bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferroelectric/ferroelastic behavior and piezoelectric response of lead zirconate titanate thin films under nanoindentation
Authors: Koval V. , Reece M. J. , Bushby A. J.
Published: March 2005

The electromechanical response of pure lead zirconate titanate (PZT) and Mn-doped PZT thin ferroelectric films under nanoindentation forces of up to 500 mN was investigated. The stress-induced current transients were measured as a function of the externally applied load on films of different thicknesses using a spherical WC–Co cermet indenter of 500 μm nominal radius. It was found that the quasi-static current generated through the direct piezoelectric effect is superimposed with a contribution from irreversible domain processes during the loading/unloading cycle. The film thickness dependency of the electrical transients and an asymmetry of the current-force curves are attributed to the in-plane clamping stress in the films produced by a dissimilar substrate. Analysis of corresponding charge-force hysteresis loops revealed a significant role for the residual stress state on the polarization switching in thin films. By the application of an indentation force, a portion of Barkhausen jumps was empirically estimated to increase as a consequence of reduction of the clamping effect on domains. The Rayleigh hysteretic charge-force curves showed recovery of the charge released during the load-unload stress cycle. For the thicker 700 nm films, the total charge released during loading was fully recovered with weak hysteresis. In contrast, strong in-plane clamping stresses in the 70 nm thick films are suggested to be reponsible for incomplete recovery upon unloading. A considerable domain-wall contribution to the electromechanical response was demonstrated by an enhanced polarization state, which was shown by an increase of the effective piezoelectric coefficient deff of about 35% of its initial value for the thin films at a maximum force of 500 mN.
Intrinsic crystalline structure of epitaxial Pb(Zr,Ti)O3 thin films
Authors: Kanno Isaku , Kotera Hidetoshi , Matsunaga Toshiyuki , Wasa Kiyotaka
Published: March 2005

We report on the intrinsic crystalline structure of epitaxial ferroelectric Pb(Zr,Ti)O3 (PZT) films, which are fully relaxed from the stress of the substrate. The PZT films with the rhombohedral composition of Zr∕Ti=68∕32 were epitaxially grown on (001)Pt∕(001)MgO substrates. Four-circle x-ray diffraction measurements revealed that the films showed not only perfect c-axis orientation, but also a tetragonal phase due to a clamping effect of the substrate. Successively, x-ray diffraction measurements using synchrotron radiation were carried out to examine the intrinsic structure of stress-free PZT films, which were powdered after substrate removal. The structure refinement by Rietveld analysis demonstrated that the films without substrates returned to a rhombohedral phase, however, 19% of the B site in the perovskite structure was occupied by Pb atoms. The phase-transition temperature from rhombohedral to cubic slightly decreased due to the anomalous structure of the stress-free PZT films. These results suggest that the deviation of the thin-film properties from the bulk ones is caused not only by in-plane epitaxial stress as an extrinsic factor, but also by the anomalous crystalline structure of the stress-free thin films.
Improved microwave dielectric properties of (Mg1−(x+y)CaxLay)(Ti1−yAly)O3 ceramics
Authors: Kutty T. R. N. , Jayanthi S.
Published: March 2005

Phase-singular solids of the composition, (Mg1−(x+y) Cax Lay)(Ti1−yAly)O3 (x=0 to 0.88; y=0.05 to 0.35) having the cubic perovskite-type structure were prepared by the substitution of La3+ and Al3+ in equivalent quantities which brought about complete miscibility between MgTiO3 and CaTiO3. These ceramics showed relative permittivities of 16.5 to 50 (at 6GHz) with increasing Ca content, high Q values of 10 000 to 30 000 and retained near-zero temperature coefficients in permittivity at optimum y values. Their dielectric characteristics are better accountable in terms of the positional disorder rather than the tolerance factor of perovskite structure.
Electronic mean free path in as-produced and purified single-wall carbon nanotubes
Authors: Kajiura H. , Nandyala A. , Coskun U. C. , Bezryadin A. , Shiraishi M. , Ata M.
Published: March 2005

The effect of purification on room temperature electronic transport properties of single-wall nanotubes (SWNT) was studied by submerging the nanotubes into liquid mercury. The conductance plots of purified SWNTs showed plateaus, indicating weak dependence of the electrical resistance on the length of the tube connecting the electrodes, providing evidence of quasiballistic conduction in SWNTs. The electronic mean free path of the purified SWNTs reached a few microns, which is longer than that of the as-produced SWNTs, and which is consistent with the calculation based on the scattering by acoustic phonons.
Platinum nitride with fluorite structure
Authors: Yu R. , Zhang X. F.
Published: March 2005

The mechanical stability of platinum nitride has been studied using first-principles calculations. By calculating the single-crystal elastic constants, we show that platinum nitride can be stabilized in the fluorite structure, in which the nitrogen atoms occupy all the tetrahedral interstitial sites of the metal lattice. The stability is attributed to the pseudogap effect from analysis of the electronic structure.
Potential imaging of Si∕HfO2/polycrystalline silicon gate stacks: Evidence for an oxide dipole
Authors: Ludeke R. , Narayanan V. , Gusev E. P. , Cartier E. , Chey S. J.
Published: March 2005

