A Microfluidic High-Capacity Screening Platform for Neurological Disorders.

Compartmentalized cell cultures (CCCs) provide the possibility to study mechanisms of neurodegenerative diseases, such as spreading of misfolded proteins in Alzheimer's or Parkinson's disease or functional changes in, e.g., chronic pain, in vitro.

Malaria Biomimetic for Tumor Targeted Drug Delivery.

Malaria infected erythrocytes utilize the parasite protein VAR2CSA to bind to a unique presentation of chondroitin sulfate (CS) for their placenta specific tropism. Interestingly, many cancers express a similar form of CS, thereby termed oncofetal CS (ofCS). The distinctive tropism of malaria infected erythrocytes and the identification of oncofetal CS, therefore, represent potentially potent tools for cancer targeting.

Oncofetal Chondroitin Sulfate Is a Highly Expressed Therapeutic Target in Non-Small Cell Lung Cancer.

Broad-spectrum therapeutics in non-small cell lung cancer (NSCLC) are in demand. Most human solid tumors express proteoglycans modified with distinct oncofetal chondroitin sulfate (CS) chains that can be detected and targeted with recombinant VAR2CSA (rVAR2) proteins and rVAR2-derived therapeutics. Here, we investigated expression and targetability of oncofetal CS expression in human NSCLC.

Bacteria-Inspired Nanomedicine.

The natural world has provided a host of materials and inspiration for the field of nanomedicine. By taking design cues from naturally occurring systems, the nanoengineering of advanced biomimetic platforms has significantly accelerated over the past decade. In particular, the biomimicry of bacteria, with their motility, taxis, immunomodulation, and overall dynamic host interactions, has elicited substantial interest and opened up exciting avenues of research.

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.

We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2-binding site. Both ACE2 and heparin can bind independently to spike protein in vitro, and a ternary complex can be generated using heparin as a scaffold.

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.

We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template.

An affinity chromatography and glycoproteomics workflow to profile the chondroitin sulfate proteoglycans that interact with malarial VAR2CSA in the placenta and in cancer.

Chondroitin sulfate (CS) is the placental receptor for the VAR2CSA malaria protein, expressed at the surface of infected erythrocytes during Plasmodium falciparum infection. Infected cells adhere to syncytiotrophoblasts or get trapped within the intervillous space by binding to a determinant in a 4-O-sulfated CS chains. However, the exact structure of these glycan sequences remains unclear.

Co-optimization of Heavy-Duty Fuels and Engines: Cost Benefit Analysis and Implications.

Heavy-duty vehicles require expensive aftertreatment systems for control of emissions such as particulate matter (PM) and nitrogen oxides (NO) to comply with stringent emission standards. Reduced engine-out emissions could potentially alleviate the emission control burden, and thus bring about reductions in the cost associated with aftertreatment systems, which translates into savings in vehicle ownership. This study evaluates potential reductions in manufacturing and operating costs of redesigned emission aftertreatment systems of line-haul heavy-duty diesel vehicles (HDDVs) with reduced engine-out emissions brought about by co-optimized fuel and engine technologies.

Detection of Tick-Borne Pathogens in Lambs Undergoing Prophylactic Treatment Against Ticks on Two Swedish Farms.

Tick-borne pathogens (TBPs), especially , cause disease in grazing livestock. Tick prophylaxis is, therefore, a routine practice in sheep flocks in Sweden, especially in central, southern, and coastal areas of the country where ixodid ticks ( and ) are present. In the present study, the status of infection by and other TBPs in lambs treated with tick prophylaxis has been assessed serologically and with polymerase chain reaction (PCR).

Virus-like particle display of HER2 induces potent anti-cancer responses.

Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms.

Restoration of seminal plasma to stallion spermatozoa selected by colloid centrifugation increases sperm progressive motility but is detrimental to chromatin integrity.

There is controversy about whether the presence of some seminal plasma (SP) in an equine insemination dose is necessary for promoting fertility. A new technique for improving stallion sperm quality, single layer centrifugation (SLC) using a species-specific colloid, Androcoll-E, selects a sperm subpopulation that is highly motile with normal morphology, intact membranes and good chromatin integrity from the rest of the ejaculate and removes SP. The present study was designed to investigate the effect of restoring homologous SP (5% and 10%) on the progressive motility, velocity, and chromatin integrity of SLC-selected stallion spermatozoa in 44 semen samples over time.

High-throughput transfection of differentiated primary neurons from rat forebrain.

Primary neurons in culture are considered to be a highly relevant model in the study of neuronal development and activity. They can be cultivated and differentiated in vitro but are difficult to transfect using conventional methods. To address this problem, a capillary electroporation system called Cellaxess Elektra was developed for efficient and reproducible transfection of primary cortical and hippocampal neurons without significant impact on cell morphology and viability.

A biohybrid dynamic random access memory.

We report that GABA(A) receptors in a patch-clamped biological cell form a short-term memory circuit when integrated with a scanning-probe microfluidic device. Laminar patterns of receptor activators (agonists) provided by the microfluidic device define and periodically update the data input which is read and stored by the receptors as state distributions (based on intrinsic multistate kinetics). The memory is discharged over time and lasts for seconds to minutes depending on the input function.

Microfluidic technologies in drug discovery.

Microfluidic systems are increasingly used as tools in various stages of the drug discovery process. Microscale systems offer several obvious advantages, such as low sample consumption and significantly reduced analysis or experiment time. These technologies raise the possibility of massive parallelization and concomitant reduction in cost per acquired data point.

Microfluidic gradient-generating device for pharmacological profiling.

We describe an on-chip microfluidic gradient-generating device that generates concentration gradients spanning nearly 5 orders of magnitude starting from a single concentration. The exiting stream of drugs held at different concentrations remains laminar in a recording chamber and can be presented as 24 discrete solutions to a cell-based sensor. The high-performance characteristics of the device are demonstrated by pharmacological screening of voltage-gated K+ channels (hERG) and ligand-gated GABA(A) receptors using scanning-probe patch-clamp measurements.

A microfluidics approach to the problem of creating separate solution environments accessible from macroscopic volumes.

We report on a microfluidic device that generates separate solution environments in macroscopic volumes. Spatially distinct patterns are created by emitting fluids from 16 different sources (closely spaced microchannels) into a solution-filled macroscopic chamber. The fluid in neighboring microchannels couples viscously in the macroscopic container, generating one single interdigitated stream.

A cell-based bar code reader for high-throughput screening of ion channel-ligand interactions.

This paper presents a microfluidics-patch clamp platform for performing high-throughput screening and rapid characterization of weak-affinity ion channel-ligand interactions. This platform integrates a microfluidic chip consisting of multiple channels entering an open volume with standard patch clamp equipment. The microfluidic chip is placed on a motorized scanning stage and the method relies on the ability to scan rapidly, on the order of milliseconds, a patch-clamped cell across discrete zones of different solutions created in the open volume.

Surface gravity waves over a two-dimensional random seabed.

We extend homogenization theory to study the two-dimensional evolution of weakly nonlinear waves in a sea where the bathymetry is random over a large area. A deterministic nonlinear Schrödinger equation is derived for the envelope of a nearly sinusoidal progressive wave train. Randomness is shown to yield a linear term with a complex coefficient depending on a certain statistical average of the bathymetry.

Tantalum-filament pulling device for fabrication of submicrometer fused-silica tips.

A simple and low-cost pulling device for fused-silica capillaries was developed. By using a tantalum heating filament and the self-tension in a bent capillary, tips and constricted regions with outer diameters of approximately 1 microm and inner diameters of a few hundred nanometers could be reproducibly pulled from 50-microm-i.d.

The Danish Cancer Registry--history, content, quality and use.

The Danish Cancer Registry is a population-based registry containing data on the incidence of cancer throughout Denmark since 1943. Reporting of cancer was made mandatory by administrative order in 1987. Details of individual cases of cancer are available according to the 7th revision of the International Classification of Diseases (ICD) for all years, and according to the ICD-O since 1978.