bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimation
Authors: Patil Anand P , Okiro Emelda A , Gething Peter W , Guerra Carlos A , Sharma Surya K , Snow Robert W , Hay Simon I
Published: August 2009

Background

Clinical malaria has proven an elusive burden to enumerate. Many cases go undetected by routine disease recording systems. Epidemiologists have, therefore, frequently defaulted to actively measuring malaria in population cohorts through time. Measuring the clinical incidence of malaria longitudinally is labour-intensive and impossible to undertake universally. There is a need, therefore, to define a relationship between clinical incidence and the easier and more commonly measured index of infection prevalence: the "parasite rate". This relationship can help provide an informed basis to define malaria burdens in areas where health statistics are inadequate.

Methods

Formal literature searches were conducted forPlasmodium falciparummalaria incidence surveys undertaken prospectively through active case detection at least every 14 days. The data were abstracted, standardized and geo-referenced. Incidence surveys were time-space matched with modelled estimates of infection prevalence derived from a larger database of parasite prevalence surveys and modelling procedures developed for a global malaria endemicity map. Several potential relationships between clinical incidence and infection prevalence were then specified in a non-parametric Gaussian process model with minimal, biologically informed, prior constraints. Bayesian inference was then used to choose between the candidate models.

Results

The suggested relationships with credible intervals are shown for the Africa and a combined America and Central and South East Asia regions. In both regions clinical incidence increased slowly and smoothly as a function of infection prevalence. In Africa, when infection prevalence exceeded 40%, clinical incidence reached a plateau of 500 cases per thousand of the populationper annum. In the combined America and Central and South East Asia regions, this plateau was reached at 250 cases per thousand of the populationper annum. A temporal volatility model was also incorporated to facilitate a closer description of the variance in the observed data.

Conclusion

It was possible to model a relationship between clinical incidence andP. falciparuminfection prevalence but the best-fit models were very noisy reflecting the large variance within the observed opportunistic data sample. This continuous quantification allows for estimates of the clinical burden ofP. falciparumof known confidence from wherever an estimate ofP. falciparumprevalence is available.
Gonadotropin-releasing hormone (GnRH)-I and GnRH-II induce cell growth inhibition in human endometrial cancer cells: Involvement of integrin beta3 and focal adhesion kinase
Authors: Park Dong Wook , Choi Kyung-Chul , MacCalman Colin D , Leung Peter CK
Published: August 2009

Endometrial carcinoma is the most common neoplasm of the female genital tract, accounting for nearly one half of all gynecologic cancers in the Western world. Although intensive research on pathological phenomena of endometrial cancer is currently going on, but exact cause and biological aspects of this disease are not well described yet. In addition to well-documented roles of gonadotropin-releasing hormone (GnRH) in hypopituitary ovarian (HPO) axis, the agonistic or antagonistic analogs (or both) of GnRH have been shown to inhibit the proliferation of a variety of human gynecologic cancers. Thus, in the present study, we further examined the possibility that GnRH induces integrin beta3 and activation of focal adhesion kinase (FAK) through mitogen-activated protein kinases (MAPKs), ERK1/2 and p38, to inhibit the growth of HEC1A endometrial cancer cell line. As a result, both GnRH-I and GnRH-II resulted in a significant increase in integrin beta3 expression and evoked the activation of FAK in a time-dependent manner in these cells. In addition, these analogs induced an activation of ERK1/2 and p38 MAPK in a time-dependent manner as downstream pathways of FAK. It appears that GnRH-II has much greater effect on the activation of FAK, ERK1/2 and p38 compared to GnRH-I in these cells. Further, we demonstrated that the growth inhibition of HEC1A cells by GnRH-I or GnRH-II is involved in the activation of integrin-FAK and ERK1/2 and p38 MAPK pathways. Taken together, these results suggest that GnRH may be involved in the inhibition of endometrial cancer cell growth via activation of integrin beta3 and FAK as a direct effect. This knowledge could contribute to a better understanding of the mechanisms implicated in the therapeutic action of GnRH and its biomedical application for the treatment against endometrial cancer.
Twelve years of clinical practice guideline development, dissemination and evaluation in Canada (1994 to 2005)
Authors: Kryworuchko Jennifer , Stacey Dawn , Bai Nan , Graham Ian D
Published: August 2009

Background

Despite the growing availability of clinical practice guidelines since the early 1990's, little is known about how guideline development and dissemination may have changed over time in Canada. This study compares Canadian guideline development, dissemination, and evaluation in two six year periods from 1994–1999 and 2000–2005.

Methods

Survey of guideline developers who submitted their clinical practice guidelines to the Canadian Medical Association Infobase (a Canadian guideline repository) between 1994 and 2005. Survey items included information about the developers, aspects of guideline development, and dissemination and evaluation activities.

