bluuebunny/crossref_metadata_2025 huggingface dataset:
Jointly Optimal Taxes and Enforcement Policies in Response to Tax Evasion
Authors: Pestieau Pierre , Possen Uri M. , Slutsky Steven M.
Published: April 2004

Assuming the government cannot fully observe either individual types or incomes and jointly picks optimal taxes and audit policies against evasion can significantly alter standard results from optimal income taxation and tax‐evasion models, which treat these separately. We consider this when individuals differ in their risk preferences and incomes. Given the resulting complexity, supplementing analytic results with numerical analysis helps explain the structure of the resulting policies and how they change when the distribution of income or the revenue requirements of the government change. We do this analysis with and without audit errors and with incomes exogenous or affected by occupational choice.
An Integrative Review of Patient Medication Compliance from 1990‐1998
Authors: Wood Wendy , Gray Jennifer
Published: April 2004

Purpose

(1)The purpose of the integrated review was to summarize studies about medication compliance and identify their implications for research and practice. Thirty research studies exploring patient medication compliance were reviewed. Study variables related to patients included characteristics that affect compliance, common medication errors, and strategies used by patients to remember to take their medications. Other studies evaluated methods for measuring compliance and interventions for improving compliance.

Conclusions

(2)There has not been a “gold standard” identified for measuring compliance, therefore it is difficult to compare results due to differences in operational definitions. Dosage frequency, patient's confidence in their provider, belief in the efficacy of a drug along with acceptance of illness have been shown to have a positive effect on compliance.

Implications

(3)Nurses and other health care providers can promote medication compliance by developing a collaborative relationship with the patient. Education and reminders are especially important at the beginning of treatment. Further research is needed to assess the efficacy of nursing interventions to promote compliance.
Kinetics of stable isotope and body composition in olive baboons (Papio anubis) estimated by deuterium dilution space: a pilot study
Authors: Garcia C. , Rosetta L. , Ancel A. , Lee P.C. , Caloin M.
Published: April 2004

Abstract:  Morphometrics and isotope‐labelled water were used to determine body composition [total body water, total body fat and fat‐free mass (FFM)] of three captive female olive baboons (Papio anubis). Mean mass was 16.5 kg, comparable with other captive settings but heavier than wild olive baboons. Average water content was 66%; FFM averaged 90.5%. Baboon females have less body fat than human counterparts. Compared with captive or wild baboons, these females were adequately nourished for their energy expenditure. A positive association between total mass and FFM existed, but due to the small sample no general relationship was observed for body fat or FFM and condition or size measures. The kinetics of deuterium equilibration in body fluids for baboons was determined as 3–4 hours after injection, similar to that for humans. Deuterium dilution technique appears to be an appropriate method for studying body composition in baboons, although a larger sample is needed for relationships between morphometric indices and body composition.
Sex differences in total body water in adolescent rhesus macaques estimated by ethanol dilution
Authors: Bennett Allyson J. , DePetrillo Paolo B.
Published: April 2004

Abstract:  Non‐human primates are widely used in research, yet relatively few studies have addressed potential pharmacokinetic differences between males and females. The present study examined the relationship between total body water, sex, age, and weight in the rhesus macaque (Macaca mulatta). Ethanol‐naïve, adolescent rhesus macaques (n = 119) were administered ethanol (males, 2.1 g/kg; females, 2.0 g/kg) intravenously, and blood samples for blood ethanol concentration obtained at 5, 10, and 60 minutes following the end of the infusion. Non‐linear regression was used to compare and contrast a series of pharmacokinetic models examining the relationship between weight, sex, age, Vd and zero‐order elimination rate. Vd (mean ± SEM) for male rhesus was 0.771 ± 0.008 l/kg and for females was 0.730 ± 0.008 l/kg, different at P < 0.00001. There were no sex differences in the rate of zero‐order ethanol elimination, estimated to be 0.0032 ± 0.0004 g/kg/minute. The data reported here may be useful in designing and interpreting pharmacokinetic studies using rhesus monkeys.
Development of a system for individual feeding of baboons maintained in an outdoor group social environment
Authors: Schlabritz‐Loutsevitch Natalia E. , Howell Kate , Rice Karen , Glover Elizabeth J. , Nevill Christian H. , Jenkins Susan L. , Bill Cummins L. , Frost Patrice A. , McDonald Thomas J. , Nathanielsz Peter W.
Published: April 2004

Abstract:  We developed a system that allows individual feeding of adult baboons, 8–15 years of age, maintained in an outdoor group social environment. The purpose of the system is to allow careful monitoring and control of individual diet. Baboons were housed in two group cages, 16 females and a single male in one and 12 females and a single male in the other. Baboons exited the group cage once daily and passed along a chute and over a scale into individual cages where they received their individual diets. Food intake was monitored during their 2‐hour stay in the individual cages. Baboons rapidly learned to use this system. Food intake and weight were stable within 20 days. Food consumed decreased during the period of sexual receptivity. The maintenance of the group social environment allowed observations on the group's dominance structure and the relationship of dominance to food consumption. Speed of food access in the group cage was related to dominance. Dominance was not related to food consumed in individual cages. The system permits study of many variables related to behavior and food intake while still retaining critical social interactions.
Proliferative activities of epithelial and connective tissue cells in the rat periodontal regeneration using argyrophilic nucleolar organizer regions staining
Authors: Usuda J. , Hashimoto S. , Enokiya Y. , Inoue T. , Shimono M.
Published: April 2004

Background and objective:  It is still an open question why long junctional epithelium can proliferate and occupies the root surface following periodontal surgery or experimentally produced periodontitis, and why the epithelium repopulated once on the root surface is replaced by the connective tissue. The aim of this study is to investigate the proliferative activity of the newly formed regenerative connective tissue and long junctional epithelium during wound healing by staining argyrophilic proteins of the nucleolar organizer regions (AgNORs).

