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the search for a physically viable theory of quantized gravitation is ongoing ; in part because the physics it ought to describe is unknown , and in part because different approaches may not the most prominent contenders are string theory and loop quantum gravity , with ample literature available on either sides . for ...
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the more - than - ten - years - long history of the large - scale laser gravitation - wave ( gw ) detectors ( the first one , tama started to operate in 1999 , and the most powerful pair , the two detectors of the ligo project , in 2001 , not to forget about the two european members of the international interferometric...
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branes have played a fundamental role in the main string theory developments of the last twenty years : the unification of the different perturbative string theories using duality symmetries [ 312 , 495 ] relied strongly on the existence of non - perturbative supersymmetric states carrying ramond - ramond ( rr ) charge...
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fundamental constants appear everywhere in the mathematical laws we use to describe the phenomena of nature . they seem to contain some truth about the properties of the physical world while their real nature seem to evade us . the question of the constancy of the constants of physics was probably first addressed by di...
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the heavy flavor corrections to deep - inelastic structure functions amount to sizeable contributions , in particular in the region of small values of the bjorken variable x . starting from lower values of the virtuality , over a rather wide kinematic range , their scaling violations are very different from those of th...
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metals and metal ions are ubiquitous in nature and account for tremendous chemical diversity . in the periodic table , from element 1 ( h ) to element 109 ( mt ) , there are 84 metals , 7 metalloids , and only 18 nonmetals . the sum of the abundances of al , fe , ca , na , k , mg , and ti in the earth s crust is 25% . ...
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for generations of researchers our solar system provided opportunities to establish and test fundamental laws of gravity . by studying the motion of planets , their moons , and comets , astronomers learned the basic rules that govern the dynamics of a system of gravitating bodies . today we apply this knowledge to stud...
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molecular self - assembly is a ubiquitous process in nature , and is also believed to play an essential role in the emergence , maintenance , and advancement of life . while the primary focus of the research on molecular self - assembly centers on the biomacromolecules ( proteins , nucleic acids , and polysaccharides )...
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halogen atoms in haloorganics are typically considered as sites of high electron density because of their high electronegativity . consistent with this well - established understanding , it is commonly accepted that halogen atoms can form attractive interactions by functioning as electron donor sites ( i.e. , nucleophi...
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our present description of the fundamental laws of nature is based on two disconnected pieces : quantum mechanics and general relativity . on the quantum - mechanics side our most significant successes were obtained applying relativistic quantum field theory , which turns out to be the appropriate formalization of ( sp...
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and i cherish more than anything else the analogies , my most trustworthy masters.they know all the secrets of nature , and they ought to be least neglected in geometry. johannes kepler figure 1artistic impression of cascading sound cones ( in the geometrical acoustics limit ) forming an acoustic black hole when supers...
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the era of precision gravitational - wave astrophysics is at our doorstep . with it , a plethora of previously unavailable information will flood in , allowing for unprecedented astrophysical measurements and tests of fundamental theories . nobody would question the importance of more precise astrophysical measurements...
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in its most general sense , gravitational lensing is a collective term for all effects of a gravitational field on the propagation of electromagnetic radiation , with the latter usually described in terms of rays . according to general relativity , the gravitational field is coded in a metric of lorentzian signature on...
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research inspired by black holes has dominated several areas of gravitational physics since the early seventies . laws of black hole mechanics brought out deep , unsuspected connections between classical general relativity , quantum physics , and statistical mechanics [ 35 , 44 , 45 , 46 ] . in particular , they provid...
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the importance of chiral biaryl compounds can not be overstated ; this motif is the central feature of many ligands and catalysts . for example , phosphoramidites derived from binol have been applied to asymmetric conjugate addition and allylic amination reactions ( figure 1 ) . a large family of binaphthyl - based amm...
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the first direct detection of gravitational waves ( gws ) , widely expected in the mid 2010s with advanced ground - based interferometers [ 219 , 2 ] , will represent the culmination of a fifty - year experimental quest . soon thereafter , newly plentiful gw observations will begin to shed light on the structure , popu...
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it is my pleasure to review progress in numerical relativity based upon characteristic evolution . in the spirit of living reviews in relativity , we are now in an era in which einstein s equations can effectively be considered solved at the local level . several groups , as reported here and in other living reviews , ...