Results

Surveys were sent to the developers of 2341 guidelines in the CMA Infobase over the 12 year period, 1664 surveys were returned (response rate 71%). Of these, 730 unique guidelines were released from 1994–1999, and 630 were released from 2000–2005. Compared to the earlier period, more recent guidelines were being produced in English only. There has been little change in the type of organizations developing guidelines with most developed by provincial and national organizations. In the recent period, developers were more likely to report using computerized search strategies (94% versus 88%), publishing the search strategy (42% versus 34%), reaching consensus using open discussion (95% versus 78%), and evaluating effectiveness of the dissemination strategies (12% versus 6%) and the impact of the CPGs on health outcomes (24% versus 5%). Recent guidelines were less likely to be based on literature reviews (94% versus 99.6%) and were disseminated using fewer strategies (mean 4.78 versus 4.12).

Conclusion

Given that guideline development processes have improved in some areas over the past 12 years yet not in others, ongoing monitoring of guideline quality is required. Guidelines produced more recently in Canada are less likely to be based on a review of the evidence and only about half discuss levels of evidence underlying recommendations. Guideline dissemination and implementation activities have actually decreased. Unfortunately, the potential positive impact on patient health outcomes will not be realized until the recommendations are adopted and acted upon.
A review of COFRADIC techniques targeting protein N-terminal acetylation
Authors: Van Damme Petra , Van Damme Jozef , Demol Hans , Staes An , Vandekerckhove Joël , Gevaert Kris
Published: August 2009

Acetylation of nascent protein Nα-termini is a common modification among archae and eukaryotes and can influence the structure and function of target proteins. This modification has been studied on an individual protein or (synthetic) peptide level or on a proteome scale using two-dimensional polyacrylamide gel electrophoresis. We recently developed mass spectrometry driven proteome analytical approaches specifically targeting the amino (N) terminus of proteins based on the concept of diagonal reverse-phase chromatography. We here review how this so-called combined fractional diagonal chromatography (COFRADIC) technique can be used in combination with differential mass-tagging strategies as to both qualitatively and quantitatively assess protein Nα-acetylation in whole proteomes.
Functional consequences of cleavage, dissociation and exocytotic release of ZP3R, a C4BP-related protein, from the mouse sperm acrosomal matrix
Authors: Buffone Mariano G. , Kim Kye-Seong , Doak Birgit J. , Rodriguez-Miranda Esmeralda , Gerton George L.
Published: August 2009

The acrosome is an exocytotic vesicle located on the apical tip of the sperm head. In addition to having different morphological regions, two biochemically distinct compartments can be defined within the acrosome: a particulate acrosomal matrix and a soluble partition. The domains within the acrosome participate in the release of acrosomal proteins from the sperm during exocytosis, depending on whether the proteins partition into either the soluble or matrix compartments of the acrosome. We have examined the mechanism of differential release by evaluating the solubilization of acrosomal matrix protein ZP3R (sp56) from mouse sperm during the course of spontaneous acrosomal exocytosis. Using indirect immunofluorescence and immunoblotting, we found that the ZP3R monomer is processed from 67,000 Mr to 43,000 Mr by proteases coincident with release from the acrosome. Sperm require a maturational step, termed capacitation, before they are competent for acrosomal exocytosis and the processing of ZP3R is dramatically reduced under non-capacitating conditions. The cleavage probably takes place in complement control protein domain (CCP) 6 or the bridge region between CCP6 and CCP7, which is not present in the guinea pig orthologue AM67. The cleaved form of ZP3R does not bind to unfertilized eggs. We have incorporated these structural considerations into a model to explain the functional consequences of acrosomal exocytosis on sperm-zona interactions.
Assessment of effective stress intensity factors using thermoelastic stress analysis
Authors: Diaz F A , Patterson E A , Yates J R
Published: August 2009

It has been demonstrated that thermoelastic stress analysis (TSA) can provide accurate information about the real crack-driving force for fatigue crack growth. Experiments were conducted using aluminium 2024 compact tension specimens which were initially pre-cracked to different crack lengths at a constant R ( R = 0). Subsequently, thermoelastic images were captured at increasing R values from 0 to 0.5 and Δ K values from 3 to 6 MPa m0.5 were calculated. The images showed a dramatic change in the stress pattern ahead of the crack tip as R decreased which was always associated with an increase in phase difference (loss of adiabatic conditions) ahead of the crack tip. This indicates that the technique is able to account for the change in conditions that arise from contact between the crack faces. To support this observation, thermoelastic results have been compared with those obtained using compliance methods. The results showed a very good level of agreement, illustrating the ability of TSA to infer successfully the effective Δ K.
Creep analysis of an internally pressurized thick cylinder made of a functionally graded composite
Authors: Singh T , Gupta V K
Published: August 2009

In the present study, a mathematical model has been developed to describe steady-state creep in an isotropic functionally graded composite cylinder. The cylinder is subjected to internal pressure and is made of functionally graded composite containing linearly varying silicon carbide particles in a matrix of pure aluminium. The cylinder is assumed to creep according to a threshold stress-based creep law having a stress exponent 5. The effect of employing a linear gradient in the distribution of reinforcement has been observed on the variation of creep stresses and creep rates in the composite cylinder. It is observed that the radial stress in the cylinder decreases throughout with the increase in reinforcement gradient, whereas the tangential, axial, and effective stresses increase significantly near the inner radius but show significant decrease towards the outer radius. The strain rates in the composite cylinder could be reduced significantly by tailoring the distribution of reinforcement while maintaining the same average amount of reinforcement. The distribution of strain rate becomes relatively uniform with increase in particle gradient.
A study of the influences of particles in the gas flow passage of a piston ring pack on the tribological performances of the piston ring
Authors: Meng F-M , Wang J-X , Xiao K
Published: August 2009

The influences of particles in the gas flow passage of a piston ring pack on the tribolo-gical performances of rings were numerically investigated based on a modified blow-by equation incorporating the particle effect and associated equations. Meanwhile, the particle effect on the blow-by of rings, inter-ring gas pressure, friction force, stresses, pressure, and deformation of the ring was solved by the Runge—Kutta method and the fast Fourier transform (FFT) technique. The numerical results show that obvious changes in the blow-by of the ring and the inter-ring gas pressure can occur if the particle effect is considered. The effect depends on the combined effect of the area, position, and number of particles. Meanwhile, the friction force of the top face of the ring, and the maximum Von Mises stress of the inner ring surface, contact pressure, deformation, and maximum shear stress of the contacting surface of the ring can obviously increase because of the particle effect.
The prediction of hot streak migration in a high-pressure turbine
Authors: Ong J , Miller R J , Denton J D
Published: August 2009

Accurate predictions of combustor hot streak migration enable the turbine designer to identify high-temperature regions that can limit component life. It is therefore important that these predictions are achieved within the short time scales of a design process. This article compares temperature measurements of a circular hot streak through a turning duct and a research turbine with predictions using a three-dimensional Reynolds-averaged Navier—Stokes solver. It was found that the mixing length turbulence model did not predict the hot streak dissipation accurately. However, implementation of a very simple model of the free stream turbulence (FST) significantly improved the exit temperature predictions on both the duct and research turbine. One advantage of the simple FST model described over more complex alternatives is that no additional equations are solved. This makes the method attractive for design purposes, as it is not associated with any increase in computational time.
The control of wave energy converters using active bipolar damping
Authors: Folley M , Whittaker T
Published: August 2009

A novel method for controlling wave energy converters using active bipolar damping is described and compared with current control methods. The performance of active bipolar damping is modelled numerically for two distinct types of wave energy converter and it is found that in both cases the power capture can be significantly increased relative to optimal linear damping. It is shown that this is because active bipolar damping has the potential for providing a quasi-spring or quasi-inertia, which improves the wave energy converter's tuning and amplitude of motion, resulting in the increase in power capture observed. The practical implementation of active bipolar damping is also discussed. It is noted that active bipolar damping does not require a reactive energy store and thereby reduces the cost and eliminates losses due to the cycling of reactive energy. It is also noted that active bipolar damping could be implemented using a single constant pressure double-acting hydraulic cylinder and so potentially represents a simple, efficient, robust and economic solution to the control of wave energy converters.
Evaluation of Compliance with a Paper-based, Multiplication-factor, Intravenous Insulin Protocol
Authors: Cyrus Rachel M , Szumita Paul M , Greenwood Bonnie C , Pendergrass Merri L
Published: August 2009

Background:

Hyperglycemia is common in critically ill patients and is an independent risk factor for in-hospital morbidity and mortality.

Objective:

To assess compliance with a paper-based, multiplication-factor, intravenous insulin protocol.

Methods:

A retrospective chart review was conducted in a 720-bed urban, academic medical center in Boston, Massachusetts. During a 1-month period, compliance with and the consequent safety and efficacy of the Brigham and Women's Hospital paper-based, multiplication-factor, intravenous insulin protocol was evaluated.

Results:

The primary endpoint of protocol compliance, defined as correct adjustment to insulin infusion rate and correct timing of bedside blood glucose concentration (BBGC) checks ±10 minutes of prespecified BBGC check according to the Brigham and Women's Hospital Intravenous Insulin Protocol (BHIP), was 47.2%. Seventy-two patients met inclusion criteria. Appropriate adjustment of infusion rates occurred 68.2% (1206/1768) of the time. Compliance with the timing of BBGC checks was found to be the majority of protocol violations. BBGCs were monitored ±5 minutes of indicated time per the protocol 26.2% (463/1768) of the time. Blood glucose concentration checks within extended timing of ±10 minutes of indicated time per the protocol occurred 793 (44.8%) times. Blood glucose concentration monitoring took place greater than 20 minutes past indicated time 450 (25.5%) times. In 1768 measurements, blood glucose concentrations between 40 and 60 mg/dL occurred 23 (1.3%) times in 12 (16.7%) patients. Blood glucose concentrations 40 mg/dL or less were detected 3 (0.17%) times in 2 (2.7%) patients. None of these hypoglycemic events led to documented complications.

