Brain topography. A comparison of two EIT systems suitable for imaging impedance changes in epilepsy. Physiological measurement. An electrical impedance tomography system for gynecological application GIT with a tiny electrode array. Electrical resistivity survey in soil science: a review. Soil and Tillage Research. Electrical resistance tomography for process applications.
Measurement Science and Technology. Determining cracks by boundary measurements. Indiana University Mathematics Journal. Application of electrical resistance tomography to interrogate mixing processes at plant scale. Chemical Engineering Science. Movement artefact rejection in impedance pneumography using six strategically placed electrodes. Andrade de coronariopatias. Figura 2: Principais componentes de um biossensor. O imunossensor apresentou bom desempenho em amostras reais. O anticorpo anti TnI foi imobilizado na matriz de ouro e caracterizado por microscopia confocal.
Os testes controle confirmaram a especificidade do dispositivo . O eletrodo foi funcionalizado com cisteamina e gluta- Tratado de Medicina Cardiovascular. Acute coronary syndromes without chest pain, an underdiagnosed and undertreated high-risk group: insights from the global registry of acute coronary events. Chest, 2 : ,  Anderson JL.
In: Goldman, L. Tratado de Medicina Interna. Eletrocardiography: Biophysical Measurement Series. Textbook of medical physiology. Cardiac markers of myocardial necrosis.
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A history and discussion of milestones and emerging new trends. Clinics in Laboratory Medicine, v. Current applications of cardiac troponin T for the diagnosis of myocardial damage. Advances in Clinical Chemistry, v. Cardiac biomarkers - the old and the new: a review. Coronary Artery Disease, v. From DNA biosensors to gene chips. Nucleic Acids Research, v. Biosensor Recognition Elements. Current issues in molecular biology, v. Sensors, v. Biosensors and bioelectrochemistry. Current Opinion in Chemical Biology, v.
Fiber-Optic Biosensors - Trends and Advances. Analytical Sciences, v. Electrochemical biosensors: recommended definitions and classification. Biosensors and Bioelectronics, v. Biosensors: Fundamentals and applications. Evaluation of antibody immobilization methods for piezoelectric biosensor application. Calorimetric biosensors. Journal of Biotechnology, v. Molecular Sensors and Nanodevices. Surface plasmon resonance analysis of dynamic biological interactions with biomaterials. Biomaterials, v. Surface Plasmon Resonance measurements of ultrathin organic films at electrode surfaces.
Electroanalytical Chemistry, v. Cardiac biomarkers in acute myocardial infarction. International Journal of Cardiology, v. A disposable single-use electrochemical sensor for the detection of uric acid in human whole blood, Sensors and Actuators B: Chemical, v. Andrade  Tymecki L, Koncki R. Thick-film potentiometric biosensor for bloodless monitoring of hemodialysis, Sensor and Actuators B: Chemical, v.
A Multivariate logistical model for identifying the compressive sensitivity of single rat tactile receptors as nanobiosensors. Journal of Nanotechnology in Engineering and Medicine, v. Biomarkers in acute coronary syndrome. Biomark Insights, v. Measurement of cardiac troponins. Annals of Clinical Biochemistry, v. Sociedade Brasileira de Cardiologia. Arquivos Brasileiros de Cardiologia, v. Troponin T is a strong marker of mortality in hospitalized patients. International Journal of Cardiology. Cardiac troponin in ischemic cardiomyocytes: Intracellular decrease before onset of cell death.
A nanostructured piezoelectric immunosensor for detection of human cardiac troponin T. Sensors Basel , v. Surface plamon resonance biosensor with high anti-fouling ability for the detection of cardiac marker troponin T. Analytica Chimica Acta, v. Gold nanoparticles mediated label-free capacitance detection of cardiac troponin I.
Sensors and actuators B: Chemical, v. Disposable immunosensor for human cardiac troponin T based on streptavidin-micros- Biomarkers and cardiovascular risk assessment for primary prevention: an update. Clinical chemistry, v. Identifying novel biomarkers for cardiovascular disease risk prediction. Journal of internal medicine, v. Metabolic biomarkers for predicting cardiovascular disease. Vascular health and risk management, v. Biochemical markers in acute coronary syndrome. Clinica chimica acta; international journal of clinical chemistry, v. Label-free detection of C-reactive protein using a carbon nanofiber based biosensor.
