Dear Wife : the Civil War letters of Chester K. Leach

Occasional paper (University of Vermont. Center for Research on Vermont) ; no. 20

Ipilimumab and Bevacizumab in Glioblastoma

The median survival in glioblastoma is just over a year, with no standard second-line therapy. Ipilimumab is an immune checkpoint inhibitor that activates the anti-tumour immune response by cytotoxic T-lymphocyte antigen-4 blockade. There is significant evidence supporting its role in the treatment of malignant melanoma, including in patients with brain metastases. The addition of the anti-angiogenesis agent, bevacizumab, seems to offer additional benefit and limit the immune-related side-effects of ipilimumab in melanoma. To date there have been no clinical trials investigating this combination in glioblastoma. In this single practice case series, 20 patients with glioblastoma were consented for and treated with ipilimumab and bevacizumab in combination. Safety, tolerability and the response to treatment were reviewed for all patients. Three patients were treated after palliative first-line radiotherapy, one patient after first-line chemoradiation and 16 patients were treated with recurrent disease. Sixty-five per cent of patients completed four cycles of 3 weekly ipilimumab therapy, administered with 2 weekly bevacizumab. Radiographic responses for patients with recurrent disease were evaluated by Response Assessment in Neuro-oncology (RANO) criteria; 31% of patients showed a partial response, 31% had stable disease and 38% had disease progression. The treatment combination was well tolerated, with treatment terminated before completion due to adverse events in two patients. Autoimmune toxicity was manageable with systemic corticosteroid therapy. Ipilimumab and bevacizumab in combination show promising activity with a predictable and manageable toxicity profile, warranting further clinical studies

Linear polarization sensitivity of SeGA detectors

Parity is a key observable in nuclear spectroscopy. Linear polarization measurements of $\gamma$-rays are a probe to access the parities of energy levels. Utilizing the segmentation of detectors in the Segmented Germanium Array (SeGA) at the NSCL and analyzing the positions of interaction therein allows the detectors to be used as Compton polarimeters. Unlike other segmented detectors, SeGA detectors are irradiated from the side to utilize the transversal segmentation for better Doppler corrections. Sensitivity in such an orientation has previously been untested. A linear polarization sensitivity $Q \approx 0.14$ has been measured in the 350-keV energy range for SeGA detectors using $\alpha$-$\gamma$ correlations from a \nuc{249}{Cf} source.Comment: 7 pages, 9 figure

IMAC capture of recombinant protein from unclarified mammalian cell feed streams

Fusion-tag affinity chromatography is a key technique in recombinant protein purification. Current methods for protein recovery from mammalian cells are hampered by the need for feed stream clarification. We have developed a method for direct capture using immobilized metal affinity chromatography (IMAC) of hexahistidine (His6) tagged proteins from unclarified mammalian cell feed streams. The process employs radial flow chromatography with 300-500 μm diameter agarose resin beads that allow free passage of cells but capture His-tagged proteins from the feed stream; circumventing expensive and cumbersome centrifugation and/or filtration steps. The method is exemplified by Chinese Hamster Ovary (CHO) cell expression and subsequent recovery of recombinant His-tagged carcinoembryonic antigen (CEA); a heavily glycosylated and clinically relevant protein. Despite operating at a high NaCl concentration necessary for IMAC binding, cells remained over 96% viable after passage through the column with host cell proteases and DNA detected at ∼8 U/mL and 2 ng/μL in column flow-through, respectively. Recovery of His-tagged CEA from unclarified feed yielded 71% product recovery. This work provides a basis for direct primary capture of fully glycosylated recombinant proteins from unclarified mammalian cell feed streams. Biotechnol. Bioeng. 2015;9999: 1-11. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc

Conceptualizing the adventure-sports coach

As a comparatively recent development, the adventure-sports coach struggles for a clear and distinct identity. The generic term ‘instructor’ no longer characterizes the role and function of this subgroup of outdoor professionals. Indeed, although the fields of adventure/outdoor education and leadership are comparatively well researched, the arrival of this ‘new kid on the block’ appears to challenge both the adventure-sports old guard and traditional views of sports coaching. In an attempt to offer clarity and stimulate debate, this paper attempts to conceptualize the adventure-sports coach in the context of the existing roles in the field and current motivations for activity in the outdoors. We identify issues that are specific to the adventure-sports coach while also recognizing those skills and competencies shared with other professionals, both in the adventure sports profession and traditional sports coaching fields. Based on this review, we offer a conceptual model which may be used to focus debate, stimulate research and, at a possible later stage, to underpin accreditation, training and professional development

Bose-Einstein Condensation in a Harmonic Potential

We examine several features of Bose-Einstein condensation (BEC) in an external harmonic potential well. In the thermodynamic limit, there is a phase transition to a spatial Bose-Einstein condensed state for dimension D greater than or equal to 2. The thermodynamic limit requires maintaining constant average density by weakening the potential while increasing the particle number N to infinity, while of course in real experiments the potential is fixed and N stays finite. For such finite ideal harmonic systems we show that a BEC still occurs, although without a true phase transition, below a certain ``pseudo-critical'' temperature, even for D=1. We study the momentum-space condensate fraction and find that it vanishes as 1/N^(1/2) in any number of dimensions in the thermodynamic limit. In D less than or equal to 2 the lack of a momentum condensation is in accord with the Hohenberg theorem, but must be reconciled with the existence of a spatial BEC in D=2. For finite systems we derive the N-dependence of the spatial and momentum condensate fractions and the transition temperatures, features that may be experimentally testable. We show that the N-dependence of the 2D ideal-gas transition temperature for a finite system cannot persist in the interacting case because it violates a theorem due to Chester, Penrose, and Onsager.Comment: 34 pages, LaTeX, 6 Postscript figures, Submitted to Jour. Low Temp. Phy

Superconducting-coil--resistor circuit with electric field quadratic in the current

It is shown for the first time that the observed [Phys. Lett. A 162 (1992) 105] potential difference Phi_t between the resistor and the screen surrounding the circuit is caused by polarization of the resistor because of the kinetic energy of the electrons of the superconducting coil. The proportionality of Phi_t to the square of the current and to the length of the superconducting wire is explained. It is pointed out that measuring Phi_t makes it possible to determine the Fermi quasimomentum of the electrons of a metal resistor.Comment: 2 pages, 1 figur

Shape and structure of N=Z 64Ge; Electromagnetic transition rates from the application of the Recoil Distance Method to knock-out reaction

Transition rate measurements are reported for the first and the second 2+ states in N=Z 64Ge. The experimental results are in excellent agreement with large-scale Shell Model calculations applying the recently developed GXPF1A interactions. Theoretical analysis suggests that 64Ge is a collective gamma-soft anharmonic vibrator. The measurement was done using the Recoil Distance Method (RDM) and a unique combination of state-of-the-art instruments at the National Superconducting Cyclotron Laboratory (NSCL). States of interest were populated via an intermediate-energy single-neutron knock-out reaction. RDM studies of knock-out and fragmentation reaction products hold the promise of reaching far from stability and providing lifetime information for excited states in a wide range of nuclei

Z=50 shell gap near 100^{100}Sn from intermediate-energy Coulomb excitations in even-mass 106−−112^{106--112}Sn isotopes

Rare isotope beams of neutron-deficient $^{106,108,110}$Sn nuclei from the fragmentation of $^{124}$Xe were employed in an intermediate-energy Coulomb excitation experiment yielding $B(E2, 0^+_1 \to 2^+_1)$ transition strengths. The results indicate that these $B(E2,0^+_1 \to 2^+_1)$ values are much larger than predicted by current state-of-the-art shell model calculations. This discrepancy can be explained if protons from within the Z = 50 shell are contributing to the structure of low-energy excited states in this region. Such contributions imply a breaking of the doubly-magic $^{100}$Sn core in the light Sn isotopes.Comment: 4 pages, 4 figure