bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin‐Like Factor 3: Where Are We Now?
Authors: IVELL RICHARD , HARTUNG STEFAN , ANAND‐IVELL RAVINDER
Published: June 2005

Abstract: Insulin‐like factor 3 (INSL3), previously known as the relaxin‐like factor (RLF), is a major peptide hormone secreted from the testicular Leydig cells of adult men and circulating in the blood at a concentration of approximately 1 ng/mL. Women also produce INSL3 in the theca interna cells of ovarian follicles, but circulating levels remain below 100 pg/mL. INSL3 is structurally related to relaxin and insulin, but unlike the latter, signals through a novel G‐protein‐coupled receptor, LGR8. Ablation of the gene for INSL3 leads primarily to cryptorchidism because of a defect in the first, transabdominal phase of testicular descent. In the adult knockout mouse, a mild phenotype is evident in the testis and ovary. We have developed a panel of antibodies specific for INSL3 from various species, which are suitable for immunohistochemistry and, more recently, for immunoassays. INSL3 is an important marker for the mature Leydig cell phenotype, where it appears to be expressed constitutively, once the mature differentiation state is achieved. It is also an indicator of differentiation status not only for Leydig cells but also for the theca interna cells of the ovary.
Insulin‐Like Factor 3: A Novel Circulating Hormone of Testicular Origin in Humans
Authors: FERLIN ALBERTO , FORESTA CARLO
Published: June 2005

Abstract: Insulin‐like factor 3 (INSL3) affects testicular descent. Mutations in the INSL3 gene or its receptor, LGR8/GREAT, can cause cryptorchidism. Expression of LGR8/GREAT in different tissues and production of INSL3 by adult‐type Leydig cells suggest additional roles for this hormonal system in adults. We used a novel radioimmunoassay kit to measure INSL3 concentrations in the serum of normal men and those with different testicular pathologies. We demonstrate that INSL3 circulates in adult men and is almost exclusively of testicular origin. Subjects with severe testicular damage (infertility) produce small amounts of INSL3, and concentrations of this hormone seem to reflect the functional status of the Leydig cells. Analysis of men treated with different combinations of hormones of the hypothalamus‐pituitary‐testis axis suggests that the production of INSL3 is related to the luteinizing hormone.
Immunohistochemical Localization of Relaxin‐Like Factor/Insulin‐Like Peptide‐3 in the Bovine Corpus Luteum
Authors: NICHOLS NICOLE , BINTA HILARY , FIELDS PHILLIP A. , DROST MAARTEN , CHANG SHOU‐MEI , IVELL RICHARD , FIELDS MICHAEL J.
Published: June 2005

Abstract: Relaxin‐like factor/insulin‐like peptide (INSL)‐3 is highly expressed in the bovine corpus luteum throughout the estrous cycle and pregnancy. Demonstration of translation of the relaxin‐like factor message was previously shown for the follicle but not the corpus luteum. In this study, relaxin‐like factor mRNA was highly expressed in the corpus luteum on days 7 and 14 of pregnancy. Tissues were fixed in 10% neutral buffered formalin, and utilizing two different antibodies to relaxin‐like factor, W3 rabbit anti‐bovine and 2‐8F mouse anti‐bovine, relaxin‐like factor was localized in fibroblast‐like cells. Staining was also observed in the Leydig cells of bovine testicular tissue. No staining was observed in small and large steroidogenic luteal cells, indicating a nonsteroidogenic source of luteal relaxin‐like factor. Definitive cell type identification is currently being determined via electron microscopy.
Evolution of the Relaxin‐Like Peptide Family: From Neuropeptide to Reproduction
Authors: WILKINSON TRACEY N. , SPEED TERRY P. , TREGEAR GEOFFREY W. , BATHGATE ROSS A.D.
Published: June 2005

Abstract: The relaxin‐like peptide family consists of relaxin‐1, relaxin‐2, and relaxin‐3 and the insulin‐like peptides (INSL)‐3, INSL4, INSL5, and INSL6 (human relaxin‐2 is equivalent to relaxin‐1 in other species). Evolution of this family has been contentious. We therefore sought to clarify the issue by performing phylogenetic analysis of all relaxin‐like peptides from the genomic databases available. Surprisingly, the phylogeny, combined with previous biologic characterizations, suggest that although relaxin's original function was likely in the brain, its reproductive role was acquired just prior to the divergence of amphibians. This phylogeny also illuminates inconsistencies in relaxin evolution in invertebrates, chickens, and cows.
Control of Self‐Renewal and Differentiation of Hematopoietic Stem Cells: HOXB4 on the Threshold
Authors: KLUMP HANNES , SCHIEDLMEIER BERNHARD , BAUM CHRISTOPHER
Published: June 2005