Conclusions:

Overall, a rather low level of compliance with a paper-based, multiplication-factor, intravenous insulin protocol was observed, which warrants further investigation. Compliance rates in this evaluation were found to be similar to the rates observed in previously evaluated fixed-dose intravenous insulin protocols. Protocol noncompliance may be associated with hypo- and hyperglycemia.
Student–Teacher Relationship Stability Across Early School Years for Children With Intellectual Disability or Typical Development
Authors: Blacher Jan , Baker Bruce L. , Eisenhower Abbey S.
Published: August 2009

Student–teacher relationships of 37 children with moderate to borderline intellectual disability and 61 with typical cognitive development were assessed from child ages 6–8 years. Student–teacher relationship quality was moderately stable for the typical development group, but less so for the intellectual disability group. At each assessment these relationships were poorer for children with intellectual disability. Child behavior problems consistently predicted more conflict, whereas social skills predicted more closeness. Accounting for these child characteristics reduced the status group difference to nonsignificance. Earlier student–teacher relationships predicted subsequent changes in child behavior problems and social skills. Student–teacher relationships in the intellectual disability group were significantly lower for children in regular than special classes by age 8.
Aberration-free laser beam in the soft x-ray range
Authors: Goddet J. Ph. , Sebban S. , Gautier J. , Zeitoun Ph. , Valentin C. , Tissandier F. , Marchenko T. , Lambert G. , Ribière M. , Douillet D. , Lefrou T. , Iaquaniello G. , Burgy F. , Maynard G. , Cros B. , Robillard B. , Mocek T. , Nejdl J. , Kozlova M. , Jakubczak K.
Published: August 2009

By seeding an optical-field-ionized population-inverted plasma amplifier with the 25th harmonic of an IR laser, we have achieved what we believe to be the first aberration-free laser beam in the soft x-ray spectral range. This laser emits within a cone of
1.34 mrad

(1∕e2)
at a repetition rate of
10 Hz
at a central wavelength of
32.8 nm
. The beam exhibits a circular profile and wavefront distortions as low as
λ∕17
. A theoretical analysis of these results shows that this high beam quality is due to spatial filtering of the seed beam by the plasma amplifier aperture.
Advanced Correlative Light/Electron Microscopy: Current Methods and New Developments Using Tokuyasu Cryosections
Authors: Cortese Katia , Diaspro Alberto , Tacchetti Carlo
Published: August 2009

Microscopy is an essential tool for analysis of cellular structures and function. With the advent of new fluorescent probes and super-resolution light microscopy techniques, the study of dynamic processes in living cells has been greatly facilitated. Fluorescence light microscopy provides analytical, quantitative, and three-dimensional (3D) data with emphasis on analysis of live cells using fluorescent markers. Sample preparation is easy and relatively inexpensive, and the use of appropriate tags provides the ability to track specific proteins of interest. Of course, only electron microscopy (EM) achieves the highest definition in terms of ultrastructure and protein labeling. To fill the gap between light microscopy and EM, correlative light and electron microscopy (CLEM) strategies have been developed. In particular, hybrid techniques based upon immuno-EM provide sensitive protein detection combined with high-resolution information on cell structures and protein localization. By adding the third dimension to EM with electron tomography (ET) combined with rapid freezing, CLEM techniques now provide additional tools for quantitative 3D analysis. Here, we overview the major methods applied and highlight the latest advances in the field of CLEM. We then focus on two selected techniques that use cryosections as substrate for combined biomolecular imaging. Finally, we provide a perspective of future developments in the field.
Cultural Brands from Emerging Markets: Brand Image across Host and Home Countries
Authors: Guzmán Francisco , Paswan Audhesh K.
Published: August 2009

Cultural brands embody a sum total of a group's cultural identity, including a surrounding myth, a tie to its cultural roots, and associations of its past and aspired future. The authors focus on two cultural brands from Mexico and analyze whether their brand images remain consistent when they cross the border into the United States. Data were collected from random samples drawn from Mexico City and the Latino community (of Mexican descent) in the Dallas–Fort Worth area. Respondents were asked to evaluate two television media brands using a brand personality scale. The results indicate that the association between the brand personality dimensions and the cultural brands from Mexico is stronger among Latinos residing in the Dallas–Fort Worth area than among their counterparts in Mexico City. This study contributes to brand personality literature and presents an important insight into the brand image of cultural brands from emerging markets.
How Brand Community Practices Create Value
Authors: Schau Hope Jensen , Muñiz Albert M. , Arnould Eric J.
Published: August 2009

Using social practice theory, this article reveals the process of collective value creation within brand communities. Moving beyond a single case study, the authors examine previously published research in conjunction with data collected in nine brand communities comprising a variety of product categories, and they identify a common set of value-creating practices. Practices have an “anatomy” consisting of (1) general procedural understandings and rules (explicit, discursive knowledge); (2) skills, abilities, and culturally appropriate consumption projects (tacit, embedded knowledge or how-to); and (3) emotional commitments expressed through actions and representations. The authors find that there are 12 common practices across brand communities, organized by four thematic aggregates, through which consumers realize value beyond that which the firm creates or anticipates. They also find that practices have a physiology, interact with one another, function like apprenticeships, endow participants with cultural capital, produce a repertoire for insider sharing, generate consumption opportunities, evince brand community vitality, and create value. Theoretical and managerial implications are offered with specific suggestions for building and nurturing brand community and enhancing collaborative value creation between and among consumers and firms.
Field studies on deterrent properties of phlorotannins in Antarctic brown algae
Authors: Iken Katrin , Amsler Charles D. , Amsler Margaret O. , McClintock James B. , Baker Bill J.
Published: August 2009

