bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic effects of glucose infusion on monochloroacetic acid exposure in rats
Authors: Shimizu Hiroyasu , Dote Tomotaro , Usuda Kan , Toshina Yumi , Kato Junko , Sakai Akiko , Furuya Eisuke , Kono Koichi
Published: April 2004

The effects of glucose infusion on monochloroacetate (MCA) exposure were examined in male rats with a view toward effective clinical treatment for MCA intoxication. Rats were injected with 80 mg/kg sodium monochloroacetate (SMCA) (single lethal dose) and then infused with saline (control group) or 5% or 10% glucose solution at 2 mL/hour for ten hours. No animal in the control group survived the total 14-day follow-up period. The survival rate in 5% glucose group was 57% at ten hours; it decreased to 14% at 14 days. The survival rate in 10% glucose group was 79% at ten hours, and all rats that survived the first ten hours also survived the 14 days. Kaplan -Meier analysis showed the survival rate in 10% glucose group to be improved upon in both the 5% glucose group and the control group. Blood glucose and lactate levels were measured every hour during infusion. Blood glucose levels decreased in the control group but remained in the glucose-infused groups. Although the blood lactate level increased in each group, there was an excellent inverse linear relation between blood glucose levels and blood lactate levels. Thus, continuous parenteral infusion of glucose solution at an early stage after exposure may be an effective clinical therapy for the prevention of hypoglycaemia and metabolic lactic acidosis caused by MCA.
A quantitative model of cellular senescence influence on cancer and longevity
Authors: Pompei Francesco , Wilson Richard
Published: April 2004

Contrary to the paradigm that cancer incidence increases indefinitely with age, significant data now suggest cancer incidence may markedly reduce beyond age 80 years for humans and beyond 800 days for mice, and is not inevitable. We show that increasing cellular senescence with age is a possible cause of this reduction, since senescent cells are removed from the pool of cells that retain proliferative ability necessary for cancer. We further show that animal interventions appearing to alter senescence, p53 mutation and melatonin dosing, support the prediction that increasing senescence rate reduces cancer while reducing lifespan, and vice versa. Studies of environmental agents associated with increased cancer might be re-examined to find if there is an association with longevity increases, which may markedly alter our view of such agents. We also show that if an agent functions by slowing both senescence and carcinogenesis, longevity is increased while reducing cancer. Dietary restriction is the only known intervention that accomplishes this, but there may be others.
Dopamine Receptor Expression and Function in Clinically Nonfunctioning Pituitary Tumors: Comparison with the Effectiveness of Cabergoline Treatment
Authors: Pivonello Rosario , Matrone Carmela , Filippella Mariagiovanna , Cavallo Luigi M. , Di Somma Carolina , Cappabianca Paolo , Colao Annamaria , Annunziato Lucio , Lombardi Gaetano
Published: April 2004

The aim of this study was to correlate dopamine receptors and D2 isoform expression with the cabergoline effect on α-subunit secretion in vitro and tumor mass in vivo in clinically nonfunctioning pituitary tumors.

Eighteen patients were subjected to neurosurgery, and a tumor sample was used for dopamine receptor and D2 isoform expression evaluation by RT-PCR and the in vitro functional studies. After neurosurgery, nine of 18 patients with persistent tumor were treated with cabergoline and tumor mass was evaluated before and after 1 yr treatment.

D2 receptor was expressed in 67% of cases. D2long was found in 50%, D2short in 17%, and both D2 isoforms in 33% of cases. D4 receptor was also expressed in 17% of cases. The in vitro inhibition of α-subunit concentration was found in 56% of cases and was associated with D2 expression (χ2 = 5.6; P < 0.05). After 1 yr of cabergoline treatment, tumor shrinkage was evident in 56% of patients and was associated with D2 expression (χ2 = 5.6; P < 0.05). The expression of D2short rather than D2long isoform is associated with the most favorable response of the tumor to cabergoline treatment.

In conclusion, this study demonstrates D2 receptor expression and function in nearly 70% of cases, suggesting a role of this drug in the treatment schedule of clinically nonfunctioning pituitary tumors.
Insulin-Like Growth Factor Binding Protein-3 Expression Is Associated with Growth Stimulation of T47D Human Breast Cancer Cells: The Role of Altered Epidermal Growth Factor Signaling
Authors: Butt Alison J. , Martin Janet L. , Dickson Kristie A. , McDougall Fiona , Firth Sue M. , Baxter Robert C.
Published: April 2004

