Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Predicting Anatomical Therapeutic Chemical (ATC) Classification of Drugs by Integrating Chemical-Chemical Interactions and Similarities

The Anatomical Therapeutic Chemical (ATC) classification system, recommended by the World Health Organization, categories drugs into different classes according to their therapeutic and chemical characteristics. For a set of query compounds, how can we identify which ATC-class (or classes) they belong to? It is an important and challenging problem because the information thus obtained would be quite useful for drug development and utilization. By hybridizing the informations of chemical-chemical interactions and chemical-chemical similarities, a novel method was developed for such purpose. It was observed by the jackknife test on a benchmark dataset of 3,883 drug compounds that the overall success rate achieved by the prediction method was about 73% in identifying the drugs among the following 14 main ATC-classes: (1) alimentary tract and metabolism; (2) blood and blood forming organs; (3) cardiovascular system; (4) dermatologicals; (5) genitourinary system and sex hormones; (6) systemic hormonal preparations, excluding sex hormones and insulins; (7) anti-infectives for systemic use; (8) antineoplastic and immunomodulating agents; (9) musculoskeletal system; (10) nervous system; (11) antiparasitic products, insecticides and repellents; (12) respiratory system; (13) sensory organs; (14) various. Such a success rate is substantially higher than 7% by the random guess. It has not escaped our notice that the current method can be straightforwardly extended to identify the drugs for their 2nd-level, 3rd-level, 4th-level, and 5th-level ATC-classifications once the statistically significant benchmark data are available for these lower levels

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.National Science Council of Taiwan (NSC 99-2221-E-039-013-)Committee on Chinese Medicine and Pharmacy (CCMP100-RD-030)China Medical University and Asia University (CMU98-TCM)China Medical University and Asia University (CMU99-TCM)China Medical University and Asia University (CMU99-S-02)China Medical University and Asia University (CMU99-ASIA-25)China Medical University and Asia University (CMU99-ASIA-26)China Medical University and Asia University (CMU99-ASIA-27)China Medical University and Asia University (CMU99-ASIA-28)Taiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004)Taiwan Department of Health. Cancer Research Center of Excellence (DOH100-TD-C-111-005

Search for Second-Generation Scalar Leptoquarks in ppˉ\bm{p \bar{p}} Collisions at s\sqrt{s}=1.96 TeV

Results on a search for pair production of second generation scalar leptoquark in $p \bar{p}$ collisions at $\sqrt{s}$=1.96 TeV are reported. The data analyzed were collected by the CDF detector during the 2002-2003 Tevatron Run II and correspond to an integrated luminosity of 198 pb$^{-1}$. Leptoquarks (LQ) are sought through their decay into (charged) leptons and quarks, with final state signatures represented by two muons and jets and one muon, large transverse missing energy and jets. We observe no evidence for $LQ$ production and derive 95% C.L. upper limits on the $LQ$ production cross sections as well as lower limits on their mass as a function of $\beta$, where $\beta$ is the branching fraction for $LQ \to \mu q$.Comment: 9 pages (3 author list) 5 figure

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

Collapse risk and residual drift performance of steel buildings using post-tensioned MRFs and viscous dampers in near-fault regions

The potential of post-tensioned self-centering moment-resisting frames (SC-MRFs) and viscous dampers to reduce the collapse risk and improve the residual drift performance of steel buildings in near-fault regions is evaluated. For this purpose, a prototype steel building is designed using different seismic-resistant frames, i.e.: moment-resisting frames (MRFs); MRFs with viscous dampers; SC-MRFs; and SC-MRFs with viscous dampers. The frames are modeled in OpenSees where material and geometrical nonlinearities are taken into account as well as stiffness and strength deterioration. A database of 91 near-fault, pulse-like ground motions with varying pulse periods is used to conduct incremental dynamic analysis (IDA), in which each ground motion is scaled until collapse occurs. The probability of collapse and the probability of exceeding different residual story drift threshold values are calculated as a function of the ground motion intensity and the period of the velocity pulse. The results of IDA are then combined with probabilistic seismic hazard analysis models that account for near-fault directivity to assess and compare the collapse risk and the residual drift performance of the frames. The paper highlights the benefit of combining the post-tensioning and supplemental viscous damping technologies in the near-source. In particular, the SC-MRF with viscous dampers is found to achieve significant reductions in collapse risk and probability of exceedance of residual story drift threshold values compared to the MRF. © 2016 Springer Science+Business Media Dordrech