Abstract: The homeodomain transcription factor HOXB4 is one of the most attractive tools to expand hematopoietic stem cells in vitro and in vivo and to promote the formation of hematopoietic cells from in vitro differentiated embryonic stem cells. However, the expression levels compatible with the favorable effect of enhanced self‐renewal without perturbing differentiation, in vivo, remain to be determined. In this paper, we discuss the necessity to define the “therapeutic width” of HOXB4 expression, based on observations from our lab and others that demonstrate that ectopic HOXB4 expression leads to a concentration‐dependent perturbation of lineage differentiation of mouse and human hematopoietic cells. In summary, the combined results argue in favor of the existence of certain threshold levels for HOXB4 activity that control the differentiation and self‐renewal behavior of hematopoietic stem and progenitor cells. Indeed, existing evidence suggests that dosage effects of ectopically expressed transcription factors may be more the rule than an exception.
Developmental Impact of Leukemic Fusion Genes on Stem Cell Fate
Authors: ENVER TARIQ , TSUZUKI SHINOBU , BROWN JOHN , HONG DENGLI , GUPTA RAJEEV , FORD TONY , EGUCCHI MINENORI‐ISHIMAE , EGUCCHI MARIKO , GREAVES MEL
Published: June 2005

Abstract: Stem and progenitor cells present attractive targets for transformation by leukemia‐associated fusion genes generated by chromosomal translocation. The mechanism by which these fusion genes corrupt the transcriptional programs of these cellular compartments remains largely unknown. We have sought to gain insight into these issues through expressing TEL‐AML1 and TEL‐TRKC fusion genes in murine stem cells and recording effects on cell behavior in a transplant setting.
The Vascular Wall as a Source of Stem Cells
Authors: TAVIAN MANUELA , ZHENG BO , OBERLIN ESTELLE , CRISAN MIHAELA , SUN BIN , HUARD JOHNNY , PEAULT BRUNO
Published: June 2005

Abstract: We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, support the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult‐type hematopoiesis. A common feature of intra‐ and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endothelial cells. We have provided evidence that a population of angiohematopoietic mesodermal stem cells, marked by the expression of flk‐1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ventral part of the aorta, where they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells. HSCs also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. This would imply that the organism does not function during its whole life on a stock of hematopoietic stem cells established in the early embryo, as is usually accepted. We next examined whether the vessel wall can contribute stem cells for other cell lineages, primarily in the model of adult skeletal muscle regeneration. By immunohistochemistry and flow cytometry, we documented the existence in skeletal muscle, besides genuine endothelial and myogenic cells, of a subset of satellite cells that coexpress endothelial cell markers. This suggested the existence of a continuum of differentiation from vascular cells to endothelial cells that was confirmed in long‐term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investigated in skeletal and cardiac muscle, and the results are being compared with those generated by satellite cells. Altogether, these results point to a generalized progenitor potential of a subset of endothelial, or endothelium‐like, cells in blood vessel walls, in pre‐ and postnatal life.
Hox Genes: From Leukemia to Hematopoietic Stem Cell Expansion
Authors: ABRAMOVICH CAROLINA , PINEAULT NICOLAS , OHTA HIDEAKI , HUMPHRIES R KEITH
Published: June 2005

Abstract: Hox genes are clearly implicated in leukemia; however, neither the specificity of the leukemogenic potential among Hox genes of different paralog groups nor the role of the homeodomain is clear. We tested the leukemogenic potential of various NUP98‐Hox fusion genes alone and with MEIS1. All genes tested had a significant overlapping effect in bone marrow cells in vitro. However, not all formed strong leukemogenic NUP98 fusion genes; but together with overexpression of MEIS1, all induced myeloid leukemia. This phenomenon was also seen with NUP98 fusions containing only the homeodomain of the corresponding Hox protein. We then exploited the strong transforming potential of NUP98‐HOXD13 and NUP98‐HOXA10 to establish preleukemic myeloid lines composed of early myeloid progenitors with extensive in vitro self‐renewal capacity, short‐term myeloid repopulating activity, and low propensity for spontaneous leukemic conversion. We also showed that MEIS1 can efficiently induce their conversion to leukemic stem cells, thus providing a novel model for the study of leukemic progression. In contrast to the leukemogenic effect of most of the Hox genes tested, HOXB4 has the ability to increase the self‐renewal of hematopoietic stem cells without disrupting normal differentiation. On the basis of the discovery that the leukemogenic gene HOXA9 can also expand hematopoietic stem cells, we compared the ability of NUP98‐Hox fusions to that of HOXB4 to trigger HSC expansion in vitro. Our preliminary results indicate that the expanding potential of HOXB4 is retained and even augmented by fusion to NUP98. Moreover, even greater expansion may be possible using Abd‐B‐like Hox fusions genes.
Engraftment of Bone Marrow‐Derived Epithelial Cells
Authors: KRAUSE DIANE S.
Published: June 2005

