cssi/SciSciGPT-SciSciNet huggingface dataset:
Transformation of inputs in a model of the rat hippocampal CA1 network

The hippocampus is one of the brain structures critically implicated in schizophrenia. Known schizophrenia-specific alterations in the hippocampal neurons are subtle. Their impact on the information processing in the hippocampus is poorly understood. A core difficulty is the lack of understanding of normal hippocampal functioning. Here, we focus on some simple but potentially fundamental characteristics of that functioning, and assess them in a model of the CA1 hippocampal network. In our study, network effects resulted from overlapping inputs to modeled CA1 principal cells; we did not consider explicit interactions between the cells. The overlap was determined on the basis of the known hippocampal anatomy [1]. We assumed that all the cells received their excitatory and inhibitory inputs synchronously, as if strongly modulated by ongoing theta and gamma rhythm [2]. Each cell was modeled by biophysically realistic multicompartment models of reconstructed CA1 principal cells using NEURON [3,4]. Our analysis of the network performance was motivated by our earlier model of the hippocampal network under normal and psychotic conditions [5]. When “normal”, that attractor model network was able to generalize similar input patterns and discriminate distinct ones. Such behavior required time sufficient for the network dynamics to converge to appropriate steady states. In the present study, we complement that approach by assessing similar abilities of generalizing and discriminating of inputs. However here we used much more realistic neuronal models and did not take into account associative properties of the network. We characterized the network performance by its response to synchronous inputs within 40 milliseconds. If a modeled CA1cell spiked within this interval it contributed “1” to the output of the network, otherwise the cell contributed “0”. In particular, we determined how the average distance between the output patterns depended on the average distance between the input patterns. We performed this analysis for CA3, entorhinal, and mixed input patterns.
Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis.

Abstract This article is part of a Special Issue “Energy Balance”. The classical estrogen receptors, estrogen receptor-α and estrogen receptor-β are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8 weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6 weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but no significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed significant reductions in two brown fat thermogenic proteins. GPER KO females, prior to their divergence in body weight, were less sensitive than WT females to the feeding-inhibitory effects of leptin and CCK. Additionally, body weight was not as modulated by ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but not GPER KO females. For the first time, GPER expression was found in the adipocyte but not the stromal fraction of adipose tissue. Together, these results provide new information elucidating a sexual dimorphism in GPER function in the development of postpubertal energy balance.
Nursing care models increase care quality while reducing costs

Unique models of care delivery, such as the Nursing Care Partnership model for practice used at the Denver Nursing Project in Human Caring, have demonstrated a reduction in inpatient admissions, mean length of stay, and total charges. This descriptive study identified and described clients' (N = 75) perceptions of care and explored the cost-effectiveness of this model. Findings suggest nursing care partnerships play a key role in reducing healthcare costs by providing services in a more cost-efficient setting and by having an impact on client utilization of services. Savings in potential hospital costs were estimated at $1,590,384 for 1993.
Analysis of myogenesis by somatic cell hybridization. II. Retention of myogenic competence and suppression of transformed properties in hybrids between differentiation competent and incompetent rat L6 myoblasts.

This study describes the characteristics of hybrids between two closely related rat myoblast lines, which differ both in the ability to express their program of differentiation and in the expression of neoplastic properties. Myogenic, nonneoplastic L6J1-S cells were hybridized with nonmyogenic, neoplastic L6J1-N1 cells. Six hybrid clones were isolated and expanded for analysis of myogenic competence, and four of these clones were also evaluated for parameters of transformation, including tumorigenicity, ability to clone in agar, and surface fibronectin. In addition to our analysis of isolated clones, we also assessed myogenic differentiation in colonies representing 226 early hybrid clones. Results of all these analyses demonstrate that the myogenic phenotype is retained and that the tumorigenic/transformed phenotype is suppressed in the hybrids. Furthermore, our results indicate that when the programs for myogenesis and neoplastic transformation are confronted within a single cell, they are expressed as mutually exclusive alternatives. In contrast to these results on myogenic × nonmyogenic L6 hybrids, it has been reported that isolated clones of A9 × L6 exhibited extinction of myogenic competence and retention of transformed properties. We have evaluated myotube formation in over 300 early hybrid clones between A9 and either diploid or subtetraploid L8 rat myoblasts. Our results demonstrate that all of these hybrid clones exhibit extinction regardless of the ploidy of the myoblast parent, and they further indicate that extinction is not a consequence of chromosome loss. These results support the conclusion that in A9 × L6 hybrids, the nonmyogenic, transformed phenotype is dominant.
Fuzzy measurement of income inequality: a class of fuzzy inequality measures

The typical practice of income inequality evaluation is by using inequality indices. Yet there is no “best” measure of inequality as we know it, and hence, any conclusion based on an inequality index must be subject to some doubts. Some authors even argued that the concept of inequality, by its very nature, is vague, and thus, cannot be measured like an exact concept. Motivated by these considerations, this paper studies axiomatic fuzzifications of inequality measures. Consequently, a systematic method of viewing the conclusions of inequality comparisons in terms of truth value statements is developed. Furthermore, it is shown that this method (or in fact, any other fuzzy inequality measure) can be used to construct confidence intervals for the crisp conclusions of inequality indices.
A titration method for bovine trypsin

Abstract p -Nitrophenyl ethyl diazomalonate can easily be synthesized from ethyldiazoacetate and phosgene and p -nitrophenol. It reacts stoichiometrically with bovine trypsin, and measurement of the optical density of the p -nitrophenol released in the enzymic reaction provides a simple assay for the enzyme.
What is an event? Domain constraints for temporal analysis of chief complaints and triage notes

In this paper we present preliminary results of a study of events represented in portions of the Emergency Department (ED) patient record. An advantage to working in such a specific domain is that we can use domain knowledge to reveal events that are not explicitly mentioned in the record. In addition, domain assumptions and constraints can be used to identify or clarify temporal characteristics of events, allowing more precise placement on an event timeline.
Chorioamnionitis, postnatal factors and proinflammatory response in the pathogenetic sequence of bronchopulmonary dysplasia

Pulmonary inflammation has a central role in the multifactorial and complex pathogenesis of bronchopulmonary dysplasia. Pre- and postnatal factors such as chorioamnionitis, oxygen toxicity, mechanical ventilation and postnatal infections can induce and perpetuate an injurious and complex inflammatory response in the airways and lung tissue of very immature infants. This inflammatory process is characterized by the accumulation of inflammatory cells and an arsenal of proinflammatory mediators such as cytokines, toxic oxygen radicals, lipid mediators and potent proteases. An imbalance between pro- and anti-inflammatory factors favoring the proinflammatory process can be considered as a hallmark of lung injury. In addition, impaired mechanisms of tissue remodeling and repair together with a subnormal generation of growth factors could affect alveolarization and vascular development with lifelong consequences for the infants with bronchopulmonary dysplasia.
Quantitative test of solvability theory for the Saffman-Taylor problem.

We report on a quantitative test of solvability theory in the case of pattern selection for viscous fingering in a rectangular Hele-Shaw cell. We construct an effective two-dimensional theory that properly takes into account the effect of film draining. In the parameter range where the theory is applicable we find excellent agreement between our predictions and the experimental data. This provides the first precise, quantitative assessment of microscopic solvability in a physical system.
Power spectra of a free space optical link in a maritime environment

Parameters characterizing the atmospheric turbulence in a 16 km maritime optical link were measured over a 6 month period in 2007, on a continuous basis as conditions allowed. Both the scintillation index and the atmospheric structure constant were found to have a strong dependence on the air - water temperature difference. Temporal-frequency spectra were also generated from the received intensity fluctuations. In this paper the frequency components of the laser irradiance are studied in order to ascertain the degree of correlation with prevailing meteorological conditions. In addition, the high frequency behavior of the power spectra is documented and shows an extensive range of values for the power-law scaling index.
Movement-related potentials are task or end-effector dependent: evidence from a multifinger experiment

In a number of recent studies, the specific sensitivity of movement-related EEG potentials toward experimental manipulations of motor tasks using the index finger as a primary end-effector is well documented. The major question in this study was whether different movement-related EEG components are primarily end-effector or task dependent. Accordingly, the experimental task (i.e., the rate of force development – a ratio of peak force to time-to-peak force) was systematically manipulated and the effects of this manipulation on movement-related potentials were examined while subjects used either the index, middle, ring or little finger. Significant effects observed in this study were due mainly to the sensitivity of movement-related potentials preceding movement onset (Bereitshaftspotential and motor potential) toward the specific finger performing the task and the sensitivity of components accompanying the task (movement-monitoring potential) toward the rate of force development. In addition, both movement-related potentials preceding and accompanying movement significantly changed as a function of the finger performing the slow task (lower rate of force development) with maximum values observed for the ring finger and minimal values observed for the index finger. Behaviorally subjects were less accurate during slow tasks regardless of the finger performing the task. In contrast, the amplitude of neither early nor late components of movement-related potentials changed as a function of the finger performing the fast task (higher rate of force development). Overall, our results are consistent with the notion that the whole complex of movement-related EEG potentials reflect a combination of factors including the selection of corresponding general motor programs as reflected in the amplitude of potentials preceding movement and specific elements of the task including rate of force development as reflected in the amplitude of potentials accompanying movement execution.
Normal Zeta Functions of Some pro-p Groups

We give an explicit formula for the number of normal subgroups of index p n of the pro-p group , and for the normal zeta function associated with this group. Let &#x1d4ac;1(s, r) be the subgroups of the Nottingham group discovered by Ershov. We observe that these groups are isospectral with . This provides us with an infinite family of noncommensurable normally isospectral groups.
Mining the human genome for new health therapies

