cssi/SciSciGPT-SciSciNet huggingface dataset:
Fracture shortly before stroke in mice leads to hippocampus inflammation and long-lasting memory dysfunction.

Cognitive impairment occurs in stroke and hip fracture patients. In mice, bone fracture (BF) exacerbates stroke-related neuronal damage and sensorimotor dysfunction. We hypothesize that BF exacerbates post-stroke cognitive impairment. Adult mice were randomly assigned into BF, stroke, BF+stroke (BF 6 h before stroke), and control (sham operated) groups. Memory function was evaluated weekly for eight weeks by Y maze test and at eight weeks post-surgeries by novel object recognition (NOR) test. The neuronal damage and inflammation in hippocampus were analyzed three days and eight weeks after the surgeries. In Y maze test, BF+stroke mice started making fewer alternations than controls two weeks after the surgeries. Significant difference between BF+stroke and stroke groups started at five weeks post-injury and continued to the end of the experiment. In NOR test, BF+stroke group spent less time on novel objective than that of other groups. Cx3cr1+ cells and CD68+ cells accumulated in the stratum lacunosum moleculare (SLM) on the ipsilateral side of stroke injury in stroke and BF+stroke mice. BF+stroke mice had a higher ratio of ipsilateral/contralateral Cx3cr1+ cell-density than that of stroke mice. Therefore, BF shortly before stroke exacerbates hippocampal inflammation and causes long-lasting memory dysfunction.
A Pilot Study Using EMR (Electronic Medical Record) and BMT (Bone Marrow Transplant) Registry Data to Evaluate Health Service Utilization in BMT Patients with Depression and Comorbid Conditions at an Academic Cancer Center

Introduction and Objectives Depression has been shown to increase health service utilization in cancer patients. Using data from EMR and BMT Registry we evaluated the impact of depression and comorbidity in BMT patients at our center. Methods A retrospective review of EMR of autologous (AUTO) and allogeneic (ALLO) stem cell transplant patients in UCSD Moores Cancer Center from 2012 to 2017. All diagnoses were defined by ICD-9/ICD-10 codes. Between group differences were assessed by t-test and chi-square test. Negative binomial modeling was performed to evaluate predictors of length of stay in the hospital (LOS) and clinic visits. The analyses were adjusted for age, gender, cancer diagnosis, comorbid conditions, GVHD status (for ALLO patients only) and Charlson Comorbidity Index (CCI). Results A total of 731 patients of whom 22.3% had depression were identified: AUTO Patients (N = 472; 18% Depressed [85]); ALLO patients (N = 259; 30.1% depressed [78]). For the entire population, we compared depressed patients (n = 540) to non-depressed patients (n = 158). Significant differences were observed for LOS (days), clinic visits, and CCI: 59.58+/-49.48 vs. 40.28 (p For AUTO patients, the corresponding LOS, clinic visit, and CCI were 35.31+/-26.14 vs. 25.40+/-22.89 days (p = 0.002), 16.3+/-11.87 vs. 10.77+/-7.29 (p For AUTO patients, depression and infection were significant predictors for increased LOS and frequent clinic visits. For ALLO patients, significant predictors for increased LOS includes COPD and chronic GVHD which was a significant predictor for frequent clinic visits (Table 1). Conclusion Depression and comorbidities had a significant impact on health service utilization. Clinicians and health systems should recognize the importance of providing care in BMT patients with depression and managing comorbid conditions.
The Ethnocentric Origins of the Learning Style Idea.

In recent years, researchers have questioned the legitimacy of the so-called myth of learning styles and expressed confusion about exactly when and why the idea first emerged. This historical study...
Combined effect of physical activity and sedentary behavior on body composition in university students.

Summary Background & aims This study aimed to evaluate the domain-specific physical activity (PA) levels and sitting time of a sample of university students and examine the association of PA with percent body fat. Methods Two hundred and twenty-one students were included in the analysis. We administered the long form of the International Physical Activity Questionnaire (IPAQ) twice within one-month interval. Total PA as well as occupational, transportation-, housework-, and leisure-related PA were assessed, in addition to sitting time. Dietary intake was derived from six non-consecutive 24-hour dietary recalls. Percent body fat (dependent variable) was analyzed using a bioelectrical impedance analyzer (BIA). Multivariate logistic regression, adjusted for potential confounders, examined the associations of domain-specific PA and sitting time with percent body fat. Results Men had higher levels of total and leisure PA than women. All participants had prolonged sitting time, with 48% having a sitting time of more than 10.15 hours/day. In multivariate analysis, moderate leisure PA, compared to vigorous PA was associated with a lower percent body fat. This association remained statistically significant even after adjustment for energy intake and sitting time. Housework-related PA was associated with a higher percent body fat. Conclusion Moderate leisure PA was highly associated with percent body fat even after adjustment for confounding variables. Adequate interventions targeting this kind of leisure should be promoted among universities students.
Doucet (Ed.): Why Detroit Matters: Decline, Renewal and Hope in a Divided City

In June 2018, Ford Motor Corporation announced it had bought the iconic Michigan Central Station as its technology hub for electric and autonomous vehicles. For 30 years this massive structure sat ...
Socially-Aware User Interfaces: Can Genuine Sensitivity Be Learnt at all?

