A homoleptic phosphine adduct of Tl(I)

A homoleptic phosphine adduct of thallium(I) supported by a tris(phosphino)borate ligand has been isolated and structurally characterized

Economic and operational appraisal of an allogeneic CAR T-cell bioprocess

Allogeneic CAR T-cell therapies face a variety of challenges from a processing point of view. Pressures to deliver cell therapies at affordable prices demand the development of efficient and cost-effective manufacturing strategies and process technologies for the manufacture of such products. Consideration must be paid to both financial and operational aspects of bioprocess designs from the early stages of product development. This work presents the application of a decisional tool to a case study which describes the manufacture of an allogeneic CAR T-cell therapy. The tool, developed at University College London, is able to quantitatively evaluate bioprocess designs from both a financial and an operational perspective. In this instance the tool has been used to carry out mass balances and equipment sizing calculations in order to compute resource utilisation and cost of goods (COG) for a range of bioprocess designs. Scenario analyses have been used to pinpoint future process improvements that result in feasible manufacturing COG. Furthermore, multi-attribute decision making (MADM) has been employed in order to allow the appraisal of optimal bioprocess designs from both a financial and an operational perspective. The tool outputs provide COG breakdowns for bioprocess designs at a range of annual demands and dose sizes. MADM has been used to provide quantitative output values to key financial and operational performance metrics. Further to this, key process bottlenecks and economic drivers have been identified; these provide a basis for the focus of future process improvements. This work presents a computational technique that can be used to drive effective decision making early on in the development of allogeneic CAR T-cell therapy bioprocesses

Testing the Unitarity of the CKM Matrix with a Space-Based Neutron Decay Experiment

If the Standard Model is correct, and fundamental fermions exist only in the three generations, then the CKM matrix should be unitary. However, there remains a question over a deviation from unitarity from the value of the neutron lifetime. We discuss a simple space-based experiment that, at an orbit height of 500 km above Earth, would measure the kinetic-energy, solid-angle, flux spectrum of gravitationally bound neutrons (kinetic energy K<0.606 eV at this altitude). The difference between the energy spectrum of neutrons that come up from the Earth's atmosphere and that of the undecayed neutrons that return back down to the Earth would yield a measurement of the neutron lifetime. This measurement would be free of the systematics of laboratory experiments. A package of mass $<25$ kg could provide a 10^{-3} precision in two years.Comment: 10 pages, 4 figures. Revised and updated for publicatio

Quenched Chiral Perturbation Theory for Vector Mesons

We develop quenched chiral perturbation theory for vector mesons made of light quarks, in the limit where the vector meson masses are much larger than the pion mass. We use this theory to extract the leading nonanalytic dependence of the vector meson masses on the masses of the light quarks. By comparing with analogous quantities computed in ordinary chiral perturbation theory, we estimate the size of quenching effects, observing that in general they can be quite large. This estimate is relevant to lattice simulations, where the $\rho$ mass is often used to set the lattice spacing.Comment: 18 pages, 8 figures, uses REVTeX and epsf.st

Kepler Presearch Data Conditioning I - Architecture and Algorithms for Error Correction in Kepler Light Curves

Kepler provides light curves of 156,000 stars with unprecedented precision. However, the raw data as they come from the spacecraft contain significant systematic and stochastic errors. These errors, which include discontinuities, systematic trends, and outliers, obscure the astrophysical signals in the light curves. To correct these errors is the task of the Presearch Data Conditioning (PDC) module of the Kepler data analysis pipeline. The original version of PDC in Kepler did not meet the extremely high performance requirements for the detection of miniscule planet transits or highly accurate analysis of stellar activity and rotation. One particular deficiency was that astrophysical features were often removed as a side-effect to removal of errors. In this paper we introduce the completely new and significantly improved version of PDC which was implemented in Kepler SOC 8.0. This new PDC version, which utilizes a Bayesian approach for removal of systematics, reliably corrects errors in the light curves while at the same time preserving planet transits and other astrophysically interesting signals. We describe the architecture and the algorithms of this new PDC module, show typical errors encountered in Kepler data, and illustrate the corrections using real light curve examples.Comment: Submitted to PASP. Also see companion paper "Kepler Presearch Data Conditioning II - A Bayesian Approach to Systematic Error Correction" by Jeff C. Smith et a

What is the Total Deuterium Abundance in the Local Galactic Disk?

Analyses of spectra obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite, together with spectra from the Copernicus and IMAPS instruments, reveal an unexplained very wide range in the observed deuterium/hydrogen (D/H) ratios for interstellar gas in the Galactic disk beyond the Local Bubble. We argue that spatial variations in the depletion of deuterium onto dust grains can explain these local variations in the observed gas-phase D/H ratios. We present a variable deuterium depletion model that naturally explains the constant measured values of D/H inside the Local Bubble, the wide range of gas-phase D/H ratios observed in the intermediate regime (log N(H I} = 19.2-20.7), and the low gas-phase D/H ratios observed at larger hydrogen column densities. We consider empirical tests of the deuterium depletion hypothesis: (i) correlations of gas-phase D/H ratios with depletions of the refractory metals iron and silicon, and (ii) correlation with the molecular hydrogen rotational temperature. Both of these tests are consistent with deuterium depletion from the gas phase in cold, not recently shocked, regions of the ISM, and high gas-phase D/H ratios in gas that has been shocked or otherwise heated recently. We argue that the most representative value for the total (gas plus dust) D/H ratio within 1 kpc of the Sun is >=23.1 +/- 2.4 (1 sigma) parts per million (ppm). This ratio constrains Galactic chemical evolution models to have a very small deuterium astration factor, the ratio of primordial to total (D/H) ratio in the local region of the Galactic disk, which we estimate to be f_d <= 1.19 +/-0.16 (1 sigma) or <= 1.12 +/- 0.14 (1 sigma) depending on the adopted light element nuclear reaction rates.Comment: 19 pages, 9 figure

