3D printing for bio-synthetic biliary stents

Three-dimensional (3D) printing is an additive manufacturing method that holds great potential in a variety of future patient-specific medical technologies. This project validated a novel crosslinked polyvinyl alcohol (XL-PVA) 3D printed stent infused with collagen, human placental mesenchymal stem cells (PMSCs), and cholangiocytes. The biofabrication method in the present study examined 3D printing and collagen injection molding for rapid prototyping of customized living biliary stents with clinical applications in the setting of malignant and benign bile duct obstructions. XL-PVA stents showed hydrophilic swelling and addition of radiocontrast to the stent matrix improved radiographic opacity. Collagen loaded with PMSCs contracted tightly around hydrophilic stents and dense choloangiocyte coatings were verified through histology and fluorescence microscopy. It is anticipated that design elements used in these stents may enable appropriate stent placement, provide protection of the stent-stem cell matrix against bile constituents, and potentially limit biofilm development. Overall, this approach may allow physicians to create personalized bio-integrating stents for use in biliary procedures and lays a foundation for new patient-specific stent fabrication techniques

Blocks of cyclotomic Hecke algebras and Khovanov-Lauda algebras

We construct an explicit isomorphism between blocks of cyclotomic Hecke algebras and (sign-modified) Khovanov-Lauda algebras in type A. These isomorphisms connect the categorification conjecture of Khovanov and Lauda to Ariki's categorification theorem. The Khovanov-Lauda algebras are naturally graded, which allows us to exhibit a non-trivial Z-grading on blocks of cyclotomic Hecke algebras, including symmetric groups in positive characteristic.Comment: 32 pages; minor changes to section

Baxter Q-operator and Separation of Variables for the open SL(2,R) spin chain

We construct the Baxter Q-operator and the representation of the Separated Variables (SoV) for the homogeneous open SL(2,R) spin chain. Applying the diagrammatical approach, we calculate Sklyanin's integration measure in the separated variables and obtain the solution to the spectral problem for the model in terms of the eigenvalues of the Q-operator. We show that the transition kernel to the SoV representation is factorized into the product of certain operators each depending on a single separated variable. As a consequence, it has a universal pyramid-like form that has been already observed for various quantum integrable models such as periodic Toda chain, closed SL(2,R) and SL(2,C) spin chains.Comment: 29 pages, 9 figures, Latex styl

Current Fluctuations of the One Dimensional Symmetric Simple Exclusion Process with Step Initial Condition

For the symmetric simple exclusion process on an infinite line, we calculate exactly the fluctuations of the integrated current $Q_t$ during time $t$ through the origin when, in the initial condition, the sites are occupied with density $\rho_a$ on the negative axis and with density $\rho_b$ on the positive axis. All the cumulants of $Q_t$ grow like $\sqrt{t}$. In the range where $Q_t \sim \sqrt{t}$, the decay $\exp [-Q_t^3/t]$ of the distribution of $Q_t$ is non-Gaussian. Our results are obtained using the Bethe ansatz and several identities recently derived by Tracy and Widom for exclusion processes on the infinite line.Comment: 2 figure

The Shapes of Dirichlet Defects

If the vacuum manifold of a field theory has the appropriate topological structure, the theory admits topological structures analogous to the D-branes of string theory, in which defects of one dimension terminate on other defects of higher dimension. The shapes of such defects are analyzed numerically, with special attention paid to the intersection regions. Walls (co-dimension 1 branes) terminating on other walls, global strings (co-dimension 2 branes) and local strings (including gauge fields) terminating on walls are all considered. Connections to supersymmetric field theories, string theory and condensed matter systems are pointed out.Comment: 24 pages, RevTeX, 21 eps figure

CX-072 (pacmilimab), a Probody® PD-L1 inhibitor, in advanced or recurrent solid tumors (PROCLAIM-CX-072): an open-label dose-finding and first-in-human study

