bluuebunny/crossref_metadata_2025 huggingface dataset:
Rebels Between Rebellions—Secret Societies in the Novel, P'eng Kung Au
Authors: Ch'en Jerome
Published: April 2006

This is a study of the social and economic functions of Chinese secret societies between the age of rebellions, 1850–1878, and the Boxer Uprising. The rebellions and their ensuing peaceful reconstruction of Chinese society brought important changes to both the secret societies and Chinese society at large. These are analyzed in detail in this essay. By so doing, the essay attempts to throw some light on the mechanism and processes of the structural changes of Chinese secret societies. It also attempts to correct some methodological defects which seem to exist still in the study of Chinese secret societies. One of these is that historians tend to focus their attention only on rebellions while neglecting the activities of the rebel elements in peace time; another is the reluctance to make better use of popular literature as a reliable source of historical information. Widi emphasis on the social and economic functions of these societies in peace time, the essay also helps to dispel the belief that all Chinese secret societies came from one mother body—a monistic myth created by the nationalist revolutionaries of the 1900's.
The Untouchable Soldier: Caste, Politics, and the Indian Army
Authors: Cohen Stephen P.
Published: April 2006

Military establishments are omnipresent if not everywhere omnipotent. While these costly bureaucracies are the bane of finance ministers around the world, they do provide an important opportunity for comparative analysis. This paper examines a military system—the Indian one—through time, and attempts to demonstrate the changing relationship of that system to Indian politics and society in general, and to the low-caste communities of India in particular. We select the low-caste untouchables because they represent an extreme challenge to the integrative capacity of both political and social systems, and because they have recently been the subject of intensive political and academic concern.
Chinese and Indian Agriculture: A Broad Comparison of Recent Policy and Performance
Authors: Bardhan Pranab K.
Published: April 2006

Abstracts

In both China and India agriculture is the key sector and yet detailed comparisons of agricultural development in the two economies are difficult to obtain. A major problem is, of course, the availability and reliability of data. This paper puts together some of the information that is now available and assesses its reliability to draw some rough generalizations.

On the whole it seems that agricultural production in the two countries has grown at fairly similar rates. In terms of absolute level Chinese yield per hectare in most crops, of course, exceeds that of India by a significant margin, but this has been true for quite a long time in the past.

In provision of inputs like organic and inorganic fertilizers and irrigation water the Chinese performance has been much better than that of India. Both countries have devoted not a very low proportion of their total gross investment to the agricultural sector. But the effectiveness of this investment has been quite unsatisfactory on account of, among other things, technical deficiencies and faulty planning in both countries, and the excesses of over enthusiastic but unskilled party cadres in China and a very much restricted framework of village institutions and administrative setup in India. In land policy much of the period under consideration was taken up in China in bold experimentations—with the inevitable advances and retreats—in search of the optimum size of land management in a backward peasant economy, while in India in spite of copious land legislation some of the crucial land relations have remained basically unaltered. The Chinese policy of moving away from age-old small-scale family farming and of emphasizing joint management of land and labour has, on the one hand, significantly strained peasant incentives, but on the other hand rid Chinese agriculture of the burden of uneconomically small and fragmented holdings, tenurial insecurity and crop sharing which still afflict a substantial part of Indian agriculture. The problem of ensuring enough marketed surplus
of foodgrains to feed the nonagricultural sector has, however, remained unsolved in both countries, in spite of all changes in institutions and production.
Liang Shih-i and the Communications Clique
Authors: MacKinnon Stephen R.
Published: April 2006

Abstracts

Through an examination of the career of Liang Shih-i (1869–1933) and the “Communications” clique of railway and financial administrators, the intention is to illuminate the nonmilitary side of the late Ch'ing to early Republic transition. Although Liang and such associates as Yeh Kung-cho and Kuan Keng-lin dealt with modernization of communications and financial institutions, the patterns of their careers fit a more traditional mold. Liang held a chin-shih degree; the others also had scholarly gentry backgrounds. Unlike their well known contemporary, Sheng Hsuan-huai, they were not entrepreneurs as well as bureaucrats. Crucial to the rise of these men first to bureaucratic and then, during the Republican period, to political power were their ties to Yuan Shih-k'ai. Between 1906 and 1911, Yuan helped nurtured Liang and his clique to control of the Ministry of Posts and Communications (Yu-ch'uan pu); during and after the revolution of 1911–12 Yuan depended on them and their communications and financial network of influence for support of his presidency of the Republic. Thus Liang and the Communications Clique represented the non-military side of Yuan Shih-k'ai's power during the late Ch'ing and early Republican periods.
The Black Hole Incident
Authors: Gupta Brijen K.
Published: April 2006

The number of persons who perished in the so-called Black Hole of Calcutta in 1756 has long been a matter of controversy, especially intense since the Indian viceroyalty of Lord Curzon of Kedleston. Two scholars, C. R. Wilson and S. C. Hill, and their patron, Lord Curzon, have maintained that HolwelPs narrative declaring that 123 persons perished in the Black Hole is substantially true. On the other hand, J. H. Little has argued that the Black Hole tragedy is a “gigantic hoax,” exaggerated beyond all proportions, since only a few men, in his opinion, were confined in the Black Hole, and of them only those who had received severe wounds during the actual fighting died. While English scholars have generally followed the Curzon- Wilson-Hill school, Indian scholars have recently come to accept Jadunath Sarkar's opinion that probably not more than sixty were confined in the Black Hole.
Looking at Southeast Asian History
Authors: Hall D. G. E.
Published: April 2006

