specific word combinations from caregivers’ speech. Furthermore, I provide a statistically rigorous demonstration that the sign use of Nim Chimpsky, the chimpanzee who was taught American Sign Language, does not show the expected productivity of a rule-based grammar. Implications for theories of language acquisition and evolution are discussed.
Motor vehicle occupant deaths in young children

Motor vehicle occupant deaths of US children aged 0 to 12 years were analyzed. Surprisingly, the death rate is highest for children less than 6 months old: 9.0/100,000, dropping to 4.5/100,000 for 1-year-olds and about 3/100,000 for children aged 6 to 12. The second and third months of age are a period of especially high risk. More attention should therefore be focused on protecting infants from injury and death resulting from motor vehicle crashes.
Two brief interventions for acute pain

This study evaluated two brief (3-5 min) interventions for controlling responses to acute pain. Eighty male subjects were randomly assigned to 1 of 2 intervention groups (Positive Emotion Induction (PEI) or Brief Relaxation (BR)) or to 1 of 2 control groups (No-instruction or Social Demand). The PEI focused on re-creating a pleasant memory, while the BR procedure involved decreasing respiration rate and positioning the body in a relaxed posture. All subjects underwent a 60-sec finger pressure pain trial. Analyses indicated that the PEI subjects reported lower ratings of pain, fear, and anxiety, and experienced greater finger temperature recovery than controls. The BR procedure resulted in greater blood pressure recovery, but did not alter ratings of pain or emotion relative to controls. Further research is needed to explore the clinical use of the PEI for acute pain management.
Embedded cluster (QM/MM) investigation of C6 diene cyclization in HZSM-5

Abstract We preformed hybrid, embedded cluster calculations at the DFT/MM level to investigate cyclization of C6 diene leading to C6 cyclic product in HZSM-5. We observe that C6 diene cyclization can occur either directly from a physisorbed olefin or by first chemisorption to form an alkoxide intermediate. Furthermore, chemisorption can occur through a double-site mechanism or a single-site mechanism. We also observe two alternative pathways for cyclization starting from chemisorbed alkoxides. Primary alkoxides preferred direct 1,6 ring closure (17.7 kcal/mol activation energy), whereas secondary alkoxides only proceeded through a 1,5 ring closure to methylcyclopentene alkoxide (22.12 kcal/mol activation energy), followed by ring expansion through a stable bicyclo[3.1.0]hexane intermediate (21.31 kcal/mol activation energy for the rate-limiting step). Thus our calculations confirm that C6 dienes are likely to be the precursors for cyclization reactions. Finally, we show that embedded cluster calculations are essential for proper analysis of C6 olefin chemistry in ZSM-5 models—with fairly important distinctions between embedded cluster and bare cluster results.
Nucleotide phosphatase in Strongylocentrotus purpuratus eggs. III. Multiple enzymatic activities in mature and immature eggs

On the basis of reaction patterns of eggs treated with activators and inhibitors and selected reactivating agents, there are at least three separate nucleotide phosphatase activities identifiable in maturing sea urchin eggs. Of these activities, the first two are sensitive to K + and Mg + +, respectively. The third activity is enhanced by both Na + and Ca + + and may represent two separate enzymes. These enzymatic activities are associated with different localizations and lead to a hypothesis of changing enzymatic patterns and localizations during the course of oogenesis.
Analysis and numerical solution of electromagnetic scattering from cavities

In this paper, we survey the mathematical study of the phenomenon of electromagnetic scattering from cavities. We consider time harmonic and transient fields, PEC and Impedance boundary conditions, fully embedded and over-filled cavities.
Experimental evaluation of analyte excitation mechanisms in the inductively coupled plasma

