cssi/SciSciGPT-SciSciNet huggingface dataset:
Interrelationships between mevalonate metabolism and the mitogenic signaling pathway in T lymphocyte proliferation.

Upon stimulation with antigen or antibodies directed at the CD3.T cell receptor complex, T lymphocytes undergo a series of biochemical events that result in DNA synthesis and cellular proliferation. The purpose of the current study was to explore the role of mevalonic acid and its metabolites in this process. Stimulation of freshly isolated human T cells with immobilized anti-CD3 monoclonal antibody (mAb) results in the induction of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase message, with maximum induction occurring at 24 h of culture, approximately 12 h before the onset of DNA synthesis. Protein kinase C (PKC) probably mediates this induction, as H7, which inhibits PKC and cyclic nucleotide-dependent protein kinases, but not HA1004, which inhibits all of these protein kinases except PKC, completely abrogates the appearance of HMG-CoA reductase message. The importance of HMG-CoA reductase induction and mevalonate production in cell cycle progression was demonstrated by the observation that either 25-hydroxycholesterol, which inhibits this induction, or lovastatin, a competitive inhibitor of HMG-CoA reductase, inhibited anti-CD3-induced T cell mitogenesis in a dose-dependent manner. The presence of lovastatin during the first 24-36 h of culture results in a progressive delay of cell cycle progression, whereas this agent, when present only for the first 12 h of culture, had no effect on T cell proliferation. These results suggest that mevalonate is required for cell cycle progression from mid-G1 into late G1. Exogenous mevalonate overcomes the antiproliferative effect of lovastatin but not of 25-hydroxycholesterol. Since 25-hydroxycholesterol suppresses the metabolism of mevalonic acid at multiple points, this result suggests that one or more metabolites of mevalonate, rather than mevalonate itself, plays an essential role in cell cycle progression. One metabolite of mevalonate, farnesol pyrophosphate, may play such a role, since free farnesol suppresses anti-CD3 mAb-induced T cell proliferation in a concentration-dependent manner. In mAb is associated with PKC-dependent induction of HMG-CoA reductase which, in turn, leads to the generation of mevalonic acid and its metabolites, one or more of which play a requisite role in cell cycle progression.
Abstract P019: Identifying Laboratory Markers of Incident Myocardial Infarction through Electronic Health Records

Background: Patients on hemodialysis (HD) are at high risk of cardiac events including myocardial infarction (MI). Electronic health records (EHRs) present a unique opportunity to observe biomedical changes in patients over time. Purpose: To assess whether there were any distinct changes in laboratory values prior to an incident MI. Methods: Using EHR data from a large dialysis organization, we identified 6,468 patients with an incident MI and selected an equal number of patients receiving dialysis on the same date without an MI. We abstracted six months of 12 regularly collected laboratory measures for their potential utility as a marker for incident MI: albumin, calcium, co2, creatinine, ferritin, hemoglobin, iron saturation, phosphorus, platelet, potassium, single pool Kt/V and white blood cell count. We used natural cubic spline regression to determine whether the trajectory of the laboratory values differed amongst patients with and without an incident MI. Results: Of the 12 laboratory measures, 7 sh...
Perioperative management of children undergoing craniofacial reconstruction surgery: a practice survey

Summary Objective/Aims: To assess current practices in the management of children undergoing craniofacial surgery and identify areas of significant practice variability with the intent to direct future research. Background: The perioperative management of infants and children undergoing craniofacial reconstruction surgery can be challenging because of the routine occurrence of significant blood loss with associated morbidity. A variety of techniques have been described to improve the care for these children. It is presently unknown to what extent these practices are currently employed. Methods: A web-based survey was sent to representatives from 102 institutions. One individual per institution was surveyed to prevent larger institutions from being over-represented in the results. Results: Requests to complete the survey were sent to 102 institutions; 48 surveys were completed. The survey was composed of two parts: management of infants undergoing strip craniectomies, and management of children undergoing major craniofacial reconstruction. Conclusions: Significant variability exists in the management of children undergoing these procedures; further study is required to determine the optimal management strategies. Clinical trials assessing the utility of central venous pressure and other hemodynamic monitoring modalities would enable evidence-based decision-making for monitoring in these children. The development of institutional transfusion thresholds should be encouraged, as there exists a body of evidence supporting their efficacy and safety.
How to Achieve Enlightenment Scientifically

A chemical engineer’s perspective on the science of enlightenment is presented. Rational but open-minded scientists have been relentlessly pursuing evidence which would support the wisdom of our enlightened ancestors. Western scientists have done an awful lot of wonderful work in recent decades that is chipping away at the mystery surrounding the phenomenon of enlightenment. The resulting ideas and concepts cut across all boundaries of religion, race, caste, cultures and nationality. The framework is made possible by ancient Eastern wisdom and the work of Western scientists. The concepts are not only for individual transformation but also for world transformation and as a subset, national transformation. While there appears to be a theoretical limit on national or world transformation and therefore the extent to which global peace can be achieved, the framework in this paper is capable of making a real difference for humanity.
Molecular cloning and characterization of the Schizosaccharomyces pombe his3 gene for use as a selectable marker

A DNA fragment which carries the his3 gene of Schizosaccharomyes pombe has been isolated and characterized for use as a selectable marker in transformations. The his3 gene encodes the imidazole acetol phosphate transaminase enzyme (E.C.2.6.1.9), which is responsible for converting imidazole acetol-P to histidinol-P in step 8 of histidine biosynthesis. The nucleotide sequences of a 2196 by gene fragment and a corresponding cDNA clone were determined. Three intron sequences punctuate the 1451 by coding region which generates a predicted polypeptide of 384 amino acids with a molecular mass of 42736 daltons. Northern analysis of his3 mRNAs indicates that the transcript is approximately 1.6 kb in size. Steady-state levels are down-regulated by nitrogen limitation but are unaffected by histidine starvation. The deduced amino acid sequence was compared to the Saccharomyces cerevisiae HIS5, Escherichia coli HisC, and Salmonella typhimurium HisC proteins, all of which are imidazole acetol phosphate transaminases. The S. pombe his3 protein was 49.5% identical to the S. cerevisiae HISS protein and 21.5% identity was found when all four proteins were compared. The shuttle vector pBGI was constructed by subcloning the smallest functional region of his3 and the S. pombe arsl sequence into pUC18 for use in transformation of His3 — S. pombe strains. New S. pombe strains in which the his3 gene was deleted have also been constructed.
dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD.

Apoptotic cell death occurs through activation of procaspases, the precursors of a group of aspartate-specific cysteine proteases known as caspases. Procaspase activation is mediated by death adapter proteins such as the mammalian proteins FADD and Apaf-1 and theCaenorhabditis elegans protein CED-4. These adapters bind to procaspases and facilitate oligomerization and subsequent auto-proteolytic processing of the zymogens. Here we report cloning and characterization of dFADD, a FADD homologue inDrosophila. dFADD contains a death domain that is highly homologous to the FADD death domain, and it also shares a novel domain with a Drosophila caspase DREDD, which we call death-inducing domain. dFADD binds to DREDD through the death-inducing domain and enhances the cell death activity and proteolytic processing of DREDD. dFADD and DREDD are stabilized by their interaction. The structural and functional similarities between dFADD and FADD suggest the existence of a FADD-like apoptosis pathway in Drosophila.
Herniation of Meckel's diverticulum into a ventriculoperitoneal shunt tract

Abstract We report a case of a 22-month old girl who presented with a ventriculoperitoneal shunt (VPS) infection, secondary to herniation of a perforated Meckel's diverticulum through a ventral abdominal wall defect from a previous VPS revision. This is the first description of the kind in the pediatric or surgical literature.
A theory for steady state creep based on the motion of interstitial type jogs

Abstract Another theory for steady state creep based on the thermally assisted motion of jogged screw dislocation is developed. This theory is based on the defendable premise that jogs on moving screw dislocation are mainly of interstitial emitting (or vacancy absorbing) type, and that activation energy for creep depends on mesh size of dislocation networks. The theory predicts low activation energy, on the order of that for vacancy self-diffusion, for creep of pure metals and single phase alloys. More interestingly, the theory predicts high activation energy, on the order of that for interstitial self-diffusion, for creep of particle strengthened engineering systems. The theory provides a very sharp stress dependence for creep of systems with high activation energies, and a less sharp stress dependence for creep of systems with low activation energies. The theory is discussed with respect to existing experimental results and found to be satisfactory.
Technology for Sex Selection: Current Status and Utilization

Research focusing on potential users of technology for sex selection and their preference for firstborn sons is reviewed in light of technological advances. Further study of personality characteristics of users is proposed as well as identification of interpersonal dynamics occurring within a couple having divergent preferences for sex of offspring.
Divergent and composite gonadotropin-releasing hormone-responsive elements in the rat luteinizing hormone subunit genes