In this paper I propose to look at Southeast Asian history for the most part before the era of European political control. My object is on the one hand to avoid the distortions of the picture caused by the wealth of writings on European activities in the area, which have tended to thrust into the background die history of the peoples of the area, and on the other hand to convey some idea of the importance of their history as a field of study today. Incidentally, it is a field in which most of the progress has been made by scholars whose names are largely unknown outside the esoteric circles of orientalism.
Bureaucratic Constraints on Nepotism in the Ch'ing Period
Authors: Marsh Robert M.
Published: April 2006

In China during the Ch'ing period, as before, many Confucian values were so family-centered as to tolerate degrees of nepotism not acceptable in some other societies. Ideally, of course, Confucian values admitted of no conflict between loyalty to the Emperor and loyalty to close relatives and friends. Nevertheless, conflicts between public and private interests were recognized at least as early as theMeng-tzuand were typified in such expressions as “robbing the public to help the private” (chiakung chi-ssu) and “putting the family first and the nation last” (hsien chia-tsu erh hou kuo-chia). But whatever may have been the nepotistic intent of officials, there was during the Ch'ing period, at least before the Taiping rebellion, a great centralization of imperial authority.
Population Reports in the Ch'ing Dynasty
Authors: Taeuber Irene B. , Wang Nai-Chi
Published: April 2006

The growth of China's population and die veracity of the figures that purport to measure it are both puzzles. Critical in die solutions to both puzzles are die records of an alien dynasty that ruled China from 1644 to 1911. All reconstructions of the growth of the population in recent centuries trace to one or the other of die two Ch'ing series—die local reports ordered by the emperor Ch'ien-lung in 1741, or the survey that began in 1909 and ended with the revolution in 1911. The results of the registration of 1953–1954 are consistent with the first Ch'ing activity. The statistics of the Republic of China had lineal descent from both series, but at a level of total population consistent with the limited results of the 1909–1911 survey.
The Economic Rehabilitation of the Samurai in the Early Meiji Period
Authors: Harootunian Harry D.
Published: April 2006

The Meiji Restoration of 1868, unquestionably the most important event in modern Japanese history, brought in its wake social and economic changes of a revolutionary nature. With the overthrow of the Tokugawa bakufu, the subsequent abolition of the han system, the equalization of classes, and the establishment of a conscript army, the need for a hereditary military class ceased to exist. Certainly, the presence of a samurai class, numbering approximately 1,800,000, or 400,000 families, stranded in a society in process of divesting itself of all feudal fetters, constituted an acute problem. The continued existence of this vast army of unemployed retainers could have easily hamstrung all efforts to modernize. And it is hardly surprising that the new Meiji leaders realized at the inception of the new regime that if the work of the Restoration was to be completed successfully, it was necessary to work out a satisfactory settlement for the samurai class.
Arts and humanities literature: Bibliometric characteristics of contributions by Turkish authors
Authors: Al Umut , Şahiner Mustafa , Tonta Yaşar
Published: April 2006

Scholarly communication in arts and humanities differs from that in the sciences. Arts and humanities scholars rely primarily on monographs as a medium of publication whereas scientists consider articles that appear in scholarly journals as the single most important publication outlet. The number of journal citation studies in arts and humanities is therefore limited. In this article, we investigate the bibliometric characteristics of 507 arts and humanities journal articles written by authors affiliated with Turkish institutions and indexed in the Arts & Humanities Citation Index (A&HCI) between the years 1975–2003. Journal articles constituted more than 60% of all publications. One third of all contributions were published during the last 4 years (1999–2003) and appeared in 16 different journals. An overwhelming majority of contributions (91%) were written in English, and 83% of them had single authorship. Researchers based at Turkish universities produced 90% of all publications. Two thirds of references in publications were to monographs. The median age of all references was 12 years. Eighty percent of publications authored by Turkish arts and humanities scholars were not cited at all while the remaining 20% (or 99 publications) were cited 304 times (an average of three citations per publication). Self‐citation ratio was 31%. Two thirds of the cited publications were cited for the first time within 2 years of their publications.
Methodology of detailed dosimetry and treatment of uncertainty and variations for in vivo studies
Authors: Kuster Niels , Torres Verónica Berdiñas , Nikoloski Neviana , Frauscher Michael , Kainz Wolfgang
Published: April 2006