Abstract: Discoveries of the ability of bone marrow‐derived cells (BMDCs) to differentiate into nonhematopoietic cells have opened up a new field of inquiry in adult stem cell plasticity. There are far more questions than there are answers to date. We and others have investigated whether differentiation occurs in response to tissue damage, what the underlying mechanisms might be, and whether this plasticity may be useful clinically. BMDC have been shown to differentiate into mature‐appearing epithelial cells in the lung, liver, gastrointestinal tract, skin, buccal mucosa, and kidney. The mechanism(s) by which cells transition to these nonhematopoietic phenotypes is not yet clear, but possibilities include cell‐to‐cell fusion, direct differentiation of a nonhematopoietic precursor cell from the BM, and transdifferentiation of a BM cell that had previously been committed to a different phenotype. Data obtained to date support the first two possibilities, and there are no data proving that transdifferentiation is responsible for the engraftment of marrow‐derived epithelial cells. Theoretically, the engraftment of marrow‐derived cells as nonhematopoietic cell types could be used in either the autologous or the allogeneic setting to restore functional epithelial cells to a diseased organ. For example, a marrow‐derived cell that has been transduced to express a specific transgene can continue to express this transgene after it engrafts as a nonhematopoietic epithelial cell in the lung. Analyses of the kinetics of this engraftment suggest that it can be increased within days to weeks following certain types of injury, depending on the tissue examined. Most reports of adult stem cell plasticity show relatively low frequencies of marrow‐derived nonhematopoietic cells, on the order of 1 in 103 to 1 in 104 epithelial cells in many organs being marrow derived. This frequency is likely to be too low to be of therapeutic relevance. Therefore, future efforts will need to be focused on enhancing levels of engraftment.
Lineage Promiscuity and Plasticity in Hematopoietic Development
Authors: AKASHI KOICHI
Published: June 2005

Abstract: Hematopoiesis has provided a valuable model for understanding how genetic programs are established to decide cell fates in multipotent stem or progenitor cells. The identification of common myeloid and lymphoid progenitors has allowed us to directly assess the regulatory mechanisms of lineage commitment. Multiple genes of hematopoietic lineages, including transcription factors, are coexpressed in hematopoietic stem cells and progenitors, a phenomenon referred to as “lineage priming.” The accessibility for multiple transcription factors promiscuously allows flexibility in cell fate commitments at the multipotent stages. The changes in the expression levels and timing of transcription factors can induce lineage conversion of committed cells, indicating that the regulation of transcription factors might be primarily critical for maintaining hierarchical hematopoietic development.
Stem Cell Biology: A View toward the Future
Authors: LEMISCHKA IHOR R.
Published: June 2005

Abstract: In this essay I have attempted to provide clues relating to novel research avenues that are likely to have a broad impact on the field of stem cell biology. The specific examples, drawn from other areas, are meant to be instructive and are representative of many more similar efforts. I have suggested that the new areas of systems and synthetic biology may provide a truly deep level of understanding for many aspects of how stem cells make fate choices. Successful application of new avenues will require an integrative approach that combines experimental and computational techniques.
Thrombopoietin and the Hematopoietic Stem Cell
Authors: KAUSHANSKY KENNETH
Published: June 2005

Abstract: The molecular mechanisms that underlie the favorable effects of thrombopoietin on stem cell survival, self‐renewal, and expansion are unknown. On the basis of known effects of HoxB4, HoxA9, and vascular endothelial cell growth factor on stem cells, we explored whether TPO might affect these pathways. We found that TPO enhances the transcription of HoxB4, induces the nuclear localization of HoxA9, and upregulates VEGF expression by reducing the ubiquination of hypoxia inducible factor.
Tracking Hematopoiesis at the Single Cell Level
Authors: SCHROEDER TIMM
Published: June 2005

Abstract: Despite intensive research, many longstanding questions of experimental hematology remain unsolved. One major reason is the fact that hematopoiesis is usually followed by analyzing populations of cells rather than individual cells, at few points in time during an experiment and without knowing (or quickly loosing) the cells' individual identities. The static picture yielded by this approach makes it impossible to appreciate the dynamic developmental processes leading to the generation of the full hematopoietic system from individual hematopoietic stem cells (HSCs). Real‐time tracking of individual cells in culture, tissues, or whole organisms would be an extremely powerful approach to fully understand the developmental complexity of hematopoiesis. To this end, a computer‐aided culture and bioimaging system is being developed to follow the fate of individual cells over long periods of time. This system is used to follow the development of multilineage cobblestone colonies from adult HSCs in stroma cocultures at the single cell level over many generations. To facilitate noninvasive detection of lineage commitment in these cultures, new subcellular forms of optimized fluorescent proteins have been developed to allow simultaneous marking of multiple hematopoietic lineages within the same animal.
Role of Telomerase in Hematopoietic Stem Cells
Authors: LANSDORP PETER M.
Published: June 2005

