New Haven, CT, United States
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.

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Yale University | Date: 2016-08-18

The present invention provides a prosthetic hand capable of multiple grasp types. The prosthetic finger units are underactuated both within and between the finger units using a differential mechanism arrangement. The locking movement of the prosthetic thumb unit is coupled to the differential mechanism. As the user repositions the prosthetic thumb unit, the differential mechanism is effected as to alter both the initial positions and force distribution of the prosthetic finger units. The present invention further provides an additive manufacturing molding method for making the same.

Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles. In some embodiments, the particles include therapeutic, diagnostic, nutraceutical, and/or prophylactic agents such as those used as sunblock compositions.

The present invention relates to the discovery of compositions and methods for therapeutic immunization for treatment of chronic hepatitis B. Methods of the invention include a method generating an evolved high titer hybrid-hepatitis B virus (HBV) vector, methods of treating and/or preventing HBV, and methods of inducing a memory T and B cell immune response against HBV infection in a subject administered the VLV composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with HBV.

Romberg N.,Yale University
Nature Genetics | Year: 2014

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.

Humphrey J.D.,Yale University
Nature Reviews Molecular Cell Biology | Year: 2014

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.

Wang X.-J.,Yale University
Physiological Reviews | Year: 2010

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.

Bogan J.S.,Yale University
Annual Review of Biochemistry | Year: 2012

To enhance glucose uptake into muscle and fat cells, insulin stimulates the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface. This response requires the intersection of insulin signaling and vesicle trafficking pathways, and it is compromised in the setting of overnutrition to cause insulin resistance. Insulin signals through AS160Tbc1D4 and Tbc1D1 to modulate Rab GTPases and through the Rho GTPase TC10α to act on other targets. In unstimulated cells, GLUT4 is incorporated into specialized storage vesicles containing IRAP, LRP1, sortilin, and VAMP2, which are sequestered by TUG, Ubc9, and other proteins. Insulin mobilizes these vesicles directly to the plasma membrane, and it modulates the trafficking itinerary so that cargo recycles from endosomes during ongoing insulin exposure. Knowledge of how signaling and trafficking pathways are coordinated will be essential to understanding the pathogenesis of diabetes and the metabolic syndrome and may also inform a wide range of other physiologies. © 2012 by Annual Reviews. All rights reserved.

Shapiro E.D.,Yale University
New England Journal of Medicine | Year: 2014

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.

Crabtree R.H.,Yale University
Chemical Reviews | Year: 2015

Active catalysts typically have labile sites that are in principle much more sensitive to all the species present in the reaction medium as well as to the ambient conditions than is a stable complex in solution. The effects of changing solvents, additives, and conditions may therefore have big effects. Avoiding impurities in the solvent or substrate can also be a help, big or small depending on the case. The relevance of the topic is not limited to catalyst chemists. Many researchers, not themselves specialists in the field, apply a homogeneous catalyst taken from the literature in the hope of obtaining a needed organic product or bringing about some desired transformation. These efforts sometimes go astray from neglect of some unstated assumption in the original work or from a change either in the substrate structure or in the conditions used in the prior reports.

Work done in the field of resolving heterogeneity problems and impurity artifacts in operationally homogeneous transition metal catalysts are discussed. Unintended heterotopy with loss of all the ligands initially present in the precatalyst are found to nullify the effect of sophisticated ligand design such as in the multifunctional ligands. Narayanan et al. have shown that nanoparticle shape and size can strongly affect activity. Finke and co-workers have now modified their conclusions for the Maitlis catalyst and find in operando X-ray absorption fine structure (XAFS), kinetic, and kinetic poisoning evidence for the predominant species and active catalyst being subnanometer Rh 4 clusters. Conlon and co-workers studied the Suzuki-Miyaura reaction catalyzed by Pd/C by estimating the solution levels of Pd by hot filtration followed by high-performance liquid chromatography (HPLC) analysis for the organics and inductively coupled plasma-mass spectrometry (ICP-MS) analysis for the palladium.

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