Surface potential profiles of the junction area of a cleaved n-Si(100)∕HfO2∕p+-polycrystalline silicon (poly-Si) gate stack reveal a dipole potential in the oxide, hole trapping at the HfO2/poly-Si interface, with the Fermi level ∼0.4eV below the Si conduction bandedge and enhanced and inhomogeneous hole depletion in the p+-poly-Si. The dipole accounts for band bending reduction in the n-Si and is consistent with flatband voltage shifts reported for similar gate stacks.
Structure - Activity Relationships for Selected Sulfur-Rich Antifungal Compounds
Authors: Baerlocher Felix Jakob , Langler Richard Francis , Frederiksen Mathias Ugelstad , Georges Noni Mandissa , Witherell Ross Davidson
Published: March 2005

A series of sulfur compounds has been prepared and tested against two kinds of
fungi: Aspergillus niger and
Aspergillus flavus. Results on various sulfone
disulfides and ester disulfides have led to the formulation of a proposed
mechanism for fungicidal behaviour that permits one to anticipate which
structures will be antifungal.
Titanium(IV) Imido Complexes of 1,3,5-Trialkyl-1,3,5-triazacyclohexanes
Authors: Baker Murray V. , Palermo Maria C. , Skelton Brian W. , White Allan H.
Published: March 2005

Reactions of the imido complex
Ti(NBut)Cl2(py)3
(py = pyridine) with 1,3,5-trialkyl-1,3,5-triazacyclo- hexanes
(R3tach) produce the corresponding imido complexes
TiCl2(NBut)(R3tach)
(R = Et, But). The new complexes have been
characterized by n.m.r. spectroscopy and, for the R = Bu
t case, by X-ray diffraction studies. The absence of a
C3v axis of
symmetry for the new complexes allowed complete and unequivocal assignment of
their 1H n.m.r. spectra by consideration of
proton{proton coupling and nuclear Overhauser effects.
Silver and Thallium Ion Complexation with Allyloxycalix[4]arenes
Authors: Couton Daniel , Mocerino Mauro , Rapley Chris , Kitamura Chitoshi , Yoneda Akio , Ouchi Mikio
Published: March 2005

A series of six calix[4]arene derivatives bearing allyl groups
and/or benzyl groups functionalized at the phenolic oxygen atoms were
synthesized and their cation-binding abilities for silver(I) and thallium(I)
ions were evaluated through solvent extraction experiments. The results showed
that both silver(I) and thallium(I) picrates were readily extracted by the
tetrasubstituted p-t-butylcalixarene derivatives, while no extraction of
sodium or potassium picrates was observed. The high extractability of
thallium(I) picrate by these ligands was independent of the functional groups
present, but the extraction of silver picrate seemed to be dependent on the
conformational rigidity of the calixarene; those locked into the cone
conformation showed the highest extractability for silver picrate.
New Macrocyclic Ligands. X. 'Reinforced' Single-Ring and Three-Ring Systems Derived from a Common Series of O2N2- and O3N2-Macrocyclic Precursors
Authors: Ahn Tae-Ho , Kim Jeong , Wang Jun , Lindoy Leonard F.
Published: March 2005

The synthesis of new ‘reinforced’
O2N2- and
O3N2-donor single macrocycles
together with isomeric three-ring products is described. The new derivatives,
which respectively incorporate intra- and inter-ring bridges between nitrogen
donor atoms, were obtained on reaction of the parent membered macrocycles with
1,3-dibromopropane (or, in the case of the monomeric ‘reinforced’
rings, also 1,2-dibromoethane).
Enhanced picture of protein-folding intermediates using organic solvents in H/D exchange and quench-flow experiments
Authors: Nishimura Chiaki , Dyson H. Jane , Wright Peter E.
Published: March 2005

Hydrogen/deuterium exchange followed by trapping of the labeled species in the aprotic solvent DMSO has been used to elucidate structure in both the burst-phase molten globule-folding intermediate of apomyoglobin and in an equilibrium intermediate that models the kinetic intermediate. Precise estimates can be made of exchange times in an interrupted exchange-out experiment at pH 4 followed by analysis in DMSO solution, giving extensive sequence-specific information about the structure of the equilibrium intermediate. In addition, the use of DMSO as a solvent for NMR measurements after quench-flow pH-pulse labeling experiments gives a greatly increased data set for the elucidation of the kinetic folding pathway. Interestingly, differences are observed in some regions of apomyoglobin between the equilibrium and kinetic intermediates. These differences are quantitative rather than qualitative; that is, the overall patterns of labeling and secondary structure formation remain similar between the two species. However, local differences are observed, which probably reflect the difference in the solution conditions for the equilibrium experiment (pH 4) vs. the kinetic experiment (pH 6) and the change in the status of the stabilizing hydrogen bond between the side chains of His-24 and His-119.
Sevoflurane versus Halothane: Postoperative Maladaptive Behavioral Changes
Authors: Kain Zeev N. , Caldwell-Andrews Alison A. , Weinberg Megan E. , Mayes Linda C. , Wang Shu-Ming , Gaal Dorothy , Saadat Haleh , Maranets Inna
Published: March 2005

Background

The authors conducted a double-blind, randomized, controlled trial to determine whether the use of sevoflurane in children undergoing anesthesia and surgery results in a higher incidence of postoperative maladaptive behavioral changes as compared with halothane.

