bluuebunny/crossref_metadata_2025 huggingface dataset:
In Conrad’s Footsteps: Critical Approaches to Africanist Travel Writing
Authors: Burroughs Robert
Published: July 2006

Travel writing about Central Africa in English reverberates with the language of Joseph Conrad’sHeart of Darkness. This essay considers how that canonical text, in shaping twentieth‐century travellers’ understandings of Central Africa and the travel genre, also shapes literary critics’ understandings of the same subjects.
The Cellular Basis of Kidney Development
Authors: Dressler Gregory R.
Published: July 2006

Mammalian kidney development has helped elucidate the general concepts of mesenchymal-epithelial interactions, inductive signaling, epithelial cell polarization, and branching morphogenesis. Through the use of genetically engineered mouse models, the manipulation of Xenopus and chick embryos, and the identification of human renal disease genes, the molecular bases for many of the early events in the developing kidney are becoming increasingly clear. Early patterning of the kidney region depends on interactions between Pax/Eya/Six genes, with essential roles for lim1 and Odd1. Ureteric bud outgrowth and branching morphogenesis are controlled by the Ret/Gdnf pathway, which is subject to positive and negative regulation by a variety of factors. A clear role for Wnt proteins in induction of the kidney mesenchyme is now well established and complements the classic literature nicely. Patterning along the proximal distal axis as the nephron develops is now being investigated and must involve aspects of Notch signaling. The development of a glomerulus requires interactions between epithelial cells and infiltrating endothelial cells to generate a unique basement membrane. The integrity of the glomerular filter depends in large part on the proteins of the nephrin complex, localized to the slit diaphragm. Despite the kidney's architectural complexity, with the advent of genomics and expression arrays, it is becoming one of the best-characterized organ systems in developmental biology.
Prognostic Associations of Activated Mitogen-Activated Protein Kinase and Akt Pathways in Glioblastoma
Authors: Pelloski Christopher E. , Lin E , Zhang Li , Yung W.K. Alfred , Colman Howard , Liu Juinn-Lin , Woo Shaio Y. , Heimberger Amy B. , Suki Dima , Prados Michael , Chang Susan , Barker Fredrick G. , Fuller Gregory N. , Aldape Kenneth D.
Published: July 2006

Purpose: Activation of mitogen-activated protein kinase (MAPK) and members of the Akt pathway have been shown to promote cell proliferation, survival, and resistance to radiation. This study was conducted to determine whether any of these markers are associated with survival time and response to radiation in glioblastoma.

Experimental Design: The expression of phosphorylated (p-)Akt, mammalian target of rapamycin (p-mTOR), p-p70S6K, and p-MAPK were assessed by immunohistochemical staining in 268 cases of newly diagnosed glioblastoma. YKL-40, a prognostic marker previously examined in these tumors, was also included in the analysis. Expression data were tested for correlations with response to radiation therapy in 131 subtotally resected cases and overall survival (in all cases). Results were validated in an analysis of 60 patients enrolled in clinical trials at a second institution.

Results: Elevated p-MAPK expression was most strongly associated with poor response to radiotherapy, a finding corroborated in the validation cohort. For survival, higher expressions of p-mTOR, p-p70S6K, and p-MAPK were associated with worse outcome (all P < 0.03). YKL-40 expression was associated with the expressions of p-MAPK, p-mTOR, and p-p70S6K (all P < 0.02), with a trend toward association with p-Akt expression (P = 0.095). When known clinical variables were added to a multivariate analysis, only age, Karnofsky performance score, and p-MAPK expression emerged as independent prognostic factors.

Conclusions: p-MAPK and activated members of the Akt pathway are markers of outcome in glioblastoma. Elevated expression of p-MAPK is associated with increased radiation resistance and represents an independent prognostic factor in these tumors.
Clinical and Pharmacokinetic Study of Clofarabine in Chronic Lymphocytic Leukemia: Strategy for Treatment
Authors: Gandhi Varsha , Plunkett William , Bonate Peter L. , Du Min , Nowak Billie , Lerner Susan , Keating Michael J.
Published: July 2006

Purpose: Based on its mechanistic similarity to fludarabine and cladribine and the success of these analogues for treatment of chronic lymphocytic leukemia (CLL), we hypothesized that clofarabine would be effective for indolent leukemias. The present study was conducted to determine the efficacy and cellular pharmacology during clinical trials of single-agent clofarabine in CLL.

Experimental Design: Previously treated patients with relapsed/refractory CLL were eligible for this study. Clofarabine was infused over 1 hour daily for 5 days. Most patients received 3 or 4 mg/m2/d × 5 days, whereas the other two were treated with 15 mg/m2/d × 5 days. Clinical outcome and associated pharmacologic end points were assessed.

Results: Myelosuppression limited the maximum tolerated dose of clofarabine to 3 mg/m2/d on this schedule. Cellular pharmacokinetic studies showed a median clofarabine triphosphate concentration in CLL lymphocytes of 1.5 μmol/L (range, 0.2-2.3 μmol/L; n = 9). In the majority of cases, >50% of the analogue triphosphate was present 24 hours after infusion, indicating prolonged retention of the triphosphate in CLL cells. Although cytoreduction was observed, no patients achieved a response. In vitro clofarabine incubation of leukemic lymphocytes from 29 CLL patients showed that clofarabine monophosphate accumulated to a higher concentration compared with the triphosphate. Nonetheless, the triphosphate increased in a dose-dependent fashion and upon successive clofarabine infusions, suggesting benefit from greater doses given at less frequent intervals.