Abstract: Studies in hematopoietic stem cell (HSC) biology are often focused on “self‐renewal” and differentiation. Implicit in the word self‐renewal is that the two daughter cells generated by a self‐renewal division are identical to the parental cell. Strictly speaking, this is not possible because DNA is continuously damaged and repaired by DNA‐repair mechanisms that are not 100% efficient. It is important to note that the efficiency of DNA repair varies greatly among different stem cell types. For example, embryonic stem cells are quite resistant to DNA damage and maintain the length of telomere repeats on serial passage, whereas HSCs are quite sensitive to DNA damage and less able to maintain telomere length. Most likely, differences between stem cell types in DNA repair and telomere maintenance pathways coevolved with cell mass, turnover, reproductive strategy, and life span. This idea has given rise to the notion that many aspects of normal aging could primarily reflect limitations in DNA repair and telomere‐maintenance pathways in the (stem) cells of the soma. In humans, levels of telomerase in HSCs are under extremely tight control, as is illustrated by the marrow failure in patients with (mild) telomerase deficiencies. Here, the role of telomerase in human HSC biology is reviewed, and it is proposed that telomerase has an important role in the repair of G‐rich DNA.
The Stem Cell Continuum
Authors: QUESENBERRY PETER J. , COLVIN GERALD A. , ABEDI MEHRDAD , DOONER GERRI , DOONER MARK , ALIOTTA JASON , KEANEY PATRICK , LUO LUGUANG , DEMERS DELIA , PETERSON ABIGAIL , FOSTER BETHANY , GREER DEBORAH
Published: June 2005

Abstract: Hematopoietic stem cells have been felt to exist in a hierarchical structure with a relatively fixed phenotype at each stage of differentiation. Recent studies on the phenotype of the marrow hematopoietic stem cell indicate that it is not a fixed entity, but rather that it fluctuates and shows marked heterogeneity. Past studies have shown that stem cell engraftment characteristics, adhesion protein, and gene expression varies with the phase of the cell cycle. More recently, we demonstrated that progenitor numbers and differentiation potential also vary reversibly during one cytokine‐induced cell cycle transit. We have also shown high levels of conversion of marrow cells to skeletal muscle and lung cells, indicating a different level of plasticity. Recently, we demonstrated that homing to lung and conversion to lung cells in a mouse transplant model also fluctuates reversibly with cell cycle transit. This could be considered plasticity squared. These data indicate that marrow stem cells are regulated on a continuum related to the cell cycle both as to hematopoietic and to nonhematopoietic differentiation.
Objective Response to Chemotherapy As a Potential Surrogate End Point of Survival in Metastatic Breast Cancer Patients
Authors: Bruzzi Paolo , Del Mastro Lucia , Sormani Maria P. , Bastholt Lars , Danova Marco , Focan Christian , Fountzilas George , Paul James , Rosso Riccardo , Venturini Marco
Published: June 2005

Purpose

To assess the validity of objective response to chemotherapy as a surrogate end point for survival in metastatic breast cancer.

Patients and Methods

We carried out a meta-analysis on individual data from 2,126 metastatic breast cancer patients who were enrolled onto 10 randomized trials comparing standard versus intensified epirubicin-containing chemotherapy.

Results

The intensified chemotherapy was associated with a significantly higher tumor response rate compared with standard chemotherapy (pooled odds ratio for nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86 to 1.04; P = .22). Tumor response was a highly significant predictor of survival (P < .0001). When tumor response was introduced in the Cox model, the hazard ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91 to 1.11; P = .92), indicating that no residual effect of the experimental treatment on survival was present once tumor response was adjusted for. This suggests that the overall survival benefit of intensified epirubicin was a result of the increase in response rate. The median survival time of patients with complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3 months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the median survival time of patients with no response was 14.6 months (95% CI, 13.9 to 15.4 months).

Conclusion

These results support the hypothesis that the achievement of an objective response to chemotherapy in metastatic breast cancer is associated with a true survival benefit. The potential role of objective response as a surrogate end point for survival in chemotherapy trials of metastatic breast cancer warrants further investigation.
Avascular Necrosis of Femoral and/or Humeral Heads in Multiple Myeloma: Results of a Prospective Study of Patients Treated With Dexamethasone-Based Regimens and High-Dose Chemotherapy
Authors: Talamo Giampaolo , Angtuaco Edgardo , Walker Ronald C. , Dong Li , Miceli Marisa H. , Zangari Maurizio , Tricot Guido , Barlogie Bart , Anaissie Elias
Published: June 2005

Purpose

To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.

