B cell maturation antigen (BCMA) has recently emerged as an attractive therapeutic target in multiple myeloma. BCMA has restricted expression on plasma cells with little to no expression on other normal tissues, but is upregulated on the surface of multiple myeloma cells. BCMA can regulate proliferation and survival of myeloma cells via binding to its ligands APRIL and BAFF and induce downstream signaling pathways. Thus, several approaches to target BCMA are currently under clinical investigation, including chimeric antigen receptor (CAR) T cell therapies, bispecific antibodies and antibody drug conjugates. The Antibody-Coupled T cell Receptor (ACTR) technology is a universal, engineered T cell therapy consisting of the extracellular domain of human CD16 and the intracellular T cell co-stimulatory and signaling domains. ACTR is designed to engage the Fc domain of therapeutic antibodies opsonized to target cells to mediate anti-tumor activity. Previous work has demonstrated ACTR T cell activity in combination with rituximab, trastuzumab, and hu14.18 K322A against CD20, Her2, and GD2 expressing cell lines, respectively (Kudo et al. Cancer Res 2014; 74:93-103). Currently ACTR is being evaluated in Phase I clinical trials with rituximab to treat relapsed refractory B cell lymphoma. Here we demonstrate a humanized afucosylated anti-BCMA antibody, SEA-BCMA, binds to ACTR expressing T cells with high affinity and mediates T cell activation, potent cytotoxicity, cytokine release and proliferation across a wide range of BCMA expressing myeloma cells. ACTR activity was specific to SEA-BCMA - opsonized target cells, dose dependent and had no activity on BCMA negative tumor lines. Furthermore, the SEA-BCMA antibody has additional properties that might contribute to a therapeutic effect, including blocking the binding of ligands to BCMA and driving natural killer cell mediated ADCC effects. These preclinical studies demonstrate a promising multi-faceted activity of ACTR T cells in combination with the anti-BCMA antibody, SEA-BCMA, for clinical consideration in multiple myeloma patients. Citation Format: Tooba Cheema, Taylor Hickman, Katie O9Callaghan, Lori Westendorf, Luke Manlove, Shyra Gardai, Allison Nelson, Ryan Boomer, Kathleen McGinness, Birgit Schultes, Seth Ettenberg, Django Sussman, Heather Huet. Efficient targeting of BCMA-positive multiple myeloma cells by antibody-coupled T-cell receptor (ACTR) engineered autologous T cells in combination with an anti-BCMA antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4605. doi:10.1158/1538-7445.AM2017-4605


This article discusses intensively the current debate between those who support and against liberalism within pluralized Indonesian muslims. The two groups are represented by JIL (Jaringan Islam Liberal) and MD (Media Dakwah). The author compares three fundamental aspects of religious interpretations: epistemological assumptions, methodological framework, and subject-matter. Epistemological assumptions deal with philosophical foundations that are employed by JIL and MD as principles to understand Islam. Methodological framework means the way the two groups understand and interpret Islam and its teaching based on their philosophical foundations. In terms of subject-matter, the author discusses six issues, namely (1) ijtihad, (2) approaches to text, (3) the meaning of truth, (4) the minority and the oppressed, (5) freedom of religion, and (6) mundane and spiritual authority. From the three fundamental aspects of religious interpretations that are compared, the author concludes that JIL is a group of muslims who understand Islam by implementing liberalism, while MD represents a group of muslim who promote conservatism, purification, and anti-liberalism within Indonesian Islam.


Action Research is being adopted as a research and project method for the higher education learning and teaching sector. A researcher new to Action Research may need to be scaffolded through the process of validating their research as Action Research, asking the question 'am I really doing Action Research?' A multi-disciplinary team of Action Research Enablers, at one metropolitan university, cogenerated a set of indicators of the enactment of Participatory Action Research in learning and teaching projects. This paper introduces the indicators, their development and the associated tool. The role of the indicators in offering systematised project evaluative data is discussed. Indicators are illustrated with qualitative data, drawing upon the reflective narratives of the Action Research Enablers who engaged in regular supported reflection sessions. The need for the continual development of descriptors and the role of metrics to provide quantitative data are presented as ongoing research issues for Action Research projects.


