cssi/SciSciGPT-SciSciNet huggingface dataset:
Electron spin resonance investigation of the interaction of the anion and glucose transport inhibitor, p-azidobenzylphlorizin, with the human red cell membrane

The membrane perturbations caused by the interaction of p-azidobenzylphlorizin (p-AzBPhz), a potential photoaffinity labeling agent of the anion and D-glucose transporters in the human erythrocyte, have been studied using electron spin resonance (ESR) spectrometry. Two lipid-specific spin labels have been employed; one of these agents, a hexadecyl-quarternary amine with the nitroxide reporter group covalently attached to the cationic nitrogen, (CAT-16), has been used to monitor changes in the physical state of the membrane's extracellular phospholipid/water interface. The other spin label, 5-doxylstearic acid (5-NS), is designed to examine the order and motion of the lipid bilayer near the cell surface. In separate experiments, intact human red cells labeled with these lipid-specific spin labels were exposed to small amounts of the phlorizin azide. A dose-dependent alteration in CAT-16 motion was observed, but the p-AzBPhz interaction with the membrane had no effect on the spectrum of 5-NS. The half-maximal effect of the phlorizin derivative on the CAT-16 spectrum occurred when about 2 million molecules were bound to each cell. This is also the combined amount of band 3 and band 4.5 present in the red cell membrane and represents the concentration necessary to inhibit both anion and glucose transport. Our results suggest that the first p-AzBPhz molecules binding to the red cell membrane interact with the anion and sugar transporters, and not with the bulk lipid bilayer.
Influence of fracture criteria on the outcome of a randomized trial of therapy

Based on a presumption that the morphometric approach to vertebral fracture assessment is beset by false positive deformities, it has been suggested that more stringent criteria should be used to assess vertebral fracture outcomes in clinical trials of osteoporosis therapies. We applied a variety of criteria in the reanalysis of a randomized trial of sodium fluoride therapy for women with established osteoporosis. Although progressively more severe criteria reduced the cumulative incidence of a new vertebral fracture in both those receiving a placebo and the fluoride-treated patients, differences between the two groups were not magnified and none of the suggested approaches produced a statistically significant result. These findings indicate that the false positive rate associated with morphometric assessment of vertebral fractures is not so great as supposed from theoretical considerations that assume independence among the measurements. Our findings also provide some reassurance that differences in the criteria used to define a vertebral fracture are not the controlling influence in the likelihood that a particular clinical trial will find a result favoring one treatment over another.
Specificity Protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B

N-Methyl-d-aspartate (NMDA) receptors are major glutamatergic receptors involved in most excitatory neurotransmission in the brain. The transcriptional regulation of NMDA receptors is not fully understood. Previously, we found that the GluN1 and GluN2B subunits of the NMDA receptor are regulated by nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2). NRF-1 and NRF-2 also regulate all 13 subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme, thereby coupling neuronal activity and energy metabolism at the transcriptional level. Specificity protein (Sp) is a family of transcription factors that bind to GC-rich regions, with Sp1, Sp3, and Sp4 all binding to the same cis- motifs. Sp1 and Sp3 are ubiquitously expressed, whereas Sp4 expression is restricted to neurons and testicular cells. Recently, we found that the Sp1 factor regulates all subunits of COX. The goal of the present study was to test our hypothesis that the Sp factors also regulate specific subunits of NMDA receptors, and that they function with NRF-1 and NRF-2 via one of three mechanisms: complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel. By means of multiple approaches we found that Sp4 functionally regulated GluN1, GluN2A, and GluN2B, but not GluN2C. On the other hand, Sp1 and Sp3 did not regulate these subunits as previously thought. Our data suggest that Sp4 operates in a complementary and concurrent/parallel manner with NRF-1 and NRF-2 to mediate the tight coupling between energy metabolism and neuronal activity at the molecular level.
Finding the dominant energy transmission paths in statistical energy analysis

A key issue for noise, vibration and harshness purposes, when modelling the vibroacoustic behaviour of a system, is that of determining how energy is transmitted from a given source, where external energy is being input, to a target where energy is to be reduced. In many situations of practical interest, a high percentage of the transmitted energy is driven by a limited set of dominant paths. For instance, this is at the core of the existence of transmission loss regulations between dwellings. In this work, it is shown that in the case of a system modelled with statistical energy analysis (SEA), the problem of ranking dominant paths can be posed as a variation of the so-called K shortest path problem in graph theory. An algorithm for the latter is then modified and adapted to obtain the sorted set of K dominant energy transmission paths in a SEA model. A numerical example to show its potential for practical applications is included.
Reticulosis of the visual system in a dog

A 7-year-old male Kerry Blue Terrier had been compensating for a visual deficit for approximately 2 months. Five days before examination, the dog had suddenly lost all vision and the pupils had become widely dilated and unresponsive to light. Ophthalmic examination revealed inflammation of the optic discs. Response to therapy was favourable but temporary. Post mortem findings consisted of granulomatous optic neuritis, meningoencephalitis and chorioretinitis, similar to reticulosis.
A field experiment in avian taphonomy