The completion of the Human Genome Project heralds advances in determining the foundations of disease and in developing new therapeutic treatments. Tests already exist for the detection of some genetic abnormalities that can cause disease, and more are being developed. In the future, pharmacogenetics will be used to tailor treatment to specific patients.
Zero–Hopf bifurcation analysis of a Kaldor–Kalecki model of business cycle with delay

Abstract The zero–Hopf singularity of a Kaldor–Kalecki model of business cycle with delay in both the gross product and the capital stock is investigated. By computing the normal forms for the system, the bifurcation diagrams such as saddle-node, pitch-fork, and Hopf bifurcations are obtained. A major obstacle is to solve singular linear systems when the third order terms in the normal form are computed. Some examples are presented to confirm the theoretical results.
Pragmatism and Ethnicity: Critique, Reconstruction, and the New Hispanic

: In this essay I examine the contributions of the pragmatist tradition to the philosophy of ethnicity. From the pragmatist philosophies of Dewey and Locke I derive a reconstructive model for the clarification and improvement of the life experiences of ethnic groups. Addressing various problems and objections, I argue that this Deweyan and Lockean reconstructive model rejects any sharp separation between race and ethnicity and avoids the pitfalls of the biologist race paradigm and the culturalist ethnicity paradigm. I explore some of the social and political implications of this reconstructive model through a discussion of Jose Marti's inspiring account of Hispanic identity.
Interaction of Ocular Hypotensive Agents (PGF2α Analogs—Bimatoprost, Latanoprost, and Travoprost) With MDR Efflux Pumps on the Rabbit Cornea

Purpose: The objectives of this work were (i) to screen ocular hypotensive prostaglandin (PGF2α) analogs—bimatoprost, latanoprost, and travoprost as well as their free acid forms—for interaction with efflux pumps on the cornea and (ii) to assess the modulation of efflux upon co-administration of these prostaglandin analogs. Methods: Cultured rabbit primary corneal epithelial cells (rPCEC) were employed as an in vitro model for rabbit cornea. Transporter-specific interaction studies were carried out using Madin-Darby canine kidney (MDCK) cells overexpressing MDR1, MRP1, MRP2, MRP5, and BCRP. Freshly excised rabbit cornea was used as an ex vivo model to determine transcorneal permeability. Results: Cellular accumulation studies clearly showed that all prostaglandin analogs and their free acid forms are substrates of MRP1, MRP2, and MRP5. Bimatoprost was the only prostaglandin analog in this study to interact with P-gp. In addition, none of these molecules showed any affinity for BCRP. K i values of these pr...
The cerebral ventricles as the avenue for the dipsogenic action of intracranial angiotensin

Abstract Using low doses of angiotensin II (1–128 ng), a mapping study was carried out to redefine the region within the brain from which the dipsogenic response can be elicited. The most sensitive sites were either close to the anterior cerebral ventricles or were at the tips of cannulae that traversed a ventricular space en route to the tissue site. Conversely, insensitve sites were remote from the ventricles and were not reached by cannulae with a ventricular trajectory. Therefore, a thorough assessment of the role of the ventricular system in the angiotensin thirst phenomenon was demanded. Further studies revealed that direct intraventricular injections were as effective as those made into any tissue site tested. Also, regardless of the similarity in the sites of their termination, cannulae which passed through a ventricular space en route to that site yielded highly sensitive preparations whereas those which did not were insensitive to the hormone. Autoradiographic and radioassay studies showed that tritiated angiotensin II injected into anterior diencephalic tissue through cannulae which traversed the ventricles was rapidly distributed throughout the ventricular system. Thus, efflux of the injected material up the cannula shaft and its entry into the ventricular system is essential for a dipsogenic response to low doses of the hormone. These results support the hypothesis of a periventricular receptor site for angiotensin. It is suggested that systematically generated angiotensin and angiotensin endogenous to the brain may use the ventricular route as a means of access to the sensitive periventricular site.
Incidence and severity of recovery agitation after ketamine sedation in young adults

Abstract Purposes Psychic recovery reactions after ketamine administration are not uncommon in adults, but yet are rare in children 15 years old and younger. The nature of such reactions has not been previously described in young adults, and accordingly we wished to quantify the incidence and severity of recovery agitation after ketamine sedation in patients aged 16 to 21 years. Basic Procedures We prospectively collected data on 26 young adults aged 16 to 21 years who received ketamine for emergency department procedures, and treating physicians rated recovery “agitation,” “crying,” and “unpleasant hallucinations or nightmares” each on a 100-mm visual analog scale (0 mm = “none,” 100 mm = “worst possible”). Main Findings Treating physicians rated agitation and crying as entirely absent (rating 0 mm) in 25 of the 26 patients, and unpleasant hallucinations or nightmares as entirely absent (0 mm) in all 26. The single occurrences each of agitation (rating 46 mm) and crying (rating 23 mm) were not severe and resolved spontaneously without treatment. Principal Conclusions In this small sample of young adults we observed no serious psychic recovery reactions, mirroring the low incidence of such responses well documented with children 15 years old and younger. This supports the expansion of ketamine use to young adults aged 16 to 21 years.
Lateral spine mechanoreceptors in limulus polyphemus