Recent years have initiated a paradigm shift from pure task-based human-machine interfaces towards socially-aware interaction. Advances in deep learning have led to anthropomorphic interfaces with robust sensing capabilities that come close to or even exceed human performance. In some cases, these interfaces may convey to humans the illusion of a sentient being that cares for them. At the same time, there is the risk that - at some point - these systems may have to reveal their lack of true comprehension of the situative context and the user’s needs with serious consequences to user trust. The talk will discuss challenges that arise when designing multimodal interfaces that hide the underlying complexity from the user, but still demonstrate a transparent and plausible behavior. It will argue for hybrid AI approaches that look beyond deep learning to encompass a theory of mind to obtain a better understanding of the rationale behind human behaviors.
Mild Dehydration Identification Using Machine Learning to Assess Autonomic Responses to Cognitive Stress.

The feasibility of detecting mild dehydration by using autonomic responses to cognitive stress was studied. To induce cognitive stress, subjects (n = 17) performed the Stroop task, which comprised four minutes of rest and four minutes of test. Nine indices of autonomic control based on electrodermal activity (EDA) and pulse rate variability (PRV) were obtained during both the rest and test stages of the Stroop task. Measurements were taken on three consecutive days in which subjects were “wet” (not dehydrated) and “dry” (experiencing mild dehydration caused by fluid restriction). Nine approaches were tested for classification of “wet” and “dry” conditions: (1) linear (LDA) and (2) quadratic discriminant analysis (QDA), (3) logistic regression, (4) support vector machines (SVM) with cubic, (5) fine Gaussian kernel, (6) medium Gaussian kernel, (7) a k-nearest neighbor (KNN) classifier, (8) decision trees, and (9) subspace ensemble of KNN classifiers (SE-KNN). The classification models were tested for all possible combinations of the nine indices of autonomic nervous system control, and their performance was assessed by using leave-one-subject-out cross-validation. An overall accuracy of mild dehydration detection was 91.2% when using the cubic SE-KNN and indices obtained only at rest, and the accuracy was 91.2% when using the cubic SVM classifiers and indices obtained only at test. Accuracy was 86.8% when rest-to-test increments in the autonomic indices were used along with the KNN and QDA classifiers. In summary, measures of autonomic function based on EDA and PRV are suitable for detecting mild dehydration and could potentially be used for the noninvasive testing of dehydration.
Alexis de Tocqueville’s Citizenship: A Model of Collective Virtue

In Democracy in America, Alexis de Tocqueville repeatedly describes psychological and behavioral traits that dispose Americans to aid their community and community members. I dub this disposition, “citizenship,” and argue that Tocqueville’s discussion smoothly lends itself to be interpreted in terms of contemporary philosophical virtue theory. While there is an important sense in which Tocqueville’s musings on citizenship fit well with contemporary virtue theory, there is an even more important sense in which it departs from this tradition. The main focus of this chapter will be explaining the way in which Tocqueville’s “citizenship” is a virtue that can be understood as methodologically distinct from virtues described in both classic and contemporary virtue theory. Importantly, Tocqueville provides a framework for understanding collective virtue.
[Etiology and epidemiological characteristics of gastroenteritis virus in food-borne diarrhea from three cities in Shandong Province, 2017].

Objective To analyze the etiology and epidemiological characteristics of gastroenteritis virus in foodborne diseases from three cities in Shandong. Methods From January to December 2017, six sentinel hospitals in Jinan, Yantai and Linyi city of Shandong Province were selected as the research sites. Stool samples of 1 397 diarrhea patients were collected, as well as basic information and clinical symptoms. Duplex quantitative RT-PCR was used to detect Norovirus genogroupⅠ (Nov GⅠ) and genogroupⅡ (Nov GⅡ), Sapovirus (SAV) and Human astrovirus (HAstV), respectively, quantitative RT-PCR was used to detect group A Rotavirus (RVA), and quantitative PCR was used to detect Enteric adenovirus (EAdV). The specific gene of the virus were sequenced and typed. It was compared that the gastroenteritis virus rate in cases with different characteristics and the clinical symptoms difference between the virus positive and negative cases. Results The median age (P25, P75) was 23 (1, 42) , mainly male, 57.48% with 803 cased and children under 5 years old, 36.36% with 508 cases. The positive rate of gastroenteritis virus was 33.93% (474 cases), and that of Jinan, Linyi and Yantai City were 32.03% (147/459), 41.54% (189/455) and 28.57% (138/483), respectively (P<0.001). Nov GⅡ had the highest positive rate, 16.54% (231 cases), which, mainly GⅡ.P16/GⅡ.2 (48.28%, 56/116), peaked in May (24.75%, 50/202) and June (19.59%, 38/194). In patients of gastroenteritis virus positive, 44.51% (211/474) had vomiting symptoms, higher than that of patients of gastroenteritis virus negative (34.13%, 315/923). The difference was statistically significant (P<0.001). Conclusion In Shandong Province, the majority of gastroenteritis patients were male and children under 5 years old. Nov GⅡ possessed highest epidemic intensity, and peaked in spring and summer. Viral gastroenteritis had atypical clinical symptoms. Key words: Diarrhea; Gastroenteritis; Food-borne diarrhea; Pathogen spectrum; Surveillance
Closing the Brief Case: Mold Infection of an Indwelling Cranial Device-a Perplexing Combination of "Classic" Laboratory Findings.

