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Search Results: 1 - 10 of 146436 matches for " Lynn F. Ten Eyck "
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A Generalized Allosteric Mechanism for cis-Regulated Cyclic Nucleotide Binding Domains
Alexandr P. Kornev,Susan S. Taylor ,Lynn F. Ten Eyck
PLOS Computational Biology , 2008, DOI: 10.1371/journal.pcbi.1000056
Abstract: Cyclic nucleotides (cAMP and cGMP) regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB) domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels) using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1) the phosphate binding cassette (PBC), which binds the cAMP ribose-phosphate, 2) the “hinge,” a flexible helix, which contacts the PBC, 3) the β2,3 loop, which provides precise positioning of an invariant arginine from the PBC, and 4) a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif). The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the β2,3 loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP) represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.
Order parametr for design of proteinlike heteropolymers
E. Nelson,L. Ten Eyck,J. Onuchic
Physics , 1998,
Abstract: preprint withdrawn. A revised version of this paper, with different authors appears in E. Nelson, P. Wolynes, and J. Onuchic, in Optimization in computational chemistry and molecular biology, C. Floudas and P. Pardalos editors, (1999)). The main failing of my approach in these papers is the fact that the Hamiltonian and order parameters are based on pair distances only, and therefore do not break the local gauge (reflection) symmetry. Consequently, the order parameters cannot detect the difference between (for example) a partially compact topology and its mirror image. I take full responsibility for this problem, the withdrawal of this preprint, and the comments made above. Erik D. Nelson
Simulation in Medical Student Education: Survey of the Clerkship Directors in Emergency Medicine
Corey Heitz,Raymond Ten Eyck,Michael Smith,Michael Fitch
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2011,
Abstract: Introduction: The objective of this study is to identify (1) the current role of simulation in medical student emergency medicine (EM) education; (2) the challenges to initiating and sustaining simulationbased programs; and (3) educational advances to meet these challenges. Methods: We solicited members of the Clerkship Directors in Emergency Medicine (CDEM) e-mail list to complete a Web-based survey addressing the use of simulation in both EM clerkships and preclinical EM curricula. Survey elements addressed the nature of the undergraduate EM clerkship and utilization of simulation, types of technology, and barriers to increased use in each setting. Results: CDEM members representing 60 EM programs on the list (80%) responded. Sixty-seven percent of EM clerkships are in the fourth year of medical school only and 45% are required. Fewer than 25% of clerkship core curriculum hours incorporate simulation. The simulation modalities used most frequently were high-fidelity models (79%), task trainers (55%), and low-fidelity models (30%). Respondents identified limited faculty time (88.7%) and clerkship hours (47.2%) as the main barriers to implementing simulation training in EM clerkships. Financial resources, faculty time, and the volume of students were the main barriers to additional simulation in preclinical years. Conclusion: A focused, stepwise application of simulation to medical student EM curricula can help optimize the ratio of student benefit to faculty time. Limited time in the curriculum can be addressed by replacing existing material with simulation-based modules for those subjects better suited to simulation. Faculty can use hybrid approaches in the preclinical years to combine simulation with classroom settings for either small or large groups to more actively engage learners while minimizing identified barriers.
A Role for Histone Chaperones in Regulating RNA Polymerase II  [PDF]
JoDi Lynn Osborn, Susanna F. Greer
Advances in Biological Chemistry (ABC) , 2015, DOI: 10.4236/abc.2015.52004
Abstract: Transcription is a highly regulated cellular process in which dysfunction leads to disease. One level of regulation is chromatin structure which protects promoters from transcription factor binding. To circumvent this blockade, histone chaperones aid in displacement of nucleosomes. In particular, the histone chaperone complex HUCA, consisting of Hira, Ubn1, Cabin1, and ASF1a, replaces histone variant H3.1 with H3.3 in front of actively transcribing RNA Polymerase II (RNAPII). The 26S proteasome is a major degrader of proteins within the cell and plays both proteolytic and non- proteolytic roles in transcriptional regulation. One major role is the degradation of irreversibly arrested RNAPII. Several interactions between HUCA, the 26S proteasome, and RNAPII have been characterized individually; we now present observations from our lab and others which directly associate elongating RNAPII with the degradation machinery through observations of involvement with the HUCA complex. Our short report presents these ideas and discusses their importance in transcriptional regulation as well as implications in disease manifestation.