Conclusion: Levels of clofarabine triphosphate at higher doses and prolonged maintenance of clofarabine triphosphate in leukemic lymphocytes provide a rationale to treat CLL in a weekly clofarabine schedule.
Complement-Induced Cell Death by Rituximab Depends on CD20 Expression Level and Acts Complementary to Antibody-Dependent Cellular Cytotoxicity
Authors: van Meerten Tom , van Rijn Rozemarijn S. , Hol Samantha , Hagenbeek Anton , Ebeling Saskia B.
Published: July 2006

Purpose: The use of the CD20-specific antibody rituximab has greatly improved the response to treatment of CD20+ follicular lymphoma. Despite the success of rituximab, resistance has been reported and prognostic markers to predict individual response are lacking. The level of CD20 expression on tumors has been related to response, but results of several studies are contradictory and no clear relationship could be established. Complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) are thought to be important effector mechanisms, but the exact mechanism of rituximab-mediated cell kill is still unknown. Importantly, no data have been reported on the combined contribution of CDC and ADCC.

Experimental Design: We have developed a system of clonally related CEM-CD20 cells by retroviral transfer of the human CD20 cDNA (n = 90). This set of cells, with the CD20 molecule as the only variable, was used to study the importance of CD20 expression level on rituximab-mediated CDC, ADCC, and the combination.

Results: We show a sigmoidal correlation of CD20 expression level and rituximab-mediated killing via CDC but not ADCC. On both high and low CD20-expressing cells, all CD20 molecules were translocated into lipid rafts after rituximab binding. Furthermore, CDC and ADCC act simultaneously and CDC-resistant cells are sensitive to ADCC and vice versa.

Conclusions: These findings suggest that CDC depends on CD20 expression level and that both CDC and ADCC act complementary. These data give new insights into novel strategies to improve the efficacy of CD20-specific antibodies for the treatment of CD20+ tumors.
Effect of the Second-Generation Vascular Disrupting Agent OXi4503 on Tumor Vascularity
Authors: Salmon Howard W. , Siemann Dietmar W.
Published: July 2006

Purpose: As first-generation small-molecule vascular disrupting agents (VDA) have begun to enter clinical trials, second-generation agents are under active development. One such agent is the combretastatin A4 disodium phosphate (CA4P) analogue OXi4503 (CA1P).

Experimental Design: C3H/HeJ mice bearing KHT sarcomas were treated with CA4P and OXi4503 and the effect on tumor vasculature was determined by evaluating the extent of vascular shutdown (Hoechst-33342 vessel staining) and tumor perfusion inhibition (dynamic contrast-enhanced magnetic resonance imaging). Dynamic contrast-enhanced magnetic resonance imaging and tumor necrosis end points also were used to examine the pathophysiologic tumor effects following repeated exposures to these agents.

Results: Single doses of either agent (CA4P, 100 mg/kg; OXi4503, 25 mg/kg) resulted in an 80% to 90% reduction in tumor perfusion 4 hours after treatment. Whereas recovery in tumor perfusion was observed 48 hours posttreatment, this recovery was significantly slower in mice treated with OXi4503. Tumors re-treated with either VDA 72 hours after the first drug exposure showed a similar reduction and recovery in tumor perfusion. Histologic evidence showed the presence of a smaller viable rim after exposure to OXi4503 than that observed after CA4P treatment. Furthermore, the extent of recovery of tumor necrosis 72 hours after drug treatment was less for OXi4053.

Conclusions: The present studies show that the second-generation VDA OXi4503 possesses significant antivascular effects in solid tumors. Importantly, the vasculature of tumors of mice that had received an initial dose this agent was as responsive to a subsequent treatment.
Natural and Synthetic Progestins Accelerate 7,12-Dimethylbenz[a]Anthracene-Initiated Mammary Tumors and Increase Angiogenesis in Sprague-Dawley Rats
Authors: Benakanakere Indira , Besch-Williford Cynthia , Schnell Jennifer , Brandt Sandra , Ellersieck Mark R. , Molinolo Alfredo , Hyder Salman M.
Published: July 2006

Purpose: Synthetic progestins are widely used therapeutically; however, there is controversy regarding their proliferative effects. We used a rat 7,12-dimethylbenz[a]anthracene (DMBA)–induced mammary tumor model to test the hypothesis that progestins increase angiogenesis and as a result decrease the latency period and increase the multiplicity of mammary tumors.

Experimental Design: Medroxyprogesterone acetate (MPA) pellets were implanted 2, 4, or 6 weeks after DMBA exposure; RU-486 was given 3 days before MPA. Experiments were concluded 70 days after DMBA administration.