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einstein s equations represent a complicated set of nonlinear partial differential equations for which some exact or approximate analytical solutions are known . but these solutions are not always suitable for physically or astrophysically interesting systems , which require an accurate description of their relativisti...
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and i cherish more than anything else the analogies , my most trustworthy masters . they know all the secrets of nature , and they ought least to be neglected in geometry. johannes kepler figure 1artistic impression of cascading sound cones ( in the geometrical acoustics limit ) forming an acoustic black hole when supe...
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the notion of conformal infinity introduced by penrose almost forty years ago is one of the most fruitful concepts within einstein s theory of gravitation . most of the modern developments in the theory are based on or at least influenced in one way or another by the conformal properties of einstein s equations in gene...
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at the time of the birth of general relativity ( gr ) , experimental confirmation was almost a side issue . einstein did calculate observable effects of general relativity , such as the perihelion advance of mercury , which he knew to be an unsolved problem , and the deflection of light , which was subsequently verifie...
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in the 5th century b.c . , democritus postulated the existence of smallest objects that all matter is built from and called them cut. thus , atomos or atom means uncuttable or indivisible . according to democritus theory of atomism , though variable in shape , democritus atoms were the hypothetical fundamental constitu...
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initially discovered by high - throughput screening at hoffman - la roche ( hlr ) in 2004 , the nutlins are cis - imidazoline small molecules that inhibit the mdm2-p53 protein protein interaction ( ppi ) . the nutlins have been widely used to study the consequences of inducing the activity of the tumor suppressor p53 w...
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the motion and associated emission of gravitational waves ( gw ) of self - gravitating systems have been a main research interest in general relativity . the problem is complicated conceptually as well as mathematically because of the nonlinearity of the einstein equations . there is no hope in any foreseeable future t...
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the notion of conformal infinity introduced by penrose almost forty years ago is one of the most fruitful concepts within einstein s theory of gravitation . most of the modern developments in the theory are based on or at least influenced in one way or another by the conformal properties of einstein s equations in gene...
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at the time of the birth of general relativity ( gr ) , experimental confirmation was almost a side issue . einstein did calculate observable effects of general relativity , such as the perihelion advance of mercury , which he knew to be an unsolved problem , and the deflection of light , which was subsequently verifie...
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for the purposes of this review , relativistic binaries are systems containing two stellar mass degenerate or collapsed objects that are in close orbits . in the galactic field , where these systems evolve in relative isolation , their final properties are set solely by their initial conditions and are the result of ma...
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tuberculosis ( tb ) is responsible for the death of 1.5 million people annually . the development of antibiotic resistant strains of the causal pathogen mycobacterium tuberculosis ( mtb ) and comorbidity with immunosuppressive conditions such as hiv and diabetes are major contributors to the current crisis and there is...
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it is my pleasure to review progress in numerical relativity based upon characteristic evolution . in the spirit of living reviews in relativity , we are now in an era in which einstein s equations can effectively be considered solved at the local level . several groups , as reported here and in other living reviews in...
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our conception of black holes has experienced several dramatic changes during the last two hundred years : while the dark stars of michell and laplace were merely regarded as peculiarities of newton s law of gravity and his corpuscular theory of light , black holes are nowadays widely believed to exist in our universe ...
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breakthroughs in modern technology have made possible the construction of extremely large interferometers both on the ground and in space for the detection and observation of gravitational waves ( gws ) . several ground - based detectors around the globe have been operational for several years , and are now in the proc...
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nowadays the exploration of the universe can be performed by a variety of observational probes and methods over a wide range of the wavelengths : the temperature anisotropy map of the cosmic microwave background ( cmb ) , the hubble diagrams of nearby galaxies and distant type ia supernovae , wide - field photometric a...
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glucosamine is a key constituent in numerous important oligosaccharides and glycoconjugates , where it can be either - or -linked . whereas the former type of linkage can be reliably installed through the use of neighboring - group participation of a c-2-amide- or carbamate - based protecting group , the latter type co...
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image - guided surgery ( igs ) systems1 or medical robots are gaining in clinical importance due to the increasing requirements for accuracy and safety of surgical interventions . these approaches in computer - assisted surgery ( cas ) are mostly based on a three - dimensional ( 3d ) image representation of the patient...
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tetracyclines are a class of antibiotics with broad spectrum antibacterial activity.(1 ) since the isolation of its first member , chlorotetracycline ( 1 , figure 1 ) , from the culture broth of streptomyces,(2 ) several generations of tetracycline analogs have been discovered and used to treat infections caused by a w...
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systemic lupus erythematosus ( sle or lupus ) is a disorder of immune regulation characterized by the breakdown of self - tolerance . the complexities of various humoral and cellular abnormalities under the influence with predisposing genetic , sex hormonal and environmental factors have been reported in pathogenesis o...
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lipopolysaccharide ( lps ) is a biomedically highly relevant glycolipid located in the outer leaflet of the cell membrane of gram - negative bacteria . lps is essential for many functions of the bacterial membrane , providing stability , a protective shield , and permeation control , and is thus indispensable for the v...
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hole argument is the english translation of the german phrase lochbetrachtung , used by albert einstein to describe his argument against the possibility of generally - covariant equations for the gravitational field , developed in late 1913 and accepted until late 1915 . einstein realized the desirability of general co...
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the accumulation and aggregation of amyloid- ( a ) peptides is believed to be one of the underlying causes of alzheimer s disease ( ad ) , which is the most common reason for cognitive decline in the elderly . ad pathology is characterized by the presence of extracellular plaques in the hippocampal and cortical regions...
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the historical development of laser interferometers for application as gravitational - wave detectors has involved the combination of relatively simple optical subsystems into more and more complex assemblies . the individual elements that compose the interferometers , including mirrors , beam splitters , lasers , modu...
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the chlorophenoxy herbicides mcpa and 2,4-d are registered for a range of agricultural and residential uses focused on control of postemergent broadleaf weeds . since 2001 , 2,4-d has been the most commonly used herbicide in the residential market at 8 to 11 million pounds annually and is the seventh most commonly used...
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the eskape pathogens ( enterococcus faecium , staphylococcus aureus , klebsiella pneumoniae , acinetobacter baumannii , pseudomonas aeruginosa , and enterobacter species ) are responsible for 51% of all u.s . s. aureus accounts for 16% of hais and is responsible for more deaths in the u.s . the organism s high morbidit...
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the task of quantizing general relativity is one of the outstanding problems of modern theoretical physics . attempts to reconcile quantum theory and general relativity date back to the 1930s ( see for a historical review ) , and decades of hard work have yielded an abundance of insights into quantum field theory , fro...
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nitric oxide ( no ) is an important biological second messenger in humans , which plays a critical role in cell and neuronal signaling , blood pressure regulation , and the immune response . no is produced from oxidation of l - arginine ( l - arg ) in the presence of nadph by a class of heme - dependent enzymes , nitri...
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n - methyl - d - aspartate ( nmda ) receptors are members of the family of ionotropic glutamate receptors that mediate excitatory neurotransmission . nmda receptors are tetrameric assemblies of two glun1 subunits , which bind the coagonist glycine , and two glun2 subunits , which bind glutamate . both glun1 and glun2 s...
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crystal nucleation in liquids has countless practical consequences in science and technology , and it also affects our everyday experience . one obvious example is the formation of ice , which influences global phenomena such as climate change , as well as processes happening at the nanoscale , such as intracellular fr...
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colloidal nanocrystals ( ncs ) have played a pivotal role in both fundamental research and in technological applications over the last 30 years . today , a rational synthetic approach to nc is of utmost importance due to the growing demand for nanomaterials having compositional diversity and that need to be engineered ...
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the cultivated tomato , lycopersicon esculentum mill . , a fruit that is often treated as a vegetable , is widely grown around the world and constitutes a major agricultural industry . worldwide , it is the second most consumed vegetable after potato ( faostat 2005 ; http: / / faostat.fao.org ) and unquestionably the m...
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absence seizures , typical for many different patients with absence epilepsy , principally differ from convulsive seizures . to illustrate , a number of widely used and efficient anticonvulsant drugs enhance absence seizures in patients and in the genetic absence models and ethosuximide is only effective in suppressing...
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cycloaddition reactions enable a versatile and straightforward access to carbocyclic or heterocyclic organic compounds . contrary to cyclization reactions , in which a single bond is formed , the hallmark of cycloaddition reactions is the formation of two or more bonds in a single operation . commonly , olefins serve a...
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as explained in more detail in our previous report , in the course of a screening campaign of new chemical entities against infectious agents , compounds 1 and 2 were found active on our whole cell measles virus replication assay ( figure 1 ) . an initial structure activity study led to confirmation of the potential of...
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gravitational waves , one of the more exotic predictions of einstein s general theory of relativity may , after decades of controversy over their existence , be detected within the next five years . sources such as interacting black holes , coalescing compact binary systems , stellar collapses and pulsars are all possi...
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inflammation , an important component of innate immunity , is a ubiquitous host response to foreign physical and / or chemical challenges , invading pathogens or tissue injury , ultimately isolating the source of disturbance , eradicating infection , and restoring normal tissue structure and function ( homeostasis ) . ...
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the mammalian transglutaminase ( tg ) family includes nine homologues , eight of which are catalytically competent ( tg17 and factor xiiia ) , whereas one ( band 4.2 ) is devoid of any known catalytic activity . these enzymes catalyze posttranslational modifications of selected glutamine residues on target peptides or ...
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the circulatory system is made up of blood vessels that specialize in providing tissues with oxygen , nutrients , and hormones to stabilize body temperature , ph , and thus maintain homeostasis . the development of a mature vascular system is a multifaceted process divided into two separate stages . the first is vascul...
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major depressive disorder ( mdd ) is the single greatest cause of disability and morbidity in adolescence and young adulthood ( jamison et al . , 2006 ) , and is associated with social and academic impairment , and recurrent illness through adulthood ( birmaher et al . by the time a young person reaches 25 years of age...
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aqueous radical emulsion polymerization is the technically most important synthetic route to polymer dispersions and is used to produce worldwide about 7.5 million metric tons of dry polymer . from a more scientific point of classification , emulsion polymerization belongs to the class of heterophase polymerizations , ...
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age - related macular degeneration ( amd ) is the leading cause of blindness for individuals aged 60 years or older . an estimated 11 million people in the united states suffer with amd , and this number is expected to increase to 22 million individuals by 2050 because of the projected demographic expansion of the agin...
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poly(adp - ribose)polymerase-1 ( parp-1 ) is an abundant , ubiquitously expressed nuclear protein that is responsible for the maintenance and repair of dna damage . parp-1 is the founding member of an expanded family of related proteins with similar enzymatic activity . parp-1 utilizes nad as a substrate to synthesize ...
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retinal and cortical processing requires that some visual pathways retain a linear representation of visual signals . however , signal transmission across synapses and via spike generation is inherently nonlinear and rectifying . this rectification distorts the original visual signal and can destroy information in a gi...
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the problem of quantizing general relativity ( gr ) is a very hard one . to this day , and despite continuing efforts , there is not a completely satisfactory theory of quantum gravity . in order to acquire the necessary intuition to deal with the very many issues whose resolution is required , it is often useful to co...
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evasion of apoptosis or programmed cell death , a key regulator of physiological growth control and regulation of tissue homeostasis , is a hallmark of cancer and a contributor to the emergence of resistance to current therapies . the b - cell lymphoma-2 ( bcl-2 ) family of proteins regulate the intrinsic ( mitochondri...
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helioseismology and asteroseismology are well known terms in classical astrophysics . from the beginning of the century the variability of cepheids has been used for the accurate measurement of cosmic distances , while the variability of a number of stellar objects ( rr lyrae , mira ) has been associated with stellar o...
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in this review we consider the problem of detection of deterministic gravitational - wave signals in the noise of a detector and the question of estimation of their parameters . the examples of deterministic signals are gravitational waves from rotating neutron stars , coalescing compact binaries , and supernova explos...
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conventional cancer chemotherapy relies heavily on drugs that trigger programmed cell death via activation of apoptosis pathways . however , many cancers harbor mutations in tumor suppressor genes that function in apoptosis signaling . combined with increased capacity for drug efflux and dna repair , these mutations at...
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particle - like objects have a very long and broad history in science , arising long before newton s corpuscles of light , and spanning the range from fundamental to astronomical . in the mid-1950s , john wheeler sought to construct stable , particle - like solutions from only the smooth , classical fields of electroma...
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apratoxins are potent cytotoxins derived from marine cyanobacteria . because of their biological activity and intriguing structures , we recently established that apratoxins prevent cotranslational translocation and thereby downregulate various receptors , including receptor tyrosine kinases ( rtks ) , and inhibit traf...
