Miracle-dz/UniFAR-FTUs huggingface dataset:
Century Epidemic Cardiovascular Disease : From Treatment to Promoting Health ; A Challenge for the Next Decade

Cardiovascular disease (CVD) is the most prevalent cause of mortality across the globe [1-2]. Of every 10 deaths worldwide, 6 are due to noncommunicable conditions; 3 to communicable, reproductive or nutritional conditions; and 1 to injuries. Of the noncommunicable conditions CVD is by far the most prevalent cause of death, accounting for at least 30-40% of mortality attributable to noncommunicable conditions [2]. Importantly, CVD can manifest in many ways, including as coronary artery disease (CAD) and myocardial infarction, stoke, renal failure, aortic aneurysm and degenerative brain disease (DBD). This massive burden of disease consumes a significant share of the world’s fiscal and health care resources, and has a major, adverse influence on the physical and mental wellbeing of patients and their families. Added to this, in many nations the looming ‘aging epidemic’ will soon compound this problem. Framed by the aging ‘baby-boomer’ cohort, the number of persons at risk for CAD and CVD is predicted to increase dramatically in the coming decade [1], which will place significant additional demands on health care resources. Meeting the challenges of the ‘aging epidemic’ is something that will assume increasing importance in the coming decade. Moreover, as can already be seen from this complex matrix of factors, attempts at reducing the morbidity and mortality attributable to CVD will require a multi-pronged approach spanning biology, treatment modalities, societal attitudes and health care resource utilization [3].
On the relations between behaviour, mechanism, and environment : explorations in artificial evolution

This thesis presents an externalist exploration of the relations between behaviour, mechanism, and environment, as they arise in a variety of agent-environment systems. It offers contributions at conceptual, methodological, and empirical levels of discourse. Externalism describes the attempt to understand the internal in terms of the external, and the thesis begins by developing a conceptual framework justifying the use of artificial evolution models in the application of this perspective to agent-environment systems. In particular, it is argued that such models play a crucial role in elaborating the distinction between behavioural and mechanistic levels of description. There follows a series of models, of both game-theoretic and evolutionary-robotic character, which focus on explaining internal ‘complexity’ in terms of adaptation to (external) environmental variability. As part of this project, accounts of the ‘evolution of complexity’ in general are critiqued, and the practical importance of noise in artificial evolution is discussed. The thesis continues with an integration of this externalist project with the well established theoretical biology methodology of ‘optimal foraging theory’. A novel methodology ‘individualbased optimal situated modelling’ is described, which extends orthodox optimal foraging theory through (1) the use of artificial evolution as an optimisation procedure and, (2) modelling agentenvironment interaction at the level of situated perception and action. The conceptual leverage afforded by this extension is illustrated in its application to the problem of behaviour coordination in a simple agent-environment system; for example, the need for a dedicated ‘action selection mechanism’ is questioned. The methodology is then addressed to a range of issues in contemporary theoretical biology and psychology: the ‘interference function’, the ‘ideal free distribution’, and the ‘individual matching law’, issues which are united by a concern with individual choice and its collective consequences. A series of models are presented which demonstrate, in these contexts, that (1) behaviours for which there is debate about the level of complexity required for their underlying mechanism, can be subserved by surprisingly simple mechanisms, and (2) behaviours which may be irrational when expressed by an isolated individual can be understood as rational in a group context. Submitted for the degree of D. Phil. University of Sussex
Key roles of retinoic acid receptors alpha and beta in the patterning of the caudal hindbrain, pharyngeal arches and otocyst in the mouse.

