cssi/SciSciGPT-SciSciNet huggingface dataset:
Improved bioavailability of orally administered mifepristone from PLGA nanoparticles.

Abstract The objective of this study was to prepare an oral dosage formulation of mifepristone that will improve the oral bioavailability of mifepristone and sustain the release of mifepristone for at least 3 days to effectively control reproduction, especially in coyotes. Nanoparticles containing mifepristone were prepared from dl -lactide/glycolide copolymers (PLGA). Encapsulation efficiency of the nanoparticles was determined by HPLC. In vitro release study was done in 30% isopropyl alcohol in water. In vivo bioavailability study was performed in male rats. Mifepristone and drug-loaded 50/50 PLGA, M W 4.4 kDa, nanoparticles (equivalent to 100 mg/kg mifepristone) were administered orally to rats. The concentration of mifepristone in serum at different time intervals was determined by HPLC. The average sizes of 50/50 PLGA ( M W 4.4 and 13 kDa) nanoparticles containing mifepristone were 516 and 468 nm, respectively. The drug encapsulation efficiency was 75.6% at 20% drug loading in 50/50 PLGA ( M W 4.4 kDa) nanoparticles. In vitro cumulative release of mifepristone from the 50/50 PLGA ( M W 4.4 and 13 kDa) nanoparticles with 20% drug loading was 60% and 48% in 72 h, respectively. In vivo studies in rats demonstrated that PLGA-1A-nanoparticles increase the bioavailability of mifepristone. We are currently using the nanoparticles containing mifepristone for efficacy studies in coyotes.
Engineered Ion Channels on Synthetic Flexible Membranes: Ion Channel Devices With Focus on Peptides

Recent studies of engineered ion channels on synthetic flexible membranes realized unprecedented materials properties. Starting with ion channels of known sequence and crystal structures, these studies outlined the structural basis for functional and regulatory properties, and developed new computational tools capable of predicting structural and functional properties of the native ion channels as well as native or engineered ion channels that were similar in structure to each other. The approaches taken to prepare the engineered composite membranes and the computational tools are generally applicable to the development, design and prediction of properties of a wide variety of materials such as selectively permeable membranes or functionalized thin films with desired chemical, electrical or optical properties. ClC-2 Cl− transporting channels and related ion channels were used for this work. The following major developments have facilitated this work. First, the X-ray crystal structure of a bacterial ClC Cl− channel was published and our group has been able to use that information in computational studies to develop structures for ClC channels and their transport mechanisms. Recent NMR and X-ray crystal structural studies have given important new information regarding the structure of the intracellular region, and this information helps to explain the structural basis for our findings that this same region is involved in phosphorylation-dependent regulation of the channel. Dissection and reconstitution of this region has already been carried out, raising our level of confidence that we can exploit this regulatory region to develop sensors in future studies. The group was then able to remove those native or engineered ion channels from cells, and place these onto a wide variety of synthetic supports without loss of function. This effort produced unique new materials with the ability to “sense” the environment and at the same time send an electrical signal reporting changes in the chemical or physical environment. These devices can sense chemicals and toxins and even shrink and swell or produce electrical energy from biochemicals. Indeed, the work contributes to a new field of engineering for producing materials with unprecedented properties. These materials can sense and report on chemical, physical and electromagnetic changes in the environment. In living cells, these ion channels other chemi-osmotic transport proteins use electrochemical gradients formed by light and chemical substrates to produce and interconvert energy, mechanical work, electrical work, osmotic work, chemical work and heat. Guided by new predictive computational approaches, these composite materials will do the same.© 2009 ASME
SOME EFFECTS OF SYNTHETICALLY PREPARED MALE HORMONE (ANDROSTERONE) IN THE RAT12

An outline of progress on the male hormone problem might be as follows: a) the demonstration by Berthold (1), in 1849, of an internal secretory action by the testis; b) emphasis directed towards hormone secretion and its function between 1900–1920 (2); c) the first successful extraction of the hormone from testicular tissue in 1927 by McGee (3); d) the crystallization of a male hormone, androsterone, from human urine by Butenandt in 1931 (4); e) the preparation in 1934 of androsterone by synthetic means from cholesterol by Ruzicka (5); f) the preparation in 1935 of a crystalline male hormone, testosterone, from fresh testicular tissue by David, Dingemanse, Freud and Laqueur (6); g) the preparation by synthetic means of testosterone in 1935 by Butenandt and Hanish (7) and Ruzicka and Wettstein (8) as well as the preparation of many other substances possessing androgenic activity (for review see 9). In addition, many facts have accumulated with regard to proper indicators for male hormone, perfection of met...
The effect of mean stress on delay in fatigue crack growth under load stepdown

Abstract The effect of mean stress together with decreasing stress range on fatigue crack propagation behaviour in mild steel is investigated. The delay period between crack arrest and reprogation is found to be a function of the maximum stress intensity factor stepdown ration, K 2max / K 1max . Delay only occurs when this ratio is less than unity. For specimen thicknesses of 1.6 to 6.4 mm, non-propagating cracks, where the affected delay cycles are 500 000 cycles or greater, appear to occur when K 2max / K 1max has a value of approximately 0.7 and the stepdown plastic zone size is about half the initial load plastic zone size, which is approximately equal to the affected crack length.
Response of an orthotropic cylindrical shell to sudden heating