Methods:  Regenerative connective tissue and long junctional epithelium were experimentally created by insertion of a rubber piece between maxillary molars of rats for 1 week. After removal of the rubber, AgNORs parameters including nuclear area (NA), AgNORs area (AA), AgNORs percentage nuclear area (APNA), AgNORs number (AN) and nuclear number (NN) in regenerative connective tissue and long junctional epithelium were measured and analyzed statistically.

Results:  APNA in long junctional epithelium after 1 and 4 weeks was over two times greater than that in the regenerative connective tissue. AA in long junctional epithelium was significantly higher than in regenerative connective tissue at 1 and at 4 weeks post‐treatment. AN was higher in the central portion than at the root surface except at 20 weeks. APNA and AA decreased remarkably in long junctional epithelium at 12 weeks post‐treatment (approximately half at 4 weeks), whereas in regenerative connective tissue, they did not change distinctly.

Conclusions:  These results imply that long junctional epithelium cannot supply sufficient epithelial cells because of their significantly low rates of proliferation, consequently long junctional epithelium becomes shorter after 12 weeks, whereas the proliferative activity of regenerative connective tissue maintains the same level of proliferation, and ultimately long junctional epithelium is replaced by regenerative connective tissue.
Causal Analysis in Population Research: An Economist's Perspective
Authors: Moffitt Robert
Published: April 2004

The problem of determining cause and effect is one of the oldest questions in the social sciences. This note provides a perspective on the analysis of causal relationships in population research, drawing upon recent discussions in the field of economics. Within economics, thinking about causal estimation has shifted markedly in the last decade toward a more pessimistic reading of what is possible and a retreat in the ambitiousness of claims of causal determination. The framework that underlies this conclusion is presented, methods for isolating causal effects are discussed, and an example from the field of population research is given.
Short Reviews
Authors: Bongaarts John , Greenhalgh Susan , McNicoll Geoffrey , Montgomery Mark , Todaro Michael P.
Published: April 2004

Books reviewed in this article:

Max Essex, Souleymane Mboup, Phyllis J. Kanki, Richard G. Marlink, and Sheila D. Tlou (eds.) AIDS in Africa, Second Edition

Virginie Guiraudon and Christian Joppke (eds.) Controlling a New Migration World

Anke Niehof and Firman Lubis (eds.) Two Is Enough: Family Planning in Indonesia under the New Order 1968–1998

Donald T. Rowland Demographic Methods and Concepts

Thomas Scharping Birth Control in China, 1949–2000: Population Policy and Demographic Development

Nelly P. Stromquist Education in a Globalized World: The Connectivity of Economic Power, Technology, and Knowledge

United Nations World Urbanization Prospects: The 2001 Revision

Yunxiang Yan Private Life Under Socialism: Love, Intimacy, and Family Change in a Chinese Village, 1949–1999
Gender and Aging in the Developing World: Where Are the Men?
Authors: Knodel John , Ofstedal Mary Beth
Published: April 2004

In recent years, both population aging and gender issues have gained prominence in international forums concerned with population. It is frequently asserted or implied that older women are universally more vulnerable to social, economic, and health disadvantages than older men. The most significant manifestation of this exclusive concern with women when considering gender and aging is the Plan of Action adopted by the Second World Assembly on Aging in 2002. The assumed relative disadvantage of elderly women is commonly attributed to gender differences in earlier life experiences. But are older women truly disadvantaged globally with respect to all or most essential aspects of well‐being? The authors provide empirical evidence that clearly shows that older women are not invariably disadvantaged vis‐à‐vis men. In particular, they call into question the wisdom and equity of a virtually exclusive emphasis on the needs of women when incorporating gender concerns into policies and programs related to aging. A more balanced perspective that recognizes gender as a potential, but not necessarily central, marker of vulnerability for various aspects of well‐being in specific settings and times, and that allows for male as well as female disadvantage, would serve the current and future elderly generations far better.
Evolution and Revolution as Organizations Grow
Authors: Greiner Larry E.
Published: April 2004

Foreword This author maintains that growing organizations move through five distinguishable phases of development, each of which contains a relatively calm period of growth that ends with a management crisis. He argues, moreover, that since each phase is strongly influenced by the previous one, a management with a sense of its own organization's history can anticipate and prepare for the next developmental crisis. This article provides a prescription for appropriate management action in each of the five phases, and it shows how companies can turn organizational crises into opportunities for the future growth. Mr. Greiner is associate professor of organizational behavior at the Harvard Business School and the author of several Harvard Business Review articles on organization development.
Is the Cost of Capital Different for Family Firms?
Authors: McConaughy Daniel L.
Published: April 2004