Antiherbivore effects of phlorotannins from eight common Antarctic brown algae were tested with three omnivorous sympatric grazers, the fish Notothenia coriiceps, the sea star Odontaster validus, and the amphipod Gondogeneia antarctica. Incidence of grazing deterrence overall was relatively low, with only a few algal species deterring each of the grazers, and with phlorotannins from different algae active against different grazers. Most activity was found in Desmarestia menziesii and Cysto-sphaera jacquinotii, which deterred two out of the three grazers, while D. anceps and Himantothallus grandifolius deterred only one grazer type each. Only weak antimicrobial effects were detected in all phlorotannin extracts against four Antarctic bacterial strains, with phlorotannins of D. anceps and Phaeurus antarcticus having the strongest effects. Phlorotannin extracts of all brown algal species tested caused strong in vitro mortality in a fouling diatom. The ecological significance of this activity remains to be tested. While the bulk tissue phlorotannin concentrations likely overestimate naturally occurring surface concentrations encountered by foulers in situ, fouler settlement may be deterred at much lower concentrations than those eliciting mortality. Overall, Antarctic phlorotannin deterrent properties were specific both to the algal species as well as the grazer, bacteria and diatom taxa tested. For grazer deterrence, we propose that, for each of the tested grazers, complex interactions between phlorotannin chemical properties and grazer digestive characteristics may determine the effectiveness of specific phlorotannins. Larger generalizations of phlorotannin-grazer patterns such as distinction between meso- and macrograzers may not be valid, at least not for Antarctic brown algal phlorotannins.
Sigma Phase and Other Effects of Prolonged Heating at Elevated Temperatures on 25 per cent Chromium — 20 per cent Nickel Steel
Authors: Emmanuel G. N.
Published: August 2009

The formation of the sigma phase (an intermetallic compound generally designated as FeCr) in high-chromium ferritic irons after certain thermal treatments is an established fact. This is indicated by the classical investigation of Bain and Griffiths (1) and by other investigators in this field (2, 3, 4). However, the precipitation of this phase directly from a balanced austenitic stainless steel matrix has not yet been completely accepted. Primarily, this paper attempts to add to the increasing evidence (5, 6, 7) that sigma may form directly from highly alloyed austenite, and it has the further purpose of determining the effects of such precipitation on the mechanical properties of the alloy. Numerous stainless steel tubing sections which have had prolonged exposure at elevated temperatures in various industrial services have been examined by the Research Department of The Babcock & Wilcox Tube Co. Under the proper conditions of temperature and time, a rapidly etching constituent tentatively identified as sigma phase has been detected in types 302B, 309, 310, 316, 317, 321, and 347. It should be pointed our that, in spite of many examinations of exposed metal, sigma phase has not been found by us in wrought type 304 material. Of the previously mentioned stainless steel grades, types 317 and 309 retain ferrite at room temperature while the remainder, with the exception of type 310, all contain, in appreciable amounts, elements with strong ferrite-forming tendencies (silicon, molybdenum, titanium, and columbium). In addition to their ferrite-forming tendencies, titanium and columbium exert a further accelerating influence on sigma formation by stabilizing the carbon, thereby permitting maintenance of a higher effective chromium content in the matrix. To avoid, as much as possible, the influence of ferrite on sigma phase formation, a steel which has no appreciable amount of ferrite-forming elements (chromium excluded) and contains enough nickel to render it austenitic under all heat treatments was chosen for the set of experiments reported herein. Because it meets the foregoing prerequisites and is, in addition, a highly utilitarian alloy finding application in many important industries, type 310 (25 per cent Cr - 20 per cent Ni) alloy was used for this investigation.
The Formation of Sigma and Its Influence on the Behavior of Stabilized 18 per cent Chromium — 8 per cent Nickel Steels in Concentrated Nitric Acid
Authors: Stewart Raymond S. , Urban Stephen F.
Published: August 2009