Abstract The parametric resonance of thin elastic orthotropic cylindrical shells in plane strain to suddenly developed uniform temperature is investigated. The shells are fabricated from laminated fiber-reinforced composite materials. The short-term analysis identifies the excitation of particular unstable modes. The long-term analysis shows that the initially unstable circumferential flexural modes exchange energy with the circular mode in a cyclic manner. If the flexural motion is excited, the resulting displacements and stresses are substantially larger than the initial membrane values. The effects of temperature applied as a step function, shell geometry, number of layers, and fiber orientation are shown.
Levels of questions: A framework for the exploration of processing activities

Abstract This article examines the research on different levels of questions inserted in prose. The first section defines the level of questions and presents a number of theoretical issues important to the research. The second section discusses a number of methodological issues which arise in the studies, such as inadequate directions to subjects. The final section provides recommendations for further research.
Near-bottom observations of 4 kHz acoustic reflectivity and attenuation

A quantitative 4-kHz seismic profiling system has been developed as part of the Deep Tow Instrumentation System of the Marine Physical Laboratory at Scripps Institution of Oceanography. The system utilizes a sea‐going digital computer system aboard ship for real‐time processing and display of the quantitative near‐bottom reflectivity data. Preliminary results from the system are presented for four diverse areas of the Pacific Ocean floor: the Samoan Passage, the Carnegie Ridge, the San Diego Trough, and, in particular, an abyssal hill region several hundred miles west of San Diego where the system was first operated in real time during a survey in May 1974. These results exhibit a number of substantial variations in observed reflectivity on a small horizontal scale. To be more specific, they show (1) several db variations in layer reflectivity for horizontal distances less than 100 m for well‐defined reflectors; (2) abrupt changes of more than 7 db in subsurface reflectivity, which are generally coinciden...
Arrival time behavior of two-year-olds in child care

Twenty two-year-old children enrolled in a full day child care program were observed as they entered each morning to determine their behavior as they separated from their parents. Over 50% of the entrances involved children showing signs of contentment by waving and smiling. Fifty-five percent of the separations involved children using materials that were available in the classroom, most often sensory materials such as sand, water, and playdoh. The second most frequent separation aid was the use of transitional objects such as stuffed animals, blankets, and other toys brought from home. As a result of the observations, recommendations are made to assist caregivers in making arrival time easier for children, parents, and teachers.
Identification of the Rostral Migratory Stream in the Canine and Feline Brain

In the adult rodent brain, neural progenitor cells migrate from the subventricular zone of the lateral ventricle towards the olfactory bulb in a track known as the rostral migratory stream (RMS). To facilitate the study of neural progenitor cells and stem cell therapy in large animal models of CNS disease, we now report the location and characteristics of the normal canine and feline RMS. The RMS was found in Nissl-stained sagittal sections of adult canine and feline brains as a prominent, dense, continuous cellular track beginning at the base of the anterior horn of the lateral ventricle, curving around the head of the caudate nucleus and continuing laterally and ventrally to the olfactory peduncle before entering the olfactory tract and bulb. To determine if cells in the RMS were proliferating, the thymidine analog 5-bromo-2-deoxyuridine (BrdU) was administered and detected by immunostaining. BrdU-immunoreactive cells were present throughout this track. The RMS was also immunoreactive for markers of proliferating cells, progenitor cells and immature neurons (Ki-67 and doublecortin), but not for NeuN, a marker of mature neurons. Luxol fast blue and CNPase staining indicated that myelin is closely apposed to the RMS along much of its length and may provide guidance cues for the migrating cells. Identification and characterization of the RMS in canine and feline brain will facilitate studies of neural progenitor cell biology and migration in large animal models of neurologic disease.
Birefringence and Microstructure of Anisotropic Borosilicate Glasses

Optically anisotropic glasses were obtained by the uniaxial stretching of phase-separated borosilicate glasses in the transformation temperature range. The sign inversion of the birefringence, induced by subsequent heat treatments, was correlated with microstructure. The positive birefringence is attributed to form birefringence and the negative birefringence to “distribution birefringence” caused by the anisotropic distribution of the separated phase.
Renormalization Invariants of the Neutrino Mass Matrix

The renormalization evolution of all parameters in the neutrino mass matrix depends only on one variable, the energy scale. This fact, coupled with rephasing considerations, leads to a set of renormalization invariants, correlating the evolution of physical parameters. For the general three flavor case, we obtain these invariants explicitly and discuss their implications.
Activity of fenretinide plus chemotherapeutic agents in small-cell lung cancer cell lines