GnRH pulses regulate gonadotropin subunit gene transcription in a frequency-dependent, subunit-specific manner. The alpha-subunit gene is stimulated by constant GnRH and by rapid to intermediate pulse frequencies, while stimulation of LHbeta subunit gene transcription requires intermediate frequency pulses. We have defined the GnRH-responsive elements of the rat LH subunit gene promoters by deletion/mutation analysis and transfection studies in rat pituitary cells and two clonal gonadotrope cell lines. The alpha-subunit gene GnRH-responsive region lies between -411 and -375 bp. The region contains two Ets-domain protein binding sites, and mutating either site obliterates the response. DNA protein binding studies demonstrate the two sites are not equivalent, and that Ets-1 does not mediate this response. Studies of the LHbeta promoter reveal a major GnRH-responsive region between -456 and -342 bp. Within this region, two Sp1 binding sites contribute to the GnRH response, and the 3'Sp1 site is also critical for basal expression. The 5'Sp1 site partially overlaps a CArG box, and mutating the CArG element specifically eliminates the response to pulsatile GnRH. DNA containing this mutation cannot form intermediate mobility complexes with nuclear proteins, but retains Sp1 binding. Mutation of the 3'Sp1 site and either the 5'Sp1 or CArG element partially restores GnRH stimulation, suggesting a downstream element contributes to the full GnRH response. These studies demonstrate that unique composite elements and transcription factors are responsible for GnRH stimulation of the LH subunit genes and may contribute to their differential responses to GnRH pulses.
Quantification of intraventricular hemorrhage with electrical impedance tomography using a spherical model

We have developed a robust EEG-based current pattern which shows promise for the detection of intraventricular hemorrhage (IVH) in neonates. Our reconstructions to date are based on a layered spherical head model. In this study, the current pattern was used to gather data from three realistic-shaped neonatal head models and a physical phantom based on one of these models. We found that a sensitivity matrix calculated from a spherical model gave us satisfactory reconstructions in terms of both image quality and quantification. Incorporating correct geometry information into the forward model improved image quality. However, it did not improve quantification accuracy. The results indicate that using a spherical matrix may be a more practical choice for monitoring IVH volumes in neonates for whom patient-specific models are not available.
Calibration and monitoring for crystal calorimetry

Crystal calorimetry provides excellent energy resolution in high energy and nuclear physics. The light output of heavy crystal scintillators, however, suffers from not negligible damage in radiation environment. A precision calibration and monitoring thus is crucial for maintaining crystal precision in situ. The performance of calibration and monitoring approaches used by BaBar, CLEO and L3 experiments are presented. The design and construction of a laser-based light monitoring system for CMS PWO calorimeter is also discussed.
Combined abdominal-perineal sonography to assist in diagnosis of transverse vaginal septum.

Background: Transperineal sonography has been used to detect incompetent cervices, placenta previa, cervical pregnancy, and vaginal and cervical atresia. Case: Transperineal sonography was used to investigate primary amenorrhea in a 14-year-old girl. A mid-transverse septum was found and confirmed surgically. Conclusion: Transperineal or translabial sonography assisted in the differentiation of primary amenorrhea, when adequate vaginal access was prohibited.
The lifetime of the OH radical in comets at 1 AU

It has been shown that the photochemical lifetime of OH in comets is a function of the comet's radial velocity. The calculated lifetime at 1 AU can vary between 69,000 and 210,000 sec for radial velocities that vary from -58 to +59 km/sec. A comparison between the scale lengths observed for three comets and those calculated based upon the theoretical lifetime has been made. This comparison shows that in two of the comets the lifetime derived from the scale lengths is a factor of 1.7 larger than the theoretical lifetime. Suggestions are made about the origin of this discrepancy.
Observations and measurements of sea urchin eggs with a centrifuge microscope.

Eggs of the sea urchins, Arbacia punctulata and Lytechinus variegatus were observed with a centrifuge microscope. The protoplasmic viscosity calculated from the displacement velocity of the nucleus in a centrifugal field is about 30 poises. The surface forces of the unfertilized egg, which were determined from the relationship between the deformations of the egg in centrifugal fields and the magnitudes of the centrifugal forces, are 0.046 dyne/cm in Arbacia and 0.087 dyne/cm in Lytechinus (mean values). Both of these values increase as the deformation of the egg increases. The cleavage plane of the first cleavage of the egg in the centrifugal field (35–140 × g) is parallel to the direction of the centrifugal force. The flattening of the fertilized egg in a constant centrifugal field changes during development, probably owing to the change in the surface force. The flattening attains a minimum shortly before the onset of cleavage and another minimum during the cleavage, corresponding to a peak of the surface before the cleavage and another peak during the cleavage.
Social Media: It’s What Students Do

In assessing the application of social media on the teaching of business communication, this article looks at MBA student use of blogs, online photo database contributions, and video contributions ...
Gender Differences in Responses to Sexual Coercion

