Cancer drugs: Highlighting the molecular mechanisms of cardiotoxicity

The treatment options for patients with cancer have increased rapidly in the last decade with the introduction of newer chemotherapy drugs, targeted agents and monoclonal antibodies. Most of these drugs are aimed at interrupting proliferative signalling, with consequent apoptosis of cancer cells. Because most of the new drugs are multi-targeted, there is a likelihood of so called “off target” effects, where other kinases which are not the primary targets of the drug, are also inhibited. This has led to unforeseen toxicities and, in this commentary, we will focus on the molecular mechanisms underlying cardiotoxicities as a result of cancer therapies. However, cardiotoxicity is not a new concern as the older generation chemotherapies, like anthracyclines, are known to commonly cause irreversible cardiomyopathy, mostly as a result of induced DNA damage and oxidative stress. Over the years, clinicians have adopted some methods of diminishing the incidence of this side-effect and therefore improving patient safety. Trying to decipher the complicated pathways underlying cardiotoxicity helps the scientifi c community to design new drugs that are tumoricidal, whilst sparing normal tissue and as such limiting unwanted side-effects. This has become ever so important, as oncologists cure more patients of cancer, and some previously incurable cancers are increasingly being converted into chronic illnesses. A relationship between the cardiologist and the oncologist has become mandatory to ensure close monitoring of such patients and offering appropriate management, should cardiotoxicities arise

Growth and characteristics of type-II InAs/GaSb superlattice-based detectors

We report on growth and device performance of infrared photodetectors based on type II InAs/Ga(In)Sb strain layer superlattices (SLs) using the complementary barrier infrared detector (CBIRD) design. The unipolar barriers on either side of the absorber in the CBIRD design in combination with the type-II InAs/GaSb superlattice material system are expected to outperform traditional III-V LWIR imaging technologies and offer significant advantages over the conventional II-VI material based FPAs. The innovative design of CBIRDS, low defect density material growth, and robust fabrication processes have resulted in the development of high performance long wave infrared (LWIR) focal plane arrays at JPL

Female Perpetrators in Internal Child Trafficking in China: An empirical study

Through an empirical study, this article explores the overall profile of female traffickers of children in China and their role and performance in the trafficking processes. Its contribution to the human-trafficking literature lies in its focus on female perpetrators in particular. The article provides an overview of the international literature on female traffickers as well as contemporary knowledge about internal child trafficking in China. Empirical data from incarcerated traffickers suggest that portraying female traffickers as active players of criminal networks obscures the structural problems affecting female child traffickers. The short-term result is that the problems of female offenders are ignored, and the long-term impact is policy making that is disconnected from the lived experiences of an important population. From a gender perspective, this study suggests that female child traffickers are offenders as well as victims of social and gender inequalities in China’s reform era. This study also proposes that internal child trafficking in China should be brought in the international and Anglo-American debates surrounding human trafficking

High-Speed Operation of Interband Cascade Lasers

Optical sources operating in the atmospheric window of 3-5 microns are of particular interest for the development of free-space optical communication link. It is more advantageous to operate the free-space optical communication link in 3-5-microns atmospheric transmission window than at the telecom wavelength of 1.5 m due to lower optical scattering, scintillation, and background radiation. However, the realization of optical communications at the longer wavelength has encountered significant difficulties due to lack of adequate optical sources and detectors operating in the desirable wavelength regions. Interband Cascade (IC) lasers are novel semiconductor lasers that have a great potential for the realization of high-power, room-temperature optical sources in the 3-5-microns wavelength region, yet no experimental work, until this one, was done on high-speed direct modulation of IC lasers. Here, highspeed interband cascade laser, operating at wavelength 3.0 m, has been developed and the first direct measurement of the laser modulation bandwidth has been performed using a unique, highspeed quantum well infrared photodetector (QWIP). The developed laser has modulation bandwidth exceeding 3 GHz. This constitutes a significant increase of the IC laser modulation bandwidth over currently existing devices. This result has demonstrated suitability of IC lasers as a mid-IR light source for multi-GHz free-space optical communications link

Quasi-coherent fluctuation measurement with the upgraded microwave imaging reflectometer in KSTAR

The microwave imaging reflectometer (MIR) is the leading diagnostic tool for study of density fluctuations in KSTAR. For last three years since 2014, major components such as the multi-frequency probe beam source, multi-channel detector array, signal processing electronic system, data acquisition system, and optical system have been gradually upgraded. In this paper, the detailed system upgrade with test results in the laboratory and/or plasma is given, and analysis results of a distinctive fluctuation structure referred to as the quasi-coherent mode (QCM) measured by the upgraded MIR system for an L-mode discharge are presented. Cross-coherence analysis with multiple channels shows that the QCM is localized in a core region and appears to be driven by electron temperature gradient for the discharg

Transcriptomic signatures associated with regional cortical thickness changes in Parkinson's disease