Purpose: Fenretinide [N-(4-hydroxyphenyl)retinamide, 4HPR], a synthetic retinoid, is a potent inducer of apoptosis in small-cell lung cancer (SCLC) cell lines that may act through the generation of reactive oxygen species, suggesting that it may enhance the activity of other cytotoxic agents. In light of 4HPR's clinical potential and potent activity against SCLC cells, we evaluated the in vitro activity of 4HPR in combination with cisplatin, etoposide or paclitaxel. Methods: The growth-inhibitory activities of single-agent 4HPR, cisplatin, etoposide or paclitaxel, and combinations of 4HPR and individual chemotherapeutic agents, were evaluated using an MTT assay in two SCLC cell lines. Each two-drug combination was studied over a range of concentrations at a fixed ratio corresponding to the ratio of the IC50 values of the individual agents. Data were analyzed by median-effect analysis as previously applied to drug combination studies. Results: All four agents inhibited growth in a dose-dependent manner in the NCI-H82 and NCI-H446 SCLC cell lines. At clinically reported drug concentrations that resulted in over 50% growth inhibition, the activities of the combinations 4HPR and cisplatin and 4HPR and etoposide were more than additive in both cell lines, and the activity of 4HPR plus paclitaxel was more than additive in NCI-H446 cells. Conclusion: 4HPR's potent single-agent activity, minimal toxicity, and potential synergy with standard cytotoxic drugs will allow for the development of promising investigational regimens for the treatment of patients with SCLC.
Intrusion and misuse detection in large-scale systems

Attacks and misuses of computer systems are major concerns in today's network-based world. With the growing concern with regard to cyberterrorism there is a need for new tools and techniques to monitor networks and systems for intrusions and misuse. The goal must be to identify an attack before an organization incurs damage, loses information (theft or otherwise), or has its integrity impugned. With today's network-based economic resources, a successful attack will negatively impact consumer confidence and decrease consumers' willingness to make electronic purchases. The authors present information visualization techniques based on a glyph metaphor for visually representing textual log information.
Pulmonary hemorrhage in systemic necrotizing vasculitis associated with hepatitis B.

Reported here is the first case of massive intrapahnonary hemorrhage emerging in the setting of systemic necrotizing vasculitis associated with hepatitis B surface antigen (HBsAG)—positive viral hepatitis. Demonstration of circulating immune complexes, cryoglobulins containing both HBsAg and HBsAb, and resolution of the symptoms following immunosuppressive therapy suggest an immune complex mediated tissue injury for this unusual complication.
Use of clay mineral (montmorillonite) for reducing poultry litter leachate toxicity (EC50).

Abstract Poultry litter (PL) has useful nutrients and is therefore used as manure. In addition to N, P and K, PL also contains some heavy metals (As, Cd, Cu, Mn, Pb and Zn), antibiotics, antioxidants, mold inhibitors and other organic compounds. Poultry litter aqueous leachate (PLL) has been shown to be toxic to many organisms; PLL is more toxic than the aqueous leachate of other animal manures used on agricultural soils. Clayey soils are known to retain toxic heavy metals. The objective of this study was to measure the change in toxicity (EC50) of PLL on the addition of clay mineral—montmorillonite. A significant reduction (124%) in toxicity of the clay poultry litter leachate (CLL) after 7 days was observed compared to the toxicity of the PLL alone after 1 day. This indicates that some of the toxic components of the litter were adsorbed by the clay.
THE EFFECTS OF DIRECTIVE AND NONDIRECTIVE PROMPTS ON NONCOMPLIANT VOCAL BEHAVIOR EXHIBITED BY A CHILD WITH AUTISM

Results of an analogue functional analysis indicated that noncompliant vocal behavior exhibited by a young girl with autism was maintained by negative reinforcement. Follow-up analyses suggested that the immediate escape contingency assessed in the demand condition did not appear to maintain the behavior. Instead, noncompliant vocal behavior occurred in response to directive prompts. Nondirective prompts reduced noncompliant vocal behavior to near zero.
Resonance Bands and Binary-Star Formation

: Numerical computations on the evolution of realistically stratified, asymmetric, sele-gravitating masses reveal the onset of an instability that is suggestive of, but not decisive for, the formation of a binary star. On the other hand, analysis of the evolution and stability of idealized models consisting of uniform-density ellipsoids has been qualitatively accurate in predicting certain features of the behavior of the more realistically stratified figures. This idealized theory is, therefore, reconsidered in an attempt to isolate additional qualitative features that may be common both to the idealized and to realistic figures, and therefore, serve not only as a guide in formulating issues to be addressed in numerical computations but also as a means of interpreting the outcomes of such calculations. Several such features are isolated in this paper, the most striking of which is the existence and importance of resonance bands of instability encountered by the evolutionary trajectories.
Can We Learn about Aging from a Study of Werner's Syndrome?

Werner's syndrome, a rare genetic condition, has many features suggestive of rapid, premature aging. However, it differs from normal aging in several important respects. Cultured skin fibroblast-like cells have markedly reduced growth potential and a characteristic pattern of multiple, variable, stable structural chromosomal rearrangements that are non-constitutional. Since Werner's syndrome is inherited in an autosomal recessive fashion, there is presumably a single gene defect or a multi-gene deletion that accounts for its multiple progeroid features. The identification of this defective protein (or proteins) would be of great interest to both basic gerontologic and clinical geriatric research, since it would shed light on the mechanisms underlying the normal aging process and the development of geriatric diseases. It is evident that such a protein(s) is not the sole determinant of youth or longevity, but the many progeroid manifestations of Werner's syndrome indicate that the basic molecular defect resides in or affects some central pathway of cellular control or homeostatic interaction.
Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466.

