292 research outputs found
Victor Horta\u27s Illusion of Space
An exploration of Victor Horta\u27s architectural illusion of space
Prostitution\u27s Positive Role in Society
Alice Cooper was a prominent brothel owner in Chattanooga during the mid nineteenth century. This research paper uses primary sources to defend the claim that her business had a positive impact on the local economy
CC‐BY: Is There Such a Thing as Too Open in Open Access?
Support and demand for researchers to publish in open access (OA) journals has been growing steadily among funding agencies, research organizations, and institutions of higher education. The Wellcome Trust and the Research Councils UK OA policies have begun imposing more finite restrictions, like publishing only under CC‐BY licenses, on researchers. CC‐BY, or Creative Commons Attribution, is one of several, and the most open, of all creative commons licensing. It most closely embodies the definition of OA, as established by the Berlin Declaration and Bethesda Statement on Open Access, by allowing for the most reuse, including the unrestricted creation of derivatives. Scholars have voiced concern that CC‐BY may not be the best license for all disciplines. Libraries, as OA publishers, custodians of institutional repositories, facilitators of scholarly research, and organizers of information, are well‐positioned to enhance a discussion on balancing the needs of scholars for minimum control over their work with the goal of OA publishing to most widely disseminate information and scholarship to the public without barriers of country, class, access, or financing
[η5-(Phenylethynyl)cyclopentadienyl](η4-tetraphenylcyclobutadiene)cobalt(I)
In the title compound, [Co(C13H9)(C28H20)], the Co atom is sandwiched between cyclopentadienyl and cyclobutadienyl rings that are inclined at a dihedral angle of 2.6 (3)°. The four phenyl rings are tilted with respect to the cyclobutadienyl plane so that the C4Ph4 unit constitutes a four-bladed propeller. The phenyl ring of the phenyl-alkyne substituent is inclined to the cyclopentadienyl ring at an angle of 34.92 (18)°. The crystal structure is stabilized solely by C—H⋯π interactions which generate a three-dimensional network
Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms
Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin
Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy
<p>Abstract</p> <p>Background</p> <p><it>KRAS </it>mutations may predict poor response to radiotherapy. Downstream events from <it>KRAS</it>, such as activation of <it>BRAF</it>, AKT and ERK, may also confer prognostic information but have not been tested in rectal cancer (RC). Our objective was to explore the relationships of <it>KRAS </it>and <it>BRAF </it>mutation status with p-AKT and p-ERK and outcomes in RC.</p> <p>Methods</p> <p>Pre-radiotherapy RC tumor biopsies were evaluated. <it>KRAS </it>and <it>BRAF </it>mutations were assessed by pyrosequencing; p-AKT and p-ERK expression by immunohistochemistry.</p> <p>Results</p> <p>Of 70 patients, mean age was 58; 36% stage II, 56% stage III, and 9% stage IV. Responses to neoadjuvant chemoradiotherapy: 64% limited, 19% major, and 17% pathologic complete response. 64% were <it>KRAS </it>WT, 95% were <it>BRAF </it>WT. High p-ERK levels were associated with improved OS but not for p-AKT. High levels of p-AKT and p-ERK expression were associated with better responses. <it>KRAS </it>WT correlated with lower p-AKT expression but not p-ERK expression. No differences in OS, residual disease, or tumor downstaging were detected by <it>KRAS </it>status.</p> <p>Conclusions</p> <p><it>KRAS </it>mutation was not associated with lesser response to chemoradiotherapy or worse OS. High p-ERK expression was associated with better OS and response. Higher p-AKT expression was correlated with better response but not OS.</p
The PI3K/Akt/mTOR axis in head and neck cancer: functions, aberrations, cross‐talk, and therapies
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113753/1/odi12206.pd
Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih
Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster
Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.
Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff
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