Abstract 1. 1. Mechanical stimulation of the lateral spines commonly elicits phasic and tonic sensory activity in the dorsal segmental nerves supplying these spines. 2. 2. The receptors responsible for this activity represent a single population having a wide range of adaptation rates. 3. 3. The phasic spike frequency codes the logarithm of the rate of spine movement, while the tonic frequency codes the amplitude of spine displacement. 4. 4. Because the tonic discharge adapts fully, the tonic discharge does not code spine position. 5. 5. The value of the lateral spine mechanosensory function to Limulus is considered.
Lifestyle Modifications to Lower or Control High Blood Pressure: Is Advice Associated With Action? The Behavioral Risk Factor Surveillance Survey

Routine lifestyle modification advice for managing high blood pressure (BP) is of questionable effectiveness. Using data from the 2005 Behavior Risk Factor Surveillance System, we examined whether receipt of advice is associated with reported adoption of lifestyle modifications. We determined proportions of hypertensive adults taking action to change eating habits, reduce salt intake, exercise, or decrease alcohol consumption to control high BP. We then determined associations between reports of advice given and corresponding actions being taken: 70.1% of respondents reported changing eating habits, 78.7% reported reducing salt intake, 67.1% reported exercising, and 57.9% of those who drank alcohol reported decreasing their consumption. Compared with those who did not recall being given advice, hypertensive adults who recalled being given advice were more likely to change their eating habits (prevalence ratio [PR], 1.62; 95% confidence interval [CI], 1.56-1.67), reduce salt (PR, 1.53; 95% CI, 1.48-1.58), exercise (PR, 1.41; 95% CI, 1.36-1.47), and reduce alcohol consumption (PR, 1.78; 95% CI, 1.70-1.87).
Escitalopram: an open-label study of bereavement-related depression and grief.

Abstract Background Approximately 8 million Americans suffer the loss of an immediate family member each year. Chronic depression may develop following bereavement—about 15% of the bereaved are depressed at 1 year. Several studies of psychotropic medications have demonstrated improvement in depression ratings, but little data exists for selective serotonin reuptake inhibitor treatment in bereavement-related depression. Methods Thirty adults were treated with escitalopram for 12 weeks in open fashion for a major depressive episode following loss of a close family member (parent, sibling, child, or spouse/significant other). Main outcome measures were the Hamilton Depression Rating Scale, the Montgomery–Asberg Rating Scale, the Texas Revised Inventory of Grief, and the Inventory of Complicated Grief. Results Twenty-nine of thirty participants returned for at least one set of efficacy measures after starting medication. Nineteen subjects (66%) experienced a 50% or greater improvement on the Hamilton Depression Scale. Fifteen subjects (52%) achieved remission, defined as a final score of 7 or less on the Hamilton Depression Scale. Escitalopram significantly reduced depressive symptoms ( P Limitations Open-label design, psychotherapy was not controlled, relatively short treatment period, variation in grief scales make comparisons to other studies difficult, all subjects with complicated grief also were clinically depressed, and gender discrepancy of sample. Conclusions Escitalopram improved depressive, anxiety, and grief symptoms in individuals experiencing a major depressive episode related to the loss of a loved one.
Responding to violence with guns: Mass shootings and gun acquisition

Abstract Although some sources have observed an increase in the number of gun purchases following mass shootings, empirical research investigating this pattern is limited. Appraisal Theory suggests that mass shootings contribute to fear of victimization through media exposure. Desire for self-protection is the primary reason many individuals own and purchase guns. This paper examines this link by assessing the effects of six mass shootings that took place in the 2000–2010 time period. This study examines effects for gun acquisition nationally and regionally as well as timing-specific patterns in gun acquisition following these events. Gun acquisition counts are approximated from the National Instant Criminal Background Check System (NICS). Results indicate a positive but delayed association between mass shootings and the number of NICS background checks. Implications of this finding for violence and possibilities for future research are discussed.
Treatment of severe reflux esophagitis.