Detailed and accurate dosimetric information is a basic precondition for acquiring adequate interpretations and valuations of in vivo studies testing radiofrequency (RF) electromagnetic fields (EMF). Instantaneous locally induced fields depend on many parameters, for example, orientation of the animal with respect to the incident field, animal size and posture, and tissue distribution. These parameters are often constrained, resulting in significant uncertainties in the dosimetric assessment of the exposure, averaged over all animals and the entire experimental phase, as well as in significant variations of the local exposures during the experiment. A sufficient analysis should therefore include (1) average and peak spatial specific absorption rate (SAR) values for the whole body and specific organs, (2) the uncertainty of each assessed SAR value, and (3) the short term and long term SAR variations between the tissues of individual animals. A methodology to obtain this pertinent information is developed and proposed in this paper. Using this methodology the dosimetry of a rat exposure apparatus operating at the carrier frequency of 1747 MHz, previously developed for a 2‐year bioassay study within the European Union project PERFORM, was obtained. We have demonstrated that comprehensive dosimetric data can be obtained with reasonable effort using the proposed method, providing that the exposure setup is soundly formulated. Bioelectromagnetics 27:378–391, 2006. © 2006 Wiley‐Liss, Inc.
DNA structures at chromosomal translocation sites
Authors: Raghavan Sathees C. , Lieber Michael R.
Published: April 2006

It has been unclear why certain defined DNA regions are consistently sites of chromosomal translocations. Some of these are simply sequences of recognition by endogenous recombination enzymes, but most are not. Recent progress indicates that some of the most common fragile sites in human neoplasm assume non‐B DNA structures, namely deviations from the Watson–Crick helix. Because of the single strandedness within these non‐B structures, they are vulnerable to structure‐specific nucleases. Here we summarize these findings and integrate them with other recent data for non‐B structures at sites of consistent constitutional chromosomal translocations. BioEssays 28: 480–494, 2006. © 2006 Wiley Periodicals, Inc.
The evolving role of microRNAs in animal gene expression
Authors: Massirer Katlin B. , Pasquinelli Amy E.
Published: April 2006

MicroRNAs (miRNAs) constitute an abundant family of 22‐nucleotide RNAs that base‐pair to target mRNAs and typically inhibit their expression. To assess the global impact of animal miRNAs on gene regulation, the expression of predicted targets and their cognate miRNAs was extensively analyzed in mammals and Drosophila.1,2 In general, targets are co‐expressed at relatively low or undetectable levels in the same tissues as the miRNAs predicted to regulate them. Additionally, genes that are highly co‐expressed with miRNAs usually lack target sites. The authors conclude that many animal genes are under evolutionary pressure to maintain or avoid complementary sites to miRNAs.1,2 Thus, the miRNA pathway broadly contributes to the complex gene regulatory networks that shape animal tissue development and identity. BioEssays 28: 449–452, 2006. © 2006 Wiley Periodicals, Inc.
From genes to aggressive behavior: the role of serotonergic system
Authors: Popova Nina K.
Published: April 2006

Recent investigations in neurogenomics have opened up new lines of research into a crucial genetic problem—the pathway from genes to behavior. This paper concentrates on the involvement of protein elements in the brain neurotransmitter serotonin (5‐HT) system in the genetic control of aggressive behavior. Specifically, it describes: (1) the effect of the knockout of MAO A, the principal enzyme in 5‐HT degradation, (2) the association of intermale aggression with the polymorphism in theTph2gene encoding the key enzyme in 5‐HT synthesis in the brain, tryptophan hydroxylase (TPH), and (3) the effect of selective breeding for nonaggressive behavior on 5‐HT metabolism, TPH activity and 5‐HT1Areceptors in the brain. The review provides converging lines of evidence that: (1) brain 5‐HT contributes to a critical mechanism underlying genetically defined individual differences in aggressiveness, and (2) genes encoding pivotal enzymes in 5‐HT metabolism (TPH and MAO A), 5‐HT‐transporter, 5‐HT1Aand 5‐HT1Breceptors belong to a group of genes that modulate aggressive behavior. BioEssays 28: 495–503, 2006. © 2006 Wiley Periodicals, Inc.
Selective forces for the origin of the eukaryotic nucleus
Authors: López‐García Purificación , Moreira David
Published: April 2006

The origin of the eukaryotic cell nucleus and the selective forces that drove its evolution remain unknown and are a matter of controversy. Autogenous models state that both the nucleus and endoplasmic reticulum (ER) derived from the invagination of the plasma membrane, but most of them do not advance clear selective forces for this process. Alternative models proposing an endosymbiotic origin of the nucleus fail to provide a pathway fully compatible with our knowledge of cell biology. We propose here an evolutionary scenario that reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium) with an autogenous generation of the contemporary nuclear membrane and ER from the bacterial membrane. We specifically state two selective forces that operated sequentially during its evolution: (1) metabolic compartmentation to avoid deleterious co‐existence of anabolic (autotrophic synthesis by the methanogen) and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2) avoidance of aberrant protein synthesis due to intron spreading in the ancient archaeal genome following mitochondrial acquisition and loss of methanogenesis. BioEssays 28: 525–533, 2006. © 2006 Wiley Periodicals, Inc.
A bioinformatician's view of the metabolome
Authors: Nobeli Irene , Thornton Janet M.
Published: April 2006

The study of a collection of metabolites as a whole (metabolome), as opposed to isolated small molecules, is a fast‐growing field promising to take us one step further towards understanding cell biology, and relating the genetic capabilities of an organism to its observed phenotype. The new sciences of metabolomics and metabonomics can exploit a variety of existing experimental and computational methods, but they also require new technology that can deal with both the amount and the diversity of the data relating to the rich world of metabolites. More specifically, the collaboration between bioinformaticians and chemoinformaticians promises to advance our view of cognate molecules, by shedding light on their atomic structure and properties. Modelling of the interactions of metabolites with other entities in the cell, and eventually complete modelling of reaction pathways will be essential for analysis of the experimental data, and prediction of an organism's response to environmental challenges. BioEssays 28: 534–545, 2006. © 2006 Wiley Periodicals, Inc.
Cross‐relaxation bottleneck in water–lysozyme proton magnetization exchange
Authors: Kakule J. F. , Sharp A. R. , Schreiner L. J. , Thompson R. T. , Kupka T. , Holly R. , Peemoeller H.
Published: April 2006