Methods

Children and their parents (n = 102) were randomly assigned to either a halothane group (n = 50) or a sevoflurane group (n = 52). The intraoperative anesthetic protocol was strictly controlled, and the postoperative analgesic consumption and pain levels were recorded. The effect of the group assignment on emergence status and maladaptive postoperative behavioral changes was assessed both by validated psychological measures and physiologic instruments (actigraphy) on postoperative days 1-7. Anxiety of the parent and child was also assessed, as was the child's postoperative recovery (Recovery Inventory).

Results

There were no group differences in preoperative state anxiety, postoperative analgesic requirements, postoperative pain, or the incidence of emergence delirium (P = not significant). Two-way repeated-measures analysis of variance showed no group differences in the incidence of postoperative maladaptive behaviors (F4,72 = 0.60, P = 0.701) or actigraphic variables such as percent sleep, number of night awakenings, and night awakenings that lasted for more than 5 min (P = not significant).

Conclusion

The authors found no increased incidence of emergence delirium, maladaptive postoperative behavior changes, or sleep disturbances in children undergoing anesthesia with sevoflurane as compared with halothane.
Tranexamic Acid Reduces Intraoperative Blood Loss in Pediatric Patients Undergoing Scoliosis Surgery
Authors: Sethna Navil F. , Zurakowski David , Brustowicz Robert M. , Bacsik Julianne , Sullivan Lorna J. , Shapiro Frederic
Published: March 2005

Background

Excessive bleeding often occurs during pediatric scoliosis surgery and is attributed to numerous factors, including accelerated fibrinolysis. The authors hypothesized that administration of tranexamic acid would reduce bleeding and transfusion requirements during scoliosis surgery.

Methods

Forty-four patients scheduled to undergo elective spinal fusion were randomly assigned to receive either 100 mg/kg tranexamic acid before incision followed by an infusion of 10 mg . kg . h during surgery (tranexamic acid group) or 0.9% saline (placebo group). General anesthesia was administered according to a standard protocol. Blood loss, transfusion requirements, coagulation parameters, and complications were assessed.

Results

In the tranexamic acid group, blood loss was reduced by 41% compared with placebo (1,230 +/- 535 vs. 2,085 +/- 1,188 ml; P < 0.01). The amount of blood transfused did not differ between groups (615 +/- 460 vs. 940 +/- 718 ml; P = 0.08). Administration of tranexamic acid was a multivariate predictor of blood loss, as was American Society of Anesthesiologists physical status and preoperative platelet count. No apparent adverse drug effects occurred in any patient.

Conclusion

Intraoperative administration of tranexamic acid significantly reduces blood loss during spinal surgery in children with scoliosis.
S-100 Protein and Neurohistopathologic Changes in a Porcine Model of Acute Lung Injury
Authors: Fries Michael , Bickenbach Johannes , Henzler Dietrich , Beckers Stefan , Dembinski Rolf , Sellhaus Bernd , Rossaint Rolf , Kuhlen Ralf
Published: March 2005

Background

Survivors of acute respiratory distress syndrome exhibit neuropsychological sequelae that might be attributable to hippocampal damage. The authors sought to determine the effects of hypoxemia in a pig model of acute lung injury on the hippocampal region and the release of S-100 protein in comparison to a control group in which hypoxemia was induced by reducing the inspired oxygen fraction.

Methods

Hypoxemia was induced in 14 female pigs by repeated lung lavages (lung injury group; n = 7) or by reducing the inspired oxygen fraction (hypoxia-only group; n = 7). Hemodynamic variables, gas exchange, and serum concentrations of S-100 protein were measured at baseline, after induction of acute lung injury, and subsequently for 12 h. Animals were euthanized, and the brains were removed for histopathologic examination.

Results

Comparable blood gases were seen in both groups. Serum S-100 protein concentrations were comparable for both groups at baseline. At all other time points, S-100 concentrations were significantly higher in the lung injury group. Neuropathologic examination showed basophilic and shrunken neurons of the pyramidal cell layer in the hippocampal CA1 subregion of all pigs in the lung injury group. Few abnormalities were seen in the hypoxia-only group.

Conclusions

The same degree of hypoxemia induced in a lavage model of acute lung injury results in greater brain damage assessed by S-100 protein and histopathologic findings when compared to a group in which hypoxemia at the same degree was induced by reducing the inspired oxygen fraction. This suggests that acute lung injury leads to neuropathologic changes independent of hypoxemia.
Endotoxemia-induced Lymphocyte Apoptosis Is Augmented by a Hyperinsulinemic–Euglycemic Clamp
Authors: Nielsen Jeppe Sylvest , Larsson Anders , Brix-Christensen Vibeke , Nyengaard Jens Randel , Ledet Thomas , Tønnesen Else
Published: March 2005

Background

Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis.

Methods

After 60 min of stabilization, 38 anesthetized and mechanically ventilated pigs (weight, 35-40 kg) were divided (by randomization performed before the experiment) into four groups and were then studied for 570 min. Group 1 received no intervention. Group 2 received a HEC (5 mm p-glucose, insulin infusion rate of 0.6 mU . kg (-1). min(-1)) for 570 min. Group 3 received a lipopolysaccharide infusion for 180 min. Group 4 was given a combination of a HEC and a lipopolysaccharide infusion. After the 570-min study period, the pigs were killed, and tissue was sampled from the spleen and frozen. In four sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number of apoptotic B and T lymphocytes was then compared using two-way analysis of variance, and the interaction between endotoxemia and the clamp (hyperinsulinemia and euglycemia) was investigated.