Excerpt To the editor: In the January issue, Lieberman and Keeffe (1) presented a well-designed study comparing a regimen of cimetidine alone to one of cimetidine and metoclopramide in the treatmen...
Charge transport in poly-[Ru(2,2′-bipyridine)2(4-vinylpyridine)2]3+/2+ films in AlCl3/N-(1-butyl)pyridinium chloride and AlCl3/1-methyl(3-ethyl)imidazolium chloride molten salts

Charge transport in poly-[Ru(2,2′-bipyridine)2(4-vinylpyridine)2]3+/2+ films has been measured by chronoamperometry, chronocoulometry, linear sweep voltammetry and mediated oxidation of [Fe(2,2′-bipyridine)3]2+. Charge transport follows diffusional behavior in both acidic and neutral AlCl3/N-(1-butyl)pyridinium chloride and AlCl3/1-methyl(3-ethyl)imidazolium chloride molten salts and in CH3CN. The charge transport diffusion coefficient did not depend upon which melt was used and an average value of 1.7×10−8 mol cm−2 s−12 was obtained. This is 2.6 times smaller than the value obtained in CH3CN. Possible reasons for this are discussed.
Bile acid biosynthesis: The metabolism of 7α-hydroxy-4-cholesten-3-one in the bile fistula rat

Abstract The two primary bile acids, cholic acid (3α,7α,12α-tri-hydroxy-5β-cholan-24-oic acid) and chenodeoxycholic acid (3α,7α-dihydroxy-5β-cholan-24-oic acid), are initially synthesized by way of identical precursors, and the point of divergence of this pathway is thought to occur at the intermediate 7α-hydroxy-4-cholesten-3-one. In order to test this hypothesis, bile fistula rats received simultaneous intra-venous infusions of 3H-7α-hydroxy-4-cholesten-3-one and 14C-cholesterol (5-cholesten-3β-ol). Assays of equal specific activities of the two bile acids from an infusion of 14C-cholesterol demonstrated the achievement of a steady state, and assays of equal specific activities from an infusion of 3H-7α-hydroxy-4-cholesten-3-one would-validate the above postulate. However, the infusion of 3H-7α-hydroxy-4-cholesten-3-one resulted in unequal specific activities in the bile acids of the rats investigated, with cholic acid always of a lower value. These results suggest that either 7α-hydroxy-4-cholesten-3-one is not the last common intermediate in the production of cholic acid and chenodeoxycholic acid, or that the infused bile acid intermediate was not metabolized in a fashion similar to that formed in the liver from cholesterol.
Quantification of MPTP-induced dopaminergic neurodegeneration in the mouse substantia nigra by laser capture microdissection

The neurotoxin MPTP is widely used to cause damage to the dopaminergic system in rodents and non-human primates to model various aspects of Parkinson's disease. In mice, depletion of striatal dopamine is the commonly used endpoint to assess neuronal damage. However, it has proved technically challenging to quantify dopaminergic cell bodies as an index of neuronal integrity. To meet this challenge, we applied laser pressure catapult microdissection (LCM) of the substantia nigra in combination with quantitative Western blot to provide an index of dopamine neurodegeneration in mice treated with MPTP. Seven days following initiation of MPTP treatment, striatal dopamine depletion was maximal and there was histological evidence of neuronal degeneration in the substantia nigra. To index the integrity of dopamine cell bodies, tyrosine hydroxylase (TH) and beta-actin were quantified by Western blot in LCM extracts. In untreated mice, TH was detected in LCM extracts of substantia nigra but was undetectable in equivalently sized extracts of cortex from the same animals. In MPTP-treated mice, there was a significant 70% reduction in TH relative to beta-actin in LCM extracts as compared to vehicle-injected controls. This reduction corresponded to decreases in striatal dopamine and loss of immunocytochemically detected TH but not beta-actin in the substantia nigra (SN). Thus, this method provides a quantitative means to measure dopamine neuron toxicity in the substantia nigra and, as such has potential application in evaluating regimens that may be neuroprotective or neurorestorative for dopaminergic neurons.
T lymphocyte subsets in the skin lesions of patients with leprosy

Lymphocyte subsets in the tissues of fourteen patients with leprosy were studied using monoclonal antibodies and a modified immunoperoxidase technic. Two immunohistologic patterns were observed. In tuberculoid leprosy, helper-inducer cells were present among the aggregates of mononuclear phagocytes (epithelioid cells), but the suppresser-cytotoxic cells were predominantly in the lymphocytic mantle surrounding the epithelioid cell aggregates. In reversal reaction and lepromatous tissues, the helper-inducer and the suppresser-cytotoxic cells were both distributed among the mononuclear phagocytes (histiocytes). In tuberculoid specimens the Langerhans cells of the epidermis were increased in number as compared to lepromatous and normal tissues. The technic used appears to be of value in studying some of the cellular components of the immune response in situ.
Recognition of topological equivalence of patterns by array automata

Abstract The complexity of array automata which compute Beyer's topological matching predicate is studied. This predicate on two n × n figures is true if and only if the trees describing their topological structure are isomorphic. An algorithm is proposed which is proved to operate in order of n 2 steps on pairs of n × n figures, a significant improvement over Beyer's order of n 4 algorithm.
Thyroid hormone induces beta1-adrenergic receptor gene transcription through a direct repeat separated by five nucleotides.