It has been suggested that the cost of capital for a family firm depends on, among other things, a “family effect,” which deals with the family's relation to its business. Financial theory regarding the cost of capital states that the cost of capital is a market-based function of the characteristics of the investment, not the investor. This theory suggests that a firm's cost of capital does not depend on a family effect. However, not all financial economists' assumptions regarding the cost of capital hold for the family firm. This paper reviews the relevant literature regarding the cost of capital and applies it to the family firm. Knowing the correct cost of capital will enable family owner-managers to make better investment and financing decisions, evaluate performance, and structure rewards for performance.
Nerve injury reduces responses of hypoglossal motoneurones to baseline and chemoreceptor‐modulated inspiratory drive in the adult rat
Authors: González‐Forero David , Portillo Federico , Sunico Carmen R. , Moreno‐López Bernardo
Published: April 2004

The effects of peripheral nerve lesions on the membrane and synaptic properties of motoneurones have been extensively studied. However, minimal information exists about how these alterations finally influence discharge activity and motor output under physiological afferent drive. The aim of this work was to evaluate the effect of hypoglossal (XIIth) nerve crushing on hypoglossal motoneurone (HMN) discharge in response to the basal inspiratory afferent drive and its chemosensory modulation by CO2. The evolution of the lesion was assessed by recording the compound muscle action potential evoked by XIIth nerve stimulation, which was lost on crushing and then recovered gradually to control values from the second to fourth weeks post‐lesion. Basal inspiratory activities recorded 7 days post‐injury in the nerve proximal to the lesion site, and in the nucleus, were reduced by 51.6% and 35.8%, respectively. Single unit antidromic latencies were lengthened by lesion, and unusually high stimulation intensities were frequently required to elicit antidromic spikes. Likewise, inspiratory modulation of unitary discharge under conditions in which chemoreceptor drive was varied by altering end‐tidal CO2 was reduced by more than 60%. Although the general recruitment scheme was preserved after XIIth nerve lesion, we noticed an increased proportion of low‐threshold units and a reduced recruitment gain across the physiological range. Immunohistochemical staining of synaptophysin in the hypoglossal nuclei revealed significant reductions of this synaptic marker after nerve injury. Morphological and functional alterations recovered with muscle re‐innervation. Thus, we report here that nerve lesion induced changes in the basal activity and discharge modulation of HMNs, concurrent with the loss of afferent inputs. Nevertheless, we suggest that an increase in membrane excitability, reported by others, and in the proportion of low‐threshold units, could serve to preserve minimal electrical activity, prevent degeneration and favour axonal regeneration.
Monoamines increase the excitability of spinal neurones in the neonatal rat by hyperpolarizing the threshold for action potential production
Authors: Fedirchuk Brent , Dai Yue
Published: April 2004

During fictive locomotion in the adult decerebrate cat, motoneurone excitability is increased by a hyperpolarization of the threshold potential at which an action potential is elicited (Vth). This lowering of Vth occurs at the onset of fictive locomotion, is evident for the first action potential elicited and is presumably caused by a neuromodulatory process. The present study tests the hypothesis that the monoamines serotonin (5‐HT) and noradrenaline (NA) can hyperpolarize neuronal Vth. The neonatal rat isolated spinal cord preparation and whole‐cell recording techniques were used to examine the effects of bath‐applied 5‐HT and NA on the Vth of spinal ventral horn neurones. In the majority of lumbar ventral horn neurones, 5‐HT (13/26) and NA (10/16) induced a hyperpolarization of Vth ranging from −2 to −8 mV. 5‐HT and NA had similar effects on Vth for individual neurones. This hyperpolarization of Vth was not due to a reduction of an accommodative process, and could be seen without changes in membrane potential or membrane resistence. These data reveal a previously unknown action of 5‐HT and NA, hyperpolarization of Vth of spinal neurones, a process that would facilitate both neuronal recruitment and firing.
FUZZY MAPPING BETWEEN PHYSICAL DOMAIN AND FUNCTION DOMAIN IN DESIGN PROCESS
Authors: GU YING-KUI , HUANG HONG-ZHONG
Published: April 2004

The contents and meanings of mapping relationships between physical domain and function domain in different design stages, such as conceptual design, detail design and enhancement design, were analyzed. According to the analysis results, the fuzzy mapping between physical domain and function domain in different design stages was established by integrating objective information and subjective information in the design process, such as expert's knowledge, designer's preferences and customer's requirements, where the fuzzy sets, fuzzy mapping and fuzzy transition were used. The property table of structure behavior parameters was established based on the fuzzy mapping relationships. The fuzzy mapping is very important to optimize product structure, perfect product function, meet the diversified and individual requirements of customers. Finally, an example was used to illustrate the fuzzy mapping relationships between physical domain and function domain in different design stages.
THE INFORMATION ENTROPY, ROUGH ENTROPY AND KNOWLEDGE GRANULATION IN ROUGH SET THEORY
Authors: LIANG JIYE , SHI ZHONGZHI
Published: April 2004

