Unrestricted Number Research Articles

Estimating Discrete-Time Gaussian Term Structure Models in Canonical Companion Form

This article formally introduces a convenient parametrization for the popular class of discrete-time essentially-affine term structure models in the spirit of Duffee (2002), and Ang and Piazzesi (2003). First, I show that if the term structure is spanned by N_f latent state variables, all pricing information must also be contained in N_f shortest-maturity forward rates. Every no-arbitrage model of the type studied is therefore observationally equivalent to a unique canonical model in which these forward rates act as factors. Second, the risk-neutral transition matrix of the canonical model is conveniently parametrized by N_f unrestricted real numbers, and the risk neutral drift is a function of factor covariance matrix, plus one extra parameter. Third, although it may appear restrictive to specify the shortest-maturity forward rates as factors, the model can be estimated using all information in observed bond prices, either by Kalman filter, or assuming perfect observability of certain combinations of yields. Monte-Carlo evidence suggests that both approaches lead to similar out-of-sample forecasting performance in artificial data sets. Finally, by using unique insights offered by the canonical companion form, I discuss some difficulties in fitting term structure models of the essentially-affine class to the standard set of Fama-Bliss discount bonds. The problems stem from the existence of factors seemingly inconsistent with the assumption of no arbitrage. This discussion may have implications for interpreting the evidence of bond return predictability, and for the question of whether imposing no arbitrage can improve yield forecasts.

ACTR-11. PHASE II STUDY OF SINGLE AGENT BUPARLISIB IN RECURRENT/REFRACTORY PRIMARY (PCNSL) AND SECONDARY CNS LYMPHOMA (SCNSL)

PCNSL is an aggressive primary brain tumor. Outcome and treatment options are poor for recurrent/refractory (r/r) patients with response rates between 30–60% and progression free survival (PFS) of 2–6 months. PI3K inhibition has shown promising response in some B-cell malignancies. This phase II trial investigates Buparlisib in patients with r/r PCNSL and SCNSL. Eligible patients had r/r PCNSL/SCNSL, age≥18, KPS≥50, normal end-organ function, unrestricted number of prior therapies. Systemic disease needed to be absent in SCNSL patients. Patients received Buparlisib 100mg daily. The trial was closed prematurely due to limited clinical response. Four patients were enrolled: age 55, 60, 68, 79 with KPS of 90, 100, 90, 60, respectively. Three were men; 50% had PCNSL. All had parenchymal disease. Median prior CNS directed treatment was 2 (range 1–3); all methotrexate regimens. Two grade 4 toxicities (lymphopenia, neutropenia) were observed that resolved after drug was held. Most common toxicities were hyperglycemia, thrombocytopenia, and lymphopenia. Overall response rate was 25% with one partial response. This patient developed psychiatric symptoms within 8 weeks of treatment and drug was discontinued. Three patients developed neurologic symptoms at a median of 37 days after trial drug initiation all due to disease progression. Median progression free survival was 39 days. Median overall survival was 196 days. Buparlisib concentrations were assessed 2h after drug treatment on day 15 in plasma and CSF. Mean plasma concentration was 1104ng/ml (range: 844–1610); mean CSF concentration 139.5ng/ml (82.9–205). CSF concentration in the trial population (medium: 340nM; range: 202–499) was below the IC50 observed to induce cell death in lymphoma cells in vitro(>500nM). CD79B mutations were found in 3/4 patients. Patients with CNS lymphoma tolerate drug with acceptable toxicities. Treatment did not result in clinical response possibly due to CNS concentration below a meaningful IC50. Additionally, Buparlisib might not have single agent activity.

335P - Phase II study of single agent buparlisib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL)

