Method for routine density measurement of sublimating solid carbon dioxide (dry ice) for cold-chain quality control

With recent development of vaccines and biologics, interest in dry ice for cold chain shipping has increased. However, understanding of how dry ice properties relate to performance is not well understood. This study introduces a simple method for measuring a key property of dry ice that has been shown to correlate to performance. The method involves a variant of the water displacement method for determining volume, where dense solid particles are used in place of water for volume determination. Three particle types (sieved sand, glass beads, and stainless-steel shot) were tested for suitability with the particle displacement method. Items of known mass and volume were used to validate the method. Direct volume measurements of dry ice cut samples using digital calipers were conducted in parallel for relative comparison. Results showed that the proposed particle displacement method using sieved sand produced density readings with an accuracy of 97-99%, whereas digital calipers underestimated density values. The sand and glass particles were less successful due to high thermal conductivity (stainless-steel shot), which led to errors due to condensation, and particles that were too fine and not sufficiently dense to prevent fluidization doe to sublimation gas flow. Sieved sand provided a good combination of particle size, density, thermal conductivity, and heat capacity for routine measurement of density of dry ice regardless of shape

Rocaglates induce gain-of-function alterations to eIF4A and eIF4F

Rocaglates are a diverse family of biologically active molecules that have gained tremendous interest in recent years due to their promising activities in pre-clinical cancer studies. As a result, this family of compounds has been significantly expanded through the development of efficient synthetic schemes. However, it is unknown whether all of the members of the rocaglate family act through similar mechanisms of action. Here, we present a comprehensive study comparing the biological activities of >200 rocaglates to better understand how the presence of different chemical entities influences their biological activities. Through this, we find that most rocaglates preferentially repress the translation of mRNAs containing purine-rich 5' leaders, but certain rocaglates lack this bias in translation repression. We also uncover an aspect of rocaglate mechanism of action in which the pool of translationally active eIF4F is diminished due to the sequestration of the complex onto RNA.P50 GM067041 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HHSPublished versio

Oxo-aglaiastatin-mediated inhibition of translation initiation

We thank Dr. Elias George (McGill University) for the kind gift of Pgp-1-expressing HeLa cells. RIM was supported by a doctoral fellowship from the Cole Foundation. This research was supported by a grant from the Canadian Institutes of Health Research (FDN-148366) to JP. J.A.P., Jr. is supported by NIH Grant R35 GM118173. Work at the Boston University Center for Molecular Discovery is supported by Grant R24 GM111625. (Cole Foundation; FDN-148366 - Canadian Institutes of Health Research; R35 GM118173 - NIH; R24 GM111625)Published versionSupporting documentatio

Biomechanical evaluation of shape-memory alloy staples for internal fixation—an in vitro study

Background: The field of orthopaedics is a constantly evolving discipline. Despite the historical success of plates, pins and screws in fracture reduction and stabilisation, there is a continuing search for more efficient and improved methods of fracture fixation. The aim of this study was to evaluate shape-memory staples and to compare them to a currently used implant for internal fracture fixation. Multi-plane bending stability and interfragmentary compression were assessed across a simulated osteotomy using single and double-staple fixation and compared to a bridging plate. Methods: Transverse osteotomies were made in polyurethane blocks (20 × 20 × 120 mm) and repairs were performed with one (n = 6), or two (n = 6) 20 mm nitinol staples, or an eight-hole 2.7 mm quarter-tubular plate (n = 6). A pressure film was placed between fragments to determine contact area and compressive forces before and after loading. Loading consisted of multi-planar four-point bending with an actuator displacement of 3 mm. Gapping between segments was recorded to determine loads corresponding to a 2 mm gap and residual post-load gap. Results: Staple fixations showed statistically significant higher mean compressive loads and contact areas across the osteotomy compared to plate fixations. Double-staple constructs were superior to single-staple constructs for both parameters (p < 0.001). Double-staple constructs were significantly stiffer and endured significantly larger loads before 2 mm gap formation compared to other constructs in the dorsoventral plane (p < 0.001). However, both staple constructs were significantly less stiff and tolerated considerably lower loads before 2 mm gap formation when compared to plate constructs in the ventrodorsal and right-to-left lateral loading planes. Loading of staple constructs showed significantly reduced permanent gap formation in all planes except ventrodorsally when compared to plate constructs. Conclusions: Although staple fixations were not as stable as plate fixations in particular loading planes, double-staple constructs demonstrated the most consistent bending stiffness in all planes. Placing two perpendicular staples is suggested instead of single-staples whenever possible, with at least one staple applied on the compression side of the anticipated loading to improve construct stability

eIF4A inhibitors suppress cell-cycle feedback response and acquired resistance to CDK4/6 inhibition in cancer

CDK4/6 inhibitors are FDA-approved drugs for estrogen receptor-positive (ER+) breast cancer and are being evaluated to treat other tumor types, including KRAS-mutant non-small cell lung cancer (NSCLC). However, their clinical utility is often limited by drug resistance. Here, we sought to better understand the resistant mechanisms and help devise potential strategies to overcome this challenge. We show that treatment with CDK4/6 inhibitors in both ER+ breast cancer and KRAS-mutant NSCLC cells induces feedback upregulation of cyclin D1, CDK4, and cyclin E1, mediating drug resistance. We demonstrate that rocaglates, which preferentially target translation of key cell-cycle regulators, effectively suppress this feedback upregulation induced by CDK4/6 inhibition. Consequently, combination treatment of CDK4/6 inhibitor palbociclib with the eukaryotic initiation factor (eIF) 4A inhibitor, CR-1-31-B, is synergistic in suppressing the growth of these cancer cells in vitro and in vivo Furthermore, ER+ breast cancer and KRAS-mutant NSCLC cells that acquired resistance to palbociclib after chronic drug exposure are also highly sensitive to this combination treatment strategy. Our findings reveal a novel strategy using eIF4A inhibitors to suppress cell-cycle feedback response and to overcome resistance to CDK4/6 inhibition in cancer.Accepted manuscrip

Effect of Red Cabbage Extract on Minced Nile Perch Fish Patties Vacuum Packaged in High and Low Oxygen Barrier Films

Oxidation of polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish causes loss of product quality. Oxidative rancidity causes loss of nutritional value and undesirable color changes. Therefore, powerful antioxidant extracts may provide a relatively low cost and natural means to reduce oxidation, resulting in longer, higher quality and higher value shelf life of foods. In this study, we measured synergistic effects of red cabbage antioxidant and vacuum packaging on lipid oxidation in fresh tilapia patties using thiobarbituric acid reactive substances (TBARS) assay, peroxide value (PV), pH and color analysis. Concentrated red cabbage extract was obtained using an efficient freeze/thawed method developed in our laboratory (citation). Fresh tilapia patties were prepared with solutions containing 68 ppm of extract concentrate for each 50 gr of fish patties. Samples were stored for 15 days at refrigeration conditions (4±1°C) and analyzed interval between two days for pH, color analysis, and lipid oxidation assessments. Results show that treated and vacuum packaged samples had lower oxidation levels than controls. Lipid peroxide values on treated samples showed benefits through day 12. This work shows that synergistic effect of red cabbage antioxidant extracts and vacuum packaging may represent an inexpensive and natural method for retarding oxidative spoilage of fresh fish