A 40-year-old woman with a history of recurrent medulloblastoma presented for outpatient evaluation of a postoperative wound of the posterior scalp. The patient was diagnosed with medulloblastoma 9 years prior and was initially managed with surgical resection and craniospinal radiotherapy. She had
Diffusional transfer function for the scanning electrical mobility spectrometer (SEMS)

The scanning electrical mobility spectrometer (SEMS), or scanning mobility particle sizer (SMPS), uses the differential mobility analyzer (DMA) operated in scanning mode to measure particle size di...
Tip60 protects against amyloid-β peptide-induced transcriptomic alterations via different modes of action in early versus late stages of neurodegenerative progression

Alzheimer9s disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-β (Aβ) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to Aβ peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptome-wide changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-β42. We show that early Aβ42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding Aβ plaque accumulation that persists into late AD stages. Correlative transcriptome-wide studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the Aβ42 fly brain protects against AD functional pathologies that include Aβ plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 protects against Aβ42-induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings reveal distinct modes of neuroepigenetic gene changes and Tip60 neuroprotection in early versus late stages in AD that can serve as early biomarkers for AD, and support the therapeutic potential of Tip60 over the course of AD progression.
Political-economy of pension plans: Impact of institutions, gender, and culture

Abstract National pension systems are an important part of financial intermediation and worker welfare in most countries, but how and why do they differ internationally? Controlling for important political, economic and social institutions, we document that international differences in pension progressivity, or how pensions reflect lifetime earnings, are negatively related to masculinity, uncertainty avoidance, individualism, long-term orientation, employment rights, average pension levels, social trust and economic inequality. We also find that pension progressivity is positively related to the economic and societal role of women, the extent of Catholicism; as well as political voice and accountability. These results provide important insights for both public policy and MNC managers.
Pulsed-light illumination optical system integrated into surgical microscope for 5-ALA-induced tumor fluorescence detection without surgical process interruption

Glioblastoma remains the deadliest type of brain tumor: half of patients do not live more than 16 months, even when treated with surgery, chemotherapy, and radiation. Tracking systems can help neurosurgeons precisely identify tumor on MRI images. Nevertheless, the tumor often regrows a few centimeters from where the original tumor was. This is because at the time of the first surgery, the actual tumor cells are already invading the healthy tissue around the tumor. These ‘invaders’ are difficult to cut out because even when looking through the surgical microscope, the tumor margins and normal brain tissue look very similar. The emerging utilization of fluorescing biomarkers (e.g., 5-ALA) sensitive to genetic downregulation present in cancer cells improves the detectability of marginal glioma, albeit requiring to switch to the surgical microscope excitation (blue light) mode and dim the operation room lights, imposing difficulties for neurosurgeons and staff. Here, we present a portable fluorescence-guided surgery optical imaging system integrated into the conventional surgical microscope to give neurosurgeons a better tool to predict which tissue is normal and which contains the start of tumor invasion without the need to switch to the excitation mode. The system operates under the microscope’s white light illumination using pulsed fluorophore excitation with gated acquisition and provides helpful tumor tissue fluorescing contrast. Tissue-mimicking phantom imaging confirmed protoporphyrin IX detection down to 0.1μg/mL concentration. Brain tissue imaging ex-vivo and pre-clinical intracranial tumor resection demonstrated the system’s capability to provide a typical operating environment with auxiliary or augmented visualization of PpIX possible.
To touch or not to touch: Variations in mouse tracking across equipment profiles during online incidental learning of novel tone categories

We measure mouse tracking during the incidental acquisition of novel tone categories, permitting a confusion matrix analysis of four novel tone categories. We present variations in mouse tracking response data that arise from inevitable differences in individual equipment profiles (e.g., touchpad, external mouse, etc.) as participants take the study online, rather than in a controlled environment.
An assessment of factors associated with neurocognitive decline in people living with HIV

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) remains a health concern. However, limited research has been done to identify...
Mixed-Mode Stress-Intensity Factor Solutions for Offshore Structural Tubular Joints

Accurate calculations of the stress-intensity factors (K) are essential for assessment of the integrity of structural components containing crack-like defects. For the complex tubular joints used in the construction of offshore structures, accurate K solutions do not exist. Only limited results using empirically derived K values are available in the literature. This paper presents a methodology for the mixed-mode K solutions for a surface crack at the weld toe of tubular joints. Example solutions were developed for tubular X-joints under brace tension and in-plane bending using three-dimensional finite-element analyses. The complex finite-element mesh was generated using a special mesh generator. The K values were obtained from the displacement solutions of quarter-point crack-tip elements. The results demonstrate the validity of the solution scheme and contribute to the understanding of the crack-tip behavior of tubular joints.
Structural Requirements in Material Substitution for Car-Weight Reduction

