julilili42/papers huggingface dataset:
Baryon structure in AdS/QCD
2013-07-11

We discuss baryon structure in a soft-wall anti-de Sitter/quantum chromodynamics model. From unified point of view we describe nucleon form factors and the electroproduction of the N(1440) Roper resonance. The Roper resonance is identified as the first radially excited state of the nucleon. The obtained results for helicity amplitudes of the Roper electroproduction are in good agreement with the recent results of the CLAS Collaboration at JLab.
Faculty Opinions recommendation of Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.
2013-07-11

Read the full review for this Faculty Opinions recommended article: Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.
Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors
2013-07-12

The caseinolytic peptidase P (CLPP) is conserved from bacteria to humans. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder together with the chaperone CLPX. In spite of a known relevance for the mitochondrial unfolded protein response, its substrates and tissue-specific roles are unclear in mammals. Recessive CLPP mutations were recently observed in the human Perrault variant of ovarian failure and sensorineural hearing loss. Here, a first characterization of CLPP null mice demonstrated complete female and male infertility and auditory deficits. Disrupted spermatogenesis already at the spermatid stage and ovarian follicular differentiation failure were evident. Reduced pre-/post-natal survival and marked ubiquitous growth retardation contrasted with only light impairment of movement and respiratory activities. Interestingly, the mice showed resistance to ulcerative dermatitis. Systematic expression studies detected up-regulation of other mitochondrial chaperones, accumulation of CLPX and mtDNA as well as inflammatory factors throughout tissues. T-lymphocytes in the spleen were activated. Thus, murine Clpp deletion represents a faithful Perrault model. The disease mechanism probably involves deficient clearance of mitochondrial components and inflammatory tissue destruction.
Parallel Fabrication of Plasmonic Nanocone Sensing Arrays
2013-07-12

Abstract A fully parallel approach for the fabrication of arrays of metallic nanocones and triangular nanopyramids is presented. Different processes utilizing nanosphere lithography for the creation of etch masks are developed. Monolayers of spheres are reduced in size and directly used as masks, or mono‐ and double layers are employed as templates for the deposition of aluminum oxide masks. The masks are transferred into an underlying gold or silver layer by argon ion milling, which leads to nanocones or nanopyramids with very sharp tips. Near the tips the enhancement of an external electromagnetic field is particularly strong. This fact is confirmed by numerical simulations and by luminescence imaging in a confocal microscope. Such localized strong fields can amongst others be utilized for high‐resolution, high‐sensitivity spectroscopy and sensing of molecules near the tip. Arrays of such plasmonic nanostructures thus constitute controllable platforms for surface‐enhanced Raman spectroscopy. A thin film of pentacene molecules is evaporated onto both nanocone and nanopyramid substrates, and the observed Raman enhancement is evaluated.
Sequential decisions on FAS sequencing guided by biomarkers in patients with lymphoproliferation and autoimmune cytopenia
2013-07-12

Clinical and genetic heterogeneity renders confirmation or exclusion of autoimmune lymphoproliferative syndrome difficult. To re-evaluate and improve the currently suggested diagnostic approach to patients with suspected FAS mutation, the most frequent cause of autoimmune lymphoproliferative syndrome, we prospectively determined 11 biomarkers in 163 patients with splenomegaly or lymphadenopathy and presumed or proven autoimmune cytopenia(s). Among 98 patients sequenced for FAS mutations in CD3(+)TCRα/β(+)CD4(-)CD8(-) "double negative" T cells, 32 had germline and six had somatic FAS mutations. The best a priori predictor of FAS mutations was the combination of vitamin B12 and soluble FAS ligand (cut-offs 1255 pg/mL and 559 pg/mL, respectively), which had a positive predictive value of 92% and a negative predictive value of 97%. We used these data to develop a web-based probability calculator for FAS mutations using the three most discriminatory biomarkers (vitamin B12, soluble FAS ligand, interleukin-10) of the 11 tested. Since more than 60% of patients with lymphoproliferation and autoimmune cytopenia(s) in our cohort did not harbor FAS mutations, 15% had somatic FAS mutations, and the predictive value of double-negative T-cell values was rather low (positive and negative predictive values of 61% and 77%, respectively), we argue that the previously suggested diagnostic algorithm based on determination of double-negative T cells and germline FAS sequencing, followed by biomarker analysis, is not efficient. We propose vitamin B12 and soluble FAS ligand assessment as the initial diagnostic step with subsequent decision on FAS sequencing supported by a probability-calculating tool.
Optimal use and outcomes of orthotopic neobladder reconstruction in men and women
2013-07-12

Both in men and in women, orthotopic neobladder should be considered as standard-of-care with excellent long-term oncologic and functional outcome. Due to lack of long-term functional and oncologic data, total intracorporeal diversion should be limited to selected patients and centers with broad expertise in robotic surgery.
New basic approach to treat non‐small cell lung cancer based on RNA‐interference
2013-07-12

Abstract Background To date the therapy for non‐small cell lung cancer ( NSCLC ) is associated with severe side effects, frustrating outcomes, and does not consider different tumor characteristics. The RNA ‐interference ( RNAi ) pathway represents a potential new approach to treat NSCLC . With small interfering ribonucleic acids ( siRNAs ), it is possible to reduce the expression of proliferation‐dependent proteins in tumor cells, leading to their apoptosis. We propose that siRNAs could be adapted to the tumor type and may cause fewer side effects than current therapy. Methods Four NSCLC cell lines were cultured under standard conditions and transfected with three different concentrations of siRNAs targeted against the hypoxia‐inducible factors 1α and 2α ( HIF1α and HIF2α ) and signal transducer and activator of transcription 3 ( STAT3 ). The expression was observed by quantitative real‐time polymerase chain reaction and western blots. For the analysis of cell growth three days after transfection, the cell number was detected using a CASY cell counter system. Results The results of the silencing of the analyzed factors differ in each cell line. Cell growth was significantly reduced in all cell lines after transfection with HIF1α ‐ and STAT3 ‐ siRNA . The silencing of HIF2α resulted in a significant effect on cell growth in squamous, and large‐cell lung cancer. Conclusions This study shows that the knockdown and viability to siRNA transfection differ in each tumor type according to the used siRNA . This implies that the tumor types differ among themselves and should be treated differently. Therefore, the authors suggest a possible approach to a more personalized treatment of NSCLC .
Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients
2013-07-13

The frequently altered phosphatidylinositol‐3‐kinase (PI3K)/Akt signaling pathway is involved in the regulation of cellular processes required for breast carcinogenesis. The aim of the project was to develop a method to identify hotspot mutations in the PIK3CA gene in circulating tumor cells (CTCs) of metastatic breast cancer (metBC) patients. From 44 enrolled CTC‐positive metBC patients a total number of 57 peripheral blood samples were analysed by CellSearch®. Genomic DNA of enriched CTCs was isolated, amplified and analyzed for PIK3CA mutations in exons 9 and 20 which lead to E542K, E545K or H1047R amino acid changes and result in increased PI3K activity. The mutations were detected by using SNaPshot‐methodology comprising PCR amplification and single nucleotide primer extension. SNaPshot analysis was established using genomic DNA from different breast cancer cell lines and then successfully transferred to investigate blood samples and single cells. Overall, twelve hotspot mutations in either exon 9/E545K (6/12, 50%) or exon 20/H1047R (6/12, 50%) could be determined within 9 out of 57 (15.8%) blood samples from 7 out of 44 (15.9%) patients; CTC counts ranged from 1 to 9748. PIK3CA variants E542K, E545G and E545A were not detected. Analysing the PIK3CA genotype of CTCs has clinical relevance with respect to drug resistance, e.g. against HER2‐targeted therapy. The herein described approach including SNaPshot technology provides a simple method to characterize hotspot mutations within CTCs enriched from peripheral blood and can be easily adopted for analysing further therapeutically relevant SNPs.
Mutual Exclusivity Analysis of Genetic and Epigenetic Drivers in Melanoma Identifies a Link Between p14ARF and RARβ Signaling
2013-07-13

