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New Haven, CT, United States

Yale University is a private Ivy League research university in New Haven, Connecticut. Founded in 1701 as the "Collegiate School" by a group of Congregationalist ministers and chartered by the Colony of Connecticut, the university is the third-oldest institution of higher education in the United States. In 1718, the school was renamed "Yale College" in recognition of a gift from Elihu Yale, a governor of the British East India Company. Established to train Connecticut ministers in theology and sacred languages, by 1777 the school's curriculum began to incorporate humanities and science. During the 19th century Yale gradually incorporated graduate and professional instruction, awarding the first Ph.D. in the United States in 1861 and organizing as a university in 1887.Yale is organized into twelve constituent schools: the original undergraduate college, the Graduate School of Arts & science, and ten professional schools. While the university is governed by the Yale Corporation, each school's faculty oversees its curriculum and degree programs. In addition to a central campus in downtown New Haven, the University owns athletic facilities in Western New Haven, including the Yale Bowl, a campus in West Haven, Connecticut, and forest and nature preserves throughout New England. The University's assets include an endowment valued at $23.9 billion as of September 27, 2014.Yale College undergraduates follow a liberal arts curriculum with departmental majors and are organized into a system of residential colleges. The Yale University Library, serving all twelve schools, holds more than 15 million volumes and is the third-largest academic library in the United States. Almost all faculty teach undergraduate courses, more than 2,000 of which are offered annually. Students compete intercollegiately as the Yale Bulldogs in the NCAA Division I Ivy League.Yale has graduated many notable alumni, including five U.S. Presidents, 19 U.S. Supreme Court Justices, 13 living billionaires, and many foreign heads of state. In addition, Yale has graduated hundreds of members of Congress and many high-level U.S. diplomats, including former U.S. Secretary of State Hillary Clinton and current Secretary of State John Kerry. Fifty-two Nobel laureates have been affiliated with the University as students, faculty, or staff, and 230 Rhodes Scholars graduated from the University. Wikipedia.

Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism. Copyright © 2010 the American Physiological Society. Source

This Review assesses the relevant data and controversies regarding the use of radiotherapy for, and locoregional management of, women with triple-negative breast cancer (TNBC). In view of the strong association between BRCA1 and TNBC, knowledge of baseline mutation status can be useful to guide locoregional treatment decisions. TNBC is not a contraindication for breast conservation therapy because data suggest increased locoregional recurrence risks (relative to luminal subtypes) with breast conservation therapy or mastectomy. Although a boost to the tumour bed should routinely be considered after whole breast radiation therapy, TNBC should not be the sole indication for post-mastectomy radiation, and accelerated delivery methods for TNBC should be offered on clinical trials. Preliminary data implying a relative radioresistance for TNBC do not imply radiation omission because radiation provides an absolute locoregional risk reduction. At present, the integration of subtypes in locoregional management decisions is still in its infancy. Until level 1 data supporting treatment decisions based on subtypes are available, standard locoregional management principles should be adhered to. © 2015 Elsevier Ltd. Source

Upon detection of pathogen-associated molecular patterns, innate immune receptors initiate inflammatory responses. These receptors include cytoplasmic NOD-like receptors (NLRs) whose stimulation recruits and proteolytically activates caspase-1 within the inflammasome, a multiprotein complex. Caspase-1 mediates the production of interleukin-1 family cytokines (IL1FCs), leading to fever and inflammatory cell death (pyroptosis). Mutations that constitutively activate these pathways underlie several autoinflammatory diseases with diverse clinical features. We describe a family with a previously unreported syndrome featuring neonatal-onset enterocolitis, periodic fever, and fatal or near-fatal episodes of autoinflammation. We show that the disease is caused by a de novo gain-of-function mutation in NLRC4 encoding a p.Val341Ala substitution in the HD1 domain of the protein that cosegregates with disease. Mutant NLRC4 causes constitutive IL1FC production and macrophage cell death. Infected macrophages from affected individuals are polarized toward pyroptosis and exhibit abnormal staining for inflammasome components. These findings identify and describe the cause of a life-threatening but treatable autoinflammatory disease that underscores the divergent roles of the NLRC4 inflammasome. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source

Humphrey J.D.,Yale University
Nature Reviews Molecular Cell Biology

Soft connective tissues at steady state are dynamic; resident cells continually read environmental cues and respond to them to promote homeostasis, including maintenance of the mechanical properties of the extracellular matrix (ECM) that are fundamental to cellular and tissue health. The mechanosensing process involves assessment of the mechanics of the ECM by the cells through integrins and the actomyosin cytoskeleton, and is followed by a mechanoregulation process, which includes the deposition, rearrangement or removal of the ECM to maintain overall form and function. Progress towards understanding the molecular, cellular and tissue-level effects that promote mechanical homeostasis has helped to identify key questions for future research. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Source

Shapiro E.D.,Yale University
New England Journal of Medicine

A 32-year-old pregnant woman from southeastern Connecticut presents to her physician in July at 26 weeks' gestation because of a skin lesion. She reports she has had fatigue, arthralgia, and headache for 2 days and a rash in her left axilla for 1 day. She lives in a wooded area and works in her garden frequently. Six weeks earlier, she had removed a small tick that was attached behind her right knee. On physical examination, she is afebrile. She has an erythematous, oval macular lesion, 7 to 8 cm in diameter, in her left axilla, with enhanced central erythema; no other abnormalities are noted. How should her case be managed? Copyright © 2014 Massachusetts Medical Society. Source

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