Tumor suppression and apoptosis of human prostate carcinoma mediated by a genetic locus within human chromosome 10pter-q11.

Prostate cancer is the second leading cause of male cancer deaths in the United States. Yet, despite a large international effort, little is known about the molecular mechanisms that underlie this devastating disease. Prostate secretory epithelial cells and androgen-dependent prostate carcinomas undergo apoptosis in response to androgen deprivation and, furthermore, most prostate carcinomas become androgen independent and refractory to further therapeutic manipulations during disease progression. Definition of the genetic events that trigger apoptosis in the prostate could provide important insights into critical pathways in normal development as well as elucidate the perturbations of those key pathways in neoplastic transformation. We report the functional definition of a novel genetic locus within human chromosome 10pter-q11 that mediates both in vivo tumor suppression and in vitro apoptosis of prostatic adenocarcinoma cells. A defined fragment of human chromosome 10 was transferred via microcell fusion into a prostate adenocarcinoma cell line. Microcell hybrids containing only the region 10pter-q11 were suppressed for tumorigenicity following injection of microcell hybrids into nude mice. Furthermore, the complemented hybrids undergo programmed cell death in vitro via a mechanism that does not require nuclear localization of p53. These data functionally define a novel genetic locus, designated PAC1, for prostate adenocarcinoma 1, involved in tumor suppression of human prostate carcinoma and furthermore strongly suggest that the cell death pathway can be functionally restored in prostatic adenocarcinoma.

Human naive and memory T lymphocytes differ in telomeric length and replicative potential.

The present study has assessed the replicative history and the residual replicative potential of human naive and memory T cells. Telomeres are unique terminal chromosomal structures whose length has been shown to decrease with cell division in vitro and with increased age in vivo for human somatic cells. We therefore assessed telomere length as a measure of the in vivo replicative history of naive and memory human T cells. Telomeric terminal restriction fragments were found to be 1.4 +/- 0.1 kb longer in CD4+ naive T cells than in memory cells from the same donors, a relationship that remained constant over a wide range of donor age. These findings suggest that the differentiation of memory cells from naive precursors occurs with substantial clonal expansion and that the magnitude of this expansion is, on average, similar over a wide range of age. In addition, when replicative potential was assessed in vitro, it was found that the capacity of naive cells for cell division was 128-fold greater as measured in mean population doublings than the capacity of memory cells from the same individuals. Human CD4+ naive and memory cells thus differ in in vivo replicative history, as reflected in telomeric length, and in their residual replicative capacity.

Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.

beta-Oxidation of long-chain fatty acids provides the major source of energy in the heart. Defects in enzymes of the beta-oxidation pathway cause sudden, unexplained death in childhood, acute hepatic encephalopathy or liver failure, skeletal myopathy, and cardiomyopathy. Very-long-chain acyl-CoA dehydrogenase [VLCAD; very-long-chain-acyl-CoA:(acceptor) 2,3-oxidoreductase, EC 1.3.99.13] catalyzes the first step in beta-oxidation. We have isolated the human VLCAD cDNA and gene and determined the complete nucleotide sequences. Polymerase chain reaction amplification of VLCAD mRNA and genomic exons defined the molecular defects in two patients with VLCAD deficiency who presented with unexplained cardiac arrest and cardiomyopathy. In one, a homozygous mutation in the consensus dinucleotide of the donor splice site (g+1-->a) was associated with universal skipping of the prior exon (exon 11). The second patient was a compound heterozygote, with a missense mutation, C1837-->T, changing the arginine at residue 613 to tryptophan on one allele and a single base deletion at the intron-exon 6 boundary as the second mutation. This initial delineation of human mutations in VLCAD suggests that VLCAD deficiency reduces myocardial fatty acid beta-oxidation and energy production and is associated with cardiomyopathy and sudden death in childhood.

The Lutheran blood group glycoprotein, another member of the immunoglobulin superfamily, is widely expressed in human tissues and is developmentally regulated in human liver.