Reusable gold nanoparticle enhanced QCM immunosensor for detecting C-reactive protein. Sensors and Actuators B: Chemical, v. Electrochemical investigations of the interaction of C-reactive protein CRP with a CRP antibody chemically immobilized on a gold surface. Analytica chimica acta, v. An optimised electrochemical biosensor for the label-free detection of C-reactive protein in blood. Multiwalled carbon nanotubes embedded molecularly imprinted polymer-modified screen printed carbon electrode for the quantitative analysis of C-reactive protein.
Nanotechnology in Biodevices. Journal of Microbiology and Biotechnology, v. Engineering Nanomaterial Surfaces for Biomedical Applications. Experimental Biology and Medicine, v. A carbon nanotube screen-printed electrode for label-free detection of the human cardiac troponin T. Introduction Among the earliest references in the literature to mosquitoes are certain passages in Aristotle s Historia Animalium. Aristotle tells that many animals live at first in water and afterwards change their form.
About years after Aristotle, the Roman author Caius Plinius Secundus, better known as Pliny the Elder, describes the gnat as an example of the wonderfulness of nature in providing on such a small scale the organs required for the five senses and other life requirements. Among other things he comments on the fineness and perfection of the small and sharp sucking tube used to suck in and convey the blood . Robert Hooke published in his microscopy observations in the book Micrographia. Seemingly the first author to do so, he describes and figures the Culex larva.
The larva is depicted as having jaws rather like a crustacean, which can be seen extracting invisible nourishment from the water. The author also shows the sequence of larva, pupa and imago. Hooke refers to spon-. One of the earliest works to give special importance to the Aedes aegypti mosquito species was done by Carlos Juan Finlay, who as early as had associated it with the transmission of yellow fever and made observations on its habits.
From onwards, it became the yellow fever mosquito and has ever since acquired a vast literature . Domestic water pots, cisterns, flower vases and shaded rooms with cupboards and hanging equipments and humans to feed upon provide suitable loci for Aedes aegypti thriving. The mosquito does not find conditions so suitable where communities are well housed with permanent water supply and good drainage system and tidier house habits .
Aedes aegypti is the usual vector species for two, namely dengue and yellow fever, among the four most important human diseases transmitted by mosquitoes: malaria, yellow fever, dengue and filariasis. It has also been the subject of considerable research before it could be established that it did not play an important role as a vector of filariasis.
Whilst Aedes aegypti plays little part in forest or sylvan yellow fever, it still remains the sole vector and cause of urban epidemics. Indeed, it is now generally recognized as the usual vector of dengue . Figure 1 shows the geographical distribution of Aedes aegypti and the prevalence of dengue. Dengue fever is a viral infection with symptoms that range from influenza like to haemorraghic and shock syndromes. Dengue has seen a four-fold increase in incidence since and is a major public health problem threatening an estimated 2.
It is also the leading cause of infant death in Asia, and this re-emergence is a serious burden for public health systems world wide [3, 6, 33]. Currently, control of Aedes aegypti populations is the only form of dengue prevention, given that at present there is neither aetiological treatment, chemoprophylaxis, nor vaccine [30, 49]. Styer et al. The longer a mosquito lives, the more likely it is to encounter an infectious host, survive the incubation period, and transmit an infectious Schechtman, D.
Villela, C. Oliveira Souza agent during subsequent feeding attempts. Their work has shown that mosquito mortality was highly age dependent in both sexes. Currently the most widely used age-grading technique for Aedes aegypti separates mosquitoes into only two age classes Figure 1: Map of dengue world distribution. Mathematical modelling of population dynamics of the Aedes aegypti mosquito, therefore, emerged as an important research topic due to the need of control of its populations at multiple localities, especially where this mosquito is a vector of diseases leading to epidemic states.
However, in order to produce meaningful predictions about the dynamics of the population, it is necessary to translate the mosquito life cycle into numbers. To achieve that, the life cycle has been modelled in many ways, either lumping together two or more stages or considering them individually. Figure 2: Schematics of the mosquito life cycle. Source: U. Centers for Disease Control and Prevention lifecycle. This last model was later improved with a delay-differential single-class model by .
