Immunotherapy of Peritoneal Carcinomatosis with the Antibody Catumaxomab in Colon, Gastric, or Pancreatic Cancer: An Open-Label, Multicenter, Phase I/II Trial

Background: Peritoneal carcinomatosis (PC) is common in gastrointestinal (GI) cancer and there is no effective standard treatment. We investigated the tolerability and maximum tolerated dose (MTD) of the trifunctional antibody catumaxomab in patients with PC. Methods: In this open-label, phase I/II clinical trial, patients with epithelial cell adhesion molecule (EpCAM)-positive PC from GI cancer received 4 sequential intraperitoneal catumaxomab infusions: day 0: 10 mu g; day 3: 10 or 20 mu g; day 7: 30, 50, or 100 mu g; and day 10: 50, 100, or 200 mu g. Dose escalation was guided by dose-limiting toxicities. Results: The MTD was 10, 20, 50, and 200 mu g on days 0, 3, 7, and 10, respectively. Catumaxomab had an acceptable safety profile: Most common treatment-related adverse events (at the MTD) were fever, vomiting, and abdominal pain. At final examination, 11/17 evaluable patients (65%) were progression free: 1 patient had a complete and 3 a partial response. Median overall survival from the time of diagnosis of PC was 502 days. Conclusions: Intraperitoneal catumaxomab is a promising option for the treatment of PC from GI cancer

The role of the cortical cytoskeleton

We generated Dictyostelium double mutants lacking the two F-actin crosslinking proteins alpha-actinin and gelation factor by inactivating the corresponding genes via homologous recombination. Here we investigated the consequences of these deficiencies both at the single cell level and at the multicellular stage. We found that loss of both proteins severely affected growth of the mutant cells in shaking suspension, and led to a reduction of cell size from 12 microns in wild-type cells to 9 microns in mutant cells. Moreover the cells did not exhibit the typical polarized morphology of aggregating Dictyostelium cells but had a more rounded cell shape, and also exhibited an increased sensitivity towards osmotic shock and a reduced rate of phagocytosis. Development was heavily impaired and never resulted in the formation of fruiting bodies. Expression of developmentally regulated genes and the final developmental stages that were reached varied, however, with the substrata on which the cells were deposited. On phosphate buffered agar plates the cells were able to form tight aggregates and mounds and to express prespore and prestalk cell specific genes. Under these conditions the cells could perform chemotactic signalling and cell behavior was normal at the onset of multicellular development as revealed by time-lapse video microscopy. Double mutant cells were motile but speed was reduced by approximately 30% as compared to wild type. These changes were reversed by expressing the gelation factor in the mutant cells. We conclude that the actin assemblies that are formed and/or stabilized by both F-actin crosslinking proteins have a protective function during osmotic stress and are essential for proper cell shape and motility

Optomechanical circuits for nanomechanical continuous variable quantum state processing

We propose and analyze a nanomechanical architecture where light is used to perform linear quantum operations on a set of many vibrational modes. Suitable amplitude modulation of a single laser beam is shown to generate squeezing, entanglement, and state-transfer between modes that are selected according to their mechanical oscillation frequency. Current optomechanical devices based on photonic crystals may provide a platform for realizing this scheme.Comment: 11 pages, 5 figure

Distill-and-Compare: Auditing Black-Box Models Using Transparent Model Distillation

Black-box risk scoring models permeate our lives, yet are typically proprietary or opaque. We propose Distill-and-Compare, a model distillation and comparison approach to audit such models. To gain insight into black-box models, we treat them as teachers, training transparent student models to mimic the risk scores assigned by black-box models. We compare the student model trained with distillation to a second un-distilled transparent model trained on ground-truth outcomes, and use differences between the two models to gain insight into the black-box model. Our approach can be applied in a realistic setting, without probing the black-box model API. We demonstrate the approach on four public data sets: COMPAS, Stop-and-Frisk, Chicago Police, and Lending Club. We also propose a statistical test to determine if a data set is missing key features used to train the black-box model. Our test finds that the ProPublica data is likely missing key feature(s) used in COMPAS.Comment: Camera-ready version for AAAI/ACM AIES 2018. Data and pseudocode at https://github.com/shftan/auditblackbox. Previously titled "Detecting Bias in Black-Box Models Using Transparent Model Distillation". A short version was presented at NIPS 2017 Symposium on Interpretable Machine Learnin