Cortical atrophy is a common manifestation in Parkinson's disease (PD), particularly in advanced stages of the disease. To elucidate the molecular underpinnings of cortical thickness changes in PD, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and patterns of cortical thickness based on T1-weighted anatomical MRI data of 149 PD patients and 369 controls. For this purpose, we used partial least squares regression to identify gene expression patterns correlated with cortical thickness changes. In addition, we identified gene expression patterns underlying the relationship between cortical thickness and clinical domains of PD. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in PD are enriched in biological pathways related to sumoylation, regulation of mitotic cell cycle, mitochondrial translation, DNA damage responses, and ER-Golgi traffic. The associated pathways were highly related to each other and all belong to cellular maintenance mechanisms. The expression of genes within most pathways was negatively correlated with cortical thickness changes, showing higher expression in regions associated with decreased cortical thickness (atrophy). On the other hand, sumoylation pathways were positively correlated with cortical thickness changes, showing higher expression in regions with increased cortical thickness (hypertrophy). Our findings suggest that alterations in the balanced interplay of these mechanisms play a role in changes of cortical thickness in PD and possibly influence motor and cognitive functions.Neuro Imaging Researc

Are There Cross-Cultural Legal Principles? Modal Reasoning Uncovers Procedural Constraints on Law

Despite pervasive variation in the content of laws, legal theorists and anthropologists have argued that laws share certain abstract features and even speculated that law may be a human universal. In the present report, we evaluate this thesis through an experiment administered in 11 different countries. Are there cross-cultural principles of law? In a between-subjects design, participants (N = 3,054) were asked whether there could be laws that violate certain procedural principles (e.g., laws applied retrospectively or unintelligible laws), and also whether there are any such laws. Confirming our preregistered prediction, people reported that such laws cannot exist, but also (paradoxically) that there are such laws. These results document cross-culturally and –linguistically robust beliefs about the concept of law which defy people's grasp of how legal systems function in practice

Interdisciplinary Transgender Veteran Care: Development of a Core Curriculum for VHA Providers

Purpose: The Veteran\u27s Health Administration (VHA) has created a training program for interdisciplinary teams of providers on the unique treatment needs of transgender veterans. An overview of this program\u27s structure and content is described along with an evaluation of each session and the program overall. Methods: A specialty care team delivered 14 didactic courses supplemented with case consultation twice per month over the course of 7 months through video teleconferencing to 16 teams of learners. Each team, consisting of at least one mental health provider (e.g., social worker, psychologist, or psychiatrist) and one medical provider (e.g., physician, nurse, physician assistant, advanced practice nurse, or pharmacist), received training and consultation on transgender veteran care. Results: In the first three waves of learners, 111 providers across a variety of disciplines attended the sessions and received training. Didactic topics included hormone therapy initiation and adjustments, primary care issues, advocacy within the system, and psychotherapy issues. Responses were provided to 39 veteran-specific consult questions to augment learning. Learners reported an increase in knowledge plus an increase in team cohesion and functioning. As a result, learners anticipated treating more transgender veterans in the future. Conclusion: VHA providers are learning about the unique healthcare needs of transgender veterans and benefitting from the training opportunity offered through the Transgender Specialty Care Access Network-Extension of Community Healthcare Outcomes program. The success of this program in training interdisciplinary teams of providers suggests that it might serve as a model for other large healthcare systems. In addition, it provides a path forward for individual learners (both within VHA and in the community) who wish to increase their knowledge

Diversity of A(H5N1) clade 2.3.2.1c avian Influenza viruses with evidence of reassortment in Cambodia, 2014-2016

In Cambodia, highly pathogenic avian influenza A(H5N1) subtype viruses circulate endemically causing poultry outbreaks and zoonotic human cases. To investigate the genomic diversity and development of endemicity of the predominantly circulating clade 2.3.2.1c A(H5N1) viruses, we characterised 68 AIVs detected in poultry, the environment and from a single human A(H5N1) case from January 2014 to December 2016. Full genomes were generated for 42 A(H5N1) viruses. Phylogenetic analysis shows that five clade 2.3.2.1c genotypes, designated KH1 to KH5, were circulating in Cambodia during this period. The genotypes arose through multiple reassortment events with the neuraminidase (NA) and internal genes belonging to H5N1 clade 2.3.2.1a, clade 2.3.2.1b or A(H9N2) lineages. Phylogenies suggest that the Cambodian AIVs were derived from viruses circulating between Cambodian and Vietnamese poultry. Molecular analyses show that these viruses contained the hemagglutinin (HA) gene substitutions D94N, S133A, S155N, T156A, T188I and K189R known to increase binding to the human-type α2,6-linked sialic acid receptors. Two A(H5N1) viruses displayed the M2 gene S31N or A30T substitutions indicative of adamantane resistance, however, susceptibility testing towards neuraminidase inhibitors (oseltamivir, zanamivir, lananmivir and peramivir) of a subset of thirty clade 2.3.2.1c viruses showed susceptibility to all four drugs. This study shows that A(H5N1) viruses continue to reassort with other A(H5N1) and A(H9N2) viruses that are endemic in the region, highlighting the risk of introduction and emergence of novel A(H5N1) genotypes in Cambodia