Rough set theory is a relatively new mathematical tool for use in computer applications in circumstances which are characterized by vagueness and uncertainty. In this paper, we introduce the concepts of information entropy, rough entropy and knowledge granulation in rough set theory, and establish the relationships among those concepts. These results will be very helpful for understanding the essence of concept approximation and establishing granular computing in rough set theory.
FINITE ${\mathbb L}$–FUZZY ACCEPTORS, REGULAR ${\mathbb L}$–FUZZY GRAMMARS AND SYNTACTIC PATTERN RECOGNITION
Authors: PEEVA KETTY
Published: April 2004

[Formula: see text]–fuzzy acceptors in relationship with formal [Formula: see text]–fuzzy languages and [Formula: see text]–fuzzy grammars are studied, where [Formula: see text] is a bounded chain. Applications of fuzzy linguistic methods in syntactic pattern recognition are described.
Platelet-induced enhancement of LS174T colon carcinoma and THP-1 monocytoid cell adhesion to vascular endothelium under flow
Authors: Burdick Monica M. , Konstantopoulos Konstantinos
Published: April 2004

This study was undertaken to characterize the adhesion of LS174T colon adenocarcinoma cells to 4-h TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) under flow in the presence and absence of platelets and erythrocytes. Cell binding to HUVECs was significantly enhanced by simultaneous perfusion of thrombin-activated, but not resting, platelets. This increase was achieved via a platelet bridging mechanism whereby a previously tethered LS174T cell (primary tether) captures a free-flowing cell (secondary tether) that subsequently attaches to the endothelium downstream of the already adherent cell. The total number of tumor cells tethering to HUVECs and the percentage of secondary tethers relative to the total amount of cell tethering depended on platelet concentration and wall shear stress. At 0.8 dyn/cm2 and a platelet-to-LS174T cell ratio of 25:1, the total amount of cell tethering nearly doubled as a result of platelet-induced enhancement compared with the amount without platelet perfusion. Moreover, the percentage of secondary tethers increased from background levels (<5%) in the absence of platelets to ∼60% at a platelet-to-LS174T cell ratio of 25:1. Platelet-mediated secondary tethering is not limited to LS174T colon carcinoma cells, as THP-1 monocytoid cells also displayed this pattern of interaction. Secondary tethering was dependent on both platelet P-selectin and αIIbβ3-integrin for LS174T cells and P-selectin alone for THP-1 cells. Furthermore, platelet-mediated secondary tethering of both cell types occurred in the presence of red blood cells. Altogether, these results reveal a novel role for platelets in promoting cell binding to endothelium through a secondary tethering mechanism.
Dynamic remodeling of K+ and Ca2+ currents in cells that survived in the epicardial border zone of canine healed infarcted heart
Authors: Dun Wen , Baba Shigeo , Yagi Takuya , Boyden Penelope A.
Published: April 2004

Action potentials (APs) of the epicardial border zone (EBZ) cells from the day 5 infarcted heart continue to be altered by day 14 postocclusion, namely, they shortened. However, by 2 mo, EBZ APs appear “normal,” yet conduction of wave fronts remains abnormal. We hypothesize that the changes in transmembrane APs are due to a change in the distribution of ion channels in either density or function. Thus we focused on the changes in Ca2+ and K+ currents in cells isolated from the 14-day (IZ14d) and 2-mo (IZ2m) EBZ and compared them with those occurring in cells from the same hearts but remote (Rem) from the EBZ. Whole cell voltage-clamp techniques were used to measure and compare Ca2+ and K+ currents in cells from the different groups. Ca2+ current densities remain reduced in cells of the 14-day and 2-mo infarcted heart and the kinetic changes previously identified in the 5-day heart begin to, but do not recover to, cells from noninfarcted epicardium (NZ) values. Importantly, ICa,L in both the EBZ and Rem regions still show a slowed recovery from inactivation. Furthermore, during the remodeling process, there is an increased expression of T-type Ca2+ currents, but only regionally, and only within a specific time window postmyocardial infarction (MI). Regional heterogeneity in β-adrenergic responsiveness of ICa,L exists between EBZ and remote cells of the 14-day hearts, but this regional heterogeneity is gone in the healed infarcted heart. In IZ14d, the transient outward K+ current ( Ito) begins to reemerge and is accompanied by an upregulated tetraethylammonium-sensitive outward current. By 2-mo postocclusion, Ito and sustained outward K+ current have completed the reverse remodeling process. During the healing process post-MI, canine epicardial cells downregulate the fast Ito but compensate by upregulating a K+ current that in normal cells is minimally functional. For recovering ICa,L of the 14-day and 2-mo EBZ cells, voltage-dependent processes appear to be reset, such that ICa,L “window” current occurs at hyperpolarized potentials. Thus dynamic changes in both Ca2+ and K+ currents contribute to the altered AP observed in 14-day fibers and may account for return of APs of 2 mo EBZ fibers.
Novel regulatory mechanism of cardiomyocyte contractility involving ICAM-1 and the cytoskeleton
Authors: Davani Ehsan Y. , Dorscheid Delbert R. , Lee Cheng-Han , van Breemen Cornelis , Walley Keith R.
Published: April 2004

