pinecone/core-2020-05-10-deduplication huggingface dataset:
Characterisation of human mesenchymal stem cells from multiple donors and the implications for large scale bioprocess development

This is an open access article published by Elsevier under the CC BY license\ud
(http://creativecommons.org/licenses/by/4.0/)Cell-based therapies have the potential to contribute to global healthcare, whereby the use of living cells\ud
and tissues can be used as medicinal therapies. Despite this potential, many challenges remain before the\ud
full value of this emerging field can be realized. The characterization of input material for cell-based therapy\ud
bioprocesses from multiple donors is necessary to identify and understand the potential implications\ud
of input variation on process development. In this work, we have characterized bone marrow derived\ud
human mesenchymal stem cells (BM-hMSCs) from multiple donors and discussed the implications of\ud
the measurable input variation on the development of autologous and allogeneic cell-based therapy\ud
manufacturing processes. The range of cumulative population doublings across the five BM-hMSC lines\ud
over 30 days of culture was 5.93, with an 18.2% range in colony forming efficiency at the end of the\ud
culture process and a 55.1% difference in the production of interleukin-6 between these cell lines. It has\ud
been demonstrated that this variation results in a range in the process time between these donor hMSC\ud
lines for a hypothetical product of over 13 days, creating potential batch timing issues when manufacturing\ud
products from multiple patients. All BM-hMSC donor lines demonstrated conformity to the ISCT\ud
criteria but showed a difference in cell morphology. Metabolite analysis showed that hMSCs from the\ud
different donors have a range in glucose consumption of 26.98 pmol cell−1 day−1, Lactate production of\ud
29.45 pmol cell−1 day−1 and ammonium production of 1.35 pmol cell−1 day−1, demonstrating the extent\ud
of donor variability throughout the expansion process. Measuring informative product attributes during\ud
process development will facilitate progress towards consistent manufacturing processes, a critical step\ud
in the translation cell-based therapies
Cosmological Problems of the String Axion Alleviated by High Scale SUSY
  of $m_{3/2}$ $\simeq$ 10-100 TeV

The string axion may provide the most attractive solution to the strong CP
problem in QCD. However, the axion energy density easily exceeds the dark
matter density in the present universe due to a large decay constant around
$10^{16}$ GeV, unless the initial value of the axion field is fine-tuned. We
show that this problem is alleviated if and only if the SUSY particle mass
scale is 10-100 TeV, since the decay of the saxion can produce a large enough
amount of entropy after the QCD phase transition, not disturbing the BBN
prediction. The saxion decay also produces a large number of the lightest SUSY
particles (LSPs). As a consequence, R-parity needs to be violated to avoid the
overproduction of the LSPs. The saxion field can be stabilized with relatively
simple Kahler potentials, not inducing a too large axion dark radiation.
Despite the large entropy production, the observed baryon number is explained
by the Affleck-Dine mechanism. Furthermore, the constraint from isocurvature
perturbations is relaxed, and the Hubble constant during inflation can be as
large as several $\times$ $10^{10}$ GeV.Comment: 12 pages, corrected typos, the version published in PL
Raman spectroscopy for medical diagnostics - From in-vitro biofluid assays to in-vivo cancer detection

This is the final version of the article. Available from the publisher via the DOI in this record.Raman spectroscopy is an optical technique based on inelastic scattering of light by vibrating molecules and can provide chemical fingerprints of cells, tissues or biofluids. The high chemical specificity, minimal or lack of sample preparation and the ability to use advanced optical technologies in the visible or near-infrared spectral range (lasers, microscopes, fibre-optics) have recently led to an increase in medical diagnostic applications of Raman spectroscopy. The key hypothesis underpinning this field is that molecular changes in cells, tissues or biofluids, that are either the cause or the effect of diseases, can be detected and quantified by Raman spectroscopy. Furthermore, multivariate calibration and classification models based on Raman spectra can be developed on large "training" datasets and used subsequently on samples from new patients to obtain quantitative and objective diagnosis. Historically, spontaneous Raman spectroscopy has been known as a low signal technique requiring relatively long acquisition times. Nevertheless, new strategies have been developed recently to overcome these issues: non-linear optical effects and metallic nanoparticles can be used to enhance the Raman signals, optimised fibre-optic Raman probes can be used for real-time in-vivo single-point measurements, while multimodal integration with other optical techniques can guide the Raman measurements to increase the acquisition speed and spatial accuracy of diagnosis. These recent efforts have advanced Raman spectroscopy to the point where the diagnostic accuracy and speed are compatible with clinical use. This paper reviews the main Raman spectroscopy techniques used in medical diagnostics and provides an overview of various applications
NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity

The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect. The onset of differentiation was enhanced by NDRG2 as determined through the myogenic regulatory factor expression profiles and myocyte fusion index. However, the overall level of differentiation in myotubes was not different. While NDRG2 up-regulated caspase 3/7 activities during differentiation, no increase in apoptosis was measured by TUNEL assay or through cleavage of caspase 3 and PARP proteins. During H2O2 treatment to induce oxidative stress, NDRG2 helped protect against the loss of proliferation and ER stress as measured by GRP78 expression with 3A-NDRG2 displaying less protection. NDRG2 also attenuated apoptosis by reducing cleavage of PARP and caspase 3 and expression of pro-apoptotic Bax while enhancing the pro-survival Bcl-2 and Bcl-xL levels. In contrast, Mcl-1 was not altered, and NDRG2 did not protect against palmitate-induced lipotoxicity. Our findings show that NDRG2 overexpression increases myoblast proliferation and caspase 3/7 activities without increasing overall differentiation. Furthermore, NDRG2 attenuates H2O2-induced oxidative stress and specific serine and threonine amino acid residues appear to contribute to its function in muscle cells
Modification of the $\rho$-meson detected by low-mass electron-positron pairs in central Pb - Au collisions at 158 A GeV/c

We present a measurement of $e^+e^-$ pair production in central Pb-Au collisions at 158$A$ GeV/$c$. As reported earlier, a significant excess of the $e^+e^-$ pair yield over the expectation from hadron decays is observed. The improved mass resolution of the present data set, recorded with the upgraded CERES experiment at the CERN-SPS, allows for a comparison of the data with different theoretical approaches. The data clearly favor a substantial in-medium broadening of the $\rho$ spectral function over a density-dependent shift of the $\rho$ pole mass at SPS energy. The in-medium broadening model implies that baryon induced interactions are the key mechanism to in-medium modifications of the $\rho$-meson in the hot fireball
Bacterioplankton and phytoplankton production in seven lakes in the Middle Rio Doce basin, south-east Brazil.

The purpose of this study was to measure the phytoplankton production (PP) and bacterial production (BP) simultaneously in seven lakes in the middle Rio Doce basin (southeast Brazil) during the dry and the rainy seasons. Limnological monitoring was conducted from 1999 to 2001 as well as both PP (radioactive carbon fixation) and BP (3H-Leucine incorporation) in four specific depths (100%, 10%, 1% of incident radiation, and aphotic zone). Furthermore, trophic state of the lakes was analyzed, considering the index proposed by Salas and Martino (1991) and Carlson (1977). In general, some parameters increased during the rainy season such as pH, conductivity, chlorophyll and total nitrogen. In the period of 1999/2000, the rain caused PP reduction in the lakes, excepting Carioca and Aguas Claras Lake, but in the years 2000/2001, the lakes did not show a similar pattern. In contrast, the rainy season of both years caused an expressive bacterioplankton production enhancing. Using Salas and Martino index, we observed that some lakes were affected by the seasonal runoff, therefore the typologie of these lakes changed from oligotrophic to mesotrophic conditions, otherwise considering the Carlson index all lakes were classified as eutrophic in both dry and rainy seasons. Indeed, Salas and Martino index demonstrated to be more appropriate to determine the trophic status of the lakes. Finally, our data indicate that until now, in spite of the lakes location, protected and unprotected area, the lakes still maintain their natural characteristics.200
On the Zarankiewicz Problem for the Intersection Hypergraphs

International audienceLet d and t be fixed positive integers, and let K d t,...,t denote the complete d-partite hypergraph with t ver-tices in each of its parts, whose hyperedges are the d-tuples of the vertex set with precisely one element from each part. According to a fundamental theorem of extremal hypergraph theory, due to Erdös [6], the number of hyperedges of a d-uniform hypergraph on n vertices that does not contain K d t,...,t as a subhypergraph, is n d− 1 t d−1. This bound is not far from being optimal. We address the same problem restricted to intersection hypergraphs of (d − 1)-dimensional simplices in R d. Given an n-element set S of such simplices, let H d (S) denote the d-uniform hypergraph whose vertices are the elements of S, and a d-tuple is a hyperedge if and only if the corresponding simplices have a point in common. We prove that if H d (S) does not contain K d t,...,t as a subhypergraph, then its number of edges is O(n) if d = 2, and O(n d−1+) for any > 0 if d ≥ 3. This is almost a factor of n better than Erd˝ os's above bound. Our result is tight, apart from the error term in the exponent. In particular, for d = 2, we obtain a theorem of Fox and Pach [7], which states that every K t,t-free intersection graph of n segments in the plane has O(n) edges. The original proof was based on a separator theorem that does not generalize to higher dimensions. The new proof works in any dimension and is simpler: it uses size-sensitive cuttings, a variant of random sampling
Turbulence characteristics of the Bödewadt layer in a large enclosed rotor-stator system

