Conformational deformation of a multi-jointed elastic loop.

A new class of deformation is presented for a planar loop structure made up of slender elastic bodies and joints. In demonstrating the circumferential shortening of the multi-jointed elastic loop, diverse three-dimensional (3D) deformations emerge through piecewise deflections and discrete rotations. These 3D morphologies correspond to conformations of molecular ring systems. Through image processing, the 3D reconstructions of the deformed structures are characterized by number, geometry, and initial imperfections of the body segments. We elucidate from measurements that the conformational deformation without self-stress results from a cyclical assembly of compressive bending of elastic bodies with high shear rigidity. The mechanical insights gained may apply in controlling the polymorphism exhibited by the cyclical structures across scales.

Potentiated antitumor effects of APS001F/5-FC combined with anti-PD-1 antibody in a CT26 syngeneic mouse model.

APS001F is a strain of Bifidobacterium longum genetically engineered to express cytosine deaminase that converts 5-fluorocytosine (5-FC) to 5-fluorouracil. In the present study, antitumor effects of APS001F plus 5-FC (APS001F/5-FC) in combination with anti-PD-1 monoclonal antibody were investigated using a CT26 syngeneic mouse model. Both of dosing of APS001F/5-FC before and after anti-PD-1 mAb in the combination dosing exhibited antitumor effects as well as prolonged survival over the nontreated control. The survival rate in the combination therapy significantly increased over the monotherapy with APS001F/5-FC and that with anti-PD-1 mAb. Regulatory T cells among CD4+ T cells in tumor decreased in the combination therapy, while the ratio of CD8+ T cells was maintained in all groups. Taken these results together, APS001F/5-FC not only demonstrates a direct antitumor activity, but also immunomodulatory effects once localized in the hypoxic region of the tumor, which allows anti-PD-1 mAb to exert potentiated antitumor effects.

Bioarchaeological evidence of decapitation from Pacopampa in the northern Peruvian highlands.

Little is known about the precise date of the emergence of decapitation in a ritual context and the presence of systematic postmortem modification patterns in the ancient Central Andes. The ceremonial complex at Pacopampa in the northern Peruvian highlands provides early osteological evidence of decapitation in six individuals dating to the latter half of the Late-Final Formative Periods (500-50 BC) and to the Early Cajamarca Period (AD 200-450). Based on osteological evidence, and when taken together with archaeological settings and settlement patterns, researchers can be certain that those whose heads were disembodied were not likely to have been involved in organized battles. In addition, the similarities in the cut-mark distribution, direction, and cross-sectional morphology of each individual's remains, as well as the characteristics of selected individuals, imply that the decapitated individuals were carefully prepared using a standardized method and that those who modified the heads may have been professional decapitators. This study offers indisputable bioarchaeological evidence of ritualistic offerings of human skulls and systematic postmortem modification patterns, which is consistent with a contemporaneous iconographic motif of decapitation and extends the chronology of this practice back to the Formative Period in the northern Peruvian highlands.

Prevalence of cribra orbitalia in Pacopampa during the formative period in Peru.

Cribra orbitalia is characterized by an aggregation of small apertures in the orbital roof in response to marrow hypertrophy. This pathological change is indicative of biological stress during youth. We examined the prevalence of this lesion in Pacopampa, a ceremonial center of the formative period, located in the northern highlands of Peru. Using this evaluation of cribra orbitalia, we reconstructed aspects of the population's health and nutritional status during the formation of Andean civilization. We examined 41 orbits of 27 adult individuals (13 males, 14 females) and recorded the macroscopic presence or absence of cribra orbitalia. The presence or absence of cribra orbitalia was the same bilaterally for all 14 individuals having both orbits preserved. The pathology was present in two of the 13 males (15.4%), one of the 14 (7.1%) females, and three of 27 individuals (11.1%) for both sexes combined. There was no difference in the frequency between sexes. The prevalence of cribra orbitalia was found to be lower in Pacopampa than in the comparative data of coastal populations. It is reasonable to assume that the increase in social complexity in Pacopampa was probably unrelated to the decline in overall health of the people.