The structural characteristics for particular automotive structural components are systematically related to representative, typical structural design criteria and design constraints for a production vehicle. Based on these relationships, we establish the structural design requirements to be satisfied when a substitute material is used in an automotive structure. A simplified method is developed for evaluating the desirability of directly substituting materials to reduce the weight of automotive structures. This is done by explicitly relating the change in weight to the corresponding changes in structural characteristics, when a specific mild steel structure is "replaced" by one differing only in material and gage. By means of this method, material trade-offs can be directly evaluated by engineers and designers early in the design stage. Examples are given for aluminum and high-strength steel as candidate substitutes for mild steel.
Cyclic oscillation of blood neutrophils in a patient with multiple myeloma

A patient with multiple myeloma developed periodic blood neutropenia (periodicity of 15–25 days) after 3 yr of intermittent treatment with cytotoxic agents. Peaks of serum colony-stimulating activity (CSA) level coincided with valleys of blood neutrophils. Fraction of marrow neutrophils in the multiplicative pool was high during blood neutrophil valleys and low during neutrophil peaks. In contrast, the maturation storage pool exhibited the reverse pattern. An increased fraction of marrow neutrophilic cells in the multiplicative pool was in active proliferation during a blood neutrophil valley and a decreased fraction during a blood neutrophil peak. These findings suggest that the marrow granulopoiesis was regulated through CSA. The defect causing the periodicity was probably related to the reduced number of neutrophils in the marrow maturation storage pool, which in turn may be related to a reduced and/or defective granulocytic stem cell pool size consequent to the long-term administration of cytotoxic drugs and/or infiltration of the marrow by myeloma cells.
Design and evaluation of a voice conversion algorithm based on spectral envelope mapping and residual prediction

The purpose of a voice conversion (VC) system is to change the perceived speaker identity of a speech signal. We propose an algorithm based on converting the LPC spectrum and predicting the residual as a function of the target envelope parameters. We conduct listening tests based on speaker discrimination of same/difference pairs to measure the accuracy by which the converted voices match the desired target voices. To establish the level of human performance as a baseline, we first measure the ability of listeners to discriminate between original speech utterances under three conditions: normal, fundamental frequency and duration normalized, and LPC coded. Additionally, the spectral parameter conversion function is tested in isolation by listening to source, target, and converted speakers as LPC coded speech. The results show that the speaker identity of speech whose LPC spectrum has been converted can be recognized as the target speaker with the same level of performance as discriminating between LPC coded speech. However, the level of discrimination of converted utterances produced by the full VC system is significantly below that of speaker discrimination of natural speech.
Tear Cathepsin S as a Candidate Biomarker for Sjögren's Syndrome

Objective The diagnosis of Sjogren's syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS. Methods A method to measure CTSS activity in tears eluted from Schirmer's test strips was developed and validated. Schirmer's tests were performed and CTSS activity measurements were obtained in 278 female subjects, including 73 with SS, 79 with rheumatoid arthritis, 40 with systemic lupus erythematosus, 10 with blepharitis, 31 with nonspecific dry eye disease, and 12 with other autoimmune diseases, as well as 33 healthy control subjects. Results The median tear CTSS activity in patients with SS was 4.1-fold higher than that in patients with other autoimmune diseases, 2.1-fold higher than that in patients with nonspecific dry eye disease, and 41.1-fold higher than that in healthy control subjects. Tear CTSS levels were equally elevated in patients with primary SS and those with secondary SS, independent of the Schirmer's test strip values or the levels of circulating anti-SSA or anti-SSB antibodies. Conclusion Markedly high levels of tear CTSS activity are suggestive of SS. CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for SS.
Rapid determination of plasma fibrinogen.

Abstract A procedure for determination of plasma fibrinogen, accurate within a standard error of 17 mg. per cent, has been developed especially for cases of severe abruptio placentae. Results can be reported within 30 to 45 minutes from the time a requests is made. The method is based on a determination of the moist weight of a fibrin clot and the use of an equation for converting this weight to plasma concentration.
Identification and Characterization of Protease-Resistant SecA Fragments: SecA Has Two Membrane-Integral Forms

We have identified and characterized the protease-resistant SecA fragments (X. Chen, H. Xu, and P. C. Tai, J. Biol. Chem. 271:29698-29706, 1996) through immunodetection with region-specific antibodies, chemical extraction, and sequencing analysis. The 66-, 36-, and 27-kDa proteolytic fragments in the membranes all start at Met1, whereas the 48-kDa fragment starts at Glu361. The overlapping of the sequences of the 66- and 48-kDa fragments indicates that they are derived from different SecA molecules. These two fragments were generated differently in response to ATP hydrolysis and protein translocation. Furthermore, the presence of membrane is required for the generation of the 48-kDa fragment but not for that of the 66-kDa fragment. These data suggest that there are two different integral forms of SecA in the membrane: SecA(S) and SecA(M). The combination of these two forms of SecA has several membrane-interacting domains. Both forms of SecA are integrated in the membrane, since both the 48- and 66-kDa fragments could be derived from urea- or Na2CO3-washed membranes. Moreover, all fragments are resistant to extraction with a high concentration of salt or with heparin, but the membrane-specific 48-kDa SecA domain is more sensitive to Na2CO3 or urea extraction. This suggests that this domain may interact with other membrane proteins in an aqueous microenvironment and therefore may form a part of the protein-conducting channel.
Current management of pectus excavatum.