One of the most recently identified serotonin (5-hydroxytryptamine (5-HT)) receptor subtypes is the 5-HT6 receptor. Although in-depth localization studies reveal an exclusive distribution of 5-HT6 mRNA in the central nervous system, the precise biological role of this receptor still remains unknown. In the present series of experiments, we report the pharmacological and neurochemical characterization of two novel and selective 5-HT6 receptor agonists. WAY-181187 and WAY-208466 possess high affinity binding (2.2 and 4.8 nM, respectively) at the human 5-HT6 receptor and profile as full receptor agonists (WAY-181187: EC50=6.6 nM, Emax=93%; WAY-208466: EC50=7.3 nM; Emax=100%). In the rat frontal cortex, acute administration of WAY-181187 (3–30 mg/kg, subcutaneous (s.c.)) significantly increased extracellular GABA concentrations without altering the levels of glutamate or norepinephrine. Additionally, WAY-181187 (30 mg/kg, s.c.) produced modest yet significant decreases in cortical dopamine and 5-HT levels. Subsequent studies showed that the neurochemical effects of WAY-181187 in the frontal cortex could be blocked by pretreatment with the 5-HT6 antagonist, SB-271046 (10 mg/kg, s.c.), implicating 5-HT6 receptor mechanisms in mediating these responses. Moreover, the effects of WAY-181187 on catecholamines were attenuated by an intracortical infusion of the GABAA receptor antagonist, bicuculline (10 μM), confirming a local relationship between 5-HT6 receptors and GABAergic systems in the frontal cortex. In the dorsal hippocampus, striatum, and amygdala, WAY-181187 (10–30 mg/kg, s.c.) elicited robust elevations in extracellular levels of GABA without producing similar effects on concentrations of norepinephrine, serotonin, dopamine, or glutamate. In contrast to these brain regions, WAY-181187 had no effect on the extracellular levels of GABA in the nucleus accumbens or thalamus. Additional studies showed that WAY-208466 (10 mg/kg, s.c.) preferentially elevated cortical GABA levels following both acute and chronic (14 day) administration, indicating that neurochemical tolerance does not develop following repeated 5-HT6 receptor stimulation. In hippocampal slice preparations (in vitro), 5-HT6 receptor agonism attenuated stimulated glutamate levels elicited by sodium azide and high KCl treatment. Furthermore, in the rat schedule-induced polydipsia model of obsessive compulsive disorder (OCD), acute administration of WAY-181187 (56–178 mg/kg, po) decreased adjunctive drinking behavior in a dose-dependent manner. In summary, WAY-181187 and WAY-208466 are novel, selective, and potent 5-HT6 receptor agonists displaying a unique neurochemical signature in vivo. Moreover, these data highlight a previously undescribed role for 5-HT6 receptors to modulate basal GABA and stimulated glutamate transmission, as well as reveal a potential therapeutic role for this receptor in the treatment of some types of anxiety-related disorders (eg OCD).
Aviation security: NextGen Flight Risk Profile

This paper discusses the concept of the NextGen Flight Risk Profile (FRP), which is envisioned to provide a common operational reference model for depicting the risk assessment information, including a computed risk level, of all active flights in the FAA National Airspace System (NAS). The FRP is stipulated in the FAA's Air Domain Security Concept of Operations [1], which states that the FAA and its security partners will jointly develop the following: • A pre-defined set of security risk profiles that reflect the spectrum of threats which may jeopardize the NAS in any form. • A pre-determined set of potential FAA Air Traffic Organization (ATO) response options for each defined risk profile.
Assessment of IP injection of [18F]fallypride for behavioral neuroimaging in rats

Great progress has been made toward using small animal PET to assess neurochemical changes during behavior. [18F]fallypride (FAL) is a D2/D3 antagonist that is sensitive to changes in endogenous dopamine, and, in theory, could be used to assess changes in dopamine during behavioral paradigms. Tail vein injections of tracer require restraint in awake animals, and catheter implantation is invasive and can cause logistical problems. Thus, administering tracer with IP injections (which are well-tolerated by rodents) would be preferable. The purpose of this study was to determine whether IP injection of FAL would produce striatal uptake similar to that seen with traditional IV tail vein injection protocols. Four male Sprague–Dawley rats underwent IP injection of FAL, followed by a 30-min uptake and subsequent dynamic image acquisition on the IndyPET III small animal scanner. Three of these rats also received traditional dynamic scanning with IV FAL injection via a tail vein. Two rats that received IP injection had moderate striatal uptake, with striatum/cerebellum ratios (SUVR) that were only ∼20% lower than ratios from IV scans. Two other rats had little to no uptake; SUVR values were ∼70% lower than IV SUVR. These latter two animals showed heavy bone uptake, evidence of defluorination of FAL. The results of this pilot study suggest that it may be possible to achieve striatal uptake of FAL after IP injection. However, this was not seen consistently across animals. Future studies are needed to validate, and then to optimize, the use of IP FAL for behavioral imaging protocols.
Utility control of residential cooling: resident-perceived effects and potential program improvements