Glycoproteins expressing the Lutheran blood group antigens were isolated from human erythrocyte membranes and from human fetal liver. Amino acid sequence analyses allowed the design of redundant oligonucleotides that were used to generate a 459-bp, sequence-specific probe by PCR. A cDNA clone of 2400 bp was isolated from a human placental lambda gt 11 library and sequenced, and the deduced amino acid sequence was studied. The predicted mature protein is a type I membrane protein of 597 amino acids with five potential N-glycosylation sites. There are five disulfide-bonded, extracellular, immunoglobulin superfamily domains (two variable-region set and three constant-region set), a single hydrophobic, membrane-spanning domain, and a cytoplasmic domain of 59 residues. The overall structure is similar to that of the human tumor marker MUC 18 and the chicken neural adhesion molecule SC1. The extracellular domains and cytoplasmic domain contain consensus motifs for the binding of integrin and Src homology 3 domains, respectively, suggesting possible receptor and signal-transduction function. Immunostaining of human tissues demonstrated a wide distribution and provided evidence that the glycoprotein is under developmental control in liver and may also be regulated during differentiation in other tissues.

Neural basis of lexical-semantic processing and integration of symbolic gestures with words

Three studies investigated the relation between symbolic gestures and words, aiming at discover the neural basis and behavioural features of the lexical semantic processing and integration of the two communicative signals. The first study aimed at determining whether elaboration of communicative signals (symbolic gestures and words) is always accompanied by integration with each other and, if present, this integration can be considered in support of the existence of a same control mechanism. Experiment 1 aimed at determining whether and how gesture is integrated with word. Participants were administered with a semantic priming paradigm with a lexical decision task and pronounced a target word, which was preceded by a meaningful or meaningless prime gesture. When meaningful, the gesture could be either congruent or incongruent with word meaning. Duration of prime presentation (100, 250, 400 ms) randomly varied. Voice spectra, lip kinematics, and time to response were recorded and analyzed. Formant 1 of voice spectra, and mean velocity in lip kinematics increased when the prime was meaningful and congruent with the word, as compared to meaningless gesture. In other words, parameters of voice and movement were magnified by congruence, but this occurred only when prime duration was 250 ms. Time to response to meaningful gesture was shorter in the condition of congruence compared to incongruence. Experiment 2 aimed at determining whether the mechanism of integration of a prime word with a target word is similar to that of a prime gesture with a target word. Formant 1 of the target word increased when word prime was meaningful and congruent, as compared to meaningless congruent prime. Increase was, however, present for whatever prime word duration. In the second study, experiment 3 aimed at determining whether symbolic prime gesture comprehension makes use of motor simulation. Transcranial Magnetic Stimulation was delivered to left primary motor cortex 100, 250, 500 ms after prime gesture presentation. Motor Evoked Potential of First Dorsal Interosseus increased when stimulation occurred 100 ms post-stimulus. Thus, gesture was understood within 100ms and integrated with the target word within 250 ms. Experiment 4 excluded any hand motor simulation in order to comprehend prime word. The effect of the prior presentation of a symbolic gesture on congruent target word processing was investigated in study 3. In experiment 5, symbolic gestures were presented as primes, followed by semantically congruent target word or pseudowords. In this case, lexical-semantic decision was accompanied by a motor simulation at 100ms after the onset of the verbal stimuli. Summing up, the same type of integration with a word was present for both prime gesture and word. It was probably subsequent to understanding of the signal, which used motor simulation for gesture and direct access to semantics for words. However, gesture and words could be understood at the same motor level through simulation if words were preceded by an adequate gestural context. Results are discussed in the prospective of a continuum between transitive actions and emblems, in parallelism with language; the grounded/symbolic content of the different signals evidences relation between sensorimotor and linguistic systems, which could interact at different levels.

Stability and sensitivity analysis of Be-CoDiS, an epidemiological model to predict the spread of human diseases between countries. Validation with data from the 2014-16 West African Ebola Virus Disease epidemic.