Results: MPA exposure 4 or 6 weeks after DMBA reduced the latency period for appearance of tumors in a dose-dependent manner and increased tumor incidence. Administration of MPA 2 weeks after DMBA administration reduced tumor incidence and was protective. Progesterone did not reduce the latency period but significantly increased tumor incidence. RU-486 delayed the latency period and decreased tumor incidence in animals exposed to MPA at 4 weeks after DMBA treatment, indicating that the progesterone receptor may be partially responsible for transmission of proliferative signals. RU-486 also delayed the latency period but failed to reduce overall tumor incidence when animals were exposed to MPA at 6 weeks after DMBA treatment, indicating that other factors may also control MPA-induced acceleration. Whereas MPA-accelerated tumors were both intraductal and tubular, progesterone-accelerated and/or DMBA-induced tumors were tubular. Progestin treatment increased vascular endothelial growth factor expression within tumors in a ligand- and cell type–dependent manner and increased angiogenesis in correlation with vascular endothelial growth factor expression. No mammary tumors or progesterone receptor were detected in DMBA-treated ovariectomized rats regardless of progestin administration.

Conclusions: We propose that progestins can accelerate the development of mammary tumors and that antiangiogenic agents and/or the use of antiprogestins that can reduce tumor incidence might be a viable therapeutic option for treatment of progestin-accelerated tumors. The model described here is a potentially useful preclinical model for rapidly screening such compounds.
Nitric oxide–releasing aspirin and indomethacin are potent inhibitors against colon cancer in azoxymethane-treated rats: effects on molecular targets
Authors: Rao Chinthalapally V. , Reddy Bandaru S. , Steele Vernon E. , Wang C-X , Liu Xiaoping , Ouyang Nengtai , Patlolla Jagan M.R. , Simi Barbara , Kopelovich Levy , Rigas Basil
Published: July 2006

Nitric oxide–releasing nonsteroidal anti-inflammatory drugs (NO-NSAID) are promising chemoprevention agents; unlike conventional NSAIDs, they seem free of appreciable adverse effects, while they retain beneficial activities of their parent compounds. Their effect on colon carcinogenesis using carcinoma formation as an end point is unknown. We assessed the chemopreventive properties of NO-indomethacin (NCX 530) and NO-aspirin (NCX 4016) against azoxymethane-induced colon cancer. Seven-week-old male F344 rats were fed control diet, and 1 week later, rats received two weekly s.c. injections of azoxymethane (15 mg/kg body weight). Two weeks after azoxymethane treatment, rats (48 per group) were fed experimental diets containing NO-indomethacin (0, 40, or 80 ppm), or NO-aspirin (1,500 or 3,000 ppm), representing 40% and 80% of the maximum tolerated dose. All rats were killed 48 weeks after azoxymethane treatment and assessed for colon tumor efficacy and molecular changes in colonic tumors and normally appearing colonic mucosa of different dietary groups. Our results suggest that NO-indomethacin at 40 and 80 ppm and NO-aspirin at 3,000 ppm significantly suppressed both tumor incidence (P < 0.01) and multiplicity (P < 0.001). The degree of inhibition was more pronounced with NO-indomethacin at both dose levels (72% and 76% inhibition) than with NO-aspirin (43% and 67%). NO-indomethacin at 40 and 80 ppm and NO-aspirin at 3,000 ppm significantly inhibited the colon tumors' (P < 0.01 to P < 0.001) total cyclooxygenase (COX), including COX-2 activity (52–75% inhibition) and formation of prostaglandin E2 (PGE2), PGF2α, and 6-keto-PGF1α, and TxB2 from arachidonic acid (53–77% inhibition). Nitric oxide synthase 2 (NOS-2) activity and β-catenin expression were suppressed in animals given NO-NSAID. In colonic crypts and tumors of animals fed these two NO-NSAIDs, there was a significant decrease in proliferating cell nuclear antigen labeling when compared with animals fed the control diet. The results of this study provide strong evidence that NO-NSAIDs possess strong inhibitory effect against colon carcinogenesis; their effect is associated with suppression of COX and NOS-2 activities and β-catenin levels in colon tumors. These results pave the way for the rational design of human clinical trials. [Mol Cancer Ther 2006;5(6):1530–8]
Therapeutic potential of antisense oligodeoxynucleotides to down-regulate thymidylate synthase in mesothelioma
Authors: Flynn Janet , Berg Randal W. , Wong Tracy , van Aken Marijke , Vincent Mark D. , Fukushima Masakazu , Koropatnick James
Published: July 2006

Malignant mesothelioma is an aggressive tumor of the serosal surfaces of the lungs, heart, and abdomen. Survival rates are poor and effective treatments are not available. However, recent therapeutic regimens targeting thymidylate synthase (TS) in malignant mesothelioma patients have shown promise. We have reported the use of an antisense oligodeoxynucleotide targeting TS mRNA (antisense TS ODN 83) to inhibit growth of human tumor cells. To test the potential for antisense targeting of TS mRNA in treatment of malignant mesothelioma, we assessed and compared the effects of antisense TS ODN 83 on three human malignant mesothelioma cell lines (211H, H2052, and H28) and human nonmalignant mesothelioma cells (HT29 colorectal adenocarcinoma, HeLa cervical carcinoma, and MCF7 breast tumor cell lines). We report that ODN 83 applied as a single agent effectively reduced TS mRNA and protein in malignant mesothelioma cell lines. Furthermore, it inhibited malignant mesothelioma growth significantly more effectively than it inhibited growth of nonmalignant mesothelioma human tumor cell lines: a difference in susceptibility was not observed in response to treatment with TS protein-targeting drugs. In malignant mesothelioma cells, antisense TS both induced apoptotic cell death and reduced proliferation. In nonmalignant mesothelioma cells, only reduced proliferation was observed. Thus, antisense TS-mediated induction of apoptosis may be the basis for the high malignant mesothelioma sensitivity to antisense targeting of TS. Further preclinical and clinical study of TS antisense oligodeoxynucleotides, alone and in combination with TS-targeting chemotherapy drugs, in mesothelioma is warranted. [Mol Cancer Ther 2006;5(6):1423–33]
Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence
Authors: Miyasaka Yoko , Barnes Marion E. , Gersh Bernard J. , Cha Stephen S. , Bailey Kent R. , Abhayaratna Walter P. , Seward James B. , Tsang Teresa S.M.
Published: July 2006

Background—

Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050.

Methods and Results—

The adult residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly (
P
=0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women (
P
=0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, assuming no further increase in age-adjusted incidence of AF, but 15.9 million if the increase in incidence continues.

Conclusions—

The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000. Whether or not this rate of increase continues, the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.
Reduced Peripheral Skeletal Muscle Mass and Abnormal Reflex Physiology in Chronic Heart Failure
Authors: Piepoli Massimo F. , Kaczmarek Agnieszka , Francis Darrel P. , Davies L. Ceri , Rauchhaus Mathias , Jankowska Ewa A. , Anker Stefan D. , Capucci Alessandro , Banasiak Waldemar , Ponikowski Piotr
Published: July 2006

Background—

The muscle hypothesis implicates abnormalities in peripheral muscle as a source for the stimulus to the symptoms and reflex abnormalities seen in chronic heart failure (CHF). We investigated the relationship between skeletal muscle mass (with dual-energy x-ray absorptiometry) and activation of the ergoreflex (a peripheral reflex originating in skeletal muscle sensitive to products of muscle work) in CHF patients and whether this rapport is affected by the progression of the syndrome.

Methods and Results—

We assessed 107 consecutive CHF patients (mean age, 61.9±10.9 years; 95% male; 25 cachectics) and 24 age-matched normal subjects (mean age, 59.0±11.1 years; 91% male). Compared with normal subjects, patients had a higher ergoreflex (in ventilation, 6.2±.6.1 versus 0.6±0.6 L/min;
P
<0.0001) and a reduction in muscle mass (51.9±10.0 versus 60.3±8.8 kg;
P
<0.001). The ergoreflex was particularly overactive in cachectics (
P
<0.05), accompanied by marked muscle mass depletion (
P
<0.0005). In CHF, ergoreceptor hyperresponsiveness in both the arm and leg correlated with reduced muscle mass, abnormal indexes of exercise tolerance (peak V̇
o
2
, V̇
e
/V̇
co
2
slope), ejection fraction, and NYHA functional class (
P
<0.0001). In the cachectic population, the ventilatory response from ergoreflex to arm exercise was strongly inversely correlated with arm (
r
=−0.65), leg (
r
=−0.64), and total (
r
=−0.61) lean tissues (
P
<0.001 for all). Multivariate analysis showed that these relationships were independent of NYHA class, peak V̇
o
2
, and V̇
e
/V̇
co
2
slope.

Conclusions—

Depleted peripheral muscle mass is associated with ergoreflex overactivity and exercise limitation in CHF, particularly in cachectic patients. The systemic activation of the muscle reflex system in CHF may reflect progression and deterioration of the clinical syndrome.
Spatiotemporal Structures and Mechanisms of the Tropospheric Biennial Oscillation in the Indo-Pacific Warm Ocean Regions*
Authors: Li Tim , Liu Ping , Fu X. , Wang B. , Meehl Gerald A.
Published: July 2006

The observed structure and seasonal evolution characteristics of the tropospheric biennial oscillation (TBO) in the warm ocean areas of the Indo-Pacific region are explored using a seasonal-sequence EOF analysis approach. The major convective activity centers associated with the TBO appear in the southeast Indian Ocean (SEIO) and western North Pacific (WNP), accompanied by anticyclonic (or cyclonic) circulation patterns with a first-baroclinic-mode structure. The convection and circulation anomalies have distinctive life cycles in the SEIO and WNP: the former have a peak phase in northern fall and the latter persist from northern winter to subsequent summer.

The mechanisms of the TBO in this region are investigated with a hybrid coupled GCM. Numerical results show that air–sea interaction in the warm ocean alone can support TBO variability that has many observed characteristics. Key processes involved in the TBO include the WNP monsoon variability and associated cross-equatorial flows, convective activity over Southeast Asia/the Maritime Continent and associated anomalous Walker circulation, and ocean dynamic responses to anomalous wind stress curl in the western Pacific. The coupled model experiment demonstrates that the essential element of the TBO in this region arises from the monsoon–warm ocean interaction.