Patients and Methods

A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.

Results

With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.

Conclusion

AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.
Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS Lymphoma
Authors: Abrey Lauren E. , Batchelor Tracy T. , Ferreri Andrés J.M. , Gospodarowicz Mary , Pulczynski Elisa J. , Zucca Emanuele , Smith Justine R. , Korfel Agnieszka , Soussain Carole , DeAngelis Lisa M. , Neuwelt Edward A. , O'Neill Brian Patrick , Thiel Eckhard , Shenkier Tamara , Graus Fransesc , van den Bent Martin , Seymour John F. , Poortmans Philip , Armitage James O. , Cavalli Franco
Published: June 2005

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.
Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer
Authors: Chan Stephen , Scheulen Max E. , Johnston Stephen , Mross Klaus , Cardoso Fatima , Dittrich Christian , Eiermann Wolfgang , Hess Dagmar , Morant Rudolph , Semiglazov Vladimir , Borner Markus , Salzberg Marc , Ostapenko Valerijus , Illiger Hans-Joachim , Behringer Dirk , Bardy-Bouxin Nathalie , Boni Joseph , Kong Steven , Cincotta Maria , Moore Laurence
Published: June 2005

Purpose

In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated.

Patients and Methods

Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus.

Results

Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%).

Conclusion

In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.
The equivalent martingale measure conditions in a general model for interest rates
Authors: Hamza Kais , Jacka Saul , Klebaner Fima
Published: June 2005

Assuming that the forward rates ftu are semimartingales, we give conditions on their components under which the discounted bond prices are martingales. To achieve this, we give sufficient conditions for the integrated processes ftu=∫0uftvdv to be semimartingales, and identify their various components. We recover the no-arbitrage conditions in models well known in the literature and, finally, we formulate a new random field model for interest rates and give its equivalent martingale measure (no-arbitrage) condition.
On the Nash equilibria for the FCFS queueing system with load-increasing service rate
Authors: Brooms A. C.
Published: June 2005

We consider a service system (QS) that operates according to the first-come-first-served (FCFS) discipline, and in which the service rate is an increasing function of the queue length. Customers arrive sequentially at the system, and decide whether or not to join using decision rules based upon the queue length on arrival. Each customer is interested in selecting a rule that meets a certain optimality criterion with regard to their expected sojourn time in the system; as a consequence, the decision rules of other customers must be taken into account. Within a particular class of decision rules for an associated infinite-player game, the structure of the Nash equilibrium routeing policies is characterized. We prove that, within this class, there exist a finite number of Nash equilibria, and that at least one of these is nonrandomized. Finally, with the aid of simulation experiments, we explore the extent to which the Nash equilibria are characteristic of customer joining behaviour under a learning rule based on system-wide data.
Geometrical characteristics of Gaussian sea waves
Authors: Azaïs Jean-Marc , León José R. , Ortega Joaquín
Published: June 2005

In this work, we study some geometrical properties of a stationary Gaussian field modeling the sea surface, using the energy spectrum. We consider the length of a crest and the mean speed of contours, which can be expressed as integrals over level sets. We also give central limit theorems for some of these quantities, using chaos expansions.
Multiperiod conditional distribution functions for conditionally normal GARCH(1, 1) models
Authors: Brummelhuis Raymond , Guégan Dominique
Published: June 2005

We study the asymptotic tail behavior of the conditional probability distributions ofrt+kandrt+1+⋯+rt+kwhen (rt)t∈ℕis a GARCH(1, 1) process. As an application, we examine the relation between the extreme lower quantiles of these random variables.
Fluid limit of generalized Jackson queueing networks with stationary and ergodic arrivals and service times
Authors: Lelarge Marc
Published: June 2005

We use a sample-path technique to derive asymptotics of generalized Jackson queueing networks in the fluid scale; that is, when space and time are scaled by the same factor n. The analysis only presupposes the existence of long-run averages and is based on some monotonicity and concavity arguments for the fluid processes. The results provide a functional strong law of large numbers for stochastic Jackson queueing networks, since they apply to their sample paths with probability 1. The fluid processes are shown to be piecewise linear and an explicit formulation of the different drifts is computed. A few applications of this fluid limit are given. In particular, a new computation of the constant that appears in the stability condition for such networks is given. In a certain context of a rare event, the fluid limit of the network is also derived explicitly.
Some Evolutionary Foundations for Price Level Rigidity
Authors: Saint-paul Gilles
Published: June 2005

