cssi/SciSciGPT-SciSciNet huggingface dataset:
Fifty years of hypersonics: where we've been, where we're going

Abstract Hypersonic flight has been with us since 22 September 1963, when Robert M. White flew the North American X-15 at 4520 mph at an altitude of 354,200 ft —a Mach number of 6.7! This remarkable achievement was accomplished over six decades due to intensive research and development by a large number of scientists and engineers. In spite of that momentous achievement, designers have found the hypersonic environment to be harsh and non-forgiving. New programs since the 1960s have often uncovered the unknown unknowns, usually the hard way—early flights of new systems have often revealed problems of which the designers were unaware. Such problems include: the ineffectiveness of the body flap for the Space Shuttle Orbiter, the viscous/inviscid interactions produced by the umbilical fairings that damaged the conical section tile protection system of the Gemini Capsule, and the shock/shock interaction that damaged the X-15A-2 when it carried the hypersonic ramjet experiment. In order to continue to make advances in hypersonic flight a sustained and visionary effort is essential to generate required knowledge and technology. In order to better prepare for future developments in hypersonic flight, this article reviews the advances made within the past 50 years and then looks into the future, not just for new technological developments, but for new ways of thinking about the unknown challenges that lie ahead.
Family, Literacy, and Skill Training in the Antebellum South: Historical-Longitudinal Evidence from Charleston

Using individual measures of adult and child literacy, this article examines human capital acquisition in one Southern city, Charleston, 1790–1840. White adult literacy rates differed greatly by sex and class and rose gradually over time. Mothers played a critical role in human capital transmission in early childhood and long after children had left their care. Both relatively recent literacy acquisition and early childhood family structure influenced the occupation to which children were apprenticed. These results are consistent with present-day studies that trace sources of adult well-being back into childhood.
Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression

Abstract Background: Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease. Methods: Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B 12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses. Results: At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m 2 ) and study B (GFR, 13 to 24 mL/min/1.73 m 2 ) were 16.9 μmol/L (median, 15.6 μmol/L) and 23.0 μmol/L (median, 20.5 μmol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were −4.35 and −3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (−0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], −0.67 to 0.15) or multivariable (−0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, −0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, −0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, −0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study. Conclusion: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B 12 levels are not independent risk factors for progression of nondiabetic kidney disease. Am J Kidney Dis 40:932-939. © 2002 by the National Kidney Foundation, Inc.
The Efficiency Distribution Approach in Data Envelopment Analysis: An Application

A method is developed here for characterizing the empirical distribution of the efficient units in data envelopment analysis. Two empirical applications illustrate the various uses of the distribution approach. One involves the cost frontier which exhibits increasing returns to scale and the other involves a dynamic production frontier, where technological change causes a shift of the production frontier over time.
Read my mind: What users want from online information

The author explores why computer users often do not use the HELP function offered by many programs. Three explanations are frequently offered for not using HELP: Asking for help: may break the user's flow of thought; disorients the user as far as navigation from screen to screen is concerned: and often does not provide the answer the user needs. Experience suggests that people have a low tolerance for unhelpful help, and that their initial expectations are quickly revised downward. What people think they want, what people expect, and implications of why users want context-dependent help are discussed. A conversational model for help is suggested. The application of a social, conversational model to human-computer interaction accounts for several phenomena that have been observed: people react badly to poor response time, people also react badly to very quick response time, and people react emotionally to programs.
A Comparison of PZT-Based and TiNi Shape Memory Alloy-Based MEMS Microactuators

Microactuators based on PbZr1-xTixO3 (PZT) and TiNi shape memory alloys (SMAs) are compared using microelectromechanical systems (MEMS) micropumps and microvalves as typical devices. The advantages of PZT-based microactuation include large actuation forces and high operating frequencies, leading to high operating pressures and flow rates. Disadvantages include high operating voltages and low strains. TiNi SMA-based microactuators can achieve high flow rates at low operating voltages, due to their high recoverable strains; however, they suffer from low operating frequencies and high power consumption. For both microactuation schemes, additional structures are usually required to realize the reciprocating motion required for MEMS devices. When used in MEMS, the thicknesses of PZT and TiNi SMA films range up to several microns. The thickness dependence of properties relevant to microactuation of PZT and TiNi SMA thin films are discussed and compared.
Vitamin Deficiencies and Excesses

The outstanding achievement of nutritional science has been the discovery of about 50 nutrients essential for man. In 1903, F. Gowland Hopkins recognized the need of organic growth factors now known as vitamins. Sixteen different vitamins have been discovered followed by isolation, elucidation of the structure, and in most cases synthesis of these substances. Identification of the role of vitamins as coenzymes was a major step in the understanding of their role in metabolism and physiology. This has been termed a golden era of nutritional research.
Randomized clinical trial of adapted mindfulness-based stress reduction versus group cognitive behavioral therapy for heterogeneous anxiety disorders.

