The antinociceptive effect of electroacupuncture at different depths of acupoints and under the needling surface

<p>Abstract</p> <p>Background</p> <p>The stimulation of acupoints along the meridians, but not the non-acupoints outside of the meridians, produces analgesia. Although the acupoint is defined at the body surface, the exact location of the acupoints is not known. This study aims to examine whether the intensity and duration of the analgesic effect of electroacupuncture (EA) at the <it>Zusanli </it>(ST36) and <it>Sanynjiao </it>acupoints (SP6) change according to the depth of the stimulation.</p> <p>Methods</p> <p>Ninety-six male Wistar rats classified as responders were arbitrarily allocated into 16 groups of six rats each. Six groups received EA with uninsulated acupuncture needles (type I) or needles that were immersed in varnish and had the varnish circularly peeled 0.2 mm from the tip (type II), 0.2 mm at 3 mm (type III) or 5 mm (type IV) from the tip, or 0.2 mm at 5 and 1 mm from the tip (type V), or EA sham for 20 min. Five groups received injection of formalin into the acupoint bilaterally at 5 mm or 1 mm deep into ST36, 5 mm below ST36 but inserting the needle at 45° to the skin surface, or 5 mm deep into non-acupoints. The remaining groups received intraplantar injection of saline, 1% or 2.5% formalin. The analgesic effects were measured by the rat tail-flick test.</p> <p>Results</p> <p>The bilateral stimulation of ST36 and SP6 by uninsulated or insulated needles produced analgesia in the rat tail-flick test. The stronger and longer lasting effects occurred after EA with the types I and V needles, or injection of formalin 5 mm deep into ST36. The remaining needles produced weaker and shorter lasting effects. Slow analgesic effect also occurred after formalin injection at 1 mm or 5 mm below ST36 by inserting the needle at 45° to the skin surface.</p> <p>Conclusion</p> <p>The experimental results suggest that the efficacy of the EA stimulation depends on the spatial distribution of the current density under the needling surface rather than only the acupoint or the depth of needling.</p

Global late Quaternary megafauna extinctions linked to humans, not climate change

The late Quaternary megafauna extinction was a severe global-scale event. Two factors, climate change and modern humans, have received broad support as the primary drivers, but their absolute and relative importance remains controversial. To date, focus has been on the extinction chronology of individual or small groups of species, specific geographical regions or macroscale studies at very coarse geographical and taxonomic resolution, limiting the possibility of adequately testing the proposed hypotheses. We present, to our knowledge, the first global analysis of this extinction based on comprehensive country-level data on the geographical distribution of all large mammal species (more than or equal to 10 kg) that have gone globally or continentally extinct between the beginning of the Last Interglacial at 132 000 years BP and the late Holocene 1000 years BP, testing the relative roles played by glacial–interglacial climate change and humans. We show that the severity of extinction is strongly tied to hominin palaeobiogeography, with at most a weak, Eurasia-specific link to climate change. This first species-level macroscale analysis at relatively high geographical resolution provides strong support for modern humans as the primary driver of the worldwide megafauna losses during the late Quaternary

Design Novel Dual Agonists for Treating Type-2 Diabetes by Targeting Peroxisome Proliferator-Activated Receptors with Core Hopping Approach

Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses

A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.Spanish Ministry of Science and Innovation (grant BIO2008-04212)Spanish Ministry of Science and Innovation (grant FIS PI 08/0440)GVA-FEDER (PROMETEO/2010/001)Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grant RD06/0020/1019)Instituto de Salud Carlos III (ISCIII)Spanish Ministry of Science and InnovationSpanish Ministry of Health (FI06/00027

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter