bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial
Authors: Escudier Bernard , Dorval Thierry , Chaput Nathalie , André Fabrice , Caby Marie-Pierre , Novault Sophie , Flament Caroline , Leboulaire Christophe , Borg Christophe , Amigorena Sebastian , Boccaccio Catherine , Bonnerot Christian , Dhellin Olivier , Movassagh Mojgan , Piperno Sophie , Robert Caroline , Serra Vincent , Valente Nancy , Le Pecq Jean-Bernard , Spatz Alain , Lantz Olivier , Tursz Thomas , Angevin Eric , Zitvogel Laurence 
Published: March 2005

Abstract
Background
DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome.

Patients and methods
Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 × 1014 molecules) or peptides (10 versus 100 μg/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression.

Results
The GMP process allowed to harvest about 5 × 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood.

Conclusion
The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.
New York City HIV superbug: fear or fear not?
Authors: Smith Stephen M 
Published: March 2005

Abstract
On February 11, 2005, the New York City Department of Health and Mental Hygiene announced that a city resident had recently been infected with a multi-drug resistant form of HIV and rapidly progressed to AIDS. The Health Commissioner, Thomas R. Frieden, called for increased vigilance against this new strain. Is this situation an emerging crisis or simply an unusual case report of rapid HIV progression?
Retrovirology highlights a quarter century of HTLV-I research
Authors: Jeang Kuan-Teh 
Published: March 2005

Abstract
In 1977, Takatsuki and co-workers described in Japan a human malignant disease termed adult T-cell leukemia (ATL). Three years later, in 1980, Gallo and colleagues reported the identification of the first human retrovirus, human T-cell leukemia virus type I (HTLV-I), in a patient with cutaneous T-cell lymphoma. This month, Retrovirology commemorates these two land mark findings by publishing separate personal recollections by Takatsuki and Gallo respectively on the discovery of ATL and HTLV.
Dengue fever: new paradigms for a changing epidemiology
Authors: Guha-Sapir Debarati , Schimmer Barbara 
Published: March 2005

AbstractDengue is the most important arthropod-borne viral disease of public health significance. Compared with nine reporting countries in the 1950s, today the geographic distribution includes more than 100 countries worldwide. Many of these had not reported dengue for 20 or more years and several have no known history of the disease. The World Health Organization estimates that more than 2.5 billion people are at risk of dengue infection. First recognised in the 1950s, it has become a leading cause of child mortality in several Asian and South American countries.This paper reviews the changing epidemiology of the disease, focusing on host and societal factors and drawing on national and regional journals as well as international publications. It does not include vaccine and vector issues. We have selected areas where the literature raises challenges to prevailing views and those that are key for improved service delivery in poor countries.Shifts in modal age, rural spread, and social and biological determinants of race- and sex-related susceptibility have major implications for health services. Behavioural risk factors, individual determinants of outcome and leading indicators of severe illness are poorly understood, compromising effectiveness of control programmes. Early detection and case management practices were noted as a critical factor for survival. Inadequacy of sound statistical methods compromised conclusions on case fatality or disease-specific mortality rates, especially since the data were often based on hospitalised patients who actively sought care in tertiary centres.Well-targeted operational research, such as population-based epidemiological studies with clear operational objectives, is urgently needed to make progress in control and prevention.
High UV‐B Exposures in the Continental USA: Towards Realistic Short‐term Exposure Regimes for Plant‐effects Research
Authors: Grant Richard H. , Slusser James R. 
Published: March 2005

ABSTRACTUnderstanding the biological effects of acute ultraviolet‐B (UV‐B) exposure requires understanding the typical intensity and duration of such exposures. The occurrence of high hourly biologically effective UV‐B (UV‐Bbe) exposures was evaluated using two response functions (1971 and 2003) for the 1997–2002 summer growing seasons (May–August) at five locations across the continental United States. The frequency of occurrence of the upper 5% of all seasonal UV‐Bbe hourly exposures of 1 h to 4 h duration in 1 day and repeating the same exposure over consecutive days was evaluated. High hourly UV‐Bbe exposures occurred most frequently during June and July. There was a 30% frequency of occurrence of a day during the growing season with 2 h of hourly exposure in the upper 5% of UV‐Bbe (1971) values across any of the five locations studied. The frequency of occurrence of 2 h of UV‐Bbe (2003) exposure in the uppermost 5% of all observed hourly values was 14%. An approach and specific experimental square‐wave enhancement exposure regimes that are consistent with the range of actual exposures and total ozone column (TOC) during the May through August period are provided. A 2 day high UV‐B event with 2 h of high UV‐Bbe occurred at least 10% of all days in the growing season, representing a reasonable short‐term high‐exposure regime. Different exposure statistics and resulting enhancement regimes would likely result if only June and July were included in the analysis.
Cover Picture: Dendritic Nanowire Growth Mediated by a Self‐Assembled Catalyst (Adv. Mater. 5/2005)
Authors: May S. J. , Zheng J.‐G. , Wessels B. W. , Lauhon L. J. 
Published: March 2005

