Thermoplastic Toughening of a Semiaromatic Polyamide with an Amino-telechelic Polyethylene.

Semiaromatic polyamides are used for metal replacement in advanced engineering applications to reduce weight and improve efficiency, but their range of application is limited by their inherent lack of ductility and toughness. Here, we combined semiaromatic polyamide poly(hexamethylene terephthalamide-co-isophthalamide) (PA6TI) with up to 30 wt % amine-terminated polyethylene (PE(NH)) by high-temperature melt compounding, which was suggested to lead to the formation of PA-PE block copolymers at the interface between the PE(NH) and the PA6TI. This resulted in PA6TI/PE(NH) blends with smaller, more uniform particle sizes than in PA6TI blended with nonfunctional PE or the commercial impact modifier, maleic anhydride-functionalized styrene-ethylene-butylene-styrene (SEBS) under the same conditions.

AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer.

Purpose: Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a high relapse rate, limited therapeutic options, and poor prognosis. We investigated the antitumor activity of AMG 757, a half-life extended bispecific T-cell engager molecule targeting delta-like ligand 3 (DLL3)-a target that is selectively expressed in SCLC tumors, but with minimal normal tissue expression.

Experimental Design: AMG 757 efficacy was evaluated in SCLC cell lines and in orthotopic and patient-derived xenograft (PDX) mouse SCLC models.

The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations.

The field of human therapeutics has expanded tremendously from small molecules to complex biological modalities, and this trend has accelerated in the last two decades with a greater diversity in the types and applications of novel modalities, accompanied by increasing sophistication in drug delivery technology. These innovations have led to a corresponding increase in the number of therapies seeking regulatory approval, and as the industry continues to evolve regulations will need to adapt to the ever-changing landscape. The growth in this field thus represents a challenge for regulatory authorities as well as for sponsors.

DLL3: an emerging target in small cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers. Despite high rates of response to first-line chemotherapy and radiotherapy, patients with extensive-stage disease eventually relapse, and very few patients survive more than 5 years from diagnosis. Treatment options for recurrent or refractory disease are limited, and the treatments that do exist are associated with significant treatment-related toxicities.

Psychological constraints on aggressive predation in economic contests.

When humans compete, they invest energy and effort to injure others and to protect against injury and exploitation. The psychology behind exploiting others and protecting against exploitation is still poorly understood and is addressed here in an incentivized economic contest game in which individuals invested in predatory attack and prey defense. Consistent with standard economic theory on production and predation, we find that individuals compete less intensely when they attack rather than defend and that attacks disproportionally often fail.

Pupil mimicry promotes trust through the theory-of-mind network.

The human eye can provide powerful insights into the emotions and intentions of others; however, how pupillary changes influence observers' behavior remains largely unknown. The present fMRI-pupillometry study revealed that when the pupils of interacting partners synchronously dilate, trust is promoted, which suggests that pupil mimicry affiliates people. Here we provide evidence that pupil mimicry modulates trust decisions through the activation of the theory-of-mind network (precuneus, temporo-parietal junction, superior temporal sulcus, and medial prefrontal cortex).

In-group defense, out-group aggression, and coordination failures in intergroup conflict.

Intergroup conflict persists when and because individuals make costly contributions to their group's fighting capacity, but how groups organize contributions into effective collective action remains poorly understood. Here we distinguish between contributions aimed at subordinating out-groups (out-group aggression) from those aimed at defending the in-group against possible out-group aggression (in-group defense). We conducted two experiments in which three-person aggressor groups confronted three-person defender groups in a multiround contest game (n = 276; 92 aggressor-defender contests).

Narrative review of strategies by organizations for building evaluation capacity.

Program evaluation is an important source of information to assist organizations to make "evidence-informed" decisions about program planning and development. The objectives of this study were to identify evaluated strategies used by organizations and program developers to build the program evaluation capacity of their workforce, and to describe success factors and lessons learned. Common elements for successful evaluation capacity building (ECB) include: a tailored strategy based on needs assessment, an organizational commitment to evaluation and ECB, experiential learning, training with a practical element, and some form of ongoing technical support within the workplace.

A guide to scaling up population health interventions.

The 'how to' of scaling up public health interventions for maximum reach and outcomes is receiving greater attention; however, there remains a paucity of practical tools to guide those actively involved in scaling up processes in high-income countries. To fill this gap, the New South Wales Ministry of Health developed Increasing the scale of population health interventions: a guide (2014). The guide was informed by a systematic review of scaling up models and methods, and a two-round Delphi process with a sample of senior policy makers, practitioners and researchers actively involved in scaling up processes.

Prevalence, circumstances and consequences of falls among community-dwelling older people: results of the 2009 NSW Falls Prevention Baseline Survey.

Aim: To describe the prevalence, circumstances and consequences of falls among community-dwelling older people in NSW using data from the 2009 NSW Falls Prevention Baseline Survey.

Methods: Telephone interviews with a random sample of 5681 NSW residents aged 65 years and over were conducted in 2009.

Results: Of those surveyed, 25.

Family health history--a role in prevention.

To harness its potential, a patient's family health history should be collected pre-emptively and proactively when the patient is well, rather than when symptoms of disease present. Unless general practitioners proactively seek and discuss family health history, opportunities for prevention may be lost.

Identification of broad-based HIV-1 protease inhibitors from combinatorial libraries.

Clinically approved inhibitors of the HIV-1 protease function via a competitive mechanism. A particular vulnerability of competitive inhibitors is their sensitivity to increases in substrate concentration, as may occur during virion assembly, budding and processing into a mature infectious viral particle. Advances in chemical synthesis have led to the development of new high-diversity chemical libraries using rapid in-solution syntheses.

Public perceptions of the threat of terrorist attack in Australia and anticipated compliance behaviours.

Objective: To determine the perceived threat of terrorist attack in Australia and preparedness to comply with public safety directives.

Methods: A representative sample of 2,081 adults completed terrorism perception questions as part of the New South Wales Population Health Survey.

Results: Overall, 30.

A copper(I)-catalyzed 1,2,3-triazole azide-alkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant.

Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X protease mutant arising from in vitro selection with compound 1, a C 2-symmetric diol protease inhibitor, has been previously described. We now show that compound 2, a copper(I)-catalyzed 1,2,3-triazole derived compound previously shown to be potently effective against wild-type protease (IC 50 = 6.

Pandemic influenza in Australia: using telephone surveys to measure perceptions of threat and willingness to comply.

Background: Baseline data is necessary for monitoring how a population perceives the threat of pandemic influenza, and perceives how it would behave in the event of pandemic influenza. Our aim was to develop a module of questions for use in telephone health surveys on perceptions of threat of pandemic influenza, and on preparedness to comply with specific public health behaviours in the event of pandemic influenza.

Methods: A module of questions was developed and field tested on 192 adults using the New South Wales Department of Health's in-house Computer Assisted Telephone Interviewing (CATI) facility.

Crystal structure of NFAT bound to the HIV-1 LTR tandem kappaB enhancer element.

The host factor, nuclear factor of activated T-cells (NFAT), regulates the transcription and replication of HIV-1. Here, we have determined the crystal structure of the DNA binding domain of NFAT bound to the HIV-1 long terminal repeat (LTR) tandem kappaB enhancer element at 3.05 A resolution.

Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.

DNA binding by NFAT1 as a dimer has been implicated in the activation of host and viral genes. Here we report a crystal structure of NFAT1 bound cooperatively as a dimer to the highly conserved kappa B site from the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR). This structure reveals a new mode of dimerization and protein-DNA recognition by the Rel homology region (RHR) of NFAT1.