This paper shows that price rigidity evolves in an economy populated by imperfectly rational agents who experiment with alternative rules of thumb. In the model, firms must set their prices in face of aggregate demand shocks. Their payoff depends on the level of aggregate demand, as well as on their own price and their “neighbor's” price. The latter assumption captures local interactions. Despite the fact that the rational expectations equilibrium (REE) is characterized by a simple pricing rule that firms can easily adopt, the economy does not converge to the REE for all parameter values. When the volatility of monetary innovations is low and interactions among firms are high, the aggregate price level exhibits rigidity, in that it does not fully react to contemporaneous aggregate demand shocks. We discuss the role of the nature of experimentation, and of path dependence driven by interactions, in explaining these results.
International Unions
Authors: Alesina Alberto , Angeloni Ignazio , Etro Federico
Published: June 2005

We model an international union as a group of countries deciding to centralize the provision of public goods, or policies, that generate externalities across union members. The trade-off between the benefits of coordination and the loss of independent policymaking endogenously determines size, composition, and scope of the union. Policy uniformity reduces the size of the union, may block the entry of new members, and induces excessive centralization. We study flexible rules with nonuniform policies that reduce these inefficiencies, focusing particularly on arrangements that are relevant to the ongoing debate on the institutional structure of the European Union.
Understanding European Real Exchange Rates
Authors: Crucini Mario J , Telmer Chris I , Zachariadis Marios
Published: June 2005

We study good-by-good deviations from the Law-of-One-Price (LOP) for over 1,800 retail goods and services between all European Union (EU) countries for the years 1975, 1980, 1985, and 1990. We find that for each of these years, after we control for differences in income and value-added tax (VAT) rates, there are roughly as many overpriced goods as there are underpriced goods between any two EU countries. We also find that good-by-good measures of cross-sectional price dispersion are negatively related to the tradeability of the good, and positively related to the share of non-traded inputs required to produce the good. We argue that these observations are consistent with a model in which retail goods are produced by combining a traded input with a non-traded input.
The Variety and Quality of a Nation's Exports
Authors: Hummels David , Klenow Peter J
Published: June 2005

Large economies export more in absolute terms than do small economies. We use data on shipments by 126 exporting countries to 59 importing countries in 5,000 product categories to answer the question: How? Do big economies export larger quantities of each good (the intensive margin), a wider set of goods (the extensive margin), or higher-quality goods? We find that the extensive margin accounts for around 60 percent of the greater exports of larger economies. Within categories, richer countries export higher quantities at modestly higher prices. We compare these findings to some workhorse trade models. Models with Armington national product differentiation have no extensive margin, and incorrectly predict lower prices for the exports of larger economies. Models with Krugman firm-level product differentiation do feature a prominent extensive margin, but overpredict the rate at which variety responds to exporter size. Models with quality differentiation, meanwhile, can match the price facts. Finally, models with fixed costs of exporting to a given market might explain the tendency of larger economies to export a given product to more countries.
State “Currencies” and the Transition to the U.S. Dollar: Clarifying Some Confusions
Authors: Michener Ronald W , Wright Robert E
Published: June 2005

Farley W. Grubb's recent papers on the early U.S. monetary system would be important contributions to the common currency area literature were not most of their historical assertions questionable and their key assumption—that the medium of exchange can be inferred from the unit of account—dubious. We contend that after 1781 most Americans eschewed government paper money in favor of fullbodied coins and convertible bank liabilities and that, contrary to Grubb's claim, bankers did not foist the constitutional clause banning state emissions onto an unsuspecting public.
Zoledronic Acid and Renal Toxicity: Data from French Adverse Effect Reporting Database
Authors: Munier Aline , Gras Valerie , Andrejak Michel , Bernard Nathalie , Jean-Pastor Marie-Josephe , Gautier Sophie , Biour Michel , Massy Ziad
Published: June 2005

BACKGROUND

Zoledronic acid–associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined.

OBJECTIVE

To analyze French cases of zoledronic acid–associated nephrotoxicity.

METHODS

We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004.

RESULTS

We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1–120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid–associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs.

CONCLUSIONS

These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.
Use of the Transtheoretical Model in the Medication Use Process
Authors: Ficke Danielle L , Farris Karen B
Published: June 2005

OBJECTIVE

To review articles published during the past 10 years relating to the transtheoretical model (TTM) and the medication use process, focusing on prescribing, dispensing, and using prescription and nonprescription medications for legitimate purposes.

