Últimos itens adicionados do Acervo: Harvard University

A Universidade de Harvard (em inglês: Harvard University) é uma universidade privada membro da Ivy League, localizada em Cambridge, Massachusetts, Estados Unidos, e cuja história, influência e riqueza tornam-a uma das mais prestigiadas universidades do mundo.

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Understory Vegetation in Old-Growth and Second-Growth Tsuga Canadensis Forests in Western Massachusetts

D’Amato, Anthony W.; Orwig, David A.; Foster, David Russell
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
EN_US
We compared the understory communities (herbs, shrubs, and tree seedlings and saplings) of old-growth and second-growth eastern hemlock forests (Tsuga canadensis) in western Massachusetts, USA. Second-growth hemlock forests originated following clear-cut logging in the late 1800s and were 108–136 years old at the time of sampling. Old-growth hemlock forests contained total ground cover of herbaceous and shrub species that was approximately 4 times greater than in second-growth forests (4.02 ± 0.41%/m^2 versus 1.06 ± 0.47%/m^2) and supported greater overall species richness and diversity. In addition, seedling and sapling densities were greater in old-growth stands compared to second-growth stands and the composition of these layers was positively correlated with overstory species composition (Mantel tests, r > 0.26, P < 0.05) highlighting the strong positive neighborhood effects in these systems. Ordination of study site understory species composition identified a strong gradient in community composition from second-growth to old-growth stands. Vector overlays of environmental and forest structural variables indicated that these gradients were related to differences in overstory tree density, nitrogen availability, and coarse woody debris characteristics among hemlock stands. These relationships suggest that differences in resource availability (e.g....

Local Geometric Langlands Correspondence: The Spherical Case

Frenkel, Edward; Gaitsgory, Dennis
Fonte: Mathematical Society of Japan Publicador: Mathematical Society of Japan
Tipo: Monograph or Book
EN_US
A module over an affine Kac–Moody algebra $\hat{g}$ is called spherical if the action of the Lie subalgebra g[[t]] on it integrates to an algebraic action of the corresponding group G[[t]]. Consider the category of spherical $\hat{g}$-modules of critical level. In this paper we prove that this category is equivalent to the category of quasi-coherent sheaves on the ind-scheme of opers on the punctured disc which are unramified as local systems. This result is a categorical version of the well-known description of spherical vectors in representations of groups over local non-archimedian fields. It may be viewed as a special case of the local geometric Langlands correspondence proposed in [FG2].; Mathematics

The Structure of DNA Overstretched from the 5'5' Ends Differs from the Structure of DNA Overstretched from the 3'3' Ends

Prentiss, Mara; Danilowicz, Claudia; Limouse, Charles; Hatch, Kristi; Conover, Alyson; Coljee, Vincent William; Kleckner, Nancy Elizabeth
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
EN_US
It has been suggested that the structure that results when double-stranded DNA (dsDNA) is pulled from the 3'3' ends differs from that which results when it is pulled from the 5'5' ends. In this work, we demonstrate, using lambda phage dsDNA, that the overstretched states do indeed show different properties, suggesting that they correspond to different structures. For 3'3' pulling versus 5'5' pulling, the following differences are observed: (i) the forces at which half of the molecules in the ensemble have made a complete force-induced transition to single stranded DNA are 141 +/- 3 pN and 122 +/- 4 pN, respectively; (ii) the extension vs. force curve for overstretched DNA has a marked change in slope at 127 +/- 3 pN for 3'3' and 110 +/- 3 pN for 5'5'; (iii) the hysteresis (H) in the extension vs. force curves at 150 mM NaCl is 0.3 +/- 0.8 pN microm for 3'3' versus 13 +/- 8 pN for 5'5'; and (iv) 3'3' and 5'5' molecules show different changes in hysteresis due to interactions with beta-cyclodextrin, a molecule that is known to form stable host-guest complexes with rotated base pairs, and glyoxal that is known to bind stably to unpaired bases. These differences and additional findings are well-accommodated by the corresponding structures predicted on theoretical grounds.; Physics