IGF binding protein (IGFBP)-3 has antiproliferative and proapoptotic effects on the growth of human breast cancer cells in vitro. However, clinical studies suggest that high levels of IGFBP-3 in breast tumor tissue are associated with large, highly proliferative tumors. In this study, we examined the effects of stable transfection with human IGFBP-3 cDNA on the growth of T47D human breast cancer cells in vitro and in vivo. Expression of IGFBP-3 initially inhibited the growth of T47D in vitro but was associated with enhanced growth in vivo. Furthermore, IGFBP-3-expressing cells in vitro became growth stimulated at higher passages post transfection, suggesting breast cancer cells may switch their response to IGFBP-3 with increasing tumorigenicity. These stimulatory effects observed in IGFBP-3-expressing cells were associated with an enhanced responsiveness to the proliferative effects of epidermal growth factor (EGF). When EGF receptor (EGFR) kinase activity was blocked using PD153035, high passage IGFBP-3 transfectants were growth inhibited compared with controls treated with inhibitor. These findings suggest that the interaction between IGFBP-3 and the EGFR system is central to whether IGFBP-3 acts as a growth stimulator or inhibitor in breast cancer cells and that therapies targeting EGFR may have increased efficacy in breast tumors expressing high levels of IGFBP-3.
Change in Estradiol and Follicle-Stimulating Hormone across the Early Menopausal Transition: Effects of Ethnicity and Age
Authors: Randolph John F. , Sowers MaryFran , Bondarenko Irina V. , Harlow Siobán D. , Luborsky Judith L. , Little Roderick J.
Published: April 2004

Serum reproductive hormone concentrations were measured longitudinally in a community-based, multiethnic population of midlife women to assess whether ethnic differences exist in the patterns of change in estradiol (E2) and FSH and, if so, whether these differences are explained by host characteristics. We studied 3257 participants from seven clinical sites in the Study of Women’s Health Across the Nation (SWAN) who were aged 42–52 yr at baseline and self-identified as African American (28.2%), Caucasian (47.1%), Chinese (7.7%), Hispanic (8.4%), or Japanese (8.6%). E2 and FSH were assayed in serum collected primarily in the early follicular phase of a spontaneous menstrual cycle in three consecutive annual visits. The primary explanatory variables included in repeated-measures regression analyses were race/ethnicity, menopausal status, age, body mass index (BMI), day of the cycle, smoking, parity, socioeconomic status, study site, and the self-report of diabetes at baseline.

At the baseline visit, 46.2% of the women were classified as being early perimenopausal, with the remaining being premenopausal. By the second follow-up visit, 5.5% of the women in that cohort were postmenopausal, 66.8% were early perimenopausal, 8.3% were late perimenopausal, and 19.4% remained premenopausal.

Serum E2 concentrations decreased significantly with age, with a steeper decline at higher ages. FSH concentrations increased significantly with age, with a steeper increase at higher ages. Similar patterns in the decline of E2 and the increase in FSH with age were found across ethnic groups, but the levels of these hormones differed by race/ethnicity. Specifically, over time, Chinese and Japanese women had lower E2 concentrations but similar FSH levels, compared with Caucasian women, and African American women had higher FSH concentrations but comparable E2 levels with those of Caucasian women. These ethnic differences in E2 and FSH were independent of menopausal status. The effect of BMI on serum E2 and FSH levels varied by menopausal status. Increasing BMI was associated with decreasing concentrations of E2 among premenopausal and early perimenopausal women but was associated with increasing concentrations of E2 among late perimenopausal and postmenopausal women. Increasing BMI was associated with decreasing concentrations of FSH, with the effect of BMI becoming larger as women transitioned through menopause.

We conclude that serum E2 levels decrease and FSH concentrations increase with increasing age in midlife women, that ethnic differences in E2 over time differ from ethnic differences in FSH and suggest ethnic differences in the pituitary-ovarian relationship, and that the effect of BMI on E2 and FSH concentrations varies by menopausal status.
Ghrelin Secretion in Childhood Is Refractory to the Inhibitory Effect of Feeding
Authors: Bellone Simonetta , Castellino Nadia , Broglio Fabio , Rapa Anna , Vivenza Daniela , Radetti Giorgio , Bellone Jaele , Gottero Cristina , Ghigo Ezio , Bona Gianni
Published: April 2004

Ghrelin, a natural GH secretagogue, is predominantly produced by the stomach. Ghrelin has other actions including orexant activity, modulation of energy balance, and modulation of endocrine and nonendocrine functions. Ghrelin secretion is increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. Ghrelin secretion does not seem to be a function of age; in fact, morning ghrelin levels after overnight fasting in prepubertal and pubertal children are similar to those in young adults. To clarify whether children and adults have the same sensitivity to the inhibitory effect of food intake, we studied the ghrelin response to a standardized light breakfast (SLB) in 10 prepubertal lean children whose results were compared with those recorded in 19 normal-weight adults. Basal ghrelin levels in children (median, 224.5; 25th to 75th percentile, 122.0–447.7 pg/ml) and adults (338.0; 238.0–512.0 pg/ml) were similar. SLB inhibited ghrelin levels in adults (263.0; 190.0–399.0 pg/ml). However, no change in ghrelin levels after SLB (206.5; 105.0–274.0 pg/ml) was recorded in children. Thus, food intake inhibits ghrelin secretion in adults but not in children. Ghrelin refractoriness to inhibition by food intake in children would reflect a peculiar functional profile of the ghrelin system in childhood.
Estrogen Controls Lipolysis by Up-Regulating α2A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor α. Implications for the Female Fat Distribution
Authors: Pedersen Steen B. , Kristensen Kurt , Hermann Pernille A. , Katzenellenbogen John A. , Richelsen Bjørn
Published: April 2004

Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation.

We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic α2A-adrenergic receptors in sc adipocytes. The increased number of α2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on α2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot.