Ebola virus disease is a lethal human and primate disease that requires a particular attention from the international health authorities due to important recent outbreaks in some Western African countries and isolated cases in European and North-America continents. Regarding the emergency of this situation, various decision tools, such as mathematical models, were developed to assist the authorities to focus their efforts in important factors to eradicate Ebola. In a previous work, we have proposed an original deterministic spatial-temporal model, called Be-CoDiS (Between-Countries Disease Spread), to study the evolution of human diseases within and between countries by taking into consideration the movement of people between geographical areas. This model was validated by considering numerical experiments regarding the 2014-16 West African Ebola Virus Disease epidemic. In this article, we propose to perform a stability analysis of Be-CoDiS. Our first objective is to study the equilibrium states of simplified versions of this model, limited to the cases of one an two countries, and to determine their basic reproduction ratios. Then, in order to give some recommendations for the allocation of resources used to control the disease, we perform a sensitivity analysis of those basic reproduction ratios regarding the model parameters. Finally, we validate the obtained results by considering numerical experiments based on data from the 2014-16 West African Ebola Virus Disease epidemic.

The International Human Rights Policies of New Democracies: Brazil and Chile in Comparative Perspective

Since the beginning of the 1990s, the majority of Latin American states have attempted to incorporate in some way or another human rights concern into their respective foreign policies, highlighting a history of human rights abuses and the return of democratic political rule as a trigger for galvanizing a commitment to assist in preventing such violations in other countries. Yet, while human rights have come to play a non-trivial role in the contemporary foreign policy of many Latin American states, there is great diversity in the ways and the extent to which they go about incorporating human rights concerns into their foreign policies. Explaining the diversity of human rights foreign policies of new Latin American democracies is at the heat of this project. The main research questions are the following: Why do new democracies incorporate human rights into their foreign policies? And what explains the different international human rights policies of new democracies? To answer these questions, this research compares the human rights foreign policies of Chile and Brazil for over two decades starting from their respective transitions to democracy. The study argues that states commitment to international human rights is the result of the intersection of domestic and international influences. At the international level, the search for international legitimacy and the desire for recognition and credibility affected the adoption of international human rights in both cases but with different degrees of impact. International values and pressures by themselves, while necessary, are an insufficient condition for human rights initiatives perceived to have not insubstantial political, economic or strategic costs. New democracies will be more or less likely to actively include human rights in their international policies depending on the following four domestic conditions: political leadership legitimizing the inclusion of human rights into a state's policies, civil society groups connected to international human rights advocacy networks with a capacity to influencing the foreign policy decisions of their government, and the Foreign Ministry's attitudes towards international human rights and the degree of influence it exercises over the outcome of the foreign policy process.

Human Motion Analysis Based on Sequential Modeling of Radar Signal and Stereo Image Features

Falls are one of the greatest threats to elderly health in their daily living routines and activities. Therefore, it is very important to detect falls of an elderly in a timely and accurate manner, so that immediate response and proper care can be provided, by sending fall alarms to caregivers. Radar is an effective non-intrusive sensing modality which is well suited for this purpose, which can detect human motions in all types of environments, penetrate walls and fabrics, preserve privacy, and is insensitive to lighting conditions. Micro-Doppler features are utilized in radar signal corresponding to human body motions and gait to detect falls using a narrowband pulse-Doppler radar. Human motions cause time-varying Doppler signatures, which are analyzed using time-frequency representations and matching pursuit decomposition (MPD) for feature extraction and fall detection. The extracted features include MPD features and the principal components of the time-frequency signal representations. To analyze the sequential characteristics of typical falls, the extracted features are used for training and testing hidden Markov models (HMM) in different falling scenarios. Experimental results demonstrate that the proposed algorithm and method achieve fast and accurate fall detections. The risk of falls increases sharply when the elderly or patients try to exit beds. Thus, if a bed exit can be detected at an early stage of this motion, the related injuries can be prevented with a high probability. To detect bed exit for fall prevention, the trajectory of head movements is used for recognize such human motion. A head detector is trained using the histogram of oriented gradient (HOG) features of the head and shoulder areas from recorded bed exit images. A data association algorithm is applied on the head detection results to eliminate head detection false alarms. Then the three dimensional (3D) head trajectories are constructed by matching scale-invariant feature transform (SIFT) keypoints in the detected head areas from both the left and right stereo images. The extracted 3D head trajectories are used for training and testing an HMM based classifier for recognizing bed exit activities. The results of the classifier are presented and discussed in the thesis, which demonstrates the effectiveness of the proposed stereo vision based bed exit detection approach.

Human Rights in the Democratic People's Republic of Korea and the Future of the Troubled State after Kim Jong-Il

Since 2008, international speculation about the viability of Kim Jong-Il's leadership in North Korea has been at the forefront of diplomatic discussions. North Korea is known to be a secretive state where human rights violations abound. This paper discusses the history of leadership and government in North Korea since World War II, the current human rights situation in the country, the role of China, and potential successors to Kim Jong-Il. The ramifications of impending regime change are discussed in terms of North Korea's human rights issues and economic problems. While current efforts at diplomacy have proved ineffective, the need for concerned nations, intergovernmental organizations, and non-governmental organizations to be prepared to engage North Korea after Kim Jong-Il is imperative.

Em busca da originalidade do patrimônio cultural na cidade-espetáculo: o caso da Casa Boehm em Joinville/SC

Este trabalho tem o intuito de discutir como um imóvel tombado na cidade de Joinville/SC vem respondendo ao mundo das influências contemporâneas da espetacularização. A Casa Boehm, hoje uma loja de calçados no comércio, foi construída em 1927 e tombada em 2001, por meio do Processo de Tombamento PFCC n. 627/003, de 10 de abril de 2000, homologado pelo Decreto n. 3.461/2001, do Governador do Estado, na época, Esperidião Amin. O imóvel vem sofrendo alterações físicas, que afetam princípios de unidade, volumetria, padrões de estilo arquitetônico, o que faz com surjam debates a respeito dos seus valores estéticos. A depender do gosto dos locatários, especialmente no que se referee às cores externas, sem autorização, vislumbra-se a partir da opinião dos participantes do Conselho de Patrimônio da cidade - COMPHAAN, a espetacularização que este bem vem suportando em nome de uma sociedade de consumo, que apenas visa o lucro, apesar de inúmeros debates teóricos acerca da preservação. Desta forma, quando se pensa em restauração de um patrimônio cultural edificado, a preocupação imanente é com a sua imagem subjetiva/simbólica, e ainda, não menos importante, no que se refere às cores utilizadas nas pinturas das edificações. A metodologia utilizada é qualitativa, por meio de pesquisa bibliográfica, documentais no Arquivo Histórico de Joinville – AHJ e na Fundação Cultural de Joinville – FCJ e, etnográfica. A etnografia, com nuances interdisciplinares, foi realizada nestes mesmos Arquivos da cidade de Joinville, nos arredores do bem em questão e analisando algumas impressões obtidas nas reuniões do Conselho de Patrimônio da cidade – COMPHAAN. Este estudo é parte integrante da pesquisa para doutoramento em Ciências Humanas, na Universidade Federal de Santa Catarina – UFSC. Parte-se da hipótese inicial de que as discussões que envolvem as cores em bens tombados têm se relacionado com a autenticidade e a integridade dos conjuntos nos centros históricos. Porém, vai além, já que o espetáculo buscado pelos gestores públicos, com intento de valorizar suas cidades, acaba por homogeneizar esses territórios em torno de uma ideia de patrimônio que tem sido questionada por alguns teóricos.

Departments of Labor, Health and Human Services, and Education, and related agencies appropriations for fiscal year 1994 : hearings before a Subcommittee of the Committee on Appropriations, United States Senate, One Hundred Third Congress, first session.

Shipping list no. 94-0642-P (pt. 1).

Technicians of Human Dignity : Bodies, Souls, and the Making of Intrinsic Worth /

Tracks the development of the concept of human dignity in post-war ethics and politics, focusing on the Vatican, the United Nations, and U.S. Federal Bioethics. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

Occupational safety & health : assuring accuracy in employer injury and illness records : report to the chairman, Subcommittee on Labor, Health and Human Services, and Education, Committee on Appropriations, U.S. Senate /

"B-232872"--P. 1.

Multiple employment training programs : overlap among programs raises questions about efficiency : report to the Chairman, Subcommittee on Labor, Health and Human Services and Education, Committee on Appropriations, U.S. Senate /

"B-257662"--P. 1.

Landmarks and surface markings of the human body ... with thirty-one illustrations.

Some of the plates accompanied by leaves with descriptive letterpress.