Abstract The inductively coupled plasma (ICP) is a justifiably popular source for atomic emission spectrometry. However, despite its popularity, the ICP is still only partially understood. Even the mechanisms of analyte excitation remain unclear; some energy levels are quite clearly populated by charge transfer while others might be populated by electron-ion recombination, by electron impact, or by Penning processes. Distinguishing among these alternatives is possible by means of a steady-state kinetics approach that examines correlations between the emission of a selected atom, ion, or level and the local number densities of species assumed to produce the excitation. In an earlier investigation, strong correlations were found between either calcium atom or ion emission and selected combinations of calcium atom or ion number densities and electron number densities in the plasma. However, all radially resolved data employed in the earlier study were produced from Abel inversion and from measurements that were crude by today's standards. Now, by means of tomographic imaging, laser-saturated atomic fluorescence, and Thomson and Rayleigh scattering, it is possible to measure the required radially resolved data without Abel inversion and with far greater fidelity. The correlations previously studied for calcium have been investigated with these more reliable data. Ion–electron recombination, either radiative or with argon as a third body, was determined to be the most likely excitation mechanism for calcium atom, while electron impact appeared to be the most important process to produce excite-state calcium ions. These results were consistent with the previous study. However, the present study suggests that collisional deactivation, rather than radiative decay, is the most likely mode of returning both calcium atoms and ions to the ground state.
Temperature programming in macrocycle-based ion chromatography

Abstract The well documented affinity of macrocyclic ligands for alkali and alkaline earth metal cations has been exploited in performing chromatographic separations of both cations and anions. It is shown that because the complexation reaction of metal ions with macrocyles is exothermic, the column capacity, and hence the retention of ions, is decreased as the column temperature is increased. While ion retention in classical ion exchange is also a function of temperature, the effect is less pronounced than in macrocycle-based systems. Temperature gradient elution of anions on macrocycle-based columns is performed based on the decrease of column capacity as the temperature is increased, showing improvements over separations performed under isothermal conditions.
JPSS data product improvement: A system engineering approach

Joint Polar Satellite System (JPSS) data product improvement requires a substantial record of on-orbit data extending over years. Such a data record now exists for the JPSS instruments developed for the Suomi National Polar Orbiting Partnership (SNPP) risk reduction mission. SNPP has now provided well over three years of on-orbit data from four JPSS instruments and derived data products. It is now feasible to apply a system engineering approach to data product improvement. In this approach on-orbit performance characteristics are traced back to instrument and algorithm design characteristics and pre-launch test data. During the instrument development phase system engineering was applied in the reverse direction, to trade off and optimize designs to meet requirements based on predicted performance. The key to data product improvement is comparison of on-orbit performance with performance predicted pre-launch and feedback of comparison findings into the design and development process for future JPSS instruments and algorithms.
Mining block correlations to improve storage performance

Block correlations are common semantic patterns in storage systems. They can be exploited for improving the effectiveness of storage caching, prefetching, data layout, and disk scheduling. Unfortunately, information about block correlations is unavailable at the storage system level. Previous approaches for discovering file correlations in file systems do not scale well enough for discovering block correlations in storage systems.In this article, we propose two algorithms, C-Miner and C-Minera, that use a data mining technique called frequent sequence mining to discover block correlations in storage systems. Both algorithms run reasonably fast with feasible space requirement, indicating that they are practical for dynamically inferring correlations in a storage system. C-Miner is a direct application of a frequent-sequence mining algorithm with a few modifications; compared with C-Miner, C-Minera is redesigned for mining block correlations by making concessions for the specific problem of long sequences in storage system traces. Therefore, C-Minera can discover 7--109p more correlation rules within 2--15 times shorter time than C-Miner. Moreover, we have also evaluated the benefits of block correlation-directed prefetching and data layout through experiments. Our results using real system workloads show that correlation-directed prefetching and data layout can reduce average I/O response time by 12--30p compared to the base case, and 7--25p compared to the commonly used sequential prefetching scheme for most workloads.
Asymptotic behavior of periodic dynamical systems on banach spaces

The concept of a periodic dynamical system on a Banach space is a generalization of periodic ordinary, functional, and partial differential equations. A theory is presented which analyzes the asymptotic behavior of such systems in the spirit of the direct method of Liapunov.
Pulmonary emphysema and fibrosis.

1)Thirty-seven patients with pulmonary emphysema and/or fibrosis have been reviewed. The outstanding symptoms are dyspnea, cyanosis and cough. The main findings on examination are barrel-shaped chest with limited respiratory excursion, hyper-resonance on percussion, hypertrophy of the auxiliary respiratory muscles and decreased pulmonary function. Roentgenograms are typical showing hyperaeration and/or fibrosis. Review of autopsy findings reveals simultaneous occurrence of emphysema and fibrosis in almost all cases. Emphysema involves either both lungs diffusely in the vesicular form or forms irregular, large "air cysts" in the bullous form. Frequent complications are recurrent pneumonia, hypertension of the lesser circulation with pulmonary atherosclerosis and cor pulmonale, spontaneous pneumothorax and cerebral changes. 2)No specific cause is known. 3)Treatment is unsatisfactory and is limited to the alleviation of symptoms, oxygen being the most effective agent. Artificial pneumoperitoneum and abdominal supports have been used to relieve dyspnea. Surgical intervention is reserved for cases with one or more giant bullae and consists of resection or drainage of the bullae. FIGURE 4Idiopathic progressive fibrosis, etiology undetermined. This condition was progressive, with increasing evidence of emphysema, cardiac involvement with extreme dyspnea. FIGURE 5Bullous emphysema.
Stein's Estimation Rule and Its Competitors- An Empirical Bayes Approach

Abstract Stein's estimator for k normal means is known to dominate the MLE if k ≥ 3. In this article we ask if Stein's estimator is any good in its own right. Our answer is yes: the positive part version of Stein's estimator is one member of a class of “good” rules that have Bayesian properties and also dominate the MLE. Other members of this class are also useful in various situations. Our approach is by means of empirical Bayes ideas. In the later sections we discuss rules for more complicated estimation problems, and conclude with results from empirical linear Bayes rules in non-normal cases.
Teebi hypertelorism syndrome (brachycephalofrontonasal dysplasia) in a U.S. family.

Teebi (Am J Med Genet 28:581-591, 1987) described a pattern of anomalies in an Arab kindred involving 16 individuals in 4 generations. Although some findings were similar to those in craniofrontonasal dysplasia, absence of craniosynostosis, normal to slightly broad nasal tip, normal nails, and male to male transmission distinguished this as a separate entity. This paper describes a U.S. family with similar findings, involving 6 individuals (2 male and 4 female) in 4 generations, with male to male transmission.
Reflecting on health: a system for students to monitor diet and exercise

Using an iterative design process, we designed and evaluated a system for college students to encourage the development and maintenance of healthy diet and exercise habits. The system has three components: a camera phone application to support photographic diet and exercise journaling, an automatic workout tracking application for exercise machines in the gym, and a visualization application to support users as they reflect on their diet and exercise activities.
A three dimensional organic–inorganic composite material constructed from cobalt-3,3′-bipyridyl networks linked through tetravanadate clusters: [{Co(3,3′-bpy)2}2V4O12]

Abstract The hydrothermal reaction of CoCl2·6H2O, 3,3′-bipyridine and NaVO3 in water at 160°C for 48 h yields the three-dimensional bimetallic oxide [{Co(3,3′-bpy)2}2V4O12] (1). The structure of 1 consists of two-dimensional {Co(3,3′-bpy)2}n2n+ networks, linked through cyclic tetranuclear {V4O12}4− clusters into a three-dimensional covalently linked assembly. Crystal data for C20H16CoN4O6V2 (1): monoclinic, P21/n, a=9.9794(6), b=16.129(1), c=13.4190(8) A, β=93.039(1)o, V=2156.9(2) A3, Z=4, Dcalc=1.753 g/cm3.
Defibrillation in the movies: A missed opportunity for public health education

Abstract Aim To characterize defibrillation and cardiac arrest survival outcomes in movies. Methods Movies from 2003 to 2012 with defibrillation scenes were reviewed for patient and rescuer characteristics, scene characteristics, defibrillation characteristics, additional interventions, and cardiac arrest survival outcomes. Resuscitation actions were compared with chain of survival actions and the American Heart Association (AHA) Emergency Cardiovascular Care (ECC) 2020 Impact Goals. Cardiac arrest survival outcomes were compared with survival rates reported in the literature and targeted by the AHA ECC 2020 Impact Goals. Results Thirty-five scenes were identified in 32 movies. Twenty-five (71%) patients were male, and 29 (83%) rescuers were male. Intent of defibrillation was resuscitation in 29 (83%) scenes and harm in 6 (17%) scenes. Cardiac arrest was the indication for use in 23 (66%) scenes, and the heart rhythm was made known in 18 scenes (51%). When the heart rhythm was known, defibrillation was appropriately used for ventricular tachycardia or ventricular fibrillation in 5 (28%) scenes and inappropriately used for asystole in 7 (39%) scenes. In 8 scenes with in-hospital cardiac arrest, 7 (88%) patients survived, compared to survival rates of 23.9% reported in the literature and 38% targeted by an AHA ECC 2020 Impact Goal. In 12 movie scenes with out-of-hospital cardiac arrest, 8 (67%) patients survived, compared to survival rates of 7.9–9.5% reported in peer-reviewed literature and 15.8% targeted by an AHA ECC 2020 Impact Goal. Conclusion In movies, defibrillation and cardiac arrest survival outcomes are often portrayed inaccurately, representing missed opportunities for public health education.
Functional units in rainbow trout (Salmo gairdneri, Richardson) liver: III. Morphometric analysis of parenchyma, stroma, and component cell types