These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic α2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype α.

These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic α2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.
Medical Cure of Plasma Cell Granuloma of the Thyroid Associated with Hashimoto’s Thyroiditis: A Case Report and Review
Authors: Laurent Silvana , Mouthon Luc , Longchampt Elisabeth , Roudaire Marie , Franc Sylvia , Krivitzky Alain , Cohen Régis
Published: April 2004

Plasma cell granuloma (PCG) is a rare, benign inflammatory tumor composed of myofibroblasts, abundant plasma cells, and lymphocytes combined with collagen. A thyroid localization of PCG is extremely rare, and surgical therapy is indicated. We report the case of a 35-yr-old woman with a thyroid PCG, associated with Hashimoto’s thyroiditis, that was responsible for tracheal compression. Surgery was performed, but the thyroid could not be removed because of the fibrotic process. The patient was treated with corticosteroids and immunosuppressive therapy. Dyspnea and dysphagia improved within 1 month, whereas thyroid volume returned to normal within 3 yr. We also review other reports of thyroid PCG in the literature and discuss the differential diagnosis and treatment. Although the use of immunosuppressive therapy has never been reported for thyroid PCG until now, this treatment may represent a good alternative to surgery in life-threatening, unresectable PCG.
Cytoplasmic Expression of Fibroblast Growth Factor Receptor-4 in Human Pituitary Adenomas: Relation to Tumor Type, Size, Proliferation, and Invasiveness
Authors: Qian Zhi Rong , Sano Toshiaki , Asa Sylvia L. , Yamada Shozo , Horiguchi Hidehisa , Tashiro Takashi , Li Chiun Chei , Hirokawa Mitsuyoshi , Kovacs Kalman , Ezzat Shereen
Published: April 2004

The pathogenesis of pituitary adenomas remains unknown. A pituitary tumor-derived (ptd) isoform of fibroblast growth factor receptor-4 (ptd-FGFR4) has been implicated in the neoplastic process. To further understand the expression of FGFR4 in sporadic human pituitary adenomas, we studied 137 pituitary adenomas of various types (102 adenomas from Japanese patients and 35 adenomas from Canadian patients) and 10 nontumorous pituitaries using a polyclonal antiserum that recognizes the C terminus of FGFR4 and analyzed possible relationships among expression of FGFR4, patient nationality, tumor type, size, invasion, and the labeling index of the proliferation marker Ki-67 using the MIB-1 antibody. Cytoplasmic expression of FGFR4 protein was observed in 57.8% of Japanese cases and 62.8% of Canadian cases. FGFR4 reactivity was absent in all 10 normal adenohypophysial tissues examined. FGFR4 expression in pituitary adenomas was restricted mainly to the cytoplasm, a pattern similar to that seen in rat pituitary cells transfected with human ptd-FGFR4 but different from that of cells transfected with wild-type FGFR4, which displayed membrane localization of staining. Protein from primary human adenomas migrated as a 65-kDa species consistent with the predicted size of ptd-FGFR4. FGFR4 protein expression was frequently found in adenomas containing GH, ACTH, or FSH/LH and was also found in null cell adenomas, but reactivity was relatively rare in prolactin-containing adenomas in both Japanese and Canadian groups. The expression of FGFR4 protein was stronger in macroadenomas than in microadenomas (P = 0.02) and high levels of FGFR4 expression (moderate or greater density staining) were more frequently observed in macroadenomas than in microadenomas (P < 0.05). High levels of FGFR4 expression also correlated significantly with the proliferation marker Ki-67 (P = 0.002) and tended (but not significantly) to be found in invasive tumors. These data are consistent with a role for ptd-FGFR4 in pituitary tumorigenesis in a majority of human pituitary adenomas. Moreover, detection of FGFR4 cytoplasmic staining may provide an ancillary diagnostic tool in the diagnosis of pituitary adenoma, particularly in equivocal cases.
A Novel Mutation in the Preprovasopressin Gene Identified in a Kindred with Autosomal Dominant Neurohypophyseal Diabetes Insipidus
Authors: Wahlstrom Justin T. , Fowler Michael J. , Nicholson Wendell E. , Kovacs William J.
Published: April 2004

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a defect in free water conservation caused by mutations in the single gene that encodes both vasopressin (VP) and its binding protein, neurophysin II (NP II). Most of the human mutations in this gene have been in the portion encoding the NP molecule; the resultant abnormal gene products are believed to cause cellular toxicity as improperly folded precursor molecules accumulate in the endoplasmic reticulum. We identified a new American kindred with ADNDI and found a novel mutation in the VP molecule. A 78-yr-old man was noted to have hypotonic polyuria and plasma hyperosmolarity; the urinary concentration defect was reversed by administration of VP. His symptomatology dated to childhood, and his family history was consistent with autosomal transmission of the polyuric syndrome, with affected members in three generations, including several females. Affected individuals were found to be heterozygous for a 3-bp deletion in exon 1 of arginine VP (AVP)-NP II, predicting a deletion of phenylalanine 3 (known to be critical for receptor binding) in the VP nonapeptide. Neuro 2A cells stably transfected with the mutant AVP-NP construct showed increased rates of apoptosis as assessed by flow cytometric methods. These observations support the concept that cellular toxicity of abnormal AVP-NP gene products underlies the development of ADNDI, and the data further demonstrate that mutations affecting the AVP moiety can result in initiation of these pathological processes.
Dichloroacetate Therapy Attenuates the Blood Lactate Response to Submaximal Exercise in Patients with Defects in Mitochondrial Energy Metabolism
Authors: Duncan G. E. , Perkins L. A. , Theriaque D. W. , Neiberger R. E. , Stacpoole P. W.
Published: April 2004

