2,406 research outputs found
Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy
Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mice, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. No significant increases in the numbers of other cell types were observed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AHCMS leads to longer survival times of mice and improved tumour growth delay in rats, as compared with untreated controls and free drug treated animals. In both animal models higher adriamycin doses were initially tolerated if the drug was formulated in microspheres, although long-term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxic effects of the drug
Gating the pore of the calcium-activated chloride channel TMEM16A
The binding of cytoplasmic Ca2+ to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca2+ and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca2+ binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively contribute to the stabilization of the gate in the closed conformation of the pore, thus explaining the low open probability of the channel in the absence of Ca2+
T5lephone: Bridging Speech and Text Self-supervised Models for Spoken Language Understanding via Phoneme level T5
In Spoken language understanding (SLU), a natural solution is concatenating
pre-trained speech models (e.g. HuBERT) and pretrained language models (PLM,
e.g. T5). Most previous works use pretrained language models with subword-based
tokenization. However, the granularity of input units affects the alignment of
speech model outputs and language model inputs, and PLM with character-based
tokenization is underexplored. In this work, we conduct extensive studies on
how PLMs with different tokenization strategies affect spoken language
understanding task including spoken question answering (SQA) and speech
translation (ST). We further extend the idea to create T5lephone(pronounced as
telephone), a variant of T5 that is pretrained using phonemicized text. We
initialize T5lephone with existing PLMs to pretrain it using relatively
lightweight computational resources. We reached state-of-the-art on NMSQA, and
the T5lephone model exceeds T5 with other types of units on end-to-end SQA and
ST
Recommended from our members
Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass.
Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity and specific peptidomimetic ligand (LLP2A) against integrin α4β1 on the MSC surface to a bisphosphonate (alendronate, Ale) that has a high affinity for bone. LLP2A-Ale induced MSC migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation studies and in immunocompetent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or as a result of estrogen deficiency. These results provide proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength
Primary tumors of the aorta and pulmonary arteries: Insights from cardiovascular magnetic resonance
- …