IL-2-armored peptide-major histocompatibility class I bispecific antibodies redirect antiviral effector memory CD8+ T cells to induce potent anti-cancer cytotoxic activity with limited cytokine release.

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells.

Association between metal implants and urinary chromium levels in US adults: a cross-sectional study from NHANES.

Metal implants play a significant role in orthopedics, commonly used for treating fractures, joint replacement surgeries, spinal procedures, and more. Chromium (Cr), crucial in these implants, may raises health concerns. However, the relationship between metal implants and urine Cr levels remains uncertain.

Robust production of monovalent bispecific IgG antibodies through novel electrostatic steering mutations at the C1-C interface.

Bispecific antibodies represent an increasingly large fraction of biologics in therapeutic development due to their expanded scope in functional capabilities. Asymmetric monovalent bispecific IgGs (bsIgGs) have the additional advantage of maintaining a native antibody-like structure, which can provide favorable pharmacology and pharmacokinetic profiles. The production of correctly assembled asymmetric monovalent bsIgGs, however, is a complex engineering endeavor due to the propensity for non-cognate heavy and light chains to mis-pair.

Improving pedicle screw path planning by vertebral posture estimation.

Robot-assisted pedicle screw placement in spinal surgery can reduce the complications associated with the screw placement and reduce the hospital return counts due to malfunctions. However, it requires accurate planning for a high-quality procedure. The state-of-the-art technologies reported in the literature either ignore the anatomical variations across vertebrae or require substantial human interactions.

The Impact of Contrast-Associated Acute Kidney Injury on All-Cause Mortality in Older Patients After Coronary Angiography:A 7.5-year Follow-Up.

Older patients (≥75 years) after coronary angiography constitute an increasing proportion, but only limited data are available regarding the prognosis of geriatric contrast-associated acute kidney injury (CA-AKI). Patients (≥75 years) undergoing coronary angiography between December 2010 and September 2013 were consecutively enrolled. CA-AKI was defined as an increase in serum creatinine of 25% or .

Condensation Separation of NO with Dimerization Reaction in the Presence of Noncondensable Gas: Critical Assessment and Model Development.

Pure nitrogen dioxide (NO) has significant economic value and is widely used in many fields, for which condensation technology plays an important role in separation and purification. However, developing cost-effective NO condensers remains challenging due to the lack of precise theoretical guidelines and comprehensive understanding of NO condensation process. In this work, NO condensation at various inlet surface subcoolings, mole fractions of noncondensable gas (NCG), and numbers was studied with a visualization experimental system.

An improved lentiviral system for efficient expression and purification of β-defensins in mammalian cells.

β-Defensins are a family of conserved small cationic antimicrobial peptides with different significant biological functions. The majority of mammalian β-defensins are expressed in epididymis, and many of them are predicted to have post-translational modifications. However, only a few of its members have been well studied due to the limitations of expressing and purifying bioactive proteins with correct post-translational modifications efficiently.

Optimal CD4 T cell priming after LPS-based adjuvanticity with CD134 costimulation relies on CXCL9 production.

LPS is a powerful adjuvant, and although LPS-mediated TLR4 signaling has been exquisitely delineated, the in vivo mechanism of how TLR4 responses impact T cell priming is far less clear. Besides costimulation, TNF and type 1 IFN are dominant cytokines released after TLR4 activation and can shape T cell responses, but other downstream factors have not been examined extensively. Depending on context, we show that IFNαR1 blockade resulted in minor to major effects on specific CD4 T cell clonal expansion.

TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation.

Staphylococcus aureus enterotoxins cause debilitating systemic inflammatory responses, but how they spread systemically and trigger inflammatory cascade is unclear. In this study, we showed in mice that after inhalation, Staphylococcus aureus enterotoxin A rapidly entered the bloodstream and induced T cells to orchestrate systemic recruitment of inflammatory monocytes and neutrophils. To study the mechanism used by specific T cells that mediate this process, a systems approach revealed inducible and noninducible pathways as potential targets.

Responses to LPS boost effector CD8 T-cell accumulation outside of signals 1 and 2.

Immunization with adjuvant plus antigen induces durable T-cell immunity and is a mainstay of vaccines. Here, the consequence of separating antigen stimulation of T cells from the adjuvant response was studied in a re-transfer model. Effector CD8 T cells in recipient mice were exposed to lipopolysaccharide (LPS), the Toll-like receptor 4 (TLR4) ligand, which significantly increased persistence.