Focks et al. They assumed life history parameters that are functions of temperature and humidity. Some parameters are also affected by density, such as larval mortality. Oliveira Souza Magori et al. In Skeeter Buster, genotypes were represented as a binary sequence of loci, i. The Skeeter Buster tool modelled multiple geographical premises independently. Each and every location hosted a specific set of containers both inside and outside of buildings, and the immature cohorts in these containers as well as the adults emerging from those were specifically assigned to that particular place.
Premises were laid out on a rectangular grid, each cell of the grid representing a single location. Adults could disperse between promises, allowance being made for both short and long range dispersal. However, to achieve such a location-specific level of accuracy, Skeeter Buster requires intensive field work to obtain a description of the container distribution and relative productivity in any particular location.
Indeed there were more than 60 required parameters to accurately describe the mosquito biology and life history in the geographical space. The uncertainties regarding these parameters were further investigated by Xu et al. Otero et al. The stochastic dynamical model for the evolution of Aedes aegypti was described in terms of a non-linear or state-dependent Markov chain. It considered four mosquito life stages: egg, larva, pupa, and adult. For every life stage, the relevant changes were modeled in terms of random events with temperature dependent rates.
The two dimensional space was a mesh or grid of rectangular patches where the local dynamics took place and adult mosquitoes could fly from patch to patch. The model therefore considered six different populations: eggs, larvae, pupae, non-parous adult females, migrating winged mosquitoes, and parous adult females.
The population of adult male mosquitoes was not taken into account explicitly. The model considered that one half of the emerging adults were females. Events occurred at rates that depended not only on population sizes at the various stages, but also on temperature, which in turn was a function of time since it changes over the course of the year. The results of the simulations, when compared with field data, indicate that the model reproduced the observed positivity in the ovitraps during spring and summer, but over-estimated the fraction of positive ovitraps in fall.
The model has shown high sensitivity to the number of breeding sites. A deterministic Aedes aegypti population dynamic model was developed by Ferreira and Yang . The model comprised four insect life stages: eggs, larvae, pupae and winged mosquitoes. The model also considered that the parameters oviposition, transformation and death rates were adjustable by temperature and humidity. Two yearly climates, summer hot and humid and winter cold and dry , were imposed upon the adjustable parameters. It was found that population control was most effective by elimination of eggs with the added benefit that there is no saturation for this type of control.
Employment of similar models allowed those researchers to investigate the influence of sterile insect release , temperature  and entomological parameters  on the population dynamics. Lana et al.
Fitting models to time series of mosquito trap data collected in Rio de Janeiro, Brazil, they found that these models fail to capture the population dynamics patterns observed at the scale of the neighbourhood. The authors conclude that models tend to predict more seasonal structure than it is observed. Yang et al. Q0 is a key parameter in population dynamics theory, and its mathematical expression depends on many of the details considered in the development of the model.
The parameter Q0 may be explained in biological terms as the number of eggs that will become female mosquitoes generated by a female mosquito that hatched from an egg and survived larval and pupal stages. Therefore, Q0 can also be in- Oliveira Souza terpreted roughly as the mean number of viable female off-springs produced by one female mosquito during the entire survival time.
Population Control As already discussed in the Introduction, there is no current approved vaccine for dengue, although there are several ongoing developments, and one has reached stage III clinical trials.
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This suggests that dengue transmission is better controlled at the vector level [37, 38]. Such control is usually done through the use of insecticides. However, despite an early success with the use of DDT, we are witnessing a global resurgence of dengue, with Aedes aegypti becoming increasingly more resistant to the currently used insecticides [7, 9, 15, 20, 46]. Development of insecticide resistance might undermine a number of control programs that exist worldwide .
Although regional and worldwide health organisations are trying to identify and manage such behaviour , alternative approaches are needed . We shall now review the work in modelling insecticide resistance, and discuss the proposals, together with some of the modeling, for biological control. Insecticide Resistance In order to study quantitatively the effects of resistance, Luz et al. The model considers five mosquito life stages: eggs, larvae, pupae, non-parous and parous adults, and assumes that the genetic evolution is in Hardy-Weinberg equilibrium.
For individuals with the resistance allele, the parameters for birth and death at each stage could be modulated by means of cost impairments attributed to insecticide resistance. The pictorial description of the model is given in Figure 3. The model was then employed to determine the effects of various regimes of insecticide application on population control. They found that the combined application of larval and adult insecticides during the dengue transmission season only, was the optimal strategy, minimizing long term evolution of resistance while maximizing population reduction effect.
