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Showing papers by "Stony Brook University published in 2007"


Journal ArticleDOI
TL;DR: This work presents a meta-analyses of the immune system’s response to chronic obstructive pulmonary disease and shows clear patterns of decline in the immune systems of elderly patients with compromised immune systems.
Abstract: Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

5,558 citations


Journal ArticleDOI
28 Jun 2007-Nature
TL;DR: A family of miRNAs, miR-34a–c, whose expression reflected p53 status is described, whose encoded genes are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo.
Abstract: A global decrease in microRNA (miRNA) levels is often observed in human cancers, indicating that small RNAs may have an intrinsic function in tumour suppression. To identify miRNA components of tumour suppressor pathways, we compared miRNA expression profiles of wild-type and p53-deficient cells. Here we describe a family of miRNAs, miR-34a-c, whose expression reflected p53 status. Genes encoding miRNAs in the miR-34 family are direct transcriptional targets of p53, whose induction by DNA damage and oncogenic stress depends on p53 both in vitro and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both primary and tumour-derived cell lines, which is consistent with the observed ability of miR-34 to downregulate a programme of genes promoting cell cycle progression. The p53 network suppresses tumour formation through the coordinated activation of multiple transcriptional targets, and miR-34 may act in concert with other effectors to inhibit inappropriate cell proliferation.

2,658 citations


Journal ArticleDOI
TL;DR: The empirical research on the functions of self-injury is reviewed, providing strong support for a self-punishment function, and modest evidence for anti-dissociation, interpersonal-influence, anti-suicide, sensation-seeking, and interpersonal boundaries functions.

1,504 citations


Journal ArticleDOI
TL;DR: Treatment and follow-up IOP continued to have a marked influence on progression, regardless of baseline IOP, and lower systolic perfusion pressure, lower syStolic BP, and cardiovascular disease history emerged as new predictors, suggesting a vascular role in glaucoma progression.

1,232 citations


Journal ArticleDOI
TL;DR: As-prepared, single-crystalline bismuth ferrite nanoparticles show strong size-dependent magnetic properties that correlate with increased suppression of the known spiral spin structure with decreasing nanoparticle size and uncompensated spins and strain anisotropies at the surface.
Abstract: As-prepared, single-crystalline bismuth ferrite nanoparticles show strong size-dependent magnetic properties that correlate with: (a) increased suppression of the known spiral spin structure (period length of ∼62 nm) with decreasing nanoparticle size and (b) uncompensated spins and strain anisotropies at the surface. Zero-field-cooled and field-cooled magnetization curves exhibit spin-glass freezing behavior due to a complex interplay between finite size effects, interparticle interactions, and a random distribution of anisotropy axes in our nanoparticle assemblies.

1,129 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigate how current and proposed observations of neutron stars can lead to an understanding of the state of their interiors and the key unknowns: the typical neutron star radius and the neutron star maximum mass.

1,024 citations


Journal ArticleDOI
TL;DR: The materials, techniques and post modification methods to functionalize electrospun nanofibrous scaffolds suitable for biomedical applications are reviewed.

948 citations


Journal ArticleDOI
TL;DR: In this paper, the role of life stress experience in modifying 5-HTT function in the brain was discussed and integration of these findings suggests that the impact of the 5HTT gene on behavior is much broader than is commonly appreciated and may have a role in social cognition.
Abstract: The gene encoding the serotonin transporter (5-HTT) contains a regulatory variation that has been associated with anxiety-related traits and susceptibility for depression. Here we highlight recent discoveries related to allelic variation of 5-HTT function with respect to emotion regulation and social behavior, drawing from an interdisciplinary perspective of behavioral genetics and cognitive neuroscience. Following a reductionistic path that leads from gene-behavior association studies to neuroimaging and epigenetic studies, we compare two models of 5-HTT-dependent modulation of brain activity and discuss the role of life stress experience in modifying 5-HTT function in the brain. Integration of these findings suggests that the impact of the 5-HTT gene on behavior is much broader than is commonly appreciated and may have a role in social cognition.