Background: Probody® therapeutics are antibody prodrugs that are activated in the tumor microenvironment by tumor-associated proteases, thereby restricting the activity to the tumor microenvironment and minimizing 'off-tumor' toxicity. We report dose-escalation and single-agent expansion phase data from the first-in-human study of CX-072 (pacmilimab), a Probody checkpoint inhibitor directed against programmed death-ligand 1 (PD-L1). Methods: In the dose-escalation phase of this multicenter, open-label study (NCT03013491), adults with advanced solid tumors (naive to programmed-death-1/PD-L1 or cytotoxic T-lymphocyte-associated antigen 4 inhibitors) were enrolled into one of seven dose-escalation cohorts, with pacmilimab administered intravenously every 14 days. The primary endpoints were safety and determination of the maximum tolerated dose (MTD). In the expansion phase, patients with one of six prespecified malignancies (triple-negative breast cancer [TNBC]; anal squamous cell carcinoma [aSCC]; cutaneous SCC [cSCC]; undifferentiated pleomorphic sarcoma [UPS]; small bowel adenocarcinoma [SBA]; and thymic epithelial tumor [TET]); or high tumor mutational burden (hTMB) tumors were enrolled. The primary endpoint was objective response (Response Evaluation Criteria In Solid Tumors v.1.1). Results: An MTD was not reached with doses up to 30 mg/kg. A recommended phase 2 dose (RP2D) of 10 mg/kg was chosen based on pharmacokinetic and pharmacodynamic findings in the expansion phase. Ninety-eight patients enrolled in the expansion phase: TNBC (n=14), aSCC (n=14), cSCC (n=14), UPS (n=20), SBA (n=14), TET (n=8), and hTMB tumors (n=14). Of 114 patients receiving pacmilimab at the RP2D, grade ≥3 treatment-related adverse events (TRAEs) were reported in 10 patients (9%), serious TRAEs in six patients (5%), and treatment discontinuation due to TRAEs in two patients (2%). Grade ≥3 immune-related AEs occurred in two patients (rash, myocarditis). High PD-L1 expression (ie, >50% Tumor Proportion Score) was observed in 22/144 (19%) patients. Confirmed objective responses were observed in patients with cSCC (n=5, including one complete response), hTMB (n=4, including one complete response), aSCC (n=2), TNBC (n=1), UPS (n=1), and anaplastic thyroid cancer (n=1). Conclusions: Pacmilimab can be administered safely at the RP2D of 10 mg/kg every 14 days. At this dose, pacmilimab had a low rate of immune-mediated toxicity and showed signs of antitumor activity in patients not selected for high PD-L1 expression

Hippocampus, Amygdala and Basal Ganglia Based Navigation Control

In this paper we present a novel robot navigation system aimed at testing hypotheses about the roles of key brain areas in foraging behavior of rats. The key components of the control network are: 1. a Hippocampus inspired module for spatial localization based on associations between sensory inputs and places; 2. an Amygdala inspired module for the association of values with places and sensory stimuli; 3. a Basal Ganglia inspired module for the selection of actions based on the evaluated sensory inputs. By implementing this Hippocampus-Amygdala-Basal Ganglia based control network with a simulated rat embodiment we intend to test not only our understanding of the individual brain areas but especially the interaction between them. Understanding the neural circuits that allows rats to efficiently forage for food will also help to improve the ability of robots to autonomously evaluate and select navigation targets

Domain wall generation by fermion self-interaction and light particles

A possible explanation for the appearance of light fermions and Higgs bosons on the four-dimensional domain wall is proposed. The mechanism of light particle trapping is accounted for by a strong self-interaction of five-dimensional pre-quarks. We obtain the low-energy effective action which exhibits the invariance under the so called \tau-symmetry. Then we find a set of vacuum solutions which break that symmetry and the five-dimensional translational invariance. One type of those vacuum solutions gives rise to the domain wall formation with consequent trapping of light massive fermions and Higgs-like bosons as well as massless sterile scalars, the so-called branons. The induced relations between low-energy couplings for Yukawa and scalar field interactions allow to make certain predictions for light particle masses and couplings themselves, which might provide a signature of the higher dimensional origin of particle physics at future experiments. The manifest translational symmetry breaking, eventually due to some gravitational and/or matter fields in five dimensions, is effectively realized with the help of background scalar defects. As a result the branons acquire masses, whereas the ratio of Higgs and fermion (presumably top-quark) masses can be reduced towards the values compatible with the present-day phenomenology. Since the branons do not couple to fermions and the Higgs bosons do not decay into branons, the latter ones are essentially sterile and stable, what makes them the natural candidates for the dark matter in the Universe.Comment: 34 pages, 2 figures, JHEP style,few important refs. adde