DATA SOURCES

MEDLINE, Cochrane database, PsychINFO, International Pharmaceutical Abstracts, and PubMed were searched from 1995 to August 2004 using the key terms models, psychological; prescriptions, drug; drugs, nonprescription; models, theoretical; self medication; patient compliance; medication compliance; decision making; drug therapy and behavior change. Additional searches included the following terms: pharmacists, community; TTM; transtheoretical model, pharmacy services, new practice patterns and physician practice patterns.

STUDY SELECTION AND DATA EXTRACTION

Studies with empirical application of any aspect of TTM were included. Abstracts were reviewed by both authors, and data were independently abstracted including, for example, specific aspects of TTM used or tested, context for model use or setting, and results and authors' suggestions for future use of TTM. The reviewers came to consensus on all abstracted information.

DATA SYNTHESIS

Eleven articles were identified that contained TTM and drug use; however, only 5 were empirical applications. There were 2 types of applications of TTM in medication use: measurement of stage of change regarding adherence and prediction of adherence using TTM concepts. A 1- and 2-item measure of adherence stage of change have been validated. Medication adherence stage of change varied by type of drug. The pros and cons of taking the medicine and stage of change were useful in predicting adherence. No intervention studies to improve adherence were identified.

CONCLUSIONS

TTM has not been used extensively to examine the medication use process. Without further research, no clear recommendation can be provided as to the effectiveness of TTM in improving the drug use process, but it remains promising.
Carotenoid-chlorophyll complexes: Ready-to-harvest
Authors: Vaswani Harsha M. , Holt Nancy E. , Fleming Graham R.
Published: June 2005

The fundamental interactions between naturally occurring pigments in light-harvesting systems are responsible for the high efficiency of the photosynthetic apparatus. We describe the role of carotenoids (Cars) in light-harvesting systems, including our work elucidating the mechanism of energy transfer from the optically dark Car singlet excited state (S1) to chlorophyll (Chl) and calculations on the electronic structure of Cars by means of time-dependent density functional theory (TDDFT). We highlight new studies on the charge-transfer state of the Car, peridinin (Per), which enhances the light-harvesting efficiency of the Car by increasing the electronic coupling to Chl. The role of another Car, zeaxanthin (Zea), is discussed with respect to its role in the mechanism of the feedback deexcitation quenching in green plants, a vital regulation process under light conditions which exceed photosynthetic capacity. Lastly, we provide insight on how the 96 Chls in Photosystem I are optimized to generate a pigment-protein complex which utilizes solar energy with near unit efficiency.
UVB and UVA radiation-mediated damage to isolated and cellular DNA
Authors: Cadet Jean , Courdavault Sophie , Ravanat Jean-Luc , Douki Thierry
Published: June 2005

The effects of solar light on cellular DNA are mostly explained by both direct excitation of nucleobases and photosensitized reactions that are mediated by UVB and UVA radiation, respectively. A large body of information is now available on the main photodynamic reactions to DNA, which involve guanine as the preferential target of both one-electron oxidation and singlet oxygen oxidation, as the result of type I and type II mechanisms. Most of the final products of the photosensitized reactions of guanine base in isolated DNA have been characterized, and comprehensive mechanisms for their formation have been proposed. Further insights into the mechanisms of solar radiation-induced modifications within cellular DNA have been gained from accurate measurement of the main photoproducts using recently designed sensitive chromatographic and biochemical methods. Thus, the distribution pattern of the 12 possible bipyrimidine photoproducts has been shown to be similar in the DNA of UVB-irradiated rodent and human cells. Cyclobutyl pyrimidine dimers are also generated at di-thymine and thymine-cytosine sites within nuclear DNA upon exposure to UVA radiation as the likely result of triplet energy transfer. In addition, oxidative reactions that involved mostly singlet oxygen, and to a lesser extent, .OH radicals are also implicated, although less efficiently.
Toward a computational photobiology
Authors: Sinicropi Adalgisa , Andruniow Tadeusz , De Vico Luca , Ferré Nicolas , Olivucci Massimo
Published: June 2005

In this paper, we discuss the results of our recent studies on the molecular mechanism, which stand at the basis of the photochemical processes occurring in photobiological systems. These results are obtained using modern, robust, and fairly accurate high-level quantum chemical methods.
Fluorescence sensor applications as detectors for DNA damage, free radical formation, and in microlithography
Authors: Scaiano J. C. , Aliaga C. , Chrétien M. N. , Frenette M. , Focsaneanu K. S. , Mikelsons L.
Published: June 2005

Fluorescence sensors have been developed to monitor radical reactions, DNA damage, acid-catalyzed processes, detection of electron-deficient molecules, and zeolite applications. The examples presented emphasize applications in polymer and supramolecular systems.
Rotaxane-based molecular machines operated by photoinduced electron transfer
Authors: Credi Alberto , Ferrer Belén
Published: June 2005