PCNSL is an aggressive primary brain tumor. Outcome and treatment options are poor for patients with recurrent/refractory disease. Response rates range between 30-60% with a progression free survival (PFS) of 2-6 months. PI3K inhibition, particular of the delta isoform, has shown promising clinical response in some B-cell malignancies. This phase II trial investigates the pan-PI3K inhibitor Buparlisib in patients with recurrent/refractory (r/r) PCNSL and SCNSL. Eligible patients had r/r PCNSL/SCNSL, age ≥ 18, KPS ≥ 50, normal end-organ function, and unrestricted number of prior therapies. In patients with SCNSL, systemic disease needed to be absent. Enrolled patients received Buparlisib 100 mg daily. The trial was closed prematurely due to limited clinical response. Four patients were enrolled at age 55, 60, 68, and 79 with a KPS of 90, 100, 90 and 60, respectively. Three were men; 50% had PCNSL. All had parenchymal disease. Median prior CNS directed treatment was 2 (range 1-3); all methotrexate regimens. Two grade 4 toxicities (lymphopenia and neutropenia) were observed that resolved after drug was held. The most common toxicities observed were hyperglycemia, thrombocytopenia, and lymphopenia. The overall response rate was 25% with one partial response. This patient developed psychiatric symptoms within 8 weeks of treatment and drug was discontinued. Three patients developed neurologic symptoms at a median of 37 days after trial drug initiation. All were found to have disease progression. The median progression free survival was 39 days with a median overall survival of 196 days. Buparlisib concentrations were assessed on day 15 of drug treatment in plasma and CSF 2h after drug dosing. Mean plasma concentration was 1104ng/ml (range: 844-1610); mean CSF concentration 139.5ng/ml (82.9-205). CSF concentration in the trial population (340nM; range 202-499) was below the IC50 observed to induce cell death in lymphoma cells in vitro (>500nM). Patients with CNS lymphoma tolerate drug with acceptable toxicities. Treatment did not result in clinical response possibly due to CNS concentrations below a meaningful IC50. Buparlisib might also not have single agent activity in this disease.

Bayesian optimization for likelihood-free inference of simulator-based statistical models

Our paper deals with inferring simulator-based statistical models given some observed data. A simulator-based model is a parametrized mechanism which specifies how data are generated. It is thus also referred to as generative model. We assume that only a finite number of parameters are of interest and allow the generative process to be very general; it may be a noisy nonlinear dynamical system with an unrestricted number of hidden variables. This weak assumption is useful for devising realistic models but it renders statistical inference very difficult. The main challenge is the intractability of the likelihood function. Several likelihood-free inference methods have been proposed which share the basic idea of identifying the parameters by finding values for which the discrepancy between simulated and observed data is small. A major obstacle to using these methods is their computational cost. The cost is largely due to the need to repeatedly simulate data sets and the lack of knowledge about how the parameters affect the discrepancy. We propose a strategy which combines probabilistic modeling of the discrepancy with optimization to facilitate likelihood-free inference. The strategy is implemented using Bayesian optimization and is shown to accelerate the inference through a reduction in the number of required simulations by several orders of magnitude.

The MPEG Internet Video-Coding Standard [Standards in a Nutshell

To address the diversified needs of the Internet, the ISO/IEC JTC1/SC29/WG11 Moving Picture Experts Group (MPEG) started the project of Internet video coding (IVC) in July 2011. It is anticipated that any patent declaration associated with the baseline profile of this standard will indicate that the patent owner is prepared to grant a free-ofcharge license to an unrestricted number of applicants worldwide. IVC has been developed in MPEG from scratch by combining well-known existing technology elements and new contributions with free-of-charge licenses. Recently, IVC's compression performance has been determined to be approximately equal to that of the advanced video coding high profile (AVC HP) for typical operational settings, both for streaming and lowdelay applications. In June 2015, the IVC project was approved as ISO/IEC 14496-33 (MPEG-4 IVC). It is believed that this standard can be highly beneficial for video services in the Internet domain. This article describes the main coding tools adopted in IVC; evaluates its performance compared with web video coding (WVC), video coding for browsers (VCB), and AVC HP; and provides the subjective comparison results between IVC and AVC HP.

Frequency Technique for Mass and Strain Measurements

A frequency technique for mass and strain measurements is proposed that uses resistance strain gauges inserted at control points of a test object and combined with external capacitors of a phasing RC circuit. Equations are derived for calculating the quasiresonance frequencies with an unrestricted number of resistance strain gauges.

Phase I study of single agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL).

2046Background: PCNSL is an aggressive primary brain tumor. Outcome and treatment options are poor for patients with recurrent/refractory disease. Response rates range between 30-60% with a progression free survival (PFS) of 2-6 months. Ibrutinib has shown promising clinical response in some B-cell malignancies. This phase I trial investigates ibrutinib in patients with recurrent/refractory (r/r) PCNSL and secondary CNS lymphoma (SCNSL). Methods: Eligible patients had r/r PCNSL or SCNSL, age ≥ 18, KPS ≥ 50, normal end-organ function, and unrestricted number and type of prior therapies. In patients with SCNSL disease, systemic disease needed to be absent. Results: Ten patients were enrolled (3 at 560 mg; 7 at 840 mg). Median age was 70 (range 21-80); 7 were women. Median ECOG was 1 (0: 1, 1: 5, 2: 4). 70% had PCNSL and 30% SCNSL. Six had parenchymal disease, 3 isolated cerebrospinal fluid (CSF) involvement and 1 both. Patients were highly pretreated: 2 (both SCNSL) had prior stem cell transplant; 3 (2 PCNS...

Low-fidelity simulator for technical connection to the cardiopulmonary bypass.

The technical simulator proposed in this study is a low-cost, reusable, reproducible and portable tool to guide trainees at all levels in order to improve their surgical skills in connection with the cardiopulmonary bypass (CPB) circuit. The simulator is a self-made portable box that can be used for an unrestricted number of procedures. It is supplied with self-made anatomical replicas that have been tested to simulate the flexible property of the real anatomy. The building process is detailed in this study.

Non-specificity in disguise: morphology – semantics mismatches in Old Portuguese nominal items

The present inquiry has been spurred by the observation of the morphological behaviour of nominal items in medieval Portuguese codices (the 13th and 14th centuries). Individuals subject to legal regulations, besides being denoted by various configurations of common nouns, are identified also by first-person pronouns. Both kinds of nominal items occur nearly exclusively in singular in defiance of the fact that norms are designed to apply to an unrestricted number of potential addressees. A series of parameters converge to explain this form-function mismatch: type of inflection (inherent vs. contextual), text genre characteristics and syntactic environment (conditional protases). The pervasiveness of the singular in each type of these nominal items is traced back to non-specificity. Out of two competing patterns accounting for instances of (non-) variation in nominal morphology, Definiteness Hierarchy is given preference over degrees of animacy: non-specifically used items, even if highly ranked on animacy scale (e.g. personal pronouns), are the least likely to surface as plural forms. Therefore, a slight modification to the inventory of elements listed in the Definiteness Hierarchy is proposed.

Phase I Study of Single Agent Ibrutinib in Recurrent/Refractory Primary and Secondary CNS Lymphoma

BACKGROUNDPrimary CNS Lymphoma (PCNSL) is an aggressive primary brain tumor. Standard treatment of PCNSL may include radiation, methotrexate-based therapy, and anti-CD20 antibody therapy (rituximab) and is associated with substantial morbidity and treatment recurrence. Outcome and treatment options for patients with recurrent/refractory disease are poor. There is only limited use of targeted agents in this patient population. Ibrutinib has shown promising clinical response in some B-cell malignancies. This phase I trial investigates the maximal tolerated dose of ibrutinib in patients with recurrent/refractory PCNSL and secondary CNS lymphoma (SCNSL). METHODSEligible patients had a recurrent or refractory PCNSL or SCNSL, age≥18, KPS≥50, normal end-organ function, and unrestricted number and type of prior therapies. In patients with SCNSL disease, systemic disease needed to be absent or not requiring any active treatment. RESULTSThree patients have been enrolled at dose level 1 (560 mg daily) and one patient at dose level 2 (840mg daily) of whom three were women with a median age of 70 years (range 21-80). Three had recurrent PCNSL and 1 recurrent SCNSL. Two patients presented with parenchymal and two with leptomeningeal relapse. Treatment was generally well tolerated. There was one drug-related grade 4 toxicity (neutropenia) that resolved after the drug was held for 4 days. No drug related grade 3 toxicities have been observed to date. Most common grade 2 toxicities were decreased neutrophil count and hyperglycemia. All patients continue on study at a median follow up of 87 days. Three out of four patient were evaluated for response so far. There were two responses: one complete (in the CSF) and one partial, both in recurrent/refractory PCNSL as well as one stable disease in the patient with recurrent SCNSL. The patient with partial response had failed multiple prior treatment regimens including methotrexate-based chemotherapy, radiation, and rituximab/temozolomide. Serum and CSF pharmacokinetic analysis is initiated. Dose level 2 (840mg) is accruing. CONCLUSIONPatients with CNS lymphoma tolerate Ibrutinib at 560 and 840mg well. Dose escalation will continue. Targeted agents might be an alternative therapeutic approach to be investigated for refractory/recurrent CNS lymphoma patients. DisclosuresNo relevant conflicts of interest to declare.