Stochastic Variation: A Comment on Lewis-Beck and Skalaban's "The R-Square"

King, Gary
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
EN_US
In an interesting and provocative article, Michael Lewis-Beck and Andrew Skalaban make an important contribution by emphasizing several philosophical issues in political methodology that have received too little attention from methodologists and quantitative researchers. These issues involve the role of systematic, and especially stochastic, variation in statistical models. After briefly discussing a few points of disagreement, hoping to reduce them to points of clarification, I turn to the philosophical issues. Examples with real data follow.; Government

Atypical visual processing in posttraumatic stress disorder☆

Mueller-Pfeiffer, Christoph; Schick, Matthis; Schulte-Vels, Thomas; O'Gorman, Ruth; Michels, Lars; Martin-Soelch, Chantal; Blair, James R.; Rufer, Michael; Schnyder, Ulrich; Zeffiro, Thomas; Hasler, Gregor
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
EN_US
Background: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. Method Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. Results: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. Conclusions: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits...

Wheel Running from a Juvenile Age Delays Onset of Specific Motor Deficits but does not Alter Protein Aggregate Density in a Mouse Model of Huntington's Disease

van Dellen, Anton; Cordery, Patricia M; Blakemore, Colin; Hannan, Anthony J; Spires, Tara L.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Background: Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. Results: We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice...

Accuracy of Electrocardiographic Criteria for Atrial Enlargement: Validation with Cardiovascular Magnetic Resonance

Agarwal, Anupam; Tsao, Connie Wei-Lee; Josephson, Mark; Hauser, Thomas Henry; O'Halloran, Thomas D.; Manning, Warren J.; Yeon, Susan B.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Background: Anatomic atrial enlargement is associated with significant morbidity and mortality. However, atrial enlargement may not correlate with clinical measures such as electrocardiographic (ECG) criteria. Past studies correlating ECG criteria with anatomic measures mainly used inferior M-mode or two-dimensional echocardiographic data. We sought to determine the accuracy of the ECG to predict anatomic atrial enlargement as determined by volumetric cardiovascular magnetic resonance (CMR). Methods: ECG criteria for left (LAE) and right atrial enlargement (RAE) were compared to CMR atrial volume index measurements for 275 consecutive subjects referred for CMR (67% males, 51 \(\pm\) 14 years). ECG criteria for LAE and RAE were assessed by an expert observer blinded to CMR data. Atrial volume index was computed using the biplane area-length method. Results: The prevalence of CMR LAE and RAE was 28% and 11%, respectively, and by any ECG criteria was 82% and 5%, respectively. Though nonspecific, the presence of at least one ECG criteria for LAE was 90% sensitive for CMR LAE. The individual criteria P mitrale, P wave axis < \(30^\circ\), and negative P terminal force in V1 (NPTF-V1) > 0.04\(s{\cdot}mm\) were 88–99% specific although not sensitive for CMR LAE. ECG was insensitive but 96–100% specific for CMR RAE. Conclusion: The presence of at least one ECG criteria for LAE is sensitive but not specific for anatomic LAE. Individual criteria for LAE...

Comparison of DNA Histograms by Standard Flow Cytometry and Image Cytometry on Sections in Barrett's Adenocarcinoma