The model was further employed as a basis for various investigations on the impact of vector activity on dengue transmission  and the economic impact of vector control . Figure 3: The mosquito life cycle genetic model describes the five life-stages by rectangular boxes. Source:  Biological Control Proposals of recent strategies for control involve biological methods due to various recent advances . Some of these advances involve the development of genetically modified Aedes aegypti strains to be used in a sterile insect pest control system in which released male mosquitoes mate with wild-type females producing non-viable progeny .
Simple deterministic population dynamic models are generally optimistic regarding the success of these techniques. The Oliveira Souza stochastic Skeeter Buster model , on the other hand, predicts that wild-type mosquito elimination or consistent reduction is highly unlikely in complex urban settings, characterized by heterogeneous landscapes where mosquito density varies in space and time as well as the efficacy of the intervention program .
It has recently been artificially introduced in several insect species [35, 47]. From the point of view of biological control, mosquitoes that are infected with Wolbachia might have reduced vector capabilities in two ways: i the reduced life span of infected individuals might avoid that the virus has time to go through its extrinsic incubation period, and so the mosquito dies before being able to transmit.
The blocking efficiency depends on the particular strain, but there are reports of near perfect blocking for some strains [21, 36]. Wolbachia is transmitted vertically, and its infection affects the host fitness usually in a negative way. In mosquitoes it reduces their survival and it might reduce its fecundity. On the other hand, Wolbachia has an advantage in its host reproduction [22, 44].
In Aedes aegypti, and in other mosquitoes in general, it induces the so-called cytoplasmic incompatibility CI : off-spring of infected males with uninfected females are less or not at all viable. This gives a transmitting advantage for off-spring with Wolbachia. In this scenario, one expects that infection-free state should be stable, and that there is threshold of infected individuals to allow for the invasion of a population infection-free. The first model to describe the dynamics of Wolbachia-infected and Wolbachia-free insect population dynamics was proposed by Turelli , using the naturally infected Drosophila fly as a biological example.
Turelli s model shows that the system is bistable with a further unstable equilibrium, whose position depends on the fitness costs versus the CI conferred advantage. Let sh denote the intensity of the cytoplasmic incompatibility, and let sv be the survival cost induced. It is A recent mathematical model that takes into account both the mosquito population dynamics, and the disease dynamics is . They start from  to construct a model with infected and uninfected mosquitoes. The system has three equilibria: uninfected, infected only and a coexistence equilibrium.
Linearised analysis shows that the coexistence equilibrium is always unstable, and the pure equilibria are always locally stable. This suggest the bi-stable behaviour mentioned above, and it was indeed verified numerically. Moreover, for such large values of R0, the final size of the epidemic is nearly unaltered. Wolbachia infection on mosquitoes and its effect on dengue was also studied by . Using a different population model, they obtain similar qualitative results of . Under some assumptions on the biological parameters and that approximately holds for literature values for Aedes aegypti they obtain a multiscale reduction that yields the bi-stable behaviour with the same threshold point obtained .
They have also calibrated the model to the first release of mosquitoes in the Australia experiment , and obtain a good agreement with the overall field data. Furthermore, using the parameters for wmel strain, they found that for several estimates of R0 in the literature, R0 should be reduced below unity upon the introduction by Wolbachia. This contrasts with the results by  who used the parameters of walb, and strengths further the 1 R0 is the number of infections caused by a single infection in the event of onset of potential epidemic.
Oliveira Souza conclusion in  that efforts in trying to establish more efficient strains of Wolbachia are worthwhile. An additional question that is now being considered is how both the virus and the mosquitoes will evolutionary react to the introduction of Wolbachia in Aedes aegypti.
In some cases, species managed to overcome the Wolbachia infection after long times, and one might speculate on the prognostics for the biological control of dengue using Wolbachia. Among their forecasts, we can single out the following: over a decade or so both life-shortening should be reduced, with the virus being selected for rapid maturation, and population suppression should also be less effective.
Transmission blocking should be overcome by the virus, but partial blocking should persist indefinitely. A mathematical modelling of this question remains an open problem. While some of the experimental and theoretical results are promising, experience has shown, however, that control methods should be taken as integrated approaches , as multiple strategies help to achieve control in an efficient manner.