929 citations


Journal ArticleDOI
TL;DR: Ecologists should start using a combination of experimental approaches borrowed from ecological genetics, novel techniques to analyse and manipulate epigenetic variation, and genomic tools, to investigate the extent and structure of epigenetics variation within and among natural populations, as well as the interrelations between epigenetic variations, phenotypic variation and ecological interactions.
Abstract: There is now mounting evidence that heritable variation in ecologically relevant traits can be generated through a suite of epigenetic mechanisms, even in the absence of genetic variation. Moreover, recent studies indicate that epigenetic variation in natural populations can be independent from genetic variation, and that in some cases environmentally induced epigenetic changes may be inherited by future generations. These novel findings are potentially highly relevant to ecologists because they could significantly improve our understanding of the mechanisms underlying natural phenotypic variation and the responses of organisms to environmental change. To understand the full significance of epigenetic processes, however, it is imperative to study them in an ecological context. Ecologists should therefore start using a combination of experimental approaches borrowed from ecological genetics, novel techniques to analyse and manipulate epigenetic variation, and genomic tools, to investigate the extent and structure of epigenetic variation within and among natural populations, as well as the interrelations between epigenetic variation, phenotypic variation and ecological interactions.

849 citations


Journal ArticleDOI
TL;DR: CNS inflammatory demyelinating disorders presenting in children and adolescents can be defined and distinguished, however, prospective research is necessary to determine the validity and utility of the proposed diagnostic categories.
Abstract: Background: The CNS inflammatory demyelinating disorders of childhood include both self-limited and lifelong conditions, which can be indistinguishable at the time of initial presentation. Clinical, biologic, and radiographic delineation of the various monophasic and chronic childhood demyelinating disorders requires an operational classification system to facilitate prospective research studies. Methods: The National Multiple Sclerosis Society (NMSS) organized an International Pediatric MS Study Group (Study Group) composed of adult and pediatric neurologists and experts in genetics, epidemiology, neuropsychology, nursing, and immunology. The group met several times to develop consensus definitions regarding the major CNS inflammatory demyelinating disorders of children and adolescents. Results: Clinical definitions are proposed for pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), recurrent ADEM, multiphasic ADEM, neuromyelitis optica, and clinically isolated syndrome. These definitions are considered operational and need to be tested in future research and modified accordingly. Conclusion: CNS inflammatory demyelinating disorders presenting in children and adolescents can be defined and distinguished. However, prospective research is necessary to determine the validity and utility of the proposed diagnostic categories.

684 citations


Journal ArticleDOI
TL;DR: The systematic process wherein items are classified for subsequent statistical processing by the PROMIS investigators is described, wherein items successfully screened through this process were sent to field testing and will be subjected to innovative scale construction procedures.
Abstract: One of the PROMIS (Patient-Reported Outcome Measurement Information System) network's primary goals is the development of a comprehensive item bank for patient-reported outcomes of chronic diseases. For its first set of item banks, PROMIS chose to focus on pain, fatigue, emotional distress, physical function, and social function. An essential step for the development of an item pool is the identification, evaluation, and revision of extant questionnaire items for the core item pool. In this work, we also describe the systematic process wherein items are classified for subsequent statistical processing by the PROMIS investigators. Six phases of item development are documented: identification of extant items, item classification and selection, item review and revision, focus group input on domain coverage, cognitive interviews with individual items, and final revision before field testing. Identification of items refers to the systematic search for existing items in currently available scales. Expert item review and revision was conducted by trained professionals who reviewed the wording of each item and revised as appropriate for conventions adopted by the PROMIS network. Focus groups were used to confirm domain definitions and to identify new areas of item development for future PROMIS item banks. Cognitive interviews were used to examine individual items. Items successfully screened through this process were sent to field testing and will be subjected to innovative scale construction procedures.

Journal ArticleDOI
TL;DR: A comprehensive review of the research work conducted on metal bipolar plates to prevent corrosion while maintaining a low contact resistance is presented in this paper, where metal bipolar plate is used as the current conductors between cells, providing conduits for reactant gases flow, and constitute the backbone of a power stack.

Journal ArticleDOI
TL;DR: The authors developed and evaluated a new measure of national attachment that is grounded in social identity theory, drawing on data from three distinct sources: two studies of undergraduate students and the 1996 General Social Survey (GSS).
Abstract: Researchers disagree over the definition, measurement, and expected political consequences of American patriotism, a situation that is fueled by the absence of a strong theoretical research foundation. We develop and evaluate a new measure of national attachment that is grounded in social identity theory (Tajfel and Turner 1979), drawing on data from three distinct sources: two studies of undergraduate students and the 1996 General Social Survey (GSS). Confirmatory factor analyses provide clear evidence that national identity is distinc tf ro mo ther measures of national attachment including symbolic, constructive, and uncritical patriotism (and nationalism). National identity has a number of other good measurement properties when compared to existing measures: it receives equal endorsement from conservatives and liberals (unlike most other measures which exhibit an ideological bias), develops with time spent in the United States among immigrants, and most importantly is the only measure of national attachment to predict political interest and voter turnout in both student and adult samples, consistent with the predictions of social identity theory. In that sense, the national identity measure outperforms all other measures of national attachment and provides unambiguous evidence that a strong American identity promotes civic involvement.