Transcription of the rat gene for the beta1-adrenergic receptor (beta1-AR) is stimulated by thyroid hormone (T3) in ventricular myocytes. To identify the domains involved in the regulation of beta1-AR gene transcription by T3, three kb of 5'-flanking sequence of the rat beta1-AR gene were ligated to a luciferase reporter gene and transiently transfected into ventricular myocytes. By generating deletions in the rat beta1-AR promoter, a region between -125 and -100 was found to mediate a three-fold induction by T3. This element was able to confer T3 responsiveness to a neutral promoter driving the luciferase reporter gene. Through site directed mutagenesis of this region, it was determined that the T3 responsive element (TRE) was organized as a direct repeat separated by five nucleotides in which the 5'-most AGGTCG half-site was between nucleotides -105 to -102 and the 3'-most AGGTCA half-site between nucleotides -116 and -113. Both the thyroid hormone receptor isoforms alpha and beta bound to the oligomer representing the sequences between -125 and -100 most efficiently as heterodimers with the retinoid X receptor. This TRE is unusual in that it is a direct repeat separated by five nucleotides which is located 3' to the transcriptional start site.
Assessment of health-related quality of life in acute in-patient settings: use of the BASES instrument in children undergoing bone marrow transplantation.

The Behavioral, Affective and Somatic Experiences Scale (BASES) represents a set of tools for assessing aspects of health-related quality of life (HRQL) in patients undergoing active, intensive therapy. Separate versions have been developed for parent, nurse and patient reports. The scales were constructed to be sensitive to change and appropriate for repeated measures in longitudinal designs. We report preliminary results with these measures from a sample of 105 children undergoing bone marrow transplantation (BMT). Adequate reliability of the instruments is documented through measures of both internal consistency and cross-informant consistency. Several analyses provide evidence of the clinical validity of the measures. Repeated-measures ANOVAs indicated reliable patterns of change over time, with trajectories that conformed to a priori predictions. Discriminative validity was demonstrated through detection of significant differences in the predicted direction between patients undergoing allogeneic and autologous BMT. Additional evidence for validity comes from the very similar symptom trajectories in parent, nurse and patient reports. Differences between the BASES and other measures of HRQL are identified and alternative uses of the instruments are discussed.
Discovery of novel oxazepine and diazepine carboxamides as two new classes of heat shock protein 90 inhibitors.

Abstract Two novel series of oxazepine and diazepine based HSP90 inhibitors are reported. This effort relied on structure based design and isothermal calorimetry to identify small drug like macrocycles. Computational modelling was used to build into a solvent exposed pocket near the opening of the ATP binding site, which led to potent inhibitors of HSP90 (25–30).
A multi-institutional experience in pediatric high-grade glioma.

ABSTRACT Introduction Pediatric high grade gliomas are rare tumors with poor outcomes and incompletely defined management. We conducted a multi-institutional retrospective study to evaluate association of clinical, pathologic, and treatment characteristics with outcomes. Materials and methods Fifty-one patients treated from 1984-2008 at Ohio State University or University of Michigan were included. Histologic subgroups were compared. Log-rank and stepwise Cox proportional hazard modeling were used to analyze progression-free survival (PFS) and overall survival (OS) within the whole group, grade III subgroup, grade IV subgroup, and subtotal resection/biopsy subgroup. Results Median OS was 27.6 months. Grade III histology, complete tumor resection, and cerebral tumor location correlated with improved PFS and OS. Temozolomide use and chemotherapy after radiotherapy or chemoradiation were associated with better PFS while seizure at presentation was associated with better OS. In multivariate analysis, complete resection and chemotherapy following radiotherapy or chemoradiation were independent predictors for improved PFS and OS. For grade III and IV subgroups, complete resection was associated with improved OS (grade III) and seizure presentation was associated with improved OS (grade IV). In the incompletely resection subgroup, temozolomide use and concurrent chemoradiation independently correlated with improved PFS, while higher radiation dose (≥ 59.4 Gy), and adjuvant chemotherapy were independently associated with improved OS. Discussion Total resection and receiving chemotherapy adjuvant to radiation or chemoradiation are most closely associated with improved PFS and OS. For higher risk incompletely-resected patients, temozolomide use and treatment intensification with concurrent chemoradiation, adjuvant chemotherapy, and higher radiation dose were associated with improved outcomes.
Cryptosporidiosis during childhood