It was found that the presence of sigma phase, rather than chromium carbide precipitation, is responsible for the low corrosion resistance of titanium-stabilized austenitic stainless steels in boiling 65 per cent nitric acid, when tested after a “sensitizing” treatment. The factors influencing the formation of sigma phase were studied, and it was found that its quantity could be minimized by rather close control of the aluminum content and of the chromium and nickel contents. A slight increase in the aluminum content increases the amount of delta ferrite to a moderate degree, but markedly increases the amount of sigma phase transformed from the ferrite present when the steel is reheated for 2 hr. at 1250 F. Data is presented to show the relation between these factors and corrosion resistance in boiling 65 per cent nitric acid of steels annealed at 1950 F. and “sensitized” 2 hr. at 1250 F. A study of the effect of annealing temperature indicates that as the temperature is increased from 1800 F. to 2300 F. the amount of sigma formed on “sensitizing” is increased and the corrosion resistance is decreased. It was found that a precipitation treatment of 4 hr. at 1700 F. to 1800 F. markedly improves the resistance to nitric acid resulting from a high-temperature anneal (2100 F. for example) by reducing the amount of sigma formed on “sensitizing.” It is shown that commercial type 321 steels can be made to yield acceptably low corrosion rates in the Huey test by means of such a precipitation before “sensitizing” and testing.
Estrogen Induces Caspase-Dependent Cell Death during Hypothalamic Development
Authors: Waters Elizabeth M. , Simerly Richard B.
Published: August 2009

The sexually dimorphic population of dopamine neurons in the anteroventral periventricular nucleus of the preoptic region of the hypothalamus (AVPV) develops postnatally under the influence of testosterone, which is aromatized to estrogen. There are fewer dopaminergic neurons labeled with tyrosine hydroxylase (TH) in the male AVPV than the female, and sex steroids determine this sex difference, yet the role of cell death in specifying numbers of dopaminergic neurons in the AVPV is unknown. Estradiol treatment of the AVPV,in vivoandin vitro, was used to manipulate TH-ir cell number.In vitro, concurrent treatment with the estrogen receptor antagonist ICI 182,780 rescued TH-ir cells. Cyclosporin A, an inhibitor of cell death dependent on the opening of a mitochondrial permeability transition pore also blocked TH-ir cell loss.In vivo, estradiol increased the number of apoptotic profiles, both TUNEL and Hoechst labeled nuclei, in the AVPV. This increased apoptosis was also dependent on the presence of the α form of the estrogen receptor. To test for caspase dependent TH-ir cell loss, the pancaspase inhibitor ZVAD (N-benzyloxycabonyl-Val-Ala-Asp-fluoromethylketone) was used to rescue TH-ir cells from estradiol-mediated reduction in number. Together, these data suggest that an intrinsic cell death pathway is activated by estrogen to regulate TH-ir cell number. Thus, in contrast to the more widespread neuroprotective actions of sex steroids in the mammalian nervous system, in the AVPV estrogen regulates dopaminergic neuron number through a caspase-dependent mechanism of apoptotic cell death.
Do We Really Need Vision? How Blind People “See” the Actions of Others
Authors: Ricciardi Emiliano , Bonino Daniela , Sani Lorenzo , Vecchi Tomaso , Guazzelli Mario , Haxby James V. , Fadiga Luciano , Pietrini Pietro
Published: August 2009

Observing and learning actions and behaviors from others, a mechanism crucial for survival and social interaction, engages the mirror neuron system. To determine whether vision is a necessary prerequisite for the human mirror system to develop and function, we used functional magnetic resonance imaging to compare brain activity in congenitally blind individuals during the auditory presentation of hand-executed actions or environmental sounds, and the motor pantomime of manipulation tasks, with that in sighted volunteers, who additionally performed a visual action recognition task. Congenitally blind individuals activated a premotor–temporoparietal cortical network in response to aurally presented actions that overlapped both with mirror system areas found in sighted subjects in response to visually and aurally presented stimuli, and with the brain response elicited by motor pantomime of the same actions. Furthermore, the mirror system cortex showed a significantly greater response to motor familiar than to unfamiliar action sounds in both sighted and blind individuals. Thus, the mirror system in humans can develop in the absence of sight. The results in blind individuals demonstrate that the sound of an action engages the mirror system for action schemas that have not been learned through the visual modality and that this activity is not mediated by visual imagery. These findings indicate that the mirror system is based on supramodal sensory representations of actions and, furthermore, that these abstract representations allow individuals with no visual experience to interact effectively with others.
M1 Receptors Mediate Cholinergic Modulation of Excitability in Neocortical Pyramidal Neurons
Authors: Gulledge Allan T. , Bucci David J. , Zhang Sunny S. , Matsui Minoru , Yeh Hermes H.
Published: August 2009

ACh release into the rodent prefrontal cortex is predictive of successful performance of cue detection tasks, yet the cellular mechanisms underlying cholinergic modulation of cortical function are not fully understood. Prolonged (“tonic”) muscarinic ACh receptor (mAChR) activation increases the excitability of cortical pyramidal neurons, whereas transient (“phasic”) mAChR activation generates inhibitory and/or excitatory responses, depending on neuron subtype. These cholinergic effects result from activation of “M1-like” mAChRs (M1, M3, and M5 receptors), but the specific receptor subtypes involved are not known. We recorded from cortical pyramidal neurons from wild-type mice and mice lacking M1, M3, and/or M5 receptors to determine the relative contribution of M1-like mAChRs to cholinergic signaling in the mouse prefrontal cortex. Wild-type neurons in layer 5 were excited by tonic mAChR stimulation, and had biphasic inhibitory followed by excitatory, responses to phasic ACh application. Pyramidal neurons in layer 2/3 were substantially less responsive to tonic and phasic cholinergic input. Cholinergic effects were largely absent in neurons from mice lacking M1 receptors, but most were robust in neurons lacking M3, M5, or both M3 and M5 receptors. The exception was tonic cholinergic suppression of the afterhyperpolarization in layer 5 neurons, which was absent in cells lacking either M1 or M3 receptors. Finally, we confirm a role for M1 receptors in behavior by demonstrating cue detection deficits in M1-lacking mice. Together, our results demonstrate that M1 receptors facilitate cue detection behaviors and are both necessary and sufficient for most direct effects of ACh on pyramidal neuron excitability.
Cerebellothalamocortical Connectivity Regulates Penetrance in Dystonia
Authors: Argyelan Miklos , Carbon Maren , Niethammer Martin , Uluğ Aziz M. , Voss Henning U. , Bressman Susan B. , Dhawan Vijay , Eidelberg David
Published: August 2009