Huang, Qin; Yu, Chenggong; Zhang, Xiaoqi; Goyal, Raj K.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Background: The purpose of this study was to compare DNA histograms obtained by standard flow cytometry (FC) and high fidelity image cytometry on sections (ICS) in normal gastrointestinal mucosa and Barrett's adenocarcinoma (BAC). Methods: Archival formalin-fixed paraffin-embedded tissue blocks of 10 normal controls from 10 subjects and 42 BAC tissues from 17 patients were examined. DNA FC was performed using standard techniques and ICS was carried out by Automated Cellular Imaging System (ACIS). DNA ploidy histograms were classified into diploid with peak DNA index (DI) at 0.9–1.1, and aneuploid with peak DI > 1.1. DI values of aneuploid peaks were determined. Additionally, for DNA ICS, heterogeneity index (HI) representing DNA content heterogeneity, and histograms containing cells with DI > G2 were also identified. Results: All control samples were diploid by both FC and ICS analyses. In BAC, FC showed diploid peaks in 29%, diploid peaks with additional aneuploid or tetraploid peaks in 57%, and 14% of the samples, respectively. In contrast, ICS showed aneuploid peaks in all the cases with peak DI > 1.25; 37 cases had peak DI between 1.25 and 2.25; and 5 cases had peak DI > 2.25. HI values (mean ± SD) were 11.3 ± 1.1 in controls and 32.4 ± 8.5 in BAC (p < 0.05). Controls had no G2 exceeding cells. However...

Prenatal Exposures to Environmental Chemicals and Children's Neurodevelopment: An Update

Bellinger, David C.
Fonte: Occupational Safety and Health Research Institute Publicador: Occupational Safety and Health Research Institute
Tipo: Artigo de Revista Científica
EN_US
This review surveys the recent literature on the neurodevelopmental impacts of chemical exposures during pregnancy. The review focuses primarily on chemicals of recent concern, including phthalates, bisphenol-A, polybrominated diphenyl ethers, and perfluorinated compounds, but also addresses chemicals with longer histories of investigation, including air pollutants, lead, methylmercury, manganese, arsenic, and organophosphate pesticides. For some chemicals of more recent concern, the available literature does not yet afford strong conclusions about neurodevelopment toxicity. In such cases, points of disagreement among studies are identified and suggestions provided for approaches to resolution of the inconsistencies, including greater standardization of methods for expressing exposure and assessing outcomes.

The Association of Near-Infrared Spectroscopy-Derived Tissue Oxygenation Measurements with Sepsis Syndromes, Organ Dysfunction and Mortality in Emergency Department Patients with Sepsis

Arnold, Ryan; Sherwin, Robert; O'Connor, Jennifer; Najarro, Gabriel; Lundy, David; Nelson, Teresa; Shapiro, Nathan Ivan; Singh, Sam; Trzeciak, Stephen W.; Jones, Alan E.; Emergency Medicine Shock Research Network
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Introduction: Near-infrared spectroscopy (NIRS) noninvasively measures peripheral tissue oxygen saturation \((StO_2)\). NIRS may be utilized along with a vascular occlusion test, in which limb blood flow is temporarily occluded and released, to quantify a tissue bed's rate of oxygen exchange during ischemia and recovery. The objective of this study was to test the hypothesis that NIRS-derived \(StO_2\) measures \((StO_2\) initial, \(StO_2\) occlusion and \(StO_2\) recovery) identify patients who are in shock and at increased risk of organ dysfunction (Sequential Organ Failure Assessment (SOFA) score ≥ 2 at 24 hours) and dying in the hospital. Methods: This prospective, observational study comprised a convenience sample of three cohorts of adult patients (age > 17 years) at three urban university emergency departments: (1) a septic shock cohort (systolic blood pressure < 90 after fluid challenge; the "SHOCK" cohort, n = 58), (2) a sepsis without shock cohort (the "SEPSIS" cohort, n = 60) and emergency department patients without infection (n = 50). We measured the \(StO_2\) initial, \(StO_2\) occlusion and \(StO_2\) recovery slopes for all patients. Outcomes were sepsis syndrome severity, organ dysfunction (SOFA score at 24 hours) and in-hospital mortality. Results: Among the 168 patients enrolled...