Hepatic stroma and parenchyma with its component cell types were quantitatively described in adult male and female actively-spawning 5-year-old rainbow trout (Salmo gairdneri, Richardson). Point-count morphometry of glycol methacrylate sections estimated volume compartments for stroma and parenchyma. Veins composed 85% of the stroma while arteries and bile ducts occupied approximately 6-7% each. Parenchyma accounted for 95% of hepatic volume. Point-count morphometry of transmission electron micrographs estimated volume compartments as well as numerical and surface density measurements for parenchymal components. Within the hepatic parenchymal compartment, hepatocytes occupied 85% and showed significant sex differences. Female hepatocytes were significantly more numerous but were smaller, only 60% of the volume of male hepatocytes. Since hepatocyte nuclear volume was equal in both sexes, differences were due to reduced cytoplasmic volume in females. Perisinusoidal macrophages of females occupied larger volumes of their respective parenchymal compartments, and their larger mean cytoplasmic volumes suggested activation. Biliary epithelial cells of preductules and ductules were numerous. Ratios of numerical density of hepatocytes to biliary epithelial cells were consistent with a tubular arrangement of hepatocytes. Factors possibly mediating the sexual dimorphism are discussed.
Thymineless Death in polA+ and polA− Strains of Escherichia coli

The extreme sensitivity of polA− cells to thymineless death is due, primarily, to the absence of an extended lag prior to the commencement of death. Once thymineless death has commenced, the rate in polA− cells is only slightly faster than in polA+ cells.
Decreasing Incidence of Herpes Zoster in the Highly Active Antiretroviral Therapy Era

We evaluated the effect of highly active antiretroviral therapy (HAART) on the incidence of herpes zoster (HZ) in human immunodeficiency virus (HIV)-infected subjects. The annual incidence of HZ per 100 person-years decreased significantly from 6.3 episodes in 1987 to 1.0 episode in 2011, probably reflecting improved immune function.
Sound Bite News: Television Coverage of Elections, 1968–1988

Based on samples of network evening news broadcasts from each presidential election from 1968 through 1988, this article shows that the average sound bite has declined from 43 to 9 seconds. This change is interpreted as part of a general shift in the style of television news toward a more mediated, journalist-centered form of journalism. Three factors help explain this change: (a) the evolution of television “know-how,” (b) the weakening of political consensus and authority during the last 20 years, and (c) changes in the economics of the industry. This change has significant consequences for journalism in the 1990s.
Performance of collision avoidance protocols in single-channel ad hoc networks

The paper presents the first analytical model to derive the saturation throughput of collision avoidance protocols in multi-hop ad hoc networks with nodes randomly placed according to a two-dimensional Poisson distribution. We show that the sender-initiated collision-avoidance scheme performs much better than the ideal CSMA scheme with a separate channel for acknowledgments. More importantly, we show that the collision-avoidance scheme can accommodate much fewer competing nodes within a region in a network infested with hidden terminals than in those cases without hidden terminals or with just a few, if reasonable throughput is to be maintained. Simulations of the popular IEEE 802.11 MAC protocol show that it cannot ensure collision-free transmission of data packets and thus throughput can degrade well below what is predicted by the analysis of a correct collision avoidance protocol. Based on these results, a number of improvements are proposed for the IEEE 802.11 MAC protocol.
Efficient array illuminator using binary-optics phase plates at fractional-Talbot planes

We describe a phase plate based on the fractional-Talbot effect that converts a single expanded laser beam into a regular array of uniformly illuminated apertures with virtually 100% efficiency. The size, spacing, and fill factor of the illuminated aperture grid can be freely chosen to interface with a variety of electro-optic devices. A binary-optics phase plate is demonstrated that converts uniform illumination into an array of square illumination cells with a fill factor of 1/16.
What the X Has to Do with It: Differences in Regulatory Variability between the Sexes in Drosophila simulans