Results

Endotoxemia induced apoptosis of B (P < 0.001) and T lymphocytes (P = 0.016) in the spleen, and this effect was independent of the clamp. The ratios of apoptotic cells in the spleen tissue of pigs with and without endotoxemia were 2.4 (confidence interval, 1.7-3.4) and 1.6 (confidence interval, 1.1-2.2) for B and T lymphocytes, respectively. Independent of endotoxin infusion, HEC increased the number of apoptotic lymphocytes (P = 0.029 and P = 0.038 for B and T lymphocytes, respectively). The ratios of the number of apoptotic spleen cells in pigs treated and not treated with HEC were 1.5 (confidence interval, 1.0-2.1) and 1.5 (confidence interval, 1.0-2.1) for B and T lymphocytes, respectively.

Conclusion

In this porcine model, both endotoxemia and a HEC increased the number of apoptotic B and T lymphocytes in the spleen. Contrary to our hypothesis, lymphocyte apoptosis during acute endotoxemia was augmented by a HEC.
Traumatic Brain Injury and Hemorrhagic Hypotension Suppress Neuroprotective Gene Expression in Injured Hippocampal Neurons
Authors: Hellmich Helen Lee , Garcia Jeanna M. , Shimamura Megumi , Shah Syed A. , Avila Marcela A. , Uchida Tatsuo , Parsley Margaret A. , Capra Bridget A. , Eidson Kristine A. , Kennedy Deborah R. , Winston John H. , DeWitt Douglas S. , Prough Donald S.
Published: March 2005

Background

After traumatic brain injury, memory dysfunction is due in part to damage to the hippocampus. To study the molecular mechanisms of this selective vulnerability, the authors used laser capture microdissection of neurons stained with Fluoro-Jade to directly compare gene expression in injured (Fluoro-Jade-positive) and adjacent uninjured (Fluoro-Jade-negative) rat hippocampal neurons after traumatic brain injury and traumatic brain injury plus hemorrhagic hypotension.

Methods

Twelve isoflurane-anesthetized Sprague-Dawley rats underwent moderate (2.0 atm) fluid percussion traumatic brain injury followed by either normotension or hemorrhagic hypotension. Animals were killed 24 h after injury. Frozen brain sections were double stained with 1% cresyl violet and 0.001% Fluoro-Jade. RNA from 10 Fluoro-Jade-positive neurons and 10 Fluoro-Jade-negative neurons, obtained from the hippocampal CA1, CA3, and dentate gyrus subfields using laser capture microdissection, was linearly amplified and analyzed by quantitative ribonuclease protection assay for nine neuroprotective and apoptosis-related genes.

Results

In injured CA3 neurons, expression of the neuroprotective genes glutathione peroxidase 1, heme oxygenase 1, and brain-derived neurotrophic factor was significantly decreased compared with that of adjacent uninjured neurons. Superimposition of hemorrhagic hypotension was associated with down-regulation of neuroprotective genes in both injured and uninjured neurons of all subregions. Expression of apoptosis-related genes did not vary between injured and uninjured neurons, with or without superimposed hemorrhage.

Conclusions

The authors show, in the first direct comparison of messenger RNA levels in injured and uninjured hippocampal neurons, that injured neurons express lower levels of neuroprotective genes than adjacent uninjured neurons.
Randomized, Double-blind Study of the Analgesic Efficacy of Morphine-6-Glucuronide versus Morphine Sulfate for Postoperative Pain in Major Surgery
Authors: Hanna Magdi H. , Elliott Kate M. , Fung Michelle
Published: March 2005

Background

Morphine-6-glucuronide (M6G) has promising preclinical characteristics and encouraging pharmacokinetic features for acute nociceptive pain. Early studies have produced a good safety profile when compared to morphine sulfate, although in surrogate pain models studies, a mixed picture emerged. A study to evaluate the efficacy and safety profile in a clinical setting was designed.

Methods

The authors conducted a double-blind, randomized, dose-finding study of patients scheduled to undergo major joint replacement. One hundred patients of both sexes were included, with 50 patients in each group. A loading dose of 10 mg of study medication was given intravenously at induction of anesthesia, and two further doses were allowed during surgery if required. Bolus doses via a patient-controlled analgesia system were given subcutaneously at 2 mg/dose and set at a 10-min lockout. Assessments of pain intensity and relief were recorded during the 24-h period.

Results

There were no statistically significant differences between the treatments for 24-h mean pain intensity. However, pain intensity was significantly higher in the M6G group than in the morphine group at 30 min and 1 h. There was no statistical difference in 24-h mean pain relief or retrospective pain scores at any time point during the 24-h period. The severity of sedation was significantly greater in the morphine group than in the M6G group at 30 min, 1 h, 2 h, and 24 h. Respiratory depression was greater in the morphine group than in the M6G group, and more patients in the morphine group withdrew from the study because of respiratory depression.