Abstract In a pilot utility direct load control (DLC) program in New Jersey, air conditioners of volunteer household were remotely cycled in order to reduce electric load demand. The resulting load savings and comfort effects of the program are analyzed. A discomfort-from-cycling index is constructed from participant logs of cooling adequacy. Load reductions are calculated from 5-min consumption data. Based on both the discomport index and reported internal temperatures, the DLC cycling did not create a comfort problem for most participants. When the DLC equipment was activated, participants reported only slight increases in temperature (from 78.4 to 79.0°F) and discomfort (increasing from 7% to 15%). Also, participants achieving higher load savings were not significantly more likely to report discomfort. Two variables which did significantly predict load savings were duty cycle and frequency of thermostatic cycling. Current DLC equipment uses a preset cycle-off time, typically 25% to 50%. This cycle-off percentage can be matched to average characteristics in a utility service area. However, since the percentage is preset it cannot be matched to the diversity in natural thermostatic cycling across houses. For example, this study finds that 16% of the houses had duty cycles below 0.50 on the hottest summer days during the hours selected for duty cycling. These houses cannot provide load savings with a DLC controller preset to 50% or less off-time. Fully 60% of the houses had duty cycles below 0.75 for this period, yielding no savings at 25% off-time and half the expected savings at 50% off-time. Two methods are proposed for improving efficiency of DLC programs: pre-screening based on measured duty cycle, and adoption of advanced DLC controllers. For the study sample, pre-screening is found to be not economical if it requires a separate site visit - surprisingly, it is cheaper to install equipment even in residences which will not yield by any load savings than to pay for screening visits. A more satisfactory improvement in DLC program efficiency would result from advanced DLC controllers with redesigned cycling logic. In place of the current fixed cycle-off percentage, an advanced controller is proposed which would choose the best cycle-off time based on each individual house's natural thermostatic duty cycle. The results indicate that this advanced controller would reduce program costs per kW saved by 29%. Such a controller would also achieve load savings more equitably, spreading cooling reductions more evenly across participants, and eliminate current programs' perverse incentive to oversize cooling equipment.
Parameterization of Infrared Absorption in Midlatitude Cirrus Clouds

Abstract Employing a new approach based on combined Raman lidar and millimeter-wave radar measurements and a parameterization of the infrared absorption coefficient σa (km−1) in terms of retrieved cloud microphysics, a statistical relation between σa and cirrus cloud temperature is derived. The relations σa = 0.3949 + 5.3886 × 10−3T + 1.526 × 10−5T2 for ambient temperature T(°C) and σa = 0.2896 + 3.409 × 10−3Tm for midcloud temperature Tm(°C) are found using a second-order polynomial fit. Comparison with two σa-versus-Tm relations obtained primarily from midlatitude cirrus using the combined lidar–infrared radiometer (LIRAD) approach reveals significant differences. However, it is shown that this reflects both the previous convention used in curve fitting (i.e., σa → 0 at ∼−80°C) and the types of clouds included in the datasets. Without such constraints, convergence is found in the three independent remote sensing datasets within the range of conditions considered to be valid for cirrus (i.e., cloud visib...
Luminal gastric somatostatin-like immunoreactivity in response to various stimuli in man

This study investigates release of somatostatin-like immunoreactivity (SLI) into the gastric lumen of five healthy human subjects in response to pharmacological stimuli (pentagastrin and secretin) and physiological stimuli (sham feeding and intrajejunal perfusion of elemental diet). Basal and poststimulation gastric juice aspirates were collected at 15-min intervals, extracted with acetone, and SLI determined by radioimmunoassay, with these results: (1) A considerable amount of SLI was secreted during the basal period. (2) Pentagastrin stimulated SLI release quickly and was associated with increased acid secretion. (3) Both secretin and sham feeding increased SLI only slightly. (4) During intrajejunal perfusion of the elemental diet, SLI increased significantly, was associated with decreased acid secretion, and rapidly returned to basal level when elemental diet was replaced by saline. Basal levels of gastric luminal SLI thus showed distinct changes in response to each stimulus. Although the physiological action of luminal SLI remains to be studied, its levels may reflect gastric D-cell activities.
Neuropsychological functioning in MRI-derived subgroups of schizophrenia

This study examined neuropsychological functioning in two subgroups of patients with familial schizophrenia. Those who showed evidence of progressive ventricular enlargement observed across serial MRI scans (n=6) were compared with subjects whose ventricular volume remained static (n=10) over an average of 28 months. No differences were found in terms of age, education, ethnicity, level of psychotic symptomatology, DSM-IV subtype, age of onset, or duration of illness. Neurocognitively, the static ventricle group was impaired across more cognitive domains and had a larger percentage of subjects falling into the impaired range on a majority of measures, with the greatest differences on measures of attention (p<0.02) and nonverbal memory (p<0.07). These results suggest that clinically meaningful differences between these two MRI-derived subgroups of patients with schizophrenia may exist, and further underscore the heterogeneity of the illness.
Nonlinear control of regulatory enzymes