We determined acute and chronic effects of dichloroacetate (DCA) on maximal (MAX) and submaximal (SUB) exercise responses in patients with abnormal mitochondrial energetics. Subjects (n = 9) completed a MAX treadmill bout 1 h after ingesting 25 mg/kg DCA or placebo (PL). A 15-min SUB bout was completed the next day while receiving the same treatment. After a 1-d washout, MAX and SUB were repeated while receiving the alternate treatment (acute). Gas exchange and heart rate were measured throughout all tests. Blood lactate (Bla) was measured 0, 3, and 10 min after MAX, and 5, 10, and 15 min during SUB. MAX and SUB were repeated after 3 months of daily DCA or PL. After a 2-wk washout, a final MAX and SUB were completed after 3 months of alternate treatment (chronic). Average Bla during SUB was lower (P < 0.05) during both acute (1.99 ± 1.10 vs. 2.49 ± 1.52 mmol/liter) and chronic (1.71 ± 1.37 vs. 2.39 ± 1.32 mmol/liter) DCA vs. PL despite similar exercise intensities between conditions (∼75 and 70% maximal exercise capacity during acute and chronic treatment). Thus, although DCA does not alter MAX responses, acute and chronic DCA attenuate the Bla response to moderate exercise in patients with abnormal mitochondrial energetics.
Complex Analysis of Flutter and Buckling of Beams under Rotational and Transverse Spring Constraints
Authors: Wang Q. , Lim Teik C.
Published: April 2004

The flutter and buckling analysis of a beam, subjected to a follower force, is studied theoretically. The beam is constrained by a pair of transverse and rotational springs at one end and fixed at the other end. The effects of the transverse and rotational spring stiffnesses are studied to obtain the transition condition differentiating two distinct types of instability that co-existed in the beam. The critical follower force is derived for both flutter and buckling of the beam. In addition, the variations of the parametric curves for the critical follower force are analyzed, and the abrupt drop or rise points in the curve are taken as the indicators of the transition between different types of instability. The research discussed in this paper may be used as a benchmark for the flutter and buckling analysis of beams. Moreover, this work may provide an accurate model in dealing with the flutter and buckling analysis and design of general beams.
Factors Influencing Spacing and Width of Cracks in Reinforced Concrete; New Prediction Formulae
Authors: Piyasena R. , Loo Yew-Chaye , Fragomeni Sam
Published: April 2004

An analytical method is used to calculate the spacing and width of cracks for a series of reinforced concrete beams having different material and sectional properties. The calculated values are used to investigate the effects of different variables on the spacing and width of cracks. Bar diameter, effective width of the beam per bar, concrete cover and the effective depth are shown to be the most significant parameters affecting the spacing and width of cracks at a given load level. A parametric study is subsequently carried out utilising the above significant parameters, and the spacing and width of cracks are re-calculated. Results of this parametric study are used to develop simplified prediction formulae. Finally a comparative study is undertaken, which indicates that the spacing and width of cracks calculated by the new formulae agree well with the test results of other investigators.
Distortional Buckling of I-Beams by Finite Element Method
Authors: Poon Choi-Ping , Ronagh Hamid Reza
Published: April 2004

Distortional buckling, unlike the usual lateral-torsional buckling in which the cross-section remains rigid in its own plane, involves distortion of web in the cross-section. This type of buckling typically occurs in beams with slender web and stocky flanges. Most of the published studies assume the web to deform with a cubic shape function. As this assumption may limit the accuracy of the results, a fifth order polynomial is chosen here for the web displacements. The general line-type finite element model used here has two nodes and a maximum of twelve degrees of freedom per node. The model not only can predict the correct coupled mode but also is capable of handling the local buckling of the web.
Acoustic and Electroacoustic Characterization of Variable-Charge Mineral Suspensions
Authors: Guerin Marianne , Seaman John C. , Lehmann Charlotte , Jurgenson Arthur
Published: April 2004