ABSTRACT Decay, disarticulation, damage, and transport of 28 carcasses of rock dove (Columba livid), ring-billed gull (Larus delawarensis), and herring gull (Larus argentatus) were studied on a stream floodplain in Maryland. Scavengers removed from the site nearly all specimens not placed in protective cages. Specimens which were not soon removed or which were placed in cages became firmly stuck to the ground within several days, and subsequent floods failed in most cases to change the positions of the carcasses or even of individual, disarticulated bones. One gull, washed into the stream and buried while still feathered and articulated, showed disarticulation and reorientation of bones. Tracks found in the mud over the buried carcass suggested trampling by racoons and dogs as a possible explanation for the changes. The length of time until complete disarticulation of a skeleton ranged from 13 days to six months. The sequence of disarticulation also showed great individual variation, although some pattern...
Personal and Cultural Adjustments Involved with an Oxford Study Abroad Experience

We report the results of a qualitative research study from in-depth interviews with 23 American students’ responses to a study abroad experience at New College, Oxford University (U.K.). Two primary themes are reported here from the analysis of students’ transcripts: maturity development and personal development. Maturity development said to have been stretched through new experiences and increased independence. Personal development was enhanced via expanded horizons and the indelible impression that was left with students following the SA experience.
Nucleolin is one component of the B cell-specific transcription factor and switch region binding protein, LR1.

LR1 is a B cell-specific, sequence-specific DNA binding activity that regulates transcription in activated B cells. LR1 also binds Ig heavy chain switch region sequences and may function in class switch recombination. LR1 contains two polypeptides, of 106 kDa and 45 kDa, and here we report that the 106-kDa component of LR1 is nucleolin. This identification, initially made by microsequence analysis, was verified by showing that (i) LR1–DNA binding activity increased in B cells transfected with a nucleolin cDNA expression construct; (ii) LR1–DNA binding activity was recognized by antibodies raised against recombinant human nucleolin; and (iii) in B cells transfected with epitope-tagged nucleolin expression constructs, the LR1–DNA complex was recognized by the anti-tag antibody. Nucleolin is an abundant nucleolar protein which is believed to play a role in rDNA transcription or organization, or rRNA processing. Homology between nucleolin and histone H1 suggests that nucleolin may alter DNA organization in response to cell cycle controls, and the nucleolin component of LR1 may therefore function to organize switch regions before, during, or after switch recombination. The demonstration that nucleolin is a component of a B cell-specific complex that binds switch region sequences suggests that the G-rich switch regions may have evolved from rDNA.
Founders and Foundresses: Revising the History, of a Kenyan Independent Church1

Abstract The Roho, or Holy, Spirit churches of Nyanza Province in Western Kenya spring from a charismatic Christian movement that emerged among the Luo during the colonial era. This article uses life narratives of active Roho participants to counter-balance existing historical literature which draws heavily on colonial records. Oral sources call into question the ‘top-down’ paradigm of schism that has dominated the discussion of African independent Christianity and emphasize the role of women in the evolution and expansion of the Roho church. This article also traces the gradual transformation of women’s involvement from the early years when—incorporating indigenous patterns of female spirit mediumship—women acted as soldiers and pastors to the present condition of Western-style institution and limited leadership opportunities for women.
Numerical simulations of the growth and deflection of a stress-corrosion notch on the interface between two reactive solids

A front-tracking finite element method is used to compute the evolution of a crack-like defect that propagates along a bi-material interface by stress driven corrosion. Depending on material properties, loading, and temperature, simulations predict five possible behaviors for the flaw: (a) The notch may blunt, so that a fatigue threshold exists for the composite; (b) The flaw may branch out of the interface, and thereafter propagate as a stable notch; (c) The notch may branch out of the interface, and then progressively sharpen at its tip, with both the notch tip curvature and stress approaching unbounded values; (d) The flaw may propagate as a stable notch parallel to the interface; (e) The notch may propagate parallel to the interface, but with the tip curvature and stress progressively increasing without limit. The range of material parameters and loading conditions that leads to each type of behavior is calculated. For conditions where steady-state interfacial notch growth occurs, the tip velocity is computed as function of material and loading.
East–west, ancient–modern relations at the rubin museum, nyc

(2012). East–west, ancient–modern relations at the rubin museum, nyc. Material Religion: Vol. 8, No. 1, pp. 119-121.
Predicting sick building syndrome at the individual and aggregate levels