Abstract Melanoma genomes contain thousands of alterations including: mutations, copy number alterations, structural aberrations, and methylation changes. The bulk of this variation is stochastic and functionally neutral, with only a small minority representing “drivers” that contribute to the genesis and maintenance of tumors. Drivers are often directly or inversely correlated across tumors, reflecting the molecular and regulatory signaling pathways in which they operate. Here, a profile of genetic and epigenetic drivers in 110 human melanoma cell lines was generated and searched for non-random distribution patterns. Statistically significant mutual exclusivity was revealed among components of each of the p16INK4A-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways. In addition, an inverse correlation was observed between promoter hypermethylation of retinoic acid receptor β (RARB) and CDKN2A alterations affecting p14ARF (P &amp;lt; 0.0001), suggesting a functional link between RARβ signaling and the melanoma-suppressive activities of p14ARF. Mechanistically, all-trans retinoic acid (ATRA) treatment increased the expression of p14ARF in primary human melanocytes and the steady-state levels of p14ARF in these cells were shown to be regulated via RARβ. Furthermore, the ability of ATRA to induce senescence is reduced in p14ARF-depleted melanocytes, and we provide proof-of-concept that ATRA can induce irreversible growth arrest in melanoma cells with an intact RARβ-p14ARF signaling axis, independent of p16INK4A and p53 status. Implications: These data highlight the power of mutual exclusivity analysis of cancer drivers to unravel molecular pathways and establish a previously unrecognized cross-talk between RARβ and p14ARF with potential implications for melanoma treatment. Mol Cancer Res; 11(10); 1166–78. ©2013 AACR.
Fluoxetine Induced Suicidal Erythrocyte Death
2013-07-15

The antidepressant fluoxetine inhibits ceramide producing acid sphingomyelinase. Ceramide is in turn known to trigger eryptosis the suicidal death of erythrocytes characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Ceramide is effective through sensitizing the erythrocytes to the pro-eryptotic effect of increased cytosolic Ca2+ activity ([Ca2+]i). In nucleated cells, fluoxetine could either inhibit or stimulate suicidal death or apoptosis. The present study tested whether fluoxetine influences eryptosis. To this end cell volume was estimated from forward scatter, phosphatidylserine exposure from annexin V binding, hemolysis from hemoglobin release and [Ca2+]i from Fluo-3 fluorescence intensity. As a result, a 48 h exposure of erythrocytes to fluoxetine (≥25 μM) significantly decreased forward scatter, increased annexin V binding and enhanced [Ca2+]i. The effect on annexin V binding was significantly blunted, but not abolished, in the absence of extracellular Ca2+. In conclusion, fluoxetine stimulates eryptosis, an effect at least in part due to increase of cytosolic Ca2+ activity.
Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly
2013-07-15

Abstract Background In rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. A specific, balanced and, to an extent, protective immunity will develop over time in response to repeated parasite encounters, with immune responses initially being poorly adapted and non-protective. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly. Results In children schistosomiasis prevailed (33%) while hookworm and Entamoeba histolytica/E. dispar was found in up to half of adults and the elderly. Mansonella perstans filariasis was only present in adults (24%) and the elderly (25%). Two or more parasite infections were diagnosed in 41% of children, while such polyparasitism was present in 34% and 38% of adults and the elderly. Cytokine and chemokine production was distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine IL-19 was activated by Entamoeba and Ascaris antigens, being low in neonates and children while IL-19 production enhanced “stepwise” in adults and elderly. In contrast, highest production of MIP-1delta/CCL15 was present in neonates and children and inducible by Entamoeba- specific antigens only. Adults and the elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably inducible by helminth- and Entamoeba- specific antigens and fungus-derived allergens. The lower cellular responsiveness in neonates and children highlighted the development of a parasite-specific cellular response profile in response to repeated episodes of exposure and re-infection. Conclusions Following repeated exposure to parasites, and as a consequence of host inability to prevent or eliminate intestinal helminth or protozoa infections, a repertoire of immune responses will evolve with lessened pro-inflammatory and pronounced regulatory cytokines and chemokines; this is required for partial parasite control as well as for preventing inadequate and excessive host tissue and organ damage.
Comparative method evaluation for size and size‐distribution analysis of gold nanoparticles
2013-07-16