The Observation of Percolation-Induced 2D Metal-Insulator Transition in a Si MOSFET
L. A. Tracy,E. H. Hwang,K. Eng,G. A. Ten Eyck,E. P. Nordberg,K. Childs,M. S. Carroll,M. P. Lilly,S. Das Sarma
Physics , 2008, DOI: 10.1103/PhysRevB.79.235307
Abstract: By analyzing the temperature ($T$) and density ($n$) dependence of the measured conductivity ($\sigma$) of 2D electrons in the low density ($\sim10^{11}$cm$^{-2}$) and temperature (0.02 - 10 K) regime of high-mobility (1.0 and 1.5 $\times 10^4$ cm$^2$/Vs) Si MOSFETs, we establish that the putative 2D metal-insulator transition is a density-inhomogeneity driven percolation transition where the density-dependent conductivity vanishes as $\sigma (n) \propto (n - n_p)^p$, with the exponent $p \sim 1.2$ being consistent with a percolation transition. The `metallic' behavior of $\sigma (T)$ for $n > n_p$ is shown to be well-described by a semi-classical Boltzmann theory, and we observe the standard weak localization-induced negative magnetoresistance behavior, as expected in a normal Fermi liquid, in the metallic phase.
Probing limits of STM field emission patterned Si:P $δ$-doped devices
M. Rudolph,S. M. Carr,G. Subramania,G. Ten Eyck,J. Dominguez,T. Pluym,M. P. Lilly,M. S. Carroll,E. Bussmann
Physics , 2014,
Abstract: Recently, a single atom transistor was deterministically fabricated using phosphorus in Si by H-desorption lithography with a scanning tunneling microscope (STM). This milestone in precision, achieved by operating the STM in the conventional tunneling mode, typically utilizes very slow ($\sim\!10^2~\mathrm{nm^2/s}$) patterning speeds. By contrast, using the STM in a high voltage ($>10~\mathrm{V}$) field emission mode, patterning speeds can be increased by orders of magnitude to $\gtrsim\!10^4~\mathrm{nm^2/s}$. We show that the rapid patterning negligibly affects the functionality of relatively large micron-sized features, which act as contacting pads on these devices. For nanoscale structures, we show that the resulting transport is consistent with the donor incorporation chemistry enhancing the device definition to a scale of $10~\mathrm{nm}$ even though the pattering spot size is $40~\mathrm{nm}$.
Cryogenic preamplification of a single-electron-transistor using a silicon-germanium heterojunction-bipolar-transistor
M. J. Curry,T. D. England,N. C. Bishop,G. Ten-Eyck,J. R. Wendt,T. Pluym,M. P. Lilly,S. M. Carr,M. S. Carroll
Physics , 2015, DOI: 10.1063/1.4921308
Abstract: We examine a silicon-germanium heterojunction bipolar transistor (HBT) for cryogenic pre-amplification of a single electron transistor (SET). The SET current modulates the base current of the HBT directly. The HBT-SET circuit is immersed in liquid helium, and its frequency response from low frequency to several MHz is measured. The current gain and the noise spectrum with the HBT result in a signal-to-noise-ratio (SNR) that is a factor of 10-100 larger than without the HBT at lower frequencies. The transition frequency defined by SNR = 1 has been extended by as much as a factor of 10 compared to without the HBT amplification. The power dissipated by the HBT cryogenic pre-amplifier is approximately 5 nW to 5 {\mu}W for the investigated range of operation. The circuit is also operated in a single electron charge read-out configuration in the time-domain as a proof-of-principle demonstration of the amplification approach for single spin read-out.