ICAM-1 mediates interaction of cardiomyocytes with the extracellular matrix and leukocytes and may play a role in altering contractility. To investigate this possibility, rat ventricular cardiomyocytes were activated using TNF-α, IL-1β, or LPS, washed, cultured with quiescent rat polymorphonuclear leukocytes (PMNs) for 4 h, and electrically stimulated to determine fractional shortening. PMNs cultured with activated cardiomyocytes reduced control fractional shortening of 20.5 ± 0.7% by −2.8 ± 0.3% per adherent PMN ( P < 0.001). Fixing PMNs with paraformaldehyde or glutaraldehyde did not prevent PMN-mediated decreases in cardiomyocyte fractional shortening. However, PMN adherence and decreased fractional shortening were prevented by anti-ICAM-1 and anti-CD18 antibodies. Reduced fractional shortening was reproduced in the absence of PMNs by ICAM-1 binding using cross-linking antibodies (reduced by 36 ± 3% from control, P < 0.01). Immunofluorescent staining demonstrated increased cortical cytoskeleton-associated focal adhesion kinase expression after ICAM-1 cross-linking, suggesting involvement of the actin cytoskeleton. Indeed, disruption of F-actin filament assembly using cytochalasin D or latrunculin A did not prevent PMN adherence but prevented decreased fractional shortening. Inhibition of the cytoskeleton-associated Rho-kinase pathway with HA-1077 prevented ICAM-1-mediated decreases in cardiomyocyte contractility, further suggesting a central role of the actin cytoskeleton. Importantly, ICAM-1 cross-linking did not alter the total intracellular Ca2+transient during cardiomyocyte contraction but greatly increased heterogeneity of intracellular Ca2+release. Thus we have identified a novel regulatory mechanism of cardiomyocyte contractility involving the actin cytoskeleton as a central regulator of the normally highly coordinated pattern of sarcoplasmic Ca2+release. Cardiomyocyte ICAM-1 binding, by PMNs or other ligands, induces decreased cardiomyocyte contractility via this pathway.
Transient induction of TGF-α disrupts lung morphogenesis, causing pulmonary disease in adulthood
Authors: Le Cras T. D. , Hardie W. D. , Deutsch G. H. , Albertine K. H. , Ikegami M. , Whitsett J. A. , Korfhagen T. R.
Published: April 2004

Clinical studies have associated increased transforming growth factor (TGF)-α and EGF receptor with lung remodeling in diseases including bronchopulmonary dysplasia (BPD). BPD is characterized by disrupted alveolar and vascular morphogenesis, inflammation, and remodeling. To determine whether transient increases in TGF-α are sufficient to disrupt postnatal lung morphogenesis, we utilized neonatal transgenic mice conditionally expressing TGF-α. Expression of TGF-α from postnatal days 3 to 5 disrupted postnatal alveologenesis, causing permanent enlargement of distal air spaces in neonatal and adult mice. Lung volume-to-body weight ratios and lung compliance were increased in adult TGF-α transgenic mice, whereas tissue and airway elastance were reduced. Elastin fibers in the alveolar septae were fragmented and disorganized. Pulmonary vascular morphogenesis was abnormal in TGF-α mice, with attenuated and occasionally tortuous arterial branching. The ratios of right ventricle weight to left ventricle plus septal weight were increased in TGF-α mice, indicating pulmonary hypertension. Electron microscopy showed gaps in the capillary endothelium and extravasation of erythrocytes into the alveolar space of TGF-α mice. Hemorrhage and inflammatory cells were seen in distal air spaces at 1 mo of age. In adult TGF-α mice, alveolar remodeling, nodules, proteinaceous deposits, and inflammatory cells were seen. Immunostaining for pro-surfactant protein C showed that type II cells were abundant in the nodules, as well as neutrophils and macrophages. Trichrome staining showed that pulmonary fibrosis was minimal, apart from areas of nodular remodeling in adult TGF-α mice. Transient induction of TGF-α during early alveologenesis permanently disrupted lung structure and function and caused chronic lung disease.
Modulation of red cell glycolysis: interactions between vertebrate hemoglobins and cytoplasmic domains of band 3 red cell membrane proteins
Authors: Weber Roy E. , Voelter Wolfgang , Fago Angela , Echner Hartmut , Campanella Estela , Low Philip S.
Published: April 2004

Several vital functions/physical characteristics of erythrocytes (including glycolysis, the pentose phosphate pathway, ion fluxes, and cellular deformability) display dependence on the state of hemoglobin oxygenation. The molecular mechanism proposed involves an interaction between deoxyhemoglobin and the cytoplasmic domain of the anion-exchange protein, band 3 (cdB3). Given that band 3 also binds to membrane proteins 4.1 and 4.2, several kinases, hemichromes, and integral membrane proteins, and at least three glycolytic enzymes, it has been suggested that the cdB3-deoxyhemoglobin interaction might modulate the pathways mediated by these associated proteins in an O2-dependent manner. We have investigated this mechanism by synthesizing 10-mer peptides corresponding to the NH2-terminal fragments of various vertebrate cdB3s, determining their effects on the oxygenation reactions of hemoglobins from the same and different species and examining binding of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase to the erythrocytic membrane of mouse erythrocytes. The cdB3 interaction is strongly dependent on pH and the number of negative and positive charges of the peptide and at the effector binding site, respectively. It lowers the O2association equilibrium constant of the deoxygenated (Tense) state of the hemoglobin and is inhibited by magnesium ions, which neutralize cdB3's charge and by 2,3-diphosphoglycerate, which competes for the cdB3-binding site. The interaction is stronger in humans (whose erythrocytes derive energy predominantly from glycolysis and exhibit higher buffering capacity) than in birds and ectothermic vertebrates (whose erythrocytes metabolize aerobically and are poorly buffered) and is insignificant in fish, suggesting that its role in the regulation of red cell glycolysis increased with phylogenetic development in vertebrates.
High bone mass gained by exercise in growing male mice is increased by subsequent reduced exercise
Authors: Wu Jian , Wang Xin Xiang , Higuchi Mitsuru , Yamada Kazuhiko , Ishimi Yoshiko
Published: April 2004

