Morphology of Buried Interfaces in Ion-Assisted Magnetron Sputter-Deposited BC-Containing Ni/Ti Multilayer Neutron Optics Investigated by Grazing-Incidence Small-Angle Scattering.

Multilayer neutron optics require precise control of interface morphology for optimal performance. In this work, we investigate the effects of different growth conditions on the interface morphology of Ni/Ti-based multilayers, with a focus on incorporating low-neutron-absorbing BC and using different ion assistance schemes. Grazing-incidence small-angle X-ray scattering was used to probe the structural and morphological details of buried interfaces, revealing that the layers become more strongly correlated and the interfaces form mounds with increasing amounts of BC.

Reflective, polarizing, and magnetically soft amorphous neutron optics with B-enriched BC.

The utilization of polarized neutrons is of great importance in scientific disciplines spanning materials science, physics, biology, and chemistry. However, state-of-the-art multilayer polarizing neutron optics have limitations, particularly low specular reflectivity and polarization at higher scattering vectors/angles, and the requirement of high external magnetic fields to saturate the polarizer magnetization. Here, we show that, by incorporating BC into Fe/Si multilayers, amorphization and smooth interfaces can be achieved, yielding higher neutron reflectivity, less diffuse scattering, and higher polarization.

Tuning the Through-Plane Lattice Thermal Conductivity in van der Waals Structures through Rotational (Dis)ordering.

It has recently been demonstrated that MoS with irregular interlayer rotations can achieve an extreme anisotropy in the lattice thermal conductivity (LTC), which is, for example, of interest for applications in waste heat management in integrated circuits. Here, we show by atomic-scale simulations based on machine-learned potentials that this principle extends to other two-dimensional materials, including C and BN. In all three materials, introducing drives the through-plane LTC to the glass limit, while the in-plane LTC remains almost unchanged compared to those of the ideal bulk materials.

ABBV-0805, a novel antibody selective for soluble aggregated α-synuclein, prolongs lifespan and prevents buildup of α-synuclein pathology in mouse models of Parkinson's disease.

A growing body of evidence suggests that aggregated α-synuclein, the major constituent of Lewy bodies, plays a key role in the pathogenesis of Parkinson's disease and related α-synucleinopathies. Immunotherapies, both active and passive, against α-synuclein have been developed and are promising novel treatment strategies for such disorders. Here, we report on the humanization and pharmacological characteristics of ABBV-0805, a monoclonal antibody that exhibits a high selectivity for human aggregated α-synuclein and very low affinity for monomers.

Extremely anisotropic van der Waals thermal conductors.

The densification of integrated circuits requires thermal management strategies and high thermal conductivity materials. Recent innovations include the development of materials with thermal conduction anisotropy, which can remove hotspots along the fast-axis direction and provide thermal insulation along the slow axis. However, most artificially engineered thermal conductors have anisotropy ratios much smaller than those seen in naturally anisotropic materials.

The distribution and mitochondrial genotype of the hydroid is correlated with its pelagic substrate type in the tropical and subtropical western Atlantic Ocean.

The pelagic brown macroalga supports rich biological communities in the tropical and subtropical Atlantic region, including a variety of epiphytic invertebrates that grow on the itself. The thecate hydroid is commonly found growing on some, but not all, forms. In this study, we examined the relationship between and its pelagic substrate across a broad geographic area over the course of 4 years (2015-2018).

Fitter frogs from polluted ponds: The complex impacts of human-altered environments.

Human-modified habitats rarely yield outcomes that are aligned with conservation ideals. Landscapes that are subdivided by roads are no exception, precipitating negative impacts on populations due to fragmentation, pollution, and road kill. Although many populations in human-modified habitats show evidence for local adaptation, rarely does environmental change yield outright benefits for populations of conservation interest.

Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy.

Synucleinopathies represent a group of neurodegenerative disorders which are characterized by intracellular accumulation of aggregated α-synuclein. α-synuclein misfolding and oligomer formation is considered a major pathogenic trigger in these disorders. Therefore, targeting α-synuclein species represents an important candidate therapeutic approach.

Impact of BC co-sputtering on structure and optical performance of Cr/Sc multilayer X-ray mirrors.

The influence of BC incorporation during magnetron sputter deposition of Cr/Sc multilayers intended for soft X-ray reflective optics is investigated. Chemical analysis suggests formation of metal: boride and carbide bonds which stabilize an amorphous layer structure, resulting in smoother interfaces and an increased reflectivity. A near-normal incidence reflectivity of 11.

Cellular Uptake of α-Synuclein Oligomer-Selective Antibodies is Enhanced by the Extracellular Presence of α-Synuclein and Mediated via Fcγ Receptors.