Abstract Pectus excavatum (PE) is one of the most common anomalies of childhood. It occurs in approximately 1 in every 400 births, with males afflicted 5 times more often than females. PE is usually recognized in infancy, becomes much more severe during adolescent growth years, and remains constant throughout adult life. Symptoms are infrequent during early childhood, but become increasingly severe during adolescent years with easy fatigability, dyspnea with mild exertion, decreased endurance, pain in the anterior chest, and tachycardia. The heart is deviated into the left chest to varying degrees causing reduction in stroke volume and cardiac output. Pulmonary expansion is confined, causing a restrictive defect. Repair is recommended for patients who are symptomatic and who have a markedly elevated pectus severity index as determined by chest X-ray or computed tomography scan. Repair using the highly modified Ravitch technique is usually performed after the age of 8 years. The optimal age for repair is between 12 and 16 years. Repair can be performed on adults with similar good results. Recent modifications in the Ravitch technique remove minimal cartilage and routinely use a temporary internal support bar for 6 months. Operation rarely takes more than 3 hours, and hospitalization rarely exceeds 3 days. Pain is mild and complications are rare, with 97% of patients experiencing a good to excellent result. The new minimally invasive Nuss repair avoids cartilage resection and takes less operating time, but is associated with more severe pain, longer hospitalization and a higher complication rate, with the bar remaining for 2 or more years. This technique is less applicable to older patients and those with asymmetric deformities. Long-term follow-up will be necessary to determine which operation may be best for any specific patient.
The Impact of Human Resource Practices and Compensation Design on Performance: An Analysis of Family-Owned SMEs

A sample of 168 family-owned fast growth small and medium enterprises (SMEs) was used to empirically examine the consequences of five human resource practices on sales growth performance. The results suggest that training and development, recruitment package, maintaining morale, use of performance appraisals, and competitive compensation were more important for high sales-growth performing firms than for low sales-growth performing firms. In addition, we examined the use of incentive compensation in the form of cash, noncash, and benefits and perks for four different levels of employees in family-owned SMEs. The findings suggest that high sales-growth performing firms used more cash incentive compensation at every level in the organization.
Development of the flow-through porous electrode cell for bromide recovery from brine solutions

A continuous electrochemical process for bromine production from brine solutions was developed based on bromide oxidation and flow-through porous electrode technology. The bromide oxidation kinetics in a three-dimensional porous graphite electrode was determined using a small test flow cell. The data were analysed and combined into a process model to evaluate the electrode performance under many different operating conditions. Bromide conversions against cell sizes for various brine throughputs were calculated using model equations and verified by experimental data collected from a 45 cm long pilot cell.
The divalent cation requirement of the mitochondrial glycerol-3-phosphate dehydrogenase.

Abstract Coupled respiration by blowfly mitochondria has been utilized to demonstrate an absolute divalent cation requirement for glycerol 3-phosphate respiration. With ADP, phosphate and EGTA, the respiration rate (state 3) decreases as a function of the amount of oxygen reduced, to approximately 15% of its maximum value, even at 40 mM dl -glycerol 3-phosphate; it can be increased to its maximum value by the addition of Ca 2+ , Sr 2+ or Mn 2+ . The decline in state 3 rate is not due to the removal of membrane-bound calcium into the matrix by the calcium carrier, since it occurs in the presence of ruthenium red. The effect is energy-dependent since the state 3 respiration does not decrease in the presence of uncouplers. The increase in respiration upon the addition of calcium is not due to the energy-dependent calcium transport since it is sensitive to oligomycin and insensitive to ruthenium red. The divalent cation effector site is located on the glycerol-3-phosphate dehydrogense, since state 3 (or state 4) pyruvate-proline respiration (NAD-linked) is not affected by EGTA. Yet the state 3 pyruvate-proline respiration removes calcium so effectively from the glycerol-3-phosphate dehydrogenase in the presence of EGTA, that added calcium stimulates glycerol 3-phosphate (26.4 mM) respiration about 22-fold. Since uncouplers stimulate the inhibited glycerol 3-phosphate respiration only to a very small extent, a calcium stimulation of the rate of phenazine methosulfate reduction by glycerol 3-phosphate (26.4 mM) which bypasses all phosphorylation sites, should be detectable. Only a 3-fold stimulation was observed. The present experiments suggest that upon complete removal of divalent cations from the dehydrogenase, glycerol 3-phosphate does not act as a homotropic effector in the coenzyme Q reductase reaction.
Transient Raman observations of heme vibrational dynamics in five-coordinate iron porphyrins