Mouse fetuses carrying targeted inactivations of both the RAR(&agr;) and the RARbeta genes display a variety of malformations in structures known to be partially derived from the mesenchymal neural crest originating from post-otic rhombomeres (e.g. thymus and great cephalic arteries) (Ghyselinck, N., Dupé, V., Dierich, A., Messaddeq, N., Garnier, J.M., Rochette-Egly, C., Chambon, P. and Mark M. (1997). Int. J. Dev. Biol. 41, 425-447). In a search for neural crest defects, we have analysed the rhombomeres, cranial nerves and pharyngeal arches of these double null mutants at early embryonic stages. The mutant post-otic cranial nerves are disorganized, indicating that RARs are involved in the patterning of structures derived from neurogenic neural crest, even though the lack of RARalpha and RARbeta has no detectable effect on the number and migration path of neural crest cells. Interestingly, the double null mutation impairs early developmental processes known to be independent of the neural crest e.g., the initial formation of the 3rd and 4th branchial pouches and of the 3rd, 4th and 6th arch arteries. The double mutation also results in an enlargement of rhombomere 5, which is likely to be responsible for the induction of supernumerary otic vesicles, in a disappearance of the rhombomere 5/6 boundary, and in profound alterations of rhombomere identities. In the mutant hindbrain, the expression domain of kreisler is twice its normal size and the caudal stripe of Krox-20 extends into the presumptive rhombomeres 6 and 7 region. In this region, Hoxb-1 is ectopically expressed, Hoxb-3 is ectopically up-regulated and Hoxd-4 expression is abolished. These data, which indicate that retinoic acid signaling through RARalpha and/or RARbeta is essential for the specification of rhombomere identities and for the control of caudal hindbrain segmentation by restricting the expression domains of kreisler and of Krox-20, also strongly suggest that this signaling plays a crucial role in the posteriorization of the hindbrain neurectoderm.
Principles of Genome Evolution in the Drosophila melanogaster Species Group

That closely related species often differ by chromosomal inversions was discovered by Sturtevant and Plunkett in 1926. Our knowledge of how these inversions originate is still very limited, although a prevailing view is that they are facilitated by ectopic recombination events between inverted repetitive sequences. The availability of genome sequences of related species now allows us to study in detail the mechanisms that generate interspecific inversions. We have analyzed the breakpoint regions of the 29 inversions that differentiate the chromosomes of Drosophila melanogaster and two closely related species, D. simulans and D. yakuba, and reconstructed the molecular events that underlie their origin. Experimental and computational analysis revealed that the breakpoint regions of 59% of the inversions (17/29) are associated with inverted duplications of genes or other nonrepetitive sequences. In only two cases do we find evidence for inverted repetitive sequences in inversion breakpoints. We propose that the presence of inverted duplications associated with inversion breakpoint regions is the result of staggered breaks, either isochromatid or chromatid, and that this, rather than ectopic exchange between inverted repetitive sequences, is the prevalent mechanism for the generation of inversions in the melanogaster species group. Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance.
The Impacts of Population Subdivision on the Viability of Brachyteles hypoxanthus

Habitat loss and fragmentation turn continuous large populations into metapopulations of smaller populations, more prone to the negative effects of stochastic processes. We modeled scenarios simulating the subdivision of Brachyteles hypoxanthus populations under different dispersal rates. Results show the existence of a population subdivision threshold, below which subdivision causes the metapopulation structure to collapse. Management should target first the increase in local populations through habitat restoration/protection, and only after populations are sufficiently large, connectivity strategies should take place.
Neural Network Models as Evidence for Different Types of Visual Representations

Cook (1995) criticizes the work of Jacobs and Kosslyn (1994) on spatial relations, shape representations, and receptive fields in neural network models on the grounds that first-order correlations between input and output unit activities can explain the results. We reply briefly to Cook's arguments here (and in Kosslyn, Chabris, Marsolek, Jacobs & Koenig, 1995) and discuss how new simulations can confirm the importance of receptive field size as a crucial variable in the encoding of categorical and coordinate spatial relations and the corresponding shape representations; such simulations would testify to the computational distinction between the different types of representations.
The psychological puzzle of Sudoku

Sudoku puzzles, which are popular worldwide, require individuals to infer the missing digits in a 9 × 9 array according to the general rule that every digit from 1 to 9 must occur once in each row, in each column, and in each of the 3-by-3 boxes in the array. We present a theory of how individuals solve these puzzles. It postulates that they rely solely on pure deductions, and that they spontaneously acquire various deductive tactics, which differ in their difficulty depending on their “relational complexity”, i.e., the number of constraints on which they depend. A major strategic shift is necessary to acquire tactics for more difficult puzzles: solvers have to keep track of possible digits in a cell. We report three experiments corroborating this theory. We also discuss their implications for theories of reasoning that downplay the role of deduction in everyday reasoning.
Sonic hedgehog signaling from the urethral epithelium controls external genital development.

External genital development begins with formation of paired genital swellings, which develop into the genital tubercle. Proximodistal outgrowth and axial patterning of the genital tubercle are coordinated to give rise to the penis or clitoris. The genital tubercle consists of lateral plate mesoderm, surface ectoderm, and endodermal urethral epithelium derived from the urogenital sinus. We have investigated the molecular control of external genital development in the mouse embryo. Previous work has shown that the genital tubercle has polarizing activity, but the precise location of this activity within the tubercle is unknown. We reasoned that if the tubercle itself is patterned by a specialized signaling region, then polarizing activity may be restricted to a subset of cells. Transplantation of urethral epithelium, but not genital mesenchyme, to chick limbs results in mirror-image duplication of the digits. Moreover, when grafted to chick limbs, the urethral plate orchestrates morphogenetic movements normally associated with external genital development. Signaling activity is therefore restricted to urethral plate cells. Before and during normal genital tubercle outgrowth, urethral plate epithelium expresses Sonic hedgehog (Shh). In mice with a targeted deletion of Shh, external genitalia are absent. Genital swellings are initiated, but outgrowth is not maintained. In the absence of Shh signaling, Fgf8, Bmp2, Bmp4, Fgf10, and Wnt5a are downregulated, and apoptosis is enhanced in the genitalia. These results identify the urethral epithelium as a signaling center of the genital tubercle, and demonstrate that Shh from the urethral epithelium is required for outgrowth, patterning, and cell survival in the developing external genitalia.
Enhanced Phosphorylation of Transcription Factor Sp1 in Response to Herpes Simplex Virus Type 1 Infection Is Dependent on the Ataxia Telangiectasia-Mutated Protein

ABSTRACT The ataxia telangiectasia-mutated (ATM) protein, a member of the related phosphatidylinositol 3-like kinase family encoded by a gene responsible for the human genetic disorder ataxia telangiectasia, regulates cellular responses to DNA damage and viral infection. It has been previously reported that herpes simplex virus type 1 (HSV-1) infection induces activation of protein kinase activity of ATM and hyperphosphorylation of transcription factor, Sp1. We show that ATM is intimately involved in Sp1 hyperphosphorylation during HSV-1 infection rather than individual HSV-1-encoded protein kinases. In ATM-deficient cells or cells silenced for ATM expression by short hairpin RNA targeting, hyperphosphorylation of Sp1 was prevented even as HSV-1 infection progressed. Mutational analysis of putative ATM phosphorylation sites on Sp1 and immunoblot analysis with phosphopeptide-specific Sp1 antibodies clarified that at least Ser-56 and Ser-101 residues on Sp1 became phosphorylated upon HSV-1 infection. Serine-to-alanine mutations at both sites on Sp1 considerably abolished hyperphosphorylation of Sp1 upon infection. Although ATM phosphorylated Ser-101 but not Ser-56 on Sp1 in vitro, phosphorylation of Sp1 at both sites was not detected at all upon infection in ATM-deficient cells, suggesting that cellular kinase(s) activated by ATM could be involved in phosphorylation at Ser-56. Upon viral infection, Sp1-dependent transcription in ATM expression-silenced cells was almost the same as that in ATM-intact cells, suggesting that ATM-dependent phosphorylation of Sp1 might hardly affect its transcriptional activity during the HSV-1 infection. ATM-dependent Sp1 phosphorylation appears to be a global response to various DNA damage stress including viral DNA replication.
Selectivity of TMC207 towards Mycobacterial ATP Synthase Compared with That towards the Eukaryotic Homologue

ABSTRACT The diarylquinoline TMC207 kills Mycobacterium tuberculosis by specifically inhibiting ATP synthase. We show here that human mitochondrial ATP synthase (50% inhibitory concentration [IC50] of >200 μM) displayed more than 20,000-fold lower sensitivity for TMC207 compared to that of mycobacterial ATP synthase (IC50 of 10 nM). Also, oxygen consumption in mouse liver and bovine heart mitochondria showed very low sensitivity for TMC207. These results suggest that TMC207 may not elicit ATP synthesis-related toxicity in mammalian cells. ATP synthase, although highly conserved between prokaryotes and eukaryotes, may still qualify as an attractive antibiotic target.
Inflammation and dental pain in man.

In the present article special interest has been focused on indicators of latent and manifest pulpal inflammation studied by psychophysical and electrophysiological techniques. Intradental A-delta nerve activity was recorded from two electrodes placed in the dentin on the labial tooth surface. The psychophysical measures were obtained by means of direct scaling methods in combination with sensory verbal descriptors. For stimulation cooling (ethyl chloride) and heating (hot guttapercha) of the tooth surface were employed. In addition, potentially algogenic substances, bradykinin and histamine, were administered on partly exposed pulps. Hot guttapercha induced a more complex neural response pattern than ethyl chloride. In all the recordings the responses evoked by heat showed a characteristic pattern consisting of three phases: an initial phase of short duration (i) followed by a depression in activity relative to the baseline (ii) and a slow spontaneously emerging activity in the absence of a physical stimulus (iii). The latter neutral event (iii) passed unnoticed by all the subjects. In the light of earlier experiments on feline pulp it was hypothesized that this third phase of the neural response was an indication of hyperexcitability in dental pulps and thus inflammation. Those subjects who experienced pulsating, dull, lingering pain (clinically diagnosed as pulpitis) showed a poor correlation between magnitude estimates of their mixed pain percepts and the total flux of A-delta nerve activity. Bradykinin and histamine evoked dull pain in the majority of cases probably caused by excitation of pulpal C fibers. In one experiment A-delta neural discharge of short duration could also be triggered by histamine. (ABSTRACT TRUNCATED AT 250 WORDS)
Microstructural and tribological characterisation of as sprayed and heat treated HVOF deposited Ni alloys

Abstract The microstructural, micromechanical (Vickers microindentation, scratch testing) and tribological (pin on disk tests against steel and alumina spherical pins) properties of three High velocity oxy–fuel (HVOF) sprayed Ni based alloy coatings, namely Diamalloy 4006 (Ni–20Cr–10W–9Mo–4Cu–1B–1C–1Fe), Tribaloy-700 (Ni–32Mo–16Cr–4Si–2Co) and Inconel-625 (Ni–22Cr–9Mo–4Nb), were characterised, both in the as sprayed condition and after thermal treatments at 600°C and 800°C. As deposited Tribaloy-700 possesses a low degree of crystallinity and lower hardness; crystalline intermetallics are formed after heat treatments, definitely improving mechanical strength and tribological resistance against 100Cr6 steel counterpart, but not against alumina counterpart. The Inconel-625 and Diamalloy 4006 as sprayed coatings consist of supersaturated crystalline solid solutions. The former is not much affected by heat treatments and has low hardness and poor tribological properties. The latter, instead, displays precipitation of secondary phases after heat treatment. Particularly, the 600°C treatment improves coating strength and wear resistance against steel, whereas the 800°C one is less effective, probably because it causes excessive crystal grain size increase.
Scaling Up Malaria Control in Zambia: Progress and Impact 2005–2008

Dear Sir: Your publication of the assessment of Zambia's National Malaria Control Program by Elizabeth Chizema-Kaweshia and others1 documents successful outcomes using evidence-based Integrated Vector Management in Zambia. World Health Organization (WHO) recommendations and goals of the Global Roll Back Malaria Partnership contributed a proven framework for implementing Zambia's national malaria control strategies. There is agreement regarding Integrated Vector Management as an important strategy for the national prevention and control of malaria in Zambia and other African Countries with endemic malaria.2 An integrated approach to vector management is critical to maintaining and improving Zambia's extensive collaborative efforts with multilateral and bilateral agencies and stakeholders globally and nationally. Between 2005 and 2008, Zambia applied Integrated Vector Management to malaria prevention and control. The results showed measurable improvements in the successful prevention and advancement of malaria control in Zambia. However, the authors did not acknowledge achievements and compare lessons learned from other African countries recording similar success with malaria control programs. There is a lack of data regarding capacity building for health communication among indigenous people in Zambia.3 Health communication tools and strategies in Zambia's Strategic Plan would support advocacy for wider rural community participation, coverage, and leadership.
Fur and the Novel Regulator YqjI Control Transcription of the Ferric Reductase Gene yqjH in Escherichia coli

ABSTRACT Iron acquisition in aerobic habitats is complicated by the low solubility of ferric hydroxides. Siderophores that bind ferric iron with high affinity are used to mobilize iron. The reduction of ferric iron to the ferrous form can be coupled to the release of iron from siderophores. Iron is also stored intracellularly as a ferric mineral in proteins, such as ferritin, and must be reduced during release. In Escherichia coli, the yqjH gene encodes a putative ferric siderophore reductase that is also part of the Fur regulon. Here we show that YqjH has ferric reductase activity and is required for iron homeostasis in E. coli. Divergently transcribed from yqjH is the yqjI gene, which encodes a novel member of the winged-helix family of transcriptional regulators and also contains an N-terminal extension similar to the Ni2+-binding C-terminal tail of SlyD. Deletion of yqjI leads to constitutive high-level activity of the yqjH and yqjI promoters. Purified YqjI binds inverted repeat target sequences within the yqjH and yqjI promoters. We also observed that YqjI-dependent transcriptional repression is reduced when cells are exposed to elevated nickel levels, resulting in increased expression of yqjH and yqjI. YqjI binding to nickel or iron reduces YqjI DNA-binding activity in vitro. Furthermore, we found that elevated nickel stress levels disrupt iron homeostasis in E. coli and that deletion of yqjH increases nickel toxicity. Our results suggest that the YqjI protein controls expression of yqjH to help maintain iron homeostasis under conditions (such as elevated cellular nickel levels) that disrupt iron metabolism.
Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages

The effects of different polyphenol-containing beverages on Fe absorption from a bread meal were estimated in adult human subjects from the erythrocyte incorporation of radio-Fe. The test beverages contained different polyphenol structures and were rich in either phenolic acids (chlorogenic acid in coffee), monomeric flavonoids (herb teas, camomile (Matricaria recutita L.)), vervain (Verbena officinalis L.), lime flower (Tilia cordata Mill.), pennyroyal (Mentha pulegium L.) and peppermint (Mentha piperita L.), or complex polyphenol polymerization products (black tea and cocoa). All beverages were potent inhibitors of Fe absorption and reduced absorption in a dose-dependent fashion depending on the content of total polyphenols. Compared with a water control meal, beverages containing 20–50 mg total polyphenols/serving reduced Fe absorption from the bread meal by 50–70 %, whereas beverages containing 100–400 mg total polyphenols/serving reduced Fe absorption by 60–90 %. Inhibition by black tea was 79–94 %, peppermint tea 84 %, pennyroyal 73 %, cocoa 71 %, vervain 59 %, lime flower 52 % and camomile 47 %. At an identical concentration of total polyphenols, black tea was more inhibitory than cocoa, and more inhibitory than herb teas camomile, vervain, lime flower and pennyroyal, but was of equal inhibition to peppermint tea. Adding milk to coffee and tea had little or no influence on their inhibitory nature. Our findings demonstrate that herb teas, as well as black tea, coffee and cocoa can be potent inhibitors of Fe absorption. This property should be considered when giving dietary advice in relation to Fe nutrition.