Pacopampa: Early evidence of violence at a ceremonial site in the northern Peruvian highlands.

OBJECTIVES: Pacopampa, a ceremonial complex in Peru's northern highlands, reveals early evidence of trauma in the Middle to Late Formative Period coinciding with the emergence of social stratification in the area. We examine the prevalence of trauma in human remains found at the site and present evidence of the circumstances surrounding the deaths of individuals who lived during the early stages of Andean civilization. MATERIALS AND METHODS: The materials are the remains of 104 individuals (38 non-adult and 66 adult) from the Middle to Late Formative Periods. We explored trauma macroscopically and recorded patterns based on skeletons' locations, age at death, sex, social class, and chronology. RESULTS: We detected trauma in remains over the Middle to Late Formative Periods. While the prevalence of trauma was minimal in the Middle Formative Period, skeletons from the subsequent era exhibit more severe disturbances. However, all the skeletons show signs of healing and affected individuals experienced a low degree of trauma. DISCUSSION: Given the archaeological context (the remains were recovered from sites of ceremonial practices), as well as the equal distribution of trauma among both sexes and a lack of defensive architecture, it is plausible that rituals, rather than organized warfare or raids, caused most of the exhibited trauma. Pacopampa was home to a complex society founded on ritual activity in a ceremonial center: this is indicated by the presence of ritual violence in a society that built impressively large, ceremonial architecture and developed social stratification without any political control of surplus agricultural goods.

A case study of a high-status human skeleton from Pacopampa in Formative Period Peru.

The Pacopampa site is located in the northern highlands of Peru and is an archaeological site belonging to the Formative Period (2500-1 BC). The excavation of the Pacopampa site yielded unusual human skeletons from the main platform of a ceremonial center of the site during the 2009 field season. The skeletal remains were associated with a pair of gold earplugs, a pair of gold earrings, and shell objects. This specimen is possibly a female aged 20-39 years. Detailed examination of the neurocranium revealed the presence of artificial cranial deformation with decreased cranial length, increased cranial breadth, and lateral bulging of the parietal bones. The estimated stature of this individual was 162 cm, which is about 15 cm higher than that of contemporary females of Pacopampa and about 20-25 cm higher than that of other Formative Period sites in northern Peru. The peculiarity of this individual, detected not only in the cultural artifacts but also in the physical features, is possible evidence for social stratification in the Formative Period.

Development of cystic embryoid bodies with visceral yolk-sac-like structures from mouse embryonic stem cells using low-adherence 96-well plate.

Cystic embryoid bodies with visceral yolk-sac-like structure (cystic EB-Vs) are used as a model for the study of early extraembryonic tissue formation containing visceral endoderm-like derivatives. In this study, we optimized the cell density of embryonic stem (ES) cells for developing cystic EB-Vs in a low-adherence 96-well plate. When ES cells were seeded at a density of 4000 cells/well, the cystic EB-Vs were most efficiently developed from ES cells via forming multicellular spherical aggregates called embryoid bodies (EBs). The suspension culture in the low-adherence plate was preferable for developing EBs into cystic EB-Vs rather than the attachment culture in the plate coated with 0.1% gelatin. The seeding cell density of 4000 cells/well was always superior to 1000 cells/well in the efficiency of cystic EB-V development. Because the high-cell density culture generally raises the limitation of oxygen and nutrient supplies, we investigated the effects of low-oxygen and low-nutrient conditions on the development of cystic EB-Vs. It was found that low oxygen tension was not a factor for promoting the development of cystic EB-Vs. It was suggested that a low-nutrient medium is preferred for developing cystic EB-Vs rather than a sufficient-nutrient medium. In conclusion, the suspension culture in the low-adherence 96-well plate seeded with 4000 ES cells/well was optimum for developing cystic EB-Vs. The low-nutrient condition may be one of the factors for promoting the development of cystic EB-Vs.