Abstract Transient resonance Raman spectroscopy has been used to study vibrational dynamics in five-coordinate, high-spin Fe II octaethyl porphyrin with a 2-methyl imidazole axial ligand. Vibrational populations of the porphyrin ground electronic state were probed by examining Stokes and anti-Stokes Raman scattering as a function of incident laser flux using ∼10 nanosecond pulses in resonance with the Soret electronic transition. Within a single pulse, each molecule goes through several excitation-decay cycles, building up a non-equilibrium, excited vibrational energy distribution that is exquisitely sensitive to the vibrational mode lifetimes and to the incident laser flux. A kinetic model illustrates these ideas and provides strong support for the interpretation of the results. The flux dependence of the Raman intensities, positions and linewidths suggests that ν 3 and ν 4 act as “bottleneck” vibrational states, while ν CH and ν 7 couple more effectively to the environment.
Target Chemistry of Zirconium and Yttrium; Isolation of Zr89 in Pure State

Radioactive Zr89 obtained by bombardment of Y2O3 with deuterons, was separated without addition of stable zirconium in quantities ∼10−10 gram. Oxychloride solutions of Zr89 mixed with inactive Zr were used for coagulation studies in the concentration range 1.5×10−4−1.5×10−11 gA/l. It was found that the fraction coagulated increased with dilution under the constant conditions used (pH−4.0; NaCl−2.5×10−2N; T−25°), to 2.7×10−6 gA/l. The log‐log plot of zirconium concentration (C) in solution against coagulated part (c) closely approaches a straight line with exponent n=1.50 and k=490. At 1.5×10−6 gA/l and lower concentrations the coagulated fraction reaches a maximum and becomes constant, k=C/c=.45. Within the range studied salt increases coagulation of zirconium above 10−5 gA/l; but below 10−6 gA/l the salt effect is reversed. Increase in pH results in increase in the fraction coagulated (r) in all concentrations studied. At a minute concentration r=(pH—K)/m, K being 1.85 with NaCl, 0.05N and 1.58 with NaCl...
3-Neopentylallyllithium I. The 1,4-addition product of tert-butyllithium and 1,3-butadiene☆

Abstract tert-Butyllithium and 1,3-butadiene react in hydrocarbon solvents in 1 1 molar ratio to yield cis- and trans-neopentylallyllithium(NpALi). Proton NMR data indicate that the ratio of trans to cis isomers under the conditions used, and that the isomers do not equilibrate up to 70°. No evidence for the secondary isomer 1-NpALi (V) is observed. The upfield chemical shift of the 3-proton in NpALi is interpreted in terms of partial delocalization of charge within the allyl system, and is consistent with IR and UV absorption data.
Conformational Basis for SH2-Tyr(P)527 Binding in Src Inactivation

Src protein-tyrosine kinase contains a myristoylation motif, a unique region, an Src homology (SH) 3 domain, an SH2 domain, a catalytic domain, and a C-terminal tail. The C-terminal tail contains a Tyr residue, Tyr527. Phosphorylation of Tyr527 triggers Src inactivation, caused by Tyr(P)527 binding to the SH2 domain. In this study, we demonstrated that a conformational contribution, not affinity, is the predominant force for the intramolecular SH2-Tyr(P)527 binding, and we characterized the structural basis for this conformational contribution. First, a phosphopeptide mimicking the C-terminal tail is an 80-fold weaker ligand than the optimal phosphopeptide, pYEEI, and similar to a phosphopeptide containing three Ala residues following Tyr(P) in binding to the Src SH2 domain. Second, the SH2-Tyr(P)527 binding is largely independent of the amino acid sequence surrounding Tyr(P)527, and only slightly decreased by an inactivating mutation in the SH2 domain. Furthermore, even the unphosphorylated C-terminal tail with the sequence of YEEI suppresses Src activity by binding to the SH2 domain. These experiments demonstrate that very weak affinity is sufficient for the SH2-Tyr(P)527 binding in Src inactivation. Third, the effective intramolecular SH2-Tyr(P)527 binding is attributed to a conformational contribution that requires residues Trp260 and Leu255. Although the SH3 domain is essential for Src inactivation by Tyr(P)527, it does not contribute to the SH2-Tyr(P)527 binding. These findings suggest a conformation-based Src inactivation model, which provides a unifying framework for understanding Src activation by a variety of mechanisms.
Effects of salmeterol on secretion of phosphatidylcholine by alveolar type II cells.

Abstract β-adrenergic agents enhance secretion of phosphatidylcholine (PC) by adult and fetal type II cells. We have previously shown that terbutaline stimulates secretion of PC by fetal type II cells, but the response wanes after 3.0 minutes. We studied the effects of salmeterol, a highly selective, long-acting β 2 -adrenergic agonist that does not cause receptor desensitization, on PC secretion by adult type II alveolar cells in primary culture. Release of lactate-dehydrogenase was 50 was 11.40 ± 1.14 nM. Propranolol inhibited the effect of salmeterol on release of PC, confirming that the effects of salmeterol are mediated by β-receptors. OT 50 , the time for onset of action, was 32.0 ± 1.6 minutes. RT 50 , the time to achieve 50% recovery from maximal stimulation was, 393.0 ± 20.2 minutes. We conclude that salmeterol stimulates PC secretion by type II cells through activation of β-adrenergic receptors and has a longer duration of action (> 6 hours) compared to other β 2 -agonists. Salmeterol may be a useful drug with which to study the role of receptor desensitization in the developmental changes in PC secretion.
SENHORAS & SENHORES: HAROLDO MARANHÃO