Acoustic and electroacoustic measurements of particle-size distribution (PSD) and zeta potential (ζ potential), respectively, were used to obtain in situ measures of the effects of suspension concentration and pH on interactions between mixed-charge clays and clay minerals from a highly weathered sediment. Measurements were obtained in concentrated suspensions as a function of weight fraction and as a function of pH during titrations. Standard dispersion and centrifugation methods were used to obtain a comparative measure of PSD. Thermogravimetric analysis and X-ray diffraction patterns were used to obtain semi-quantitative and descriptive analyses, respectively, of the sediment, which is composed of Fe oxide minerals, kaolinite, gibbsite, quartz, crandallite, chlorite and traces of other clay minerals. Acoustic measurements showed that the PSD of the clay fraction varied with suspension concentration, and electroacoustic measurements showed the ‘bulk’ ζ potential increased in absolute value as the suspension concentration decreased. Titration results were also sensitive to suspension concentration. Acoustic measurements indicated that the suspensions became unstable at ∼pH 7.5–8.0, as the attenuation spectra changed character near this pH and the calculated PSD shifted to a larger particle size. This pH value is near the points of zero charge of goethite and gibbsite, as verified by titrations on mineral standards. The results confirm the central role oxide minerals play in regulating clay mineral interactions in highly weathered sediments, and indicate that the average ζ potential of a suspension may be a poor indicator of controls on suspension stability.
The Ordering of HDTMA in the Interlayers of Vermiculite and the Influence of Solvents
Authors: Slade Phil G. , Gates Will P.
Published: April 2004

X-ray basal reflections of several HDTMA-vermiculites show that when these contain co-adsorbed molecules of HDTMA-Br, their interlayer spacings are ∼29.5 Å. After HDTMA-Br has been leached out with ethanol, spacings decrease to ∼26 Å, but when exposed to toluene vapor the spacings increase to ∼36 Å, and to ∼45 Å in toluene liquid. Transmission X-ray diffraction photographs of HDTMA-vermiculites, both with and without co-adsorbed HDTMA-Br, indicate that they have highly ordered interlayer structures. The structure of HDTMA-Br-free vermiculite flakes is more open with the interlayer cations arranged in a 3a × b superstructure. In the HDTMA-Br containing HDTMA vermiculite flakes, HDTMA-Br molecules occupy interstitial positions between the HDTMA cations. Swelling in toluene vapor does not disorder the 2-dimensional arrangement of interlayer cations, but disorder does occur in toluene liquid. In toluene vapor, the aliphatic chains of the cations remain partially interdigitated, but in toluene liquid the interdigitation disappears. In response to the layer-charge density, the organization of the interlayer HDTMA units is caused by the self-assembly process responsible for hydrocarbon close packing.
Crystal-Chemical Changes in an Oxidative Weathering Front in a Georgia Kaolin Deposit
Authors: Schroeder Paul A. , Pruett Robert J. , Melear Nathan D.
Published: April 2004

The Eocene Huber Formation, exposed in the CFI Hall mine south of Irwinton, in Wilkinson County, Georgia, displays colored zones that are a consequence of an oxidative weathering front. These zones vary from very light gray (gray) to pinkish white (pink) to very pale yellow (cream) (Munsell N8, 5YR 8/2 and 2.5Y 8/2, respectively) with increasing degree of oxidation. A representative sample from each zone was collected and analyzed for its chemical, crystallographic and Raman spectroscopic properties. The comparison of these genetically related samples allowed for a quantitatively accurate assessment of anatase’s contribution to the total TiO2 content. All samples contain ∼1.5 wt.% TiO2. Progressing from gray to pink to cream, anatase contents range from half to nearly all the TiO2. The a lattice parameter for anatase is constant in all three kaolins (3.7916 Å), suggesting a constant 4.6 mol.% isomorphous substitution of Fe for Ti.

Phase characterization and mass-balance considerations of the gray, pink and cream kaolins indicate that ilmenite and pyrite are precursor Ti- and Fe-bearing phases in the gray kaolin that undergo oxidation. Pseudorutile is a proposed intermediate phase resulting from the anodic corrosion of ilmenite. Hematite, goethite and anatase are the dominant end-products via dissolution-precipitation from the reactants pyrite and pseudorutile. The removal of Fe sulfides and organic matter and addition of hematite and goethite causes kaolin colors to change from gray to pink. Oxygen diffusing from groundwater in permeable overlying and underlying formations facilitates a process that probably involves aerobic and anaerobic bacteria that utilize Fe from pyrite, hematite and goethite. We postulate that the end result is the mobilization of Fe by siderophores and a kaolin color change from pink to cream.
Formation and Properties of a Continuous Crystallinity Series of Synthetic Ferrihydrites (2- to 6-line) and their Relation to FeOOH Forms
Authors: Schwertmann Udo , Friedl Josef , Kyek Andreas
Published: April 2004

Ferrihydrite is a poorly crystalline Fe oxide of which 2-(XRD)line and 6-line varieties are commonly used in experiments, although species with intermediate numbers of peaks have been found in nature. To simulate nature, we synthesized two continuous series of ferrihydrites with between 2 and 6–7 peaks at room temperature in two different ways: (1) by varying the rate of hydrolysis of an Fe(NO3)3 solution (HR series); and (2) by oxidizing an FeCl2 solution containing up to 73 mmol Si/L (Si series), both at pH 7. Mössbauer spectra at 4.2 K showed that the ferrihydrites of the HR series had a constant magnetic hyperfine field (Bhf) at 4.2 K of 48.8 T whereas Bhf in the Si series dropped from 49.4 to 46.7 T as the Si content of the ferrihydrites increased from 0 to 74.7 g/kg of Si. Temperature scans between 4 and 170 K illustrate that the magnetic order breaks down at a temperature which is lower the higher the hydrolysis rate and the Si concentration in the ferrihydrite.
Developing capability through learning networks
Authors: Bessant John , Kaplinsky Raphael , Morris Mike
Published: April 2004