Recombinant immunotoxin engineered for low immunogenicity and antigenicity by identifying and silencing human B-cell epitopes.

Recombinant immunotoxins (RITs) are hybrid proteins used to treat cancer. These proteins are composed of an Fv that reacts with cancer cells joined to a portion of Pseudomonas exotoxin A, which kills the cell. Because the toxin is a foreign protein, it can induce neutralizing antibodies and thereby limit the number of doses a patient can receive.

A recombinant immunotoxin engineered for increased stability by adding a disulfide bond has decreased immunogenicity.

Recombinant immunotoxins (RITs) are anti-cancer agents that combine the Fv of an antibody against cancer cells with a protein toxin from bacteria or plants. Since RITs contain a non-human protein, immunogenicity can be an obstacle in their development. In this study, we have explored the hypothesis that increasing stability can reduce the immunogenicity of a RIT using HA22-LR, which is composed of an anti-CD22 Fv fused to domain III of Pseudomonas exotoxin A.

The influence of domain structures on the signal transduction of chimeric receptors derived from the erythropoietin receptor.

Although cytokine receptors regulate many cellular functions, contribution of receptor's domains and their conformation to signal transduction remains unclear. In this study, we designed a series of chimeric erythropoietin receptor (EpoR) variants encoding a haemagglutinin epitope-tagged anti-fluorescein single-chain Fv and different combinations of extracellular D1/D2 domain(s) of EpoR as the extracellular domain to allow the receptor to be activated by multiple ligands. Furthermore, one to four Ala residues were inserted at the intracellular juxtamembrane region of each chimeric receptor to modulate the conformation of the intracellular domain.

[Non-conditional logistic regression analysis on risk factors of central venous catheter-related infection].

Objective: To study the correlation of indwelling central venous catheter and systemic infection, to study the causative microorganisms and factors contributing to infections, and the diagnosis and treatment of such infection.

Methods: All the central venous catheters were produced by American or German companies. Subclavian vein, internal jugular vein, or femoral vein was chosen.

Construction of a fluorescein-responsive chimeric receptor with strict ligand dependency.

Since many cell functions are regulated by members of the cytokine receptor superfamily, the artificial mimicry of the cytokine receptor system would be attractive for cellular engineering. We previously showed that an antibody/cytokine receptor chimera can transduce a growth signal in response to non-natural ligands, such as fluorescein-conjugated BSA. However, considerable background of cell proliferation was observed without antigen.

Real-time spectral imaging in three spatial dimensions.

We report what is to our knowledge the first volume-holographic optical imaging instrument with the capability to return three-dimensional spatial as well as spectral information about semitranslucent microscopic objects in a single measurement. The four-dimensional volume-holographic microscope is characterized theoretically and experimentally by use of fluorescent microspheres as objects.

Beam-width-dependent filtering properties of strong volume holographic gratings.

The finite dimension of the incident beam used to read out volume holographic gratings has interesting effects on their filtering properties. As the readout beam gets narrower, there is more deviation from the ideal response predicted for monochromatic plane waves. In this paper we experimentally explore beam-width-dependent phenomena such as wavelength selectivities, angular selectivities, and diffracted beam profiles.

Diffraction from deformed volume holograms: perturbation theory approach.

We derive the response of a volume grating to arbitrary small deformations, using a perturbative approach. This result is of interest for two applications: (a) when a deformation is undesirable and one seeks to minimize the diffracted field's sensitivity to it and (b) when the deformation itself is the quantity of interest and the diffracted field is used as a probe into the deformed volume where the hologram was originally recorded. We show that our result is consistent with previous derivations motivated by the phenomenon of shrinkage in photopolymer holographic materials.

Volume holographic hyperspectral imaging.

A volume hologram has two degenerate Bragg-phase-matching dimensions and provides the capability of volume holographic imaging. We demonstrate two volume holographic imaging architectures and investigate their imaging resolution, aberration, and sensitivity. The first architecture uses the hologram directly as an objective imaging element where strong aberration is observed and confirmed by simulation.

Folded shift multiplexing.

Shift multiplexing is a holographic recording method that uses a spherical reference wave. We extend the principle to a thin slab of holographic material that acts as a waveguide. Total internal reflection folds the reference spherical beam in one dimension.