Abstract Cryptosporidium parvum is a coccidial protozoan that causes diarrhea in immunocompetent and immunocompromised children. Whereas the illness usually is only mild to moderately severe in otherwise healthy children, the symptoms in immunocompromised patients often are severe and prolonged. Most cases of cryptosporidiosis occur sporadically; however, outbreaks of illness have occurred in day care centers. The most massive outbreak of cryptosporidiosis occurred in Milwaukee during 1993, when 403,000 individuals developed diarrhea because of a contaminated public water supply. Progress has been made in improving the sensitivity and specificity of diagnosing cryptosporidiosis. Although there is no well-established treatment for cryptosporidial infections and no drug has been found to be reproducibly curative, anecdotal reports and small controlled trials have shown that certain medications may be tried in certain children with cryptosporidiosis. This article reviews the clinical features of cryptosporidiosis in pediatric patients, with special focus on diagnosing and treating this intestinal parasitic infection. Copyright © 2000 by W.B. Saunders Company
A system for the three-dimensional reconstruction of biological structures

A system of programs for building three-dimensional models of biological structures was developed. Outlines of features such as cells, tissue edges, and neuron pathways are traced into a computer from tissue sections mounted on a light microscope or projected onto a data tablet. The three-dimensional models are built from a series of the two-dimensional outlines. The cathode ray tube displays of the three-dimensional models can be smoothly rotated for study, and a static display with hidden lines removed can be produced. Volume and surface area calculations for the models can be done. It is possible to obtain further anatomical data by counting and mapping silver grains in autoradiographs of tissue sections. The density of grains reveals pathways and boundaries in the structure. Displays of silver grain maps and counts can be superimposed on displays of the model of the structure.
Structural and Electronic Properties of Reduced Transition Metal Oxide Clusters, M3O8 and M3O8− (M = Cr, W), from Photoelectron Spectroscopy and Quantum Chemical Calculations

We report a comparative study of reduced transition metal oxide clusters, M3O8− (M = Cr, W) anions and their neutrals, via anion photoelectron spectroscopy (PES) and density functional theory (DFT) and molecular orbital theory (CCSD(T)) calculations. Well-resolved PES spectra are obtained for M3O8− (M = Cr, W) at 193 and 157 nm photon energies. Different PES spectra are observed for M = Cr versus M = W. Extensive DFT and CCSD(T) calculations are performed to locate the ground and low-lying excited states for the neutrals and anions. The ground states of Cr3O8 and Cr3O8− are predicted to be the 3B2 and 4B2 states of a C2v structure, respectively, revealing ferromagnetic spin coupling for Cr 3d electrons. In contrast, the ground states of W3O8 and W3O8− are predicted to be the 1A′ state (Cs symmetry) and the 2A1 state (C2v symmetry), respectively, showing metal−metal d−d bonding in the anion. The current cluster geometries are in qualitative agreement with prior DFT studies at the PBE level for M = Cr and t...
Digital pre-distortion of radio frequency front-end impairments in the design of spectrally agile multicarrier transmission

In this paper, we analyze the impact of radio frequency (RF) front-end component impairments on spectrally agile multicarrier waveform transmission, and explain how these impairments can be compensated for on the digital side via preprocessing baseband modules. Although there has been a substantial amount of research conducted on digital signal processing techniques and RF front-end design, to the best of the authors' knowledge, there has not been extensive research on PHY abstraction methodology that takes into consideration RF front-end impairment compensation for more realistic performance prediction of spectrally agile transceivers. Our goal is to show how it is both necessary and beneficial to model RF front-end impairment predistortion in PHY abstraction in order to predict instantaneous link performance for wireless communication systems in Dynamic Spectrum Access (DSA) networks. RF front-end impairments, such as nonlinearities caused by power amplifiers (PA), are investigated and digital predistortion (PD) approaches are proposed to compensate for these impairments. Simulation results show that baseband implementation of digital PD can effectively alleviate these distortions.
The Invisible Hand of James Madison

Scholars have disagreed about how to interpret James Madison's Federalist essays 10 and 51, in which he explains and justifies the underlying principles of the new Constitution. Was Madison the architect of a structure of counterpoise, which would force individuals, interests, and institutions to obstruct one another so as to avoid tyranny, or was he a republican statesman, designing a system that would recruit virtuous citizens to public office? I argue that these clashing interpretations can be reconciled by viewing Madison as a theorist who was applying Adam Smith's economic concepts to political phenomena By putting into practice Smith's insight that competition among self-interested actors can achieve the public interest, Madison incorporated both umpired strife and virtuous citizenship into the meta-principles of the Constitution.
Purification and characterization of hevain, a serine protease from Hevea brasiliensis

Abstract A serine protease of MW 69000 has been isolated, in homogeneous form, from the latex of Hevea brasiliensis . The enzyme, named hevain, has only limited esterolytic and proteolytic abilities, a maximum activity in the pH range 6.5–7.5, and a pI of 4.3. Hevain has a notably high content of acidic amino acids, while the aromatic residues are present in relatively minor amounts.
Analysis of buckled and pre-bent fixed-end columns used as vibration isolators