Abstract A sample of 4479 workers from 27 air conditioned office buildings completed a questionnaire on environmental conditions, sick building syndrome (SBS) symptoms, job satisfaction, job stress, and occupational and personal information while indoor air quality measures were taken. Indoor air quality met current American Society of Heating, Refrigerating, and Air-conditioning Engineers, Inc. (ASHRAE) guidelines in all buildings. Logistic regression analyses conducted for individual symptoms revealed environmental correlates for workers' reports of environmental conditions, but few environmental correlates for reports of SBS symptoms. The number of SBS symptoms per worker was related linearly to computer use, job stress, job satisfaction, number of allergies, migraine, and eye wear, with separate intercepts necessary for each gender and interactions of gender with age and perceived indoor air quality (PIAQ). Allergy did not replace gender in the regression equations. Effects of environmental conditions and SBS symptoms on work disruption were assessed.
Laminar Natural Convection under Nonuniform Gravity

Laminar natural convection is analyzed for cases in which gravity varies with the distance from the leading edge of an isothermal plate. The study includes situations in which gravity varies by virtue of the varying slope of a surface. A general integral solution method which includes certain known integral solutions as special cases is developed to account for arbitrary position-dependence of gravity. A series method of solution is also developed for the full equations. Although it is more cumbersome it provides verification of the integral method.
Reconstruction of alveolar bone defects after extraction of mandibular third molars: A pilot study

Abstract Introduction A documented complication of mandibular third molar extraction is the development of bony defects on the distal aspect of the adjacent second molar. The primary study purpose was to determine the efficacy of grafting third molar extraction sites with demineralized bone powder to prevent the formation of periodontal defects. Material/Methods With a randomized clinical trial study design and a third molar extraction surgical model, we enrolled a study sample composed of patients who required extraction of bilateral third molars. Demineralized bone powder was placed in one randomly selected extraction site per patient. The remaining extraction site served as a control. Patients served as their own controls. To assess periodontal healing, we measured plaque and gingival indexes and periodontal attachment loss on the distobuccal aspect of the adjacent second molar preoperatively and 6 months postoperatively. Results Of 14 patients enrolled, 7 patients with a mean age of 21.7±3.7 years completed the study protocol. No statistically significant differences were noted between patients who did and did not complete the study protocol (all p values ≥0.42). There were no statistically significant differences for the various anatomic, operative, or periodontal measures between the control and treatment teeth preoperatively (all p values ≥0.46). Six months postoperatively, there were no statistically significant changes in the plaque or gingival indexes for the control or experimental sites. At the control sites, there was a nonstatistically significant decrease in mean attachment loss from 3.1±1.3 mm preoperatively to 1.4±1.6 mm 6 months postoperatively ( p =0.06). At experimental sites, there was a statistically significant decrease in mean attachment loss from 3.3±1.4 mm preoperatively to 0.6±0.8 mm 6 months postoperatively ( p =0.02). Conclusions The study results suggest that demineralized bone powder may decrease attachment loss on the distal aspect of the second molar after extraction of the adjacent third molar. Additional studies are indicated to confirm the results of this pilot study. We recommend that future studies limit their study samples to patients at high risk for developing periodontal defects after third molar extraction.
Effects of solution mass transport on the ECC ozonesonde background current

Measurement of the mass transport rate constant for the electrochemical concentration cell in an ozonesonde as a function of the pressure is reported. The investigation was performed to accurately model the residual current present in the ECC cell in the absence of ozone. The convective mass transport for two sondes were determined while maintaining a sufficiently negative cathodic potential to eliminate electron transfer at the cathode surface. A sonde was placed in a bell jar and subjected to varying pressure levels. When the background current was kept below 0.1 microamp and pressure was from 100-1000 mb, the necessary correction term for the pressure was independent of pressure. However, below 100 mb, a logarithmic decrease in the background current with pressure is expected. Present practices, involving a sensitivity to oxygen, are calculated to result in overestimation of the total ozone between 1000-10 mb by 0.0096 atm-cm with a background current of 0.1 microamp at 1000 mb.
Potential role of recombinant human erythropoietin in the peri-surgical setting

Abstract For patients participating in autologous blood programs, one factor influencing the likelihood of homologous blood exposure is the number of available autologous units. To study the role of human recombinant erythropoietin (rhEpo) in increasing the amount of autologous blood that can be obtained prior to surgery, we conducted a randomized double-blind controlled trial of rhEpo in 47 adult patients scheduled for elective orthopedic procedures. Patients received either rhEpo (600 U/kg) or placebo i.v. twice weekly over a 21-day study period, during which up to six units of blood were collected. Patients were deferred from donation for hematocrit less than 34%. All patients received FeSO4, 325 mg orally three times daily. The mean number of units collected was 5.4 +/- 0.2 and 4.1 +/- 0.2 (mean +/- SE) for the rhEpo and placebo patients, respectively. Mean red blood cell volume donated by rhEpo patients was 41% greater than placebo patients (961 ml vs. 683 ml, p less than 0.05) Only one of 23 patients (4%) treated with rhEpo were unable to donate greater than or equal to 4 U, compared to seven of 24 (29%) placebo patients. No adverse effects were attributed to rhEpo. We conclude that rhEpo is efficacious in increasing autologous blood donated in elective surgical patients.
Safety evaluation of topically applied amitriptyline in porcine full-thickness wounds.