Este ensaio e consequencia de duas situacoes: uma entrevista com o Autor, no Rio, em 1987, e uma conversa com Benedito Nunes, nos EUA, em 1990. O resultado e a tentativa de ver, atraves do diario Senhoras & senhores, de 1989, parte da materia-prima que da base ao processo de ficcionalizacao na obra de Haroldo Maranhao.
The hydrothermal alteration of oceanic basalts by seawater

Thesis. 1977. Ph.D.--Massachusetts Institute of Technology. Dept. of Earth and Planetary Sciences.
In vivo activation of cAMP-dependent protein kinase by aminophylline and 1-methyl, 3-isobutylxanthine.

Summary Aminophylline and 1-methyl, 3-isobutylxanthine, inhibitors of phosphodiesterases, caused an increase in the cyclic AMP level and an elevation in the activity of cyclic AMP-dependent protein kinase in the liver of the rat within 10–20 min of administration. The activation of cyclic AMP-dependent protein kinase appeared to be a more accurate measure of cyclic AMP-dependent events than cyclic AMP concentration and was statistically more reliable. After Sephadex chromatography, the protein kinase yielded the same activation pattern as measurable in the crude supernatant of liver.
Antidepressant-like activity of compounds with varying efficacy at 5-HT1A receptors.

Abstract Three novel compounds (WY-48,723, WY-50,324, WY-47,846 [zalospirone]), with high affinity but varying efficacy for the 5-HT1A receptor, were examined for producing the 5-HT behavioral syndrome and for potential antidepressant activity in the forced swimming test (FST). WY-50,324 was more potent than WY-48,723 at producing the 5-HT syndrome, but unlike WY-48,723, it produced only some of the behaviors of the 5-HT syndrome and its profile resembles that of a partial agonist. WY-48,723 appeared to be a full agonist because it produced behavioral effects similar to those of 8-OH-DPAT. The syndrome produced by these compounds was antagonized by pretreatment with pindolol. Zalospirone did not produce the syndrome but it antagonized the syndrome produced by 8-OH-DPAT. WY-48,723 and WY-50,324 reduced immobility time in the FST. These effects were similar to those produced by the tricyclic antidepressant desipramine and the 5-HT1A agonist 8-OH-DPAT. Zalospirone did not reduce immobility time, but increased it, which made it difficult to evaluate in this screen. These results suggest that the full agonist WY-48,723 and the partial agonist WY-50,324 may both possess antidepressant activity. Antidepressant-like activity appears to be a characteristic of compounds with a medium to high efficacy for activating 5-HT1A receptors.
Neurogenesis in the optic tectum of larval Rana pipiens following unilateral enucleation.

DNA synthesis and interlayer migrations of cells in the optic tectum of larval Rana pipiens were investigated, using several series of larvae which had been subjected to unilateral enucleation at stage 25, the last embryonic stage. It has been found that DNA synthesis occurs in all cellular layers of the tectum with least activity in peripheral layers. The location of the most active DNA synthesis during the larval period is the same as the location of cell division in the larval tectum, namely, in the layers bordering the ventricle of the optic lobe Unilateral enucleation of stage 25 embryos results in a decrease in DNA synthesis in all cellular layers of the optic tectum contralateral to the operation when compared to the corresponding layers in the ipsilateral tectum. The differences in rate of incorporation of 3H-thymidine between the control and affected lobes become greater during development. Fewer cells are found in each layer of the affected larval tectum than in the corresponding layer of the control tectum. The decrease is greatest in more peripheral layers, whose cells are more intimately associated with the visual circuit than are cells of the deeper layers. Peripheral to layers 1 and 2, the percentages of labeled cells found in each layer are very similar on the two sides, suggesting common factors which control migration. Differences in cell number, therefore, reflect differential cell production rather than differential cell migrations. The distribution of label resulting from 3H-thymidine incorporation at stage III indicates that the distribution of mitotic activity is not uniform in the cephalocaudal axis of the tectum. Greater cell proliferation occurs in the posterior portion of the tectum than in the anterior region throughout larval development. The peripheral control of mitotic divisions in the frog optic tectum remains unknown. The data in the present study, however, support the hypothesis that influences from afferent fibers of the optic tract modify the rates or timing of DNA synthesis in the optic tectum. The data support the notion that the deepest tectal cells respond earliest to the stimulus and these may be ependymal cells which have processes extending to the outer surface of the tectum.
Guanylyl Cyclase C Suppresses Intestinal Tumorigenesis by Restricting Proliferation and Maintaining Genomic Integrity