In highly complex metabolic systems, composed of interlocking and overlapping biosynthetic and degradative pathways, the control of certain strategic enzyme activities is more critical to the maintenance of fine balance between the various metabolic functions than is the control of others. The overall regulatory plan of such pathways depend largely on the nature of the biochemical reactions, the extent of branching as well as the physiological requirements of the given organism. It is now recognized that various different kinds of feedback control mechanisms have been evolved in order to accommodate the regulation of such divergent pathways; the specific control characteristics of regulatory enzymes determine the desired regulatory patterns.
Human–Urban Wildlife Interface: Interactions Around Tilden Regional Park, San Francisco Bay Area, California

With more Americans now living in cities (Vandruff, Bolen, & San Julian, 1994), a better understanding of the relationships between people, wildlife, and the environment is necessary to formulate p...
ACELLULAR PERTUSSIS VACCINES IN ADULTS

The pathogenesis of pertussis, and the epidemiology and clinical manifestations of pertussis after childhood are reviewed as a background for a discussion of recent clinical trials of acellular pertussis vaccines in adults, and the vaccines' potential for routine use in adolescents and adults.
Diagnosis of acute bone/bone marrow infarction of the mandible in sickle hemoglobinopathy: Report of a case

Vasooclusive involvement of bones is a common cause of acute morbidity in patients with sickle cell hemoglobinopathy. Although the literature contains only two reports of infarction of the mandible in sickle cell vasooclusive crisis, earlier authors were often limited to the clinical examination as their primary or only diagnostic method. This article presents a sickle cell patient in vasoocclusive crisis who subsequently developed infarction of the right mandible without an infectious or inflammatory cause and was ultimately diagnosed by nuclear bone imaging scans.
Sex in the City: The Politics of Sexual Liberalism in Los Angeles, 1963–79

In Los Angeles, Hollywood in particular, straight-themed pornography and gay male nightlife became more visible and, moral reformers believed, of grave public concern between the early 1960s and the early 1970s. As a result, defining the limits of sexual freedom became a problem for urban public officials, who resolved the dilemma by casting heterosexual sex entertainment as disruptive of neighbourhood quality of life, making it a question of property values and crime, and reframing gay nightlife as an issue of privacy and the right of public assembly. The article considers battles over commercial pornography and battles over gay male rights and culture. As the civil rights and black power movements commanded, then lost, the attention of liberals, sexual libertarians and a mobilised gay rights movement forced urban politicians to reconsider the place of sex and sexual identity in public life. A new generation of urban liberals faced a difficult challenge: to respond to their constituents' libertarian views of sex and sexuality while not appearing to endorse civic disorder and economic decline. They had to defend both privacy rights and property rights.
Rem2-Targeted shRNAs Reduce Frequency of Miniature Excitatory Postsynaptic Currents without Altering Voltage-Gated Ca2+ Currents

Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) plays important roles in neuronal cell development and function. Rem2 is a member of the RGK (Rad, Rem, Rem2, Gem/Kir) subfamily of small GTPases that confers potent inhibition upon VGCCs. The physiologic roles of RGK proteins, particularly in the brain, are poorly understood. Rem2 was implicated in synaptogenesis through an RNAi screen and proposed to regulate Ca2+ homeostasis in neurons. To test this hypothesis and uncover physiological roles for Rem2 in the brain, we investigated the molecular mechanisms by which Rem2 knockdown affected synaptogenesis and Ca2+ homeostasis in cultured rat hippocampal neurons. Expression of a cocktail of shRNAs targeting rat Rem2 (rRem2) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) measured 10 d after transfection (14 d in vitro), but did not affect mEPSC amplitude. VGCC current amplitude after rRem2-targeted knockdown was not different from that in control cells, however, at either 4 or 10 d post transfection. Co-expression of a human Rem2 that was insensitive to the shRNAs targeting rRem2 was unable to prevent the reduction in mEPSC frequency after rRem2-targeted knockdown. Over-expression of rRem2 resulted in 50% reduction in VGCC current, but neither the mEPSC frequency nor amplitude was affected. Taken together, the observed effects upon synaptogenesis after shRNA treatment are more likely due to mechanisms other than modulation of VGCCs and Ca2+ homeostasis, and may be independent of Rem2. In addition, our results reveal a surprising lack of contribution of VGCCs to synaptogenesis during early development in cultured hippocampal neurons.
Costa Rica después del TLC: ¿LA CALMA QUE SIGUE A LA TEMPESTAD?

