A neutralizing antibody prevents postfusion transition of measles virus fusion protein.

Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use.

Evaluation of a Multiplex Bead Assay against Single-Target Assays for Detection of IgG Antibodies to SARS-CoV-2.

Serological assays for SARS-CoV-2 antibodies must be validated for performance with a large panel of clinical specimens. Most existing assays utilize a single antigen target and may be subject to reduced diagnostic specificity. This study evaluated a multiplex assay that detects antibodies to three SARS-CoV-2 targets.

Engineered jumpers overcome biological limits via work multiplication.

For centuries, scientists have explored the limits of biological jump height, and for decades, engineers have designed jumping machines that often mimicked or took inspiration from biological jumpers. Despite these efforts, general analyses are missing that compare the energetics of biological and engineered jumpers across scale. Here we show how biological and engineered jumpers have key differences in their jump energetics.

Evaluation of anti-factor VIII antibody levels in patients with haemophilia A receiving immune tolerance induction therapy or bypassing agents.

Introduction: Bleeding episodes in patients who have haemophilia A (HA), a hereditary bleeding disorder caused by a deficiency in factor VIII (FVIII), are treated or prophylactically prevented with infusions of exogenous FVIII. Neutralizing antibodies, referred to as inhibitors, against infusion products are a major complication experienced by up to 30% of patients who have severe HA. Bypassing agents (BPA), a class of therapeutics given to patients who have inhibitors, bypass the need for FVIII in the coagulation cascade, and long-term inhibitor eradication is accomplished using immune tolerance induction therapy (ITI).

[Illustration Techniques in Ophthalmic Textbooks 200 Years Ago - a Platform for the Rostock Glass Eye Collection of Anterior Segment Pathologies from 1860].

Very recent research results have demonstrated that the "Rostock Artificial Eye Collection" - assembled 150 years ago with 132 glass modelled exhibits of anterior segment pathologies - is mainly based on the figures of the Atlas of Ophthalmology published by Antoine Pierre Demours in 1818. This article focusses on the analyses of the imaging techniques of this atlas. Present knowledge implies that the author used different colour etching concepts which were partially re-coloured individually.

An Observational Study from Long-Term AAV Re-administration in Two Hemophilia Dogs.

Adeno-associated virus (AAV) vectors have been successfully applied in hemophilia clinical trials. However, this approach is limited to patients without AAV-neutralizing antibodies (NAbs). In this study, we explored the feasibility of AAV re-administration in hemophilia A dogs treated initially 8 years ago with AAV8.

Complete correction of hemophilia B phenotype by FIX-Padua skeletal muscle gene therapy in an inhibitor-prone dog model.

Skeletal muscle–directed expression of FIX-Padua resulted in complete correction of HB phenotype in an inhibitor-prone dog model. Long-term immune tolerance to FIX is sustained over years upon multiple challenges with recombinant FIX protein in 2 HB models.

AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice.

Emerging successful clinical data on gene therapy using adeno-associated viral (AAV) vector for hemophilia B (HB) showed that the risk of cellular immune response to vector capsid is clearly dose dependent. To decrease the vector dose, we explored AAV-8 (1-3 × 10(12) vg/kg) encoding a hyperfunctional factor IX (FIX-Padua, arginine 338 to leucine) in FIX inhibitor-prone HB dogs. Two naïve HB dogs showed sustained expression of FIX-Padua with an 8- to 12-fold increased specific activity reaching 25% to 40% activity without antibody formation to FIX.

Inpatient trial of an artificial pancreas based on multiple model probabilistic predictive control with repeated large unannounced meals.

Background: Closed-loop control of blood glucose levels in people with type 1 diabetes offers the potential to reduce the incidence of diabetes complications and reduce the patients' burden, particularly if meals do not need to be announced. We therefore tested a closed-loop algorithm that does not require meal announcement.

Materials And Methods: A multiple model probabilistic predictive controller (MMPPC) was assessed on four patients, revised to improve performance, and then assessed on six additional patients.

Force-sensitive detents improve user performance for linear selection tasks.

Haptic technology, providing force cues and creating a programmable interface, can assist users in more accurately using an interface. This paper investigates haptic assistance in combination with auditory feedback instead of visual feedback. A user test is carried out in which participants select fundamental frequencies from a continuous range to play brief musical melodies.

Decreased hematopoietic progenitor cell mobilization in pearl mice.

Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) assay, bone marrow lineage negative (lin(-)), Sca(+) and c-kit(+) cells (LSK cells), bone marrow elastase, myeloperoxidase, and cathepsin G enzyme activity were compared in C57Bl6 (Bl/6) and pearl mice.

Feedback control of acoustic musical instruments: collocated control using physical analogs.

Traditionally, the average professional musician has owned numerous acoustic musical instruments, many of them having distinctive acoustic qualities. However, a modern musician could prefer to have a single musical instrument whose acoustics are programmable by feedback control, where acoustic variables are estimated from sensor measurements in real time and then fed back in order to influence the controlled variables. In this paper, theory is presented that describes stable feedback control of an acoustic musical instrument.

