CAR'TCR-T cells co-expressing CD33-CAR and dNPM1-TCR as superior dual-targeting approach for AML treatment.

Acute myeloid leukemia (AML), a fast-progressing hematological malignancy affecting myeloid cells, is typically treated with chemotherapy or hematopoietic stem cell transplantation. However, approximately half of the patients face relapses and 5-year survival rates are poor. With the goal to facilitate dual-specificity, boosting anti-tumor activity, and minimizing the risk for antigen escape, this study focused on combining chimeric antigen receptor (CAR) and T cell receptor (TCR) technologies.

Automated manufacture of ΔNPM1 TCR-engineered T cells for AML therapy.

Acute myeloid leukemia (AML) is a heterogeneous malignancy that requires further therapeutic improvement, especially for the elderly and for subgroups with poor prognosis. A recently discovered T cell receptor (TCR) targeting mutant nucleophosmin 1 (ΔNPM1) presents an attractive option for the development of a cancer antigen-targeted cellular therapy. Manufacturing of TCR-modified T cells, however, is still limited by a complex, time-consuming, and laborious procedure.

Principles and procedures for revising the hierarchical taxonomy of psychopathology.

Quantitative, empirical approaches to establishing the structure of psychopathology hold promise to improve on traditional psychiatric classification systems. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a framework that summarizes the substantial and growing body of quantitative evidence on the structure of psychopathology. To achieve its aims, HiTOP must incorporate emerging research in a systematic, ongoing fashion.

Combining CSPG4-CAR and CD20-CCR for treatment of metastatic melanoma.

The prognosis for patients with metastatic melanoma is poor and treatment options are limited. Genetically-engineered T cell therapy targeting chondroitin sulfate proteoglycan 4 (CSPG4), however, represents a promising treatment option, especially as both primary melanoma cells as well as metastases uniformly express CSPG4. Aiming to prevent off-tumor toxicity while maintaining a high cytolytic potential, we combined a chimeric co-stimulatory receptor (CCR) and a CSPG4-directed second-generation chimeric antigen receptor (CAR) with moderate potency.

Factor analysis in personality disorders research: Modern issues and illustrations of practical recommendations.

The development of factor analysis is uniquely situated within psychology, and the development of many psychological theories and measures are likewise tethered to the common use of factor analysis. In this article, we review modern methodological controversies and developments of factor analytic techniques through concrete demonstrations that span the exploratory-confirmatory continuum. Also, we provide recommendations for working through common challenges in personality disorders research.

Grain-size distribution dataset of supercritical flow sediments from a Gilbert-type delta that are associated with disaggregation bands.

This is a dataset of grain-size distribution in sub- and supercritical flow sediments of a Gilbert-type delta from an outcrop in North Germany. Thirteen samples of ca 2.5 kg were dried (at 105°C), and homogenised twice with a sample divider.

Automated, scaled, transposon-based production of CAR T cells.

Background: There is an increasing demand for chimeric antigen receptor (CAR) T cell products from patients and care givers. Here, we established an automated manufacturing process for CAR T cells on the CliniMACS Prodigy platform that is scaled to provide therapeutic doses and achieves gene-transfer with virus-free Sleeping Beauty (SB) transposition.

Methods: We used an advanced CliniMACS Prodigy that is connected to an electroporator unit and performed a series of small-scale development and large-scale confirmation runs with primary human T cells.

Towards construct validity of relational aggression: An examination of the Children's Social Behavior Scale.

Relational aggression-or behavior intended to harm the relationships of its victims-has been the focus of interdisciplinary study across developmental, clinical, personality, and social psychology in the last several decades. One of the primary measures used to assess relational aggression in youth is the Children's Social Behavior Scale (CSBS; Crick & Grotpeter, 1995), but despite its common usage, the construct validity of this measure has not been comprehensively assessed. In the present study, we used a multistage construct validity framework to thoroughly investigate the nature of relational aggression across six community samples totaling 3,102 youth and their caregivers.

Automated generation of gene-edited CAR T cells at clinical scale.

The potential of adoptive cell therapy can be extended when combined with genome editing. However, variation in the quality of the starting material and the different manufacturing steps are associated with production failure and product contamination. Here, we present an automated T cell engineering process to produce off-the-shelf chimeric antigen receptor (CAR) T cells on an extended CliniMACS Prodigy platform containing an in-line electroporation unit.

Facet-level personality development in the transition to adolescence: Maturity, disruption, and gender differences.

The transition to adolescence is marked by enormous change in social, biological, and personality development. Although accumulating evidence has offered insight into the nature of higher-order personality trait development during this period, much less is known about the development of lower-order personality traits, or "facets." The current study used a cohort-sequential longitudinal design to examine domain- and facet-level trajectories for mother-reported personality traits during the early adolescent transition.

The latent structure of depressive symptoms across clinical high risk and chronic phases of psychotic illness.

Depressive symptoms are highly prevalent in psychotic populations and result in significant functional impairment. Limited knowledge of whether depressive symptoms are invariant across stages of illness curtails our ability to understand how these relate to illness progression. Clarifying the latent structure of depressive symptoms across stages of illness progression would aid etiological conceptualizations and preventive models.

Gadd45α modulates aversive learning through post-transcriptional regulation of memory-related mRNAs.