16 pagesInternational audienceA three-dimensional (3D) direct numerical simulation is combined with a laboratory study to describe the turbulent flow in an enclosed annular rotor-stator cavity characterized by a large aspect ratio G=(b-a)/h=18.32 and a small radius ratio a/b=0.152, where a and b are the inner and outer radii of the rotating disk and h is the interdisk spacing. The rotation rate Omega under consideration is equivalent to the rotational Reynolds number Re=Omegab2/nu=9.5 x 104, where nu is the kinematic viscosity of the fluid. This corresponds to a value at which an experiment carried out at the laboratory has shown that the stator boundary layer is turbulent, whereas the rotor boundary layer is still laminar. Comparisons of the 3D computed solution with velocity measurements have given good agreement for the mean and turbulent fields. The results enhance evidence of weak turbulence at this Reynolds number, by comparing the turbulence properties with available data in the literature. An approximately self-similar boundary layer behavior is observed along the stator side. The reduction of the structural parameter a1 under the typical value 0.15 and the variation in the wall-normal direction of the different characteristic angles show that this boundary layer is three-dimensional. A quadrant analysis of conditionally averaged velocities is performed to identify the contributions of different events (ejections and sweeps) on the Reynolds shear stress producing vortical structures. The asymmetries observed in the conditionally averaged quadrant analysis are dominated by Reynolds stress-producing events in this Bödewadt layer. Moreover, case 1 vortices (with a positive wall induced velocity) are found to be the major source of generation of special strong events, in agreement with the conclusions of Lygren and Andersson
Near-IR absorbing BODIPY derivatives as glutathione-activated photosensitizers for selective photodynamic action

Enhanced spatiotemporal selectivity in photonic sensitization of dissolved molecular oxygen is an important target for improving the potential and the practical applications of photodynamic therapy. Considering the high intracellular glutathione concentrations within cancer cells, a series of BODIPY-based sensitizers that can generate cytotoxic singlet oxygen only after glutathione-mediated cleavage of the electron-sink module were designed and synthesized. Cell culture studies not only validate our design, but also suggest an additional role for the relatively hydrophobic quencher module in the internalization of the photosensitizer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
iOD907, the first genome-scale metabolic model for the milk yeast Kluyveromyces lactis

We describe here the first genome-scale metabolic model of Kluyveromyces lactis, iOD907. It is partially compartmentalized (4 compartments), composed of 1867 reactions and 1476 metabolites. The iOD907 model performed well when assessing the positive growth of K. lactis to Biolog experiments and to an online catalogue of strains that provides information on carbon sources in which K. lactis is able to grow. Chemostat experiments were used to adjust non-growth-associated energy requirements, and the model proved accurate when predicting the biomass, oxygen and carbon dioxide yields. In silico knockouts predicted in vivo phenotypes accurately when compared to published experiments. The iOD907 genome-scale metabolic model complies with the MIRIAM standards for the annotation of enzymes, transporters, metabolites and reactions. Moreover, it contains direct links to KEGG (for enzymes, metabolites and reactions) and to TCDB for transporters, allowing easy comparisons to other models. Furthermore, this model is provided in the well-established SBML format, which means that it can be used in most metabolic engineering platforms, such as OptFlux or Cobra. The model is able to predict the behavior of K. lactis under different environmental conditions and genetic perturbations. Furthermore, it can also be important in the design of minimal media and will allow insights on the milk yeast's metabolism, as well as identifying metabolic engineering targets for the improvement of the production of products of interest by performing simulations and optimizations.The authors thank strategic Project PEst-OE/EQB/LA0023/2013 and project "BioInd - Biotechnology and Bioengineering for improved Industrial and Agro-Food processes, REF. NORTE-07-0124-FEDER-000028" co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER. The authors would also like to acknowledge Steve Sheridan for proof reading this manuscript
Long working hours and risk of coronary heart disease and stroke : a systematic review and meta-analysis of published and unpublished data for 603 838 individuals

Background: Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. 
Methods: We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. 
Findings: We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603 838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528 908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5.1 million person-years (mean 8.5 years), in which 4768 events were recorded, and for stroke was 3.8 million person-years (mean 7.2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (>= 55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1.13, 95% CI 1.02-1.26; p=0.02) and incident stroke (1.33, 1.11-1.61; p=0.002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1.30-1.42). We recorded a dose-response association for stroke, with RR estimates of 1.10 (95% CI 0.94-1.28; p=0.24) for 41-48 working hours, 1.27 (1.03-1.56; p=0.03) for 49-54 working hours, and 1.33 (1.11-1.61; p=0.002) for 55 working hours or more per week compared with standard working hours (p(trend)<0.0001). 
Interpretation: Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours
Search for a heavy bottom-like quark in pp collisions at √s=7 TeV

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for pair-produced bottom-like quarks in pp collisions at √ s = 7 TeV is conducted with the CMS experiment at the LHC. The decay b' →tW is considered in this search. The b'b' →tW−tW+ process can be identified by the distinctive signature of trileptons and same-sign dileptons. With a data sample corresponding to an integrated luminosity of 34 pb−1, no excess above the standard model background predictions is observed and a b' quark with a mass between 255 and 361 GeV/c2 is excluded at the 95% confidence levelWe wish to congratulate our colleagues in the CERN accelerator departments for the excellent performance of the LHC machine. We thank the technical and administrative staff at CERN and other CMS institutes, and acknowledge support from: FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLPFAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA
Measurement of zero degree single photon energy spectra for sqrt(s) = 7 TeV proton-proton collisions at LHC

In early 2010, the Large Hadron Collider forward (LHCf) experiment measured very forward neutral particle spectra in LHC proton-proton collisions. From a limited data set taken under the best beam conditions (low beam-gas background and low occurance of pile-up events), the single photon spectra at sqrt(s)=7TeV and pseudo-rapidity (eta) ranges from 8.81 to 8.99 and from 10.94 to infinity were obtained for the first time and are reported in this paper. The spectra from two independent LHCf detectors are consistent with one another and serve as a cross check of the data. The photon spectra are also compared with the predictions of several hadron interaction models that are used extensively for modeling ultra high energy cosmic ray showers. Despite conservative estimates for the systematic errors, none of the models agree perfectly with the measurements. A notable difference is found between the data and the DPMJET 3.04 and PYTHIA 8.145 hadron interaction models above 2TeV where the models predict higher photon yield than the data. The QGSJET II-03 model predicts overall lower photon yield than the data, especially above 2TeV in the rapidity range 8.81<eta<8.99
Underlying A(4) symmetry for the neutrino mass matrix and the quark mixing matrix

The discrete non-Abelian symmetry A4, valid at some high-energy scale, naturally leads to degenerate neutrino masses, without spoiling the hierarchy of charged-lepton masses. Realistic neutrino mass splittings and mixing angles (one of which is necessarily maximal and the other large) are then induced radiatively in the context of softly broken supersymmetry. The quark mixing matrix is also calculable in a similar way. The mixing parameter Ue3 is predicted to be imaginary, leading to maximal CP violation in neutrino oscillations. Neutrinoless double beta decay and τ→μγ should be in the experimentally accessible range
Large scale separation and resonances within LHC range from a prototype
  BSM model

Many theories describing physics beyond the Standard Model rely on a large
separation of scales. Large scale separation arises in models with mass-split
flavors if the system is conformal in the ultraviolet but chirally broken in
the infrared. Because of the conformal fixed point, these systems exhibit
hyperscaling and a highly constrained resonance spectrum. We derive
hyperscaling relations and investigate the realization of one such system with
four light and eight heavy flavors. Our numerical simulations confirm that both
light-light and heavy-heavy resonance masses show hyperscaling and depend only
on the ratio of the light and heavy flavor masses. The heavy-heavy spectrum is
qualitatively different from QCD and exhibits quarkonia with masses not
proportional to the constituent quark mass. These resonances are only a few
times heavier than the light-light ones, which would put them within reach of
the LHC.Comment: 6 pages, 3 figures. Version published in PLB, updated figures show in
  addition data at a second beta value strengthening our conclusion