Conclusions

Overall, M6G has an analgesic effect similar to that of morphine over the first 24 h postoperatively. However, M6G may be slower onset initially than morphine; therefore, a larger initial dose may be required.
Pulmonary Atelectasis
Authors: Duggan Michelle , Kavanagh Brian P. , Warltier David C.
Published: March 2005

Atelectasis occurs in the dependent parts of the lungs of most patients who are anesthetized. Development of atelectasis is associated with decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury. The adverse effects of atelectasis persist into the postoperative period and can impact patient recovery. This review article focuses on the causes, nature, and diagnosis of atelectasis. The authors discuss the effects and implications of atelectasis in the perioperative period and illustrate how preventive measures may impact outcome. In addition, they examine the impact of atelectasis and its prevention in acute lung injury.
The Apgar Score Has Survived the Test of Time
Authors: Finster Mieczyslaw , Wood Margaret , Raja Srinivasa N.
Published: March 2005

In 1953, Virginia Apgar, M.D. published her proposal for a new method of evaluation of the newborn infant. The avowed purpose of this paper was to establish a simple and clear classification of newborn infants which can be used to compare the results of obstetric practices, types of maternal pain relief and the results of resuscitation. Having considered several objective signs pertaining to the condition of the infant at birth she selected five that could be evaluated and taught to the delivery room personnel without difficulty. These signs were heart rate, respiratory effort, reflex irritability, muscle tone and color. Sixty seconds after the complete birth of the baby a rating of zero, one or two was given to each sign, depending on whether it was absent or present. Virginia Apgar reviewed anesthesia records of 1025 infants born alive at Columbia Presbyterian Medical Center during the period of this report. All had been rated by her method. Infants in poor condition scored 0-2, infants in fair condition scored 3-7, while scores 8-10 were achieved by infants in good condition. The most favorable score 1 min after birth was obtained by infants delivered vaginally with the occiput the presenting part (average 8.4). Newborns delivered by version and breech extraction had the lowest score (average 6.3). Infants delivered by cesarean section were more vigorous (average score 8.0) when spinal was the method of anesthesia versus an average score of 5.0 when general anesthesia was used. Correlating the 60 s score with neonatal mortality, Virginia found that mature infants receiving 0, 1 or 2 scores had a neonatal death rate of 14%; those scoring 3, 4, 5, 6 or 7 had a death rate of 1.1%; and those in the 8-10 score group had a death rate of 0.13%. She concluded that the prognosis of an infant is excellent if he receives one of the upper three scores, and poor if one of the lowest three scores.
Bioreactors for Decreasing the Growth of Brain Tumors
Authors: Carroll Rona S. , Machluf Marcelle
Published: March 2005

Malignant gliomas are the most common primary brain tumors. They are highly aggressive tumors characterized by a recurrence rate of virtually 100%. Despite significant advances in neuroimaging and neurosurgical techniques, the median survival time of patients with glioblastoma multiforme remains 12 to 18 months. Malignant gliomas are characterized by rapidly dividing cells, which invade into the normal brain, and a high degree of vascularity. Recent experimental evidence indicates that tumor-related angiogenesis contributes significantly to the malignant phenotype.
Reversing the Negative Genomic Effects of Aging with Short-Term Calorie Restriction
Authors: Spindler Stephen R.
Published: March 2005

According to government figures, total health care spending in the U.S. in 1999 was $1.316 trillion. The government projects an increase in health care costs to $2.176 trillion by 2008. If we project this growth rate to 2020, health care costs will reach $4.009 trillion. Today, people often spend more health care dollars during the last year of their lives than in all previous years combined. Medical treatment in the last few years of life is usually very expensive and often futile. With the baby-boom generation now moving through middle age, the prescription for the U.S. health care system will be disastrous unless we learn how to keep people healthier longer. This dramatic increase in health care costs leaves us with only one acceptable alternative to rationed health care or financial ruin — to discover interventions that make people functionally younger, healthier, and less susceptible to debilitating, age-related diseases.
Back from the Tip of the Nose
Authors: Cossu Giulio
Published: March 2005

About 130 years ago, Giulio Bizozzero, then in Pavia, made a seminal observation [1]. He divided the tissues of the vertebrate body into three categories: those that divide constantly (labile), such as blood and skin, those that never divide, such as striated muscle and brain (perennial), and those that normally do not divide but can do so if injured (stable). As a consequence, diseases that perturb cell division, such as cancer, affect labile tissues, while degenerative diseases affect perennial tissues where repair is inefficient. Epithelia and blood possess a reservoir of cells that divide and maintain a progenitor pool throughout life (the stem cells) whereas striated muscle and brain were supposed not to contain stem cells. Furthermore, stem cells were supposed to generate only the cells of the tissue where they belong.
Signaling Pathway Puts the Break on Fat Cell Formation
Authors: MacDougald Ormond A.
Published: March 2005

Obesity is approaching epidemic proportions in the western industrialized world, and is also becoming a major problem among young people in eastern and developing countries [1,2,3]. Unfortunately, excess fat or adipose tissue is associated with a wide array of health problems, including increased incidence of type II diabetes, cardiovascular disease, hypertension, sleep apnea, and skeletomuscular problems [4,5,6]. Obesity is the second leading cause of death from “unnecessary” causes in the U.S. (after smoking), and costs individuals and society billions of dollars worldwide to treat. Despite common wisdom that “one just needs to eat less and exercise more” and a multi-billion-dollar diet industry, epidemiological data indicate that the incidence of obesity will continue to rise. This alarming trend is, in part, due to the unprecedented availability of energy-dense foods and an increasingly sedentary lifestyle. These environmental factors may be complicated in some individuals by an unfavorable genetic predisposition. Pharmaceutical companies lead active research programs to identify drugs that target weight control centers in the body and which may help individuals control their weight; however, no satisfactory magic bullet to fight obesity has yet come through the pipeline [7,8].
New Biochemical Pathway May Control Erection
Authors: Mills Thomas M.
Published: March 2005