Conclusion Dengue fever is currently one of the most modeled diseases. Still, many questions are open to mathematical investigation. From the purely academic perspective, some questions are: what are the evolutionary forces limiting the number of virus serotypes to four? What forces explain the cycling of virus serotypes between epidemics?
What are the forces modulating the dynamics of mild and severe dengue cases? Why dengue dynamics is characterized by a succession of small and large outbreaks? From a more pragmatic perspective, policy makers need tools to assess the cost-benefit of new control strategies. Some of them were illustrated in this document but many others will emerge in the next years, as result of large investment in new technologies.
Many vaccine candidates are also under test and proper use will require careful modeling. Models are also necessary to investigate the impact of climate change on dengue spread to temperate countries This modelling efforts require a cross-disciplinary approach as indeed found in many of the current international projects aiming to reduced and or eliminate dengue . While the task is daunting, the stakes for the benefit of the worldwide population are high. References   N.
Barton and M. Spatial waves of advance with bistable dynamics: cytoplasmic and genetic analogues of allee effects. Bhatt, P. Gething, O. Brady, J. Messina, A. Farlow, C. Moyes, J. Drake, J. Brownstein, A. Hoen, O. Sankoh, M. Myers, D. George, T. Jaenisch, G. Wint, C. Simmons, T. Scott, J. Farrar, and S. The global distribution and burden of dengue. Nat, Adv. Online, Apr  W. Brogdon and J. Insecticide resistance and vector control. Bull and M.
Wolbachia versus dengue evolutionary forecasts. Evolution, Medicine, and Public Health, 1 : ,  M. Burattini, M. Chen, A. Chow, F. Coutinho, K. Goh, L. Lopez, S. Ma, and E. Modelling the control strategies against dengue in Singapore. Chan and J. Permethrin resistance in Aedes albopictus Diptera: Culicidae and associated fitness costs. Aedes Aegypti L. The Journal of Animal Ecology, 53 1 : , Feb. Oliveira Souza  L. Esteva and H. Mathematical model to assess the control of Aedes aegypti mosquitoes by the sterile insect technique.
Mathematical Biosciences, 2 : , Dec  C. Ferreira and H. Focks, D. Haile, E. Daniels, and G. GiLpin and G. Systems analysis of the yellow fever mosquito aedes aegypti. Fortschritte der Zoologie, 25,  M. Gilpin, G. McClelland, and J. Space, time, and the stability of laboratory mosquito populations. American naturalist, pages ,  D. Dengue and dengue hemorrhagic fever. Clinical microbiology reviews, 11 3 : ,  M. Hassell, J.
Lawton, and R. Patterns of dynamical behaviour in single- -species populations. Ecol, 45 2 : ,  J. Hemingway and H. Insecticide resistance in insect vectors of human disease.
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Hoffmann, B. Montgomery, J. Popovici, I. Iturbe-Ormaetxe, P. Johnson, F. Muzzi, M. Greenfield, M. Durkan, Y. Leong, Y. Dong, et al. Successful establishment of wolbachia in aedes populations to suppress dengue transmission. Nature, : ,  A. Hoffmann, M. Turelli, and L. Factors affecting the distribution of cytoplasmic incompatibility in Drosophila simulans. Genetics, 4 : ,  H. Hughes and N. Modelling the use of wolbachia to control dengue fever transmission. Bul letin of mathematical biology, 75 5 : ,. Population Dynamics. Koiller, M. Da Silva, M. Souza, C. Iggidr, G. Sallet, et al.
Aedes, wolbachia and dengue  R. Lana, T. Carneiro, N. Seasonal and nonseasonal dynamics of Aedes aegypti in Rio de Janeiro, Brazil: fitting mathematical models to trap data. Legros, C. Xu, K. Okamoto, T. Scott, A. Morrison, A. Lloyd, and F. Assessing the feasibility of controlling Aedes aegypti with transgenic methods: a model-based evaluation. Luz, C. Ruy Falc o manifestando prestigiar garotada? Palacio bunda cearense eleita representante questionando Agnelo Queiroz pilantra notici rios represantante pobre necessitados?