Exercise-induced bone gains are lost if exercise ceases. Therefore, continued exercise at a reduced frequency or intensity may be required to maintain these benefits. In this study, we evaluated whether 4 wk of reduced exercise after 4 wk of running exercise in growing male mice results in the maintenance of high bone mass. Five-week-old mice were divided into the following groups: 1) baseline control; 2) 4-wk control; 3) 4-wk exercise; 4) 8-wk control; 5) 4-wk exercise followed by 4-wk cessation of training; and 6) 4-wk exercise followed by reduced exercise at half the frequency. The regimen consisted of exercise 6 days/wk, and the reduced exercise regimen consisted of running 3 days/wk on a treadmill for 30 min/day, at 12 m/min on a 10° uphill slope. Running exercise significantly increased bone mineral density of the femur, periosteal mineral apposition rate, bone formation rate, percent labeled perimeter at the midfemur, and osteogenic activity of bone marrow cells. However, these parameters declined to the age-matched sedentary control after cessation of training. In contrast, the reduced exercise group had significantly higher mineral apposition rate compared with those of the sedentary control and cessation of training groups. Furthermore, bone mineral density for the reduced exercise group was significantly higher than those for the other groups. These results suggest that the high bone formation gained through exercise can be maintained, and bone mass was further increased by subsequent exercise even if the exercise frequency is reduced.
Homocysteine and Folic Acid Are Inversely Related in Black Women With Preeclampsia
Authors: Patrick Thelma E. , Powers Robert W. , Daftary Ashi R. , Ness Roberta B. , Roberts James M.
Published: April 2004

Black women have an increased risk of preeclampsia compared with white women. Plasma homocysteine is increased in preeclampsia. Homocysteine concentrations are affected by nutritional deficiencies, particularly decreased folic acid and B12, leading to increased homocysteine. Previous studies have reported racial differences in nutritional intake including folic acid. Therefore, we investigated whether there were racial differences in plasma homocysteine, folic acid, and vitamin B12 among women with preeclampsia. We tested for an association between homocysteine and folic acid and B12, and we hypothesized an inverse relationship of homocysteine and folic acid in preeclampsia, more so in black women in whom preeclampsia developed. Black women with preeclampsia (n=26) had elevated homocysteine concentrations (8.7±1.4 μmol/L) compared with black women with normal pregnancy (n=52, 7.6±0.5 μmol/L), white women with preeclampsia (n=34, 7.5±0.6 μmol/L), and white women with normal pregnancy (n=48, 5.5±0.3 μmol/L). Folic acid concentrations were lower in black women (14.1±0.8 ng/mL) compared with white women (18.5±0.9 ng/mL,
P
<0.01). However, plasma homocysteine was inversely related to folic acid only among black women with preeclampsia (
r
=−0.23,
P
=0.01). These racial differences may have implications for the higher rates of preeclampsia in this group and may have long-term implications for future cardiovascular risk. Racial differences in diet, adherence to folic acid supplementation, or interactions of nutritional and maternal factors warrant further study by race and pregnancy status.
Prevention of Cardiac Hypertrophy by Angiotensin II Type-2 Receptor Gene Transfer
Authors: Metcalfe Beverly L. , Huentelman Matthew J. , Parilak Leonard D. , Taylor David G. , Katovich Michael J. , Knot Harm J. , Sumners Colin , Raizada Mohan K.
Published: April 2004

The role of the angiotensin II type-2 receptor (AT
2
R) in cardiac hypertrophy remains elusive despite its demonstrated involvement in cardiovascular development. We have previously shown that a lentiviral vector gene delivery system is able to transduce cardiac tissue with high efficiency in vivo. Using such an approach, our objectives in the present study were 2-fold: (1) to overexpress the AT
2
R in cardiac tissue after completion of natural embryonic development of the heart and (2) to determine the effects of this overexpression on cardiac hypertrophy and basal blood pressure (BP). A lentiviral vector encoding the AT
2
R (lenti-AT
2
R) was administered (1.5×10
8
transducing units) into the left ventricular space of 5-day-old spontaneously hypertensive rats (SHRs). AT
2
R transgene expression increased in these animals and persisted for 30 weeks. In contrast, the expression of the angiotensin II type-1 receptor remained unchanged following lenti-AT
2
R treatment. At 21 weeks following gene transduction, the lenti-AT
2
R–treated SHRs exhibited decreased left ventricular wall thickness compared with control animals. In contrast, basal BP did not differ between the two SHR groups. Finally, heart weight to body weight ratios indicated a significant decrease in lenti-AT
2
R-treated SHRs compared with SHR controls. Our data indicate that AT
2
R overexpression attenuates cardiac hypertrophy in the SHR. This beneficial outcome was observed despite the existence of elevated BP.
RhoA Activation by Hypoxia in Pulmonary Arterial Smooth Muscle Cells Is Age and Site Specific
Authors: Bailly Karine , Ridley Anne J. , Hall Susan M. , Haworth Sheila G.
Published: April 2004