Gold nanoparticles ( GNP s) are popular colloidal substrates in various sensor, imaging, and nanomedicine applications. In separation science, they have raised some interest as a support for sample preparation. Reasons for their popularity are their low cost, ability for size‐controlled synthesis with well‐defined narrow nanoparticle size distributions, as well as straightforward surface functionalization by self‐assembling (thiol‐containing) molecules on the surface, which allows flexible introduction of functionalities for the selective capture of analytes. Most commonly, the method of first choice for size determination is dynamic light scattering ( DLS ). However, DLS has some serious shortcomings, and results from DLS may be misleading. For this reason, in this contribution several distinct complementary nanoparticle sizing methodologies were utilized and compared to characterize citrate‐capped GNP s of different diameters in the range of 13–26 nm. Weaknesses and strengths of DLS , transmission electron microscopy, asymmetrical‐flow field‐flow fractionation and nanoelectrospray gas‐phase electrophoretic mobility molecular analysis are discussed and the results comparatively assessed. Furthermore, the distinct GNP s were characterized by measuring their zeta‐potential and surface plasmon resonance spectra. Overall, the combination of methods for GNP characterization gives a more realistic and comprehensive picture of their real physicochemical properties, (hydrodynamic) diameter, and size distribution.
A novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal dementia-like family
2013-07-17

Triggering receptor expressed on myeloid cells 2 (TREM2) homozygous mutations cause Nasu-Hakola disease, an early-onset recessive form of dementia preceded by bone cysts and fractures. The same type of mutations has recently been shown to cause frontotemporal dementia (FTD) without the presence of any bone phenotype. Here, we further confirm the association of TREM2 mutations with FTD-like phenotypes by reporting the first compound heterozygous mutation in a Turkish family.
How Do We Continue Treatment in Patients With Type 2 Diabetes When Therapeutic Goals Are Not Reached With Oral Antidiabetes Agents and Lifestyle? Incretin versus insulin treatment
2013-07-17

The pandemic of type 2 diabetes necessitates early and effective treatment to delay or prevent micro- and macrovascular complications associated with diabetes (1–3). However, the majority of patients with type 2 diabetes do not reach their therapeutic goals as a result of insufficient treatment. The cardiovascular mortality risk is increased, and 75% of patients with type 2 diabetes die of cardiovascular events. Type 2 diabetes is the main cause of end-stage renal disease and dialysis in many countries (4). The vascular complication risk can be lowered by improved metabolic control (2,3). However, further important treatment goals such as body weight reduction or the prevention of hypoglycemia are seldom accomplished. In type 2 diabetes, a stepwise escalation of therapy is suggested along the course and progression of the disease. Metformin is widely accepted as the first-line therapy, but owing to partly lacking evidence, with regard to further therapeutic steps there is room for various individual treatment choices. Recently, a Position Statement by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) tried to value and position second- and third-line therapies according to their efficacy, side effects, hypoglycemia incidence, body weight development, and costs (5). Adding another oral agent to metformin in order to escalate therapy when necessary presently gives the choice of sulfonylureas, glinides, dipeptidyl peptidase (DPP)-4 inhibitors, pioglitazone, and α-glucosidase inhibitors. The efficacy of these agents as add-on medication to metformin is only modest, and on average an additional HbA1c reduction of ~0.5–1% can be expected. Furthermore, the treatment with sulfonylureas, glinides, and pioglitazone is associated with body weight gain. Sulfonylurea and glinide therapy is also associated with a risk of hypoglycemia. α-Glucosidase inhibitors predominantly lower postprandial hyperglycemia and therefore show less HbA1c reduction in most studies. ...
Recognizing Genetic Forms of Parkinsonism
2013-07-17