Inflection – semantics interfaces in a typological setting: number and non-specific nominal items in Old Spanish legal codices

Abstract Mikołaj Nkollo & Magdalena Tkaczyk. Inflection - semantics interfaces in a typological setting: number and non-specific nominal items in Old Spanish legal codices. The Poznań Society for the Advancement of Arts and Sciences, PL ISSN 0079-4740, pp. 17-29 The present inquiry has been spurred by the observation of the morphological behaviour of human-denoting common nouns in Old Spanish codices (13th to 15th century). In spite of the fact that legal norms are designed to apply to an unrestricted number of potential addressees, this class of nominal items surfaces nearly exclusively in the singular, with plural forms being strongly underrepresented. A series of parameters converge to account for this form - function mismatch, thus revealing an essentially interdependent nature of linguistic mechanisms underlying it: type of inflection (inherent vs. contextual), text genre characteristics (distance pole vs proximate pole) and syntactic environment (conditional protases). The pervasiveness of the singular is traced back to non-specificity. Out of two mutually exclusive typological clines accounting for the likelihood of inflectional variation in noun morphology, Definiteness Hierarchy is given preference over degrees of animacy: non-specifically used items, even if highly ranked on animacy scale, are the least likely to surface as plural forms. Competing motivations are assumed to provide a suitable analytical framework to account for typological conflicts such as the one exemplified in Old Spanish legal codices.

An Efficient and Practical Smart Card Based Anonymity Preserving User Authentication Scheme for TMIS using Elliptic Curve Cryptography.

In the last few years, numerous remote user authentication and session key agreement schemes have been put forwarded for Telecare Medical Information System, where the patient and medical server exchange medical information using Internet. We have found that most of the schemes are not usable for practical applications due to known security weaknesses. It is also worth to note that unrestricted number of patients login to the single medical server across the globe. Therefore, the computation and maintenance overhead would be high and the server may fail to provide services. In this article, we have designed a medical system architecture and a standard mutual authentication scheme for single medical server, where the patient can securely exchange medical data with the doctor(s) via trusted central medical server over any insecure network. We then explored the security of the scheme with its resilience to attacks. Moreover, we formally validated the proposed scheme through the simulation using Automated Validation of Internet Security Schemes and Applications software whose outcomes confirm that the scheme is protected against active and passive attacks. The performance comparison demonstrated that the proposed scheme has lower communication cost than the existing schemes in literature. In addition, the computation cost of the proposed scheme is nearly equal to the exiting schemes. The proposed scheme not only efficient in terms of different security attacks, but it also provides an efficient login, mutual authentication, session key agreement and verification and password update phases along with password recovery.

Comprehensive Middle-Fidelity Simulator for Training in Aortic Root Surgery

The current training in aortic root surgery is affected by several factors: complexity of surgical procedures and the complex 3-dimensional anatomy of the aortic root. The aortic root simulator proposed in this study is an additional low-cost, reusable, and portable tool to improve surgical skills in a middle-fidelity model. The aortic root surgery simulator is a self-made portable box that can be used for an unrestricted number of procedures. It is supplied with a self-made aortic root substitute, which was tested to simulate the flexible property of the aortic root components. The building process is detailed in this study. Aortic root procedures were performed by use of this simulator, in which surgical handling was tested. The total cost was calculated in euros. Building the aortic root simulator resulted in the development of a new training tool for aortic root surgery. The use of silicone led to the construction of the aortic root components with similar diameters and properties as those of a real aortic root, which permitted performing the surgical procedures in unrestricted numbers. This involved the aortic valve including all types of aortic valve replacements such as interrupted and semicontinuous, and all types of aortic root procedures like enlargement, remodeling, reimplantation, and replacement. Moreover, the silicone allowed modeling of various pathological replicas of the aortic valve, which resulted in facilitating the practice of aortic valve repair techniques according to El Khoury׳s classification. The cost was approximately €1. Surgical skills in aortic root surgery could be improved by using a middle-fidelity simulator. The high cost of the training for residents and junior surgeons could be reduced effectively through the use of this low-cost, portable, reusable simulator and its accessories (aorta and valves). Familiarity with performing the surgical procedures could reduce the time consumed in the operation room.