The mechanistic basis of regulatory variation and the prevailing evolutionary forces shaping that variation are known to differ between sexes and between chromosomes. Regulatory variation of gene expression can be due to functional changes within a gene itself (cis) or in other genes elsewhere in the genome (trans). The evolutionary properties of cis mutations are expected to differ from mutations affecting gene expression in trans. We analyze allele-specific expression across a set of X substitution lines in intact adult Drosophila simulans to evaluate whether regulatory variation differs for cis and trans, for males and females, and for X-linked and autosomal genes. Regulatory variation is common (56% of genes), and patterns of variation within D. simulans are consistent with previous observations in Drosophila that there is more cis than trans variation within species (47% vs. 25%, respectively). The relationship between sex-bias and sex-limited variation is remarkably consistent across sexes. However, there are differences between cis and trans effects: cis variants show evidence of purifying selection in the sex toward which expression is biased, while trans variants do not. For female-biased genes, the X is depleted for trans variation in a manner consistent with a female-dominated selection regime on the X. Surprisingly, there is no evidence for depletion of trans variation for male-biased genes on X. This is evidence for regulatory feminization of the X, trans-acting factors controlling male-biased genes are more likely to be found on the autosomes than those controlling female-biased genes.
Hypothesis: β amyloid precursor protein is a key sorting and targeting receptor for neuropeptidases

A testable hypothesis, that the β-amyloid precursor protein (AβPP) is a key sorting and targeting receptor for neuropeptidases and other proteases in the secretory system, is developed. After delivery of these neuropeptidases to the synapse, AβPP is cleaved by an extracellular protease called an α-secretase which generates a non-amyloidogenic C-terminal fragment. This cleavage which occurs after depolarization of the presynaptic membrane and concomitant neurotransmitter release, frees the AβPP bound peptidases to hydrolyse neuropeptides, analogous to acetylcholine hydrolysis by acetylcholinesterase. Some of these bound neuropeptidases with β-secretase activity can also cleave AβPP to generate a C-terminal amyloidogenic fragment which can then be processed further to generate amyloid beta, a key pathogenic molecule in AlzheimerS disease. We discuss possible explanations for why mutations in AβPP itself presenilins 1 and 2 or apolipoprotein E can either cause or produce high risk for Alzheimer's disease; in...
Freeman‐Sheldon (whistling face) syndrome. Anaesthetic and airway management

We describe the anaesthetic management of Freeman-Sheldon syndrome in a two-and-a-half year old undergoing club foot correction. Following an inhalational induction using halothane, tracheal intubation by direct laryngoscopy proved impossible. A laryngeal mask airway was inserted and intubation with a 4.5 tracheal tube was successfully achieved using a fibreoptic bronchoscope passed through the LMA. The child had an uneventful anaesthetic course. A caudal epidural was used for postoperative analgesia and the child was discharged home on day two. The anaesthetic and airway management options of this syndrome are outlined.
IMPORTANCE OF INSULIN ABSORPTION, SUBCUTANEOUS BLOOD FLOW, AND RESIDUAL BETA‐CELL FUNCTION IN INSULIN THERAPY

. Lauritzen, T., Binder, C. and Faber, O. K. (Steno Memorial Hospital, Gentofte, Denmark). Importance of insulin absorption, subcutaneous blood flow, and residual beta-cell function in insulin therapy. Acta Paediatr Scand, Suppl. 283: 81, 1980.—The interaction between variation in insulin absorption and beta-cell function was studied as well as the possible relation between subcutaneous blood flow through the region of injection and the variability in insulin absorption. The results indicate that the dose of insulin, the type of insulin preparation and the local blood flow influence the insulin absorption. Residual endogenous insulin secretion, governed by the blood glucose values, serves as a modulator.
Dynamic simulation as a design tool for a microactuator array