Thirty million men in the U.S. suffer from erectile dysfunction (ED) defined by their inability to achieve or maintain a penile erection sufficient for intercourse. An unestimated number of women also suffer from sexual dysfunction resulting from many of the same causes that lead to ED in men. There are a variety of treatments available for ED including intracavernosal injection, transurethral therapy, surgery, vacuum therapy, and oral medication. Unfortunately, not all patients benefit from these currently available forms of therapy, and side effects are not uncommon. Sildenafil (Viagra) has been a highly successful drug for the treatment of ED but it does not work in all men [5]. Some may experience a variety of side effects, and Viagra is contraindicated to some cardiac medications. These problems point to the need for new and different approaches to the treatment of sexual problems.
Environment as a Risk Factor for Male Infertility
Authors: Multigner Luc , Oliva Alejandro
Published: March 2005

Infertility affects 15% of couples in Western countries. Infertility is defined as the inability to conceive after 1 year of attempts without contraception, but it is not synonymous with sterility. Between 30 and 50% of infertile couples are infertile due to male reasons, mainly due to sperm production disorders. Although some risk factors, most of which are infectious, have been identified, there is still much uncertainty about the origins of male infertility.
Identification of Molecular Substrate for the Attenuation of Anxiety: A Step Toward the Development of Better Anti-Anxiety Drugs
Authors: Rudolph Uwe
Published: March 2005

Anxiety disorders affect some 19 million people in the U.S. alone, costing $46.6 billion, or one third of the nation’s total mental health bill in 1990. Benzodiazepine tranquilizers like the prototypic diazepam are among the most widely used anti-anxiety agents. In addition to their anxiolytic action, they also induce sedation and may impair motor coordination, both of which are undesired side effects when they are used as anxiolytics. Not surprisingly, road traffic accidents may be increased for patients on classical benzodiazepines. In addition, these drugs carry the risk of dependence liability. Benzodiazepines augment the action of the inhibitory neurotransmitter g-aminobutyric acid (GABA) at contact points between two nerve cells called synapses, points at which information is transmitted from one nerve cell to the next. Synaptically released GABA binds to postsynaptic GABAA receptors, thus causing an influx of negatively charged chloride ions into the postsynaptic neuron. This leads to a hyperpolarization and thus functional inhibition of the postsynaptic cell. Benzodiazepines bind to a site on the GABAAreceptor which is different from the GABA binding site, thus increasing the chloride current. Benzodiazepines like diazepam bind to GABAAreceptors containing the α subunits α1, α2, α3, or α5, most likely in abgabg combinations.
Symbiotic Gene Activation is Interrupted by Endocrine Disrupting Chemicals
Authors: Fox Jennifer E. , Burow Matthew E. , McLachlan John A.
Published: March 2005

Endocrine disrupting chemicals (EDCs) include organochlorine pesticides, plastics manufacturing by-products, and certain herbicides[1]. These chemicals have been shown to disrupt hormonal signaling in exposed wildlife, lab animals, and mammalian cell culture by binding to estrogen receptors (ER-α and ER-β) and affecting the expression of estrogen responsive genes[2,3]. Additionally, certain plant chemicals, termed phytoestrogens, are also able to bind to estrogen receptors and modulate gene expression, and as such also may be considered EDCs[4]. One example of phytoestrogen action is genistein, a phytochemical produced by soybeans, binding estrogen receptors, and changing expression of estrogen responsive genes which certain studies have linked to a lower incidence of hormonally related cancers in Japanese populations[5]. Why would plants make compounds that are able to act as estrogens in the human body? Obviously, soybeans do not intentionally produce phytoestrogens to prevent breast cancer in Japanese women.
Lactococcus lactis, A Tool for the Delivery of Therapeutic Proteins Treatment of IBD
Authors: Steidler Lothar
Published: March 2005

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases that consists of ulcerative colitis (UC), an inflammation of the large intestine, and Crohn�s disease (CD), which can affect any part of the gastrointestinal tract. IBD affects approximately 1 in every 1000 individuals in western countries. There is a marked tendency in the age of onset toward gradually younger people. IBD represents a genuine problem in public health because of the absence of etiologic treatment. The clinical image is characterized by recurrent segmental or total inflammatory involvement of the large and/or small intestine, often resulting in a chronic, unpredictable course. The symptoms of both are extremely unpleasant and impact all aspects of quality of life. They include diarrhea, abdominal pain, rectal bleeding, fever, nausea, weight loss, lethargy, and loss of appetite. If left untreated, malnutrition, dehydration, and anemia follow, which, in extreme cases, can even lead to death. Although many patients are managed successfully with conventional medical therapy, such as anti-inflammatory corticosteroid treatment, some stay refractory to treatment, most will have recurrent activity of disease, and two thirds will require surgery. Administered orally or by injection, only a fraction of the active components of most conventional drugs reaches the intended target site, the inflamed intestinal lining. This is not only an inefficient way to deliver drugs, but, more important, means that patients are often subject to a spectrum of unpleasant side effects that result from the high levels of the drugs in other, otherwise healthy tissues and organs of the body.
Emerging Technologies to Control Oocyte Apoptosis Are Finally Treading on Fertile Ground
Authors: Tilly Jonathan L.
Published: March 2005