Cryptanalysis and Design of a Three-Party Authenticated Key Exchange Protocol Using Smart Card

Three-party authenticated key exchange protocol (3PAKE) is used to provide security protection on the transmitted data over the insecure communication by performing session key agreement between the entities involved. Comparing with the 2PAKE protocol, 3PAKE protocol is more suitable for managing unrestricted number of users. Recently, several researchers have proposed many 3PAKE protocols using smart card. However, we have scrutinized carefully recently published Yang et al.’s protocol, and it has been observed that the same protocol suffers from several security weaknesses such as insider attack, off-line password guessing attack, many logged-in users’ attack and replay attack. Moreover, we have justified a serious security issue of the password change phase of the same scheme. In order to fix the above-mentioned shortcomings, this paper proposes an efficient 3PAKE protocol using smart card based on the cryptographic one-way hash function. The formal security analysis proves that proposed protocol provides strong security protection on the relevant security attacks including the above-mentioned security weaknesses. Moreover, the simulation results of the proposed scheme using AVISPA tool show that the same protocol is SAFE under OFMC and CL-AtSe models. The performance comparisons are also made, which ensure that the protocol is relatively better than the existing related schemes. To the best of our knowledge, the proposed scheme should be implemented in practical application, as it provides well security protection on the relevant security attacks, provides relatively better complexities than the existing schemes, achieves proper mutual authentication along with user-friendly password change phase.

Low-Fidelity Simulation of Mitral Valve Surgery: Simple and Effective Trainer

Training in mitral valve (MV) surgery is difficult because of its complex 3-dimentional anatomy and sophisticated surgical techniques. The goal of this study was to create an effective and simple simulator to enable the trainee in performing MV repair and replacement techniques in a low-fidelity environment. The MV surgery simulator is a self-shaped sponge integrated into a portable box that can be used for an unrestricted number of procedures. The building process is detailed in this study. MV procedures were performed in which the surgical handling was tested. The total cost was calculated in euros. The building of the MV simulator resulted in the development of a new low-cost tool for training in MV surgery. The usage of the sponge led to building the MV components with flexible properties and allowing the surgical procedures to be performed in unrestricted numbers. This involved MV replacement in both intra- and supra-annular fashion and MV repair according to the Carpentier classification. Surgical skills in mitral surgery could be improved by usage of the low-fidelity simulator. The high cost of the training for residents and junior surgeons could be effectively reduced by using this low-cost, portable, reusable simulator and its accessories (ring and band).

Introduction

Introduction Melvin I. Urofsky We begin our fortieth year ofpublication with pride and optimism. Pride that over the years we have been able to bring to our readers interesting articles about many dif­ ferent aspects of U.S. Supreme Court history written by some ofthe leading scholars in the field. Optimism that we can continue to do this in the years to come. This issue suggests that our optimism is not unfounded. Historians have long puzzled over John Jay and his decision to step down as Chief Justice, and then a few years later to decline an offer to re-establish him in that position. A leading figure of the Revolutionary period, a statesman,jurist, a co-author ofTheFederalist Papers, governor of New York, a diplomat, and our nation’s first ChiefJustice, there is no question that his place in American history is honored and secure. He failed, however, to see the opportunity that leading the High Court could provide to help shape the new nation’s destiny. When he resigned, he claimed that the judiciary would never be an important part of the government. Matthew Van Hook explores Jay’s ambivalence about the Court, and tries to make sense of it in light of Jay’s own ambitions and talents. Mr. Van Hook is a Ph.D. candidate in political science at the University ofNotre Dame. One can hardly pick up the newspaper these days, nor turn on the radio or television news, without another story about immigra­ tion. Historians are well aware that immigra­ tion did notjust become a contentious issue in the past few years. During the Progressive Era there was a great national debate over the wisdom of continuing to allow unrestricted numbers of people, especially those from eastern and southern Europe, to enter the country. The debate finally ended in the 1924 statute severely limiting migration into the United States. In the nineteenth century the debate involved those who came from China, many of whom helped build the transconti­ nental railroad. A question then, as now, is who had the power to regulate that migration—the states or the federal government. While we pay little attention to those decisions now, the Supreme Court heard several cases on the matter, and whether there was a federal police power that could be called into service. Adam Carrington, v vi JOURNAL OF SUPREME COURT HISTORY an assistant professor of politics at Hillsdale College, looks at one of the most important Justices of the latter nineteenth century, Stephen J. Field, and his evolving views on this subject. When legal scholarsplay the game of “Who Are the Great Justices?” it is fairly certain to say that William Rufus Day is never mentioned. Day, appointed by Theodore Roosevelt in the spring of 1903, served on the Court until his resignation in November 1922, nearly two full decades, and in that time heard hundreds of important cases. He is remembered, if at all, as the author ofthe majority opinion in Hammer v. Dagenhart (1918). Yet Jesse Bair thinks Day’s service is underappreciatedandthat he deserves a re-evaluation. Mr. Bair, a student of Professor Brad Snyder while at the University of Wisconsin Law School, won the Society’s Hughes-Gossett Student Prize for 2014 with this article. He is now an associate at the Madison, Wisconsin, office of Perkins Cole LLP. We now come to the second installment of Barry Cushman’s “The Clerks of the Four Horsemen,” dealing with those men serving George Sutherland and Pierce Butler. We know farmore about the clerks ofthe “great Justices,” such as Holmes and Brandeis, who often wrote about the wonderful year they spent with “their” Justice. The diary of a frustrated McReynolds clerk sent Professor Cushman— who is the John P. Murphy Foundation Professor at Notre Dame Law School—on a quest to see how other clerks fared with these four, particularly in theirpost-clerkship careers. Finally serendipity—as it often does— played a role in securing our last article. I was one ofthe speakers at a symposium sponsored by his clerks held at the Court last spring to mark the seventy-fifth anniversary ofWilliam O. Douglas’s appointment to the Bench. The keynote...