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measurements of the heavy quarkonium production in hadron collisions can be used to test predictions of quantum chromodynamics ( qcd ) in the perturbative and non - perturbative regimes . several theoretical models have been developed within the framework of qcd to describe the quarkonium production cross - section and...
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antibiotic resistance is an urgent world health concern that is aggravated by a lack of novel antibiotic discovery . the vast majority of antibiotic classes on the market today were discovered between 1940 and 1960 , a period of time known as the golden era of antibiotic discovery . since this time , however , only two...
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patients or individuals may not respond in similar ways when administered with the same drug in a standard dose . both genetic and non - genetic factors including age , gender , nutrition , concomitant medications , organ function however , to a great extent the inter - individual variability in drug response is attrib...
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it is my pleasure to review progress in numerical relativity based upon characteristic evolution . in the spirit of living reviews , we have entered an era in which einstein s equations can effectively be considered solved at the local level . several groups , as reported here and in other living reviews , have develop...
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accurate and reliable measurements of clinical features of electrocardiogram ( ecg ) signal are most important for effective diagnosis of cardiovascular diseases . in practice , ecg signals are mostly corrupted with different kinds of noise and artefacts such as baseline wander ( bw ) , power - line interference ( pli ...
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infectious diseases are still a major concern worldwide [ 1 , 2 ] . in spite of the improved living conditions and advances in drug therapy leading to an increased protection from pathogen caused illnesses in industrialized countries , the ongoing research for new drugs is particularly important due to development of r...
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exponent is a consulting firm that provides scientific analysis and advice in areas that include toxicology and risk assessment ; georgetown university school of medicine is a provider of medical education . although none of the authors on this assessment have previously consulted for the european glyphosate task force...
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malaria is still one of the most menacing infectious diseases worldwide with estimated 207 million clinical cases and 627,000 death cases ( who ; ) . the treatment of malaria is complicated by the increasing development of resistance to the currently used medicaments and by the pathogen 's unique biological characteris...
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the structural range and biological importance of functional 1,7-naphthyridines have made them attractive targets of research for many years . their derivatives are found in various natural alkaloids such as eburnamonine , anisopusine , and tacamonine ( figure 1 ) , which have appreciable chemical and biological import...
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s - adenosylmethionine decarboxylase ( adometdcaaabbreviations : adometdc , s - adenosylmethionine decarboxylase ; adomet , s - adenosylmethionine ; odc , ornithine decarboxylase ; ssat , spermidine / spermine n - acetyltransferase ; dfmo , -difluoromethylornithine ; mgbg 1 , methylglyoxal bis(guanylhydrazone ) ; mhzpa...
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c h functionalization logic is rapidly permeating the way organic chemists approach synthesis and deconstruct target molecules . with methodological advances developing at an increasing pace , new disconnections and strategies once thought impossible are now available for consideration during synthesis planning . while...
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is expected to double by the year 2020.57 there are two major clinical presentations of amd : non - exudative or atrophic amd , which is characterized by the degeneration of choriocapillaries , retinal pigment epithelium ( rpe ) and neurosensory retina ; and neovascular or exudative amd , which is characterized by the ...
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in general relativity , kinetic theory has been used relatively sparsely to model phenomenological matter in comparison to fluid models , although interest has increased in recent years . from a mathematical point of view there are fundamental advantages to using a kinetic description . in non - curved spacetimes kinet...
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because of the emergence and spread of multidrug resistant microorganisms and pathogenic bacterial infections , novel chemotype antibacterial agents demonstrating distinct modes of action from existing antibiotics are urgently needed . natural products are known as rich sources of bioactive molecules and chemical diver...
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pseudomonas aeruginosa is one of the most opportunistic and challenging pathogenic bacteria , with constant evolution of resistance and the complexity of multidrug resistant phenotypes due to the extensive use of antibacterial agents by monotherapeutic strategy.1 multidrug resistant phenotypes in p. aeruginosa occur th...
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the case for ribonucleic acid ( rna ) being involved in the origin of life has been strengthened by the recent observation that pyrimidine ribonucleoside-2,3-cyclic phosphates can be assembled from simple building blocks under prebiotically plausible conditions . oligomerization of these activated pyrimidine ribonucleo...
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atomistic molecular dynamics ( md ) simulations have become an integral component of the tool set used to examine biomolecular systems . since the first md simulation of a protein in 1977 , the time scales and sizes of computationally tractable simulations have grown by orders of magnitude . systems may now be simulate...