A closed-loop artificial pancreas based on risk management.

Background: Control algorithms that regulate blood glucose (BG) levels in individuals with type 1 diabetes mellitus face several fundamental challenges. Two of these are the asymmetric risk of clinical complications associated with low and high glucose levels and the irreversibility of insulin action when using only insulin. Both of these nonlinearities force a controller to be more conservative when uncertainties are high.

Probabilistic evolving meal detection and estimation of meal total glucose appearance.

Background: Automatic compensation of meals for type 1 diabetes patients will require meal detection from continuous glucose monitor (CGM) readings. This is challenged by the uncertainty and variability inherent to the digestion process and glucose dynamics as well as the lag and noise associated with CGM sensors. Thus any estimation of meal start time, size, and shape is fundamentally uncertain.

Neutrophil elastase-processing defect in cyclic hematopoietic dogs.

Objective: Canine cyclic hematopoiesis (CH), a model of human cyclic neutropenia and severe congenital neutropenia, is characterized by a periodic reduced neutrophil count and decreased neutrophil elastase (NE) enzymatic activity. Canine CH is caused by a mutation of AP3B1 encoding the beta3A subunit of adaptor protein complex-3 (AP-3). It has been proposed that trafficking of elastase is affected by AP-3.

Laser-Machined Shape Memory Alloy Sensors for Position Feedback in Active Catheters.

Catheter-based interventions are a form of minimally invasive surgery that can decrease hospitalization time and greatly lower patient morbidity compared to traditional methods. However, percutaneous catheter procedures are hindered by a lack of precise tip manipulation when actuation forces are transmitted over the length of the catheter. Active catheters with local shape-memory-alloy (SMA) actuation can potentially provide the desired manipulation of a catheter tip, but hysteresis makes it difficult to control the actuators.

Neural stem/progenitor cells modulate immune responses by suppressing T lymphocytes with nitric oxide and prostaglandin E2.

We and others have reported that neural stem/progenitor cells (NSCs) may exert direct anti-inflammatory activity. This action has been attributed, in part, to T-cell suppression. However, how T-cells become suppressed by NSCs remains unresolved.

Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy.

Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)-mediated gene therapy for hemophilia B. In an 8-year study, inhibitor-prone hemophilia B dogs (n = 2) treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy (n = 3) had a bleed frequency similar to untreated FIX-deficient dogs. Coagulation tests (whole blood clotting time [WBCT], activated clotting time [ACT], and activated partial thromboplastin time [aPTT]) have remained at the upper limits of the normal ranges in the 2 dogs that received liver-directed gene therapy.

Statistical hypoglycemia prediction.

Background: Hypoglycemia presents a significant risk for patients with insulin-dependent diabetes mellitus. We propose a predictive hypoglycemia detection algorithm that uses continuous glucose monitor (CGM) data with explicit certainty measures to enable early corrective action.

Method: The algorithm uses multiple statistical linear predictions with regression windows between 5 and 75 minutes and prediction horizons of 0 to 20 minutes.

Hematopoietic chimerism induces renal and skin allograft tolerance in DLA-identical dogs.

Objective: Hematopoietic chimerism, a state where donor and recipient bone marrow cells coexist, is associated with donor-specific tolerance. Nonmyeloablative bone marrow transplantation (BMT) has been shown to induce stable mixed hematopoietic chimerism in dog leukocyte antigen (DLA)-matched dogs. The potential for inducing renal and skin allograft tolerance with nonmyeloablative BMT was investigated in DLA-identical and DLA-haploidentical dogs in this study.

ERG components of negative polarity from the inner retina and the optic nerve response.

ERG components of negative polarity in the light-adapted and in the dark-adapted inner retina are reviewed from a clinical perspective and include consideration of experimental research. Field potentials are inherently complex including summating contributions from specialized neurons as well as from glial elements. This property applies to the PERG, PhNR and to the STR.

Improving contact realism through event-based haptic feedback.

Tapping on surfaces in a typical virtual environment feels like contact with soft foam rather than a hard object. The realism of such interactions can be dramatically improved by superimposing event-based, high-frequency transient forces over traditional position-based feedback. When scaled by impact velocity, hand-tuned pulses and decaying sinusoids produce haptic cues that resemble those experienced during real impacts.

Quantitative analysis of OCT characteristics in patients with achromatopsia and blue-cone monochromatism.

Purpose: To quantify optical coherence tomography (OCT) images of the central retina in patients with blue-cone monochromatism (BCM) and achromatopsia (ACH) compared with healthy control individuals.

Methods: The study included 15 patients with ACH, 6 with BCM, and 20 control subjects. Diagnosis of BCM and ACH was established by visual acuity testing, morphologic examination, color vision testing, and Ganzfeld ERG recording.

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation.

Objective: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression.

Study Design: Prospective study.

Animals: Ten healthy adult mongrel dogs.