Journal ArticleDOI
TL;DR: Psychotherapies that emphasize emotion regulation, functional assessment, and problem solving appear to be most effective in treating self-injury.
Abstract: Non-suicidal self-injury is the intentional destruction of body tissue without suicidal intent and for purposes not socially sanctioned. In this practice-friendly review, the authors summarize the empirical research on who self-injures, why people self-injure, and what treatments have demonstrated effectiveness. Self-injury is more common in adolescents and young adults as compared to adults. Common forms include cutting, severe scratching, burning, and banging or hitting; most individuals who self-injure have used more than one method. Although diagnostically heterogeneous, self-injurers typically exhibit two prominent characteristics: negative emotionality and self-derogation. Self-injury is most often performed to temporarily alleviate intense negative emotions, but may also serve to express self-directed anger or disgust, influence or seek help from others, end periods of dissociation or depersonalization, and help resist suicidal thoughts. Psychotherapies that emphasize emotion regulation, functional assessment, and problem solving appear to be most effective in treating self-injury.

Journal ArticleDOI
TL;DR: There was a significant dose-dependent increase in risk of proteinuria and hypertension in patients with cancer who received bevacizumab.

Journal ArticleDOI
01 Jun 2007-Pain
TL;DR: Although prevalence rates of back/neck pain were generally lower than in previous reports, mental disorders were associated with chronic back/ neck pain and the strength of association was stronger for mood and anxiety disorders than for alcohol abuse/dependence.
Abstract: This paper reports cross-national data concerning back or neck pain comorbidity with mental disorders. We assessed (a) the prevalence of chronic back/neck pain, (b) the prevalence of mental disorders among people with chronic back/neck pain, (c) which mental disorder had strongest associations with chronic back/neck pain, and (d) whether these associations are consistent across countries. Population surveys of community-dwelling adults were carried out in 17 countries in Europe, the Americas, the Middle East, Africa, Asia, and the South Pacific (N=85,088). Mental disorders were assessed with the Composite International Diagnostic Interview, third version (CIDI 3.0): anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, posttraumatic stress disorder, and social anxiety disorder), mood disorders (major depression and dysthymia), and alcohol abuse or dependence. Back/neck pain was ascertained by self-report. Between 10% and 42% reported chronic back/neck pain in the previous 12 months. After adjusting for age and sex, mental disorders were more common among persons with back/neck pain than among persons without. The pooled odds ratios were 2.3 [95% CI=2.1-2.5] for mood disorders, 2.2 [95% CI=2.1-2.4] for anxiety disorders, and 1.6 [95% CI=1.4-1.9] for alcohol abuse/dependence in people with versus without chronic back/neck pain. Although prevalence rates of back/neck pain were generally lower than in previous reports, mental disorders were associated with chronic back/neck pain. The strength of association was stronger for mood and anxiety disorders than for alcohol abuse/dependence. The association of mental disorders with back/neck pain showed a consistent pattern across both developed and developing countries.

Journal ArticleDOI
TL;DR: The experiments test the hypothesis that chronic dietary poisoning by aristolochic acid is responsible for EN and its associated urothelial cancer and conclude that dietary exposure to AA is a significant risk factor for ENand its attendant transitional cell cancer.
Abstract: Endemic (Balkan) nephropathy (EN), a devastating renal disease affecting men and women living in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, is characterized by its insidious onset, invariable progression to chronic renal failure and a strong association with transitional cell (urothelial) carcinoma of the upper urinary tract. Significant epidemiologic features of EN include its focal occurrence in certain villages and a familial, but not inherited, pattern of disease. Our experiments test the hypothesis that chronic dietary poisoning by aristolochic acid is responsible for EN and its associated urothelial cancer. Using (32)P-postlabeling/PAGE and authentic standards, we identified dA-aristolactam (AL) and dG-AL DNA adducts in the renal cortex of patients with EN but not in patients with other chronic renal diseases. In addition, urothelial cancer tissue was obtained from residents of endemic villages with upper urinary tract malignancies. The AmpliChip p53 microarray was then used to sequence exons 2-11 of the p53 gene where we identified 19 base substitutions. Mutations at A:T pairs accounted for 89% of all p53 mutations, with 78% of these being A:T --> T:A transversions. Our experimental results, namely, that (i) DNA adducts derived from aristolochic acid (AA) are present in renal tissues of patients with documented EN, (ii) these adducts can be detected in transitional cell cancers, and (iii) A:T --> T:A transversions dominate the p53 mutational spectrum in the upper urinary tract malignancies found in this population lead to the conclusion that dietary exposure to AA is a significant risk factor for EN and its attendant transitional cell cancer.

Journal ArticleDOI
TL;DR: The authors applied 10 distinct modelling techniques to presence-only data for 50 species in five different regions, to test whether a 10-fold coarsening of resolution affects predictive performance of SDM, and any observed effects are dependent on the type of region, modelling technique, or species considered.
Abstract: Predictive species distribution modelling (SDM) has become an essential tool in biodiversity conservation and management. The choice of grain size (resolution) of environmental layers used in modelling is one important factor that may affect predictions. We applied 10 distinct modelling techniques to presence-only data for 50 species in five different regions, to test whether: (1) a 10-fold coarsening of resolution affects predictive performance of SDMs, and (2) any observed effects are dependent on the type of region, modelling technique, or species considered. Results show that a 10 times change in grain size does not severely affect predictions from species distribution models. The overall trend is towards degradation of model performance, but improvement can also be observed. Changing grain size does not equally affect models across regions, techniques, and species types. The strongest effect is on regions and species types, with tree species in the data sets (regions) with highest locational accuracy being most affected. Changing grain size had little influence on the ranking of techniques: boosted regression trees remain best at both resolutions. The number of occurrences used for model training had an important effect, with larger sample sizes resulting in better models, which tended to be more sensitive to grain. Effect of grain change was only noticeable for models reaching sufficient performance and/or with initial data that have an intrinsic error smaller than the coarser grain size.

Journal ArticleDOI
TL;DR: This study assesses the cortisol rise after awakening on 6 consecutive days to conclude that the CAR of a single day is determined to a great extent by situational factors and only for a small proportion by trait factors and from two to six days are necessary to achieve reliable trait measures.

Journal ArticleDOI
A. Adare1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +442 moreInstitutions (48)
TL;DR: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured electrons with 0.3 < p(T) < 9 GeV/c at midrapidity (y < 0.35) from heavy-flavor (charm and bottom) decays in Au + Au collisions at root s(NN) = 200 GeV as mentioned in this paper.
Abstract: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured electrons with 0.3 < p(T) < 9 GeV/c at midrapidity (y < 0.35) from heavy-flavor (charm and bottom) decays in Au + Au collisions at root s(NN) = 200 GeV. The nuclear modification factor R-AA relative to p + p collisions shows a strong suppression in central Au + Au collisions, indicating substantial energy loss of heavy quarks in the medium produced at RHIC energies. A large azimuthal anisotropy v(2) with respect to the reaction plane is observed for 0.5 < p(T) < 5 GeV/c indicating substantial heavy-flavor elliptic flow. Both R-AA and v(2) show a p(T) dependence different from those of neutral pions. A comparison to transport models which simultaneously describe R-AA(p(T)) and v(2)(p(T)) suggests that the viscosity to entropy density ratio is close to the conjectured quantum lower bound, i.e., near a perfect fluid.

Journal ArticleDOI
TL;DR: The magnitude of the feedback negativity is sensitive to violations of reward prediction, but that this effect may depend on the close coupling of prediction and outcome.
Abstract: The reinforcement learning theory suggests that the feedback negativity should be larger when feedback is unexpected. Two recent studies found, however, that the feedback negativity was unaffected by outcome probability. To further examine this issue, participants in the present studies made reward predictions on each trial of a gambling task where objective reward probability was indicated by a cue. In Study 1, participants made reward predictions following the cue, but prior to their gambling choice; in Study 2, predictions were made following their gambling choice. Predicted and unpredicted outcomes were associated with equivalent feedback negativities in Study 1. In Study 2, however, the feedback negativity was larger for unpredicted outcomes. These data suggest that the magnitude of the feedback negativity is sensitive to violations of reward prediction, but that this effect may depend on the close coupling of prediction and outcome.


Journal ArticleDOI
TL;DR: Data reinforce the growing awareness that non-coding RNAs are key players in tumour development by placing miRNAs in a central role in a well-known tumour-suppressor network.
Abstract: Several recent studies have found a conserved microRNA (miRNA) family, the miR-34s, to be direct transcriptional targets of p53. miR-34 activation can recapitulate elements of p53 activity, including induction of cell-cycle arrest and promotion of apoptosis, and loss of miR-34 can impair p53-mediated cell death. These data reinforce the growing awareness that non-coding RNAs are key players in tumour development by placing miRNAs in a central role in a well-known tumour-suppressor network.