Abstract Objective To compare a mindfulness-based intervention with cognitive behavioral therapy (CBT) for the group treatment of anxiety disorders. Method One hundred five veterans (83% male, mean age = 46 years, 30% minority) with one or more DSM-IV anxiety disorders began group treatment following randomization to adapted mindfulness-based stress reduction (MBSR) or CBT. Results Both groups showed large and equivalent improvements on principal disorder severity thru 3-month follow up (ps Conclusions CBT and adapted MBSR were both effective at reducing principal diagnosis severity and somewhat effective at reducing self-reported anxiety symptoms within a complex sample. CBT was more effective at reducing anxious arousal, whereas adapted MBSR may be more effective at reducing worry and comorbid disorders.
Book review: 5 days at memorial: life and death in a storm-ravaged hospital

Sheri Fink draws the reader into Memorial Hospital and expresses the thoughts of those who struggled with the impossible during Hurricane Katrina. What was unknown is that health care providers, including nurses, were faced with the unthinkable: assisting critically ill patients to die. Fink is unflinching in telling the story, including investigation of the deaths, and clearly critiques disaster preparedness in health care settings. This book will help nurses prepare for ethical decision making in times of crisis.
Intractable epilepsy: management and therapeutic alternatives

Summary More than half of patients with newly diagnosed epilepsy achieve complete seizure control without major side-effects. Patients who continue to have seizures after initial medical therapy should have an early and detailed assessment to confirm the diagnosis, to determine the underlying cause and epilepsy syndrome, and to choose an adequate treatment strategy. The risks and potential benefits of surgical procedures or experimental therapy have to be weighed against the chance of improvement and the potential side-effects of additional medical therapy. Surgery for temporal lobe epilepsy, the most common cause of focal epilepsy, can control seizures and improve quality of life in appropriately selected patients. However, around 20–30% of patients do not respond to medical or surgical treatment. The management of chronic intractable epilepsy requires comprehensive care to address the adverse events of medical treatment, quality of life issues, and comorbid disorders. Much research focuses on the experimental treatment options that offer hope of seizure reduction or cure.
Atrial fibrillation and waveform characterization

The surface electrocardiogram (ECG) is a convenient, cost effective, and noninvasive tool for the study of atrial fibrillation (AF). It can be used to examine the hypothesized mechanisms of AF as well as to quantify and assess the effect of electrophysiological remodeling and the effectiveness of treatment on different types of AF. Time domain methods can be used to characterize the signal in the surface ECG. The authors described observations that can be obtained directly from the signal, such as the general characteristics of AF in the surface ECG and the ventricular response to AF. A discussion on commonly used methods to characterize atrial activity is also presented. These methods include cancellation techniques, vector analysis, and autocorrelation. Observations show that combining time and frequency domain methods provides a more thorough understanding of the characteristics of the atrial activity in the surface ECG. Whether the study of atrial activity in the surface ECG can be used to distinctively distinguish between different mechanisms of AF is not yet known, but further investigation can improve our understanding of these mechanisms and help with the management of this common arrhythmia
Associations among 25-hydroxyvitamin D, diet quality, and metabolic disturbance differ by adiposity in adults in the United States.

Context: Recent evidence indicates that a higher plasma level of 25-hydroxyvitamin D [25(OH)D] is associated with lower adiposity and a reduced number of metabolic disturbances (MetD). Objectives: We examined associations among dietary quality, 25(OH)D, percent body fat (%BF), and MetD, and a pathway linking them, across central obesity. Design: This cross-sectional nationally representative study used extensive data from the National Health and Nutrition Examination Surveys of 2001–2004. Participants: U.S. adults aged at least 20 yr were stratified by central obesity (CO) status. Sample sizes ranged from 1943 (all MetD combined) to 7796 (each component). Main Outcome Measures: %BF was measured using dual-energy x-ray absorptiometry, and MetD was measured with individual continuous nonadiposity outcomes (e.g. fasting plasma glucose) and with a composite count index of binary MetD with prespecified cutoff points (Index I). Results: A higher 25(OH)D was associated with better dietary quality, lower %BF, and...
Surface State Magnetization and Chiral Edge States on Topological Insulators

We study the interaction between a ferromagnetically ordered medium and the surface states of a topological insulator with a general surface termination that were identified recently [F. Zhang et al. Phys. Rev. B 86, 081303(R) (2012)]. This interaction is strongly crystal face dependent and can generate chiral states along edges between crystal facets even for a uniform magnetization. While magnetization parallel to quintuple layers shifts the momentum of the Dirac point, perpendicular magnetization lifts the Kramers degeneracy at any Dirac points except on the side face, where the spectrum remains gapless and the Hall conductivity switches sign. Chiral states can be found at any edge that reverses the projection of the surface normal to the stacking direction of quintuple layers. Magnetization also weakly hybridizes noncleavage surfaces.
Cause and Country: The Politics of Ambivalence and the American Vietnam War Resistance in Canada

