ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.

ENPP1/CD203a is a membrane-bound ectonucleotidase capable of hydrolyzing ATP, cGAMP and other substrates. Its enzymatic activity plays an important role in the balance of extracellular adenine nucleotides and the modulation of purinergic signaling, in soft tissue calcification, and in the regulation of the cGAS/STING pathway. However, a detailed analysis of ENPP1 surface expression on human immune cells has not been performed.

Allosteric substrate release by a sialic acid TRAP transporter substrate binding protein.

The tripartite ATP-independent periplasmic (TRAP) transporters enable Vibrio cholerae and Haemophilus influenzae to acquire sialic acid, aiding their colonization of human hosts. This process depends on SiaP, a substrate-binding protein (SBP) that captures and delivers sialic acid to the transporter. We identified 11 nanobodies that bind specifically to the SiaP proteins from H.

Assessment of functional performance in self-rectifying passive crossbar arrays utilizing sneak path current.

Self-rectifying memristive devices have emerged as promising contenders for low-power in-memory computing, presenting numerous advantages. However, characterizing the functional behavior of passive crossbar arrays incorporating these devices remains challenging due to sophisticated parasitic currents stemming from rich memristive dynamic behavior. Conventional methods using read margin assessments to evaluate functional behavior in passive crossbars are hindered by the voltage divider effect from the pull-up resistor.

ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice.

Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire.

Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'.

Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction.

Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3 T cells isolated from the peripheral blood ( = 20), malignant ascites ( = 16), and tumor tissue ( = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8 T cells in OVCA tissue and malignant ascites.

Generation and characterization of antagonistic anti-human CD39 nanobodies.

CD39 is the major enzyme controlling the levels of extracellular adenosine triphosphate (ATP) via the stepwise hydrolysis of ATP to adenosine diphosphate (ADP) and adenosine monophosphate (AMP). As extracellular ATP is a strong promoter of inflammation, monoclonal antibodies (mAbs) blocking CD39 are utilized therapeutically in the field of immune-oncology. Though anti-CD39 mAbs are highly specific for their target, they lack deep penetration into the dense tissue of solid tumors, due to their large size.

Analytical modelling of the transport in analog filamentary conductive-metal-oxide/HfO ReRAM devices.

The recent co-optimization of memristive technologies and programming algorithms enabled neural networks training with in-memory computing systems. In this context, novel analog filamentary conductive-metal-oxide (CMO)/HfO redox-based resistive switching memory (ReRAM) represents a key technology. Despite device performance enhancements reported in literature, the underlying mechanism behind resistive switching is not fully understood.

Reliability effects of lateral filament confinement by nano-scaling the oxide in memristive devices.

Write-variability and resistance instability are major reliability concerns impeding implementation of oxide-based memristive devices in neuromorphic systems. The root cause of the reliability issues is the stochastic nature of conductive filament formation and dissolution, whose impact is particularly critical in the high resistive state (HRS). Optimizing the filament stability requires mitigating diffusive processes within the oxide, but these are unaffected by conventional electrode scaling.

[When does StäB (not) Work? A Qualitative, Multi-Perspective Survey on Factors that can Affect the Outcome of Inpatient-Equivalent Home Treatment (IEHT)].

Objective: There are always cases in which an already started inpatient equivalent home treatment is terminated. Aim of our study was to reach a better understanding of the circumstances leading to a termination of IEHT that has already begun.

Methods: 17 qualitative interviews were conducted with patients, relatives as well as practitioners and therapists.

The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.

The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients).

Learning hyperparameter predictors for similarity-based multidisciplinary topology optimization.

Topology optimization (TO) plays a significant role in industry by providing engineers with optimal material distributions based exclusively on the information about the design space and loading conditions. Such approaches are especially important for current multidisciplinary design tasks in industry, where the conflicting criteria often lead to very unintuitive solutions. Despite the progress in integrating manufacturing constraints into TO, one of the main factors restricting the use of TO in practice is the users' limited control of the final material distribution.

Intranasal trigeminal sensitivity to mechanical stimuli is associated with the perception of nasal patency.

Purpose: The aim of this prospective study was to examine the characteristics of a clinical test for the assessment of nasal trigeminal sensitivity to mechanical stimuli and its association with the perception of nasal patency.

Methods: Thirty-two normosmic healthy subjects participated (17 women and 15 men; age = 26 ± 3 years). Precisely defined air puffs were used with a flow rate of 2L/min for mechanical stimulation.

Olfactory Function and Olfactory Disorders.

The sense of smell is important. This became especially clear to patients with infection-related olfactory loss during the SARS-CoV-2 pandemic. We react, for example, to the body odors of other humans.

Review on Resistive Switching Devices Based on Multiferroic BiFeO.

This review provides a comprehensive examination of the state-of-the-art research on resistive switching (RS) in BiFeO (BFO)-based memristive devices. By exploring possible fabrication techniques for preparing the functional BFO layers in memristive devices, the constructed lattice systems and corresponding crystal types responsible for RS behaviors in BFO-based memristive devices are analyzed. The physical mechanisms underlying RS in BFO-based memristive devices, i.

Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb.

Introduction: Current scientific developments seem to allow for an "olfactory implant" in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear.

Methods: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB.

[Public mental health and patient autonomy-an area of conflict?].

Public mental health (PMH) interventions aim to promote and improve the well-being of members of a society. PMH is based on a normative understanding of what well-being is and what factors contribute to it. Without necessarily disclosing it, measures of a PMH program may affect the autonomy of individuals if their personal perceptions regarding their own individual well-being differ from PMH's prescriptions for well-being oriented toward societal goals.

Platelet-instructed SPP1 macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner.

Fibrosis represents the common end stage of chronic organ injury independent of the initial insult, destroying tissue architecture and driving organ failure. Here we discover a population of profibrotic macrophages marked by expression of Spp1, Fn1, and Arg1 (termed Spp1 macrophages), which expands after organ injury. Using an unbiased approach, we identify the chemokine (C-X-C motif) ligand 4 (CXCL4) to be among the top upregulated genes during profibrotic Spp1 macrophage differentiation.

Future therapeutic strategies for olfactory disorders: electrical stimulation, stem cell therapy, and transplantation of olfactory epithelium-an overview.

Olfactory disorders may be temporary or permanent and can have various causes. Currently, many COVID-19 patients report a reduced or complete loss of olfactory function. A wide range of treatment options have been investigated in the past, such as olfactory training, acupuncture, medical therapy, transcranial magnetic stimulation, or surgical excision of olfactory epithelium, e.