We use dynamic simulation to optimize the design of an existing micro-electromechanical (MEM) device, called the manipulation chip (M-Chip). This device contains an excess of 10000 moving actuators, called resonators, which oscillate torsionally at a few kHz. Parts dropped on the chip's surface are conveyed towards a unique direction. Given the enormous number of moving parts, it is impractical to attempt to measure the device's (or part's) dynamic state during a manipulation task. Yet, knowing this information is crucial for redesign and optimization. We make use of a powerful dynamic simulation tool, called "Impulse", to generate synthetic measurements over a range of experiments. From these results, we suggest redesign options which debug existing problems and improve the feed rate. The array is found to behave similar to a viscous spring-loaded conveyor belt; most of its energy is spent on driving the part vertically, calling for a more efficient design.
Dual GABAA receptor‐mediated inhibition in rat presympathetic paraventricular nucleus neurons

The inhibitory neurotransmitter GABA plays a key role in the modulation of paraventricular nucleus (PVN) neuronal excitability and sympathoexcitatory outflow, under both physiological and pathological conditions. In addition to mediating conventional synaptic transmission (phasic inhibition), GABAA receptors of distinct biophysical, molecular and pharmacological properties have been recently found to underlie a slower, persistent form of inhibition (tonic inhibition). Whether the ‘tonic’ inhibitory modality is present in presympathetic PVN neurons, and what its role is in modulating their activity is at present unknown. Here, we combined tract-tracing techniques with patch-clamp electrophysiology to address these questions. Recordings obtained from PVN-RVLM (rostral ventrolateral medulla) projecting neurons show that besides blocking GABAA-mediated inhibitory postsynaptic currents (IPSCs, Iphasic), the GABAA receptor blockers bicuculline and picrotoxin caused an outward shift in the holding current (Itonic). Conversely, the high affinity GABAA blocker gabazine blocked Iphasic without affecting Itonic. THIP, a GABAA receptor agonist that preferentially activates δ- over γ-containing receptors, enhanced the magnitude of Itonic. Our results also indicate that during conditions of strong and/or synchronous synaptic activity, Itonic may be activated by spillover of synaptically released GABA. Blockade of Itonic induced membrane depolarization, increased firing activity, and enhanced the input–output function of PVN-RVLM neurons. Altogether, our results support the presence of a persistent GABAA-mediated inhibitory modality in presympathetic PVN neurons, which plays a major role in modulating their excitability and firing activity.
Terminating Architecture: Mega-Development in Hong Kong

This paper examines large development projects as a function of finance in the context of Hong Kong, taking Kowloon Station as an exceptionally revealing case. Hong Kong's property market is one of the most established in Asia, and it points to the ways in which large-scale development schemes proliferate along efficient and affordable mass transit railway systems with great speed and success. At Kowloon Station, finance redefines architecture; instead of focusing on aesthetics and community, it is now promoting standardization, market visibility and semantic control. The financial viability of these developments depends entirely on these new goals; mega-developments such as Kowloon Station – and those in other parts of Asia – are successful in inventing major mass transit railway stations as terminals, in capturing commuters within spatial enclosures surrounded by barrier-like physical features, and in terminating architecture as it has long been established as a discipline. Mega-development is increasin...
What are candidate biobehavioral mechanisms underlying the association between secondhand smoke exposure and mental health

Abstract There is a consistent positive and significant association between secondhand smoke exposure and mental health outcomes in the literature. There are potential genetic and behavioral confounders (e.g., psychological stress, maternal depression, and family functioning) were discussed, as well as potential causal neurobiological pathways (e.g., dopamine system). Further neurobiological research to establish causal pathways is needed as well as the integration of positive observational findings into clinical and public health prevention practices.
Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes.