Recent research has indicated that, although females comprise the majority of sexual assault victims, males may experience sexual coercion by a partner at a similar rate. This study of 734 college undergraduate students explores not only the frequency of sexual coercion victimization but the emotional responses to it. This study reveals that males and females report similar levels of victimization. However, females have more negative reactions to the experience. A large percentage of males report a positive emotional reaction to having been sexually coerced. This study explores possible explanations for these differences.
Optimized Geometries, Vibrational Frequencies, and Thermochemical Properties of Mixed Boron- and Nitrogen-Containing Three-Membered Rings

Abstract As a follow-up to our paper on a carbon–boron–nitrogen three-membered ring, we present here the predicted structures, vibrational frequencies, and thermochemical properties of all possible mixed boron- and nitrogen-containing rings. Of the seven possible compounds, we were able to characterize minimum-energy structures for four of them. G2, G3, CBS, and DFT methods were employed.
Antiretroviral Restriction Factors

Studies of retroviruses have been instrumental in revealing the existence of an array of antiviral proteins, or restriction factors, and the mechanisms by which they function. Some restriction factors appear to specifically inhibit retrovirus replication, while others have a broader antiviral action. Here, we briefly review current understanding of the mechanisms by which several such proteins exert antiviral activity. We also discuss how retroviruses have evolved to evade or antagonize antiviral proteins, including through the action of viral accessory proteins. Restriction factors, their viral targets and antagonists have exerted evolutionary pressure on each other, resulting in specialization and barriers to cross-species transmission. Potentially, this recently revealed intrinsic system of antiviral immunity might be mobilized for therapeutic benefit.
Spatial analysis of the relationship between housing values and investments in transportation infrastructure

The relationship between residential location, location value and accessibility has been of long interest to regional scientists. Studies investigating the relationship between house price and changes in accessibility, however, have been fewer in number, and predominantly have centered upon the house price impact of fixed rail investments. Neglected have been the impacts of smaller road investments made on a regular basis by municipalities and state departments of transportation. This research therefore reports on the spatial relationship between house price and investment in road-based transportation infrastructure by combining two spatial databases, both centered on Columbus, OH. The first contains information on all single-family detached houses sold in 1990. The second contains detailed spatial and temporal information on all accessibility-changing road investments in the same area, since 1978. Results indicate that while moderate, past, current and approved (but not begun) road investments have distinct and significant impacts on house price.
The Impact of Work Stressors on the Life Satisfaction of Social Service Workers: A Preliminary Study

During the past several decades, there has been an increase in the number of studies that have examined the impact of the work environment on social service employees. Much of this research has focused on how the work environment helps shape the job satisfaction, job stress, and burnout of workers. Very little research has been conducted on the impact of the work environment on the life satisfaction of employees of social service agencies. This study explored the effects of work stressors (e.g., job dissatisfaction, work-on-family conflict, family-on-work conflict, job stress, role ambiguity, role conflict, role overload, and dangerousness) on overall life satisfaction of employees of social service agencies, as well as the effects of life satisfaction on turnover intent. Multivariate analyses revealed that job dissatisfaction, work-on-family conflict, role ambiguity, and dangerousness had statistically significant effects on life satisfaction, and that age and life satisfaction had significant inverse re...
Shang Fa Yang: Pioneer in plant ethylene biochemistry

Shang Fa Yang was born in Taiwan in 1932. After receiving his B.S. and M.S. degrees in Agricultural Chemistry from the National Taiwan University, he came to the United States in 1958 to pursue a Ph.D. degree at Utah State University. Following three postdoctoral years, he was hired at the University of California, Davis, in 1966 where he was a biochemist and professor for 28 years. After retiring early from UC Davis, he subsequently established a research program at the Hong Kong University of Science and Technology and served as Vice President of Academia Sinica in Taiwan. Yang’s research achievements included discovering the biochemical pathway for the synthesis of ethylene by identifying the key steps by which S-adenosylmethionine (SAM) is converted into 1-aminocyclopropane-1-carboxylic acid (ACC) and subsequently into ethylene. Yang further demonstrated how the methylthio and ribose moieties from SAM were recycled back into methionine in order to sustain high rates of ethylene synthesis, as in ripening fruits. This recycling pathway is now known as the Yang Cycle. Yang also contributed to the isolation, characterization and cloning of ACC synthase and ACC oxidase, the two enzymes in the ethylene biosynthetic pathway, and to the elucidation of their structure and reaction mechanisms. He made important contributions to auxin, cytokinin, cyanide and sulfur metabolism in plants as well. His work formed the basis for subsequent research that has established ethylene as the most thoroughly characterized of the hormonal biosynthesis and signaling pathways in plants. # 2008 Elsevier Ireland Ltd. All rights reserved.
Looking closer: forensic nursing

With a keen eye, you can foster comprehensive care to victims; protect your organization from allegations of abuse, negligence, and malpractice; and offer a care environment that recognizes the complexities of our current society.
Epicuticular wax load and water-use efficiency in bloomless and sparse-bloom mutants of Sorghum bicolor L.

