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Dressing for Bioelectronic Smart Bandage

Chronic wounds affect over 6.5 million people in the United States costing more than $25B annually. 23% of military blast and burn wounds do not close, affecting a military patient's bone, skin, nerves. Moreover, 64% of military trauma have abnormal bone growth into soft tissue. Slow healing of recalcitrant wounds is a known and persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. Precise control of wound healing depends on physician's evaluation, experience. Physicians generally provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy. One potential unmet clinical need is related to todays rigid form factors. Modern delivery systems lack adequate conformal capability to adapt to complex surfaces (e.g., feet, joints, curved surfaces) where chronic wounds frequently occur. If modern devices have semi-flexible printed circuit boards they have not maintained consistent wound contact during patient movement, leading to variable delivery rates and reduced efficacy.

Portable Therapy Delivery

Chronic wounds affect over 6.5 million people in the United States costing more than $25B annually. 23% of military blast and burn wounds do not close, affecting a military patient's bone, skin, nerves. Moreover, 64% of military trauma have abnormal bone growth into soft tissue. Slow healing of recalcitrant wounds is a known and persistent problem, with incomplete healing, scarring, and abnormal tissue regeneration. Precise control of wound healing depends on physician's evaluation, experience. Physicians generally provide conditions and time for body to either heal itself, or to accept and heal around direct transplantations, and their practice relies a lot on passive recovery. While newer static approaches have demonstrated enhanced growth of non-regenerative tissue, they do not adapt to the changing state of wound, thus resulting in limited efficacy. Advanced wound healing devices generally lack true portability and home-use capability due to bulk, complexity, and/or power requirements. One potential unmet clinical need is the integration of a portable wearable design with modern and sometimes de novo components e.g., specialized microfluidic channels, reliable iontophoretic actuators, and programmable temporal controls.

Using Class I Lasso Peptides to Inhibit the Bacterial Type III Secretion System

Antibiotic resistance is a major issue in infectious disease treatment and prevention. In bacteria, the type III secretion system (T3SS) secretes effector proteins in the host cell, allowing the pathogen to infect. The T3SS is largely found on pathogens and not beneficial bacteria, so targeting the T3SS might have an advantage over using classic antibiotics, which disturb the beneficial human microbiome.

Selection Of DNA-Encoded Libraries For Membrane-Permeable Scaffolds

Combinatorial encoded library technologies can provide a set of tools for discovering protein-targeting ligands (molecules) and for drug discovery. These techniques can accelerate ligand discovery by leveraging chemical diversity achievable through genetically encoded combinatorial libraries, for example, by combinatorial permutation of chemical building blocks. Although display technologies such as mRNA and phage display use biological translation machinery to produce peptide-based libraries, hits from these libraries often lack key drug-like properties, for example, cell permeability. This limitation can arise from the peptide backbone's inherent polarity and the tendency to select compounds with polar/charged side chains. Backbone N-methylation can increase scaffold lipophilicity in mRNA display; however, codon table constraints can necessitate longer sequences to fully utilize the available space.DNA-encoded libraries (DELs) offer an alternative approach towards discovering hits against drug targets. However, like other encoded library techniques, DELs face significant obstacles in affinity selections, which tend to enrich library members bearing polar and/or charged moieties, which can have low (poor) passive cell membrane permeability, especially in larger molecular weight libraries, resulting in hits with poor drug-like properties. This selection bias is especially problematic for larger constructs beyond the rule of 5, where fine-tuning lipophilicity can be critical. Furthermore, DNA-encoded libraries can be of low quality. Although algorithmic predictions of lipophilicity exist, these two-dimensional (2D) atomistic calculations cannot capture conformational effects exhibited by larger molecules like peptide macrocycles. Despite over a decade of DEL technology development, no method exists to measure physical properties of encoded molecules across an entire DNA-encoded library. That is, successful translation of hits from encoded library selections can be impeded by low quality libraries and enrichment of highly polar members which tend to have poor passive cell permeability, especially for larger molecular weight libraries.DELs are produced through split-pool synthesis with DNA barcoding to encode the building block of each chemical step. Although this approach can draw on a large number of building blocks and allow for the formation of non-peptidic libraries with a large number of members, synthetic challenges persist. The formation of DELs can be synthetically inefficient. Truncations multiply ( are compounded) throughout synthesis, reducing the representation of properly synthesized constructs. Although strategies to improve library purity, to enable reaction monitoring for macrocycle formation, and to identify problematic chemistry affecting DNA tag amplification may be applied, a direct method for assessing DEL quality on a library-wide basis has yet to be developed.   

Queue-Sharing Multiple Access Protocol

Medium Access Control (MAC) protocols determine how multiple devices share a single communication channel. This started with Additive Links On-Line Hawaii Area (ALOHA) channel protocol and advanced to Carrier Sense Multiple Access (CSMA) protocols, variants of which are used today as WiFi standards. Such random access protocols are generally divided into contention-based methods like ALOHA and CSMA which are simple yet can have collisions at high traffic loads, and contention-free methods like Time Division Multiple Access (TDMA) which offer high efficiency but require complex clock synchronization and inflexible time slotting. While distributed queuing concepts have been pitched to help bridge this gap (e.g., DQDB or DQRAP) they have traditionally relied on physical time slots, dual buses, and/or complex signaling that makes them less suitable for the modern demands of wireless networks.

Robust Memristive Switching

Historically, radio frequency and microwave switches have historically relied on either electromechanical switches (which suffer from limited speed and reliability) or solid-state switches such as PIN diodes and field-effect transistors (FETs), both of which require continuous bias current to maintain their states, consuming significant power in modern communication systems. In particular, solid-state switches (PIN diodes and FETs) require continuous DC power to maintain their ON or OFF states, leading to substantial energy consumption particularly problematic for battery-operated devices and large-scale systems like 5G/6G base stations and Internet of Things networks. Emerging non-volatile RF switches based on phase-change materials (PCM) and other memristive devices have shown promise but are constrained by large switching energies, limited resistance modulation ratios (typically < three orders of magnitude), volatile behavior requiring thermal maintenance above transition temperatures, and low endurance.

Rippled Beta-Sheets From Mixed Chirality Linear And Cyclic Peptides

Researchers at UC Santa Cruz have expanded the knowledge on the rippled β-sheet, a protein structural motif formed by certain racemic peptides. Rippled β-sheets already show potential for Alzheimer’s research and drug delivery and leads to formation of hydrogels with enhanced properties. Researchers at UC Santa Cruz have further added to the structural foundation of rippled β-sheets, better understanding how rippled β-sheet formation can be controlled at the molecular level.

Rippled Beta-Sheets and Related Materials and Methods

Amyloid-β (Aβ) is a protein that is implicated in Alzheimer’s disease. Aβ oligomers aggregate to form amyloid plaques, which are found in the brains of individuals with Alzheimer’s disease. These plaques have high polydispersity; they vary in shape and size. Previously, researchers at UC Santa Cruz demonstrated that using a racemic mixture of Aβ promoted fibril formation, an aggregation that is less neurotoxic than plaques of high polydispersity. Furthermore, these racemic counterparts form rippled β-sheets.