BACKGROUND Optimal use of stereotactic radiosurgery (SRS) vs external beam radiation therapy (EBRT) for treatment of residual/recurrent atypical meningioma is unclear. OBJECTIVE To analyze features associated with progression after radiation therapy. METHODS Fifty radiation-naive patients who received SRS or EBRT for residual and/or recurrent atypical meningioma were examined for predictors of progression using Cox regression and Kaplan-Meier analyses. RESULTS Thirty-two patients (64%) received adjuvant radiation after subtotal resection, 12 patients (24%) received salvage radiation after progression following subtotal resection, and 6 patients (12%) received salvage radiation after recurrence following gross total resection. Twenty-one patients (42%) received SRS (median 18 Gy), and 7 (33%) had tumor progression. Twenty-nine patients (58%) received EBRT (median 54 Gy), and 13 (45%) had tumor progression. Whereas tumor volume (P = .53), SRS vs EBRT (P = .45), and adjuvant vs salvage (P = .34) were not associated with progression after radiation therapy, spontaneous necrosis (hazard ratio [HR] = 82.3, P < .001), embolization necrosis (HR = 15.6, P = .03), and brain invasion (HR = 3.8, P = .008) predicted progression in univariate and multivariate analyses. Tumors treated with SRS/EBRT had 2- and 5-year actuarial locoregional control rates of 91%/88% and 71%/69%, respectively. Tumors with spontaneous necrosis, embolization necrosis, and no necrosis had 2- and 5-year locoregional control rates of 76%, 92%, and 100% and 36%, 73%, and 100%, respectively (P < .001). CONCLUSION This study suggests that necrosis may be a negative predictor of radiation response regardless of radiation timing or modality. ABBREVIATIONS AM, atypical meningiomaEBRT, external beam radiation therapyGTR, gross total resectionLC, locoregional controlOS, overall survivalPOE, preoperative embolizationRT, radiation therapySRS, stereotactic radiosurgerySTR, subtotal resection.
The Approach to the Critically Ill Infant

The ongoing maturation of the small infant creates a unique state of physiologic transition. Severe illness during this transition may be due to a congenital disorder not initially apparent at birth (i.e. congenital heart disease, inborn errors of metabolism) or, alternatively, due to environmental forces that overwhelm the small infant (i.e. infections, trauma). Due to the variety of disorders that can compromise a small infant, the physician faces a considerable challenge in establishing the correct diagnosis. The initial stabilization of such an infant can be technically difficult and requires expertise in airway, respiratory, circulatory and neurological support.
The Role of Intermediate (10-nm) Filaments in the Development and Integration of the Myofibrillar Contractile Apparatus in the Embryonic Mammalian Heart

Most eukaryotic cells possess three major distinct classes of fibrous organelles that are independently organized and function as elements of the cytoskeleton. These elements of the cytoskeleton include microtubules (25 nm), which form elaborate cytoplasmic networks; actin or thin filaments (6 nm), which form cytoplasmic stress fibers; and the intermediate filaments (10 nm). The term “intermediate” filaments has been applied to this third class of cytoplasmic fibrous proteins because their mean diameter at the ultrastructural level lies between the mean diameter of actin and microtubules. Investigations have shown that both actin (Clarke and Spudeck, 1977; Pollard and Werhing, 1974; Stossel, 1978) and microtubules (Stephens and Edds, 1976) are involved in various aspects of cell motility and also in the movement of cellular organelles. The role of the intermediate filaments in cell function is unresolved at present. The intermediate filaments were initially regarded as a disaggregation, or degradation product, or myosin and/or microtubules and thus until recently attracted little attention. Current biochemical and immunofluorescent methods have established the intermediate filaments as a distinct class of cytoplasmic proteins that differ with respect to the physical properties of their subunits. In contrast to the proteins actin and tubulin, which are the major structural protein subunits of microfilaments and microtubules, respectively, the intermediate-filament proteins do not appear to be highly conserved (Bennett et al., 1979; Lazarides and Balzer, 1978; Shelanski and Liem, 1979) and exhibit a relatively high degree of tissue specificity. The intermediate filaments have been divided into several subclasses on the basis of biochemical and immunochemical data, and their constituent proteins have been named accordingly. These subclasses at present include: (1) prekeratin tonofilaments found in epithelial cells (Franke et al.,1978a,b, 1979b; Sun et al., 1979) and cells of epithelial origin; (2) vimentin or decamin filaments (Bennett et al., 1978b, 1979; Franke et al.,1978a, 1979a) found in fibroblasts and other cells of mesenchymal orgin; (3) desmin filaments (Izant and Lazarides, 1974; Lazarides and Hubbard, 1976; Lazarides, 1978a; Lazarides and Balzer, 1978) or skeletin (Campbell et al.,1979) of smooth muscle, which have also been identified in the cytoplasm and Z lines of skeletal and cardiac muscle; (4) neurofilaments of neurons; and (5) glial filaments, which are present in astrocytes (Shelanski and Liem, 1979) but not in all types of glial cells (Liem et al., 1978; Schlaepfer, 1977; Schlaepfer and Lynch, 1977). Current studies have shown that it is not uncommon to find two of these classes of intermediate filaments coexisting in the same cell type. It is also quite possible that more than two classes of intermediate filaments can be present in a single cell type (Lazarides, 1980).
Efficacy of MK-0457 (VX-680) in combination with docetaxel in a p53 shRNA/vector dual flank NSCLC xenograft model