AbstractThe dendritic nanostructures shown on the cover background were generated by self‐assembled Mn clusters deposited from the vapor phase during vapor–liquid–solid growth of InAs nanowires. By carefully controlling the timing and amount of the Mn precursor, on p. 598 Lauhon and co‐workers demonstrate a route to the formation of ordered hierarchical nanowire structures shown from various perspectives in the cover insets.
Finite element analysis in functional morphology
Authors: Richmond Brian G. , Wright Barth W. , Grosse Ian , Dechow Paul C. , Ross Callum F. , Spencer Mark A. , Strait David S. 
Published: March 2005

AbstractThis article reviews the fundamental principles of the finite element method and the three basic steps (model creation, solution, and validation and interpretation) involved in using it to examine structural mechanics. Validation is a critical step in the analysis, without which researchers cannot evaluate the extent to which the model represents or is relevant to the real biological condition. We discuss the method's considerable potential as a tool to test biomechanical hypotheses, and major hurdles involved in doing so reliably, from the perspective of researchers interested in functional morphology and paleontology. We conclude with a case study to illustrate how researchers deal with many of the factors and assumptions involved in finite element analysis. © 2005 Wiley‐Liss, Inc.
The Magnetic Behaviour of [NnBu4]4[Ni16Pd16(CO)40]: An Even‐Electron Homoleptic Carbonyl–Metal Cluster Anion Displaying aJ=2 Ground State
Authors: Riccò Mauro , Shiroka Toni , Carretta Stefano , Bolzoni Fulvio , Femoni Cristina , Iapalucci M. Carmela , Longoni Giuliano 
Published: March 2005

AbstractThe magnetic behaviour of the even‐electron [Ni16Pd16(CO)40]4−cluster, in its [NnBu4]+salt, has been investigated by magnetometry and muon spin rotation/relaxation (μSR) spectroscopy. The susceptibility measurements show an exceptionally high magnetic moment corresponding to a total spin valueJ=2. This suggests a Hund filling of a quadruplet ground state, quite unique in carbonyl–metal clusters. SQUID magnetometry shows a departure from the Curie–Weiss law, forT>150 K, and strong deviation from a Brillouin behaviour of the magnetisation curves. μSR spectroscopy in zero applied field shows a temperature independent decay of the muon spin polarisation, similar to that of a purely paramagnetic system. The observed muon spin repolarisation in a moderate external longitudinal field, however, invalidates this simple picture and suggests the presence of a local anisotropy field acting on the cluster's magnetic moment. A consistent interpretation of magnetometry and μSR results implies the occurrence of an additional interaction of the cluster spin with an effective crystalline field. The inclusion of this interaction in a model Hamiltonian allows us to successfully reproduce both the susceptibility and magnetisation data.
Loss of Ammine from Platinum(II) Complexes: Implications for Cisplatin Inactivation, Storage, and Resistance
Authors: Lau Justin Kai‐Chi , Deubel Dirk V. 
Published: March 2005

AbstractPotential consequences of the binding of the anticancer drug cisplatin to various biomolecules in the cell have been investigated by using a combined density functional theory and continuum dielectric model approach. Since the ammine ligands remain coordinated at the metal upon formation of the most frequent DNA adducts, whereas they were found to be displaced from the metal upon formation of drug metabolites, we have analyzed the factors governing ammine loss from platinum(II) complexes as a possible pathway of cisplatin inactivation. The calculations systematically show the effect of 1) the trans ligand, 2) the charge of complex, 3) the nucleophile, and 4) the environment on the thermodynamic instability and kinetic lability of the platinum–ammine bonds. After initial binding of cisplatin hydrolysis products to thioethers or thiols, loss of the ammine trans to this sulfur ligand rather than replacement of the sulfur ligand itself by other nucleophiles like guanine‐N7 is predicted to be the predominant reaction. The results of this study contribute to an understanding of the modes of cisplatin inactivation prior to DNA binding, for example, by elevated glutathione levels in cisplatin‐resistant cancer cells.
Designing the “Search Pathway” in the Development of a New Class of Highly Efficient Stereoselective Hydrosilylation Catalysts
Authors: César Vincent , Bellemin‐Laponnaz Stéphane , Wadepohl Hubert , Gade Lutz H. 
Published: March 2005