The proton spin‐lattice relaxation parameters in natural and deuterated lysozyme solutions have been measured as a function of temperature (0–50°C). The variation of the apparent magnitudes of the water proton magnetizations in the solutions with temperature indicates that magnetic coupling mixes protein and water proton magnetizations. The results are consistent with an exchange cross‐relaxation model (Hills, B. P., Mol Phys 1992, 76, 489–508) in which the cross‐relaxation acts between the labile and nonlabile protons, rather than between water and protein protons. Although this cross‐relaxation pathway clearly affects the observed magnetization fractions in this protein solution, its influence on the relaxation rates is less apparent. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 11–19, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Characterization of copper binding to the peptide amyloid‐β(1–16) associated with Alzheimer's disease
Authors: Ma Qing‐Feng , Hu Jia , Wu Wei‐Hui , Liu Hua‐Dong , Du Jin‐Tang , Fu Yuan , Wu Yong‐Wei , Lei Peng , Zhao Yu‐Fen , Li Yan‐Mei
Published: April 2006

Amyloid‐β peptide (Aβ) is the principal constituent of plaques associated with Alzheimer's disease (AD) and is thought to be responsible for the neurotoxicity associated with the disease. Copper binding to Aβ has been hypothesized to play an important role in the neruotoxicity of Aβ and free radical damage, and Cu2+ chelators represent a possible therapy for AD. However, many properties of copper binding to Aβ have not been elucidated clearly, and the location of copper binding sites on Aβ is also in controversy. Here we have used a range of spectroscopic techniques to characterize the coordination of Cu2+ to Aβ(1–16) in solution. Electrospray ionization mass spectrometry shows that copper binds to Aβ(1–16) at pH 6.0 and 7.0. The mode of copper binding is highly pH dependent. Circular dichroism results indicate that copper chelation causes a structural transition of Aβ(1–16). UV‐visible absorption spectra suggest that three nitrogen donor ligands and one oxygen donor ligand (3N1O) in Aβ(1–16) may form a type II square‐planar coordination geometry with Cu2+. By means of fluorescence spectroscopy, competition studies with glycine and L‐histidine show that copper binds to Aβ(1–16) with an affinity of Ka ∼ 107M–1 at pH 7.8. Besides His6, His13, and His14, Tyr10 is also involved in the coordination of Aβ(1–16) with Cu2+, which is supported by 1H NMR and UV‐visible absorption spectra. Evidence for the link between Cu2+ and AD is growing, and this work has made a significant contribution to understanding the mode of copper binding to Aβ(1–16) in solution. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 20–31, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Matrix metalloproteinase‐9,‐3 and tissue inhibitor of matrix metalloproteinase‐1 in colorectal cancer: relationship to clinicopathological variables
Authors: İşlekel Hüray , Oktay Gülgün , Terzi Cem , Canda Aras Emre , Füzün Mehmet , Küpelioğlu Ali
Published: April 2006

The balance between matrix metalloproteinases (MMPs) and their physiological tissue inhibitors of matrix metalloproteinases (TIMPs) is crucial in tumour invasion and progression. The aim of this study was to investigate the levels of MMP‐9, MMP‐3 and TIMP‐1 in colorectal cancer (CRC) and to evaluate these proteinases and their inhibitor with respect to clinicopathological variables. Activities of pro‐ and active MMP‐9 were measured in paired tumour and distant normal tissue specimens from 43 patients with CRC using gelatin zymography. ELISA was employed for the determination of MMP‐9, MMP‐3 and TIMP‐1 protein expressions. The activity levels of pro‐ and active MMP‐9 and protein expression levels of MMP‐9, MMP‐3 and TIMP‐1 were higher in tumour tissues than in the corresponding normal tissues; the differences being significant for all (p < 0.05), except TIMP‐1. Similarly, active MMP‐9/proMMP‐9 and the ratio of protein expression level of MMP‐9–TIMP‐1 were found to be significantly higher in tumour tissues ( p < 0.01). Among all the clinicopathological variables investigated, significant correlations were found between MMP‐9 and presence of perineural invasion, MMP‐3 and lymph node status, TIMP‐1 and tumour differentiation, MMP‐9/TIMP‐1 ratio and histological types ( p < 0.05). In conclusion, MMP‐3 was not as notably increased as MMP‐9 in tumour tissues. However, different roles may be attributed to MMP‐9 and MMP‐3 in CRC development and progression. Additionally, assessment of TIMP‐1 in relation to MMPs appeared to be crucial in CRC studies to provide a basis for the re‐evaluation of the clinical usefulness of TIMP‐1 in colorectal cancer. Copyright © 2006 John Wiley & Sons, Ltd.
Biologic and immunomodulatory events after CTLA‐4 blockade with ticilimumab in patients with advanced malignant melanoma
Authors: Reuben James M. , Lee Bang‐Ning , Li Changping , Gomez‐Navarro Jesus , Bozon Viviana A. , Parker Charla A. , Hernandez Ingrid M. , Gutierrez Carolina , Lopez‐Berestein Gabriel , Camacho Luis H.
Published: April 2006

BACKGROUND

T‐regulatory (TR) cells expressing cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) maintain peripheral immune tolerance and negatively affect host immune responses against cancer. The immunobiologic effects of ticilimumab, a human monoclonal antibody against CTLA‐4, was administered to patients with metastatic melanoma who participated in a Phase I/II clinical trial.