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tuberculosis ( tb ) has been declared a global health emergency by the world health organization ( who ) . it is estimated that about one third of the worlds population is currently infected with the responsible actinobacteria mycobacterium tuberculosis ( mtb).1 resistance of mtb to available antibiotics has increased ...
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a child with a disorder of sexual differentiation ( dsd ) poses a variety of challenges for the treating physician as well as for the parents and family . although appropriate management has long been a matter of concern and often contention , no clinical practice guidelines have been established to help physicians inf...
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aging of the world population has amplified the visibility of several human diseases and neurodegenerative disorders such as parkinson s , alzheimer s diseases and several forms of ataxia [ 1 - 3 ] . the onset of these and of more than fifty further related pathologies is associated at the molecular level with the prol...
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nitrogen heterocycles are ubiquitous in nature : a large number of biochemical pathways involve n - heterocycles as substrates , products , or coenzymes . this ensures their prominence among top pharmaceuticals , with 23 out of the 50 top - selling drugs in the us in 2012 containing n - heterocycles . it is not surpris...
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in the discovery and development of new medicines , attrition rates are still very significant , despite the comprehensive measures taken by the chemical and pharmaceutical industry to lower the risk of failure . in pharmaceuticals , toxicity is a major contributor to the withdrawal of new drugs and often the underlyin...
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blood brain barrier ( bbb ) is a vasculature of the central nervous system ( cns ) that is formed by capillary endothelial cells . this is not a fixed structure but its function depends on the complex interplay between the different cell types such as the endothelial cells , astrocytes , pericytes , and the extracellul...
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substituted tetrahydropyrans and tetrahydropyranones are a common motif in numerous biologically active natural products ( figure 1 ) . synthesis of tetrahydropyran-4-ones ( thpos ) , followed by reduction of the ketone , has been used to form 4-hydroxytetrahydropyran rings . tetrahydropyranones are commonly prepared w...
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the c-19 methyl - substituted indole alkaloids represented in figure 1 are a relatively rare class of alkaloids belonging to the sarpagine ajmaline series with over 17 members isolated to date . in addition to the asymmetric centers at c-3(s ) , c-5(s ) , and c-15(r ) of the sarpagine / ajmaline framework , these alkal...
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more than 10 years after the pandemic caused by the sars ( severe acute respiratory syndrome ) coronavirus ( cov ) , no anticoronaviral regimens have been developed for the treatment of sars - cov or any other human coronaviruses ( hcov ) infection . sars - cov was established as the causative agent of the fatal global...
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scheme 1 outlines the synthesis of novel thioacetamide ( compounds 4a4z ) and sulfinylacetamide ( compounds 5a5 g ) analogues of ( )-1 . the thioacetamide analogues 4a4z were generated via three different synthetic routes . the first route ( procedure a ) affords the thioacetamides in one step and was employed in the s...
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over the past 90 years , the basic ingredients of general relativity have been tested in many different ways and in many different settings . from the solar eclipse expedition of 1917 to the modern observations of double neutron stars , general relativity has passed all tests with flying colors . yet , our inability to...
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synapses transfer information from sensory cells or neurons to other neurons or distinct target cell types , such as muscle cells . a plethora of presynaptic proteins orchestrate neurotransmitter release at the presynaptic active zone ( az ) . these proteins are organized into three main compartments , which are ultras...
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the objectives of the present paper include to give an overview of the wide spectrum of substances having endocrine - disrupting properties ; to list a series of observations suggesting that endocrine disruptors contribute to human health problems , however , without attempting to bring an all - inclusive review for ea...
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malaria is one of the most prevalent infectious diseases of the developing world . in excess of 3 billion people are at risk , and it currently leads to the deaths of around 655,000 people each year , with the majority of these occurring in sub - saharan africa among children under five years of age . resistance to exi...
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the contributors to this special issue read delusions and other irrational beliefs and provided insightful and constructive criticism of its main theses . now i am grateful for the opportunity to revisit and clarify some of my arguments in the light of their commentaries . in the book , i argued that there is a tendenc...
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we briefly introduce the topic of this review article in two ways : by definition , and in a historical context . an isolated system in general relativity typically ends up in one of three distinct kinds of final state . it either collapses to a black hole , forms a stable star , or explodes and disperses , leaving emp...