La resolucion del conflicto politico alrededor de la ratificacion del Tratado de Libre Comercio con los Estados Unidos, Centroamerica, y la Republica Dominicana (DRCAFTA ) represento una importante oportunidad politica para Costa Rica en el 2008. No obstante, el gobierno no logro aprovechar la coyuntura para avanzar en problemas de fondo mas alla de la Agenda de Implementacion del Tratado. Su incapacidad de establecer un espacio de encuentro con la oposicion, aunada a la debilidad de su mandato y a los obstaculos estructurales del sistema politico, coartaron la posibilidad de construir consensos. En suma, la ausencia de una conduccion estrategica hizo del ano una oportunidad perdida para alcanzar logros politicos sustantivos.
Community Mobilization Prospects for the Future

In this brief essay, we seek to add to the discussion on the prospects of community mobilization by offering four major points. The impact of human agency, not only structural conditions, must be c...
The rat TSHβ gene contains distinct response elements for regulation by retinoids and thyroid hormone

Abstract We have previously shown that thyroid stimulating hormone- β (TSH β ) mRNA levels are modulated by vitamin A status in vivo and using transient transfection, that suppression of rat TSH β gene promoter activity by all- trans retinoic acid (RA) requires RA receptor (RAR) and retinoid X receptor (RXR). In this paper we have used deletion analysis to delineate the sequences of the rTSH β gene involved in RA regulation, their relationship to the rTSH β gene negative thyroid hormone response elements and the retinoid receptor species that interact with these sequences. Using transient transfection in CV-1 cells, we found that the −204/+9 region of the rat TSH β gene, when fused to a luciferase reporter, was sufficient for suppression by all- trans -RA in the presence of RAR/RXR. Thus, regulation by RA did not involve the major rTSH β negative TRE located between +15 and +43. Mutational analysis also showed that the minor rTSH β negative TRE between −11 and +5 was not required by suppression by RA. However, in a heterologous promoter this sequence element acted as a strong positive RARE. The combination of RA and T3 treatment caused synergistic inhibition of rat TSH β gene expression in the presence of RAR/RXR and TR. EMSA analysis demonstrated that the −204/−79 sequence binds RAR/RXR heterodimer. Therefore, we conclude that there are separate response elements for RA and T3 on the rat TSH β gene, that the RARE binds RAR/RXR heterodimer and that RA and T3 interact functionally via these elements in the negative regulation of rat TSH β gene expression.
The influence of temperature and spatial distribution on the susceptibility of southern leopard frog eggs to disease

Since host defenses to infectious disease are often costly, one would expect hosts to use their defenses only when the threat of infection is high. Southern leopard frogs (Rana sphenocephala) at Ellenton Bay in South Carolina (USA) have an extended breeding season and their eggs are exposed to a wide range of temperatures depending on the time of year when they are laid. Adults aggregate their egg masses in cold temperatures, but separate them in warm temperatures. The spatial aggregation of egg masses may insulate eggs from cold temperatures, but may also affect the transmission of pathogens between the eggs. I examined the effects of temperature, pathogens, and spatial distribution on the survival of R. sphenocephala in the egg stage. Field observations found that temperature had little effect on the number of infected eggs within egg masses, but that egg masses in colder water were more likely to be aggregated together. In a controlled laboratory experiment, the presence of aquatic oomycetes led to higher mortality in cold temperatures than they did at warmer temperatures. Infectious disease may be a selective force that favors R. sphenocephala adults that aggregate their offspring when the threat of disease is high. Host aggregation can reduce the risk of infection when pathogens have a slow generation time that hinders them from responding to an abundance of hosts.
Effect of stress on oral morphine and fentanyl self-administration in rats.

Abstract The effect of immobilization stress (15 min/day) or no stress on oral morphine (0.25–0.5 mg/ml) or fentanyl (5–20 μg/ml) self-administration was examined in rats. Animals had access to a morphine or fentanyl solution for 4 days, followed by a single-choice day of access to the opioid solution and a separate water bottle. This 5-day cycle was repeated five times for 7 h/day in home cages. Morphine consumption and preference were assessed for an additional 30 days (i.e., six more cycles) in a subgroup of subjects. Plasma corticosterone levels in the stress groups indicated that the stress manipulation was effective. Over the course of the experiment, animals in the stress groups significantly increased their preference for the opioid solutions during choice days compared to nonstress controls. Morphine preference after 55 days was twice as high in the stress group (70% morphine/30% water) in comparison to controls (34% morphine/66% water). These results indicate that stress increases oral opioid self-administration in rats. Future directions and the implications of this work are discussed.
Comparison of similar narrow molecular weight polystyrenes

Discrepancies between the level of the viscosity at 200°C of the Dow series of polystyrenes and another narrow molecular weight distribution polystyrenes have been pointed out by Toosi, Porter, and Johnson in 1969. Penwell and Graessley have shown in 1974 that over a wide range in temperature one member of this series, S109, has a significantly lower viscosity than samples of similar molecular weight from other sources. Fetters has established the presence of high molecular weight tails in several of the much studied series. The investigation being reported here reveals the effect of the high molecular weight tail in the viscoelastic behavior of the S109 in the terminal zone of response. In addition, it is shown by an enhanced rate of creep in the glass to rubber-like dispersion that the glass temperature of the S109 is depressed by about 4°C.
Bioelectronics: A positive future for squid proteins.