A possible connection between the TBO and ENSO variability is further studied in another model that excludes the delayed oscillator dynamics. The key in causing the biennial variability of ENSO arises from teleconnections between the tropical Pacific and Indian Oceans, with three “atmospheric bridges”: 1) the north–south teleconnection that connects the WNP monsoon and the SEIO, 2) the east–west teleconnection that connects the Indian Ocean and the Pacific cold tongue, and 3) the El Niño–WNP monsoon teleconnection.
Dissecting the regulatory landscape of theAbd-Bgene of the bithorax complex
Authors: Mihaly Jozsef , Barges Stéphane , Sipos Laszlo , Maeda Robert , Cléard Fabienne , Hogga Ilham , Bender Welcome , Gyurkovics Henrik , Karch François
Published: July 2006

The three homeotic genes of the bithorax complex (BX-C), Ubx,abd-A and Abd-B control the identity of the posterior thorax and all abdominal segments. Large segment-specific cis-regulatory regions control the expression of Ubx, abd-A or Abd-B in each of the segments. These segment-specific cis-regulatory regions span the whole 300 kb of the BX-C and are arranged on the chromosome in the same order as the segments they specify. Experiments with lacZ reporter constructs revealed the existence of several types of regulatory elements in each of the cis-regulatory regions. These include initiation elements, maintenance elements, cell type- or tissue-specific enhancers, chromatin insulators and the promoter targeting sequence. In this paper, we extend the analysis of regulatory elements within the BX-C by describing a series of internal deficiencies that affect the Abd-B regulatory region. Many of the elements uncovered by these deficiencies are further verified in transgenic reporter assays. Our results highlight four key features of the iab-5,iab-6 and iab-7 cis-regulatory region of Abd-B. First,the whole Abd-B region is modular by nature and can be divided into discrete functional domains. Second, each domain seems to control specifically the level of Abd-B expression in only one parasegment. Third, each domain is itself modular and made up of a similar set of definable regulatory elements. And finally, the activity of each domain is absolutely dependent on the presence of an initiator element.
Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity
Authors: Alexandre Paula , Bachy Isabelle , Marcou Morgane , Wassef Marion
Published: July 2006

The roof plate (RP) of the midbrain shows an unusual plasticity, as it is duplicated or interrupted by experimental manipulations involving the mid/hindbrain organizer or FGF8. In previous experiments, we have found that FGF8 induces a local patterning center, the isthmic node, that is essential for the local development of a RP. Here, we show that the plasticity of the midbrain RP derives from two apparently antagonistic influences of FGF8. On the one hand, FGF8 widens beyond the neural folds the competence of the neuroepithelium to develop a RP by inducing the expression of LMX1B and WNT1. Ectopic overexpression of these two factors is sufficient to induce widely the expression of markers of the mature RP in the midbrain. On the other hand,FGF8 exerts a major destabilizing influence on RP maturation by controlling signaling by members of the TGFβ superfamily belonging to the BMP, GDF and activin subgroups. We show in particular that FGF8 tightly modulates follistatin expression, thus progressively restraining the inhibitory influence of activin B on RP differentiation. These regulations, together with FGF8 triggered apoptosis, allow the formation of a RP progress zone at some distance from the FGF8 source. Posterior elongation of the RP is permitted when the source of FGF8 withdraws. Growth of the posterior midbrain neuroepithelium and convergent extension movements induced by FGF8 both contribute to increase the distance between the source of FGF8 and the maturing RP. Normally, the antagonistic regulatory interactions spread smoothly across the midbrain. Plasticity of midbrain RP differentiation probably results from an experimentally induced imbalance between regulatory pathways.
Wnt9a signaling is required for joint integrity and regulation ofIhhduring chondrogenesis
Authors: Später Daniela , Hill Theo P. , O'Sullivan Roderick J. , Gruber Michaela , Conner David A. , Hartmann Christine
Published: July 2006

Joints, which separate skeleton elements, serve as important signaling centers that regulate the growth of adjacent cartilage elements by controlling proliferation and maturation of chondrocytes. Accurate chondrocyte maturation is crucial for endochondral ossification and for the ultimate size of skeletal elements, as premature or delayed maturation results predominantly in shortened elements. Wnt9a has previously been implicated as being a player in joint induction, based on gain-of function experiments in chicken and mouse. We show that loss of Wnt9a does not affect joint induction, but results to synovial chondroid metaplasia in some joints. This phenotype can be enhanced by removal of an additional Wnt gene, Wnt4, suggesting that Wnts are playing a crucial role in directing bi-potential chondro-synovioprogenitors to become synovial connective tissue, by actively suppressing their chondrogenic potential. Furthermore, we show that Wnt9a is a temporal and spatial regulator of Indian hedgehog (Ihh), a central player of skeletogenesis. Loss of Wnt9a activity results in transient downregulation of Ihh and reduced Ihh-signaling activity at E12.5-E13.5. The canonical Wnt/β-catenin pathway probably mediates regulation of Ihh expression in prehypertrophic chondrocytes by Wnt9a, because embryos double-heterozygous for Wnt9a and β-catenin show reduced Ihh expression, and in vivo chromatin immunoprecipitation demonstrates a direct interaction between the β-catenin/Lef1 complex and the Ihh promoter.
α-Actinin-dependent cytoskeletal anchorage is important for ICAM-5-mediated neuritic outgrowth
Authors: Nyman-Huttunen Henrietta , Tian Li , Ning Lin , Gahmberg Carl G.
Published: July 2006

Intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a dendrite-expressed membrane glycoprotein of telencephalic neurons in the mammalian brain. By deletion of the cytoplasmic and membrane-spanning domains of ICAM-5, we observed that the membrane distribution of ICAM-5 was determined by the cytoplasmic portion. Therefore we have characterized the intracellular associations of ICAM-5 by using a bacterially expressed glutathione S-transferase (GST) fusion protein encompassing the cytoplasmic part of ICAM-5. One of the main proteins in the neuronal cell line Paju that bound to the ICAM-5 cytodomain was α-actinin. ICAM-5 expressed in transfected Paju cells was found in α-actinin immunoprecipitates, and ICAM-5 colocalized with α-actinin both in Paju cells and in dendritic filopodia and spines of primary hippocampal neurons. We were also able to coprecipitate α-actinin from rat brain homogenate. Binding to α-actinin appeared to be mediated mainly through the N-terminal region of the ICAM-5 cytodomain, as the ICAM-5857-861 cytoplasmic peptide (KKGEY) mediated efficient binding to α-actinin. Surface plasmon resonance analysis showed that the turnover of the interaction was rapid. In a mutant cell line, Paju-ICAM-5-KK/AA, the distribution was altered, which implies the importance of the lysines in the interaction. Furthermore, we found that the ICAM-5/α-actinin interaction is involved in neuritic outgrowth and the ICAM-5857-861 cytoplasmic peptide induced morphological changes in Paju-ICAM-5 cells. In summary, these results show that the interaction between ICAM-5 and α-actinin is mediated through binding of positively charged amino acids near the transmembrane domain of ICAM-5, and this interaction may play an important role in neuronal differentiation.
A New Salt Bridge Based on the Hydrophobic Room-Temperature Molten Salt
Authors: Kakiuchi Takashi , Yoshimatsu Takahiro
Published: July 2006

A conceptually new salt bridge based on a hydrophobic room-temperature molten salt (ionic liquid) has been demonstrated to be a promising alternative to traditional salt bridges based on a concentrated aqueous KCl phase. 1-Methyl-3-octylimidazolium bis(trifluoromethylsulfonyl)imide (C8mimC1C1N), which is immiscible with water and forms a liquid–liquid two-phase system, exhibits a stable phase-boundary potential when sandwiched by two aqueous electrolyte solutions. The phase-boundary potential between the interface is determined by the partition of C8mim+ and C1C1N− ions in the aqueous phase (W) and is little affected by the type of electrolytes and their concentrations in W, provided that ions dissolved in W are hydrophilic enough. The gelation of the molten salt phase does not affect the phase-boundary potential. The new salt bridge is free from most of the problems inherent to KCl-based salt bridges.
Professor Tsuyoshi Sasada 1941–2005
Authors: Kvan Thomas
Published: July 2006

Tsuyoshi Sasada, known as Tee to so many of us, died on 30 September 2005 at the age of 64 after a long illness. Tee retired from Osaka University in 2004 upon reaching the mandatory retirement age but retained his association as Emeritus Professor. At the time of his death he held appointments as Honorary Professor, National Chiao Tung University (Taiwan) and Expert Researcher, National Institute of Information and Communications Technology. He had been with Osaka University since 1970, having earned his bachelor, master and doctoral degrees at Kyoto University. In 1988 he was appointed Professor in Osaka and established his laboratory, known as the Sasada Lab, from which over 200 students have graduated.
A Framework for Generating and Evolving Building Designs
Authors: Janssen Patrick H. T. , Frazer John H. , Tang Ming-Xi
Published: July 2006

This paper describes a comprehensive framework for generative evolutionary design. The key problem that is identified is generating alternative designs with an appropriate level of variability. Within the proposed framework, the design process is split into two phases: in the first phase, the design team develops and encodes the essential and identifiable character of the designs to be generated and evolved; in the second phase, the design team uses an evolutionary system to generate and evolve designs that embody this character. This approach allows design variability to be carefully controlled. In order to verify the feasibility of the proposed framework, a generative process capable of generating controlled variability is implemented and demonstrated.
A Polynomial Lag Formulation of Milk Production Response
Authors: Chen Dean , Courtney Richard , Schmitz Andrew
Published: July 2006

For much of agricultural production, output response to some given price change is hypothesized to increase first through time and then decline. To detect this type of response, a polynomial price lag model is estimated for milk production. For comparison purposes, a geometrically declining price lag model is also estimated. Although the estimates of long‐run supply elasticities do not critically depend on the type of model used, the response for each period of time and for various short‐run intervals does.
An Open Econometric Model of the Canadian Beef Cattle Sector
Authors: Kulshreshtha S. N. , Wilson A. G.
Published: July 2006

Limited information is available concerning the relationships existing among demand, supply, and price within the Canadian beef cattle sector. Since the sector is very dependent on exports to the U.S.A., an open econometric model is developed to estimate the simultaneous relationships prevailing among the demand, supply and price, and export variables. The two‐stage least squares procedure is adopted to obtain a solution. It was estimated that by 1975 both Canadian domestic demand for beef and farm prices of beef will increase, but exports of live cattle will decline. The model also revealed that the price and production levels of feed grains are important factors in accommodating the expansion of demand.
Linear Programming Approximation of Least‐Cost Feed Mixes with Probability Restrictions
Authors: Rahman Sabir A. , Bender F. E.
Published: July 2006