Abstract A mutation breeding approach was utilized to obtain near-isogenic lines of sorghum [Sorghum bicolor (L.) Moench.] with altered epicuticular wax. Seeds of three bloomless mutants (bm-15, bm-22 and bm-38) and one sparse-bloom mutant (h-19) were obtained from the M4 generation, and responses of mutants were compared to their corresponding normal, non-mutant sib lines (designated N-15, N-22, N-38 and N-19). Net CO2 assimilation rate, stomatal conductance, transpiration rate and water-use efficiency were measured on the uppermost, fully expanded leaves in irrigated and non-irrigated 43-day-old plants using a LiCor LI-6200 portable photosynthesis system. Epicuticular wax load (EWL) and cumulative water loss from excised leaves (CWL) were measured, and the relationships among EWL, CWL and water-use efficiency were assessed. Differences in response to irrigation level varied among the four lines. Among irrigated plants, h-19 exhibited a higher water-use efficiency than N-19. Among non-irrigated plants, bm-15, bm-22 and h-19 exhibited lower water-use efficiencies than N-15, N-22 and N-19, respectively. Water-use efficiency measured in non-irrigated bm-22, a mutant line with no visible wax structures on the abaxial leaf surface, was more than 40% below that measured in N-22. The water loss from excised leaves was greater in bloomless and sparse-bloom lines than in normal lines. Water-use efficiency varied linearly with epicuticular wax load under irrigated (r = 0.72) and non-irrigated (r = 0.94) conditions.
Study of evaporation and recharge in desert soil using environmental tracers, New Mexico, USA

The purpose of this study is to investigate the rates and mechanisms of recharge and evaporation in soils of a desert environment using two environmental tracers (chloride and oxygen-18). The profiles of chloride concentration and oxygen-18 enrichment in soil-water, together with the depth distribution of water content in soil, reveal information about long-term recharge and instantaneous evaporation processes without needing to know the physical properties of the soil. Three holes were hand-augured, in different desert settings in southeastern New Mexico. The chloride concentration profiles were used, with the chloride mass balance method, to estimate long-term recharge rates in these three holes as 0.5, 0.8, and 2.4 mm yr–1. Analysis using a bimodal flow and transport model shows that possibly 85% of the recharge occurs via movement of water through preferred pathways in the root zone. Preferential flow was evident in all three sampling sites. Clay layers have a noticeable effect on the development of water content distribution and thus on oxygen-18 enrichment and chloride concentration profiles. The spatial variation in clay layering partly explains the variation in recharge rate estimates.
Width-increased dual-pump enhanced coherent anti-Stokes Raman spectroscopy

Width-increased dual-pump enhanced coherent anti-Stokes Raman spectroscopy (WIDECARS) is a technique that is capable of simultaneously measuring temperature and species mole fractions of N(2), O(2), H(2), C(2)H(4), CO, and CO(2). WIDECARS is designed for measurements of all the major species (except water) in supersonic combustion flows fueled with hydrogen and hydrogen/ethylene mixtures. The two lowest rotational energy levels of hydrogen detectable by WIDECARS are H(2) S(3) and H(2) S(4). The detection of these lines gives the system the capability to measure temperature and species concentrations in regions of flow containing pure hydrogen fuel at room temperature.
Controlling the Location of Nanoparticles in Colloidal Assemblies of Amphiphilic Polymers by Tuning Nanoparticle Surface Chemistry

Here, we report a simple method to control the location of nanoparticles in colloidal block-copolymer assemblies by using nanoparticles modified with mixed surface ligands. The binary self-assembly of amphiphilic polymers of polystyrene-b-poly(acrylic acid) (PS-b-PAA) and gold nanoparticles (AuNPs) modified with a hydrophobic ligand, dodecanethiol (DT), led to polymer micelles with nanoparticles segregated in the core of polymer micelles. On the other hand, AuNPs modified with mixed ligands of mercaptoundecanol (MUL) and DT were distributed at the PS–PAA interface, reducing the interfacial energy between the two polymers. This result was in good agreement with the prediction by the surface energy calculations. We also showed that the AuNPs with mixed ligands can decorate preformed polymer assemblies by the interfacial self-assembly. Furthermore, we demonstrated the compartmentalization of two different types of nanoparticles in colloidal polymer assemblies based on the strategy.
Dispositional Mindfulness Co-varies with Self-Reported Positive Reappraisal

Emerging research suggests that mindfulness is associated with positive reappraisal and that mindfulness practice may be a means of encouraging positive reappraisal capacities. These findings, linking mindfulness with the promotion of cognitive coping strategies, challenge traditional Western conceptualizations of mindfulness as non-discursive. This study explored the relationship between dispositional mindfulness and self-reported positive reappraisal across five distinct samples: a general sample of American adults, contemplative practitioners, college students chronic pain outpatients, and alcohol dependent inpatient. Results indicate that dispositional mindfulness is positively related with self-reported positive reappraisal in all five studies as well as in an aggregated analysis combining all five studies. Furthermore, a second set of analyses statistically controlling for factors previously associated with positive reappraisal (i.e., psychological well-being, positive affect, and positive refocusing), provided evidence that mindfulness is uniquely associated with self-reported positive reappraisal. While more research is needed to refine our understanding of the relationship between mindfulness and positive reappraisal, the present investigation contributes to the growing evidence base supporting the hypothesized link between dispositional mindfulness and self-reported reappraisal by demonstrating a significant association between these constructs across a variety of samples and in the largest combined dataset on this phenomenon collected to date (N=819).
Contractile agonists preferentially activate CL- over K+ currents in arterial myocytes.

Abstract Simultaneous patch-clamp and Ca 2+ fluorescence measurements have revealed depolarising oscillations in the membrane potential of arterial (pulmonary) myocytes in response to adenosine 5′-triphosphate (ATP) and endothelin-1 (ET-1). These oscillations (i) are due to the preferential activation of Ca 2+ -activated Cl − , over K + currents, (ii) occur through a mechanism involving Ca 2+ release from intracellular Ca 2+ stores and (iii) are likely to promote constriction. These results provide a novel perspective into the relative contribution and importance of Ca 2+ activated Cl − and K + channels in controlling membrane potential of arterial smooth muscle in response to contractile agonists.
Biology of the histones

Abstract The biological roles of the histones are multiple; by complexing to DNA they cause such DNA to be inactive as a template for RNA polymerase; they cause supercoiling of the DNA which would appear to be a fundamental requirement for further orders of supercoiling, presumable exemplified by metaphase chromosomes; a particular histone even forms interpolypeptide disulfide bridges during metaphase, apparently stabilizing the chromosomes in a highly condensed state. It is no doubt because of this multiplicity of functions that the primary structure of the individual histone species has been conserved to an extraordinary degree since the time of the common ancestor of the higher eukaryotes.
Amino-Terminal Pro–Brain Natriuretic Peptide, Brain Natriuretic Peptide, and Troponin T for Prediction of Mortality in Acute Heart Failure

Background: Combining testing for natriuretic peptides [amino-terminal pro–brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)] and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF). Methods: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation. Results: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year ( P <0.001 and P <0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 μg/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point ( P <0.001). Mortality rates were low (<4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P <0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CI), 3.06–17.8; BNP plus cTnT: HR, 6.82; 95% CI, 2.99–16.5]. Conclusions: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HF.
Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca × P product less than 55 mg2/dL2. Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca × P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.
Flow cytometric DNA analysis as a diagnostic aid for cervical condyloma and cancer

Flow cytometric DNA analysis data (FCDA) were obtained from 324 samples provided through the Gynecology-Oncology Clinic. These samples consisted of 294 combined endoectocervical and vaginal smears and 30 peritoneal washings. Using a conventional scheme for G0/G1, S + G2/M and the coefficient of variation with computer correction for the cell-cycle kinetics, it was possible to assign a diagnostic Class I, II, III or V similar to that used by the Cytology Laboratory. These data were then compared with the histopathologic and colposcopic diagnoses. The correlation between FCDA and cytologic results were essentially similar to the previous data obtained from only endocervical sampling. The most interesting finding in this study was the recognition of an FCDA pattern showing a higher DNA content in the G0/G1 and the early S regions in 70 of 94 (74.5%) of samples from patients with condyloma acuminata. All condyloma samples were diagnosed either by cytologic, histopathologic, or colposcopic examination, or a combination of two or three. All biopsy specimens were then reviewed by one pathologist to verify any discrepancies. The relationship of this pattern to the viral etiology of this disease is discussed with the three methods of diagnosis and electron microscopic observations. It is suggested that, based on this study. FCDA analysis of pap smears may also be useful in determining the presence of condyloma in a gynecology clinic. The potential value of FCDA analysis from peritoneal washings for the diagnosis of gynecologic cancer can not be ascertained in this preliminary investigation because of insufficient samples.
Heritability of event-related brain potentials in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Estimates of heritability are presented for amplitude and latency of the N1 and P3 components of the ERP measured at 19 scalp locations in response to visual and auditory stimuli for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. Significant heritabilities were found for visual P3 amplitude in response to all stimuli and for visual P3 latency in response to target and novel, but not non-target, stimuli. Heritability of visual N1 latencies was uniformly low, whereas heritability of visual N1 amplitude was significant for all electrodes in response to the non-target stimuli but only for posterior electrodes in the other two stimulus conditions. Heritabilities for auditory target P3 were similar to those of the visual stimuli, with auditory target P3 amplitudes and latencies both demonstrating significant heritability. For auditory P2 in response to non-target stimuli, peak amplitude was heritable, but latency was not. Auditory N1 amplitude and latency were significantly heritable for both target and non-target conditions and did not demonstrate the anterior/posterior patterning obtained for visual N1 amplitude. This study represents the first systematic assessment of heritability of these potential neurophysiological markers in families with a history of alcoholism and suggests that many of these ERP phenotypes have heritabilities strong enough to justify genomic screening for loci jointly influencing ERP abnormalities and liability to alcoholism.
Principles of Cerebrovascular Disease