Flexible Antigen-Specific Redirection of Human Regulatory T Cells Via a Novel Universal Chimeric Antigen Receptor System

Based on compelling evidence from a vast number of in vitro and in vivostudies, Tregs have become an attractive cell population to treat or even prevent auto- and alloimmunity including Graft-versus-Host disease (GvHD). However, several safety concerns still exist as for example the risk of global immunosuppression using polyclonal Tregs. In fact, experiments in mice showed that adoptive transfer or induction of antigen-specific Tregs is more potent regarding suppression of pathogenic immune responses when compared to polyclonal Treg populations. Unfortunately, the isolation and expansion of naturally occurring antigen-specific Tregs is technically difficult, labour-intensive, and time-consuming. An attractive way to overcome these limitations and to endow polyclonal Treg populations with a desired antigen-specificity is their engraftment with chimeric antigen receptors (CARs). In this context, CAR-modification represents a promising approach to redirect polyclonal Tregs in an antigen-specific manner to suppress ongoing self-destructive immune responses at the site of inflammation.Nevertheless, until now redirection of CAR-engineered T cells is limited to a single target antigen, restricting this approach to an unflexible monospecific therapy. Therefore, we developed a more flexible universal CAR (UCAR) platform that allows redirection of T cells to an in principal unrestricted number of surface antigens. T cells are engrafted with UCARs that bind to a small peptide epitope derived from a human nuclear protein. Cross-linkage to target cells is mediated by independent target modules that provide antigen-specificity and comprise the peptide epitope recognized by the UCAR. In order to target different tissue antigens, the target modules can easily be exchanged. Thereby, once established, the treatment strategy can easily be applied to various auto- and alloimmune diseases.At present, the CD45RA+ population is the Treg subset of choice for a clinical application as these cells have the highest capacity to maintain phenotypic and functional Treg properties upon prolonged ex vivo expansion. Here we show that highly pure, sorted CD4+CD25+CD127lowCD45RA+ Tregs can be genetically manipulated using lentiviral gene transfer, resulting in approximately 70 % of UCAR-expressing Treg cells. The transduction procedure itself did not affect the phenotype of UCAR-engineered Tregs as it was similar to non-transduced wildtype cells. Both Treg populations presevered FOXP3 expression even after prolonged in vitro cultivation (> 95 % FOXP3+). Upon incubation with antigen-positive target cells and a respective target module UCAR-engineered Tregs upregulate the activation markers CD69 and LAP demonstrating that the cells can be restimulated antigen-specifically. Most importantly, UCAR-engrafted Tregs were functionally activated upon antigen encounter, demonstrated by suppression of proliferation and expansion of cocultured autologous T effector cells.Taken together, our results pave the way towards an application of UCAR technology for a site-specific recruitment of CAR-modified Tregs into inflamed tissues aiming at re-establishing immune homeostasis. Due to its high flexibility UCAR-engrafted Tregs can easily and universally be used for treatment of various autoimmune diseases or GvHD just by exchanging the tissue-specific target modules. DisclosuresCartellieri:Cellex Patient Treatment GmbH: Employment. Ehninger:GEMoaB GmbH: Employment, Patents & Royalties. Ehninger:GEMoaB GmbH: Consultancy, Patents & Royalties. Bachmann:GEMoaB GmbH: Consultancy, Patents & Royalties.