There is widespread recognition that firms need continuous upgrading of their operations and capabilities to be able to retain a competitive edge in a highly uncertain market environment. This raises questions about the mechanisms available for them to learn and develop capability.
One area of topical enquiry is that of inter-firm learning. For individual firms, the advantages of learning in a network context include access to the experiences of others and peer-group support, reduction of risks in R-and-D experimentation, and the potential for creativity and innovation
arising as a response to competitive challenges. Examples of such network configurations can be found in regional clusters, sector groupings, heterogeneous groups sharing a common topic of interest, user groups concerned with learning around a particular technology or its application and in
supplychain learning. Learning in such configurations does not, however, take place automatically. This paper addresses some of the management challenges involved in setting up and nurturing learning networks. It draws particularly on a case of a learning network in the timber products industry
in South Africa.
Diffusion of environmentally friendly technologies by multinational corporations in developing countries
Authors: Chudnovsky Daniel , Lopez Andres
Published: April 2004

Multinational corporations (MNCs) can be an important source of environmentally friendly technologies for developing countries since their affiliates are often more advanced than local firms in the adoption of modern environmental technologies and management practices. This does not mean, however, that MNC affiliates in developing countries invariably employ the same standards, technologies and management approaches adopted by their parent companies or by affiliates operating in developed countries. The contribution of MNC affiliates to sustainable development depends on the quality of their operation and the characteristics of the host countries where they operate. The former is conditioned by such factors as the nature of the sectors where MNCs direct their investments, the kind of assets brought by MNCs, and the role played by the affiliates within the MNC global network. The latter is mainly about the availability of skills, the state of domestic technological infrastructure, the competitiveness of local suppliers, the nature of national environmental regulations and the extent to which these regulations are enforced. The paper notes the need for more robust empirical studies on the environmental role of MNCs to guide policy aimed at enhancing the effectiveness of foreign direct investment (FDI) initiatives in promoting sustainable development.
La formation-action: une modalité de l’apprentissage organisationnel
Authors: Larrasquet Jean-Michel , Franchisteguy Isabelle , Rodriguez Mañalich Emilio
Published: April 2004

Les méthodes mises en œuvre par notre équipe lors de nos interventions en accompagnement des projets de changement en entreprises ou organisations sont essentielles pour entreprendre de tels chantiers. Le contexte doit cependant être compris comme un collectif
humain, et donc faire la place à toute l’approche ‘soft’, psycho-sociologique et cognitive, qui caractérise au niveau intime les dynamiques collectives. Cette identification théorique de la nature et de la dynamique des liens entre individus et groupes,
notamment sur le plan cognitif, implique des caractéristiques et des modalités de mise en œuvre de ces démarches d’amélioration. Notre position est que la formation action est particulièrement bien adaptée à cet objectif, à
condition de la mettre en œuvre comme un projet, d’une façon qui respecte les individus et qui leur ménage un espace de ‘micro-socialisation’ et de réalisation personnelle et collective. Sous un certain nombre de conditions, certes difficiles à
mettre en œuvre, nous proposons d’examiner si nos savoir-faire sont transférables aux environnements cubains et sud américains.
Book Reviews
Authors: Common Mick , Ferguson Hugh
Published: April 2004

World Development Report 2003: Sustainable Development in a Dynamic World – Transforming Institutions, Growth, and Quality of Life, The World Bank, (2003) New York: Oxford University Press, xxi + 250 pp., ISBN 0-8213-5150-8, £16.50

Greening the Corporation:
Management Strategy and the Environmental Challenge, Peter T. Robbins (2001) London: Earthscan Publications, 190 pp. (incl. 34 pp. of endnotes and 15 pp. of references), ISBN 1-85383-772-5 (paperback), £17.95; ISBN 1-85383-771-7 (hardback), £47.50
Dissociating Detection from Localization of Tactile Stimuli
Authors: Harris Justin A. , Thein Thida , Clifford Colin W. G.
Published: April 2004

In what they described as “a tactile analog of blindsight,” Paillard et al. (1983) reported the case of a woman with damage to the left parietal cortex who was profoundly impaired in detecting tactile stimuli but could nonetheless correctly identify their location (also Rossetti et al., 1995). This stands in direct contrast to reports of neurological patients who were unable to accurately locate stimuli that they could successfully detect (Head and Holmes, 1911; Halligan et al., 1995; Rapp et al., 2002). The combination of these findings suggests that detecting and locating tactile stimuli are doubly dissociable processes, presumably mediated by different neural structures. We conducted four psychophysical experiments seeking evidence for such a double dissociation in neurologically intact subjects. We compared people's accuracy in detecting versus locating a tactile stimulus presented to one of four fingers and followed by a vibrotactile mask presented to all four fingers. Accuracy scores for both the yes–no detection and four-alternative forced-choice location judgments were converted to a bias-free measure (d′), which revealed that subjects were better at detecting than locating the stimulus. Detection was also more sensitive than localization to manipulations involving the mask: detection accuracy increased more steeply than localization accuracy as the target-mask interval increased, and detection, but not localization, was affected by changes in the mask frequency. By comparing these results with simulated data generated by computational models, we conclude that detection and localization are not mutually independent as previous neurological studies might suggest, but rather localization is subsequent to detection in a serially organized sensory processing hierarchy.
Odors Detected by Mice Deficient in Cyclic Nucleotide-Gated Channel Subunit A2 Stimulate the Main Olfactory System
Authors: Lin Weihong , Arellano Julie , Slotnick Burton , Restrepo Diego
Published: April 2004