Background and Objectives: The tricyclic antidepressant amitriptyline is frequently used in pain clinics for management of pain. It has also been suggested that topical application of amitriptyline could be useful for the treatment of neuropathic pain. In this report we investigated the effect of amitriptyline on porcine full thickness wounds resembling excised burn wounds. We assessed if daily topical application of amitriptyline into the wound chambers for 10 days impedes wound healing as measured by (1) wound contraction and (2) histopathological findings. Methods: Full-thickness wounds measuring 1.5 cm square were created on the dorsum of Yorkshire pigs and were enclosed in polyurethane wound chambers. Amitriptyline was applied daily at various concentrations. Bupivacaine (0.5%) or normal saline were used as controls. Daily wound serum levels were obtained and the level of amitriptyline and nortriptyline obtained. Pictures were taken daily and the wound surface analyzed for contraction. Cross-sectional, full-thickness skin biopsies were obtained at days 2, 8 and 10 and evaluated microscopically for re-epithelialization, inflammation, and necrosis. Results: The high serum level of amitriptyline and nortriptyline did not affect wound healing; re-epithelialization, wound contraction, and inflammation were not significantly different between amitriptyline and control groups. Conclusion: Amitriptyline at the concentrations of 0.0625% and 0.125% applied daily via chambers covering wounds in a full-thickness pig excision model has no overt toxic effect on wound healing as measured by wound contraction and histological assessment.
New approaches to bridge nerve gaps: Development of a novel drug-delivering nerve conduit

Contemporary bridging techniques for repairing nerve gaps caused by trauma require autologous nerve grafts, which are difficult to harvest and handle and result in significant donor site deficit. Several nerve conduits with axon growth-enhancing potential have been proposed, developed and tested over the past fifteen years. In this work, prototypes of a nerve conduit designed to bridge large nerve gaps (≥10mm) end-to-end were incorporated with concentric drug reservoirs for constant and controlled drug delivery to enhance axon growth. These devices were designed, fabricated and tested in vitro in amber glass vials with bovine serum albumin in order to determine the drug release kinetics for future application. Our devices have shown the capability to deliver the drug of interest over a 6-day period.
Purification and plasticity of human cord blood mesenchymal stem cells

Human cord blood is well known to contain hemapoetic stem cells capable of differentiating into blood related cell types. However, it is possible to derive another type of stem cell, referred to as a stromal, or in this study, mesenchymal stem cells, which are capable of producing other differentiated cell types which can include fat, muscle, bone and cartilage. It has also become apparent that neural cells can be derived from mesenchymal stem cells taken from bone marrow, another source like cord blood, of both hemapoetic and mesenchymal stem cells. Recently, Sanchez-Ramos and coworkers published a study demonstrating that mesenchymal stem cells from total nucleated cord blood differentiate into cells expressing neural antigens. This work indicated the potential of this starting material as a valuable therapeutic source of human neural progenitors. Derivation and definition of these cord blood derived neural cells is unclear since the antigenic characterization of the cord blood mesenchymal stem cells still remains unknown. In this study we are using stem cell antigens such as CD34, CD90, CD117, CD133, to identify the cellular pool of cord blood mesenchymal stem cells and purify them using positive magnetic bead selection. Each population will be antigenically tested for their ability to differentiate into neural cells using defined culture conditions previously used to generate neural cells from multipotent starting material such as; ES cells; bone marrow mesenchymal stem cells; and CNS-derived multipotent neural stem cells.
Mammary transfer of vitamin A alcohol and ester in lactating dairy cows.

Abstract The effect of intravenous injection of vitamin A alcohol and vitamin A ester on the vitamin A concentration of bovine milk was studied. Holstein cows received either an intravenous injection of 1million international units (IU) of vitamin A alcohol, 1million international units of vitamin A palmitate, or served as controls. Blood serum and milk were sampled at intervals prior to and following injection. Mean concentrations of vitamin A in milk at time 0 were 59.0, 52.0, and 58.4 μ g/100ml for the control, alcohol, and palmitate treatments. Mean concentrations of vitamin A in milk, expressed as μ g/100ml or μ g/g fat of cows receiving vitamin A alcohol at +195, +451, and +678min postinjection, were greater than concentrations for either control cows or cows receiving palmitate. Partition of milk Vitamin A at +195min postinjection for cows injected with vitamin A alcohol showed 4.1% of the recovered vitamin A in the alcohol and 95.9% in the ester form. Injection of vitamin A palmitate had little effect on milk vitamin A concentration. Vitamin A in serum μ g/100ml) at 195min after vitamin A alcohol injection was higher (100.4) than for either control (84.0) or cows injected with vitamin A palmitate (89.0).
Role of Milk-Borne Factors in Weaning and Intestinal Development

To determine whether a factor appearing in the milk at the beginning of the 3rd postnatal week elicits the appearance of jejunal sucrase activity in the pups, pups were raised with dams that had been
Protest and the Politics of Blame: The Russian Response to Unpaid Wages