Neil Smelser's (1998) Presidential Address to the American Sociological Association is a critique of rational choice theory that seeks to shift the focus from reason and opportunity to ambivalence, for example, in studies of social change processes involving migration and social movements. Smelser emphasizes that ambivalence is an intrapsychic process that operates beyond reason and opportunity. I critique and reconceive Smelser's ideas about ambivalence in considering the largest political exodus from the United States since the American Revolution, the migration of more than 50,000 young Americans to Canada during the Vietnam War. The concepts of reconstructed identity and residual ties, and the reduction and persistence of ambivalence they respectively imply, help to mediate responses to political opportunity and opposition encountered by American Vietnam War resisters in Canada. These concepts can be used to rearticulate the meaning of ambivalence in ways that are consistent with Stryker's structured symbolic interactionist theory of identity and role choice. Census and interview data confirm the reconceived mediating role of ambivalence: Although most of the young Americans who came to Canada stayed, and most of those who stayed reconstructed their identities as unambivalent Canadians, those who came during the imposition of the Canadian War Measures Act were most likely to return to the United States, or if they settled in Canada, to remain less reconstructed in identity and more residually tied to the United States. The latter more ambivalent war resisters who settled in Canada are still today less likely to participate politically by voting in Canadian federal elections.
Role of Insulin, Thyroxin and Cortisol in Luteinization of Porcine Granulosa Cells Grown in Chemically Defined Media

In order to determine the exact hormonal requirements for luteinizationin vitro, porcine granulosa cells obtained from small (1-2 mm), medium (3-5 mm) and large (6-12 mm) follicles were grown in serum-free media in the presence of various combinations of luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, cortisol and thyroxin. Morphology as well as progestin secretion was monitored throughout an 8-10 day culture period. The cells were grown in either medium “199D,” which consisted of medium 199 plus 0.4 percent bovine serum albumin (BSA) and 0.2 percent lactalbumin hydrolysate, or the serumless medium of Neuman and Tytell (“SMD”), which already contains 0.2 percent lactalbumin hydrolysate, plus 0.4 percent BSA. Additional cells were grown in the presence of 15 percent pig serum in a balance of medium 199 (medium Y). Cell adherence to the glass and cell maintenance were both less in the serum free media compared to serum-containing medium V. In contrast, progestin secretion expressed per cell was consistently greater when the cells were grown in serum-free compared to serum-containing medium V. Cells harvested from large follicles were able to secrete more progestin compared to cells obtained from small or medium-sized follicles in both types of serum-free media. If cells were grown in serum-free media, addition of 1 mU/mI insulin had some stimulatory (50-200 percent) action upon cell maintenance as well as a small, slow developing stimulatory action upon progestin secretion. The insulin treatment led to an increase in cytoplasmic vacuoles and lipid droplets. Addition of either iO’� M triiodothyronine or thyroxine or 0.01 Mg/mI cortisol along with 1.0-10 mU/mI insulin led to a 3-5 fold stimulation of progestin secretion by cells harvested from small and large follicles. The thyroxin in combination with insulin brought about an increase in oil red 0 and hematoxylin and eosin stainable material present within the cytoplasmic. The cortisol brought about an increase in distinctness of nucleolar material. Addition of either cortisol or thyroxin in the absence of insulin consistently brought about cellular necrosis. In cultures of cells grown in serum-free medium obtained from small follicles, addition of a mixture of 0.1 jig/mI human LH plus 0.1 jig/mI human FSH, 1.0 mU/mI insulin plus either i07 M thyroxin or 0.01 Mg/mI cortisol brought about morphological luteinization and a 4-14 fold increase in progestin secretion above when LH and FSH were added alone. The LH and FSH failed to bring about full morphological luteinization in the absence of these hormones. Addition of a complete mixture of all these hormones brought about the best morphological luteinization and stimulation in progestin secretion. It can be concluded that spontaneous and LH- and FSH-induced granulosa cell luteinization in serum-free culture media is enhanced by the inclusion of a mixture of insulin, cortisol and thyroxin.
The history of poisoning in the future: lessons from Star Trek.

Background: The Arts are replete with examples of presaged events of the future. Since a unique glimpse of the 23rd century is afforded by the television series Star Trek, a survey of the toxin-related events as chronicled by the crew of the USS Starship Enterprise may provide insight to prepare toxicologists for the future. Methods: An investigation of the logs of the Enterprise was undertaken for the years 2266 to 2269 which were part of its first 5-year mission. Internet sites, published databases, and selected recorded episodes from the original Star Trek television series were searched for poisonings or toxin-related incidents. Results: Out of the 79 Star Trek episodes, 28 (35%) involved toxin-related incidents. A total of 31 poisoning incidents were documented with 13 environmental, 9 intentional, 5 unintentional, and 4 homicidal circumstances. Biotoxins (10 incidents) were the most frequently involved toxin followed by neurotoxins (9), radiation (3), cytotoxins (3), temporal toxins (3), acids (2), ...
EXCITATION OF LONG INTERNAL WAVES BY GROUPS OF SHORT SURFACE WAVES INCIDENT ON A BARRIER

Examen pour un ocean bicouche, de l'effet de la diffraction par une longue barriere (brise-lames) sur des ondes longues au second ordre, forcees par des ondes incidentes, courtes, modulees sinusoidalement. Lorsque la v de groupe des ondes courtes se tient entre les v de phase des modes barocline et barotrope les plus longs, les ondes internes longues (de frequence egale a 2 fois celle de modulation des ondes courtes) rayonnent a partir du rayon-frontiere qui separe la region d'ombre geometrique due a la barriere, de la region «eclairee» par les ondes incidentes. En particulier, les ondes baroclines peuvent penetrer dans la region d'ombre. Cette penetration a lieu lorsque les ondes internes longues ne sont pas mises en resonance par les ondes incidentes courtes
Investing in Democracy: Engaging Citizens in Collaborative Government

Book review of Investing in Democracy: Engaging Citizens in Collaborative Government by Carmen Sirianni.
THE FINE STRUCTURE OF TESTICULAR INTERSTITIAL CELLS IN GUINEA PIGS

In guinea pig testes perfused with either glutaraldehyde or osmium tetroxide fixative, the cytoplasm of the interstitial cells contains an exceptionally abundant agranular endoplasmic reticulum. The reticulum in central regions of the cell is a network of interconnected tubules, but in extensive peripheral areas the reticulum is commonly organized into closely packed, flattened cisternae which are fenestrated. Occasional small patches of the granular reticulum occur in the cytoplasm and connect freely with the agranular reticulum. The mitochondria have a dense matrix and contain cristae and some tubules. The Golgi complex is disperse and shows no evidence of secretory material. The cytoplasm also contains lipid droplets. Lipofuscin pigment granules are probably polymorphic residual bodies and contain three components: (1) a dense material which at high magnification shows a 75-A periodicity; (2) a medium-sized lipid droplet; and (3) a cap-like structure. In glutaraldehyde-perfused testis the interstitial cell cytoplasm appears to have the same density from cell to cell, and the agranular reticulum is tubular or cisternal but not in the form of empty vesicles. Thus the "dark" and "light" cells and the vesicular agranular reticulum sometimes encountered in other fixations may be artifacts. Biochemical results from other laboratories, correlated with the present findings, indicate that the membranes of the agranular endoplasmic reticulum in guinea pig interstitial cells are the site of at least two enzymes of androgen biosynthesis, the 17-hydroxylase and the 17-desmolase.
Response to Letters Regarding Article, “Bayesian Methods Affirm the Use of Percutaneous Coronary Intervention to Improve Survival in Patients With Unprotected Left Main Coronary Artery Disease”

Dr Diamond explores the important issue of relating statistical inference to clinical significance in our recent report.1 He raises a specific concern about the width of the 95% Bayesian credible interval of the odds ratio, ranging from 0.68 to 1.45, and questions whether the approach that we used actually affirms that percutaneous coronary intervention (PCI) should be considered as an alternative to coronary artery bypass (CABG) surgery for selected patients with unprotected left main coronary artery disease, as suggested by the Class IIa recommendation from the American Heart Association Foundation/American Heart Association.2 The Bayesian credible intervals in our analysis were similar to the classical confidence intervals and included the value 1.0, suggesting that the 1-year mortality after PCI or CABG was similar. The seemingly wide Bayesian credible intervals were the consequences of sample size. To illustrate this, we note from the data that the 1-year mortality rate after CABG was 6.56%1 and estimate that a sample size of 90 000 per treatment arm would be …
President Bush's image repair discourse on Hurricane Katrina

Abstract Hurricane Katrina struck New Orleans and the surrounding area on August 29, 2005. This storm was devastating, causing death, injury, dislocation, and massive property damage. President Bush came under fire for the apparently slow and inept federal response. On September 15 President Bush gave a speech to repair his image. He employed three principal strategies: bolstering, defeasibility, and corrective action. An evaluation of how these strategies were used in his persuasive message judged his image repair effort to be largely ineffective. Bolstering did not counteract the slow response (e.g., Bush waited days to visit the area). Defeasibility is risky for a president to use because it explicitly portrays him as unable to solve the problem. Corrective action was too little (often proposals rather than direct action—and proposals with important unanswered questions) too late. Evidence of the public reaction is consistent with this unfavorable evaluation.
Immunological Properties of the β-Subunit of Human Chorionic Gonadotropin. I. Effect of Chemical and Enzymatic Modifications*

The β-subunit of hCG (hCGβ) displays immunological cross-reactivity with human LH (hLH). A detailed study was undertaken to investigate the effect of chemical and enzymatic modifications on the immunological behavior of hCGβ, particularly on its cross-reactivity with hLH, with a view to obtaining a highly hCG-specific antigen. hCGβ was modifiedin both the carbohydrate and protein parts of the molecule. The carbohydrate part was modified enzymatically by sequential cleavage of monosaccharides by specific glycosidases, and the protein portion was modified chemically in the amino and carboxyl groups and in the cystinyl, tyrosyl, histidyl, and arginylresidues. These derivatives were immunologically evaluated by RIAs; their hCGβ activities were measured in the [125I]hCGβ- anti-hCGβ system, and the hLH cross-reactivity in the [125I]hLH-anti-hLH system. The present studies have led to the following conclusions. 1) The carbohydrate does not play a signific nt role in the immunological activity of hCGβ. 2) The ant...
Enzyme-Selective Effects of Nitric Oxide on Affinity and Maximum Velocity of Various Rat Cytochromes P450

Nitric oxide (NO) has recently been shown to decrease cytochrome P450 (P450) enzyme activity rapidly (≤30 min), concentration dependently, and enzyme-selectively in the rat liver. Interestingly, among all the studied P450 enzymes, only CYP2D1 was not affected by NO donors. However, these studies were conducted using only a single concentration of the substrates, thus lacking information about the possible simultaneous changes in both maximum velocity ( V max ) and affinity ( K m ) of the enzymes. In the present study, we systematically evaluated the effects of NO on the enzyme kinetic parameters of marker substrates for a range of P450 enzymes, including 2D1. Livers were perfused (1 h) in the absence (control) or presence of two NO donors with different mechanisms of NO release. At the end of the perfusion, microsomes were prepared and used for kinetic analysis. Except for 2D1, NO reduced the V max of all the model reactions studied, although to a varying degree. However, the effects of NO donors on K m were more diverse. Whereas the K m values for testosterone 6β-hydroxylation (3A2) and 16α-hydroxylation (2C11) significantly decreased, the values for chlorzoxazone 6-hydroxylation (2E1), dextromethorphan N -demethylation (3A2), and high affinity ethoxyresorufin O -dealkylation (1A1/2) significantly increased in the presence of NO donors. Furthermore, the K m values for the high-affinity component of dextromethorphan O -demethylation and benzyloxyresorufin O -dealkylation remained unchanged. These results indicate that NO can potentially change both the V max and K m of various substrates selectively and confirm our previous findings that the activity of CYP2D1 is not affected by NO donors.
Measurement Characteristics and clinical Utility of the Brief pain Inventory-Short Form for individuals with multiple sclerosis

This Rehabilitation Measures Database summary provides a review of the psychometric properties of the BPI in individuals with MS. A full review of the BPI as well as reviews of over 330 other instruments can be found at www.rehabmeasures.org.
Laboratory Measurements of Acoustic Properties of Periplatform Carbonate Sediments

Geoacoustic models of the seafloor are essential components of underwater and seafloor acoustic studies. Propagation velocities for compressional and shear waves in the seafloor material are important geoacoustic parameters. Previously reported values for shear wave velocities in seafloor carbonate oozes have shown wide disparity. New laboratory measurements of compressional and shear wave geoacoustic parameters have been made as a function of effective stress. Periplatform carbonate samples from the Little Bahama Bank and Exuma Sound in the western North Atlantic Ocean were used for these measurements. Conventional pulse timing compressional wave velocities were measured. Shear wave parameter measurements were made with a new technique using duomorph sensors embedded in the seafloor sample. The resulting compressional wave velocity values are consistent with previously reported measurements for similar material (e.g. Hamilton). The shear wave dynamic property values obtained are more consistent with the lower shear wave velocity values reported, for example by Schultheiss. These lower shear wave velocities also agree with values obtained by pulse timing measurements with bender bimorph transducers in samples from the same seafloor region.
Spinal surgery: Who is in charge anyway?

One answer to the problem of medical management of hospitalized surgical patients is the hospitalist. Is that not a part of their job?
A Curious Convergent Series

(1914). A Curious Convergent Series. The American Mathematical Monthly: Vol. 21, No. 2, pp. 48-50.
Parkinsonism-Dementia-ALS Complex (PDA) Phenotype in an African-American Patient (P07.189)

Objective: To report a case of PDA phenotype in an African-American patient. Background Amyotrophic lateral sclerosis (ALS)/Parkinsonism dementia complex (PDC) is an endemic disorder described in patients from Guam and the Kii peninsula of Japan. Patients with this disorder exhibit features of Parkinsonism, akinesia, masked facies, dysarthria, mental slowness, apathy, depression and gait abnormalities and features of ALS. An environmental cause has been suggested. However, recently 4 patients from central Europe were reported to satisfy criteria for PDA, supporting the notion that this complex disorder may not be purely environmental in origin. Design/Methods: Case report. Results: A 59-year old previously healthy, functional African-American man developed progressive cognitive decline over a period of 2 years. The patient was initially found to have subtle memory disturbances, which quickly evolved to an inability to work. Within the next few months, the patient lost his ability to speak, eat and swallow. On neurological exam, the patient was awake and alert, but anarthric, able to follow simple commands. He had normal extra-ocular movements, bifacial diplegia, dysphagia, and positive Glabellar sign. Motor exam showed normal strength, diffuse muscular atrophy, rigidity and bradykinesia. Diffuse hyper-reflexia with sustained ankle clonus, positive jaw jerk reflex, primitive reflexes and frontal release signs were noted. Cerebrospinal fluid evaluation, including 14-3-3, was normal. Brain MRI showed fronto-temporal atrophy. Brain FDG-PET showed fronto-temporal hypometabolism. EMG/NCS revealed diffuse, ongoing denervation in 3 body segments. Conclusions: Here we describe an African-American patient with constellation of signs similar to what has been previously described in PDA patients from Guam/Kii. To our knowledge, this is the first report of a non-Guamanian, non-caucasian patient from the American continent, with PDA, supporting a possible non-environmental, genetic cause. Additional neuropathological and molecular studies will be helpful in analyzing this disease further. Disclosure: Dr. Kassar has nothing to disclose. Dr. Iyadurai has nothing to disclose.
Multiple virus infection of monkey kidney cells in culture.

SummaryDouble infection of SV40 and measles virus occurred in single cells of kidney cultures prepared from a green monkey. Nuclei infected with both viruses could be recognized by using acridine orange fluorescence at pH 8.0. Cultures triply infected with SV40, measles, and SV5 viruses did not interfere with poliovirus yield, but poliovirus stocks derived from such cultures were contaminated with several viral agents. Therefore, it would be advisable to examine un-inoculated cultures for the presence of possible endogenous contaminants.
The Strength of Long Ties (WITHDRAWN)

Granovetter's article on the strength of weak ties is one of the most widely cited in the social sciences in the past 40 years. Compared to a strong tie, a weak tie tends to span long network dista...
Three-Dimensional Structures Associated with Photoreceptor Cilia by Cryo-Electron Tomography

The outer segment of rod and cone photoreceptor cells is a modified primary cilium. Specialized machinery is needed to assemble and maintain its structure, and to carry out the transport and sorting of molecular components between the inner segment, where most biosynthesis occurs, and the outer segment, where those components are utilized for phototransduction. The narrow connection between the inner and outer segment, known as the connecting cilium, is the location of proteins encoded by genes implicated in inherited diseases known as ciliopathies. Its structural core is a nine + zero microtubule-based axoneme that emerges from a centriole termed the basal body complex. Conserved features of this organelle include the transition fibers and transition zone with a ciliary necklace studding the ciliary membrane. We used cryo-electron tomography to determine the structures of the second basal body (daughter centriole), the connecting cilium and associated machinery in wildtype mice. Recently we used computational sub-tomogram averaging to determine the three-dimensional structure of the basal bodies. The 3D density map reveals a tapered cylindrical structure composed of nine MT bundle from the plus (triplet) end to the minus (doublet) end of the centriole. Additional densities that represent non-tubulin proteins attached to the triplet were revealed, which presumably stabilize the entire basal body. In addition, we have observed transition fibers, located at the ciliary base, connecting to microtubule triplets. The transition zone connects the microtubule doublets of the axoneme to the membrane near the basal body and extends into the connecting cilium toward the outer segment. These structural features in wildtype cilia will help us to understand the normal mechanisms and functions of the many proteins essential for cilium function and photoreceptor survival, and shed light on the ciliopathies that arise from defects in those proteins.
Determination of Di-methyl Di-carbamidine in Plasma by Agilent RRLC/6410 QQQ

A traditional HPLC and a rapid resolution (RRLC) method coupled with triple Q MS was established to determine the di-methyl di-carbamidine in plasma.Result showed that RRLC-MS/MS obtained a low LOD at 0.14 pg on column compared to 0.83 pg by conventional HPLC-MS/MS and thus increased sensitivity by 6 times,shortened analytical time by 3 times while maintaining a satisfactory testing result using Agilent LCQQQ.
A study on assessment standard for height and body weight of children aged 6～11 years in urban Shanghai

To develop the standards of height for age (HFA), weight for age (WFA) and weight for height (WFH) for children aged 6～11 years in urban Shanghai and compare with those of WHO. ①Randomized stratified clustered sampling method was used. The data of height, weight measured in May, 1999 and the birthdays of 25981 children (13220 boys, 12761 girls) were collected from 31 primary schools of 12 districts in urban Shanghai. ②According to percentage the P 3～P 97, P 50±1s, P 50±2s and P 50±3s of HFA, WFA and WFH were calculated. Their standards were developed by exponential regression curve fitting soft ware. The P 50 curves of HFA, WFA and WFH for boys and girls in Shanghai were compared with those from WHO respectively. The trend of curves of HFA, WFA and WFH for boys aged 6～11y in urban Shanghai were similar to that in WHO, and the average value of height and weight in Shanghai was higher than those from WHO. This trend was also seen in girls. And the average value of HFA and WFA in Shanghai was higher than those from WHO, but that of WFH in Shanghai was a bit lower than that from WHO. [Conclusion] There is an obvious difference in the standards of HFA, WFA and WFH for children aged 6～11 years from urban Shanghai and WHO. The new standard can be used for assessment of growth and development for children aged 6～11y of Shanghai urban.
Coda to Chapter 1: A “Legion of Wollstonecrafts”

It has become a critical commonplace that Mary Wollstonecraft’s death in 1797 and William Godwin’s subsequent account of her life in the Memoirs of the Author of the Rights of Woman (1798) marks the end of revolutionary feminism.1 Indeed, Godwin’s revelations about Wollstonecraft’s passion for the painter Henry Fuseli, her love affair with Gilbert Imlay and two suicide attempts after its end, as well as the philosophers’ own pre-marital relationship, gave rise to slanderous attacks against Wollstonecraft in the conservative press. The Anti-Jacobin Review carried out an extensive campaign to discredit Wollstonecraft’s political ideas by identifying her as a “prostitute” and “whore” rather than as a writer and social critic. In a review of the Memoirs, the Anti-Jacobin makes the following judgment: “We must observe, that Mary’s theory, that it is the right of women to indulge their inclinations with every man they like, is so far from being new, that it is as old as prostitution” (1: 97). And as late as 1801, the magazine printed “The Vision of Liberty”, a poem that included the following lines about Wollstonecraft’s Vindication of the Rights of Woman: Such license loose-tongued liberty adores, Which adds to female speech exceeding graces; Lucky the maid that on her volume pores, A scripture, archly fram’d, for propagating w—s. (9: 518)
Mesenchymal-Epithelial Interactions in the Growth and Development of the Urogenital Tract

Mesenchymal-epithelial interactions are known to be of prime importance during development. In many developing organs, mesenchyme influences epithelial growth, induces specific patterns of ductal branching morphogenesis, specifies epithelial morphology and spatial organization, and elicits specific patterns of epithelial cytodifferentiation and functional activity (1–5). In the genital tract, mesenchymal-epithelial interactions are also known to regulate the expression of specific hormone receptors (6–7). Although it has been formerly thought that hormonal effects on epithelial cells are elicited directly by intra-epithelial receptors, investigation of androgenic and estrogenic responses in male and female genital tracts, respectively, suggests that a spectrum of hormonal effects elicited by sex steroids in epithelial cells are elicited via indirect processes regulated by mesenchyme. While all organogenetic processes are initiated prenatally, organs of the reproductive system are rudimentary at birth, and most of the developmental processes as well as the onset of functional activity occur over extended periods postnatally. In laboratory rodents, organogenesis of the reproductive tract takes place in the period from the latter third of gestation to about 2 months postpartum, during which time new tissue architecture forms. It is likely that postnatal morphogenesis proceeds by the same fundamental developmental mechanisms that are operative during earlier prenatal periods. However, the question arises as to the exact role of mesenchymal-epithelial interactions in adulthood after morphological and functional maturity is attained.
Destabilization of Atoh1 by E3 Ubiquitin Ligase Huwe1 and Casein Kinase 1 Is Essential for Normal Sensory Hair Cell Development

Abstract Proneural basic helix-loop-helix transcription factor, Atoh1, plays a key role in the development of sensory hair cells. We show here that the level of Atoh1 must be accurately controlled by degradation of the protein in addition to the regulation of Atoh1 gene expression to achieve normal cellular patterning during development of the cochlear sensory epithelium. The stability of Atoh1 was regulated by the ubiquitin proteasome system through the action of Huwe1, a HECT-domain, E3 ubiquitin ligase. An interaction between Huwe1 and Atoh1 could be visualized by a proximity ligation assay and was confirmed by co-immunoprecipitation and mass spectrometry. Transfer of a lysine 48-linked polyubiquitin chain to Atoh1 by Huwe1 could be demonstrated both in intact cells and in a cell-free system, and proteasome inhibition or Huwe1 silencing increased Atoh1 levels. The interaction with Huwe1 and polyubiquitylation were blocked by disruption of casein kinase 1 (CK1) activity, and mass spectrometry and mutational analysis identified serine 334 as an important phosphorylation site for Atoh1 ubiquitylation and subsequent degradation. Phosphorylation by CK1 thus targeted the protein for degradation. Development of an extra row of inner hair cells in the cochlea and an approximate doubling in the number of afferent synapses was observed after embryonic or early postnatal deletion of Huwe1 in cochlear-supporting cells, and hair cells died in the early postnatal period when Huwe1 was knocked out in the developing cochlea. These data indicate that the regulation of Atoh1 by the ubiquitin proteasome pathway is necessary for hair cell fate determination and survival.
Treatment of growth hormone deficiency in children, adolescents and at the transitional age

Recombinant human growth hormone (rhGH) has been available since 1985. Before 1985 growth hormone (GH) was extracted from cadaveric pituitary glands, but this was stopped in most countries that year, following the recognition that it could transmit Creutzfeldt–Jacob disease. The primary goal of rhGH treatment in GHD patients is to normalize height during childhood and adolescence and attain an adult height within the normal range and within the target height range (genetic potential). Genome-wide association studies have been used increasingly to study the genetic influence on height. There is a wide response to rhGH therapy, likely due to compliance issues, severity of GH deficiency and patient's sensitivity to rhGH. While some pediatric endocrinologists will use a fixed dose of rhGH, most will use an auxology-based dosing approach. This will involve starting at the lower end of the dose range and then titrating upwards based on the patient's response to therapy with measurement of IGF-1 concentrations to ensure that the patient is not over treated or undertreated. Although treatment of children with GHD with rhGH has generally been safe, careful follow-up by a pediatric endocrinologist in partnership with the pediatrician or primary care physician is recommended. The aim of this paper is to review the strategies and recommendations for treatment of GHD in children and patients in the transition to adult care.
The Odds Meet the Great Martingale.

ROULETTE is an intriguing game. Thousands flock each weekend to Las Vegas to try to outwit Lady Luck at the roulette wheel. More than a few of these weekend gamblers have seen their fortunes come and go with the spin of the wheel. Many of them are unaware that their des tiny at the wheel is dependent on predetermined odds rather than on Lady Luck. Others are aware of the odds but are convinced that they have found a system that will allow them to beat the odds. One
Hydrocephalus: Diagnosis and Current Trends

(1976). Hydrocephalus: Diagnosis and Current Trends. American Journal of EEG Technology: Vol. 16, No. 3, pp. 109-115.
"Be Grateful You Don't Have a Real Disease": Understanding Rare Disease Relationships

We characterize how people with rare diseases consider their support needs as being met or neglected by different sources. After a 22-week study with 11 participants, we found that people with rare diseases identify strongly with their conditions but demonstrate a range of outlooks on their condition (positive, negative, and accepting). We found that participants think of themselves as being in a separate "Rare World" from the "normal" people in their lives and that relationships with friends and family members are strained. On the other hand, online communities were described as valuable sources of many forms of support, but do not adequately compensate for the lack of tangible support in offline relationships. We propose an approach to facilitating tangible support that leverages existing research on social matching, towards facilitating support among people with different rare diseases to overcome geographic and symptomatic challenges of coordinating support between people with the same rare disease.
Abstract 5088: Tumor penetrating RNA delivery for therapeutic benefit of pancreatic cancer

Pancreatic cancer remains a deadly disease with a median survival of less than one year, in part because we lack effective therapeutic strategies. Mutations of the oncogene KRAS and the tumor suppressor genes TP53, INK4A, and DPC4 play important roles in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC); however, these driver events have proven to be challenging targets for drug development. RNA interference through small interfering RNA (siRNA) delivery has the potential to have an impact on silencing ‘undruggable’ targets; however, siRNA delivery in tumors has been challenging in general and worsened in PDAC by the stromal barriers to drug delivery. Herein, we integrated biomedical engineering, materials science, and pre-clinical investigation to establish a novel class of tumor-penetrating nanoparticles (TPNs) to enhance delivery of siRNAs in PDAC for therapeutic benefit. Specifically, we adapted self-assembled nanoparticles comprised of siRNA complexed with tandem tumor-penetrating and membrane-translocating peptides, which enabled the specific delivery of siRNA deep into the tumor parenchyma. Specifically, to establish efficacious siRNA delivery vehicles, we characterized and selected tandem peptides that incorporate novel tumor-penetrating peptide domains known to target PDAC in mice. In parallel, we optimized the particle stability through incorporation of hydrophilic molecules, focusing on achieving desirable pharmacokinetic properties which will reduce off-target delivery and increase potency of a given siRNA dose. The resulting TPNs carry siRNA into the cytosol of monolayer cultures of tumor cells, and also exhibit penetration in pancreas organoids derived from primary mouse and human tumors. As a proof-of-concept, we used TPN in vivo to knockdown KRAS in a murine PDAC model, using subcutaneously-implanted, autochthonous KRASG12D/+p53-/- tumors. Treatment of tumor-bearing mice with systemically administrated KRAS-specific TPNs suppressed the growth of established tumors. With the delivery platform established, the ongoing goals of this project are to identify siRNA targets that synergize with the suppression of oncogenic KRAS, and to validate synthetic lethal targets by interfering with signature PDAC driver events uncovered by functional genomic efforts. Together, these studies will provide a foundation for translational studies involving new targets and delivery technology in pancreatic cancer. Citation Format: Liangliang Hao, Justin Lo, Sangeeta Bhatia. Tumor penetrating RNA delivery for therapeutic benefit of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5088. doi:10.1158/1538-7445.AM2017-5088
Can Extracurricular Activities Reduce Adolescent Race/Ethnic Friendship Segregation?

High school extracurricular activities (ECAs) can bring diverse adolescents together and promote friendships that reduce outgroup prejudices. This chapter examines two seemingly contradictory processes and explain how, in fact, they can occur in tandem. At the macro level, ECAs can promote homophily (i.e., in-group friendship) by homogenizing the pool of available friends, whereas at the micro level, ECAs can decrease the relative salience of attributes such as race/ethnicity during friend selection. The analysis presented in this chapter uses data on friendships and participation in 30 ECAs from 108 schools in the National Longitudinal Study of Adolescent Health. It is found that around 60% of the ECAs were more homogenous than the broader school context in which they are embedded. On average, ECAs did not predict preferences for homophily, but did predict the frequency of cross-group friendships. ECAs may thus provide many of the desired benefits of integration despite not producing short-term changes in friendship preferences.