It is believed that odor transduction in the mammalian main olfactory system only involves the cAMP-signaling pathway. Here, we report on odor responsiveness in mice with a disrupted cyclic nucleotide-gated (CNG) channel subunit A2. Several odorants, including putative pheromones, can be detected and discriminated by these mice behaviorally. These odors elicit responses in the olfactory epithelium, main olfactory bulb, and olfactory (piriform) cortex of CNGA2 knock-out mice. In addition, responses to odors detected by CNGA2 knock-out mice are relatively insensitive to inhibitors of the cAMP pathway. These results provide strong evidence that cAMP-independent pathways in the main olfactory system of mammals participate in detecting a subset of odors.
Dendritic Control of Spontaneous Bursting in Cerebellar Purkinje Cells
Authors: Womack Mary D. , Khodakhah Kamran
Published: April 2004

We investigated the mechanisms that contribute to spontaneous regular bursting in adult Purkinje neurons in acutely prepared cerebellar slices. Bursts consisted of 3–20 spikes and showed a stereotypic waveform. Each burst developed with an increase in firing rate and was terminated by a more rapid increase in firing rate and a decrease in spike height. Whole-cell current-clamp recordings showed that each burst ended with a rapid depolarization followed by a hyperpolarization. Dual dendritic and somatic extracellular recordings revealed that each burst was terminated by a dendritic calcium spike. The contributions of T- and P/Q-type calcium current, large (BK) and small (SK) conductance calcium-activated potassium currents, and hyperpolarization-activated (IH) current to bursting were investigated with specific channel blockers. None of the currents, except for P/Q, were required to sustain spontaneous bursting or the stereotypic burst waveform. T-type calcium, BK, and SK channels contributed to interspike and interburst intervals. The effect of T-type calcium channel block was more pronounced after BK channel block and vice versa, indicating that these two currents interact to regulate burst firing. Block ofIHcurrent had no effect on bursting. Partial block of P/Q-type calcium channels concurrently eliminated dendritic calcium spikes and caused a switch from regular bursting to tonic firing or irregular bursting. Dendritic calcium spikes persisted in the presence of tetrodotoxin, indicating that their initiation did not require somatic sodium spikes. Our results demonstrate an important role for dendritic conductances in burst firing in intact Purkinje neurons.
Inhibition of Glutamate Receptor 2 Translation by a Polymorphic Repeat Sequence in the 5′-Untranslated Leaders
Authors: Myers Scott J. , Huang Yunfei , Genetta Thomas , Dingledine Raymond
Published: April 2004

Previous studies have identified multiple transcription initiation sites for the glutamate receptor 2 (GluR2) gene, resulting in a heterogeneous population of GluR2 transcriptsin vivothat differ in the length of their 5′-untranslated leaders (5′-UTR). We designed a series of monocistronic and dicistronic GluR2 cDNA constructs that model the naturalin vivotranscripts and investigated their translation efficiencies in rabbit reticulocyte lysates,Xenopusoocytes, and primary cultured neurons. Transcripts containing long 5′ leaders (429 and 481 bases) were translated poorly compared with those with shorter leaders (341 or fewer bases). None of the five initiation codons in the 5′-UTR or the leader length per se were responsible for translation regulation. Rather, control of translation was mediated by a sequence containing a 34–42 nucleotide imperfect GU repeat predicted to form secondary structurein vivo. This translation suppression domain is included in some but not all rat and human GluR2 transcriptsin vivo, depending on the site of transcription initiation. Rat cortex GluR2 transcripts that lack the translation suppression sequence were preferentially associated with polyribosomes. Furthermore, the GU-repeat cluster was found to be polymorphic in humans, raising the possibility that expansion or contraction of the GU-repeat cluster in certain populations might modify the level of GluR2 protein expression in neurons.
Neurobeachin Is Essential for Neuromuscular Synaptic Transmission
Authors: Su Yuhua , Balice-Gordon Rita J. , Hess Darren M. , Landsman Douglas S. , Minarcik Jeremy , Golden Jeffrey , Hurwitz Ivy , Liebhaber Stephen A. , Cooke Nancy E.
Published: April 2004

We report a random disruption in the mouse genome that resulted in lethal paralysis in homozygous newborns. The disruption blocked expression of neurobeachin, a protein containing a BEACH (beigeandChediak-Higashi) domain implicated in synaptic vesicle trafficking and an AKAP (A-kinase anchor protein) domain linked to localization of cAMP-dependent protein kinase activity.nbea-null mice demonstrated a complete block of evoked synaptic transmission at neuromuscular junctions, whereas nerve conduction, synaptic structure, and spontaneous synaptic vesicle release were completely normal. These findings support an essential role for neurobeachin in evoked neurotransmitter release at neuromuscular junctions and suggest that it plays an important role in synaptic transmission.
Selective Expression of Heteromeric AMPA Receptors Driven by Flip–Flop Differences
Authors: Brorson James R. , Li Dongdong , Suzuki Takeshi
Published: April 2004