Hepatic lymphangiomas are extremely rare; moreover cystic lymphangiomas usually arise in areas such as the neck and axilla, where loose connective tissue allows the expansion of lymphatic channels. The case of a 65-year old male is described, who presented with a solitary lymphangioma in the liver. The lesion was discovered incidentally and due to diagnostic uncertainty was removed surgically. A short review of histology, clinical presentation and preoperative diagnostic difficulties of hepatic lymphangiomas is given.


We study how a decision maker uses his reputation to simultaneously influence the actions of multiple receivers with heterogenous biases. The reputational payoff is single-peaked around a bliss reputation at which the incentives of the average receiver are perfectly aligned. We establish the existence of two equilibria characterized by repositioning toward this bliss reputation that only differ through a multiplier capturing the efficiency of reputational incentives. Repositioning is moderate in the more efficient equilibrium, but the less efficient equilibrium features overreactions, and welfare may then be lower than in the no-reputation case. We highlight how strategic audience management (e.g., centralization, delegation to third parties with dissenting objectives) alleviates inefficient reputational incentives, and how multiple organizational or institutional structures may arise in equilibrium as a result.


Land preparation is an integral and, as yet, indispensable component of the farmingpractices followed by inhabitants of the middle hills of Nepal. Most farmers continue to follow age-old traditional soil tillage practices using locally fabricated ploughs and hand implements. Farming in the mid-hills involves a huge labour investment due in part to the nature of the land and part to the lagely manual methods used by the 'fanners. Recent years have seen substantial increases in land-use intensification in the agricultural sector throughout the mid-hill areas of Nepal. Such intensification is mainly in the form of increased off-season vegetable and horticultural production. The development and adoption of new technologies for increased labour eficiency, reduced costs, and minimised soil tillage and exposure to erosion are required to ensure the sustainability of farming in the middle hills of Nepal. An integrated approach involving soil and water conservation practices, as well as, diversified, carefully managed cropping, soil fertility, organic matter; and weedfpest control systems are needed. This paper provides a preliminary review of existing traditional practices and innovative techniques for land preparation in the mid-hills of Nepal.


Current 3D scene stylization methods transfer textures and colors as styles using arbitrary style references, lacking meaningful semantic correspondences. We introduce Reference-Based Non-Photorealistic Radiance Fields (Ref-NP R) to address this limitation. This controllable method stylizes a 3D scene using radiance fields with a single stylized 2D view as a reference. We propose a ray registration process based on the stylized reference view to obtain pseudo-ray supervision in novel views. Then we exploit semantic correspondences in content images to fill occluded regions with perceptually similar styles, resulting in non-photorealistic and continuous novel view sequences. Our experimental results demonstrate that Ref-NPR out-performs existing scene and video stylization methods regarding visual quality and semantic correspondence. The code and data are publicly available on the project page at https://ref-npr.github.io.