This article presents a method for solving linear programming problems in which elements of the tableau are stochastic. Using least‐cost poultry rations as an example, the authors demonstrate the procedure developed. Sufficiently accurate results are obtained with less time and complexity than required by alternative methods. The authors conclude that the largest obstacle to examining related problems is in the limitations imposed by lack of data, in this case with regard to biological minima.
Personality Characteristics and Successful Use of Credit by Farm Families
Authors: Krause Kenneth R. , Williams Paul L.
Published: July 2006

Farm financial management and the use of credit are becoming more important; resource suppliers, including lenders, are seeking ways to better identify and appraise farm operators' and entrepreneurs' potential to successfully use farming resources and credit. A behavioral model that included motivation, ability, and biographic variables was tested on a group of South Dakota farm borrowers and their wives. The selected behavioral‐personality variables are described and were related to change in financial position. The strongest results were obtained by including personality measures of both husbands and wives and suggest that personality variables can be developed for use in evaluation of farm credit applications.
An Empirical Application and Evaluation of Discrete Stochastic Programming in Farm Management
Authors: Rae Allan N.
Published: July 2006

Discrete stochastic programming has been suggested as a means of solving sequential decision problems under uncertainty, but as yet little or no empirical evidence of the capabilities of this technique in solving such problems has appeared. This paper presents in some detail an empirical application of discrete stochastic programming, including a discussion of data requirements, matrix construction, and solution interpretation. Based on this empirical evidence, the problem‐solving potential of the technique is evaluated.
Returns to Scale and Input Elasticities for Sugarcane: The Case of Sao Paulo, Brazil
Authors: Alcantara Reinaldo , Prato Anthony A.
Published: July 2006

Returns to scale and input elasticities are estimated from cost functions based on standard and generalized Cobb‐Douglas production functions. Returns to scale increased up to 161 thousand tons and decreased thereafter. Elasticities were. 340 for labor, .285 for land, .351 for fertilizer, .113 for pesticides, and —.089 for machinery and equipment.
Hedging and Income Stability: Concepts, Implications, and an Example
Authors: Peck Anne E.
Published: July 2006

The variability in prices often of concern to producers is that which occurs after a production decision has been made but before the commodity can be marketed. A portfolio‐type analysis is used to formalize this problem and describe the role futures markets can perform in facilitating the management of this risk. Data from the egg market are used to illustrate hedging opportunities for an egg producer. The results show that hedging a substantial percentage of expected production can significantly reduce a producer's exposure to the risk. Additionally, a total hedging scheme performed nearly as well as an optimal scheme.
External Costs of Land Subsidence Houston‐Baytown Area
Authors: Warren John P. , Jones Lonnie L. , Lacewell Ronald D. , Griffin Wade L.
Published: July 2006

Groundwater withdrawal from underground aquifers in excess of natural recharge is causing land surface subsidence along the Texas coast. External costs of subsidence are estimated from a survey of damages and losses in property value in the Houston‐Baytown area of Texas. Estimates of total costs, primarily in fresh‐ and saltwater flooding, are used in a break‐even analysis to compare areal costs of groundwater to costs of water from surface sources. Substitution of surface water for all groundwater that results in subsidence is suggested as a means of minimizing total water costs to the area.
A Note on Uncertainty and Nonmarket Cost
Authors: Chapman Duane
Published: July 2006

A generalization of the Friedman‐Savage hypothesis of utility maximization under risk proves that in the presence of a convex nonmarket cost function and a joint probability density function of future output and nonmarket cost, expected nonmarket cost can exceed the nonmarket cost of anticipated output.
The Impact of Benefit Spillovers upon Economic Efficiency in Public School Finance
Authors: Holland David W.
Published: July 2006

The hypothesis that public school funding is sensitive to gain or loss of residence related external benefits was tested using two stage least squares. No statistically significant relationship was detected. Arguments for providing school funding relief to declining rural areas must be defended upon equity rather than efficiency grounds.
Price Support versus Input Subsidy for Food Self‐Sufficiency in Developing Countries
Authors: Barker Randolph , Hayami Yujiro
Published: July 2006

Self‐sufficiency in food grains has been a publicized goal of government policy in many developing countries. Among various alternatives to achieve this goal, two policy options, output price support and input subsidy, both characterized by the government intervention into market pricing, are evaluated by applying a simple demand‐supply model to the Philippine rice economy. The results demonstrate a possibility that a subsidy applied to modern inputs, such as fertilizer, that are being used below optimum can be more beneficial than supporting product prices.
A Spatial Equilibrium Analysis of Electrical Energy Pricing and Allocation
Authors: Uri Noel D.
Published: July 2006

Based upon a spatial equilibrium model, this study argues that society can gain with increased regional coordination of generation and transmission activities of the U.S. electrical energy industry. In 1973 society suffered a loss in welfare because of minimal regional coordination, reflecting that consumers in regions where relatively inexpensive electrical energy was available were permitted to consume more and pay less than what would have been optimal at the expense of consumers in less efficient producing regions. The policy implications suggest that regional coordination be more actively pursued, involving the use of legislated authority by the Federal Power Commission.
The Journal as a Reference Source—1959–1968
Authors: Finley Robert M. , Barger Richard B.
Published: July 2006

Journal references were examined for the period 1959 to 1968. The extent that certain articles and authors were cited was a major consideration. Particularly interesting were comparisons of articles and references in the regular issues and the December issue; the 38 authors most frequently cited; and AAEA “Prize Winners” as references.
Environmental Perceptions and Policy Misconceptions
Authors: Ditwiler C. Dirck
Published: July 2006

