Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Total Internal Reflection Accounts for the Bright Color of the Saharan Silver Ant

The Saharan silver ant Cataglyphis bombycina is one of the terrestrial living organisms best adapted to tolerate high temperatures. It has recently been shown that the hairs covering the ant’s dorsal body part are responsible for its silvery appearance. The hairs have a triangular cross-section with two corrugated surfaces allowing a high optical reflection in the visible and near-infrared (NIR) range of the spectrum while maximizing heat emissivity in the mid-infrared (MIR). Those two effects account for remarkable thermoregulatory properties, enabling the ant to maintain a lower thermal steady state and to cope with the high temperature of its natural habitat. In this paper, we further investigate how geometrical optical and high reflection properties account for the bright silver color of C. bombycina. Using optical ray-tracing models and attenuated total reflection (ATR) experiments, we show that, for a large range of incidence angles, total internal reflection (TIR) conditions are satisfied on the basal face of each hair for light entering and exiting through its upper faces. The reflection properties of the hairs are further enhanced by the presence of the corrugated surface, giving them an almost total specular reflectance for most incidence angles. We also show that hairs provide an almost 10-fold increase in light reflection, and we confirm experimentally that they are responsible for a lower internal body temperature under incident sunlight. Overall, this study improves our understanding of the optical mechanisms responsible for the silver color of C. bombycina and the remarkable thermoregulatory properties of the hair coat covering the ant’s body.     

Popliteal-based filleted lower leg musculocutaneous free-flap coverage of a hemipelvectomy defect.

A 33-year-old man suffered from locally recurrent malignant fibrous histiocytoma of his left thigh unresponsive to previous excision, radiation therapy, chemotherapy, and hyperthermic treatment. He underwent radical hemipelvectomy for cure. Because of extensive tumor involvement, a free flap consisting of his distal left leg based on the popliteal artery was utilized to close the defect. Both the tibia and fibula were removed from their periosteal sheaths, and the foot was excised from the flap. The popliteal artery and vein were anastomosed to the iliac vessels. The flap survived, and the patient was discharged home after physical rehabilitation. We suggest that uninvolved portions of the distal leg may be utilized as a free flap to successfully close hemipelvectomy defects in selected patients when conventional pedicle flaps are unavailable.     

Mathematical modelling of immunity to malaria

A comparison of two epidemiological models of immunity to malaria shows that different characterizations of immunity boosted by exposure to infection generate qualitatively different results. Attempts to control disease by reducing transmission or increasing the recovery rate can produce an increase in prevalence in the compartmental model with discrete epidemiological states. However, the parasite density always decreases in response to disease control in the model with continuous epidemiological variables. Each model accounts for some epidemiological patterns. The increase in prevalence seen in the compartmental model is in accord with observed effects of variation in transmission. Parasite suppression in areas of antimalarial drug use is consistent with the effect of an increased recovery rate in the density model. Future work should combine the two approaches, perhaps by using the compartmental model over the low to moderate range of infection rates and switching to the density model at high infection rates. In any case, the validation of models needs to take account of the usage of antimalarial drugs as well as the intensity of transmission.     

Metabolic cost of walking: equation and model

Twenty years of published experience with the Workman-Armstrong equation for predicting walking VO2 is reviewed. The equation is reexpressed in currently accepted terminology, and it is shown that the equation serves well as a basic model of normal walking. Employing this model to analyze VO2/step leads to the elaboration of a three-compartment model of the metabolic cost of walking. This three-compartment model provides a rational estimate of the fraction of walking's metabolic cost that powers the actual walking movement. Doubt is expressed that "comfortable speed of walking" is definable in energy terms. It is suggested that the requirements of maintaining balance while walking may determine both the comfortable speed of walking and the curvilinearity of the relationship between ground-speed and freely chosen step frequency of walking.     

Nucleoprotein hybridization: a method for isolating specific genes as high molecular weight chromatin

We describe a new technique designed to isolate specific eukaryotic genes as native oligonucleosome fragments. The isolation method consists of hybridization of single-stranded termini of chromatin restriction fragments to complementary mercurated DNA probes, followed by isolation of the hybrids by sulfhydryl-Sepharose chromatography. SV40 minichromosomes were used to test the effectiveness of the technique. About 80% of KpnI- or BamHI-restricted and lambda exonuclease treated SV40 minichromosomes hybridized to an appropriate DNA probe after a 12-h hybridization reaction under mild conditions (0.1 M aqueous salt, 37 degrees C, pH 8). When the restricted minichromosomes were mixed with a 15-fold excess of "background" chromatin from sea urchin embryos, nucleoprotein hybridization was able to reisolate the SV40 chromatin to 88% purity with a 63% yield. This represented a 115-fold enrichment of specific genes as chromatin. Results of electron microscopy and polyacrylamide gel electrophoresis indicate that the hybridized SV40 chromatin has not lost the major chromosomal proteins characteristic of SV40 nor acquired significant amounts of protein due to exchange with background chromatin. Our experimental results show that it is currently possible to isolate repeated genes from higher eukaryotes for structural and biochemical study of the proteins involved with gene regulation.