Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia. We conducted a phase II single-arm study at a single center. Patients received ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000 mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including 29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients received the full course without dose reductions or delays. The overall response rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67% partial response, 14% stable disease and 5% progressive disease. After a median follow-up of 31 months, the median progression-free survival was 9.9 months and the median time to next treatment was 12.1 months. The median overall survival has not yet been reached. The combination of high-dose methylprednisolone and ofatumumab is an effective and tolerable treatment regimen. This regimen may be useful for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments

Electrostatic Modulation of the Electronic Properties of Dirac Semimetal Na3Bi

Large-area thin films of topological Dirac semimetal Na$_3$Bi are grown on amorphous SiO$_2$:Si substrates to realise a field-effect transistor with the doped Si acting as back gate. As-grown films show charge carrier mobilities exceeding 7,000 cm$^2$/Vs and carrier densities below 3 $\times$10$^{18}$ cm$^{-3}$, comparable to the best thin-film Na$_3$Bi. An ambipolar field effect and minimum conductivity are observed, characteristic of Dirac electronic systems. The results are quantitatively understood within a model of disorder-induced charge inhomogeneity in topological Dirac semimetals. Due to the inverted band structure, the hole mobility is significantly larger than the electron mobility in Na$_3$Bi, and when present, these holes dominate the transport properties.Comment: 5 pages, 4 figures; minor corrections and revisions for readabilit

Quantum dynamics of propagating photons with strong interactions: a generalized input-output formalism

There has been rapid development of systems that yield strong interactions between freely propagating photons in one dimension via controlled coupling to quantum emitters. This raises interesting possibilities such as quantum information processing with photons or quantum many-body states of light, but treating such systems generally remains a difficult task theoretically. Here, we describe a novel technique in which the dynamics and correlations of a few photons can be exactly calculated, based upon knowledge of the initial photonic state and the solution of the reduced effective dynamics of the quantum emitters alone. We show that this generalized "input-output" formalism allows for a straightforward numerical implementation regardless of system details, such as emitter positions, external driving, and level structure. As a specific example, we apply our technique to show how atomic systems with infinite-range interactions and under conditions of electromagnetically induced transparency enable the selective transmission of correlated multi-photon states

Meridional Transport in the Stratosphere of Jupiter

The Cassini measurements of C$_2$H$_2$ and C$_2$H$_6$ at $\sim$5 mbar provide a constraint on meridional transport in the stratosphere of Jupiter. We performed a two-dimensional photochemical calculation coupled with mass transport due to vertical and meridional mixing. The modeled profile of C$_2$H$_2$ at latitudes less than 70$^\circ$ follows the latitude dependence of the solar insolation, while that of C$_2$H$_6$ shows little latitude dependence, consistent with the measurements. In general, our model study suggests that the meridional transport timescale above 5-10 mbar altitude level is $\gtrsim$1000 years and the time could be as short as 10 years below 10 mbar level, in order to fit the Cassini measurements. The derived meridional transport timescale above the 5 mbar level is a hundred times longer than that obtained from the spreading of gas-phase molecules deposited after the impact of Shoemaker-Levy 9 comet. There is no explanation at this time for this discrepancy.Comment: 11 pages, 3 figures, 1 table. ApJL in pres

Neurocognitive Correlates of Treatment Response in Children with Tourette\u27s Disorder

This paper examined neurocognitive functioning and its relationship to behavior treatment response among youth with Tourette\u27s Disorder (TD) in a large randomized controlled trial. Participants diagnosed with TD completed a brief neurocognitive battery assessing inhibitory functions, working memory, and habit learning pre- and post-treatment with behavior therapy (CBIT, Comprehensive Behavioral Intervention for Tics) or psychoeducation plus supportive therapy (PST). At baseline, youth with tics and Attention Deficit Hyperactivity Disorder (ADHD) exhibited some evidence of impaired working memory and simple motor inhibition relative to youth with tics without ADHD. Additionally, a small negative association was found between antipsychotic medications and youth\u27s performance speed. Across treatment groups, greater baseline working memory and aspects of inhibitory functioning were associated with a positive treatment response; no between-group differences in neurocognitive functioning at post-treatment were identified. Within the behavior therapy group, pre-treatment neurocognitive status did not predict outcome, nor was behavior therapy associated significant change in neurocognitive functioning post-treatment. Findings suggest that co-occurring ADHD is associated with some impairments in neurocognitive functioning in youth with Tourette\u27s Disorder. While neurocognitive predictors of behavior therapy were not found, participants who received behavior therapy exhibited significantly reduced tic severity without diminished cognitive functioning