TANIA chegar destino proposto? Sumiram grana? Que indecente antoniomiguelense foi? Looping loops? Procurador Geral? Quanto Samu?? Lucas Denevitas caseiros Isadoras Elianas denuncia abusos corajosos coniventes ohmygodo verdadeiro Car ssimo d zimo partido? Machado inscrita Federal? Acendam luzes mortoCuba fingimento eternizar mazela tremenda netos rombo financeiro trupe incluindo praticada tios firma sobrinho aperrear telefone sobrinha dentista consultrio gracinha mijado encher bocas predicado ele?
ChiiiiiiiiiiiiiA tem exagerando mas… memor veis m… esculhambam eles? Nero Napole o gasolina? He wanted it so much, in fact, that he tried to con the world into believing he had done it. So he bio-engineers pigs and cows to study disease, tinkers with resurrecting the woolly mammoth, and runs his lucrative cloning empire, delivering little , and beyond. There will always, it seems, be another grief-stricken customer, desperate to replace a lost companion: another Barbra Streisand, visiting the grave of her beloved Sammie, with Miss Violet and Miss Scarlett perched next to her in their stroller—two identical puffs of white fur, gazing at the tombstone of the dog they are.
An award-winning science journalist and best-selling author, Duncan is C. BBG Making carbon storage work is critical to fighting climate change. The question is where to put it all. A Cold War-era joke has an American economist asking a Soviet peer how the communist economy is progressing.
So it goes this century with the rapidly changing energy industry. In China, researchers have been looking for ways to accelerate CCS. They decided to look out to sea. There will be more than 20 large-scale capture facilities available by the end of the year, according to the Global CCS Institute. The same can be said for the idea China has about burying CO2 at sea.
The study should provide some confidence, they write, that ocean CO2 storage remains a viable tool in the push to reduce emissions of the most dangerous heat-trapping gas, even as commercialization of the process remains way off. In the meantime, there are other questions to answer, including how CO2 may behave differently under different kinds of geological conditions.
Fractures in the subsea sediment, either preexisting or created by tectonics or CO2 injection itself, could open a pathway for CO2 to escape—though significant uncertainty remains. He announced his support for the idea at a White House meeting of the National Space Council as the administration presented a directive for setting a goal for a new moon landing within 10 years.
Congress would have to approve a new military service, and lawmakers have been divided on the idea. Much of the push to formalize an off-planet branch of the U.
Russia under President Vladimir Putin has become increasingly aggressive, annexing Crimea, deploying more sophisticated nuclear weapons and waging conventional warfare in eastern Ukraine and Syria. He, too, has aspirations for a military role in space. On peaceful space exploration, the administration announced a goal to send robotic explorers to the moon as early as next year and do another human lunar landing within 10 years.
The directive also calls for better tracking and monitoring of space debris as commercial and civil space traffic increases. The s-era Apollo program to land U. That goal was achieved by the crew of Apollo 11 in Professor Christopher Shaw, a specialist in motor neurone disease, explains how physicist and author Stephen Hawking lived so long with his rare form of the disease.
He was Hawking died peacefully at his home in Cambridge in England in the early hours of Wednesday morning, a spokesman for his family said in an emailed statement. His courage and persistence with his brilliance and humor inspired people across the world. A Cambridge University professor, Hawking redefined cosmology by proposing that black holes emit radiation and later evaporate. The book outlined the basics of cosmology for the general reader. After his degenerative muscle disorder was diagnosed, he defied medical opinion by living five decades longer than expected.
He communicated his ideas through an American-accented speech synthesizer after a life-saving tracheotomy in took away his ability to speak. To the layman, the robot-like voice only seemed to give his words added authority. Hawking applied quantum theory — governing the subatomic world — to black holes, which he claimed discharge radiation that causes them to disappear.
This process helps explain the notion that black holes have existed at a micro level since the Big Bang, and the smaller they are, the faster they evaporate. Black holes are formed when a massive star collapses under the weight of its own gravity. Detected by the movement of surrounding matter, they devour everything in their path and may play a role in the birth of galaxies. With Hartle, Hawking later tried to marry relativity with quantum theory by proposing the no-boundary principle, which held that space-time is finite and the laws of physics determined how the universe began in a self-contained system, without the need for a creator or prior cause.
The Nobel Prize in Physics proved elusive for Hawking, whose theories required observational data to win the praise of the awarding committee in Stockholm. The Nobel Foundation excludes posthumous nominees. His mother, Isobel, was a tax inspector and a secretary. He had two younger sisters and a brother. At age 8, Hawking moved with his family to St. Albans, where he went to school. While he was a doctoral candidate at Cambridge, Hawking was diagnosed with ALS, also known as motor neuron disease. He was told he had only a few years to live.
As the illness progressed slower than expected and he found inspiration in his girlfriend, Jane Wilde, Hawking began to work at his studies for the first time. He completed his doctorate on the origins of the universe, became a research fellow at Caius College and married Wilde in In , Hawking realized the mathematical approaches he developed with Penrose could be applied to black holes, a term coined by physicist John Wheeler.
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Hawking separated from his wife in and married his nurse, Elaine Mason, four years later. They divorced in Spreading out may be the only thing that saves us from ourselves. I am convinced that humans need to leave Earth. A mini ice age that would freeze major rivers could hit Britain in less than two decades, according to research from universities in the UK and Russia. A team led by maths professor Valentina Zharkova at Northumbria University built on work from Moscow to predict the movements of two magnetic waves produced by the Sun. It predicts rapidly decreasing magnetic waves for three solar cycles beginning in and lasting 33 years.
Very low magnetic activity on the Sun correspond with historically documented cold periods on Earth. But she cautions that her mathematical research cannot be used as proof that there will be a mini ice age this time around, not least because of global warming. Researchers can grow stem cells into tiny clumps of cells, called organoids, that display similar activity and structure to human brains.
Some of the axons grew as much as 1. The aim of this kind of research is noble: to work out how lab-grown clusters of brain cells could be used to understand or even treat brain diseases or injuries. Por todo o mundo os eleitores descontentes recusam-se a comparecer nas urnas. Como sanar o conflito resultante? GUA After thousands of years of failure, some scientists believe a breakthrough might finally be in sight.
By Nicola Davison. The name is a problem, for starters. In almost every Indo-European language, one of the words for the disease relates to low temperature, yet experiments have shown that low temperature neither increases the likelihood of catching a cold, nor the severity of symptoms. It is hard to think of another disease that inspires the same level of collective resignation. The common cold slinks through homes and schools, towns and cities, making people miserable for a few days without warranting much afterthought.
Adults suffer an average of between two and four colds each year, and children up to 10, and we have come to accept this as an inevitable part of life. Public understanding remains a jumble of folklore and false assumption. In , researchers at the University of Wisconsin-Madison decided to investigate one of the best-known ways of catching a cold. They infected volunteers with a cold virus and instructed them to kiss healthy test subjects on the mouth for at least one minute. Sixteen healthy volunteers were kissed by people with colds.
The result: just one confirmed infection. The most common beliefs about how to treat the disease have turned out to be false. Dubious efficacy has done little to deter humankind from formulating remedies. In , US President Calvin Coolidge sat down in an airtight chlorine chamber and inhaled the pungent, noxious gas for almost an hour on the advice of his physicians, who were certain that his cold would be cured quickly. Some contain paracetamol, an effective analgesic, but the dosage is often sub-optimal. Taking vitamin C in regular doses does little to ward off disease.
Antibiotics do nothing for colds. The only failsafe means of avoiding a cold is to live in complete isolation from the rest of humanity. Although modern science has changed the way medicine is practised in almost every field, it has so far failed to produce any radically new treatments for colds. The difficulty is that while all colds feel much the same, from a biological perspective the only common feature of the various viruses that cause colds is that they have adapted to enter and damage the cells that line the respiratory tract. Otherwise, they belong to quite different categories of organisms, each with a distinct way of infecting our cells.
This makes a catch-all treatment extremely tricky to formulate. Scientists today identify seven virus families that cause the majority of colds: rhinovirus, coronavirus, influenza and parainfluenza virus, adenovirus, respiratory syncytial virus RSV and, finally, metapneumovirus, which was first isolated in Each has a branch of sub-viruses, known as serotypes, of which there are about Rhinovirus, the smallest cold pathogen by size, is by far the most prevalent, causing up to three-quarters of colds in adults.
To vanquish the cold we will need to tackle all of these different families of virus at some stage. But, for now, rhinovirus is the biggest player. Scientists first attempted to make a rhinovirus vaccine in the s. They used a reliable method, pioneered by French biologist Louis Pasteur in the s, in which a small amount of virus is introduced to a host in order to provoke a defensive immunological reaction that then protects the body from subsequent infection. Even so, those who had been vaccinated caught colds just as easily as those who had not.