As the medical community strives to improve on the efficacy of anticancer treatments, a critical issue not to be overlooked since the overall quantity of life has been substantially increased in many cancer survivors is the quality of that life post-therapy. Indeed, one of the most worrisome side effects of conventional cancer treatments is damage to the gonads. This problem is compounded in females since the ovaries, unlike the testes, are incapable of germ cell renewal in postnatal life. As a consequence, the inappropriate destruction of female germ cells (oocytes) following exposure to chemotherapeutic drugs and radiation is irreparable, often leading to premature menopause and infertility [1]. Considering recent estimates that 1 in 52 human females between birth and age 39 (i.e., the pre-reproductive and reproductive years) will be diagnosed with, and presumably treated for, cancer [2], new strategies to minimize or prevent gonadal damage during such treatments would have a profound positive impact on millions of lives.
In vivo Adenoviral Gene Transfer of CGRP and Related Peptides to the Rat and Mouse
Authors: Bivalacqua Trinity , Heistad Donald , Kadowitz Philip , Kass David , Champion Hunter
Published: March 2005

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) play an important role in maintaining low pulmonary vascular resistance (PVR) and may be involved in modulating the pulmonary vascular response to chronic hypoxia. Adenoviral vectors encoding prepro-CGRP (AdRSVCGRP) and ADM (AdRSVADM) were used to examine the effects of in vivo gene transfer of the peptides to the lung on increases in PVR, right ventricular mass, and pulmonary vascular remodelling that occurs in chronic hypoxia in the mouse. Intratracheal administration of AdRSVCGRP or AdRSVADM, followed by 16 days of chronic hypoxia (FIO2 0.10), increased lung CGRP and ADM levels, respectively. The increase in pulmonary arterial pressure (PAP), PVR, right ventricular mass, and pulmonary vascular remodeling in response to chronic hypoxia was attenuated in animals overexpressing prepro-CGRP or ADM whereas systemic arterial pressure was not altered. In chronically hypoxic mice, increases in PAP in response to i.v. injections of angiotensin II and endothelin-1 were attenuated following in vivo gene transfer. These data show that in vivo transfer of the CGRP or ADM gene to the lung attenuates the increase in PVR and right ventricular mass, pulmonary vascular remodeling, and responsiveness in chronically hypoxic mice with little effect on the systemic circulation. In order to study the roles of RAMP 1, 2, and 3 in mediating responses to CGRP and related peptides in the pulmonary and systemic vascular beds, gene transfer of adenovirus vectors encoding CRLR and RAMP 1, 2, or 3 were delivered to the lung and/or hindlimb of the mouse. Transfection of CRLR and RAMP 2 to the pulmonary and hindlimb vascular beds of the mouse resulted in enhanced vasodilator responses to ADM, but not CGRP.
Structural Determinants in the Calcitonin Receptor-Like Receptor (Crlr) Important for Cgrp and Adrenomedullin (Am) Receptor Function of Crlr/Receptor-Activity-Modifying Protein (Ramp) 1 and Crlr/Ramp2 Heterodimers
Authors: Born W. , Leuthauser K. , Gujer R. , Muff R. , Fischer J.A.
Published: March 2005

Cell surface protein cross-linking, coimmmunoprecipitation, and confocal microscopy identified CRLR/RAMP1-, CRLR/RAMP2-, and calcitonin receptor isotype 2 (CTR2)/RAMP1 heterodimers as CGRP-, AM-, and CGRP/amylin receptors, linked to cAMP production. Along these lines, effects of structural alterations in the N-terminal extracellular domain of the human CRLR on cell surface expression as well as the association with RAMP and CGRP or AM have been investigated.
Nicotinic Receptor Activity Alters Synaptic Plasticity
Authors: Dani John A.
Published: March 2005

Studies using specific agonists, antagonists, and lesions have shown that nicotinic cholinergic systems participate in attention, learning, and memory[1,2]. The nicotinic manipulations usually have the greatest influence on difficult tasks or on cognitively impaired subjects[2]. For example, Alzheimer's disease is characterized by a loss of cholinergic projections and nicotinic acetylcholine receptors (nAChRs) in the cortex and hippocampus[3]. Nicotine skin patches can improve learning rates and attention in Alzheimer's patients[4].
Assessment of Land-Use Impact on Macroinvertebrate Communities in the Zwalm River Basin (Flanders, Belgium) Using Multivariate Analysis and Geographic Information Systems
Authors: Adriaenssens Veronique , Goethals Peter L. M. , De Pauw Niels
Published: March 2005

Relationships between land-use and river water quality assessed by means of biological and physical-chemical variables and habitat characteristics were analysed for the Zwalm River basin in Flanders (Belgium). The research focussed on three zones within this river basin, each characterized by different land uses, and consequently, different types of pollution, mainly of diffuse origin. Environmental data have been integrated within a Geographic Information System. Possible relationships between aquatic ecosystem and land-use variables were searched for by means of multivariate analysis.
Japanese Application of Bioassays for Environmental Management
Authors: Kusui Takashi
Published: March 2005

The increasing number of existing and new chemicals demands ecotoxicological data as well as toxicological data for pre- and postmarketing risk assessments. Although human health has been the major concern in Japanese environmental management, ecosystem health is becoming the big issue as the need for preserving the diversity of ecosystems has been recognized. This recognition is changing the regulatory framework in Japan, resulting in new actions toward establishment of water-quality standards for aquatic organisms and ecotoxicological assessment of existing chemicals. At the same time, the need to assess complex liquids that contain several kinds of chemicals is increasing. The ecotoxicological study of Japanese effluents shows that the present chemical-specific standards are not enough to protect aquatic ecosystems. These two factors encourage the application of ecotoxicological tests as well as the toxicological data.
Inteins in Microbial Genomes: Distribution, Mechanism, and Function
Authors: Southworth Maurice W. , Perler Francine B.
Published: March 2005

Inteins are self-splicing protein elements (134 to 608 amino acids). Over 125 inteins have been cataloged in InBase, the on-line intein database (http://www.neb.com/neb/inteins.html), which includes the Intein Registry[1]. Inteins naturally present in pathogenic microbes represent novel, yet unexploited drug targets. Understanding the chemistry of the splicing reaction has allowed the manipulation of inteins, which are now used in many protein engineering applications[2].
Did the CP Audits Promote the Enterprises’ CP? A Case Study in Beijing
Authors: Yu Gang , Huang Jun , Chen Qing
Published: March 2005

Seven enterprises that have had recent Cleaner Production (CP) audits in Beijing were interviewed to identify whether these enterprises implemented the audit recommendations. If enterprises did implement the recommendations, their reasons and the results were analyzed. Finally, some suggestions on how to promote enterprise-wide CP were given.
Effective Monitoring of Small River Basins
Authors: Symader W. , Bierl R. , Krein A.
Published: March 2005

As the transport of many pollutants occurs during high floods monitoring programs must focus on these intermittent events. In small rivers the pollutants start their travel as short pulses often associated with fine particles, but disperse on their way downstreams. Therefore the chemical data of a flood event are only representative of a small part of the basin adjacent to the monitoring station. This is usually not taken into account by evaluating water quality data.
Adverse Environmental Impact: 30-Year Search for a Definition
Authors: Mayhew David A. , Muessig Paul H. , Jensen Loren D.
Published: March 2005

Since passage of the Clean Water Act in 1972, there has been a long, unresolved struggle to define a key phrase in Section 316(b) of the act: “adverse environmental impact” (AEI). Section 316(b) requires that the best technology available be used in cooling-water intake structures to minimize AEI due to entrainment and impingement of aquatic organisms. Various attempts were made to evaluate and define AEI, including focused national conferences on impact assessment. Unresolved arguments regarding AEI were reinvigorated following the 1995 Consent Decree requiring EPA to propose new rules to implement Section 316(b). This article reviews and compares eight proposed definitions of AEI. Six of the definitions define AEI as impact expressed at the population or higher level of biological organization. The two remaining definitions are unrelated to populations: a 1% cropping of the near-field organisms and “one fish equals AEI”. The latter definition is based on the desire of some stakeholders to define AEI as the loss of any public trust resources. Equating loss of public trust resources with AEI hampers consensus on a definition because a societal-based policy concept (public trust resources) is commingled with science-based definitions based on population effects. We recommend that a population-based definition of AEI be incorporated into Section 316(b) guidance and observe that this will not preclude a state from exercising its law and policy to protect public trust resources.
Scientific and Societal Considerations in Selecting Assessment Endpoints for Environmental Decision Making
Authors: Strange Elizabeth M. , Lipton Joshua , Beltman Douglas , Snyder Blaine D.
Published: March 2005

It is sometimes argued that, from an ecological point of view, population-, community-, and ecosystem-level endpoints are more relevant than individual-level endpoints for assessing the risks posed by human activities to the sustainability of natural resources. Yet society values amenities provided by natural resources that are not necessarily evaluated or protected by assessment tools that focus on higher levels of biological organization. For example, human-caused stressors can adversely affect recreational opportunities that are valued by society even in the absence of detectable population-level reductions in biota. If protective measures are not initiated until effects at higher levels of biological organization are apparent, natural resources that are ecologically important or highly valued by the public may not be adequately protected. Thus, environmental decision makers should consider both scientific and societal factors in selecting endpoints for ecological risk assessments. At the same time, it is important to clearly distinguish the role of scientists, which is to evaluate ecological effects, from the role of policy makers, which is to determine how to address the uncertainty in scientific assessment in making environmental decisions and to judge what effects are adverse based on societal values and policy goals.
Determination and Commitment of Mechanosensory Hair Cells
Authors: Kelley Matthew W.
Published: March 2005

Sound and movement are perceived through the vibration of modified ciliary bundles located on the apical surfaces of specialized mechanosensory hair cells. These hair cells derive from specific regions of the otocyst that become determined to develop initially as sensory epithelia and ultimately as either hair cells or supporting cells. The number of hair cells in an individual vertebrate is surprisingly small and the ability to replace these cells varies among different classes. The molecular and cellular factors that specify hair cell identity are not known, but the results of recent experiments have begun to identify some of the signaling pathways that play important roles in hair cell development. This review will describe recent findings related to the factors that influence the final choice of a progenitor cell to develop as a hair cell and discuss their implications for the overall development of the auditory and vestibular systems.