Immunotherapy targeting aggregated α-synuclein has emerged as a potential treatment strategy against Parkinson's disease and other α-synucleinopathies. We have developed α-synuclein oligomer/protofibril selective antibodies that reduce toxic α-synuclein in a human cell line and, upon intraperitoneal administration, in spinal cord of transgenic mice. Here, we investigated under which conditions and by which mechanisms such antibodies can be internalized by cells.

Vector-encoded Helicobacter pylori neutrophil-activating protein promotes maturation of dendritic cells with Th1 polarization and improved migration.

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. Both HP-NAP protein and oncolytic viruses encoding HP-NAP have been suggested as immunotherapeutic anticancer agents and adjuvants for vaccination but with little known about its mode of action to activate adaptive immunity.

Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[A30P] α-synuclein mice.

Several lines of evidence suggest that accumulation of aggregated alpha-synuclein (α-synuclein) in the central nervous system (CNS) is an early pathogenic event in Parkinson's disease and other Lewy body disorders. In recent years, animal studies have indicated immunotherapy with antibodies directed against α-synuclein as a promising novel treatment strategy. Since large α-synuclein oligomers, or protofibrils, have been demonstrated to possess pronounced cytotoxic properties, such species should be particularly attractive as therapeutic targets.

Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo.

Antibody-mediated blockade of CTLA4 has been shown to be effective in treating a select group of patients with late-stage melanoma. The precise mechanism underlying the clinical activity of CTLA4 immunotherapy is poorly understood, although recent experimental findings indicate that antibody-mediated depletion of regulatory T cells (Tregs) in the tumor microenvironment plays a key role in efficacious antitumor responses. In the current study, we used an experimental model of pancreatic adenocarcinoma to compare the antitumor efficacy of peritumoral low-dose anti-CTLA4 monoclonal antibody (mAb) administration to that of a commonly utilized systemic high-dose anti-CTLA4 regimen.

DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer.

We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment.

An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors.

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. HP-NAP can mediate antitumor effects by recruiting neutrophils and inducing Th1-type differentiation in the tumor microenvironment.

Rapid expansion of T cells: Effects of culture and cryopreservation and importance of short-term cell recovery.

Background: Successful cell therapy relies on the identification and mass expansion of functional cells for infusion. Cryopreservation of cells is an inevitable step in most cell therapies which also entails consequences for the frozen cells.

Material And Methods: This study assessed the impact of cryopreservation and the widely used protocol for rapid expansion of T lymphocytes.

T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells.

To produce genetically engineered T cells directed against prostate and breast cancer cells, we have cloned the T-cell receptor recognizing the HLA-A2-restricted T-cell receptor γ-chain alternate reading-frame protein (TARP)(4-13) epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli.

Age-related somatic structural changes in the nuclear genome of human blood cells.

Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants.

Adenovirus with hexon Tat-protein transduction domain modification exhibits increased therapeutic effect in experimental neuroblastoma and neuroendocrine tumors.

Adenovirus serotype 5 (Ad5) is widely used as an oncolytic agent for cancer therapy. However, its infectivity is highly dependent on the expression level of coxsackievirus-adenovirus receptor (CAR) on the surfaces of tumor cells. Furthermore, infected cells overproduce adenovirus fiber proteins, which are released prior to cell lysis.

Skin electroporation: effects on transgene expression, DNA persistence and local tissue environment.

Background: Electrical pulses have been used to enhance uptake of molecules into living cells for decades. This technique, often referred to as electroporation, has become an increasingly popular method to enhance in vivo DNA delivery for both gene therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination (gene delivery followed by electroporation) is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers.

Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients.

Electroporation has, during the last years, proven to be a very successful delivery method for DNA vaccines and has now reached clinical evaluation. Although intramuscular electroporation is practical in animal models, intradermal electroporation might be more suitable for clinical administration. Skin is the most accessible organ of the body and has professional antigen-presenting cells in large amounts; thus, skin is an ideal target for DNA vaccine delivery.

Expression of immunomodulating genes in prostate cancer and benign prostatic tissue.

Objective: To investigate the expression of immunomodulating genes in prostate cancer and benign prostatic tissue.

Study Design: We investigated by quantitative real-time polymerase chain reaction the expression of indoleamine 2,3-dioxygenase, arginase 1, arginase 2, inducible form of nitric oxide synthase, cyclooxygenase 2 (COX-2), programmed death ligand 1 and interleukin 10 in 36 matched pairs of samples from prostate cancer and benign prostatic tissue.

Results: Among the genes analyzed, arginase 2 and COX-2 showed statistically significant up-regulation and down-regulation, respectively, in malignant compared to benign prostate tissue.