Dystonia is a brain disorder characterized by sustained involuntary muscle contractions. It is typically inherited as an autosomal dominant trait with incomplete penetrance. While lacking clear degenerative neuropathology, primary dystonia is thought to involve microstructural and functional changes in neuronal circuitry. In the current study, we used magnetic resonance diffusion tensor imaging and probabilistic tractography to identify the specific circuit abnormalities that underlie clinical penetrance in carriers of genetic mutations for this disorder. This approach revealed reduced integrity of cerebellothalamocortical fiber tracts, likely developmental in origin, in both manifesting and clinically nonmanifesting dystonia mutation carriers. In these subjects, reductions in cerebellothalamic connectivity correlated with increased motor activation responses, consistent with loss of inhibition at the cortical level. Nonmanifesting mutation carriers were distinguished by an additional area of fiber tract disruption situated distally along the thalamocortical segment of the pathway, in tandem with the proximal cerebellar outflow abnormality. In individual gene carriers, clinical penetrance was determined by the difference in connectivity measured at these two sites. Overall, these findings point to a novel mechanism to explain differences in clinical expression in carriers of genes for brain disease.
Systemic Lipopolysaccharide Protects the Brain from Ischemic Injury by Reprogramming the Response of the Brain to Stroke: A Critical Role for IRF3
Authors: Marsh Brenda , Stevens Susan L. , Packard Amy E. B. , Gopalan Banu , Hunter Brian , Leung Philberta Y. , Harrington Christina A. , Stenzel-Poore Mary P.
Published: August 2009

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury through activation of its receptor, Toll-like receptor 4 (TLR4). Paradoxically, TLR activation by endogenous ligands after ischemia worsens stroke damage. Here, we define a novel, protective role for TLRs after ischemia in the context of LPS preconditioning. Microarray analysis of brains collected 24 h after stroke revealed a unique set of upregulated genes in LPS-pretreated animals. Promoter analysis of the unique gene set identified an overrepresentation of type I interferon (IFN)-associated transcriptional regulatory elements. This finding suggested the presence of type I IFNs or interferon regulatory factors (IRFs), which upregulate interferon-stimulated genes. Upregulation of IFNβ was confirmed by real-time reverse transcription-PCR. Direct administration of IFNβ intracerebroventricularly at the time of stroke was sufficient for neuroprotection. TLR4 can induce both IFNβ and interferon-stimulated genes through its adapter molecule Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) and the IRF3 transcription factor. We show in oxygen glucose deprivation of cortical neurons, anin vitromodel of stroke, that activation of TRIF after stroke reduces neuronal death. Furthermore, mice lacking IRF3 were not protected by LPS preconditioning in ourin vivomodel. Our studies constitute the first demonstration of the neuroprotective capacity of TRIF/IRF3 signaling and suggest that interferon-stimulated genes, whether induced by IFNβ or by enhanced TLR signaling to IRF3, are a potent means of protecting the brain against ischemic damage.
Cortical Inhibition during Burst Suppression Induced with Isoflurane Anesthesia
Authors: Ferron Judy-Fay , Kroeger Daniel , Chever Oana , Amzica Florin
Published: August 2009

Isoflurane is a widely used anesthetic which safely and reversibly induces deep coma and associated burst suppression (BS) electroencephalographic patterns. Here we investigate possible underlying causes for the state of cortical hyperexcitability which was recently shown to be one of the characteristics of BS. Our hypothesis was that cortical inhibition is diminished during isoflurane-induced BS. Experiments were performedin vivousing intracellular recordings of cortical neurons to assess their responsiveness to stimulations of connected thalamic nuclei. We demonstrate that during BS EPSPs were diminished by 44%, whereas inhibitory potentials were completely suppressed. This finding was supported by additional results indicating that a decrease in neuronal input resistance normally found during inhibitory responses under low isoflurane conditions was abolished in the BS condition. Moreover, removal of inhibition occasionally revealed excitatory components which were absent during recordings before the induction of BS. We also show that the absence of inhibition during BS is not caused by a blockage of GABA receptors, since iontophoretically applied GABA shows receptor availability. Moreover, the concentration of extracellular chloride was increased during BS, as would be expected after reduced flow of chloride through GABAAreceptors. Also inhibitory responses were reinstated by selective blockage of glial glutamate transporters with dihydrokainate. These results suggest that the lack of inhibition during BS is caused by reduced excitation, probably resulting from increased glial uptake of glutamate stimulated by isoflurane, which creates a diminished activation of cortical interneurons. Thus cortical hyperexcitability during BS is favored by suppressed inhibition.
Cornering the Fear Engram: Long-Term Synaptic Changes in the Lateral Nucleus of the Amygdala after Fear Conditioning
Authors: Kwon Jeong-Tae , Choi June-Seek
Published: August 2009