AbstractThe direct coupling of oxazolines and N‐heterocyclic carbenes leads to chelating C,N ancillary ligands for asymmetric catalysis that combine both an “anchor” unit and a stereodirecting element. Reacting various N‐substituted imidazoles with 2‐bromo‐4(S)‐tert‐butyl‐ and 2‐bromo‐4(S)‐isopropyloxazoline gave the imidazolium precursors of the stereodirecting ancillary ligands. A library of ten different ligand precursors was obtained by using this simple procedure (65–97 % yield). These protioligands were metalated in a subsequent step by reaction with [{Rh(μ‐OtBu)(nbd)}2] (nbd=norbornadiene), generated in situ from KOtBu and [{RhCl(nbd)}2] giving the corresponding N‐heterocyclic carbene complexes [RhBr(nbd)(oxazolinyl‐carbene)] 4 a–j in good yields. X‐ray diffraction studies of two of the rhodium complexes, 4 d and 4 j, established a distorted square‐pyramidal coordination geometry with the bromo ligand occupying the apical position. The rhodium–carbene bond length was found to be 2.070(4) Å (4 d) and 2.012(3) Å (4 j). Complexes 4 a–j were treated with AgBF4 in dichloromethane, giving the active cationic square‐planar catalysts for the hydrosilylation of ketones. As a reference reaction for the catalyst optimisation, the hydrosilylation of acetophenone with diphenylsilane was studied and the system optimised with respect to the counterion (BF4−), solvent (THF) and the silane reducing agent (diphenylsilane). The reaction product (1‐phenylethanol) was obtained with the highest enantiomeric excess (ee) by carrying out the reaction at −60 °C, whilst the enantioselectivity drops upon going both to lower and higher temperatures. The observation that the temperature dependence of the ee values goes through a maximum indicated a change in the rate‐determining step as the temperature is varied. The determination of the initial reaction rate in the hydrosilylation of acetophenone upon varying the catalyst (4 d) and substrate concentrations at −55 °C established a rate law for the initial conversion which is first‐order in both substrates as well as the catalyst (Vi=k[4][PhCOMe][Ph2SiH2]). The catalytic system derived from complex 4 d was found to afford high yields and good enantioselectivities in the reduction of various aryl alkyl ketones (acetophenone: 92 % isolated yield and 90 % ee, 2‐naphtyl methyl ketone: 99 % yield, 91 % ee). The selectivity for the reduction of prochiral dialkyl ketones is comparable or even superior to the best previously reported for prochiral nonaromatic ketones; whereas cyclopropyl methyl ketone is hydrosilylated with an enantioselectivity of 81 % ee, the increase of the steric demand of one of the alkyl groups leads to improved ee's, reaching 95 % ee in the case of tert‐butyl methyl ketone. Linear chain n‐alkyl methyl ketones, which are particularly challenging substrates, are reduced in good asymmetric induction, such as 2‐octanone (79 % ee) and even 2‐butanone (65 % ee).
Cryosurgical ablation of the prostate
Authors: Prepelica Kristofer L. , Okeke Zephaniah , Murphy Alana , Katz Aaron E. 
Published: March 2005

AbstractBACKGROUNDThe authors report their experience with cryosurgical ablation of the prostate in men with high‐risk features for prostate carcinoma who were unwilling to undergo radical surgery or radiation therapy.METHODSBetween January 1998 and April 2002, 65 men underwent primary cryosurgery for prostate carcinoma with high‐risk features. All patients had biopsy‐proven prostate carcinoma without evidence for metastatic disease on magnetic resonance images, computed tomography scans, or radionuclide images of bones. High‐risk parameters were defined as either a prostate‐specific antigen (PSA) level ≥ 10 ng/mL, or a Gleason sum score ≥ 8, or both. Patients who had undergone prior surgery, radiation therapy, or cryoablation for prostate carcinoma were excluded from the study. Patients were monitored with physical examination and PSA screening every 3 months and with radiologic imaging when indicated.RESULTSThe median patient age was 72 years (range, 41–86 years), and t he median follow‐up was 35 months (range, 4–77 months). There were 2 patients (3.1%) with rectal pain and incontinence. Durable PSA biochemical disease‐free survival was noted in 83.3% of patients according to the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria. A 6‐year Kaplan–Meier analysis revealed an 81.7% ASTRO survival probability as well as PSA nadir < 4.0 ng/mL and PSA nadir < 1.0 ng/mL projections of 50% and 35%, respectively. One of 8 postcryosurgery biopsies (12.5%) were positive. No patient had progressed at last follow‐up, and the overall survival rate was 100%.CONCLUSIONSCryoablation was a feasible treatment option in patients with organ‐confined prostate carcinoma who had high‐risk features. Longer follow‐up will be necessary to determine the effectiveness of this approach. Cancer 2005. © 2005 American Cancer Society.
Toxin‐based selection of insulin‐producing cells with improved defense properties for islet cell transplantation
Authors: Bloch Konstantin , Vardi Pnina 
Published: March 2005