Logarithmic deformations of the rational superpotential/Landau-Ginzburg construction of solutions of the WDVV equations

The superpotential in the Landau-Ginzburg construction of solutions to the Witten-Dijkgraaf-Verlinde-Verlinde (or WDVV) equations is modified to include logarithmic terms. This results in deformations - quadratic in the deformation parameters- of the normal prepotential solutions of the WDVV equations. Such solutions satisfy various pseudo-quasi-homogeneity conditions, on assigning a notional weight to the deformation parameters. These solutions originate in the so-called `water-bag' reductions of the dispersionless KP hierarchy. This construction includes, as a special case, deformations which are polynomial in the flat coordinates, resulting in a new class of polynomial solutions of the WDVV equations

Policy Process Editor for P3BM Software

A computer program enables generation, in the form of graphical representations of process flows with embedded natural-language policy statements, input to a suite of policy-, process-, and performance-based management (P3BM) software. This program (1) serves as an interface between users and the Hunter software, which translates the input into machine-readable form; and (2) enables users to initialize and monitor the policy-implementation process. This program provides an intuitive graphical interface for incorporating natural-language policy statements into business-process flow diagrams. Thus, the program enables users who dictate policies to intuitively embed their intended process flows as they state the policies, reducing the likelihood of errors and reducing the time between declaration and execution of policy

Spin and Rotations in Galois Field Quantum Mechanics

We discuss the properties of Galois Field Quantum Mechanics constructed on a vector space over the finite Galois field GF(q). In particular, we look at 2-level systems analogous to spin, and discuss how SO(3) rotations could be embodied in such a system. We also consider two-particle `spin' correlations and show that the Clauser-Horne-Shimony-Holt (CHSH) inequality is nonetheless not violated in this model.Comment: 21 pages, 11 pdf figures, LaTeX. Uses iopart.cls. Revised introduction. Additional reference

Designer Reagents for Mass Spectrometry-Based Proteomics: Clickable Cross-Linkers for Elucidation of Protein Structures and Interactions

We present novel homobifunctional amine-reactive clickable cross-linkers (CXLs) for investigation of three-dimensional protein structures and protein–protein interactions (PPIs). CXLs afford consolidated advantages not previously available in a simple cross-linker, including (1) their small size and cationic nature at physiological pH, resulting in good water solubility and cell-permeability, (2) an alkyne group for bio-orthogonal conjugation to affinity tags via the click reaction for enrichment of cross-linked peptides, (3) a nucleophilic displacement reaction involving the 1,2,3-triazole ring formed in the click reaction, yielding a lock-mass reporter ion for only clicked peptides, and (4) higher charge states of cross-linked peptides in the gas-phase for augmented electron transfer dissociation (ETD) yields. Ubiquitin, a lysine-abundant protein, is used as a model system to demonstrate structural studies using CXLs. To validate the sensitivity of our approach, biotin-azide labeling and subsequent enrichment of cross-linked peptides are performed for cross-linked ubiquitin digests mixed with yeast cell lysates. Cross-linked peptides are detected and identified by collision induced dissociation (CID) and ETD with linear quadrupole ion trap (LTQ)-Fourier transform ion cyclotron resonance (FTICR) and LTQ-Orbitrap mass spectrometers. The application of CXLs to more complex systems (e.g., in vivo cross-linking) is illustrated by Western blot detection of Cul1 complexes including known binders, Cand1 and Skp2, in HEK 293 cells, confirming good water solubility and cell-permeability

Spatial links between subchondral bone architectural features and cartilage degeneration in osteoarthritic joints

Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression