Broadly Applicable Research Articles

THE ARCONS PIPELINE: DATA REDUCTION FOR MKID ARRAYS

The Array Camera for Optical to Near-IR Spectrophotometry, or ARCONS, is a camera based on Microwave Kinetic Inductance Detectors (MKIDs), a new technology that has the potential for broad application in astronomy. Using an array of MKIDs, the instrument is able to produce time-resolved imaging and low-resolution spectroscopy constructed from detections of individual photons. The arrival time and energy of each photon are recorded in a manner similar to X-ray calorimetry, but at higher photon fluxes. The technique works over a very large wavelength range, is free from fundamental read noise and dark-current limitations, and provides microsecond-level timing resolution. Since the instrument reads out all pixels continuously while exposing, there is no loss of active exposure time to readout. The technology requires a different approach to data reduction compared to conventional CCDs. We outline here the prototype data reduction pipeline developed for ARCONS, though many of the principles are also more broadly applicable to energy-resolved photon counting arrays (e.g., transition edge sensors, superconducting tunnel junctions). We describe the pipeline's current status, and the algorithms and techniques employed in taking data from the arrival of photons at the MKID array to the production of images, spectra, and time-resolved light curves.

Development of an Air-Stable, Broadly Applicable Nickel Source for Nickel-Catalyzed Cross-Coupling

The synthesis of NiCl(o-tolyl)(TMEDA) (3; TMEDA = tetramethylethylenediamine) and its application in coupling reactions is described. In combination with a suitable ligand, precatalyst 3 was applied to a wide range of transformations, such as Suzuki, amination, Kumada, Negishi, Heck, borylation, and reductive coupling. Yields of products obtained with 3 are equal or superior to those obtained with common Ni sources such as Ni(cod)2 (1) and NiCl2(dme) (2). Importantly, and unlike 1, complex 3 is stable for months in air as a solid, which eliminates the need for a glovebox and greatly facilitates the reaction setup. Thus, complex 3 is the first highly versatile Ni source that combines the broad applicability of 1 with the air stability of 2.

Patient’s Experience of the Outcomes of Engaging in a Broadly Applicable Health Promotion Intervention for Individuals Facing Chronic Illness

The aim of this study was to explore the health-related outcomes of a new health promotion intervention designed to be broadly applicable among people diagnosed with chronic illness. Qualitative process analysis was applied and a purposeful sample of 52 patients, representing a variety of long-term conditions, was invited to participate in the pilot-implementation and evaluation of the program. Participants attended individually or in groups in seven sessions held over a six-month period. A lay-based conceptual framework that revealed the bodily knowledge of patients with chronic illness as a resource for health was used as the frame for the program content and interdisciplinary health professionals who had undergone 80 hours of training led the program. The pedagogical approaches were varied in order to engage patients in health promotion work. In-depth evaluation interviews took place soon after program completion and data were analyzed in-depth by means of content analysis in order to identify patterns of health-related themes and the program’s possible active ingredients. The intervention was implemented successfully across clinical sites and diagnostic categories. Participants reported improved ability to manage illness-related problems and greater awareness and utilization of personal resources for health after they had participated in the program. They were able to think more positively about their own capabilities, gained greater understanding of factors that made their health condition better or worse, and became more active. Participants identified empowerment and social participation as important outcomes of engaging in the new program.

PRM6 - A Novel Broadly Applicable Risk Score for Predicting Mortality of Patients with Circulatory System Diseases within Hospitalization Duration

PRM6 - A Novel Broadly Applicable Risk Score for Predicting Mortality of Patients with Circulatory System Diseases within Hospitalization Duration

ChemInform Abstract: Broadly Applicable Z‐ and Diastereoselective Ring‐Opening/Cross‐Metathesis Catalyzed by a Dithiolate Ru Complex.

AbstractAll the products are obtained with excellent (Z)‐selectivities.

A Broadly Applicable Strategy for Entry into Homogeneous Nickel(0) Catalysts from Air-Stable Nickel(II) Complexes.

A series of air-stable nickel complexes of the form L2Ni(aryl) X (L = monodentate phosphine, X = Cl, Br) and LNi(aryl)X (L = bis-phosphine) have been synthesized and are presented as a library of precatalysts suitable for a wide variety of nickel-catalyzed transformations. These complexes are easily synthesized from low-cost NiCl2·6H2O or NiBr2·3H2O and the desired ligand followed by addition of 1 equiv of Grignard reagent. A selection of these complexes were characterized by single-crystal X-ray diffraction, and an analysis of their structural features is provided. A case study of their use as precatalysts for the nickel-catalyzed carbonyl-ene reaction is presented, showing superior reactivity in comparison to reactions using Ni(cod)2. Furthermore, as the precatalysts are all stable to air, no glovebox or inert-atmosphere techniques are required to make use of these complexes for nickel-catalyzed reactions.

Institutional Corruption as a Problem of Institutional Design: A General Framework

Even though developed to explain institutional dysfunction in Congress, the concept of institutional corruption has been applied to different types of organizations and industries. This application has generated insights about the problems affecting different sectors, but it has also raised questions about the accuracy of using the concept in other, non-Congress, contexts. This paper argues that the concept of institutional corruption has broad applicability, but it needs some conceptual adaptation when used in contexts different from the original one. By analyzing the institutional corruption features with this adaptation in mind, this paper proposes a more general framework for the theory that is broadly applicable to different settings while retaining its internal coherence. To do so, this paper approaches institutional corruption from the lens of organizational design. In this perspective, institutional corruption will be described as a type of failure in achieving the institutional purpose that happens because of the institutional design, rather than because of unsatisfactory performance. This paper explains the institutional mechanisms that cause this failure, and concludes with some theoretical implications of the framework proposed.

A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis

A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.

A Broadly Applicable Surgical Teaching Method: Evaluation of a Stepwise Introduction to Cataract Surgery

Although cataract surgery is one of the most commonly performed surgeries in the country, it is a microsurgical procedure that is difficult to learn and to teach. This study aims to assess the effectiveness of a new method for introducing postgraduate year (PGY)-3 ophthalmology residents to cataract surgery. Hospital-based ophthalmology residency program. Retrospective cohort study. PGY-3 and PGY-4 residents of the Harvard Medical School Ophthalmology Residency from graduating years 2010 to 2012. In July 2009, a new method of teaching PGY-3 ophthalmology residents cataract surgery was introduced, which was termed "the stepwise introduction to cataract surgery." This curriculum aimed to train residents to perform steps of cataract surgery by deliberately practicing each of the steps of surgery under a structured curriculum with faculty feedback. Assessment methods included surveys administered to the PGY-4 residents who graduated before the implementation of these measures (n = 7), the residents who participated in the first and second years of the new curriculum (n = 16), faculty who teach PGY-4 residents cataract surgery (n = 8), and review of resident Accreditation Council for Graduate Medical Education surgical logs. Resident survey response rate was 100%. Residents who participated in the new curriculum performed more of each step of cataract surgery in the operating room, spent more time practicing each step of cataract surgery on a cataract surgery simulator during the PGY-3 year, and performed more primary cataract surgeries during the PGY-3 year than those who did not. Faculty survey response rate was 63%. Faculty noted an increase in resident preparedness following implementation of the new curriculum. There was no statistical difference between the precurriculum and postcurriculum groups in the percentage turnover of cataracts for the first 2 cataract surgery rotations of the PGY-4 year of training. The introduction of cataract surgery to PGY-3 residents in an organized, stepwise manner improved resident preparedness for the PGY-4 year of residency. This surgical teaching method can be easily applied to other surgical specialties.

Acute on-chip HIV detection through label-free electrical sensing of viral nano-lysate.

Development of portable biosensors has broad applications in environmental monitoring, clinical diagnosis, public health, and homeland security. There is an unmet need for pathogen detection at the point-of-care (POC) using a fast, sensitive, inexpensive, and easy-to-use method that does not require complex infrastructure and well-trained technicians. For instance, detection of Human Immunodeficiency Virus (HIV-1) at acute infection stage has been challenging, since current antibody-based POC technologies are not effective due to low concentration of antibodies. In this study, we demonstrated for the first time a label-free electrical sensing method that can detect lysed viruses, i.e. viral nano-lysate, through impedance analysis, offering an alternative technology to the antibody-based methods such as dipsticks and Enzyme-linked Immunosorbent Assay (ELISA). The presented method is a broadly applicable platform technology that can potentially be adapted to detect multiple pathogens utilizing impedance spectroscopy for other infectious diseases including herpes, influenza, hepatitis, pox, malaria, and tuberculosis. The presented method offers a rapid and portable tool that can be used as a detection technology at the POC in resource-constrained settings, as well as hospital and primary care settings.

MuteinDB: the mutein database linking substrates, products and enzymatic reactions directly with genetic variants of enzymes

Mutational events as well as the selection of the optimal variant are essential steps in the evolution of living organisms. The same principle is used in laboratory to extend the natural biodiversity to obtain better catalysts for applications in biomanufacturing or for improved biopharmaceuticals. Furthermore, single mutation in genes of drug-metabolizing enzymes can also result in dramatic changes in pharmacokinetics. These changes are a major cause of patient-specific drug responses and are, therefore, the molecular basis for personalized medicine. MuteinDB systematically links laboratory-generated enzyme variants (muteins) and natural isoforms with their biochemical properties including kinetic data of catalyzed reactions. Detailed information about kinetic characteristics of muteins is available in a systematic way and searchable for known mutations and catalyzed reactions as well as their substrates and known products. MuteinDB is broadly applicable to any known protein and their variants and makes mutagenesis and biochemical data searchable and comparable in a simple and easy-to-use manner. For the import of new mutein data, a simple, standardized, spreadsheet-based data format has been defined. To demonstrate the broad applicability of the MuteinDB, first data sets have been incorporated for selected cytochrome P450 enzymes as well as for nitrilases and peroxidases.Database URL: http://www.MuteinDB.org

Electrostatic force microscopy as a broadly applicable method for characterizing pyroelectric materials

A general method based on the combination of electrostatic force microscopy with thermal cycling of the substrate holder is presented for direct, nanoscale characterization of the pyroelectric effect in a range of materials and sample configurations using commercial atomic force microscope systems. To provide an example of its broad applicability, the technique was applied to the examination of natural tourmaline gemstones. The method was validated using thermal cycles similar to those experienced in ambient conditions, where the induced pyroelectric response produced localized electrostatic surface charges whose magnitude demonstrated a correlation with the iron content and heat dissipation of each gemstone variety. In addition, the surface charge was shown to persist even at thermal equilibrium. This behavior is attributed to constant, stochastic cooling of the gemstone surface through turbulent contact with the surrounding air and indicates a potential utility for energy harvesting in applications including environmental sensors and personal electronics. In contrast to previously reported methods, ours has a capacity to carry out such precise nanoscale measurements with little or no restriction on the sample of interest, and represents a powerful new tool for the characterization of pyroelectric materials and devices.

Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells

Leukocytes are central regulators of inflammation and the target cells of therapies for key diseases, including autoimmune, cardiovascular, and malignant disorders. Efficient in vivo delivery of small interfering RNA (siRNA) to immune cells could thus enable novel treatment strategies with broad applicability. In this report, we develop systemic delivery methods of siRNA encapsulated in lipid nanoparticles (LNP) for durable and potent in vivo RNA interference (RNAi)-mediated silencing in myeloid cells. This work provides the first demonstration of siRNA-mediated silencing in myeloid cell types of nonhuman primates (NHPs) and establishes the feasibility of targeting multiple gene targets in rodent myeloid cells. The therapeutic potential of these formulations was demonstrated using siRNA targeting tumor necrosis factor-α (TNFα) which induced substantial attenuation of disease progression comparable to a potent antibody treatment in a mouse model of rheumatoid arthritis (RA). In summary, we demonstrate a broadly applicable and therapeutically relevant platform for silencing disease genes in immune cells.

A Broadly Applicable Copper Reagent for Trifluoromethylations and Perfluoroalkylations of Aryl Iodides and Bromides

A Broadly Applicable Copper Reagent for Trifluoromethylations and Perfluoroalkylations of Aryl Iodides and Bromides

A Broadly Applicable Copper Reagent for Trifluoromethylations and Perfluoroalkylations of Aryl Iodides and Bromides

Well compatible: The trifluoromethylations and perfluoroalkylations of aryl iodides and some aryl bromides with trifluoromethyl and perfluoroalkylcopper(I) phenanthroline complexes occur with broad scope at 25–50 °C (see scheme). The trifluoromethyl complex is prepared from inexpensive reagents and can be used in situ or isolated. The reactions tolerate a range of substituents and also occur with heteroaromatic systems.

A Broadly Applicable 3-D Neuron Tracing Method Based on Open-Curve Snake

This paper presents a broadly applicable algorithm and a comprehensive open-source software implementation for automated tracing of neuronal structures in 3-D microscopy images. The core 3-D neuron tracing algorithm is based on three-dimensional (3-D) open-curve active Contour (Snake). It is initiated from a set of automatically detected seed points. Its evolution is driven by a combination of deforming forces based on the Gradient Vector Flow (GVF), stretching forces based on estimation of the fiber orientations, and a set of control rules. In this tracing model, bifurcation points are detected implicitly as points where multiple snakes collide. A boundariness measure is employed to allow local radius estimation. A suite of pre-processing algorithms enable the system to accommodate diverse neuronal image datasets by reducing them to a common image format. The above algorithms form the basis for a comprehensive, scalable, and efficient software system developed for confocal or brightfield images. It provides multiple automated tracing modes. The user can optionally interact with the tracing system using multiple view visualization, and exercise full control to ensure a high quality reconstruction. We illustrate the utility of this tracing system by presenting results from a synthetic dataset, a brightfield dataset and two confocal datasets from the DIADEM challenge.