METHODS

Thirty patients who received ticilimumab at a dose of 10 mg/kg monthly (n = 20) or 15 mg/kg every 3 months (n = 10) were studied at study entry and at 14‐day intervals thereafter to assess lymphocyte immunophenotypes, interleukin (IL)‐2 and IL‐10 production, and the expression of TR‐related genes in peripheral blood mononuclear cells (PBMC) from a subset of patients was studied by real‐time polymerase chain reaction.

RESULTS

Four of 12 patients with immune‐related adverse events (IRAE) attained objective antitumor responses (ATR), whereas only 1 of 18 patients without IRAE attained ATR (χ2 = 4.0; P = .0455). Patients with ATR had significant reductions in TR cells and constitutive IL‐10 production accompanied by a significant increase in IL‐2 production by activated T cells. Although IRAE+/ATR+ patients demonstrated a positive correlation between CTLA‐4 and glucocorticoid‐induced tumor necrosis factor receptor (GITR) transcripts (Spearman rho = .522; P = .015), IRAE−/ATR− patients had a positive correlation between the transcripts of CTLA‐4 and program death‐1 (PD‐1) receptor (Spearman rho = .891; P = .000).

CONCLUSIONS

Antitumor responses in patients with metastatic melanoma who were treated with ticilimumab were found to be correlated with reductions in TR cells and constitutive secretion of IL‐10, an increase in IL‐2 production, and a positive correlation between transcripts of CTLA‐4 and GITR. Conversely, a lack of ATR was found to be correlated with steady levels of TR cells and constitutive IL‐10 secretion, and a positive correlation between the transcripts of CTLA‐4 and PD‐1. Cancer 2006. © 2006 American Cancer Society.
Phase II study of mitoxantrone and ketoconazole for hormone‐refractory prostate cancer
Authors: Eklund John , Kozloff Mark , Vlamakis Joy , Starr Alexander , Mariott Margaret , Gallot Lilia , Jovanovic Borko , Schilder Lawrence , Robin Erwin , Pins Michael , Bergan Raymond C.
Published: April 2006

BACKGROUND

Doxorubicin plus ketoconazole has exhibited significant activity in patients with advanced prostate cancer. However, overall and cardiac‐specific toxicity was reported to be high. Mitoxantrone has activity similar to that of doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer. The current study sought to evaluate the toxicity and activity of mitoxantrone plus ketoconazole in a cohort of patients with hormone‐refractory prostate cancer.

METHODS

Progression after medical or surgical castration and, for those patients receiving antiandrogens, progression after withdrawal was required, as was objective evidence of metastasis, castrate levels of testosterone, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and intact cardiac function. After enrollment onto a multicenter local consortium study, subjects were treated with mitoxantrone at a dose of 12 mg/m2 intravenously every 3 weeks plus continuous oral ketoconazole at a dose of 400 mg 3 times daily and ascorbic acid at a dose of 250 mg. Replacement doses of hydrocortisone were given.

RESULTS

For 40 enrolled subjects, the median prostate‐specific antigen and ECOG performance status were 68 and 1, respectively, 53% had Gleason scores of 8 to 10, and all had metastasis. Predominant Grade 3/4 toxicities were: neutropenia in 13%, neutropenic fever in 10%, and anemia in 13%. Of 37 evaluable patients, 8% achieved a complete remission (CR) and 62% achieved a partial remission (PR), for a CR plus PR rate of 70%. For soft tissue and bone disease, overall response rates were 13% and 8%, respectively. The median progression‐free survival and overall survival were 10 months and 18 months, respectively.

CONCLUSIONS

Mitoxantrone plus ketoconazole is well tolerated, is active in hormone‐refractory prostate cancer, and should be studied further. Cancer 2006. © 2006 American Cancer Society.
Sensitivity and specificity of confocal laser‐scanning microscopy for in vivo diagnosis of malignant skin tumors
Authors: Gerger Armin , Koller Silvia , Weger Wolfgang , Richtig Erika , Kerl Helmut , Samonigg Hellmut , Krippl Peter , Smolle Josef
Published: April 2006

BACKGROUND

Melanoma and nonmelanoma skin cancer are the most frequent malignant tumors by far among whites. Currently, early diagnosis is the most efficient method for preventing a fatal outcome. In vivo confocal laser‐scanning microscopy (CLSM) is a recently developed potential diagnostic tool.

METHODS

One hundred seventeen melanocytic skin lesions and 45 nonmelanocytic skin lesions (90 benign nevi, 27 malignant melanomas, 15 basal cell carcinomas, and 30 seborrheic keratoses) were sampled consecutively and were examined using proprietary CLSM equipment. Stored images were rated by 4 independent observers.