AbstractInsulin‐producing pancreatic β‐cells are known to be extremely susceptible to destruction, primarily by autoimmune mechanisms, infectious agents, and by chemical toxins that cause overt type I diabetes. As development of highly protected insulin‐producing cells would be important for successful cell therapy of diabetic patients, gene transfection technique was utilized by several investigators in order to improve the defense properties of transplanted cells. In this article, we summarize other approaches based on a selection strategy that has been developed in our laboratory and by other research groups that engineer pancreatic β‐cells to provide protection against diabetogenic toxins (streptozotocin and alloxan), oxidative stress and cytokines. Selection strategies based on acute repeated or long‐term continuous treatment of cell lines with cytotoxic agents have resulted in the selection of highly resistant cell subpopulations. We discuss possible involvement of different expression of cytoprotective genes in the selection of cell subpopulations, which demonstrate a broad spectrum of resistance. Importantly, toxin‐based selection did not impair functional activity of the cells as it was shown in vitro. In addition, selected cells preserved their improved metabolic characteristics following encapsulation in alginate and subsequent implantation in diabetic animals. Identifying the mechanisms through which cell defense properties act will help clarify the process responsible for β‐cell regeneration in type I diabetes patients. Such knowledge might be useful in developing strategies focusing on the regeneration of β‐cell resistant populations. Copyright © 2005 John Wiley & Sons, Ltd.
Forced vibration testing of buildings using the linear shaker seismic simulation (LSSS) testing method
Authors: Yu Eunjong , Whang Daniel H. , Conte Joel P. , Stewart Jonathan P. , Wallace John W. 
Published: March 2005

AbstractThis paper describes the development and numerical verification of a test method to realistically simulate the seismic structural response of full‐scale buildings. The result is a new field testing procedure referred to as the linear shaker seismic simulation (LSSS) testing method. This test method uses a linear shaker system in which a mass mounted on the structure is commanded a specified acceleration time history, which in turn induces inertial forces in the structure. The inertia force of the moving mass is transferred as dynamic force excitation to the structure. The key issues associated with the LSSS method are (1) determining for a given ground motion displacement, xg, a linear shaker motion which induces a structural response that matches as closely as possible the response of the building if it had been excited at its base by xg (i.e. the motion transformation problem) and (2) correcting the linear shaker motion from Step (1) to compensate for control–structure interaction effects associated with the fact that linear shaker systems cannot impart perfectly to the structure the specified forcing functions (i.e. the CSI problem). The motion transformation problem is solved using filters that modify xg both in the frequency domain using building transfer functions and in the time domain using a least squares approximation. The CSI problem, which is most important near the modal frequencies of the structural system, is solved for the example of a linear shaker system that is part of the NEES@UCLA equipment site. Copyright © 2005 John Wiley & Sons, Ltd.
Application of morphological approaches to determine unit hydrographs of urban catchments
Authors: Rodriguez Fabrice , Cudennec Christophe , Andrieu Hervé 
Published: March 2005

AbstractDetermining the hydrological response of urban catchments is of great interest for urban water management. Since most urban catchments are ungauged, this response must be deduced from catchment features, the description of which can be processed more easily today thanks to the availability of urban databases and geographical information systems within many cities. We compare three complementary methods for determining unit hydrographs, with varying degrees of catchment morphology description. The first method, displaying a high degree of description (URBS‐UH), is derived from the analysis of urban databases and yields an explicit description of runoff production areas and their downstream flow channels. The second method (H2U), which corresponds to a moderate degree of description, consists of a gamma law whose parameters are based on both the Strahler's catchment order and the average hydraulic length of water paths through the drainage system. The third method, corresponding to a low degree (FDTF), derives the unit hydrograph by means of an iterative deconvolution identification technique using observed rainfall and flow data. The three methods have all been applied to two urban catchments (of 60 and 180 ha), located within the Nantes metropolitan area (western France). Their comparison is discussed and reveals encouraging results: the variability of unit hydrographs due to rainfall intensity is observed with all three of the methods. Deriving unit hydrographs from the morphology of an ungauged catchment would appear beneficial for hydrological purposes, and the degree of information inclusion regarding this morphology can be adapted depending on the availability of geographical data on the catchment studied. Copyright © 2005 John Wiley & Sons, Ltd.