Use-dependent synaptic modifications in the lateral nucleus of the amygdala (LA) have been suggested to be the cellular analog of memory trace after pavlovian fear conditioning. However, whether neurophysiological changes in the LA are produced as a direct consequence of associative learning awaits additional proof. Using microstimulation of the medial geniculate nucleus of the thalamus as the conditioned stimulus (CS), we demonstrated that contingent pairings of the brain-stimulation CS and a footshock unconditioned stimulus lead to enhanced synaptic efficacy in the thalamic input to the LA, supporting the hypothesis that localized synaptic alterations underlie fear memory formation.
Two polymorphs of 9-[(E)-2-(4-methylphenyl)ethenyl]-9H-carbazole, both with Z′ = 4
Authors: Kubicki Maciej , Prukala Wieslaw , Marciniec Bogdan
Published: August 2009

The crystal structures of two polymorphic forms of 9-[(E)-2-(4-methylphenyl)ethenyl]-9H-carbazole have been determined. One of the structures is monoclinic: P21, a = 10.627(2) Å, b = 30.475(5) Å, c = 10.671(3) Å, β = 118.60(2)°, and the other is triclinic: P-1, a = 10.6266(5) Å, b = 30.9003(13) Å, c = 10.6696(5) Å, α = 99.004(4)°, β = 118.683(4)°, γ = 87.852(3)°, and in both forms there are four symmetry-independent molecules in the asymmetric unit. The geometric parameters defining these molecules are similar with the normal probability plots showing that the differences between molecules are of a statistical rather than a systematic nature. In both structures there is a high degree of pseudo-symmetry between the symmetrically independent molecules. The crystal packing modes of both polymorphs are quite similar, the differences are found at the level of the composition of structural building blocks: stacks, layers and bi-layers.
Consistent approaches to van der Waals radii for the metallic elements
Authors: Hu Sheng-Zhi , Zhou Zhao-Hui , Robertson B. E.
Published: August 2009

Due to the paucity of data on non-bonding interactions for metal atoms, no complete tabulation is available for crystallographic van der Waals radii for metallic elements. In this work several sets of van der Waals radii for metal atoms are derived indirectly. Unique data resources used for the derivation are (i) average volumes of elements in crystals, (ii) single covalent radii, (iii) Allinger´s van der Waals radii, as well as (iv) bond valence parameters formetal-oxygenbonds. The van der Waals radii for metal atoms deduced from these various approaches are basically comparable with each other, but are strikingly different from those from Bondi’s system of van der Waals radii. A complete set of new values for metallic elements up to Am, derived from bond valence parameters, are recommended.
Lipoatrophy in GH deficient patients treated with a long-acting pegylated GH
Authors: Touraine Philippe , D'Souza Gwyn A , Kourides Ione , Abs Roger , Barclay Paul , Xie Rujia , Pico Antonio , Torres-Vela Elena , Ekman Bertil
Published: August 2009

Objective

Changes observed during adult GH deficiency (GHD) are most often reversed with the administration of recombinant human GH (rhGH). To avoid daily injections, a long-acting GH molecule has been obtained by covalent binding of polyethylene glycol (PEG) with rhGH (PEG–GH), allowing weekly s.c. injections. This study was designed to assess its efficacy and safety, in adult GHD subjects.

Design and methods

This was a randomized, double-blind, placebo-controlled, multiple-dose, parallel group study. Subjects were recruited from 34 centers. A total of 105 subjects with GHD were assigned a treatment. They received 6 weekly injections of either PEG–GH or placebo. Subjects were randomized into one out of four treatment groups (Groups A–D) or placebo (Group E). Groups A, B, and C received 1, 3, and 4 mg PEG–GH respectively, for the first 3 weeks followed by 2, 6, and 8 mg PEG–GH respectively, for the remaining 3 weeks. Group D received 4 mg PEG–GH for 6 weeks. Group E received placebo. The study was suspended because of the development of lipoatrophy in certain subjects and restarted with an injection rotation plan, before being terminated due to further subjects developing lipoatrophy.

Results

A total of 13 cases of injection-site lipoatrophy were reported, of which ten were in females and three occurred after the first injection; all cases were independent of PEG–GH dose or IGF1 levels, either basal or under treatment.

Conclusion

The unpredictable occurrence of injection-site lipoatrophy with weekly long-acting pegylated GH molecules may be a limiting factor for their development.