A computational tool to design and generate crystal structures

The evolution of computers, more specifically regarding the increased storage and data processing capacity, allowed the construction of computational tools for the simulation of physical and chemical phenomena. Thus, practical experiments are being replaced, in some cases, by computational ones. In this context, we can highlight models used to simulate different phenomena on atomic scale. The construction of these simulators requires, by developers, the study and definition of accurate and reliable models. This complexity is often reflected in the construction of complex simulators, which simulate a limited group of structures. Such structures are sometimes expressed in a fixed manner using a limited set of geometric shapes. This work proposes a computational tool that aims to generate a set of crystal structures. The proposed tool consists of a) a programming language, which is used to describe the structures using for this purpose their characteristic functions and CSG (Constructive Solid Geometry) operators, and b) a compiler/interpreter that examines the source code written in the proposed language, and generates the objects accordingly. This tool enables the generation of an unrestricted number of structures, which can be incorporated in simulators such as the Monte Carlo Spin Engine, developed by our group at UFJF.

A combinatorial double auction resource allocation model in cloud computing

Users and providers have different requirements and objectives in an investment market. Users will pay the lowest price possible with certain guaranteed levels of service at a minimum and providers would follow the strategy of achieving the highest return on their investment. Designing an optimal market-based resource allocation that considers the benefits for both the users and providers is a fundamental criterion of resource management in distributed systems, especially in cloud computing services. Most of the current market-based resource allocation models are biased in favor of the provider over the buyer in an unregulated trading environment. In this study, the problem was addressed by proposing a new market model called the Combinatorial Double Auction Resource Allocation (CDARA), which is applicable in cloud computing environments. The CDARA was prototyped and simulated using CloudSim, a Java-based simulator for simulating cloud computing environments, to evaluate its efficiency from an economic perspective. The results proved that the combinatorial double auction-based resource allocation model is an appropriate market-based model for cloud computing because it allows double-sided competition and bidding on an unrestricted number of items, which causes it to be economically efficient. Furthermore, the proposed model is incentive-compatible, which motivates the participants to reveal their true valuation during bidding.

Elements of concern in fillets of bighead and silver carp from the Illinois River, Illinois

Efforts to control invasive bighead (Hypophthalmichthys nobilis) and silver carp (H. molitrix) may include harvest for human consumption. We measured concentrations of arsenic (As), mercury (Hg), and selenium (Se) in fillets from silver and bighead carp collected from the lower Illinois River, Illinois, USA, to determine whether concentrations were of health concern and differed by species, size, and location. Concentrations of total As were below detection limits in most bighead (92%) and silver (77%) carp fillets, whereas inorganic As was below detection limits in all samples. Mean Hg concentrations were greater in bighead (0.068mgkg−1) than in silver carp (0.035mgkg−1), and were smallest in carp from the confluence of the Illinois and Mississippi rivers. Mercury concentrations in fillets were positively correlated with body mass in both species. Concentrations of Hg were below the US Food and Drug Administration’s (USFDA) action level (1ppm as methyl-Hg); however, concentrations in some bighead (70%) and silver (12%) carp fell within the range that would invoke a recommendation to limit meals in sensitive cohorts. Mean Se concentrations were greater in silver (0.332mgkg−1) than in bighead (0.281mgkg−1) carp fillets, and were below the 1.5mgkg−1 limit for an unrestricted number of meals/month. The mean molar ratio of Se:Hg in fillets was lower in bighead (14.0) than in silver (29.1) carp and was negatively correlated with mass in both species Concentrations of Hg in bighead and silver carp fillets should be considered when assessing the risks associated with the use of these species as a protein source.