Variation in karyotype and chromsome numbers in CHO cell lines and subclones

Genomic rearrangements are a common phenomenon in rapidly growing cell lines such as Chinese hamster ovary cells, a feature that, while it provides the ability to adapt to different conditions and to select the rare variants with high productivity, in the final production clone may lead to batch irreproducibility and instability. Few methods exist to assess such genome wide instability. Here we use the population distribution of chromosome numbers per cell as well as chromosome painting to identify large scale chromosomal rearrangements for quantification of karyotypic variation in several CHO cell lines, including host and recombinant cell lines, both at the pool, minipool and subclone level. Apart from investigating differences between cell lines and subclones, we followed changes in chromosome number distribution and chromosome pattern over a period of 6 months for stability assessment. Please click Additional Files below to see the full abstract

Superconducting pairing symmetry in MoTe2_{2}

Topological superconductors have long been sought for their potential use in quantum computing. The type-II Weyl semimetal MoTe$_{2}$ is an obvious candidate, exhibiting a superconducting state below 500 mK at ambient pressure, but the question remains whether the pairing is conventional $s^{++}$ or topological $s^{+-}$. The application of external pressure favors the superconducting state in MoTe$_{2}$ and suppresses the structural transition from $1T'$ to $T_{d}$. The competition between the two structures leads to a mixed phase that strongly enhances the disorder present in the system, remarkably without affecting the superconducting transition temperature, in contrast to the expectation of $s^{+-}$ pairing superconductivity. Our thorough analysis of the electrical and Hall resistivities as a function of pressure yields the most accurate temperature-pressure phase diagram available to date for MoTe$_{2}$ and a detailed view of the relationship between disorder and superconductivity, supporting a conventional $s^{++}$ pairing symmetry

Magnetism and unconventional superconductivity in Cen_nMm_mIn3n+2m_{3n+2m} heavy-fermion crystals

We review magnetic, superconducting and non-Fermi-liquid properties of the structurally layered heavy-fermion compounds Ce$_n$M$_m$In$_{3n+2m}$ (M=Co, Rh, Ir). These properties suggest d-wave superconductivity and proximity to an antiferromagetic quantum-critical point.Comment: submitted 23rd International Conference on Low Temperature Physics (LT-23), Aug. 200

IgG light chain-independent secretion of heavy chain dimers: consequence for therapeutic antibody production and design

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here we show that some humanised heavy chains can fold, form dimers and be secreted even in the absence of light chain. Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the heavy chain CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the light chain CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent upon the heavy chain variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will impact on the efficient production of both humanised antibodies as well as the design of novel antibody formats

The Bivariate Normal Copula

We collect well known and less known facts about the bivariate normal distribution and translate them into copula language. In addition, we prove a very general formula for the bivariate normal copula, we compute Gini's gamma, and we provide improved bounds and approximations on the diagonal.Comment: 24 page

Environmental and Economically Conscious Magnesium Production: Solar Thermal Electrolytic Production of Mg from MgO

One method to improve the fuel efficiency of American made vehicles is to reduce vehicle weight by substituting steel components with lighter magnesium (Mg) components. Unfortunately, U.S. produced Mg currently costs approximately $3.31 per kg, over seven times the price of steel. Furthermore, Mg production has a staggering energy and environmental impact, consuming up to 102 kW-hr/kg-Mg of energy and producing 36 kg of CO2/kg-Mg. To reduce the overwhelming economic and environmental impact of Mg, a new solar thermal electrolytic process has been developed for the production of Mg from MgO. Through this process, liquid Mg is produced in a solar reactor utilizing both thermal and electrical energy. At elevated temperatures, the thermal energy from concentrated sunlight reduces the required electrical work below that of current processes. The reactor absorbs the concentrated solar energy, heating a molten salt-MgO mixture in an electrolytic cell. Electricity is then supplied to the cell, producing liquid Mg and CO. It is estimated that this new process will produce Mg at$2.50 per kg, with costs decreasing as the technology is further developed. This process requires approximately 8.3 kW-hr/kg-Mg of energy and produces only 3.44 kg of CO2/kg-Mg, large reductions compared to current processes

Response of the Heavy-Fermion Superconductor CeCoIn5_5 to Pressure: Roles of Dimensionality and Proximity to a Quantum-Critical Point

We report measurements of the pressure-dependent superconducting transition temperature $T_c$ and electrical resistivity of the heavy-fermion compound CeCoIn$_5$. Pressure moves CeCoIn$_5$ away from its proximity to a quantum-critical point at atmospheric pressure. Experimental results are qualitatively consistent with theoretical predictions for strong-coupled, d-wave superconductivity in an anisotropic 3D superconductor.Comment: 9 pages, 5 figure

CeIr3_{3}Ge7_{7}: a local moment antiferromagnetic metal with extremely low ordering temperature

CeIr$_3$Ge$_7$ is an antiferromagnetic metal with a remarkably low ordering temperature $T_{\rm N}$ = 0.63 K, while most Ce-based magnets order between 2 and 15 K. Thermodynamic and transport properties as a function of magnetic field or pressure do not show signatures of Kondo correlations, interaction competition, or frustration, as had been observed in a few antiferromagnets with comparably low or lower $T_{\rm N}$. The averaged Weiss temperature measured below 10 K is comparable to $T_{\rm N}$ suggesting that the RKKY exchange coupling is very weak in this material. The unusually low $T_{\rm N}$ in CeIr$_3$Ge$_7$ can therefore be attributed to the large Ce-Ce bond length of about 5.7 {\AA}, which is about 1.5 {\AA} larger than in the most Ce-based intermetallic systems.Comment: 4 figure

Optimal treatment allocations in space and time for on-line control of an emerging infectious disease

A key component in controlling the spread of an epidemic is deciding where, whenand to whom to apply an intervention.We develop a framework for using data to informthese decisionsin realtime.We formalize a treatment allocation strategy as a sequence of functions, oneper treatment period, that map up-to-date information on the spread of an infectious diseaseto a subset of locations where treatment should be allocated. An optimal allocation strategyoptimizes some cumulative outcome, e.g. the number of uninfected locations, the geographicfootprint of the disease or the cost of the epidemic. Estimation of an optimal allocation strategyfor an emerging infectious disease is challenging because spatial proximity induces interferencebetween locations, the number of possible allocations is exponential in the number oflocations, and because disease dynamics and intervention effectiveness are unknown at outbreak.We derive a Bayesian on-line estimator of the optimal allocation strategy that combinessimulation–optimization with Thompson sampling.The estimator proposed performs favourablyin simulation experiments. This work is motivated by and illustrated using data on the spread ofwhite nose syndrome, which is a highly fatal infectious disease devastating bat populations inNorth America

HopScotch - a low-power renewable energy base station network for rural broadband access

The provision of adequate broadband access to communities in sparsely populated rural areas has in the past been severely restricted. In this paper, we present a wireless broadband access test bed running in the Scottish Highlands and Islands which is based on a relay network of low-power base stations. Base stations are powered by a combination of renewable sources creating a low cost and scalable solution suitable for community ownership. The use of the 5~GHz bands allows the network to offer large data rates and the testing of ultra high frequency ``white space'' bands allow expansive coverage whilst reducing the number of base stations or required transmission power. We argue that the reliance on renewable power and the intelligent use of frequency bands makes this approach an economic green radio technology which can address the problem of rural broadband access