Engineering Monovalent Quantum Dot−Antibody Bioconjugates with a Hybrid Gel System

Monovalent nanoparticles are of strong current interest in biological imaging and detection due to their potential for stoichiometric binding with target molecules. We report the preparation of monovalent quantum dot-antibody bioconjugates using a high-resolution hybrid gel system specially designed for fractionation of nanoparticle bioconjugates. A key feature of this technology is that it is broadly applicable to many types of nanoparticle-antibody complexes without the need of genetically engineered proteins. This is particularly important because antibodies are still the dominant molecular targeting probes, despite new discoveries made with other targeting probes such as aptamers and peptides. Furthermore, we show experimental evidence of improved quantification capability using the monovalent probes, whose advantages over their multivalent counterparts had largely been a theoretic prediction previously. This new class of nanoprobe should find broad application in quantitative biological detection and imaging in vitro and in vivo.

Introduction to Special Section: Sustainability and Horticultural Education

N ow more than ever, horticultural educators must make efforts to construct meaningful curricula in light of profound environmental concerns. This can be achieved by the sharing of professional practices, curriculum, and pedagogy, as well as by making accessible new research that pertains to the concepts of site sustainability in the horticultural topic areas of soils, hydrology, vegetation, resources, and human wellness. In the words of the Sustainable Sites Initiative (SSI), ‘‘sustainability is defined as design, construction, operations, and maintenance practices that meet the needs of the present without compromising the ability of future generations to meet their own needs’’ (SSI, 2009). In this special topics section, six articles having a common theme of teaching and sustainability were selected in an effort to share best practices from faculty engaging diverse student populations in various facets of sustainability. Each article has broad applicability for the field, and collectively, they serve to address teaching, assessing, and challenging students to think within a more sustainable context. The focus of each article is unique, offering enlightened and innovative pedagogical perspectives. Several authors solve the need for more time on task by using a multisemester or independent study approach, whereas others make outstanding use of technology, as in the Online Knowledge Center for water, nutrient, and crop health management. Most of the articles introduce topics in which multiand/or interdisciplinary collaboration is imperative, and several offer an outreach component to ensure that classroom efforts are shared with members of the community. As lead author, J.D. Lea-Cox from the University of Maryland suggests that there is a ‘‘need for efficient management of resources to mitigate production impacts on the environment.’’ While specifically speaking about container nursery and greenhouse system production impacts, this concept is broadly applicable to all aspects of sustainable horticultural education and practices. For example, in their article, B. Lamba and G. Chapman of Temple University describe the challenges they experienced during construction of a sustainable flower show exhibit. While endeavoring to mitigate production impacts from their exhibit at the Philadelphia Flower Show, members of two separate classes (landscape architecture and horticulture) were introduced to concepts regarding sustainability in production and material impacts. The article details the students’ creative solutions for handling these issues. This special issue may serve as a catalyst for future research and practice, a forum to share new ideas, as well as a place to gain insights into methods used by horticultural educators to reach out to a broader audience. These articles represent unique curricula designed by caring faculty who clearly work to ensure that students graduate with a foundation that will allow them to be thought-leaders in their individual fields. Future teaching imperatives in the realm of sustainability might include life cycle analysis (International Organization for Standardization, 2006; U.S. Environmental Protection Agency, 2009) and agrosystem analysis because these subject areas give credence and information about true measurements of sustainability, and serve to underscore the importance of food security concerns, both nationally and internationally.

Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels

Hydrogels can provide a controllable cell microenvironment for numerous applications in regenerative medicine, and delivery of gene therapy vectors can be employed to enhance their bioactivity. We investigated the delivery of lentiviral vectors from hydrogels, and employed the immobilization of lentivirus to hydroxylapatite (HA) nanoparticles as a means to retain and stabilize vectors within hydrogels, and thereby increase delivery efficiency. Entrapment of the vector alone within the hydrogel maintained the activity of the virus more effectively compared to the absence of a hydrogel, and release was slowed with an increasing solid content of the hydrogel. Association of the lentivirus with HA increased the activity of the complexes, with HA increasing the virus activity for 72 hours. Cells seeded onto lentivirus-HA-loaded hydrogels had a decreased number of infected cells outside of the hydrogel relative to the absence of HA. In vivo studies with collagen hydrogels loaded with lentivirus and HA-lentivirus demonstrated sustained and localized transgene expression for at least 4 weeks, with increased expression using the lentivirus-HA complex. This strategy of nanoparticle immobilization to stabilize and retain vectors is broadly applicable to hydrogels, and may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine.

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment.