cssi/SciSciGPT-SciSciNet huggingface dataset:
Stimulus hierarchy generalization in systematic desensitization

Abstract A group of snake phobic Ss were desensitized to the first 5 items of a standard 7 item snake fear hierarchy in which the items were ordered on the basis of distance from a snake. This group and a no-treatment control group (which did not receive the desensitization) were treated for fear of all the hierarchy stimuli in terms of ratings both before and after the desensitization. The Ss rated their fear responses to all the stimuli as presented to them in (1) real form (2) by slide, and (3) in imaginal form. The results verified all four experimental hypotheses: (1) The experimental Ss showed greater fear reduction than the control Ss to both the training stimuli (the stimuli on which desensitization done) and the generalization stimuli (the other two stimuli), (2) The systematic desensitization (SD) group showed (a) more fear reduction to the last training stimuli than to the lower generalization stimulus and (b) more to the latter than to the higher generalization stimulus, (3) The SD group showed less fear reduction to the generalization stimuli in their real form than in both the slide and imaginai modalities (in the desensitization each stimulus presentation was done first in slide form and then in imaginal form), and (4) There were significant overall individual differences in generalization of fear reduction to the generalization stimuli.
Comparison of responses to isoproterenol and epinephrine during head-up tilt in suspected vasodepressor syncope.

Abstract Head-up tilt is known to play an important role in establishing the diagnosis of vasodepressor syncope in patients with syncope of unknown etiology. 1–5 Although passive head-up tilt alone may trigger a vasodepressor response, recent studies show that an infusion of isoproterenol significantly increases the sensitivity of head-up tilt in reproducing vasodepressor syncope. 1–5 However, isoproterenol is not endogenously produced and the role of endogenous catecholamines, such as epinephrine, in provoking vasodepressor syncope is unknown. Therefore, we compared the responses to isoproterenol and epinephrine during head-up tilt in patients suspected of having vasodepressor syncope.
Response of epithelioid haemangioendothelioma to liposomal doxorubicin

Epithelioid haemangioendothelioma is a rare tumour of vascular origin, most commonly involving soft tissues, lung, and liver. It has various clinical presentations— ranging from haemangioma-like behaviour with little potential to cause malignant disease, to that of an aggressive tumour similar to angiosarcoma. Therefore, definition of the optimum treatment strategy for patients with epithelioid haemangioendothelioma is difficult. For some patients, surgery is curative, but for those who cannot have surgery the best strategy for palliation is unknown. We report a patient with aggressive hepatic epithelioid haemangioendothelioma with bony involvement who responded to a protracted course of liposomal doxorubicin.
Electrostatic interpretation for the zeros of certain polynomials and the Darboux process

The purpose of this paper is to extend the electrostatic interpretation of Stieltjes to the zeros of a larger class of important polynomials.To keep things simple I consider polynomials that are obtained from those considered by Stieltjes by means of the so-called Darboux process applied to the di7erence operator featuring in their three term recursion relation.It will turn out that some of the beauty in the results of Stieltjes is preserved in this process.It would be interesting to interpret the Darboux process at the electrostatic level and this paper gives “experimental data” that might help in this direction. c 2001 Elsevier Science B.V. All rights reserved.
Predictors of physical activity in patients with chronic heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

To identify predictors of physical activity levels in patients with chronic heart failure, 43 patients, aged 33 to 91 years, who had well-compensated heart failure were asked to perform a symptom-limited exercise treadmill test and to complete activity logs for 2 consecutive days while wearing an ambulatory heart rate activity monitor. Activity logs included information on the type of activity, duration, rating of perceived exertion, symptoms experienced, and the intensity of symptoms. Subjects also completed the Duke Activity Status Index, a brief self-administered questionnaire that assesses physical functioning, and a self-efficacy for general activity questionnaire. Simultaneous multiple regression analysis was used to predict physical activity levels from a model that included: personal variables of physical fitness (peak oxygen consumption); knowledge, attitudes, and beliefs including self-efficacy for general activity, and rating of perceived exertion during daily activity; and environmental factors such as social support (marital status). The overall model explained 38% of the variance (p < 0.001). Self-efficacy (p = 0.015) was the strongest predictor of physical activity in this group. From this initial descriptive study, we conclude that self-efficacy is a better predictor of performance of physical activity than measures of physical fitness or rating of perceived exertion during activity. Additional studies are needed to examine other behavioral and physiologic mediators as well as behavioral strategies that may be used to increase participation in physical activity programs. Particularly promising are strategies to enhance self-efficacy for exercise.
Quartet Inference from SNP Data Under the Coalescent Model

Motivation: Increasing attention has been devoted to estimation of species-level phylogenetic relationships under the coalescent model. However, existing methods either use summary statistics (gene trees) to carry out estimation, ignoring an important source of variability in the estimates, or involve computationally intensive Bayesian Markov chain Monte Carlo algorithms that do not scale well to whole-genome datasets. Results: We develop a method to infer relationships among quartets of taxa under the coalescent model using techniques from algebraic statistics. Uncertainty in the estimated relationships is quantified using the nonparametric bootstrap. The performance of our method is assessed with simulated data. We then describe how our method could be used for species tree inference in larger taxon samples, and demonstrate its utility using datasets for Sistrurus rattlesnakes and for soybeans. Availability and implementation: The method to infer the phylogenetic relationship among quartets is implemented in the software SVDquartets, available at www.stat.osu.edu/∼lkubatko/software/SVDquartets. Contact: ude.uso.tats@oktabukl Supplementary information: Supplementary data are available at Bioinformatics online.
Synthesis and Targeting of Insulin-like Growth Factor-I to the Hormone Storage Granules in an Endocrine Cell Line*

Export of growth factors is generally believed to be restricted to the constitutive secretory pathway, whereas peptide hormones are typically secreted in a regulated manner. Here we show that insulin-like growth factor (IGF)-I, a growth factor released constitutively from the liver, is synthesized and secreted from the mouse pituitary AtT-20 cell line via the regulated pathway. IGF-I production is 1500-fold less than the peptide hormone ACTH. Secretagogue induces IGF-I secretion in a manner similar to ACTH. Like ACTH, IGF-I is sorted into the regulated pathway >35-fold more efficiently than a constitutively secreted protein. Dense core granules isolated from cells transfected with a human IGF-I cDNA contain both ACTH and human IGF-I. AtT-20 cells also synthesize IGF-binding proteins, and at least one of these is secreted by the regulated pathway. Human IGF-I does not exhibit milieu-induced, concentration-dependent aggregation, in contrast to secretogranin II which sorts by a proposed aggregation mechanism. These data suggest that 1) growth factors are not solely released from tissues via the constitutive pathway, 2) IGF-I may contain information for correct granular targeting, and 3) IGF-I may be sorted by a mechanism distinct from that proposed for the secretogranins.
In and Out, Good and Bad News, of Generalizability of SWOG Treatment Trial Results

The issue of generalizability of clinical trial results has challenged researchers and practitioners of adult cancer patients for years. It is one reason why the adult cancer cooperative group enterprise in the United States is undergoing yet another transformation (1). Figure 1 may capture the essence of the situation. Its foreground shows the most recent data available to this commentator on the estimated proportion of cancer patients in the United States entered onto cooperative group treatment trials as a function of individual year of patient age. The background shows the rest of the United States. With only 2% to 4% of adults aged 20 to 65 years entered onto clinical trials, how can we rely on such a small sample size to be applicable to the general population? In a comparison of survival outcomes among cancer patients treated in and out of clinical trials published in this issue of the Journal, Unger and colleagues analyzed 21 SWOG treatment trials enrolled during the period from 1986 to 2007 with comparable patients in the US Surveillance, Epidemiology and End Results (SEER) database (2). Their primary subset analysis was good- vs poor-prognosis trials defined by a 2-year average study-specific survival rate of greater than 50% or less than or equal to 50%, respectively. The former had 11 trials that included melanoma, myeloma, and carcinoma of the breast, bladder, uterine cervix, and prostate. The latter had 10 trials that included acute myelogenous leukemia, brain tumors, lung cancer, and pancreatic carcinoma. The results may be interpreted as a series of good- vs bad-news scenarios (Table 1), with several advantages as a source of disadvantage and vice versa. Among the best news is that patients in SWOG trials had a survival benefit, albeit only in poor-prognosis trials. The bad news for them was that it “endured for only 1 year” (2). However, according to Supplementary Figure 2 in the Unger et al. report (2), which shows the SWOG and SEER survival curves for each of 10 poor-prognosis trials, the survival benefit is better than the authors concluded, lasting at least 5 years in two trials, 3 years in three trials, and 2 years in two trials. In only two of the 10 trials was it less than 1 year. Whether or not the apparent benefit of the SWOG trial in patients with a poor prognosis is more durable than concluded, the striking difference between the broad categories of good and poor prognosis as defined has major implications for the interpretation of cancer clinical trial outcomes and application to the general population:
Jack Gherty, president and CEO of Land O'Lakes, on leading a branded food and farm supply cooperative

Executive Overview Cooperatives are a unique form of organization compared to the more familiar corporate forms of ownership, limited liability companies, partnerships, and proprietorships. Users of the cooperative's services are also voting members who control the cooperative, the owners who provided the equity capital, and patrons who received the benefits of use. Profits or net income are usually distributed as patronage-based refunds. Globally, farmer-owned cooperatives are important suppliers in the world food economy. Cyclical downturns in agriculture contributed to the recent bankruptcy of two large cooperatives. Farmland Industries and Agway, and caused financial stress in others. Like other businesses, cooperatives have become increasingly aware of the need to more proactively manage uncertainty in the food economy. A unique aspect of leading a cooperative includes educating its member-owners, who must understand the risks and rewards of growing a modern cooperatively organized company in the foo...
Temporal and spatial variations of travel-time residuals in central California for Novaya Zemlya events

Eight large nuclear explosions in Novaya Zemlya, from October 1969, through November 1974, were used to monitor long-term variations in crustal seismic velocity near the San Andreas fault in central California. Relative P -wave travel-time residuals appear to be accurate to approximately ±0.1 sec. Of the over 100 stations used, none show clearly significant temporal variations in residual greater than this amount, corresponding to about a 4 per cent change in velocity in the upper crust. Average relative residuals at individual stations show a large spatial variation of about 1.5 sec. These variations reflect both a complex crustal geology and changes in crustal thickness and provide a potentially powerful tool for studying crustal structure.
Disability and sleep duration: evidence from the American Time Use Survey.

Abstract Background Regular short and long sleep durations are associated with increased mortality and morbidity. While previous research shows significant sleep disparities between people with and without disabilities, less is known about the association between different types of disability and high-risk sleep using nationally representative data. Objective We examine the association between short and long sleep durations and having a work disability or an impairment in sensory, cognitive, or physical functioning among a nationally representative sample of working-age adults in the United States. Methods We estimate multinomial logistic regression models using data from the 2003–2012 American Time Use Survey to identify how different types of disabling conditions – net of other sociodemographic factors – relate to the likelihood of reporting short (6 h or fewer) or long (9 h or more) sleep, versus mid-range (between 6 and 9 h) sleep. Results For respondents with work disabilities versus those without work disabilities, the relative risk of short and long sleep is 1.4 and 1.5 times (respectively) that of those with mid-range sleep. The risk of short and long sleep durations is also higher among respondents with cognitive, physical, or multiple impairments. Conclusions Individuals with disabilities are less likely than those without disabilities to have optimal sleep durations. These results demonstrate the importance of health promotion services among this population, with specific attention to sleep hygiene interventions.
Differences in Activity Limitation Between 2 Low Back Pain Subgroups Based on the Movement System Impairment Model

Objective To examine if activity limitation differs between 2 low back pain (LBP) subgroups in the Movement System Impairment (MSI) model. Design Cross-sectional observational study. Setting University medical center musculoskeletal analysis laboratory. Participants Convenience sample of 83 subjects with chronic LBP who were subgrouped as rotation (Rot) or rotation with extension (RotExt) according to the MSI model. Interventions Not applicable. Main Outcome Measurements Subjects completed the modified Oswestry Low Back Pain Disability Questionnaire and the physical function subscale of the 36-Item Short-Form Health survey (SF-36 PFS) to assess activity limitation. Subjects also completed baseline measures related to demographics, LBP history, pain intensity, habitual activity level, general health status, and fear-avoidance behavior. Independent-samples t -tests, χ 2 tests of independence, and 2-way analysis of variance tests were used to analyze the data. Results Subjects in the Rot subgroup reported greater activity limitation on the modified Oswestry Questionnaire ( P = .02) and SF-36 PFS ( P = .03) than subjects in the RotExt subgroup. No other differences between LBP subgroups were significant ( P > .05), except gender. More women (71%) than men (29%) were in the RotExt subgroup ( P = .03). However, there was no main effect of gender and no interaction effect of gender and LBP subgroup on the modified Oswestry Questionnaire or the SF-36 PFS ( P > .05). Conclusions These results support that the Rot and RotExt LBP subgroups based on the MSI model differ with regard to variables that index activity limitation, with the Rot subgroup reporting greater limitation on both activity limitation measures. These differences are not the result of differences in other baseline measures.
Transcatheter Embolization of Extremity Vascular Malformations: The Long-term Success of Multiple Interventions

Vascular malformations of the extremities present a difficult therapeutic challenge. Ligation of feeding vessels may lead to tissue necrosis and limb loss and can make subsequent attempts at transcatheter therapy impossible. The purpose of this study was to review our results with transcatheter embolization therapy in symptomatic vascular malformations in the upper and lower extremities in 50 patients. A retrospective review was conducted of a computerized database of all patients undergoing transcatheter therapy of peripheral vascular malformations at our institution. The mean age of the patients was 22 years (range 1-51 years), and 34% were male. The most common presenting symptoms included pain (80%), swelling (68%), ulceration or distal ischemia (18%), and hemorrhage (6%). Previous unsuccessful surgical treatment or embolization had been performed in 24% and 18% of patients, respectively. Predominantly venous lesions were treated by sclerotherapy with injection of ethanol. Arteriovenous and arterial lesions were treated by embolization via the arterial branch feeding vessels with cyanoacrylate. The most common vessels involved and treated were branches of the profunda femoris and tibial arteries (83% of lower extremity lesions), and branches of the brachial and radial arteries (82% of upper extremity lesions). Patients required a mean of 1.6 embolization procedures (range 1-5) over a mean period of 57 months. Sixteen patients (32%) underwent more than one embolization procedure. Of these, one was a planned staged procedure and 15 were performed secondary to residual or recurrent symptoms. Adjunctive surgical procedures were performed subsequent to embolization in three cases (6%). Ninety-two percent of patients remained asymptomatic or improved at a mean follow-up of 56 months. There was one case of limb loss (2%). Diffuse extremity vascular malformations are difficult to eradicate completely and recurrences are common. Although patients may require multiple embolization procedures and occasional adjunctive surgical resection, directed transcatheter embolization should be the treatment of choice for symptomatic extremity vascular malformations.
Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjögren's syndrome.

Objective Primary Sjogren's syndrome (SS) is a systemic autoimmune disease with incompletely understood etiology. This study was undertaken to investigate the role of epigenetic dysregulation in the pathogenesis of primary SS. Methods A genome-wide DNA methylation study was performed in naive CD4+ T cells from 11 patients with primary SS compared to age-, sex-, and ethnicity-matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array, and the data were validated using bisulfite sequencing. Results Genome-wide analyses identified 553 hypomethylated CpG sites and 200 hypermethylated CpG sites in naive CD4+ T cells from patients with primary SS as compared to healthy controls, representing 311 hypomethylated and 115 hypermethylated gene regions. The hypomethylated genes in patients with primary SS included LTA (encoding lymphotoxin α). Other relevant genes, such as CD247, TNFRSF25, PTPRC, GSTM1, and PDCD1, were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18, and IFITM1. A group of genes encoding members of the solute carrier proteins were differentially methylated. In addition, the transcription factor gene RUNX1 was hypermethylated in patients with primary SS, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. Conclusion This is the first epigenome-wide DNA methylation study in patients with primary SS. These findings highlight a role for DNA methylation in primary SS and identify disease-associated DNA methylation changes in several genes and pathways in naive CD4+ T cells from patients with primary SS that may be involved in the pathogenesis of this disease.
Clinical symptoms and alpha band resting-state functional connectivity imaging in patients with schizophrenia: implications for novel approaches to treatment.

Background Schizophrenia (SZ) is associated with functional decoupling between cortical regions, but we do not know whether and where this occurs in low-frequency electromagnetic oscillations. The goal of this study was to use magnetoencephalography (MEG) to identify brain regions that exhibit abnormal resting-state connectivity in the alpha frequency range in patients with schizophrenia and investigate associations between functional connectivity and clinical symptoms in stable outpatient participants. Methods Thirty patients with SZ and 15 healthy comparison participants were scanned in resting-state MEG (eyes closed). Functional connectivity MEG source data were reconstructed globally in the alpha range, quantified by the mean imaginary coherence between a voxel and the rest of the brain. Results In patients, decreased connectivity was observed in left prefrontal cortex (PFC) and right superior temporal cortex, whereas increased connectivity was observed in left extrastriate cortex and the right inferior PFC. Functional connectivity of left inferior parietal cortex was negatively related to positive symptoms. Low left PFC connectivity was associated with negative symptoms. Functional connectivity of midline PFC was negatively correlated with depressed symptoms. Functional connectivity of right PFC was associated with other (cognitive) symptoms. Conclusions This study demonstrates direct functional disconnection in SZ between specific cortical fields within low-frequency resting-state oscillations. Impaired alpha coupling in frontal, parietal, and temporal regions is associated with clinical symptoms in these stable outpatients. Our findings indicate that this level of functional disconnection between cortical regions is an important treatment target in SZ.
New constraints on mechanisms of remotely triggered seismicity at Long Valley Caldera

[1] Regional-scale triggering of local earthquakes in the crust by seismic waves from distant main shocks has now been robustly documented for over a decade. Some of the most thoroughly recorded examples of repeated triggering of a single site from multiple, large earthquakes are measured in geothermal fields of the western United States like Long Valley Caldera. As one of the few natural cases where the causality of an earthquake sequence is apparent, triggering provides fundamental constraints on the failure processes in earthquakes. We show here that the observed triggering by seismic waves is inconsistent with any mechanism that depends on cumulative shaking as measured by integrated energy density. We also present evidence for a frequency-dependent triggering threshold. On the basis of the seismic records of 12 regional and teleseismic events recorded at Long Valley Caldera, long-period waves (>30 s) are more effective at generating local seismicity than short-period waves of comparable amplitude. If the properties of the system are stationary over time, the failure threshold for long-period waves is ∼0.05 cm/s vertical shaking. Assuming a phase velocity of 3.5 km/s and an elastic modulus of 3.5 × 1010Pa, the threshold in terms of stress is 5 kPa. The frequency dependence is due in part to the attenuation of the surface waves with depth. Fluid flow through a porous medium can produce the rest of the observed frequency dependence of the threshold. If the threshold is not stationary with time, pore pressures that are >99.5% of lithostatic and vary over time by a factor of 4 could explain the observations with no frequency dependence of the triggering threshold.
Tunneled Catheter-Associated Atrial Thrombi: Successful Treatment with Chronic Anticoagulation.

Tunneled dialysis catheter–associated right atrial thrombus (RAT) is a rarely reported complication. We reviewed hospital records of 10 patients from a teaching hospital dialysis unit, in whom RAT was diagnosed by trans-esophageal echocardiography (TEE). Patients were treated with chronic anticoagulation (heparin followed by warfarin) and followed over time. The group included 7 women; 6 patients were African American, 3 were Caucasian, and 1 was Hispanic. The average age was 52.1 ± 15.3 years. The most common presenting symptom was poor catheter flow on hemodialysis followed by fever and chills. On average, the patients had had 3.4 ± 2.7 catheter insertions before diagnosis of RAT, and the tunneled dialysis catheter (TC) had been in place for a mean of 91 ± 89.4 days when the thrombi were diagnosed. Trans-thoracic echocardiography (2-D echo) was done in 4 patients, but it identified RAT in only 1 patient. The catheter tip was at the junction of the superior vena cava and right atrium (SVC/RA) in most patients. Thrombolysis (unsuccessful) was attempted with urokinase in 3 patients, complicated in 2 patients by hemorrhage. After anticoagulation, 90% of the RAT resolved on repeated TEE. One patient had persistent RAT for 23 weeks and underwent surgical thrombolysis, but died postoperatively. We conclude that RAT is a frequently missed complication of a TC. Positioning the tip of the TC at the SVC/RA junction may not prevent RAT. Trans-esophageal echocardiography is a more sensitive diagnostic tool than 2-D echo and should be obtained early. Most patients can be successfully treated with anticoagulation alone. Thrombolytic therapy and surgical thrombolysis have high morbidity and mortality.
Development and Validation of a Measure of Leader Rapport Management: The LRM Scale

The purpose of this study is to develop and validate a scale to measure the construct of leadership rapport management (LRM) and demonstrate its potential impact on relationships between supervisors and subordinates. A brief review of the construct is presented along with its anticipated theoretical and empirical relationships with constructs that might be closely related such as LMX, perceived supervisor support, trust, and interactional justice. Construct definitions are developed and items for an LRM measure are evaluated using a three-sample validation study. Exploratory and confirmatory factor analysis results reveal a three-factor model of LRM and preliminary evidence of reliability and construct validity is provided.
The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2.

Abstract The yeast ADR1 protein contains two zinc finger domains that are essential for its role in transcriptional activation of alcohol dehydrogenase (ADH2). These domains are thought to function as DNA-binding structures. An ADR1-beta-galactosidase fusion protein made in Escherichia coli and containing the finger domains of ADR1 binds in vitro in a zinc-dependent manner to DNA fragments containing the two ADH2 upstream activation sequences. The strongest binding is to upstream activation sequence 1, a 22-base-pair palindrome.
Carbohydrate Metabolism In Male Infertility And Female Fertility-Control Patients

Carbohydrate metabolism in male infertility and female fertility con trol patients is reviewed. There is a general agreement among investiga tors that the reproductive capacity of men with diabetes mellitus is imparied. 3 common problems appear to be involved: semen quality impotence and inadequate ejaculation. These patients can often be helped and pregnancy established. Contraception and carbohydrate metabolism was reviewed with the following main topics: frequency of abnormal results types of women at great risk mechanism of action reversibility of change individual steroid effects (estrogens-progestogens) and clinical implications. The physician should utilize the high-risk historic data to identify the population who will require careful laboratory predrug evaluation and monitoring or another method of contraception.
Peptidyl-Prolyl Isomerase Pin1: A Common Therapeutic Target for Synaptic Dysfunction and Protein Misfolding in Alzheimer's Disease (SC02.008)

Objective: The Pin1 protein, a peptidyl-prolyl isomerase, facilitates proper folding of proteins. Loss of Pin1 in mice induces formation of misfolded beta-amyloid and hyperphosphorylated tau at dendritic rafts, which suggests that Pin1 may pathologically alter dendritic rafts and the post-synaptic density (PSD) in Alzheimer9s disease (AD). In this study, we observed Pin1 associations with synaptic proteins and compared Pin1 pathological changes in AD patients against controls. Background The structural basis for memory formation lies in the neuronal excitatory synapse. Unique to this synapse and underlying its function are integrated detergent-resistant dendritic rafts and PSD within the postsynaptic structure. The association of the pathological hallmarks of AD--misfolded oligomers of beta-amyloid and hyperphosphorylated tau--with these detergent-resistant microdomains may lead to synaptic dysfunction and loss. Design/Methods: Human cortices from 12 AD patients and 10 age-matched controls were prepared using a tissue extraction protocol, followed by SDS-PAGE, Western and Dot blot analyses. Mice cortical neurons were cultured and visualized using immunocytochemistry, immunoblot, and confocal microscopy. Results: We found that in AD, Pin1 proteins coincidently associated with NMDA receptor 1, Shank3 proteins, and misfolded proteins at dendritic rafts and the PSD. The protein levels of Pin1 were pathologically increased in dendritic rafts and decreased in the PSD of AD brains. In cultured neurons, Pin1 proteins co-localized with NMDA receptor 1 and Shank3, and dendritic spines degenerated after Pin1 activity was blocked. Conclusions: Our findings suggest that pathological distribution and loss of Pin1 at the synapse may have a direct effect on phosphorylation and homeostasis of proteins beside beta-amyloid and hyperphosphorylated tau in AD development. Pin1 may prove to be a common therapeutic target for both the treatment of synaptic dysfunction and misfolding of beta-amyloid and phosphorylated tau at synapses in early stages of AD. Disclosure: Dr. Chow has nothing to disclose. Dr. Tsai has nothing to disclose. Dr. Lippa has received personal compensation in an editorial capacity for Sage Publications.Dr. Lippa has received research support from UCB Pharma and DUCOM. Dr. Gong has nothing to disclose.
Influence of chilling at 5°C, IB A, suckering and top growth on root regeneration in seedlings of Malus spp.

SummaryFour experiments were conducted to separate the enhancement of root growth by chilling at 5°C from the promoting effects of the growth of new shoots and suckers (adventitious shoots from roots) during forcing in apple. Various combinations of low temperatures (5°C), detaching plants at the soil surface, girdling, and/or IBA were used to suppress new shoot and sucker growth during forcing after subjecting Malus seedlings to increasing levels of chilling. Following increasing duration of chilling at 5°C (CH), forcing intact Malus domestica Borkh. seedlings at a 20°C soil and air temperature caused initial bud- break, shoot extension, and root growth to occur earlier, faster, and to reach a greater final magnitude. Detaching M. domestica seedlings at the soil surface prior to chilling was ineffective as a means of separating root and top growth responses to chilling as it stimulated production of suckers and/or watersprouts near the soil surface. Root numbers and fresh weights in M. domestica, Malus a...
49 EFFECT OF PKC STIMULATION ON SODIUM CHLORIDE COTRANSPORTER FUNCTION AND SURFACE EXPRESSION IN MAMMALIAN CELLS.

The sodium chloride cotransporter (NCC) belongs to the family of electroneutral cation-chloride transporters (SLC12). It is the site of action of one of the most effective classes of antihypertensive medications, thiazide diuretics. NCC is the principal salt-absorptive pathway in the mammalian distal convoluted tubule, but its regulatory mechanisms have been principally studied in the Xenopus oocyte expression system and have not been well defined in mammalian models. Therefore, we have developed a cell model system to assess NCC function in a mammalian cell line that natively expresses NCC, the mouse distal convoluted (mDCT) cell line. We now use this system to assess the effects of activators of PKA (forskolin), PKC (TPA), or neither (4α-PDD, a non-PKC-stimulating phorbol ester) on function and surface expression of NCC. This is the first reported correlation of NCC function (22Na+ uptakes) with surface expression in mammalian cells. For this, mDCT cells were grown to 90% confluence in 12-well plates and then placed in Cl − -free media for 30 minutes. The cells were then incubated in medium-containing vehicle (DMSO), TPA, forskolin, or 4α-PDD. For functional assessment, cells were then incubated in a 22Na + -containing medium with or without thiazides and then washed with ice-cold wash buffer and lysed. Radioactivity was counted, protein concentrations of the lysates were determined, and uptakes were normalized to nmol/mg. Thiazide-sensitive uptake was given by the difference of the uptakes with and without thiazide. For assessment of surface expression, the cells were washed with ice-cold PBS and incubated with NHS-SS-biotin at 40°C for 30 minutes. The cells were lysed, and labeled protein was isolated. The biotinylated protein was eluted in SDS sample buffer with DTT. Protein concentration was measured using the lysate from each group. Biotinylated surface protein and the corresponding amount of total NCC in the cell lysates were analyzed by Western blotting and were quantified by densitometric analysis. TPA completely suppressed NCC function, essentially eliminating thiazide-sensitive uptake (statistically no different from zero for TPA vs 43.4 ± 8.68 nmol/mg for vehicle, p p
Apoptosis of endoplasmic reticulum stress-specific induced endoplasmic by Aβ and effect of tetrahydroxy stilbene glucoside on it

Objective: To observe the effect of tetrahydroxy stilbene glucoside(TSG) on the behavior of rat model and the expression of caspase12 related with endoplasmic reticulum stress induced by Aβ1-42.Methods: Eighty rats were equally randomized into 4 groups(n=20):the control group,the shamoperated group,the model group and the TSG group.Except for the control group,animal models of AD was induced by Aβ1-42 using stereotactic microinjection to hippocampus.The behavior of rats was measured by using Y-maze and Morris water maze.The expression of caspase 12 in rats hippocampus was detected by Western blotting and RT-PCR at the different time points(0,3 and 21 d).Results: The number of electric-stimulus in hippocampus significantly increased and the Morris water maze test showed that the escape latency prolonged,swimming distance increased and the times of crossing the exact former platform location decreased both in the model and TSG groups after 21 days compared with those in control group.A large number of apoptotic cells can be found in CA1 area of model rats.Further analysis showed that the expression of caspase12 upgrade and was highest at 3 d and in model group.compared to model group,apoptotic cells was significantly reduced in TSG group.The expression of caspase 12 was decreased at 3 d in TSG group.Conclusion: Initiation of caspase12 apoptosis pathway is possible one of the mechanisms that priming endoplasmic reticulum apoptosis pathway in Aβ neurotoxic injury.TSG from Poly-gonum multiflorum have protective effection on it.
A Longitudinal Study Predicting Heroin and Alcohol Use Among Young Puerto Ricans

Substance usage patterns obtained in 1975 by interview were predicted from data collected in 1968 by questionnaire from 657 young Puerto Ricans residing in Bayamon, Puerto Rico.
Experimental studies on spinal cord injuries in the last fifteen years.

AbstractExperimental studies on spinal cord (SC) injuries published from 1975 to 1989 in some of the most widely circulating neurosurgical journals were reviewed. The relatively large number of animal species utilized as well as the intensely variable dynamic or static methods employed to induce SC injury represent elements of confusion more than objective necessities in this field of research. In fact, the objective of SC injury research should be to solve the problem of severe SC injuries by either preventing and/or repairing SC damage, rather than looking for modalities to provoke a large spectrum of SC injuries with the result of establishing a correlation between for example, the clinical picture and trauma magnitude. It should be time to study all variables and treatments mainly in only one experimental model. The rat with a permanent paraplegia should represent such a model; the abdominal aorta occlusion for 45 minutes, distal to the renal arteries in rabbits should be the experimental model of cho...
Aberration in 3-Photon Transcranial Calcium Imaging of Cortical Activity

3-photon excitation permits fluorescence microscopy through the intact skull, but is highly sensitive to aberration. We estimate aberration encountered in focusing 1250 nm light through a glass-on-acrylic window for chronic transcranial in vivo imaging.
The World Bank, Development, and Health

This chapter introduces the central puzzle guiding the book: how is it that the World Bank, viewed as a neoliberal hegemon, was unable to effect sweeping market-oriented reforms in health in Latin America, a region mired by economic crisis and recession and needful of external funding? I set up the theoretical framework that guides the book, drawing from the literatures on global governance, neoliberalism and the Washington and possible post-Washington consensus, and health systems research. I introduce the concepts of state autonomy and capacity in health as well as the paradigmatic goals (equity and efficiency) and policy instruments (in particular, I examine (1) decentralization and deconcentration, (2) performance-based financing, (3) separation of functions across and within institutions, (4) targeting, (5) private sector involvement, and (6) primary health care model) framework which guides my analysis. I discuss my research design and provide historical background on the health sectors of Argentina, Costa Rica, and Peru’s in order to contextualize these countries’ different responses and episodes of health sector reform between 1980 and 2005, setting the stage for the developments discussed in the book.
Barriers to global health development: An international quantitative survey.

Background Global health’s goal of reducing low-and-middle-income country versus high-income country health disparities faces complex challenges. Although there have been discussions of barriers, there has not been a broad-based, quantitative survey of such barriers. Methods 432 global health professionals were invited via email to participate in an online survey, with 268 (62%) participating. The survey assessed participants’ (A) demographic and global health background, (B) perceptions regarding 66 barriers’ seriousness, (C) detailed ratings of barriers designated most serious, (D) potential solutions. Results Thirty-four (of 66) barriers were seen as moderately or more serious, highlighting the widespread, significant challenges global health development faces. Perceived barrier seriousness differed significantly across domains: Resource Limitations mean = 2.47 (0–4 Likert scale), Priority Selection mean = 2.20, Corruption, Lack of Competence mean = 1.87, Social and Cultural Barriers mean = 1.68. Some system-level predictors showed significant but relatively limited relations. For instance, for Global Health Domain, HIV and Mental Health had higher levels of perceived Social and Cultural Barriers than other GH Domains. Individual–level global health experience predictors had small but significant effects, with seriousness of (a) Corruption, Lack of Competence, and (b) Priority Selection barriers positively correlated with respondents’ level of LMIC-oriented (e.g., weeks/year spent in LMIC) but Academic Global Health Achievement (e.g., number of global health publications) negatively correlated with overall barrier seriousness. Conclusions That comparatively few system-level predictors (e.g., Organization Type) were significant suggests these barriers may be relatively fundamental at the system-level. Individual-level and system-level effects do have policy implications; e.g., Priority Selection barriers were among the most serious, yet effects on seriousness of how LMIC-oriented a professional was versus level of academic global health achievement ran in opposite directions, suggesting increased discussion of priorities between LMIC-based and other professionals may be useful. It is hoped the 22 suggested solutions will provide useful ideas for addressing global health barriers.
An Improved Synthesis of Me4PCP and DMPE

We present a new synthetic method for the bis(dimethyl)phosphines Me4PCP (C6H4-2,6-(CH2P(CH3)2)2) and DMPE ((CH3)2PCH2CH2P(CH3)2) that starts from an aminophosphine, Et2NPMe2. Two equivalents of Et2NPMe2 react with the corresponding bis(alkyl bromide) to afford an oxygen- and moisture-stable aminophosphonium salt. NaAlH4 selectively reduces the aminophosphonium salt to the desired phosphine. Each step is high yielding and requires minimal purification.
Sciences of learning and development: Some thoughts from the learning sciences

This commentary extends and amplifies aspects of the Cantor, Osher, Berg, Steyer and Rose (2018) discussion about what we know about the nature of learning and its implications for how we educate s...
Dendritic Cell-Based ELISpot Assay for Assessing T-Cell IFN-γ Responses in Human Peripheral Blood Mononuclear Cells to Dengue Envelope Proteins

Dengue envelope (E) protein is a dominant antigen for vaccine development and E-based vaccines have shown partial or full protection against live-virus challenge in non-human primates. Generally, T cell responses can be investigated with peptides. However, hundreds of over-lapping peptides need to be synthesized to cover the whole sequence of a protein, which brings the cost up to a much higher level than purchasing a protein. We have developed an enzyme-linked immunospot (ELISpot) assay that uses intact E proteins instead of peptides for assessing IFN-gamma (IFN-γ) responses. The assay relies on professional antigen presenting cells, dendritic cells, to process and present the E proteins to stimulate T cells.Peripheral blood mononuclear cells (PBMCs) from dengue-exposed and naive subjects were selected for the assay development. IFN-γ production ranged from 53 to 513 spot forming units (SFUs) and 0-45 SFUs per million PBMCs in dengue-exposed and naive subject groups, respectively. The assay allowed quantification of E-specific IFN-γ secreting memory T cells in subjects 9 years after exposure to a live-attenuated virus vaccine and live-virus challenge. Our results suggest that the dendritic cell-based IFN-γ assay is a useful tool for assessing immunological memory for clinical research.
Treatment of T3N0 non-small cell lung cancer with chest wall invasion using stereotactic body radiotherapy.

Abstract Objectives Chest wall invasion (CWI) is observed in 5% of localized non-small cell lung cancer (NSCLC). The role of stereotactic body radiotherapy (SBRT) in these patients is unknown. We investigate the safety and efficacy of SBRT in patients with T3N0 NSCLC due to CWI. Methods Patients with T3N0 NSCLC due to CWI were identified using a prospective registry. CWI was defined as radiographic evidence of soft tissue invasion or bony destruction. We excluded patients with recurrent or metastatic disease. All patients were treated with definitive SBRT. Prescribed dose was 50 Gy in 5 fractions for most patients. Kaplan-Meier analysis was used to estimate survival outcomes. Results We identified 12 patients treated between 2006 and 2017. Median age was 70 (range, 58–85). Median tumor diameter was 3.0 cm (range, 0.9–7.2). Median survival was 12.0 months (range, 2.4–63). At a median follow-up of 8.9 months (range, 2.1–63), 1-year primary tumor control was 89%, involved lobar control was 89%, local–regional control was 82%, distant control was 91%, and survival was 63%. Of the 4 patients with pre-treatment chest wall pain, 3 reported improvement after SBRT. Two patients reported new grade 1–2 chest wall pain. No grade 3+ toxicity was reported, with 1 patient experiencing grade 1 skin toxicity and 3 patients experiencing grade 1–2 radiation pneumonitis. Conclusions SBRT for CWI NSCLC is safe, with high early tumor control and low treatment-related toxicity. Most patients with pre-treatment chest wall pain experienced relief after SBRT, with no grade 3+ toxicity observed.
Acetate Metabolism in Physiology, Cancer, and Beyond.

Acetate and the related metabolism of acetyl-coenzyme A (acetyl-CoA) confer numerous metabolic functions, including energy production, lipid synthesis, and protein acetylation. Despite its importance as a nutrient for cellular metabolism, its source has been unclear. Recent studies have provided evidence to support the existence of a de novo pathway for acetate production derived from pyruvate, the end product of glycolysis. This mechanism of pyruvate-derived acetate generation could have far-reaching implications for the regulation of central carbon metabolism. In this Opinion, we discuss our current understanding of acetate metabolism in the context of cell-autonomous metabolic regulation, cell–cell interactions, and systemic physiology. Applications relevant to health and disease, particularly cancer, are emphasized.
Remote magnetometry using fluorescence resonance in sodium vapor (Conference Presentation)

Measurement and monitoring of geomagnetic field in the mesosphere has many potential applications such as detection of oceanic currents, mapping of large-scale magnetic structures, and study of electric-current fluctuations in the ionosphere. Remote measurement of the geomagnetic field can be performed by optical pumping of sodium atoms in the mesosphere with an amplitude modulated (AM) light at the Larmor precession frequency, and observing the magnetic resonance in fluorescence at a ground station. In this context, we have conducted an experiment in the laboratory to demonstrate remote magnetic field measurement using fluorescence signal from a sodium cell. Sodium atoms in the cell are interrogated with AM light produced by an acousto-optic modulator (AOM), introduced in the beam path of a frequency-doubled amplified sodium laser made in our laboratory. Magnetic resonance observed in sodium cell fluorescence is studied as a function of varying magnetic field intensity. Characteristics of the magnetic resonance such as linewidth and contrast (or SNR), and their dependence on optical power density, AM duty cycle, B-field orientation and intensity are studied. Theoretical modeling and experimental measurements are also carried out to determine the sensitivity of the magnetometer for realizing remote magnetometry with mesospheric sodium atoms.
Vaccines for Health Care Personnel.

Abstract Medical Center Occupational Health (MCOH) programs must protect health care personnel (HCP) against the occupational risk of vaccine-preventable diseases. This thematic review outlines the rationale for the use of recommended vaccines in HCP; summarizes the available evidence regarding vaccine effectiveness, administration, and assessment of immunity; and provides guidance for MCOH programs navigating challenging situations.
Gating Tegucigalpa, Honduras: The Paradoxical Effects of "Safer Barrios"

This paper analyzes the paradoxical political and socio-spatial dynamics created by “Safer Barrios,” a security program that redefines notions of citizenship, governance, participation, and space i...