SUMMARY It has been generally recognized that, in most cases of Parkinson's disease (PD), the causes are a result of the complex interaction of genetic and environmental factors. Only approximately 10–15% of PD cases appear to be rare forms with a Mendelian genetic cause. There has been an increasing need and demand in daily clinical work to look for a molecular diagnosis, although a number of neurologists feel uneasy when dealing with the growing number of possible genes and risk factors related to PD that are accessible for diagnosis. Research has highlighted the consequences not only for hereditary but also sporadic forms of PD. This review will provide an overview of the principal aspects of the genetics of PD. It will focus on their differences and similarities, and discuss several useful tools for clinicians, and the role and importance of a neurogeneticist.
Determining the Higgs Spin and Parity in the Diphoton Decay Channel
2013-07-18

We calculate the diphoton distribution in the decay of arbitrary spin-0 and spin-2 bosons produced from gluon fusion, taking into account the fact that gluons inside an unpolarized proton are generally linearly polarized. The gluon polarization brings about a difference in the transverse momentum distribution of positive and negative parity states. At the same time, it causes the azimuthal distribution of the photon pair to be nonisotropic for several spin-2 coupling hypotheses, allowing one to distinguish these from the isotropic scalar and pseudoscalar distributions.
WIPI β-propellers in autophagy-related diseases and longevity
2013-07-18

Autophagy is a catabolic pathway in which the cell sequesters cytoplasmic material, including long-lived proteins, lipids and organelles, in specialized double-membrane vesicles, called autophagosomes. Subsequently, autophagosomes communicate with the lysosomal compartment and acquire acidic hydrolases for final cargo degradation. This process of partial self-eating secures the survival of eukaryotic cells during starvation periods and is critically regulated by mTORC1 (mammalian target of rapamycin complex 1). Under nutrient-poor conditions, inhibited mTORC1 permits localized PtdIns(3)P production at particular membranes that contribute to autophagosome formation. Members of the human WIPI (WD-repeat protein interacting with phosphoinositides) family fulfil an essential role as PtdIns(3)P effectors at the initiation step of autophagosome formation. In the present article, we discuss the role of human WIPIs in autophagy, and the identification of evolutionarily conserved amino acids of WIPI-1 that confer PtdIns(3)P binding downstream of mTORC1 inhibition. We also discuss the PtdIns(3)P effector function of WIPIs in the context of longevity and autophagy-related human diseases, such as cancer and neurodegeneration.
GRO J1008 57: a laboratory for accretion physics
2013-07-18

We present timing and spectroscopic results of three outbursts of the transient high mass X-ray binary GRO J1008−57 in 2005, 2007, and 2011. The orbital parameters from the literature are not in agreement with the measured pulse arrival times. We therefore updated the orbital solution, specifically the orbital period and the time of periastron passage, using pointed observations with RXTE, Swift, and Suzaku. We confirmed our results with an analysis of RXTE-ASM lightcurves. We show that GRO J1008−57’s outbursts occur mostly at the same orbital phase and therefore make predictions of outbursts and, thus, scheduled observations possible. The X-ray spectrum of GRO J1008−57 during an outburst can be well described by a cutoff power law with an additional black body at energies below 10 keV. We found that the same spectral model describes GRO J1008−57 during the rise and the decline of the outburst at fluxes changing by two orders of magnitude. In particular, the photon index of the power law and the black body flux show a correlation with the total X-ray flux. Other parameters such as the black body temperature and the folding energy are independent of flux and remain the same over all analyzed outbursts.