Protein-based protonic conductivity plays an important role in nature, but has been explored little outside of a biological setting. Now, proton conductors have been developed based on the squid protein reflectin, and integrated with devices for potential bioelectronic applications.
Declining Rates of Osteoporosis Management Following Fragility Fractures in the U.S., 2000 Through 2009

Background: Clinical practice recommendations state that patients with fragility fractures should be evaluated for osteoporosis and treated for the disease if it is present. The purpose of this study was to assess osteoporosis evaluation and treatment patterns for patients with fragility fractures and assess whether anti-osteoporosis pharmacotherapy initiated immediately following a fragility fracture is associated with improved adherence to the treatment protocol. Methods: This retrospective cohort study involved data from a large commercially insured population seen in the period from 2001 through 2009. Patients were community-dwelling individuals aged fifty years or older who had a new low-energy fracture at the hip, vertebra, wrist, or humerus with no evidence of a fragility fracture, osteoporosis treatment, malignant disease, or Paget disease for twelve months preceding the fracture. Rates of diagnostic testing and pharmacotherapy for osteoporosis within twelve months post-fracture were evaluated. Patients treated with oral bisphosphonates were evaluated to determine whether twelve-month adherence to the treatment protocol differed between those who had initiated therapy sooner (at zero to ninety days) and those who initiated it later (at ninety-one to 365 days) following the fracture. Results: The 88,571 women and 41,984 men had an average age of 72.3 years and 70.5 years, respectively. Nineteen percent (16,464) of the women and 10% (4014) of the men initiated osteoporosis pharmacotherapy, and 30% (26,481) of the women and 15% (6427) of the men underwent diagnostic testing and/or pharmacotherapy following fracture. Treatment rates were highest following vertebral fracture and lowest following wrist or humeral fracture. Treatment rates significantly decreased over time (from 2001 through 2009). The average twelve-month adherence (medication possession ratio) was 56% and 61% among women and men, respectively. Adherence was similar between patients who had initiated treatment sooner after the fracture and those who had initiated it later after the fracture. Conclusions: Clinical guidelines for evaluation and treatment following fragility fracture were met for less than one-third of women and less than one-sixth of men. While primary fracture prevention remains the ideal, secondary prevention is critical and there is a need to reverse the downward trend in adherence to post-fracture guidelines. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Triad Tasks, a Multipurpose Tool to Elicit Similarity Judgments: The Case of Tzotzil Maya Plant Taxonomy:

The universality of multipurpose taxonomies has been widely established in folk biology. However, recent studies with nonprofessional fish experts in the United States as well as with tree experts in the Chicago area suggest that different goals can affect category organization of natural kinds. This article reports the results of a triad task study exploring specific aspects of the multipurpose plant taxonomy among the Tzotzil Maya of Zinacantan in the Highlands of Chiapas. Despite previously encountered differences with respect to saliency, no corresponding differences with respect to conceptual organization could be detected. A balanced incomplete block design was applied. Resolution was enhanced by allowing participants to judge the three items as either “too similar” or “too different” in addition to single out one item as different. Analyses explore (1) the pattern of informant agreement (as a precondition for), (2) the content of existing models, and (3) the saliency of responses.
Identification of a specific gene expression pattern associated with HCV-induced pathogenesis in HCV- and HCV/HIV-infected individuals.

Gene expression profiling was performed on liver biopsies from 28 patients (12 HCV and 16 HCV/HIV infected) in an attempt to understand the mechanisms of HCV liver disease in the presence and absence of HIV coinfection. The data were compared with clinical observations and a gene expression database obtained for transplant HCV-infected samples. This is the first report of functional genomics being used to compare intrahepatic gene expression profiles of HCV- and HCV/HIV-infected individuals. Significantly, the intrahepatic global gene expression profiles do not differ between HCV- and HCV/HIV-infected individuals. However, a subset of patients was identified who share a specific pattern of gene expression, termed the enhanced gene expression (EGE) pattern. Specifically, the EGE (+) patients show a dramatic decreased expression of multiple genes associated with the FAS-apoptosis pathway and increased expression of lymphocyte adhesion molecules and lymphocyte-specific genes. The EGE (+) patients also have partially impaired Type I and II IFN-mediated antiviral responses, including a lack of induction of the anti-fibrogenic cytokine IFN-γ. Importantly, the pattern of gene expression observed in EGE (+) patients has similarities to patients who developed fibrosis within 1 year of receiving a liver transplant.
Argument and Decision Making in Computer‐Mediated Groups

Following Gouran (1994), the authors proposed four hypotheses that predict the probability of computer-mediated groups (CMGs) endorsing proposals based on (a) the number of reasons offered for them, (b) the number of members advancing these reasons, (c) the net number of positive reactions to the reasons advanced, and (d) the development of support for the reasons. Results from 11 groups that had long collaborated exclusively through computer-mediated means indicated that members in support of a proposal relative to those in opposition as well as the development of their arguments were significant predictors of decision outcomes. Moreover, the number of responses for/against a proposal and the difference in the positive and negative reactions to decision proposals were good independent predictors of decision outcomes.