Learning is essential for survival and is controlled by complex molecular mechanisms including regulation of newly synthesized mRNAs that are required to modify synaptic functions. Despite the well-known role of RNA-binding proteins (RBPs) in mRNA functionality, their detailed regulation during memory consolidation is poorly understood. This study focuses on the brain function of the RBP Gadd45α (growth arrest and DNA damage-inducible protein 45 alpha, encoded by the gene).

From the talking cure to a disease of silence: Effects of ethical violations in a psychoanalytic institute.

This article presents an in-depth study of one institute's efforts to recover from effects of ethical violations by two senior members. Qualitative data analysis from voluntary member interviews details the damage that spread throughout the institute, demonstrating that a violation of one is a violation of many. Members at all levels reported feeling disturbed in ways that affected their emotional equilibrium, their thinking processes, and their social and professional relationships.

Leveraging the Open Science Framework in clinical psychological assessment research.

The last decade has seen enormous advances in research transparency in psychology. One of these advances has been the creation of a common interface for openness across the sciences-the Open Science Framework (OSF). While social, personality, and cognitive psychologists have been at the fore in participating in open practices on the OSF, clinical psychology has trailed behind.

Psychology's Replication Crisis and Clinical Psychological Science.

Despite psychological scientists' increasing interest in replicability, open science, research transparency, and the improvement of methods and practices, the clinical psychology community has been slow to engage. This has been shifting more recently, and with this review, we hope to facilitate this emerging dialogue. We begin by examining some potential areas of weakness in clinical psychology in terms of methods, practices, and evidentiary base.

Does Psychosocial Stress Impact Cognitive Reappraisal? Behavioral and Neural Evidence.

Cognitive reappraisal (CR) is regarded as an effective emotion regulation strategy. Acute stress, however, is believed to impair the functioning of prefrontal-based neural systems, which could result in lessened effectiveness of CR under stress. This study tested the behavioral and neurobiological impact of acute stress on CR.

A comparison of salivary testosterone measurement using immunoassays and tandem mass spectrometry.

Enzyme immunoassays (EIAs) are widely used to measure salivary testosterone. However, little is known about how accurately different EIAs assess testosterone, partially because estimates across various EIAs differ considerably. We compared testosterone concentrations across EIAs of three commonly used manufacturers (DRG International, Salimetrics, and IBL International) to liquid chromatography tandem mass spectrometry (LC-MS/MS).

Mutation scanning in a single and a stacked genetically modified (GM) event by real-time PCR and high resolution melting (HRM) analysis.

Genetic mutations must be avoided during the production and use of seeds. In the European Union (EU), Directive 2001/18/EC requires any DNA construct introduced via transformation to be stable. Establishing genetic stability is critical for the approval of genetically modified organisms (GMOs).

Controlling protein-particle adsorption by surface tailoring colloidal alumina particles with sulfonate groups.

In this study, we demonstrate the control of protein adsorption by tailoring the sulfonate group density on the surface of colloidal alumina particles. The colloidal alumina (d(50)=179±8nm) is first accurately functionalized with sulfonate groups (SO(3)H) in densities ranging from 0 to 4.7SO(3)H nm(-2).

Highly efficient enzyme-functionalized porous zirconia microtubes for bacteria filtration.

In contrast to polymer membranes, ceramic membranes offer considerable advantages for safe drinking water provision due to their excellent chemical, thermal, and mechanical endurance. In this study, porous ceramic microtubes made of yttria stabilized zirconia (YSZ) are presented, which are conditioned for bacteria filtration by immobilizing lysozyme as an antibacterial enzyme. In accordance with determined membrane pore sizes of the nonfunctionalized microtube of ≤200 nm, log reduction values (LRV) of nearly 3 (i.

A self-sustaining, light-entrainable circadian oscillator in the Drosophila brain.

Background: The circadian clock of Drosophila is able to drive behavioral rhythms for many weeks in continuous darkness (DD). The endogenous rhythm generator is thought to be generated by interlocked molecular feedback loops involving circadian transcriptional and posttranscriptional regulation of several clock genes, including period. However, all attempts to demonstrate sustained rhythms of clock gene expression in DD have failed, making it difficult to link the molecular clock models with the circadian behavioral rhythms.

A secreted soluble form of ApoE receptor 2 acts as a dominant-negative receptor and inhibits Reelin signaling.

Specialized neurons throughout the developing central nervous system secrete Reelin, which binds to ApoE receptor 2 (ApoER2) and very low density lipoprotein receptor (VLDLR), triggering a signal cascade that guides neurons to their correct position. Binding of Reelin to ApoER2 and VLDLR induces phosphorylation of Dab1, which binds to the intracellular domains of both receptors. Due to differential splicing, several isoforms of ApoER2 differing in their ligand-binding and intracellular domains exist.

Mapping of elements involved in regulating normal temporal period and timeless RNA expression patterns in Drosophila melanogaster.

Although transcriptional regulation is a major force in generating circadian oscillations of clock molecules, posttranscriptional mechanisms also contribute to molecular rhythms. Applying novel transgenic period-luciferase constructs in transgenic Drosophila, the authors show that sequences within per's 5'-untranslated region mediate posttranscriptional regulation at the RNA level. Further mapping suggests that the relevant sequences for the correct phasing of period mRNA expression are located within the first intron.