Harold P. Adams, Jr, MD 564 pages. New York, NY: McGraw-Hill; 2006. $159.00. ISBN 0071416536 In the decade since the US Food and Drug Administration approved intravenous thrombolysis, the use of evidence-based therapy in the treatment of stroke patients has become increasingly prevalent. This has occurred because of the growing weight of evidence-based medicine in general and the increased availability of clinical studies in stroke outcomes in particular. As a consequence, guidelines set by the American Heart Association influence modern stroke management more than at any time in the past. Emphasis continues to shift from an understanding of the underlying concepts of cerebrovascular pathology to the delivery of care to the patient. Published studies that show that dedicated stroke units improve patient outcomes have led the American Heart Association to encourage the integration of different disciplines of health care into independent stroke centers. The comprehensive stroke center as a distinct service, physically separate within the hospital, has arisen as the model for modern stroke treatment. As multidisciplinary entities, the efficacy of these centers depends not on whether they are staffed by neurologists or internists, but on whether the attending physicians have a broad knowledge of all facets of stroke management. To oversee such a program requires training in rehabilitation and prevention as well as emergency management and intensive care. The recent Accreditation Council for Graduate Medical Education accreditation of stroke training programs and board certification in …
Genomic Landscape of a Three-Generation Pedigree Segregating Affective Disorder

Bipolar disorder (BPD) is a common psychiatric illness with a complex mode of inheritance. Besides traditional linkage and association studies, which require large sample sizes, analysis of common and rare chromosomal copy number variants (CNVs) in extended families may provide novel insights into the genetic susceptibility of complex disorders. Using the Illumina HumanHap550 BeadChip with over 550,000 SNP markers, we genotyped 46 individuals in a three-generation Old Order Amish pedigree with 19 affected (16 BPD and three major depression) and 27 unaffected subjects. Using the PennCNV algorithm, we identified 50 CNV regions that ranged in size from 12 to 885 kb and encompassed at least 10 single nucleotide polymorphisms (SNPs). Of 19 well characterized CNV regions that were available for combined genotype-expression analysis 11 (58%) were associated with expression changes of genes within, partially within or near these CNV regions in fibroblasts or lymphoblastoid cell lines at a nominal P value <0.05. To further investigate the mode of inheritance of CNVs in the large pedigree, we analyzed a set of four CNVs, located at 6q27, 9q21.11, 12p13.31 and 15q11, all of which were enriched in subjects with affective disorders. We additionally show that these variants affect the expression of neuronal genes within or near the rearrangement. Our analysis suggests that family based studies of the combined effect of common and rare CNVs at many loci may represent a useful approach in the genetic analysis of disease susceptibility of mental disorders.
Stable-isotope geochemistry of saline near-surface ground water: East-central Michigan basin

Near-surface (<100 m) ground water in east-central Michigan basin is characterized by high total dissolved solids (100 to 53,000 mg/l). The source of the salinity and the cause of its distribution are unclear. The hypothesis investigated was that the source of the salinity is brines advecting or diffusing upward into near-surface meteoric water, and the cause of the salinity distribution is the slow flushing of water in the argillaceous sediments by recent meteoric water. δ18O, δD, δ13C, δ34S, 3H, and selected geochemical variables were studied in the glacial-drift and bedrock aquifers composing the ground-water system. The following isotopic ranges were found: δ18O, 6.93‰ to -18.46‰ δD, -47.3‰ to -137.4‰ δ13C, -6.26‰ to -20.65‰ and δ34S, +3.56‰ to +67.44‰. δ18O and δD plot along the meteoric-water line, and most are extremely light. δ13C is skewed to lighter values, and δ34S becomes heavier with decreasing dissolved SO4 concentration. The results are interpreted to indicate that the saline ground water is a mix of modern-day, meteoric water and water that recharged the aquifers at a time when the climate was much cooler. The cause of the salinity distribution is the slow flushing of the aquifers by present-day recharge water. The source of the salinity could be the upward diffusion or advection of Michigan basin formation water, but this has not been confirmed. Microbial reduction of SO4 is occurring, affecting the concentrations of SO4 and HCO3 and the values of δ13C and δ34S.
Creation of a shikimate pathway variant.

The competition between the Escherichia coli carbohydrate phosphotransferase system and 3-deoxy-d-arabino-heptulosonate 7-phosphate (DAHP) synthase for phosphoenolpyruvate limits the concentration and yield of natural products microbially synthesized via the shikimate pathway. To circumvent this competition for phosphoenolpyruvate, a shikimate pathway variant has been created. 2-Keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolases encoded by Escherichia coli dgoA and Klebsiella pneumoniae dgoA are subjected to directed evolution. The evolved KDPGal aldolase isozymes exhibit 4−8-fold higher specific activities relative to that for native KDPGal aldolase with respect to catalyzing the condensation of pyruvate and d-erythrose 4-phosphate to produce DAHP. To probe the ability of the created shikimate pathway variant to support microbial growth and metabolism, growth rates and synthesis of 3-dehydroshikimate are examined for E. coli constructs that lack phosphoenolpruvate-based DAHP synthase activity and rely ...
Secondary structure and dynamics of micelle bound β- and γ-synuclein

We have used solution state NMR spectroscopy to characterize the secondary structure and backbone dynamics of the proteins β- and γ-synuclein in their detergent micelle-bound conformations. Comparison of the results with those previously obtained for the Parkinson's disease-linked protein α-synuclein shows that structural differences between the three homologous synuclein family members are directly related to variations in their primary amino acid sequences. An 11-residue deletion in the lipid-binding domain of β-synuclein leads to the destabilization of an entire segment of the micelle-bound helical structure containing the deletion site. The acidic C-terminal tail region of γ-synuclein, which displays extensive sequence divergence, is more highly disordered than the corresponding regions in the other two family members. The observed structural differences are likely to mediate functional variations between the three proteins, with differences between α- and β-synuclein expected to revolve around their lipid interactions, while differences in γ-synuclein function are expected to result from different protein–protein interactions mediated by its unique C-terminal tail.
Level of kidney function as a risk factor for cardiovascular outcomes in the elderly.

Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Background There is a high prevalence of both reduced kidney function as well as cardiovascular disease (CVD) in the elderly. We evaluated whether the level of kidney function is an independent risk factor for CVD outcomes in the Cardiovascular Health Study (CHS), a cohort of subjects whose age at baseline was 65 years old or older. Methods Cox proportional-hazards regression was used to evaluate the association of predicted glomerular filtration rate (GFR) with CVD after adjustment for the major CVD risk factors. We searched for nonlinear relationships between GFR and CVD, as well as interactions between level of kidney function and major CVD risk factors on CVD. Results A total of 4893 subjects with predicted GFR of 15 to 130 mL/min/1.73 m 2 were included in the analysis. Fifty-six percent were female and the mean age was 73.4 years. Of the subjects, 549 (11.2%) died and 1229 (25.1%) experienced CVD events in 5.05 years of follow-up. Each 10 mL/min/1.73 m 2 lower GFR was associated with an adjusted hazard ratio for CVD, de novo CVD, recurrent CVD and all-cause mortality of 1.05 (1.02, 1.09), 1.07 (1.01, 1.12), 1.04 (0.99, 1.09), and 1.06 (1.00, 1.12), respectively. There was no significant interaction between level of GFR and other traditional CVD risk factors on CVD outcomes. A linear model best described the relationship between GFR and CVD. Conclusion The level of GFR is an independent risk factor for CVD, de novo CVD, and all-cause mortality in the elderly.
Going beyond heart rate: autonomic space and cardiovascular assessment of mental workload.

Psychophysiological assessment of pilot mental workload using heart rate should be augmented with an autonomic space model of cardiovascular function. This model proposes that autonomic nervous system influences on the heart may change with psychological processing in ways that are not evident in heart rate. A method of mental-workload assessment was proposed that used multiple psychophysiological measures of cardiovascular responsivity to derive the underlying sympathetic and parasympathetic information needed to represent the autonomic space for heart rate. Principal-components analysis was used to extract Sympathetic and Parasympathetic components from heart period, residual heart period, respiratory sinus arrhythmia, and Traube-Hering-Mayer wave in three experiments that manipulated perceptuallcentral processing and physical task demands. This initial evaluation of the method concluded that the autonomic components were valid and that the components had greater diagnosticity, and for some manipulation...