Giant cell tumor of soft tissue of hand: simple but rare diagnosis, which is often missed
Sarwan Kumar,Lynn F. Carter
Clinics and Practice , 2011, DOI: 10.4081/cp.2011.e54
Abstract: Giant cell tumor of soft tissue originally described in 1972 in two different series by Salm and Sissons is a rare entity, which is clinically and histopathologically indistinguishable from giant cell tumor of bone. Usually involve thigh, trunk, and lower extremities but rarely involve the hands. GCT-ST is a benign tumor, which can transform into malignant form and also has potential for recurrence and metastasis. We present an otherwise healthy, middle age female who originally presented with swellings on her left finger was diagnosed with giant cell tumor of soft tissue hand.
A rapid and sensitive bioassay to measure bone morphogenetic protein activity
Lior Zilberberg, Peter ten Dijke, Lynn Y Sakai, Daniel B Rifkin
BMC Cell Biology , 2007, DOI: 10.1186/1471-2121-8-41
Abstract: Two cells lines, C2C12 and HepG2 were stably transfected with a reporter plasmid consisting of BMP-responsive elements from the Id1 promoter fused to a luciferase reporter gene. Exposure of cells containing this construct to BMPs induces the expression of luciferase, which can be quantified with a luminometer. The bioassay is specific for BMPs and can detect BMP-4 activity at a concentration as low as 3 pM. Related family members, such as TGF-beta1, TGF-beta2 and TGF-beta3, do not induce the reporter gene.The assay is rapid (less than 24 hours) and can be used, as described in this paper, to measure BMP activity in complex solutions and in cell culture in a simple and efficient way.Bone morphogenic proteins (BMPs) are members of the transforming growth factor beta (TGF-β) superfamily that consists of a number of structurally related polypeptides that control a broad array of cellular processes, including cell proliferation, apoptosis and differentiation [1,2]. Although BMPs originally were identified as proteins that induced formation of bone when implanted into the muscle of adult rats [3,4], BMPs also play crucial roles in dorsoventral patterning of the mesoderm, neural patterning, skeletal development, and limb formation [5]. Altered BMP signaling pathways are associated with several human diseases including arthritis, osteoporosis, kidney diseases, cancer and pulmonary hypertension [6-10].BMPs are synthesized as precursor proteins. After dimerization, the precursor molecules are proteolytically cleaved within the cell by proprotein convertases at the multibasic motif RXXR to yield the active, carboxy-terminal mature protein dimer [11-13]. BMPs exert their biological activity through combinations of type I and type II serine/threonine kinase receptors. Three distinct BMP type I receptors, i.e. activin receptor-like kinase (ALK)-2, ALK3 (also termed BMPRIA) and ALK6 (BMPRIB) and three distinct type II receptors, i.e. BMP type II receptor (BMPRII) and two activin t
Graves’ Disease and Down Syndrome: Case Report  [PDF]
Fábio Ferreira do Espírito Santo, Denise Rosso Tenório Wanderley Rocha, Alberto Krayyem Arbex
Open Journal of Endocrine and Metabolic Diseases (OJEMD) , 2016, DOI: 10.4236/ojemd.2016.61004
Abstract: Down syndrome (DS) is the most common chromosomal abnormality in humans, and the most frequent cause of mental retardation. Patients affected by this syndrome show an increased prevalence of autoimmune diseases. The most common of those is Hypothyroidism. We present a case report describing the association of Down syndrome with Hyperthyroidism. An 18-year-old patient presented with a history of recurrent throat infections and intermittent diarrhea, having developed a totalalopecia areatawithin one month from the first visit to the physician. After consultations with general practitioners, he was directed to an Endocrinology Ambulatory and diagnosed with a clear case of Graves’ disease associated with Down syndrome. Treatment was started with methimazole 20 mg/day, and after two months, was adjusted to 40 mg/day. The patient reached adequate clinical and laboratory balance after five months of treatment. Thus, the association between Down syndrome and Graves’ Disease is relevant in medical practice, due to its specific characteristics on diagnosis, and the need of an adequate treatment regarding this disease association.
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