RESULTS

Differentiation between melanoma and all other lesions based solely on CLSM examination was achieved with a positive predictive value of 94.22%. Malignant lesions (melanoma and basal cell carcinoma) as a group were diagnosed with a positive predictive value of 96.34%. Assessment of distinct CLSM features showed a strong interobserver correlation (κ >0.80 for 11 of 13 criteria). Classification and regression tree analysis yielded a 3‐step algorithm based on only 3 criteria, facilitating a correct classification in 96.30% of melanomas, 98.89% of benign nevi, and 100% of basal cell carcinomas and seborrheic keratoses.

CONCLUSIONS

In vivo CLSM examination appeared to be a promising method for the noninvasive assessment of melanoma and nonmelanoma skin tumors. Cancer 2006. © 2006 American Cancer Society.
Distribution of substance P reveals a novel subdivision in the hippocampus of parasitic South American cowbirds
Authors: Nair‐Roberts Radha G. , Erichsen Jonathan T. , Reboreda Juan C. , Kacelnik Alex
Published: April 2006

Parasitic cowbirds monitor potential hosts' nests and return to lay when appropriate, a task that is likely to involve spatial recall. Seasonal and sexual behavioral variations in the cowbirds correlate with anatomical changes in the hippocampal formation. During the breeding season, parasites have larger hippocampal formations than nonparasites. In parasitic species in which females alone perform nest bookkeeping, females have larger hippocampal formations than males. We investigated the distribution of the neuropeptide substance P (SP) in three sympatric cowbirds: two obligate parasites (shiny cowbird and screaming cowbird) and one nonparasite (bay‐winged cowbird). Distribution of SP was similar to that in other songbirds, except for a previously undescribed field of dense SP‐rich terminals within the hippocampus that we call thehippocampal SP terminal field(SPh). We found robust species differences in the volume of this new area, measured relative to the remainder of the telencephalon. SPh was largest in the generalist parasite (shiny cowbird) and smallest in the nonparasitic species (bay‐winged cowbird). In the specialist parasite (screaming cowbird), SPh was smaller than in the generalist parasite but larger than in the nonparasitic species. SPh overlaps with two subdivisions described in the pigeon that have been related to the mammalian dentate gyrus and subiculum. The area containing SPh receives a major input from the lateral mammillary nucleus, which is probably the avian equivalent of the mammalian supramammillary nucleus (SUM), the main source of extrinsic SP input to mammalian hippocampus. SPh may be the termination of a pathway homologous to the SP‐rich projection from SUM to the hippocampus in mammals. J. Comp. Neurol. 496:610–626, 2006. © 2006 Wiley‐Liss, Inc.
Dynamic expression of retinoic acid‐synthesizing and ‐metabolizing enzymes in the developing mouse inner ear
Authors: Romand Raymond , Kondo Takako , Fraulob Valérie , Petkovich Martin , Dollé Pascal , Hashino Eri
Published: April 2006

Retinoic acid signaling plays essential roles in morphogenesis and neural development through transcriptional regulation of downstream target genes. It is believed that the balance between the activities of synthesizing and metabolizing enzymes determines the amount of active retinoic acid to which a developing tissue is exposed. In this study, we investigated spatiotemporal expression patterns of four synthesizing enzymes, the retinaldehyde dehydrogenases 1, 2, 3, and 4 (Raldh1, Raldh2, Raldh3, and Raldh4) and two metabolizing enzymes (Cyp26A1 and Cyp26B1) in the embryonic and postnatal mouse inner ear by using quantitative reverse transcriptase polymerase chain reaction (RT‐PCR), in situ hybridization, and Western blot analysis. Quantitative RT‐PCR analysis and Western blot data revealed that the expression of CYP26s was much higher than that of Raldhs at early embryonic ages but that Cyp26 expression was downregulated during embryonic development. Conversely, the expression levels of Raldh2 and ‐3 increased during development and were significantly higher than the Cyp26 levels at postnatal day 20. At this age, Raldh3 was expressed predominantly in the cochlea, whereas Raldh2 was present in the vestibular end organ. At early embryonic stages, as observed by in situ hybridization, the synthesizing enzymes were expressed only in the dorsoventral epithelium of the otocyst, whereas the metabolizing enzymes were present mainly in mesenchymal cells surrounding the otic epithelium. At later stages, Raldh2, Raldh3, and Cyp26B1 were confined to the stria vascularis, spiral ganglion, and supporting cells in the cochlear and vestibular epithelia, respectively. The downregulation of Cyp26s and the upregulation of Raldhs after birth during inner ear maturation suggest tissue changes in the sensitivity to retinoic acid concentrations. J. Comp. Neurol. 496:643–654, 2006. © 2006 Wiley‐Liss, Inc.
Synaptic organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey
Authors: Freese Jennifer L. , Amaral David G.
Published: April 2006