18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Management of Aggressive Non-Hodgkin's B-Cell Lymphoma

O'Connor, O. J.; McDermott, Shaunagh; Blake, Michael; Shelly, Martin J.
Fonte: International Scholarly Research Network Publicador: International Scholarly Research Network
Tipo: Artigo de Revista Científica
EN_US
18-Fluorodeoxyglucose (FDG-PET/CT) is an established imaging modality that has been proven to be of benefit in the management of aggressive B-cell non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and advanced stage follicular lymphoma. The combination of anatomic and functional imaging afforded by FDG-PET/CT has led to superior sensitivity and specificity in the primary staging, restaging, and assessment of response to treatment of hematological malignancies when compared to FDG-PET and CT alone. The use of FDG-PET/CT for posttreatment surveillance imaging remains controversial, and further study is needed to ascertain whether this modality is cost effective and appropriate for use in this setting.

There Can Be No Turing-Test--Passing Memorizing Machines

Shieber, Stuart M.
Fonte: Michigan Publishing Publicador: Michigan Publishing
Tipo: Artigo de Revista Científica
EN_US
Anti-behaviorist arguments against the validity of the Turing Test as a sufficient condition for attributing intelligence are based on a memorizing machine, which has recorded within it responses to every possible Turing Test interaction of up to a fixed length. The mere possibility of such a machine is claimed to be enough to invalidate the Turing Test. I consider the nomological possibility of memorizing machines, and how long a Turing Test they can pass. I replicate my previous analysis of this critical Turing Test length based on the age of the universe, show how considerations of communication time shorten that estimate and allow eliminating the sole remaining contingent assumption, and argue that the bound is so short that it is incompatible with the very notion of the Turing Test. I conclude that the memorizing machine objection to the Turing Test as a sufficient condition for attributing intelligence is invalid.; Engineering and Applied Sciences

Premenopausal endogenous steroid hormones and breast cancer risk: results from the Nurses' Health Study II

Fortner, Renée T; Eliassen, A Heather; Spiegelman, Donna; Willett, Walter C; Barbieri, Robert L; Hankinson, Susan E
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Introduction: Prior research supports an association between endogenous sex steroids and breast cancer among postmenopausal women; the association is less clear among premenopausal women. Methods: We evaluated the associations between estrogens, androgens, progesterone and sex hormone binding globulin (SHBG) and breast cancer in a nested case-control study in the Nurses' Health Study II. Between 1996 and 1999, 29,611 participants provided blood samples; 18,521 provided samples timed in early follicular and mid-luteal phases of the menstrual cycle. A total of 634 women, premenopausal at blood collection, developed breast cancer between 1999 and 2009 and were matched to 1,264 controls (514 cases and 1,030 controls with timed samples). We used conditional logistic regression controlling for breast cancer risk factors for overall analyses; unconditional logistic regression additionally controlling for matching factors was used for subgroup analyses. Results: In analyses of premenopausal estrogens including breast cancers diagnosed both before and after menopause, there was no association between follicular estradiol, estrone and free estradiol and risk of either total or invasive breast cancer. Luteal estradiol was positively associated with estrogen receptor positive (ER+)/progesterone receptor positive (PR+) cancers (5th vs. 1st quintile odds ratio (OR): 1.7 (95% confidence interval (CI): 1.0 to 2.9)...

Traumatic Brain Injury, Microglia, and Beta Amyloid

Mannix, Rebekah Christina; Whalen, Michael Jerome
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN_US
Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (A\(\beta\)). Data from both AD and TBI studies suggest that microglia play a central role in A\(\beta\) accumulation after TBI. This paper focuses on the current research on the role of microglia response to A\(\beta\) after TBI.

Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease

Wilkinson, Kim; El-Khoury, Joseph B.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN_US
Alzheimer's disease (AD) is increasing in prevalence with the aging population. Deposition of amyloid-\(\beta\) (A\(\beta\)) in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with A\(\beta\) appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear A\(\beta\), but binding of microglia to A\(\beta\) also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS). Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for A\(\beta\). Of particular interest are SCARA-1 (scavenger receptor A-1), CD36, and RAGE (receptor for advanced glycation end products). SCARA-1 appears to be involved in the clearance of A\(\beta\), while CD36 and RAGE are involved in activation of microglia by A\(\beta\). In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with A\(\beta\) and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD.

Targeting mRNA for Alzheimer's and Related Dementias

Wolfe, Michael S.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN_US
Brain deposition of the amyloid beta-protein (Aβ) and tau are characteristic features in Alzheimer's disease (AD). Mutations in the Aβ precursor protein (APP) and a protease involved in Aβ production from APP strongly argue for a pathogenic role of Aβ in AD, while mutations in tau are associated with related disorders collectively called frontotemporal lobar degeneration (FTLD). Despite intense effort, therapeutic strategies that target Aβ or tau have not yet yielded medications, suggesting that alternative approaches should be pursued. In recent years, our laboratory has studied the role of mRNA in AD and FTLD, specifically those encoding tau and the Aβ-producing protease BACE1. As many FTLD-causing tau mutations destabilize a hairpin structure that regulates RNA splicing, we have targeted this structure with small molecules, antisense oligonucleotides, and small molecule-antisense conjugates. We have also discovered that microRNA interaction with the 3′-untranslated region of tau regulates tau expression. Regarding BACE1, we found that alternative splicing leads to inactive splice isoforms and antisense oligonucleotides shift splicing toward these inactive isoforms to decrease Aβ production. In addition, a G-quadruplex structure in the BACE1 mRNA plays a role in splice regulation. The prospects for targeting tau and BACE1 mRNAs as therapeutic strategies will be discussed.

Novel Characterization and Live Imaging of Schlemm's Canal Expressing Prox-1

Truong, Tan N.; Li, Hannah; Hong, Young-Kwon; Chen, Lu
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Schlemm's canal is an important structure of the conventional aqueous humor outflow pathway and is critically involved in regulating the intraocular pressure. In this study, we report a novel finding that prospero homeobox protein 1 (Prox-1), the master control gene for lymphatic development, is expressed in Schlemm's canal. Moreover, we provide a novel in vivo method of visualizing Schlemm's canal using a transgenic mouse model of Prox-1-green fluorescent protein (GFP). The anatomical location of Prox-1+ Schlemm's canal was further confirmed by in vivo gonioscopic examination and ex vivo immunohistochemical analysis. Additionally, we show that the Schlemm's canal is distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis occurred in the cornea. Taken together, our findings offer new insights into Schlemm's canal and provide a new experimental model for live imaging of this critical structure to help further our understanding of the aqueous humor outflow. This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.

The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's-like disease

Enger, Tone Berge; Samad-Zadeh, Arman; Bouchie, Meghan; Skarstein, Kathrine; Galtung, Hilde Kanli; Mera, Toshiyuki; Walker, Janice; Menko, A. Sue; Varelas, Xaralabos; Faustman, Denise L.; Jensen, Janicke Liaaen; Kukuruzinska, Maria
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
EN_US
Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin plays pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating organ size, cell proliferation and differentiation. We now show that Hippo signaling is required for SMG branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from NOD mice, a mouse model for SS...

Optimal Income Transfers

Kaplow, Louis
Fonte: Kluwer Academic Publishers Publicador: Kluwer Academic Publishers
Tipo: Artigo de Revista Científica
EN_US
A substantial literature addresses the design of transfer programs and policies, including the negative income tax, other means-tested transfers, the earned income tax credit, categorical assistance, and work inducements. This work is largely independent of that on the optimal nonlinear income tax, yet formulations of such a tax necessarily address how low-income individuals should be treated. This paper draws on the optimal income taxation literature to illuminate the analysis of transfer programs, including the level and shape of marginal tax rates (including phase-outs), the structure of categorical assistance, and the role of work inducements in an optimal income transfer scheme.

Louis B. Sohn: Recollections of a Co-conspirator

Kennedy, David W.
Fonte: Harvard University, Harvard Law School Publicador: Harvard University, Harvard Law School
Tipo: Artigo de Revista Científica
EN_US