Hypoxia induces vasoconstriction of pulmonary arteries through contraction of smooth muscle cells (SMCs). The GTPase RhoA regulates smooth muscle contractility and actin cytoskeletal remodeling through the Rho-associated kinase (ROCK). We previously found that the postnatal fall in pulmonary vascular resistance was associated with actin cytoskeletal remodeling in porcine pulmonary arterial SMCs (PASMCs) in vivo. Here, we investigated the effects of acute and chronic hypoxia on the morphology and RhoA activity of PASMCs from fetal and neonatal piglets. Acute hypoxia enhanced actin stress fiber formation and RhoA activity in both inner and outer medial PASMCs from the fetus but only in the inner medial PASMCs from normal 3-day-old piglets. The increased stress fiber formation was dependent on Rho and ROCK. In outer medial PASMCs from 14-day-old animals, acute hypoxia decreased RhoA activity. Interestingly, outer medial PASMCs from animals exposed to chronic hypoxia had fewer stress fibers associated with a lower basal RhoA activity. Treatment of PASMCs from normal 3-day-old piglets with Rho or ROCK inhibitors for 24 hours induced a similar morphology. Rac activity was not altered by either acute or chronic hypoxia. These data show that acute hypoxia induces RhoA activation only in PASMCs from young animals, whereas chronic hypoxia selectively downregulates RhoA activity in outer medial PASMCs leading to an altered phenotype.
In Acute Ischemic Stroke, Are Asymptomatic Intracranial Hemorrhages Clinically Innocuous?
Authors: Kent David M. , Hinchey Judith , Price Lori Lyn , Levine Steven R. , Selker Harry P.
Published: April 2004

Background—

In patients with acute ischemic stroke, intracranial hemorrhages are categorized as symptomatic or asymptomatic based on the presence or absence of a clinically detectable neurological deterioration. Asymptomatic intracranial hemorrhages are believed by many to be clinically innocuous. We examined whether the occurrence of an asymptomatic intracranial hemorrhage affects functional outcome in patients with acute ischemic stroke (AIS) treated or not treated with recombinant tissue plasminogen activator (rt-PA).

Methods—

We combined data from the NINDS rt-PA Stroke Trial and the ATLANTIS Trials, excluding patients with symptomatic intracranial hemorrhage (n=1193). We used generalized estimating equations to test whether asymptomatic intracranial hemorrhage altered the likelihood of a normal or near-normal outcome at 90 days, as measured across 4 commonly used functional outcome scales, controlling for other variables that affect outcome. To look at additional outcomes, including the likelihood of disability and death, we used logistic regression equations. Additionally, we systematically reviewed previous studies that assessed the effect of intracranial hemorrhage in AIS.

Results—

In the combined database, the rate of asymptomatic intracranial hemorrhage was higher in rt-PA treated than in nontreated patients (9.9% versus 4.2%, P<0.0001). Controlling for other prognostic factors, the odds of a normal or near-normal outcome was lower when a patient had an asymptomatic intracranial hemorrhage, but this effect did not reach statistical significance (OR=0.69, 95% CI: 0.43 to 1.12, P=0.13). Similarly, the odds of not being moderately to severely disabled (modified Rankin Score ≤2) was also lower for patients with asymptomatic intracranial hemorrhage (OR=0.60, 95% CI: 0.33 to 1.08, P=0.09). Despite using a larger sample than any previously published study, the power in our study to detect a 30% decrease in the odds of a good outcome was inadequate (≈32%).

Conclusion—

We could not confirm or exclude a clinically significant effect for asymptomatic intracranial hemorrhages based either on our analysis or on any previously published trial. Analysis of substantially larger databases are needed to assess the import of this common clinical event.
Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation
Authors: Holler Ernst , Rogler Gerhard , Herfarth Hans , Brenmoehl Julia , Wild Peter Johannes , Hahn Joachim , Eissner Günther , Schölmerich Jürgen , Andreesen Reinhard
Published: April 2004

Single nucleotide polymorphisms (SNPs) of the NOD2/CARD15 gene resulting in a diminished nuclear factor-κB (NF-κB) response to bacterial cell wall products have been associated with an increased incidence of Crohn disease. To assess a possible contribution of NOD2/CARD15 mutations to graft-versus-host disease (GvHD) and complications following allogeneic stem cell transplantation, we retrospectively typed DNA from donor/recipient pairs in 169 consecutive patients receiving transplants from related or unrelated donors. Mutated alleles were observed in 21% of patients and in 14% of donors. Cumulative incidence of 1-year, transplant-related mortality rose from 20% in donor/recipient pairs without mutated SNPs to 49% in pairs with recipient mutations (P = .03) and 59% in pairs with donor mutations (P < .005), and was highest in 12 pairs with mutated alleles in both donor and recipients (83%; P < .001). Similar associations were observed for severe overall and severe gastrointestinal GvHD. The impact of NOD2/CARD15 mutations was more prominent for HLA-identical sibling transplantations but was also observed in unrelated donor transplantation. Mutations proved to be independent risk factors for transplant-related mortality. Our findings indicate a major role of monocyte/macrophage dysfunction in the pathophysiology of GvHD and strongly suggest a future risk assessment or even donor selection through NOD2/CARD15 typing.
Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants
Authors: Mitra-Kaushik Shibani , Harding John C. , Hess Jay L. , Ratner Lee
Published: April 2004