Author(s): Behn, Andrew Paul | Advisor(s): Bell, Alexis T; Head-Gordon, Martin | Abstract: The use of theoretical chemistry techniques in the investigation of catalytic reactions has been able to provide strong insights into the inner workings of various chemical mechanisms. In tandem with experimental results, such studies often provide information by computing reaction rates with transition state theory, predicting and/or confirming various spectroscopic experiments, and elucidating the identities and structures of key stable intermediates and short-lived transition states. The present work is concerned with the application of these techniques to the study of the oxidative carbonization of toluene to toluic acid over Rh(III) and Pd(II), as well as the development of theoretical techniques to efficiently find ab initio transition states for use in such studies. Previous work has shown that the oxidative carbonylation of toluene to form toluic acid is possible with Rh(III) and Pd(II) with acetic acid. These reactions are believed to operate via a rate-limiting electrophilic mechanism in which toluene binds to the metal complex and has a C-H bond activated. Previous works have suggested that the active catalyst for the Rh(III) system is Rh(CF3COO)3(CO)2, and Pd(CF3COO)2 for the Pd(II) system, though these were not rigorously confirmed. In this work, we properly identify the Rh(III) species as the active catalyst through a series of ab initio spectroscopic calculations with comparison to experiments. Additionally, an unprecedented interaction between an acetate and carbonyl ligand on the Rh(CF3COO)2(CO)2 catalyst is investigated and found to be the result of an unusual charge balance within the structure. Prior work has shown that using trifluoroacetic acid instead of acetic acid significantly increases the rate of reaction, without investigating further. This work demonstrates that the reaction rate passes through a maximum for intermediate strength acids, which is due to competition between the two sub-steps of the rate-limiting step. Weakly basic anionic ligands increase the positive charge on the metal center and increase the rate of toluene binding while decreasing the ability of the same ligands to accept the activated proton. A similar trend and explanation were found with a model catalyst for the Pd(II) system as the ligands were varied. The second part of this work concerns the development of efficient transition state searching algorithms. The calculation of theoretical rate constants often employs transition state theory, but requires the user to possess the transition state structure. The local search for such a structure requires an extremely good guess, and is most practically obtained with the help of an automated guess generator. The most commonly used algorithms operate by optimizing a chain of molecular images connecting known reactant and product structures into the reaction pathway. One such routine, the Growing String Method (GSM), grows a chain of states inward from the known endpoints while optimizing these points. The original GSM algorithm relies upon cartesian coordinates with cubic splines for adding new structures to the chain, however this often leads to unrealistic images which require many steps to relax into the reaction pathway. By replacing the cartesian coordinate interpolation with Linear Synchronous Transit interpolation, the computational cost of optimizing complex reaction pathways may be cut approximately in half. Additionally, by simplifying the algorithm to focus computational effort on the location of just the transition state rather than the entire reaction pathway, the overall cost may be reduced even further. In this new method, the Freezing String Method, nodes are iteratively added to a growing chain, optimized for several steps, and then frozen in place for the remainder of the execution.


OBJECTIVE
To examine the effects of chronic H2 receptor antagonist treatment and pulmonary complications, length of stay in intensive care (ITU), high dependency (HDU), and stay in hospital in patients who undergo pulsatile cardiopulmonary bypass.

DESIGN
An analysis from a prospective database of patients undergoing cardiac surgery with pulsatile perfusion during cardiopulmonary bypass.

SETTING
Hammersmith Hospital, regional cardiothoracic surgical centre.

SUBJECTS
2,642 patients who had undergone cardiac surgery involving pulsatile perfusion. Of these, 255 were on H2 receptor antagonist treatment.

MAIN OUTCOME
Time to extubation, re-intubation rate, incidence of pulmonary oedema, measures incidence of lobar collapse and consolidation, incidence of antibiotic treatment for pulmonary infection, length of ITU, HDU and total hospital stay.

RESULTS
75.8% of patients on H2 receptor antagonists compared with 74.5% of control patients had no respiratory complications after cardiac surgery (P > 0.5). There was no significant difference between collapse and consolidation (P > 0.5), collapse and consolidation requiring antibiotics (P > 0.5), re-intubation (P > 0.5), pulmonary oedema (P > 0.5), time to extubation (P > 0.5), length of ITU stay (P > 0.5), length of HDU stay (P > 0.5), length of hospital stay (P > 0.5), and mortality (P > 0.5).

CONCLUSION
Chronic H2 receptor antagonist treatment has no effect on pulmonary complications after cardiac surgery.


ABSTRACT Pyrolysis is a thermal method in which volatile matter present in a biomass will be degraded to lower molecular substances. This study aims at evaluation of kinetics of lignocellulosic biomass of leaves and stems of Hibiscus rosa sinensis and Nerium oleander under pyrolytic conditions, their proximate and ultimate analyses and their calorific values. Pyrolysis experiments were carried out using a thermogravimetric balance, which combines heat flux type differential thermal analysis (DTA) with thermogravimetric analysis (TGA) at different heating rates under a nitrogen atmosphere. The results were analyzed using weight loss vs. temperature and derivative weight vs. temperature profiles obtained from DTA and TGA curves. Three kinetic stages apart from moisture evaporation were observed based on the type of biomass. Kinetic parameters such as the pre-exponential factor and activation energy for each degradation step were calculated using first-order kinetics. The assumption of first-order kinetics was also proved from the experimental data. The results showed that Nerium oleander leaves are more suitable for fuel production through pyrolysis due to their higher percentage of volatile matter, low sulfur content, lower ash content, higher calorific value and lower activation energy required to decompose constituents of biomass, namely hemicellulose, cellulose and lignin.


The effect of electron dose rate on phase separation induced by electronic excitation in GaSb nanoparticles has been studied in order to see whether a nonlinear relation between density of excited states introduced and the efficiency of the phase separation is found or not. The phase separation to two phases consisting of an antimony core and a gallium shell proceeds after incubation time with increasing electron dose and does only at the dose rate above a threshold value. It is suggested that such nonlinear behaviors take place as a cooperative phenomenon among electronic-excitation effect, nano-size effect and temperature.


In this study, we considered the numerical solution of the nonlinear Burgers equation using the Variational Iteration Method (VIM). The method seeks to examine the convergence of solutions of the Burgers equation at the expense of the parameters x and t of which the amount of errors depends. Numerical experimentation was carried out on the Burgers equation with the Variational Iteration Method (VIM). The resulting solution showed that the rate of convergence decreases with increase in the values of the parameters x and t at each iterate level. However, as the number of iterations increases, there is a rapid rate of convergence of the approximate solution to the analytic solution. Results obtained with the Variational Iteration Method (VIM) on the Burgers equation were compared with the exact found in literature. All computational framework of the research were performed with the aid of Maple 18 software. Keywords : Variational Iteration Method, Burgers Equation, Partial Differential Equations, Approximate Solution, Mean Value Theorem, Schwartz Inequality.


Sex-determination methods are very diverse as they have become an enduring research field. Understanding the causes of gonadal development and elucidating the main factors involved in sex-determination of offspring required relating information from far-ranging areas such as cytology, embryology, morphology, molecular biology and even ecology and evolution. This article presents an overview of sex-determination in placental mammals, encompassing several levels of biological organization. The importance of the underlying molecular tools in the context of sex-determination assays and their implications in conservation genetics is also discussed.


Electrical storm (ES) is a clinical condition characterized by three or more ventricular arrhythmia episodes leading to appropriate implantable cardioverter-defibrillator (ICD) therapies in a 24 h period. Mostly, arrhythmias responsible of ES are multiple morphologies of monomorphic ventricular tachycardia (VT), but polymorphic VT and ventricular fibrillation can also result in ES. Clinical presentation is very dramatic in most cases, strictly related to the cardiac disease that may worsen electrical and hemodynamic decompensation. Therefore ES management is challenging in the majority of cases and a high mortality is the rule both in the acute and in the long-term phases. Different underlying cardiomyopathies provide significant clues into the mechanism of ES, which can arise in the setting of structural arrhythmogenic cardiomyopathies or rarely in patients with inherited arrhythmic syndrome, impacting on pharmacological treatment, on ICD programming, and on the opportunity to apply strategies of catheter ablation. This latter has become a pivotal form of treatment due to its high efficacy in modifying the arrhythmogenic substrate and in achieving rhythm stability, aiming at reducing recurrences of ventricular arrhythmia and at improving overall survival. In this review, the most relevant epidemiological and clinical aspects of ES, with regard to the acute and long-term follow-up implications, were evaluated, focusing on these novel therapeutic strategies of treatment.