Initial models of AMPA receptor assembly postulated the unrestricted stochastic association of individual subunits. The low Ca2+permeability and nonrectified current–voltage relationship of most native AMPA receptors were ascribed to dominant effects of the glutamate receptor 2 (GluR2) subunit. A recent model, however, proposes instead the preferred assembly of GluR1 and GluR2 subunits into tetrameric complexes as pairs of identical heteromeric dimers. To compare unrestricted versus selective models of GluR1 and GluR2 assembly, these subunits, in both flip and flop isoforms, were expressed in varying ratios in human embryonic kidney 293 cells.

Coexpression of pairs of wild-type subunits produced expression of a predominance of heteromeric over homomeric receptors. Only a single functional type of heteromeric receptor was observed, indicating a pattern of apparent dominance not only of GluR2 for ion selectivity, but also of the flip isoform for receptor desensitization. Expression of wild-type GluR1 flip, however, with a mutant form of the same subunit carrying an arginine residue at the glutamine/arginine site (GluR1Rflip) demonstrated a lack of dominance of GluR1Rin determination of ion selectivity, whereas expression of GluR1Rflip with GluR1 flop reproduced the pattern of apparent complete dominance. Together, the data support the selective expression of heteromeric receptors and are compatible with an equilibrium model of assembly of tetramers as pairs of identical heteromeric dimers. Expression of co-assemblies of the flip and flop isoforms, like that of the GluR1 and GluR2 subunits, is strongly favored over that of homomeric assemblies.
Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain
Authors: Takahashi Reisuke H. , Almeida Claudia G. , Kearney Patrick F. , Yu Fangmin , Lin Michael T. , Milner Teresa A. , Gouras Gunnar K.
Published: April 2004

Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate thein vivolocalization and accumulation of Aβ42 with time in culture. Furthermore, we demonstrate that Aβ42 aggregates into oligomers within endosomal vesicles and along microtubules of neuronal processes, both in Tg2576 neurons with time in culture and in Tg2576 and human AD brain. These Aβ42 oligomer accumulations are associated with pathological alterations within processes and synaptic compartments in Tg2576 mouse and human AD brains.
Molecular Determinants of Synapsin Targeting to Presynaptic Terminals
Authors: Gitler Daniel , Xu Yimei , Kao Hung-Teh , Lin Dayu , Lim Sangmi , Feng Jian , Greengard Paul , Augustine George J.
Published: April 2004

Although synapsins are abundant synaptic vesicle proteins that are widely used as markers of presynaptic terminals, the mechanisms that target synapsins to presynaptic terminals have not been elucidated. We have addressed this question by imaging the targeting of green fluorescent protein-tagged synapsins in cultured hippocampal neurons. Whereas all synapsin isoforms targeted robustly to presynaptic terminals in wild-type neurons, synapsin Ib scarcely targeted in neurons in which all synapsins were knocked-out. Coexpression of other synapsin isoforms significantly strengthened the targeting of synapsin Ib in knock-out neurons, indicating that heterodimerization is required for synapsin Ib to target. Truncation mutagenesis revealed that synapsin Ia targets via distributed binding sites that include domains B, C, and E. Although domain A was not necessary for targeting, its presence enhanced targeting. Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals.
Identification of a Novel Basic Helix-Loop-Helix Gene,Heslike, and Its Role in GABAergic Neurogenesis
Authors: Miyoshi Goichi , Bessho Yasumasa , Yamada Shuichi , Kageyama Ryoichiro
Published: April 2004

Neuronal subtype specification depends on multiple transcription factors such as basic helix-loop-helix (bHLH) factors. However, transcription factor codes for most neurons remain to be determined. Here, we report identification of a novel mouse bHLH factor, termed Heslike, that has Hes1-like bHLH domain and transcriptional repressor activity. Heslike is coexpressed with the bHLH factor Mash1 in brain regions that give rise to GABAergic neurons. In the mesencephalon and the caudal diencephalon, coexpression of Heslike and Mash1 is initially restricted to small regions but expanded dorsally from embryonic day 9.5 onward, and this expansion of coexpression is followed by GABAergic neurogenesis. Misexpression ofHeslikein mouse embryos generates ectopic GABAergic neurons only from the Mash1+region. In contrast, in the mesencephalon and the caudal diencephalon ofMash1-null mice, GABAergic neurons are almost completely missing and, instead, other neurons are generated, although Heslike is still expressed. Furthermore, coexpression ofHeslikeandMash1significantly promotes formation of GABAergic neurons, compared with each gene alone, in neural precursor cell culture. Thus, Heslike or Mash1 alone is not sufficient, but their coexpression may be important for generation of GABAergic neurons. These results suggest that combinations of distinct bHLH factors promote formation of distinct neuronal subtypes, thereby increasing neuronal diversity.