Journal ArticleDOI
TL;DR: It is shown that certain modelling techniques are particularly robust to a moderate level of locational error and that useful predictions of species distributions can be made even when occurrence data include some error.
Abstract: Summary 1. Species distribution modelling is used increasingly in both applied and theoretical research to predict how species are distributed and to understand attributes of species’ environmental requirements. In species distribution modelling, various statistical methods are used that combine species occurrence data with environmental spatial data layers to predict the suitability of any site for that species. While the number of data sharing initiatives involving species’ occurrences in the scientific community has increased dramatically over the past few years, various data quality and methodological concerns related to using these data for species distribution modelling have not been addressed adequately. 2. We evaluated how uncertainty in georeferences and associated locational error in occurrences influence species distribution modelling using two treatments: (1) a control treatment where models were calibrated with original, accurate data and (2) an error treatment where data were first degraded spatially to simulate locational error. To incorporate error into the coordinates, we moved each coordinate with a random number drawn from the normal distribution with a mean of zero and a standard deviation of 5 km. We evaluated the influence of error on the performance of 10 commonly used distributional modelling techniques applied to 40 species in four distinct geographical regions. 3. Locational error in occurrences reduced model performance in three of these regions; relatively accurate predictions of species distributions were possible for most species, even with degraded occurrences. Two species distribution modelling techniques, boosted regression trees and maximum entropy, were the best performing models in the face of locational errors. The results obtained with boosted regression trees were only slightly degraded by errors in location, and the results obtained with the maximum entropy approach were not affected by such errors. 4. Synthesis and applications . To use the vast array of occurrence data that exists currently for research and management relating to the geographical ranges of species, modellers need to know the influence of locational error on model quality and whether some modelling techniques are particularly robust to error. We show that certain modelling techniques are particularly robust to a moderate level of locational error and that useful predictions of species distributions can be made even when occurrence data include some error. Journal of Applied Ecology (2007)

Journal ArticleDOI
A. Adare1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +438 moreInstitutions (46)
TL;DR: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured J/psi production for rapidities -2.2 < y < 2.2 in Au+Au collisions at root s(NN)=200 GeV as mentioned in this paper.
Abstract: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured J/psi production for rapidities -2.2 < y < 2.2 in Au+Au collisions at root s(NN)=200 GeV. The J/psi invariant yield and nuclear modification factor R-AA as a function of centrality, transverse momentum, and rapidity are reported. A suppression of J/psi relative to binary collision scaling of proton-proton reaction yields is observed. Models which describe the lower energy J/psi data at the CERN Super Proton Synchrotron invoking only J/psi destruction based on the local medium density predict a significantly larger suppression at RHIC and more suppression at midrapidity than at forward rapidity. Both trends are contradicted by our data.

Journal ArticleDOI
TL;DR: The basic structure of gap junction channels and the function of connexin genes that have been associated with human disorders are discussed to explore the physiology of intercellular communication in skin.

Journal ArticleDOI
TL;DR: Indentation is a remarkably flexible mechanical test due to its relative experimental simplicity as discussed by the authors, and the ease of implementation has made indentation a ubiquitous research tool for a number of different systems across size scales (nano to macro) and scientific/engineering disciplines.

Journal ArticleDOI
09 Nov 2007-Science
TL;DR: To detect low concentrations of NPCs in vivo, a signal processing method was developed that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans.
Abstract: The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.

Journal ArticleDOI
TL;DR: This article begins to outline why and how a new Extended Evolutionary Synthesis (EES) may need to be extended, and how it may come about.
Abstract: The Modern Synthesis (MS) is the current paradigm in evolutionary biology. It was actually built by expanding on the conceptual foundations laid out by its predecessors, Darwinism and neo-Darwinism. For sometime now there has been talk of a new Extended Evolutionary Synthesis (EES), and this article begins to outline why we may need such an extension, and how it may come about. As philosopher Karl Popper has noticed, the current evolutionary theory is a theory of genes, and we still lack a theory of forms. The field began, in fact, as a theory of forms in Darwin's days, and the major goal that an EES will aim for is a unification of our theories of genes and of forms. This may be achieved through an organic grafting of novel concepts onto the foundational structure of the MS, particularly evolvability, phenotypic plasticity, epigenetic inheritance, complexity theory, and the theory of evolution in highly dimensional adaptive landscapes.

Journal ArticleDOI
TL;DR: Receptor tyrosine kinases are essential components of signal transduction pathways that mediate cell-to-cell communication and by which signals are propagated from the activated receptors to downstream targets in the cell.