The primate amygdaloid complex projects to a number of visual cortices, including area V1, primary visual cortex, and area TE, a higher‐order unimodal visual area involved in object recognition. We investigated the synaptic organization of these projections by injecting anterograde tracers into the amygdaloid complex ofMacaca fascicularismonkeys and examining labeled boutons in areas TE and V1 using the electron microscope. The 256 boutons examined in area TE formed 263 synapses. Two hundred twenty‐three (84%) of these were asymmetric synapses onto dendritic spines and 40 (15%) were asymmetric synapses onto dendritic shafts. Nine boutons (3.5%) formed double asymmetric synapses, generally on dendritic spines, and 2 (1%) of the boutons did not form a synapse. The 200 boutons examined in area V1 formed 211 synapses. One hundred eighty‐nine (90%) were asymmetric synapses onto dendritic spines and 22 (10%) were asymmetric synapses onto dendritic shafts. Eleven boutons (5.5%) formed double synapses, usually with dendritic spines. We conclude from these observations that the amygdaloid complex provides an excitatory input to areas TE and V1 that primarily influences spiny, probably pyramidal, neurons in these cortices. J. Comp. Neurol. 496:655–667, 2006. © 2006 Wiley‐Liss, Inc.
Organization of noradrenergic efferents to arousal‐related basal forebrain structures
Authors: España Rodrigo A. , Berridge Craig W.
Published: April 2006

Norepinephrine acts within select basal forebrain regions to modulate behavioral state and/or state‐dependent processes, including the general regions encompassing the medial septal area, the medial preoptic area, and the substantia innominata. The present study examined the origin and organization of noradrenergic efferents to these basal forebrain regions by using combined immunohistochemical identification of noradrenergic neurons with retrograde tracing. Results indicate that the locus coeruleus provides the majority of noradrenergic input to these regions. Lesser, although at times substantial, contributions from the A1/C1 and A2/C2 adrenergic cell groups were also observed, particularly in the case of the medial preoptic region. Given the prominent state‐modulating actions of the locus coeruleus, additional studies examined: 1) lateralization of locus coeruleus efferents to these regions; 2) the topographical organization of basal forebrain‐projecting locus coeruleus neurons; and 3) the degree of collateralization of individual locus coeruleus neurons across these regions. Approximately 80–85% of locus coeruleus efferents to these regions project ipsilaterally. In general, basal forebrain‐projecting neurons were distributed throughout the entire dorsoventral and rostrocaudal extent of the locus coeruleus. Additionally, a large proportion of locus coeruleus neurons project simultaneously to these basal forebrain terminal fields. Combined, these observations indicate coordinated actions of locus coeruleus neurons across these basal forebrain regions implicated in the regulation of behavioral state and/or state‐dependent processes. J. Comp. Neurol. 496:668–683, 2006. © 2006 Wiley‐Liss, Inc.
Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain
Authors: Visel Axel , Alvarez‐Bolado Gonzalo , Thaller Christina , Eichele Gregor
Published: April 2006

Adenylate cyclases (Adcys) are components of several developmentally, neurophysiologically, and pharmacologically relevant signaling pathways. A prominent feature of Adcys is their ability to integrate multiple signaling pathways into a single second messenger pathway, the production of cAMP. Nine isoforms of membrane‐bound Adcys are known, each encoded by a distinct gene. These isoforms differ in their response to regulatory upstream pathways as well as in their distribution in the brain and elsewhere. Use of various detection methods and animal species has, however, hampered a direct comparison of expression patterns, so the potential contribution of single isoforms to Adcy activity in different brain regions remains unclear. We have determined the expression patterns of all nine Adcy genes in the embryonic, postnatal day 7, and adult mouse brain by nonradioactive robotic in situ hybridization (ISH). Here we describe the salient features of these patterns. Regional colocalization of Adcy transcripts encoding isoforms with different regulatory properties was detected in the cortex, subregions of the hippocampus, olfactory bulb, thalamus, and striatum. Hence, our expression data support models for modulation of cAMP signaling by combinatorial action of multiple Adcy isoforms. However, in several instances, the expression domains of genes encoding isoforms with similar regulatory properties spatially exclude each other, which is most evident in not previously described expression domains of the embryonic midbrain roof. This is suggestive of functional specialization. J. Comp. Neurol. 496:684–697, 2006. © 2006 Wiley‐Liss, Inc.
Imaging spectrometer fundamentals for researchers in the biosciences—A tutorial
Authors: Lerner Jeremy M.
Published: April 2006

Over the last 2 years there has been a dramatic increase in the number of bioscience laboratories using wavelength dispersive spectroscopy to study in vivo, in situ fluorescence. Transforming spectral information into an image provides a graphic means of mapping localized ionic, molecular, and protein–protein interactions. Spectroscopy also enables fluorophores with overlapping spectral features to be delineation. In this study, we provide the tools that a researcher needs to put into perspective instrumental contributions to a reported spectrum in order to gain greater understanding of the natural emission of the sample. We also show how to deduce the basic capabilities of a spectral confocal system. Finally, we show how to determine the true spectral bandwidth of an object, the illuminated area of a laser‐excited object, and what is needed to optimize light throughput. © 2006 International Society for Analytical Cytology
Embryonic and larval expression of zebrafish voltage‐gated sodium channel α‐subunit genes
Authors: Novak Alicia E. , Taylor Alison D. , Pineda Ricardo H. , Lasda Erika L. , Wright Melissa A. , Ribera Angeles B.
Published: April 2006