NR-2L: A Two-Level Predictor for Identifying Nuclear Receptor Subfamilies Based on Sequence-Derived Features

Nuclear receptors (NRs) are one of the most abundant classes of transcriptional regulators in animals. They regulate diverse functions, such as homeostasis, reproduction, development and metabolism. Therefore, NRs are a very important target for drug development. Nuclear receptors form a superfamily of phylogenetically related proteins and have been subdivided into different subfamilies due to their domain diversity. In this study, a two-level predictor, called NR-2L, was developed that can be used to identify a query protein as a nuclear receptor or not based on its sequence information alone; if it is, the prediction will be automatically continued to further identify it among the following seven subfamilies: (1) thyroid hormone like (NR1), (2) HNF4-like (NR2), (3) estrogen like, (4) nerve growth factor IB-like (NR4), (5) fushi tarazu-F1 like (NR5), (6) germ cell nuclear factor like (NR6), and (7) knirps like (NR0). The identification was made by the Fuzzy K nearest neighbor (FK-NN) classifier based on the pseudo amino acid composition formed by incorporating various physicochemical and statistical features derived from the protein sequences, such as amino acid composition, dipeptide composition, complexity factor, and low-frequency Fourier spectrum components. As a demonstration, it was shown through some benchmark datasets derived from the NucleaRDB and UniProt with low redundancy that the overall success rates achieved by the jackknife test were about 93% and 89% in the first and second level, respectively. The high success rates indicate that the novel two-level predictor can be a useful vehicle for identifying NRs and their subfamilies. As a user-friendly web server, NR-2L is freely accessible at either http://icpr.jci.edu.cn/bioinfo/NR2L or http://www.jci-bioinfo.cn/NR2L. Each job submitted to NR-2L can contain up to 500 query protein sequences and be finished in less than 2 minutes. The less the number of query proteins is, the shorter the time will usually be. All the program codes for NR-2L are available for non-commercial purpose upon request

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Hyponatremia revisited: Translating physiology to practice

The complexity of hyponatremia as a clinical problem is likely caused by the opposite scenarios that accompany this electrolyte disorder regarding pathophysiology (depletional versus dilutional hyponatremia, high versus low vasopressin levels) and therapy (rapid correction to treat cerebral edema versus slow correction to prevent osmotic demyelination, fluid restriction versus fluid resuscitation). For a balanced differentiation between these opposites, an understanding of the pathophysiology of hyponatremia is required. Therefore, in this review an attempt is made to translate the physiology of water balance regulation to strategies that improve the clinical management of hyponatremia. A physiology-based approach to the patient with hyponatremia is presented, first addressing the possibility of acute hyponatremia, and then asking if and if so why vasopressin is secreted non-osmotically. Additional diagnostic recommendations are not to rely too heavily of the assessment of the extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis as a diagnosis of exclusion, and to rationally investigate the pathophysiology of hyponatremia rather than to rely on isolated laboratory values with arbitrary cutoff values. The features of the major hyponatremic disorders are discussed, including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise-associated hyponatremia. The treatment of hyponatremia is reviewed from simple saline solutions to the recently introduced vasopressin receptor antagonists, including their promises and limitations. Given the persistently high rates of hospital-acquired hyponatremia, the importance of improving the management of hyponatremia seems both necessary and achievable. Copyrigh