Kepler Presearch Data Conditioning II - A Bayesian Approach to Systematic Error Correction

With the unprecedented photometric precision of the Kepler Spacecraft, significant systematic and stochastic errors on transit signal levels are observable in the Kepler photometric data. These errors, which include discontinuities, outliers, systematic trends and other instrumental signatures, obscure astrophysical signals. The Presearch Data Conditioning (PDC) module of the Kepler data analysis pipeline tries to remove these errors while preserving planet transits and other astrophysically interesting signals. The completely new noise and stellar variability regime observed in Kepler data poses a significant problem to standard cotrending methods such as SYSREM and TFA. Variable stars are often of particular astrophysical interest so the preservation of their signals is of significant importance to the astrophysical community. We present a Bayesian Maximum A Posteriori (MAP) approach where a subset of highly correlated and quiet stars is used to generate a cotrending basis vector set which is in turn used to establish a range of "reasonable" robust fit parameters. These robust fit parameters are then used to generate a Bayesian Prior and a Bayesian Posterior Probability Distribution Function (PDF) which when maximized finds the best fit that simultaneously removes systematic effects while reducing the signal distortion and noise injection which commonly afflicts simple least-squares (LS) fitting. A numerical and empirical approach is taken where the Bayesian Prior PDFs are generated from fits to the light curve distributions themselves.Comment: 43 pages, 21 figures, Submitted for publication in PASP. Also see companion paper "Kepler Presearch Data Conditioning I - Architecture and Algorithms for Error Correction in Kepler Light Curves" by Martin C. Stumpe, et a

The complete management of extremity vascular injury in a local population: A wartime report from the 332nd Expeditionary Medical Group/Air Force Theater Hospital, Balad Air Base, Iraq

Background: Although the management of vascular injury in coalition forces during Operation Iraqi Freedom has been described, there are no reports on the in-theater treatment of wartime vascular injury in the local population. This study reports the complete management of extremity vascular injury in a local wartime population and illustrates the unique aspects of this cohort and management strategy. Methods: From September 1, 2004, to August 31, 2006, all vascular injuries treated at the Air Force Theater Hospital (AFTH) in Balad, Iraq, were registered. Those in non-coalition troops were identified and retrospectively reviewed. Results: During the study period, 192 major vascular injuries were treated in the local population in the following distribution: extremity 70% (n = 134), neck and great vessel 17% (n = 33), and thoracoabdominal 13% (n = 25). For the extremity cohort, the age range was 4 to 68 years and included 12 pediatric injuries. Autologous vein was the conduit of choice for these vascular reconstructions. A strict wound management strategy providing repeat operative washout and application of the closed negative pressure adjunct was used. Delayed primary closure or secondary coverage with a split-thickness skin graft was required in 57% of extremity wounds. All patients in this cohort remained at the theater hospital through definitive wound healing, with an average length of stay of 15 days (median 11 days). Patients required an average of 3.3 operations (median 3) from the initial injury to definitive wound closure. Major complications in extremity vascular patients, including mortality, were present in 15.7% (n = 21). Surgical wound infection occurred in 3.7% (n = 5), and acute anastomotic disruption in 3% (n = 4). Graft thrombosis occurred in 4.5% (n = 6), and early amputation and mortality rates during the study period were 3.0% (n = 4) and 1.5% (n = 2), respectively. Conclusions: To our knowledge, this study represents the first large report of wartime extremity vascular injury management in a local population. These injuries present unique challenges related to complex wounds that require their complete management to occur in-theater. Vascular reconstruction using vein, combined with a strict wound management strategy, results in successful limb salvage with remarkably low infection, amputation and mortality rates

Preferential Depletion of Zinc Within Costa Rica Upwelling Dome Creates Conditions for Zinc Co-Limitation of Primary Production

The Costa Rica Dome (CRD) is a wind-driven feature characterized by high primary production and an unusual cyanobacterial bloom in surface waters. It is not clear whether this bloom arises from top-down or bottom-up processes. Several studies have argued that trace metal geochemistry within the CRD contributes to the composition of the phytoplankton assemblages, since cyanobacteria and eukaryotic phytoplankton have different transition metal requirements. Here, we report that total dissolved zinc (Zn) is significantly depleted relative to phosphate (P) and silicate (Si) within the upper water column of the CRD compared with other oceanic systems, and this may create conditions favorable for cyanobacteria, which have lower Zn requirements than their eukaryotic competitors. Shipboard grow-out experiments revealed that while Si was a limiting factor under our experimental conditions, additions of Si and either iron (Fe) or Zn led to higher biomass than Si additions alone. The addition ofFe and Zn alone did not lead to significant enhancements. Our results suggest that the depletion of Zn relative to P in upwelled waters may create conditions in the near-surface waters that favor phytoplankton with low Zn requirements, including cyanobacteria