Longitudinal Tibia Stress Fracture Risk During High-Volume Training: A Multiscale Modeling Pipeline Incorporating Bone Remodeling.

Tibia stress fractures are prevalent during high-intensity training, yet a mechanistic model linking longitudinal training intensity, bone health, and long-term injury risk has yet to be demonstrated. The objective of this study was to develop and validate a multiscale model of gross and tissue level loading on the tibia including bone remodeling on a timescale of week. Peak tensile tibial strain (3517 μstrain) during 4 m/s running was below injury thresholds, and the peak anteromedial tibial strain (1248 μstrain) was 0.

Investigation on the Microscopic/Macroscopic Mechanical Properties of a Thermally Annealed Nafion Membrane.

The Nafion electrolyte membrane, which provides a proton pathway, is an essential element in fuel cell systems. Thermal treatment without additional additives is widely used to modify the mechanical properties of the membrane, to construct reliable and durable electrolyte membranes in the fuel cell. We measured the microscopic mechanical properties of thermally annealed membranes using atomic force microscopy with the two-point method.

Series of M-MOF-184 (M = Mg, Co, Ni, Zn, Cu, Fe) Metal-Organic Frameworks for Catalysis Cycloaddition of CO.

In light of the chemical exploitation of CO, new reusable materials for efficiently catalyzing the cycloaddition of CO and epoxides under moderate conditions are needed. Herein, a new series of isostructural metal-organic frameworks (MOFs) M(EDOB) [EDOB = 4,4'-(ethyne-1,2-diyl)bis(2-oxidobenzoate), M = Mg, Ni, Co, Zn, Cu, Fe], known as M-MOF-184, analogous to a well-studied MOF-74 structure, were synthesized and fully characterized. The M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks exhibit accessible mesopore channels (24 Å) and high porosity.

'Seeing' Strain in Soft Materials.

Several technologies can be used for measuring strains of soft materials under high rate impact conditions. These technologies include high speed tensile test, split Hopkinson pressure bar test, digital image correlation and high speed X-ray imaging. However, none of these existing technologies can produce a continuous 3D spatial strain distribution in the test specimen.

Dominant B-cell epitopes from cancer/stem cell antigen SOX2 recognized by serum samples from cancer patients.

Human sex determining region Y-box 2 (SOX2) is an important transcriptional factor involved in the pluripotency and stemness of human embryonic stem cells. SOX2 plays important roles in maintaining cancer stem cell activities of melanoma and cancers of the brain, prostate, breast, and lung. SOX2 is also a lineage survival oncogene for squamous cell carcinoma of the lung and esophagus.

Enhancing whole-tumor cell vaccination by engaging innate immune system through NY-ESO-1/dendritic cell interactions.

NY-ESO-1 is a cancer/germline antigen (Ag) with distinctively strong immunogenicity. We have previously demonstrated that NY-ESO-1 serves as an endogenous adjuvant by engaging dendritic cell (DC)-surface receptors of calreticulin (CRT) and toll-like receptor (TLR) 4. In the present study, NY-ESO-1 was investigated for its immunomodulatory roles as a molecular adjuvant in whole-tumor cell vaccines using the Renca kidney cancer model.

Nm23-h1 indirectly promotes the survival of acute myeloid leukemia blast cells by binding to more mature components of the leukemic clone.

Nm23-H1 plays complex roles in the development of diverse cancers including breast carcinoma, high-grade lymphomas, and acute myeloid leukemia (AML). In the case of AML and lymphomas, serum Nm23-H1 protein is elevated with the highest levels correlating with poorest prognosis. A recent study identified that this association is most likely causal in AML and that Nm23-H1 acts as an AML cell survival factor.

The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice.

Current experimental models of blast injuries used to study blast-induced neurotrauma (BINT) vary widely, which makes the comparison of the experimental results extremely challenging. Most of the blast injury models replicate the ideal Friedländer type of blast wave, without the capability to generate blast signatures with multiple shock fronts and refraction waves as seen in real-life conditions; this significantly reduces their clinical and military relevance. Here, we describe the pathophysiological consequences of graded blast injuries and BINT generated by a newly developed, highly controlled, and reproducible model using a modular, multi-chamber shock tube capable of tailoring pressure wave signatures and reproducing complex shock wave signatures seen in theater.

Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo.

Purpose: The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has multiple antitumor effects against a variety of human cancers.

Experimental Design: We treated several anaplastic and papillary thyroid cancer cell lines with SAHA to determine if it could inhibit the growth of these cells in vitro and in vivo.

Results: SAHA effectively inhibited 50% clonal growth of the anaplastic thyroid cancer cell lines, ARO and FRO, and the papillary thyroid cancer cell line, BHP 7-13, at 1.

Vitamin D compounds: activity against microbes and cancer.

Vitamin D3 is produced in skin and is sequentially metabolized by the liver and kidney to the biologically active form 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is a seco-steroid hormone that regulates calcium homeostasis within the body. The genomic actions of 1,25(OH)2D3 are modulated through the vitamin D receptor (VDR).

Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene.

Lipid kinase PIK3CA mutations have been described in several cancers. They clustered in two 'hot spots' located in helical (exon 9) and kinase (exon 20) domains associated with increased kinase activity strongly suggesting oncogenic potential. Mutational analysis of previously unexamined tumors showed an amino acid change from threonine to alanine (T1025A) in exon 20 in one of 28 endometrial cancer samples and 6 endometrial cell lines.

Vitamin D compounds in leukemia.

The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D3,] possess in vitro multiple anti-cancer activities including growth arrest, induction of apoptosis and differentiation of a variety of different types of malignant cells. However, its use as a therapeutic agent is hindered by its calcemic effects. Analogs of 1,25(OH)(2)D3 have enhanced anti-tumor activity, with reduced calcemic effects.

The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs.

We and others have demonstrated expression of the aldo-keto reductase AKR1C3 in myeloid leukemia cell lines and that inhibitors of the enzyme, including nonsteroidal anti-inflammatory drugs (NSAIDs), promote HL-60 differentiation in response to all-trans retinoic acid (ATRA) and 1alpha,25-dihydroxyvitamin D3 (D3). Here, we demonstrate that overexpression of AKR1C3 reciprocally desensitizes HL-60 cells to ATRA and D3, thus confirming the enzyme as a novel regulator of cell differentiation. AKR1C3 possesses marked 11-ketoreductase activity converting prostaglandin (PG) D2 to PGF2alpha.

Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells.

Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for clinical depression and a range of anxiety-related disorders. They are well tolerated over extended periods with more than 50 million people worldwide benefiting from their use. Here we show that 3 structurally distinct SSRIs--fluoxetine, paroxetine, and citalopram--act directly on Burkitt lymphoma (BL) cells to trigger rapid and extensive programmed cell death.