Whereas it is known that voltage‐gated calcium channels play important roles during development, potential embryonic roles of voltage‐gated sodium channels have received much less attention. Voltage‐gated sodium channels consist of pore‐forming α‐subunits (Nav1) and auxiliary β‐subunits. Here, we report the embryonic and larval expression patterns for all eight members of the gene family (scna) coding for zebrafish Nav1 proteins. We find that eachscnagene displays a distinct expression pattern that is temporally and spatially dynamic during embryonic and larval stages. Overall, our findings indicate thatscnagene expression occurs sufficiently early during embryogenesis to play developmental roles for both muscle and nervous tissues. Developmental Dynamics 235:1962–1973, 2006. © 2006 Wiley‐Liss, Inc.
Prostate cancer cells use genetic and epigenetic mechanisms for progression to androgen independence
Authors: Murillo Horacio , Schmidt Lucy J. , Karter Melissa , Hafner Kari A. , Kondo Yasushi , Ballman Karla V. , Vasmatzis George , Jenkins Robert B. , Tindall Donald J.
Published: April 2006

Studies on the genetic basis of prostate cancer (PCa) have lead to mixed results with the only consensus being that PCa is a complex disease. Our goal was to gain insight into potential events involved in the acquisition of the androgen‐refractory phenotype in PCa cells regardless of DNA‐change dependence. To this end, we examined two LNCaP PCa cell line models of progression—one developed in vivo and one developed in vitro—using molecular cytogenetic and microarray gene expression analyses and extended this investigation of specific events into PCa tumors. The chromosomal changes observed in both in vivo and in vitro androgen‐independent cell lines are similar to those seen in PCa during tumor progression. Correspondingly, gene expression analysis showed significant heterogeneity in the genes expressed among androgen‐independent cells, but with some common gene expression changes that correlated with the acquired androgen‐independent phenotype. Thus, growth conditions under which the cells progress appeared to impact the mechanisms used for progression, albeit within tumor‐type‐specific pathways. Our findings suggest that a dynamic and adaptable combination of epigenetic and DNA‐change‐dependent events can be used by PCa cells for the acquisition of the androgen‐independent phenotype. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2006 Wiley‐Liss, Inc.
EphB4 provides survival advantage to squamous cell carcinoma of the head and neck
Authors: Masood Rizwan , Kumar S. Ram , Sinha Uttam K. , Crowe David L. , Krasnoperov Valery , Reddy Ramachandra K. , Zozulya Sergey , Singh Jasbir , Xia Guangbin , Broek Daniel , Schönthal Axel H. , Gill Parkash S.
Published: April 2006

The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in blood vessel maturation, and are frequently overexpressed in a wide variety of cancers. We studied the aberrant expression and biological role of EphB4 in head and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4‐specific siRNA and antisense oligonucleotides (AS‐ODN) on cell growth, migration and invasion, and the effect of EphB4 AS‐ODN on tumor growth in vivo. All HNSCC tumor samples express EphB4 and levels of expression correlate directly with higher stage and lymph node metastasis. Six of 7 (86%) HNSCC cell lines express EphB4, which is induced either by EGFR activation or by EPHB4 gene amplification. EphrinB2 was expressed in 65% tumors and 5 of 7 (71%) cell lines. EphB4 provides survival advantage to tumor cells in that EphB4 siRNA and AS‐ODN significantly inhibit tumor cell viability, induce apoptosis, activate caspase‐8, and sensitize cells to TRAIL‐induced cell death. Furthermore, EphB4‐specific AS‐ODN significantly inhibits the growth of HNSCC tumor xenografts in vivo. Expression of EphB4 in HNSCC tumor cells confers survival and invasive properties, and thereby provides a strong rationale for targeting EphB4 as novel therapy for HNSCC. © 2006 Wiley‐Liss, Inc.
Alcohol consumption and prostate cancer risk: Results from the Melbourne collaborative cohort study
Authors: Baglietto Laura , Severi Gianluca , English Dallas R. , Hopper John L. , Giles Graham G.
Published: April 2006

Although there is little evidence to support an association between alcohol consumption and prostate cancer risk, questions remain concerning the effect on aggressive and nonaggressive tumours and the pattern and type of alcohol consumed. In a prospective cohort of 16,872 men aged 27–70 years at recruitment and followed‐up from 1994 to the end of 2003, 732 incident prostate cancers were identified through the local population cancer registry, including 132 aggressive cases and 53 prostate cancer deaths. Detailed information on alcohol consumption was taken at baseline by trained interviewers using a structured questionnaire. Overall, alcohol intake was not associated with prostate cancer incidence. Compared to abstainers, men consuming 1–19 g/d of alcohol had a slightly reduced incidence of aggressive prostate cancers (hazard ratio 0.67; 95% confidence interval (CI) 0.43, 1.06) and prostate cancer mortality (hazard ratio 0.56; 95% CI 0.28, 1.14), but their risk of nonaggressive prostate cancers was close to unity (hazard ratio 1.09; 95% CI 0.85, 1.40). No significant association with pattern of drinking or type of alcoholic beverage was found. Our results show that alcohol consumption does not influence overall prostate cancer incidence but we found suggestive evidence that alcohol consumption might decrease the incidence of aggressive prostate cancer and mortality. © 2006 Wiley‐Liss, Inc.