The use of a buckled or pre-bent column with fixed ends as a vibration isolator is analyzed. The column is designed to have a high axial stiffness under the weight that it supports, so that the static displacement of the weight is not excessive, and then to have a low stiffness during excitation. The base of the column is assumed to have an axial motion which is simple harmonic or a linear combination of two simple harmonic functions. The column is modeled as an elastica. First the equilibrium shape under the supported weight is determined. Then small steady-state vibrations about the equilibrium configuration are obtained numerically using a shooting method. The inertia of the supported weight and the transverse and axial inertias of the column are included. The axial displacement transmissibility is computed, and the effects of external and internal damping, column stiffness, supported weight, and initial curvature are investigated. For the two-frequency excitation, the effects of the relative amplitudes and frequencies of the excitation components are considered.
Antianginal and Antiischemic Efficacy of Monotherapy Extended-Release Nisoldipine (Coat Core) in Chronic Stable Angina

A double-blind, randomized, placebo-controlled study was conducted to test the peak and trough antianginal and antiischemic monotherapy efficacy and safety of a new extended-release formulation of nisoldipine (nisoldipine Coat Core [Bayer Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study patients had a history of chronic, stable angina pectoris, exercise-induced angina in association with ST segment depression, and exercise test reproducibility. Of the 483 patients enrolled in the study, results were valid for safety analysis for 312 and for efficacy analysis for 284. There was a statistically significant improvement in total exercise time at both peak and trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients taking placebo, but the group taking 60 mg was not better than the group taking 20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar for the secondary endpoints (time to onset of angina and time to 1 mm ST segment depression). No correlation was evident between plasma nisoldipine levels and total exercise duration. Headache and peripheral edema were the most frequently reported adverse events and were dose related. There were no discontinuations due to adverse events in patients randomized to the 20-mg nisoldipine group. No deaths occurred while patients were receiving active nisoldipine therapy. Therapy with this extended-release formulation of nisoldipine is an effective once-daily treatment for chronic stable angina pectoris. It represents one of the few dihydropyridine calcium channel antagonists that has shown efficacy when administered as monotherapy to patients with angina.
In vivo evaluation of 2′-deoxy-2′-[18F]fluoro-5- iodo-1-β-D-arabinofuranosyluracil ([18F]FIAU) and 2′-deoxy-2′-[18F]fluoro-5-ethyl-1-β-D- arabinofuranosyluracil ([18F]FEAU) as markers for suicide gene expression

FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [14C]FIAU and [3H]FEAU. PET imaging was performed using [18F]FIAU and [18F]FEAU. In vitro uptake of [14C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p < 0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [3H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p < 0.001) than in wild type cells at the same time points. In vivo uptake of [14C]FIAU at 2 h in HSV1-tk positive tumors was 15.48 ± 3.94, 6.7-fold higher (p < 0.001) than in wild type tumors. Uptake of [3H]FEAU in transduced tumors was 9.98 ± 1.99, 5.0-fold higher (p < 0.001) than in wild type tumors. Micro-PET images using [18F]FIAU and [18F]FEAU also showed very high uptake in HSV-tk tumors. [18F]FIAU and [18F]FEAU appear to be potential PET imaging agents for gene expression.
Systematic Framework for Environmentally Conscious Chemical Process Design: Early and Detailed Design Stages

This paper presents a systematic and hierarchical approach for incorporating environmental considerations into all stages of chemical process design. The complexity of the environmental and economic assessments increases as the design proceeds. The design method integrates computer-aided process simulation with a suite of environmental impact, economic, and decision analysis software tools. At the earliest design stage, the environmental assessment includes emission estimates from major process equipment, considers pollution control efficiency, and generates nine risk-based environmental impact indices. The economic assessment is based on the cost of raw materials and reaction stoichiometry. This assessment method was applied to the selection of alternative feedstocks for a reaction step: benzene versus n-butane for maleic anhydride (MA) production. Using known yields and selectivities, the n-butane route was shown to be superior to the benzene route in both the raw material cost and environmental impact...
To tell a morphologically complex tale: investigating the story-telling abilities of children and adults with low literacy skills

This study examined differences between adults with low literacy skills and typically achieving children, who were matched on decoding ability, on their production of morphologically complex words (MC) in oral and written stories. In addition, we collected data on their morphological awareness, spelling, and vocabulary skills. Both adults and children were more likely to produce MC words in their oral stories compared to their written stories. While children were much more skilled at using –ed forms to produce past tense verbs than adults, adults were more likely to add –s to a verb and to produce contractions compared to children. Children and adults were comparable in pluralizing words, adding –ing to verbs, and producing derived MC words. For all of the literacy measures (morphological awareness, spelling, and vocabulary) adults always outperformed children. Thus, while adults were stronger in morphological awareness, spelling, and vocabulary, those skills did not seem to aid in the growth of explicitly applying morphological knowledge in the story-telling tasks.