C215 BACKGROUND: : MK-0457 (VX-680) reversibly inhibits aurora kinases A, B and C (Ki’s of 0.7, 18 and 4.6 nM, respectively). Clinical investigation is ongoing in patients with solid tumors and hematologic malignancies. In pre-clinical models, MK-0457 has demonstrated potent single agent activity against a broad panel of tumor cell lines both in vitro and in vivo. Over-expression of aurora A is reported to reduce taxane sensitivity and knock down of aurora A restores sensitivity. Previous in vitro studies showed additive/synergistic activity of MK-0457 in combination with docetaxel (DXT) in colony formation assays. The objective of these studies was (1) to evaluate the combination activity of MK-0457 and DXT in a xenograft model of NSCLC (A549) and (2) to determine the effect, if any, of p53 status on tumor sensitivity to MK-0457 in combination with DXT. METHODS: In two independent studies, MK-0457 and DXT were administered as single agents and in combination to athymic nude mice (n= 10 per group) bearing dual flank A549 tumors expressing either p53 shRNA (p53-) or an empty vector control (p53+). Tumor measurements and body weights were recorded twice weekly for 4 weeks. In Experiment #1, a non-efficacious dose/regimen of MK-0457 (50 mg/kg IP BID for 2 days) was combined with DXT at 50% of its MTD (7.5 mg/kg IV, q7d) in two different combination sequences. In Experiment #2, different MK-0457 schedules (50 mg/kg BID for 1 or 2 days; 100 mg/kg BID for 1 day) were combined with a higher dose of DXT (12.5 mg/kg; 75% of MTD) in both simultaneous and sequential regimens. RESULTS: All MK-0457/DXT combinations demonstrated synergistic anti-tumor activity compared to the single agents, independent of the combination sequence and DXT dose level (T/C range of 15% to -10%). In both experiments, p53- tumors were more sensitive to MK-0457/DXT combinations than p53+ tumors, with an incidence of regression in p53- tumors of 41% compared to 16% in p53+ tumors (Experiment #2). MK-0457/DXT combination regimens induced additive reductions in body weight and white blood cell counts compared to single agents. A separate pharmacokinetic study in non-tumor bearing animals confirmed the absence of a drug-drug interaction between MK-0457 and DXT. CONCLUSION: Additive/synergistic anti-tumor activity was observed forMK-0457 combined with DXT independent of the sequence of MK-0457 or DXT administration. Anti-tumor activity was more significant in p53- tumors suggesting the observed synergy is influenced by p53 status. These findings support clinical investigation of MK-0457 in combination with DXT in solid tumor indications for which DXT is the standard of care.
Transactivation of the p21 promoter by BRCA1 splice variants in mammary epithelial cells: evidence for both common and distinct activities of wildtype and mutant forms

We have evaluated the transcriptional activation of a human p21 promoter reporter construct by transfection of BRCA1 expression constructs into tumorigenic and nontumorigenic human breast cell lines. Two cell lines with wildtype p53 (MCF-7 and MCF10A) demonstrated transcriptional activation of the p21 promoter by full-length BRCA1 (BRCA1L) as well as by two splice variants that lack most of exon 11 (BRCA1S and BRCA1S-9,10). In contrast, two cell lines with mutant p53 (MDA-231 and HCC1937) were inactive. Co-transfection of BRCA1L with BRCA1S or BRCA1S-9,10 exhibited synergistic p21 promoter activation, due to augmented expression of the cytomegalovirus promoter-based BRCA1 expression constructs. We examined the transcriptional activity of two known sequence alterations in BRCA1, one that results in a carboxy-terminal truncation of BRCA1 and is clearly pathogenic, and the other a missense mutation that is suspected of predisposing to cancer. Although both mutations have been shown to be defective in some assays of transactivation, we observed both mutations to be fully active in activation of the p21 promoter when incorporated in the full-length BRCA1L. In contrast, these mutations rendered BRCA1S inactive. These observations indicate that such transcriptional assays cannot serve as the basis for a functional appraisal of BRCA1 sequence alterations encountered in the course of genetic testing.