Protest and the Politics of Blame: The Russian Response to Unpaid Wages. By Debra Javeline. Ann Arbor: University of Michigan Press, 2003. 312p. $60.00.Why, in the face of massive delays in the payment of wages throughout the Russian Federation during the 1990s, did so few Russian workers engage in organized protest? This empirical puzzle has important implications not only for understanding how the fragile post-Soviet regime managed to endure more than a decade of severe socioeconomic crisis, but also for general theories of social mobilization. In her highly original and thought-provoking book, Debra Javeline argues that the relative quiescence of Russian workers can be explained parsimoniously: In the face of the complexities of post-Soviet political and economic transition, workers could not collectively decide who was to blame for wage arrears, and hence could not organize effective protests against any particular individual or institution.
A Modified Janus Cassette (Sweet Janus) to Improve Allelic Replacement Efficiency by High-Stringency Negative Selection in Streptococcus pneumoniae

The Janus cassette permits marker-free allelic replacement or knockout in streptomycin-resistant Streptococcus pneumoniae (pneumococcus) through sequential positive and negative selection. Spontaneous revertants of Janus can lead to high level of false-positives during negative selection, which necessitate a time-consuming post-selection screening process. We hypothesized that an additional counter-selectable marker in Janus would decrease the revertant frequency and reduce false-positives, since simultaneous reversion of both counter-selectable makers is much less likely. Here we report a modified cassette, Sweet Janus (SJ), in which the sacB gene from Bacillus subtilis conferring sucrose sensitivity is added to Janus. By using streptomycin and sucrose simultaneously as selective agents, the frequency of SJ double revertants was about 105-fold lower than the frequency of Janus revertants. Accordingly, the frequency of false-positives in the SJ-mediated negative selection was about 100-fold lower than what was seen for Janus. Thus, SJ enhances negative selection stringency and can accelerate allelic replacement in pneumococcus, especially when transformation frequency is low due to strain background or suboptimal transformation conditions. Results also suggested the sacB gene alone can function as a counter-selectable marker in the Gram-positive pneumococcus, which will have the advantage of not requiring a streptomycin-resistant strain for allelic replacement.
Crisis transitions in excitable cell models

Abstract It is believed that sudden changes both in the size of chaotic attractor and in the number of unstable periodic orbits on chaotic attractor are sufficient for interior crisis. In this paper, some interior crisis phenomena were discovered in a class of physically realizable dissipative dynamical systems. These systems represent the oscillatory activity of membrane potentials observed in excitable cells such as neuronal cells, pancreatic β-cells, and cardiac cells. We examined the occurrence of interior crises in these systems by two means: (i) constructing bifurcation diagrams and (ii) calculating the number of unstable periodic orbits on chaotic attractor. Bifurcation diagrams were obtained by numerically integrating the simultaneous differential equations which simulate the activity of excitable membranes. These bifurcation diagrams have shown an apparent crisis activity. We also demonstrate in terms of the associated Poincare maps that the number of unstable periodic orbits embedded in a chaotic attractor suddenly increases or decreases at the crisis.
Kidney Disease in HIV-Infected Persons

Kidney disease is more prevalent among persons living with HIV, and may arise from a combination of comorbidities, co-infections, and medication-associated toxicities. Additional effects of HIV-1 viral replication, immunodeficiency and genetic factors also contribute to kidney disease. As is true in the general population, persons of African descent exhibit a disproportionate risk for severe kidney disease. Antiretroviral therapy (ART) modifies the natural history of HIV-associated nephropathy (HIVAN), and renal benefits of ART may not be limited to persons with HIVAN. Robust associations between proteinuria and cardiovascular disease imply that common mechanisms of vascular endothelial dysfunction may contribute to both processes.
Laryngotracheoesophageal cleft in a newborn

Summary A case of laryngotracheoesophageal cleft in a newborn is presented. A newborn presenting with respiratory distress underwent contrast radiographic studies, direct laryngoscopy, bronchoscopy, and esophagoscopy, demonstrating a complete laryngotracheoesophageal cleft, esophageal diverticulum and microgastria. Attempts to maintain an adequate airway by ligation of the salivary ducts and ligation of the distal esophagus were unsuccessful. Continued biliary drainage per endotracheal tube postoperatively afforded a presumptive diagnosis of bronchobiliary fistula. The child expired on its fourth day of life. A review of the literature and modalities of therapy for these rare and unusual combinations of foregut anomalies is discussed. This is the first reported case of a newborn with the combination of laryngotracheoesophageal cleft, bronchobiliary fistula, microgastria and esophageal diverticulum.
The origins of auditor liability to third parties under United States common law