Background & Aims: The most commonly lost gene products in colorectal carcinogenesis include guanylin and uroguanylin, endogenous ligands for guanylyl cyclase C (GCC). Beyond intestinal fluid balance, GCC mediates diarrhea induced by bacterial enterotoxins, and an inverse relationship exists between enterotoxigenic Escherichia coli infections producing the exogenous GCC ligand ST and colorectal cancer worldwide. However, the role of GCC in neoplasia remains obscure. Methods: Intestinal tumorigenesis was examined in wild-type (Gcc+/+) and GCC-deficient (Gcc−/−) mice carrying mutations in Apc (ApcMin/+) or exposed to the carcinogen azoxymethane. Markers of DNA damage, loss of Apc heterozygosity, and β-catenin mutations were used to assess genomic integrity. Hyperproliferation was explored using Ki67 and cell cycle markers. Apoptosis was quantified by transferase biotin-dUTP nick end labeling analysis. Results: In colons of ApcMin/+ mice, deletion of Gcc increased tumor incidence and multiplicity, reflecting uncoupling of loss of genomic integrity and compensatory apoptosis. Conversely, in the small intestine, elimination of Gcc increased tumorigenesis by enhancing proliferation without altering genomic integrity. Moreover, these distinct but mutually reinforcing mechanisms collaborate in azoxymethane-exposed mice, and deletion of Gcc increased tumor initiation and growth associated with hypermutation and hyperproliferation, respectively, in conjunction with attenuated apoptosis. Conclusions: GCC suppresses tumor initiation and growth by maintaining genomic integrity and restricting proliferation. This previously unrecognized role of GCC in inhibiting tumorigenesis, together with the invariant disruption in guanylin and uroguanylin expression early in carcinogenesis, and the uniform over-expression of GCC by tumors, underscores the potential of oral administration of GCC ligands for targeted prevention and therapy of colorectal cancer.
Television Commercials in Violent Programming: An Experimental Evaluation of their Effects on Children

Using an experimental method, this study found that when a commercial was viewed immediately following a high-violence dramatic programming segment, children’s ad copy recognition scores were significantly lower and attitudes toward the ad and the advertised brand were significantly less favorable than when the commercial was viewed following a low-violence (but otherwise near-identical) program segment. The influence of program violence level on some advertising response measures was more pronounced when the commercial was positioned immediately following the dramatic programming segment than when immediately preceding it. The study cautions advertisers to examine carefully whether, in reaching for high audience ratings and cost efficiency through violent television programs, they may be sacrificing communication effectiveness of their brand advertising.
Aristolochene synthase: mechanistic analysis of active site residues by site-directed mutagenesis.

Incubation of farnesyl diphosphate (1) with Penicillium roqueforti aristolochene synthase yielded (+)-aristolochene (4), accompanied by minor quantities of the proposed intermediate (S)-(−)germacrene A (2) and the side-product (−)-valencene (5) in a 94:4:2 ratio. By contrast, the closely related aristolochene synthase from Aspergillus terreus cyclized farnesyl diphosphate only to (+)-aristolochene (4). Site-directed mutagenesis of amino acid residues in two highly conserved Mg2+-binding domains led in most cases to reductions in both kcat and kcat/Km as well as increases in the proportion of (S)-(−)germacrene A (2), with the E252Q mutant of the P. roqueforti aristolochene synthase producing only (−)-2. The P. roqueforti D115N, N244L, and S248A/E252D mutants were inactive, as was the A. terreus mutant E227Q. The P. roqueforti mutant Y92F displayed a 100-fold reduction in kcat that was offset by a 50-fold decrease in Km, resulting in a relatively minor 2-fold decrease in catalytic efficiency, kcat/Km. The f...
Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy.

Objective Pneumonia is a major cause of mortality and morbidity in rheumatoid arthritis (RA). This study was undertaken to determine the rate and predictors of hospitalization for pneumonia and the extent to which specific RA treatments increase pneumonia risk. Methods RA patients (n = 16,788) were assessed semiannually for 3.5 years. Pneumonia was confirmed by medical records or detailed patient interview. Covariates included RA severity measures, diabetes, pulmonary disease, and myocardial infarction. Cox proportional hazards regression was used to determine the multivariable risk associated with RA treatments. Results After adjustment for covariates, prednisone use increased the risk of pneumonia hospitalization (hazard ratio [HR] 1.7 [95% confidence interval 1.5–2.0]), including a dose-related increase in risk (≤5mg/day HR 1.4 [95% confidence interval 1.1–1.6], >5–10 mg/day HR 2.1 [95% confidence interval 1.7–2.7], >10 mg/day HR 2.3 [95% confidence interval 1.6–3.2]). Leflunomide also increased the risk (HR 1.2 [95% confidence interval 1.0–1.5]). HRs for etanercept (0.8 [95% confidence interval 0.6–110]) and sulfasalazine (0.7 [95% confidence interval 0.5–1.0]) did not reflect an increased risk of pneumonia. HRs for infliximab, adalimumab, and methotrexate were not significantly different from zero. Conclusion There is a dose-related relationship between prednisone use and pneumonia risk in RA. No increase in risk was found for anti–tumor necrosis factor therapy or methotrexate. These data call into question the belief that low-dose prednisone is safe. Because corticosteroid use is common in RA, the results of this study suggest that prednisone exposure may have important public health consequences.