Magellan LDSS3 emission confirmation of galaxies hosting metal-rich Lyman-alpha absorption systems

Using the Low Dispersion Survey Spectrograph 3 at the Magellan II Clay Telescope, we target {candidate absorption host galaxies} detected in deep optical imaging {(reaching limiting apparent magnitudes of 23.0-26.5 in $g, r, i,$ and $z$ filters) in the fields of three QSOs, each of which shows the presence of high metallicity, high $N_{\rm HI}$ absorption systems in their spectra (Q0826-2230: $z_{abs}$=0.9110, Q1323-0021: $z_{abs}=0.7160$, Q1436-0051: $z_{abs}=0.7377, 0.9281$). We confirm three host galaxies {at redshifts 0.7387, 0.7401, and 0.9286} for two of the Lyman-$\alpha$ absorption systems (one with two galaxies interacting). For these systems, we are able to determine the star formation rates (SFRs); impact parameters (from previous imaging detections); the velocity shift between the absorption and emission redshifts; and, for one system, also the emission metallicity.} Based on previous photometry, we find these galaxies have L$>$L$^{\ast}$. The [O II] SFRs for these galaxies are in the range $11-25$ M$_{\odot}$ yr$^{-1}$ {(uncorrected for dust)}, while the impact parameters lie in the range $35-54$ kpc. {Despite the fact that we have confirmed galaxies at 50 kpc from the QSO, no gradient in metallicity is indicated between the absorption metallicity along the QSO line of sight and the emission line metallicity in the galaxies.} We confirm the anti-correlation between impact parameter and $N_{\rm HI}$ from the literature. We also report the emission redshift of five other galaxies: three at $z_{em}>z_{QSO}$, and two (L$<$L$^{\ast}$) at $z_{em}<z_{QSO}$ not corresponding to any known absorption systems.Comment: 14 pages, 7 figures, 4 tables, accepted to MNRA

Asymmetric Surface Brightness Structure of Caustic Crossing Arc in SDSS J1226+2152: A Case for Dark Matter Substructure

We study the highly magnified arc SGAS J122651.3+215220 caused by a star-forming galaxy at $z_s=2.93$ crossing the lensing caustic cast by the galaxy cluster SDSS J1226+2152 ($z_l=0.43$), using Hubble Space Telescope observations. We report in the arc several asymmetric surface brightness features whose angular separations are a fraction of an arcsecond from the lensing critical curve and appear to be highly but unequally magnified image pairs of underlying compact sources, with one brightest pair having clear asymmetry consistently across four filters. One explanation of unequal magnification is microlensing by intracluster stars, which induces independent flux variations in the images of individual or groups of source stars in the lensed galaxy. For a second possibility, intracluster dark matter subhalos invisible to telescopes effectively perturb lensing magnifications near the critical curve and give rise to persistently unequal image pairs. Our modeling suggests, at least for the most prominent identified image pair, that the microlensing hypothesis is in tension with the absence of notable asymmetry variation over a six-year baseline, while subhalos of $\sim 10^6$--$10^8\,M_\odot$ anticipated from structure formation with Cold Dark Matter typically produce stationary and sizable asymmetries. We judge that observations at additional times and more precise lens models are necessary to stringently constrain temporal variability and robustly distinguish between the two explanations. The arc under this study is a scheduled target of a Director's Discretionary Early Release Science program of the James Webb Space Telescope, which will provide deep images and a high-resolution view with integral field spectroscopy.Comment: New version accepted by MNRAS; 18 pages including references and appendices, 13 figures and 4 tables; major revision of Sec. 3.2 and Figure 4 presenting improved data analysis; original conclusion strengthened