This article traces the origins of auditor liability to third parties under United States common law, with a particular emphasis on the role of Benjamin Cardozo as Chief Judge of the New York Court of Appeals in the period from 1917 to 1932. Prior to the Ultramares decision, written by Chief Judge Cardozo in 1931, auditors were relatively shielded from liability against lawsuits brought by third parties (those who are not the client). In the Ultramares decision, Cardozo opened the door to a possible expansion of auditor liability to third parties through the introduction of a relatively new theory of law, that is that an auditor's negligence was heedless to such an extent that it was equivalent to fraud (that is, gross negligence). Subsequent to Ultramares, it appeared likely that the liability of auditors for negligent acts would be extended beyond their clients to the third parties who rely upon audited financial statements. However, because Ultramares has been interpreted in various ways in different j...
Evolution of Neuronal Patterning in Free-Living Rhabditid Nematodes I: Sex- Specific Serotonin-Containing Neurons

As a first step toward understanding the evolution of neuronal patterning and function in a group of simple animals, we have examined serotonin-containing neurons in 17 species of free-living rhabditid nematodes and compared them with identified neurons of Caenorhabditis elegans. We found many serotonin-immunoreactive (serotonin-IR) neurons that are likely homologs of those in C. elegans; this paper focuses on sex-specific neurons such as the egg laying hermaphrodite-specific neurons (HSNs), VCs, and male CAs, CPs, and ray sensory neurons known to function in mating. These cells vary in number and position in the species examined but are consistent with a current molecularly based phylogeny. Two groups (Oscheius and Pristionchus) appear independently to have lost a serotonin-IR HSN. Oscheius furthermore has no serotonin-IR innervation of the vulval region, in contrast to every other species we examined. We also saw variation in the location of somas of putative HSN, consistent with evolutionary changes in HSN migration. In C. elegans, the HSN soma migrates during embryogenesis from the tail to the central body, where it innervates its major postsynaptic targets, the vulval muscles. For other species, we observed putative HSN homologs along the anterior-posterior axis from the head to the tail, but typically HSNs were located near the vulva, which also varies in anterior-posterior position among the species we examined. The varying positions of the HSN somas in other species are reminiscent of phenotypes seen in various C. elegans mutants with altered HSN migration, suggesting possible mechanisms for the evolutionary differences we observed. J. Comp. Neurol. 502: 736 –767, 2007. © 2007 Wiley-Liss, Inc.
Unfiltered Administration of the YMRS and CDRS-R in a Clinical Sample of Children.

The objective of this study is to evaluate discriminative validity of the Young Mania Rating Scale (YMRS) and Children's Depression Rating Scale–Revised (CDRS-R) in a clinical sample of children when administered in an unfiltered manner (i.e., regardless of whether symptoms occur in a mood episode). The Kiddie Schedule for Affective Disorders and Schizophrenia is the gold standard for assessing psychiatric disorders in children and was used to make diagnoses in this study. Using a sample of 707 treatment-seeking youth (ages 6–12 years, Mage = 9.7 years, 67.6% male), receiver operating curve analyses were performed and diagnostic likelihood ratios (DLRs) were calculated to evaluate the ability to change the odds and differentiate bipolar disorder from other disorders (using the YMRS) and depression from other disorders (using the CDRS-R). Using unfiltered administration, the YMRS achieved good discriminative validity when classifying bipolar disorder compared to other disorders (Area Under the Curve [AUC] ...
JC Virus PCR Detection Is Not Infallible: A Fulminant Case of Progressive Multifocal Leukoencephalopathy with False-Negative Cerebrospinal Fluid Studies despite Progressive Clinical Course and Radiological Findings

We describe a case with a false-negative PCR-based analysis for JC virus in cerebrospinal fluid (CSF) in a patient with clinical and radiological findings suggestive of progressive multifocal leukoencephalopathy (PML) who was on chronic immunosuppressive therapy for rheumatoid arthritis. Our patient developed rapidly progressive global decline with clinical and radiographic findings suggestive of PML, but JC virus PCR in CSF was negative. The patient passed away 3 months from the onset of her neurological symptoms. Autopsy confirmed the diagnosis of PML with presence of JC-polyoma virus by immunohistochemical staining. This case highlights the potential of false-negative JC virus PCR in CSF when radiographic and clinical features are suggestive of “possible PML.” We review the plausible causes of potential false-negative CSF results and suggest that when the clinical presentation is suspicious for PML repeat CSF analysis utilizing ultrasensitive PCR assay and subsequent brain biopsy should be considered if CSF remains negative. Additionally, appropriate exclusion of other neurologic conditions is essential.
Disruption of Cell–Substrate Adhesion Activates the Protein Tyrosine Kinase pp60c-src

Treatment of confluent chicken embryo fibroblasts (CEFs) with trypsin results in a dose- and time-dependent increase in c-Src protein tyrosine kinase (PTK) activity. A similar, but less marked, increase in c-Src PTK activity occurs upon incubation of CEFs in calcium-free phosphate-buffered saline, which also causes a decrease in cell-substrate adhesion. The increase in c-Src PTK activity following disruption of cell-substrate adhesion correlates with a decrease in the phosphorylation of c-Src at the regulatory site, Tyr527. The phosphotyrosine phosphatase inhibitor phenylarsine oxide blocks the increase in c-Src PTK activity seen following treatment with trypsin and the morphological changes associated with the disruption of cell-substrate adhesion. In contrast, disruption of cell-substrate adhesion causes a decrease in FAK PTK activity that rapidly returns to control levels when the cells are plated on fibronection-coated dishes. Treatment of cells with cytochalasin D, which disrupts actin filaments but not cell-substrate adhesion, causes only a slight increase in c-Src PTK activity. Thus, these studies demonstrate a ligand-independent mechanism for the activation of c-Src that is consistent with its role in both cell adhesion and cell motility. Furthermore, these data suggest that similar to adhesion, loss of adhesion is not a passive process but can activate specific signaling pathways that may have significant effects on cellular function.
Glucose, insulin, potassium (GIK) and the concept of metabolic support for the postischaemic heart

Abstract Successful reperfusion has moved the frontier of treatment for acute myocardial ischaemia from coronary arteries to the heart muscle itself. Here we update the concept of metabolic support for the postischaemic heart which is based on an understanding of an earlier review on the same topic. The ischaemic heart is an energy-depleted organ. A mismatch of ATP production and utilisation leads to the uncoupling of ATP-dependent Ca 2+ -mediated excitation-contraction coupling necessary for normal contractile function. Sustained ischaemia leads to adaptive changes of either programed cell survival, cell death or cell necrosis. We are presenting a working hypothesis on the metabolic and ionic consequences of myocardial ischaemia that lead to progressive contractile dysfunction. Based on this hypothesis we develop a rationale for the use of GIK in the support of substrate metabolism by replenishing depleted energy stores to reverse the deleterious events in the postischaemic state. Possible mechanisms include replenishment of depleted cellular glycogen stores and restoration of efficient energy transfer through moiety-conserved cycles. The usefulness of this concept has been demonstrated in the improved survival of patients in cardiogenic shock after hypothermic ischaemic arrest of the heart and in patients with acute myocardial infarction treated with GIK.
Brain stimulation in psychiatric disorders: part I.

I have a vivid memory of reading Mohr & Mohr's Brain, behavior, connections, and implications: Psychodynamics no more (2001). I literally jumped from my seat, saying “Yes, Yes, Yes” as I danced aro...
Combining expert system and analytical redundancy concepts for fault-tolerant flight control

A technique for rule-based fault-tolerant flight control is presented. The objective is to define methods for designing control systems capable of accommodating a wide range of aircraft failures, including sensor, control, and structural failures. A software architecture that integrates quantitative analytical redundancy techniques and heuristic expert system concepts for the purpose of in-flight, real-time fault tolerance is described. The resultant controller uses a rule-based expert system approach to transform the problem of failure accommodation task scheduling and selection into a problem of search. Control system performance under sensor and control failures using linear discrete-time deterministic simulations of a tandem-rotor helicopter's dynamics is demonstrated. It is found that the rule-based control technique enhances existing redundancy management systems, providing smooth integration of symbolic and numeric computation, a search-based decision-making mechanism, straightforward system organization and debugging, an incremental growth capability, and inherent parallelism for computational speed.
The Terri Schiavo Case: Legal, Ethical, and Medical Perspectives

Although tragic, the plight of Terri Schiavo provides a valuable case study. The conflicts and misunderstandings surrounding her situation offer important lessons in medicine, law, and ethics. Despite media saturation and intense public interest, widespread confusion lingers regarding the diagnosis of persistent vegetative state, the judicial processes involved, and the appropriateness of the ethical framework used by those entrusted with Terri Schiavo's care. First, the authors review the current medical understanding of persistent vegetative state, including the requirements for patient examination, the differential diagnosis, and the practice guidelines of the American Academy of Neurology regarding artificial nutrition and hydration for patients with this diagnosis. Second, they examine the legal history, including the 2000 trial, the 2002 evidentiary hearing, and the subsequent appeals. The authors argue that the law did not fail Terri Schiavo, but produced the highest-quality evidence and provided the most judicial review of any end-of-life guardianship case in U.S. history. Third, they review alternative ethical frameworks for understanding the Terri Schiavo case and contend that the principle of respect for autonomy is paramount in this case and in similar cases. Far from being unusual, the manner in which Terri Schiavo's case was reviewed and the basis for the decision reflect a broad medical, legal, and ethical consensus. Greater clarity regarding the persistent vegetative state, less apprehension of the presumed mysteries of legal proceedings, and greater appreciation of the ethical principles at work are the chief benefits obtained from studying this provocative case.
An investigation of the adoption of an assessment instrument for capstone design courses

