Buckling without bending: a new paradigm in morphogenesis

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out-of-phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in-phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2d morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluid-like film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential". Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale-invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bio-inspired applications, and address how our model is and is not unique to the developing nervous system.Comment: version accepted by Physical Review

At the limits of ‘Capability’: The sexual and reproductive health of women migrant workers in Malaysia

Despite the centrality of sexual and reproductive health (SRH) to UN Sustainable Development Goals (SDGs), women migrant workers in Malaysia face an environment inimical to their SRH needs. Drawing on qualitative case study material, we present the first empirical application of the Capability Approach (CA) to explore the reproductive health needs of women migrant workers in a developing country, offering an original analysis of the capability for SRH of these women. Specifically, we explore the resources available to them; their opportunities and freedoms (‘capabilities’); and factors which mediate transformation of resources into capability sets (‘conversion factors’). While SRH information and healthcare is notionally available, women migrant workers face multiple challenges in converting resources into functionings, constraining the achievement of capability for SRH. Challenges include language barriers, personal beliefs, power relations between workers and employers and the consequences of current migration policy. We consider the scale of the challenges facing these women in securing SRH rights, the difficulties of operationalising the CA within such a setting, and the implications of our findings for the adequacy of the CA in supporting marginalised populations

An objective method for the assessment of fluid injection-induced seismicity and application to tectonically active regions in central California

Changes in seismicity rates, whether of tectonic or of induced origin, can readily be identified in regions where background rates are low but are difficult to detect in seismically active regions. We present a novel method to identify likely induced seismicity in tectonically active regions based on short-range spatiotemporal correlations between changes in fluid injection and seismicity rates. The method searches through the entire parameter space of injection rate thresholds and determines the statistical significance of correlated changes in injection and seismicity rates. Applying our method to Kern County, central California, we find that most earthquakes within the region are tectonic; however, fluid injection contributes to seismicity in four different cases. Three of these are connected to earthquake sequences with events above M4. Each of these sequences followed an abrupt increase in monthly injection rates of at least 15,000 m^3. The probability that the seismicity sequences and the abrupt changes in injection rates in Kern County coincide by chance is only 4%. The identified earthquake sequences display low Gutenberg-Richter b values of ∼0.6–0.7 and at times systematic migration patterns characteristic for a diffusive process. Our results show that injection-induced pressure perturbations can influence seismic activity at distances of 10 km or more. Triggering of earthquakes at these large distances may be facilitated by complex local geology and faults in tectonically active regions. Our study provides the first comprehensive, statistically robust assessment of likely injection-induced seismicity within a large, tectonically active region

Evaluating human cancer cell metastasis in zebrafish

BACKGROUND: In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. METHODS: Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. RESULTS: To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with invasion potential. We also demonstrate, using lung cancers, that the zebrafish model can evaluate the metastatic ability of cancer cells isolated from primary tumors. CONCLUSIONS: The zebrafish model described here offers a rapid, robust, and inexpensive means of evaluating the metastatic potential of human cancer cells. Using this model it is possible to critically evaluate whether genetic manipulation of signaling pathways affects metastasis and whether primary tumors contain metastatic cells

Automatic recognition of lactating sow behaviors through depth image processing

Manual observation and classification of animal behaviors is laborious, time-consuming, and of limited ability to process large amount of data. A computer vision-based system was developed that automatically recognizes sow behaviors (lying, sitting, standing, kneeling, feeding, drinking, and shifting) in farrowing crate. The system consisted of a low-cost 3D camera that simultaneously acquires digital and depth images and a software program that detects and identifies the sow’s behaviors. This paper describes the computational algorithm for the analysis of depth images and presents its performance in recognizing the sow’s behaviors as compared to manual recognition. The images were acquired at 6 s intervals on three days of a 21-day lactation period. Based on analysis of the 6 s interval images, the algorithm had the following accuracy of behavioral classification: 99.9% in lying, 96.4% in sitting, 99.2% in standing, 78.1% in kneeling, 97.4% in feeding, 92.7% in drinking, and 63.9% in transitioning between behaviors. The lower classification accuracy for the transitioning category presumably stemmed from insufficient frequency of the image acquisition which can be readily improved. Hence the reported system provides an effective way to automatically process and classify the sow’s behavioral images. This tool is conducive to investigating behavioral responses and time budget of lactating sows and their litters to farrowing crate designs and management practices

Effects of hydroxyapatite and PDGF concentrations on osteoblast growth in a nanohydroxyapatite-polylactic acid composite for guided tissue regeneration

The technique of guided tissue regeneration (GTR) has evolved over recent years in an attempt to achieve periodontal tissue regeneration by the use of a barrier membrane. However, there are significant limitations in the currently available membranes and overall outcomes may be limited. A degradable composite material was investigated as a potential GTR membrane material. Polylactic acid (PLA) and nanohydroxyapatite (nHA) composite was analysed, its bioactive potential and suitability as a carrier system for growth factors were assessed. The effect of nHA concentrations and the addition of platelet derived growth factor (PDGF) on osteoblast proliferation and differentiation was investigated. The bioactivity was dependent on the nHA concentration in the films, with more apatite deposited on films containing higher nHA content. Osteoblasts proliferated well on samples containing low nHA content and differentiated on films with higher nHA content. The composite films were able to deliver PDGF and cell proliferation increased on samples that were pre absorbed with the growth factor. nHA–PLA composite films are able to deliver active PDGF. In addition the bioactivity and cell differentiation was higher on films containing more nHA. The use of a nHA–PLA composite material containing a high concentration of nHA may be a useful material for GTR membrane as it will not only act as a barrier, but may also be able to enhance bone regeneration by delivery of biologically active molecules

Data production models for the CDF experiment

The data production for the CDF experiment is conducted on a large Linux PC farm designed to meet the needs of data collection at a maximum rate of 40 MByte/sec. We present two data production models that exploits advances in computing and communication technology. The first production farm is a centralized system that has achieved a stable data processing rate of approximately 2 TByte per day. The recently upgraded farm is migrated to the SAM (Sequential Access to data via Metadata) data handling system. The software and hardware of the CDF production farms has been successful in providing large computing and data throughput capacity to the experiment.Comment: 8 pages, 9 figures; presented at HPC Asia2005, Beijing, China, Nov 30 - Dec 3, 200