Over the next decade, as the techniques for isolating cold viruses were refined, it became clear that there were many more rhinoviruses than first predicted. Researchers realised it would not be possible to make a vaccine in the traditional way. Producing dozens of single-serotype vaccines, each one targeting a different strain, would be impractical. The consensus that a rhinovirus vaccine was not possible deepened. The last human clinical trial took place in Then, in January last year, an editorial appeared in the Expert Review of Vaccines that once again raised the prospect of a vaccine.
It was worded cautiously, yet the claim it made was striking. One virologist told me it was as if a door that had been closed for many, many years had been re-opened. I asked Johnston if he was optimistic. He pointed out that because their studies so far have only been in mice, they are not sure that the vaccine will work in humans. Theirs is an undertaking that, more than anything, has been defined by consistent disappointment.
T he first scientist to try and fail to make a rhinovirus vaccine was also the first scientist to distinguish it from the jumble of other cold viruses. In , an epidemiologist called Winston Price was working at Johns Hopkins University in Baltimore when a group of nurses in his department came down with a mild fever, a cough, sore throat and runny nose — symptoms that suggested the flu. Price took nasal washings from the nurses and grew their virus in a cell culture. What he found was too small to be influenza virus. Price decided to try to develop a vaccine using a bit of dead rhinovirus.
When the immune system encounters an invading virus — even a dead or weakened virus — it sets out to expel it. One defence is the production of antibodies, small proteins that hang around in the blood system long after the virus is gone. If the virus is encountered a second time, the antibodies will swiftly recognise it and raise the alarm, giving the immune system the upper hand.
At first, Price was encouraged. In a trial that involved several hundred people, those vaccinated with JH virus had eight times fewer colds than the unvaccinated. Newspapers across the US wanted to know: had the common cold been cured? The celebration would be short-lived. This indicated that more than one rhinovirus was out there. By the late s, dozens of rhinoviruses had been discovered.
Even in the alien menagerie of respiratory disease, this level of variation in one species was unusual; there are just three or four influenza viruses circulating at any one time. Scientists at the University of Virginia decided to try a different tactic. Instead of inoculating patients with a single strain of rhinovirus, they combined 10 different serotypes in one injection.
But after this, too, failed to shield participants from infection, they were out of ideas. As hope for a vaccine receded, scientists began investigating other ways to combat colds. From until it closed in , most research into respiratory viruses in the UK was undertaken at the Common Cold Unit CCU , a facility backed by the Medical Research Council that occupied a former wartime military hospital in the countryside near Salisbury. In its four decades of operation, some 20, volunteers passed through the doors of the CCU, many to be willingly infected with cold virus in the name of scientific progress.
An early experiment at the CCU involved a group of volunteers being made to take a bath and then to stand dripping wet and shivering in a corridor for 30 minutes. After they were allowed to get dressed, they had to wear wet socks for several hours. Despite a drop in body temperature, the group did not get any more colds than a control group of volunteers who had been kept cosy. The CCU began focusing on cold treatments in the s and 70s, when research into a substance produced by the human body called interferon was gaining momentum.
Interferons are proteins that are secreted by cells when they are attacked by a virus. They act as messengers, alerting nearby cells to the invader. In , researchers at the CCU decided to investigate whether interferon could be used as a treatment for colds. They infected 32 volunteers with rhinovirus and then sprayed either interferon or placebo up their noses.
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Of the 16 given a placebo, 13 came down with colds. But of the 16 given interferon, only three got ill. A rush of interferon research got underway. But, once again, the excitement was premature. A review by the CCU in the s uncovered a fatal flaw: interferon only worked when it was given to the patient at the same time as the virus. But in real life — that is, outside the lab — a rhinovirus enters the nose between eight and 48 hours before the onset of cold symptoms.
By the time you feel a cold coming on, it is already too late. As the 20th century drew to a close, attempts to find a cure grew more desperate. At the CCU, molecules that were found in traditional Chinese medicine, Japanese tea and oranges were all seriously interrogated. In , the CCU closed.
The centre had done much to advance our understanding of the virology of the cold, yet it had also exposed the enormity of the task of defeating it. In the s, as many virologists focused on HIV and Aids, research into the cold tailed off.