A molecular machine is an assembly of a definite number of molecular components designed to perform mechanical motions as a result of an appropriate external stimulation. Like their macroscopic counterparts, nanoscale machines need energy to operate. Energy can be supplied through (i) chemical reactions, (ii) electrochemical processes, and (iii) photoinduced processes. Although most molecular motors of the biological world are fueled by chemical reactions, for several reasons light is a very good choice to operate artificial molecular machines. Rotaxanes, owing to their peculiar architecture, are attractive candidates for the construction of artificial nanoscale machines. By adopting an incrementally staged design strategy, photoinduced electron-transfer processes have been engineered within rotaxane-type structures with the purpose of obtaining light-powered molecular machines. Such an approach is illustrated by describing the behavior of prototypes investigated in our laboratories.
Return electron transfer in radical ion pairs of triplet multiplicity
Authors: Roth Heinz D.
Published: June 2005

Return electron transfer (RET) in radical ion pairs may populate the reagent ground states or, in the case of triplet pairs, one reagent triplet state. The efficiency of triplet RET is governed by the free energies of singlet and triplet RET and by the topologies of the potential surfaces of parent molecules, radical ions, and accessible triplet states or biradicals. RET in triplet radical ion pairs is exemplified for two distinct relationships between the three potential surfaces.
A Pulse-Operated Microwave-Induced Plasma Source
Authors: Mohamed M. M. , Uchida T. , Minami S.
Published: June 2005

A new pulse-operated microwave-induced plasma (MIP) source is described. To avoid operational difficulties of the MIP due to Joule heating and to obtain spectral emission lines of high peak intensities, one energizes the MIP source with a TM010 cavity with a microwave pulse of large peak power and short duration, which is superposed on a low-bias dc microwave. A peak power of 400 W, which is two times the maximum output ratings of a magnetron under a normal dc operation, can be generated by applying a −500 V pulse to the cathode of the magnetron operating under the bias mode. The pulsed-MIP requires no special cooling system since the mean power remains low during the entire operation. Some of the considerations taken into account in the design and construction of the microwave generator are presented. The electrical and spectral characteristics of the MIP source are also described in detail.
A Photodiode-Array-Based Near-Infrared Spectrophotometer for the 600–1100 nm Wavelength Region
Authors: Mayes David M. , Callis James B.
Published: June 2005

We describe a silicon photodiode-array (PDA)-based near-infrared spectrophotometer for making molecular absorption/diffuse reflectance measurements in the 600–1100 nm wavelength range. Absorptions in this spectral region arise from both low-lying electronic states and vibrational overtones of CH, NH, and OH functional groups and combination bands. One disadvantage of silicon-based array detectors is their decreasing quantum efficiency at wavelengths longer than 950 nm. For transmission measurements, this can be compensated for by the technique of spectral plane masking, which markedly improves the consistency and overall level of baseline noise as well as the dynamic range. The instrument's performance is evaluated in the areas of spectral resolution, baseline noise, stray light, and dynamic range, and a comparison is made with a state-of-the-art mechanically scanned instrument. In the study, the PDA spectrometer attained a signal-to-noise ratio two times better than that of the commercial instrument with a time efficiency advantage of twelve, while achieving a spectral resolution three times greater. Finally, the application of analyzing caustic brine solutions by rapid-scanning NIR spectroscopy is illustrated.
Polycyclic Aromatic Hydrocarbon Solute Probes. Part IV: Effect of Solvent Polarity on the Fluorescence Emission Fine Structures of Select Pyrene and Pentaphene Derivatives
Authors: Waris Riaz , Street Kenneth W. , Acree William E. , Fetzer John C.
Published: June 2005

Fluorescence properties of benzo[e]pyrene, benzo[a)pyrene, dibenzo[a,ejpyrene (naphtho[1,2,3,4def]chrysene), 1-chloropyrene, tribenzo[de, kl,rst]pentaphene, dinaphtho[2,1,8,7defg,2′,1,8′,7'ijkl]pentaphene, benz [rst]anthra[9,1,2cde]pentaphene, and dibenzo[fg,ij]phenanthro[2,1,10,9,8,7pqrstuv]pentaphene dissolved in solvents of varying polarity are reported. Measurements indicate that emission intensities of benzo[e)pyrene (BePy) and dibenzophenanthropentaphene (DBPP) depend on solvent polarity. Two new polarity scales are defined, BePy = I/IV and DBPP = I/II, on the basis of the ratio of the fluorescence intensities of select vibronic bands. For fluorescence spectra for the remaining six compounds studied, either the spectra were not clearly resolvable or the calculated intensity ratios remained nearly constant, irrespective of solvent polarity.