Several social institutional states and environmental perception processes are analyzed to ascertain why examination of environmental problems and solutions within a holistic framework often does not lead to expected rational solutions. Implication of these factors for policy analyses leads to the conclusion that such analyses can be improved by expanding the scope of the traditional economic model.
A Short‐Run Price Prediction Model for Eggs
Authors: Miller Bill R. , Masters Gene C.
Published: July 2006

The volume of eggs traded in open markets is extremely small relative to total volume of eggs produced. One result has been criticism that current price quotes are formed from insufficient information. The model presented here projects a current quote based on information from a national sample of producers.
Technological Change and Relative Factor Shares in Indian Agriculture: An Empirical Analysis
Authors: Srivastava Uma K. , Heady Earl O.
Published: July 2006

Distribution of sectoral gains between labor and nonlabor input factors attains importance in view of the growing concern about rural poverty and unemployment despite recent increases in output and total revenue in Indian agriculture. Using cross section data, this study aims at measuring changes in the relative factor share.
Estimation of Demand Parameters under Consumer Budgeting: An Application to Argentina
Authors: De Janvry A. , Bieri J. , Nuñez A.
Published: July 2006

This study assumes that consumer expenditures occur in a stepwise fashion in which income is fist allocated to budget categories and then to optimum quantities within each category. With this assumption, a model was developed to estimate the price and icome elasticities of demand of all items in one budget category—like food—and the cross‐price elasticities of these items with all others. The approach permits one to specify the changes in expenditure levels on budget categories from cross‐section information and the flexibility of money. The model was empirically applied to Argentine consumption data.
Strategies for the Creation and Transfer of the Farm Estate
Authors: Boehlje Michael D. , Eisgruber Ludwig M.
Published: July 2006

This article develops an estate management model that considers interrelationships between estate creation and transfer, as well as the uncertainty of the parent's(s') death. The estate management problem is conceptualized as an adaptive sequential decision problem and the simulation model used in the empirical analysis is briefly reviewed. Empirical results suggest that high growth rate creation and transfer plans which include substantial lifetime gifts are essential elements of high response estate management strategies. Implications for business organization and coordination of the entry and exit processes of farmers are briefly discussed.
Minimum Wages and the Farm Labor Market
Authors: Gardner Bruce
Published: July 2006

Effects of U. S. minimum wage legislation on farm wage rates and employment are investigated by a reduced‐form supply‐demand model of the hired farm labor market. Results indicate the extension of minimum wages to some farm labor has significantly increased farm wages and reduced employment, as the marginal productivity theory of factor demand would predict.
Changing Federal Income Tax Rates and Optimum Farm Size
Authors: Carman Hoy F.
Published: July 2006

Substantial reductions in income tax rates occurring over the last decade increase optimum farm size and thus contribute to the current movement toward fewer and larger farm units in the United States.
The Von Thuenen Paradigm, the Industrial‐Urban Hypothesis, and the Spatial Structure of Agriculture
Authors: Katzman Martin T.
Published: July 2006

The industrial‐urban hypothesis has stimulated considerable empirical research on the spatial structure of agriculture. The alternative paradigm of von Thuenen has had almost no such impact on agricultural research, but has been the mainstay of urban economic analysis. The two models are compared as scientific theories of agricultural land use in an attempt to identify their similarities and contradictions. After reinterpreting several industrial‐urban studies from a von Thuenen viewpoint, an empirical discrimination between the two models is attempted with Brazilian data. A synthesis of the two paradigms provides a better explanation of agricultural structure than either alone.
Risk, Learning, and the Adoption of Fertilizer Responsive Seed Varieties
Authors: Hiebert L. Dean
Published: July 2006

The effect of uncertainty due to imperfect information on the decision to adopt fertilizer responsive seed varieties is examined. Additional information and enhanced ability to “decode” information are shown to increase the likelihood of adoption. Relevant empirical evidence for the Philippines is summarized.
Unemployment Insurance, Estimated Cost Rates, Benefits, and Tax Burden by Type of Farm
Authors: Elterich Joachim G.
Published: July 2006

Unemployment insurance cost rates for newly covered employers and the corresponding tax burden under two sets of tax structures by type of farm are estimated by state. Livestock, dairy, and poultry farmers generally more than support the benefits their workers receive, which is not the case for fruit and vegetable farms. Under experience rating livestock and dairy farms tend to pay the minimum rate in half the states, while the maximum rate applies for fruit and vegetable farms in many states. Benefits received by workers vary also by type of farm and state and tend to be related to the cost rate.
Determinants of Supply Elasticity in Interdependent Markets
Authors: Gardner Bruce L.
Published: July 2006

This paper draws out the implications of equilibrium in a two‐product, two‐factor model for elasticity of product supply, which is found to depend upon input supply elasticities, alternative product demand elasticity, elasticity of substitution between production inputs, relative factor intensity of the product, and relative importance of the product in its use of resources. These factors interact in a complex manner to determine supply elasticity. The author discusses related approaches of Buse, Muth, and Powell and Gruen, and considers several simplified examples in an attempt to provide an intuitive grasp of the workings of the model.