This paper presents some preliminary findings of an examination of the adoption of an assessment instrument designed for use in capstone design courses. These courses have been garnering increased attention due to their central position in helping students develop design skills, and some of ABET's “softer” skills. These assessment instruments have been designed to aid in developing and assessing those skills. Interviews were conducted with participants from three different populations: (1) the developers of the instruments who are also users; (2) users of the instruments who are not involved in their development; and (3) faculty, administrators and researchers who have attended workshops about the instruments. Analysis of these interviews was conducted using Rogers' Diffusion of Innovations (DI) theory to describe trends and patterns. Preliminary findings from the interviews highlight the central importance of (1) previous beliefs about assessment as they relate to the compatibility and relative advantage of the assessment instrument; and (2) faculty beliefs about their role in the capstone course as they affect their perception of the assessment instrument's complexity.
Neocrystallization or cooling? 40Ar/39Ar ages of white micas from low-grade mylonites

Abstract 40 Ar/ 39 Ar data for white micas from quartzite mylonites from a thrust system are evaluated with respect to whether the minerals record cooling ages or, alternatively, ages of deformation-induced neocrystallization. To address these interpretations three types of information are needed: (1) the effective diffusion length scale controlling volume diffusion of argon in white micas; (2) an estimate of the diffusion parameters for volume diffusion of argon; and (3) the thermal history. Completely recrystallized quartzites exhibit smooth grain size distributions for white micas, with good exponential or power law fits, suggesting that the grains grew under similar conditions. The microstructures indicate that the grains grew over a narrow range in time near the end of the deformation history. Measured grain size distributions provide a maximum limit for the diffusion length scale. Thermal histories are estimated by 40 Ar/ 39 Ar diffusion experiments on K-feldspars using the multi-diffusion-domain method of Lovera [Lovera, O.M., Richter, F.M., Harrison, T.M., 1989. The 40 Ar/ 39 Ar thermochronometry for slowly cooled samples having a distribution of diffusion domain sizes. J. Geophys. Res. 94, 17917–17935.]. These results are consistent with the expected temperature-time path for the thrusting environment, and predict maximum temperatures of 250–350°C during the time span recorded by the white micas. Experimentally and empirically calibrated diffusion parameters for white micas are applied to a cylindrical diffusion geometry to explore the question of cooling ages versus neocrystallization ages. Forward modeling of the passage of the white micas through the closure window for argon diffusion, using the thermal histories derived from the K-feldspars, indicates that the white micas record neocrystallization rather than cooling, and supports the idea that the white micas record the timing of when ductile deformation ceased.
Stable isotope labeling strategy for protein-ligand binding analysis in multi-component protein mixtures.

Described here is a stable isotope labeling protocol that can be used with a chemical modification- and mass spectrometry-based protein–ligand binding assay for detecting and quantifying both the direct and indirect binding events that result from protein–ligand binding interactions. The protocol utilizes an H216O2 and H218O2 labeling strategy to evaluate the chemical denaturant dependence of methionine oxidation in proteins both in the presence and absence of a target ligand. The differential denaturant dependence to the oxidation reactions performed in the presence and absence of ligand provides a measure of the protein stability changes that occur as a result of direct interactions of proteins with the target ligand and/or as a result of indirect interactions involving other protein–ligand interactions that are either induced or disrupted by the ligand. The described protocol utilizes the 18O/16O ratio in the oxidized protein samples to quantify the ligand-induced protein stability changes. The ratio is determined using the isotopic distributions observed for the methionine-containing peptides used for protein identification in the LC-MS-based proteomics readout. The strategy is applied to a multi-component protein mixture in this proof-of-principle experiment, which was designed to evaluate the technique’s ability to detect and quantify the direct binding interaction between cyclosporin A and cyclophilin A and to detect the indirect binding interaction between cyclosporin A and calcineurin (i.e., the protein–protein interaction between cyclophilin A and calcineurin that is induced by cyclosporin A binding to cyclophilin A).
Checking Java Implementation of a Naming Architecture Using Testera

Abstract TestEra is a novel framework for automated testing of Java programs. We have built TestEra upon Alloy, a lightweight first-order relational language, and the Alloy Analyzer, a fully automatic simulation and checking tool. Checking a Java program with TestEra involves modeling the correctness criteria for the program in Alloy and specifying abstraction and concretization translations between instances of Alloy models and Java data structures. TestEra automatically generates all non-isomorphic test cases within a given input size and verifies the correctness. We present our initial evaluation of TestEra performed by checking the Java implementation of a naming architecture for resource discovery in dynamic networked environments. Our study delineates the use of TestEra in testing methods for manipulating complex data structures.
Focus Issue: Networking Cancer Treatment Strategies

Receptor tyrosine kinases and the signaling networks that they control contribute to cancer and resistance to therapies. Therefore, understanding these networks, how they vary within and among tumors and how they adapt to enable cancer cells to circumvent treatment, should lead to more effective therapeutic strategies in treating the diverse disease that is cancer. As Science Signaling highlights in this week’s issue, systems biology and computational biology are shining light on these complex networks and enabling integration of diverse information about genetics, proteomics, and network activity to effectively predict therapeutic response and identify key components to target for intervention.