Recent studies have shown that the transcription factor nuclear factor κB (NF-κB) regulates critical survival pathways in a variety of cancers, including human T-cell leukemia/lymphotrophic virus 1 (HTLV-1)–transformed CD4 T cells. The activation of NF-κB is controlled by proteasome-mediated degradation of the inhibitor of nuclear factor κBα (IκBα). We investigated the effects of PS-341, a peptide boronate inhibitor of the proteasome in HTLV-1 Tax transgenic tumors in vitro and in vivo. In Tax transgenic mice, PS-341 administered thrice weekly inhibited tumor-associated NF-κB activity. Quantitation of proliferation, apoptosis, and interleukin 6 (IL-6) and IL-10 secretion by tumor cells in culture revealed that the effects of PS-341 on cell growth largely correlated with inhibition of pathways mediated by NF-κB. However, the effect of PS-341 on the growth of tumors in Tax transgenic mice revealed heterogeneity in drug responsiveness. The tumor tissues treated with PS-341 show no consistent inhibition of NFκB activation in vivo. Annexin V staining indicated that PS-341 response in vivo correlated with sensitivity to apoptosis induced by γ irradiation. On the other hand, transplanted Tax tumors in Rag-1 mice showed consistent inhibition of tumor growth and prolonged survival in response to the same drug regimen. TUNEL staining indicated that PS-341 treatment sensitizes Tax tumors to DNA fragmentation.
Managing NPD: Cost and Schedule Performance in Design and Manufacturing
Authors: Bajaj Akhilesh , Kekre Sunder , Srinivasan Kannan
Published: April 2004

In this field study, conducted at a leading avionics guidance systems manufacturer, we gathered primary data on time and cost performance of both the design and manufacturing phases of new product development (NPD). We modeled the impact of the management levers relating to oversight, the intensity of design specialization, and the level of interaction with the customer. The study highlights the necessity of leveraging the interdependencies between the design and manufacturing phases in NPD.
Beckett's Tattered Syntax
Authors: BANFIELD ANN
Published: April 2004

ABSTRACT Joyce and Beckett aimed to create a language which, unlike world English, is no one's mother tongue, Joyce by exploiting the phonological and morphological principles for the production of new words, the lexicon's open-class “dictionary.” Beckett, after imitating but ultimately resisting Joyce's lexical inventiveness, extracted the late minimalist style from the lexicon's nonproductive grammatical function words.
Meglitinides: Basic Aspects and Clinical Uses
Authors: Davies M.J. , Chatterjee Sudesna
Published: April 2004

The meglitinides offer an opportunity to target specifically the postprandial hyperglycemia that occurs commonly in patients with type 2 diabetes. Their rapid onset and short duration of action leads to more “physiological” release of insulin and partially restores the pattern of postprandial insulin secretion that is defective in type 2 diabetes mellitus. This potentially allows tighter glycemic control while reducing the risk of hypoglycemia. As prandial glucose regulators they allow flexible dosing such that a tablet need only be taken before a patient has a meal. Repaglinide in particular has been shown to reduce HbA1cand is well‐tolerated by patients both as monotherapy and in combination with other agents. It appears to have some advantages from head‐to‐head studies with sulfonylureas. Nateglinide appears to produce a faster early‐phase insulin response that gives it the potential to produce less hypoglycemia, but randomized controlled trials in comparison with sulfonylureas are lacking. Both agents are more expensive than sulfonylureas. Formal data regarding cost‐effectiveness are not currently available. However, their flexible administration may be of benefit in certain subgroups such as shift‐workers and those with flexible lifestyles. Efficacy in early diabetes and impaired glucose tolerance is currently being investigated. The ability to flexibly dose with these agents makes them useful in patients with flexible lifestyles. Macrovascular and microvascular outcome data for the meglitinides are awaited.
Psychological Problems and Management of Patients with Diabetes Mellitus
Authors: Jacobson Alan M.
Published: April 2004

Diabetes is a complex chronic illness placing intense personal demands on patients and their families. The change process requires a successful relationship with the health care team. One major activity of the team is to promote and assist patient self‐care success. Recognizing barriers that impede this success is a critical part of the assessment process. Moreover, psychological problems such as depression, eating disorders, and anxiety are key aspects of patient functioning. These problems occur at increased frequency among patients with diabetes. Thus a clear understanding of these mental health problems and their role in the treatment process are critical aspects of the knowledge base for clinicians who treat such patients. Specific psychological and quality‐of‐life measures may be very useful in the assessment of diabetic patients in order to guide intervention strategies.
Carbon Nanotube Film Sensors
Authors: Li Z. , Dharap P. , Nagarajaiah S. , Barrera E. V. , Kim J. D.
Published: April 2004

A carbon nanotube film (see Figure) can be used as a strain sensor at the macroscale, due to the dependence of the electrical properties of single‐walled carbon nanotubes on mechanical deformation at the nanoscale.