Constrained Emergence of Universals and Variation in Syllable Systems

A computational model of emergent syllable systems is developed based on a set of functional constraints on syllable systems and the assumption that language structure emerges through cumulative change over time. The constraints were derived from general communicative factors as well as from the phonetic principles of perceptual distinctiveness and articulatory ease. Through evolutionary optimization, the model generated mock vocabularies optimized for the given constraints. Several simulations were run to understand how these constraints might define the emergence of universals and variation in complex sound systems. The predictions were that (1) CV syllables would be highly frequent in all vocabularies evolved under the constraints; (2) syllables with consonant clusters, consonant codas and vowel onsets would occur much less frequently; (3) a relationship would exist between the number of syllable types in a vocabulary and the average word length in the vocabulary; (4) different syllable types would emerge according to, what we termed, an <EM iterative principle of syllable structure> and their frequency would be directly related to their complexity; and (5) categorical differences would emerge between vocabularies evolved under the same constraints. Simulation results confirmed these predictions and provided novel insights into why regularities and differences may occur across languages. Specifically, the model suggested that both language universals and variation are consistent with a set of functional constraints that are fixed relative to one another. Language universals reflect underlying constraints on the system and language variation represents the many different and equally-good solutions to the unique problem defined by these constraints

An unexpected alliance between stress responses to drive oncogenesis.

XBP1 is a well-characterized regulator of the unfolding protein response that is activated in response to unfolded or misfolded proteins or nutrient deprivation. The conventional wisdom is that XBP1 is activated to coordinate the unfolded protein response and promote cellular survival under stresses. A recent study provides intriguing evidence that, in triple-negative breast cancer, XBP1 plays a major role in promoting oncogenesis and cancer stem cell properties. Unexpectedly, XBP1 accomplishes this by recruiting hypoxia-inducible factor 1α and activating oncogenic transcriptional programs. This study reveals a surprising hierarchy and alliance between two stress regulators with distinct transcriptional outputs to promote an aggressive oncogenic state

Ethnicity and generation of audiences in the use of midwifery in two cities in southern Mexico.

En el sur de México la partería tiene un papel importante en la atención de la salud materna de mujeres y familias de diferentes estratos sociales. La presente investigación se enmarca en las ciudades de Felipe Carrillo Puerto y Tumben Kuxtal, donde examino procesos de construcción de públicos (según Warner, 2008) que recurren a la partería. El análisis se basa en dos tipos de prácticas de partería: parteras autónomas que ofrecen sus servicios en una ciudad turística y atraen a un público nacional e internacional, de clase media y alta (según Bourdieu). El segundo modelo de partería corresponde a las parteras tradicionales que brindan atención en la ciudad de Felipe Carrillo Puerto a un público indígena y de estratos más populares. La elección de la partería por mujeres y familias de clase media-alta se relaciona con la construcción social del gusto. Este público toma en cuenta características socialmente construidas como el regreso a “lo natural” para el cuidado de la salud, el respeto de la decisión de las mujeres sobre sus cuerpos y representaciones de la ancestralidad e indigenidad de “lo maya”.In southern Mexico, midwifery has an important role in the maternal health care of women and families from different social strata. The present research was carried out in the cities of Felipe Carrillo Puerto and Tumben Kuxtal where I examined the construction of publics through midwifery. The analysis is based on two types of midwifery practices: autonomous midwives that offer their services in a tourist city and attract a multicultural, middle class and high (sensu Bourdieu); traditional midwives of Felipe Carrillo Puerto and help an indigenous public of more popular strata. The choice of midwifery by women from upper-middle class families is related to the social construction of taste. This public takes into account socially constructed characteristics such as the return to "the natural" for health care, respect for the decision of women on their bodies and representations of the ancestrality and indigenity of "the Mayan.

Measuring impacts and risks to the public of a privately operated toll road project by considering perspectives in cost-benefit analysis

Decision making about transport infrastructure investment is based on the net impacts and risks to the community. The private sector is often involved in toll road projects, including various schemes to design, build, operate and/or finance the project either in a partnership with a host government, independently, or in some combination. Cost-Benefit Analysis of a privately operated toll road require careful allocations of project impacts, in order to properly reflect the net impacts and risks to the community from the host government’s perspective. This study investigates whether alternative assumptions are valid from differing perspectives, when toll roads are delivered and operated privately rather than by a host government. Treatments of tolls and other toll road project related payments are considered from different perspectives. Cost-Benefit Analysis is conducted for a synthesised toll tunnel project case by considering alternating treatments of some impacts. This leads to the exploration of analyses outcomes when the treatment of tolls differ when two perspectives of “toll as a transfer payment” and “toll as an end user cost” are considered. Various scenarios are explored including public versus private operations. The Monte Carlo simulation approach is used to account the risks of variables in the analysis. The synthesised case study revealed that, for privately operated toll roads, treating toll charges as a transfer payment, and alternatively as an end user cost, can both be valid approaches but from two perspectives. Moreover, the analysis outcomes under different perspectives are particularly helpful to make decisions on the basis of the impacts and risks solely from the perspective of the host government. The proposed methodology can examine various scenarios other than the ones examined in this study and is extremely useful in the project evaluation of privately operated toll road projects

Ocular manifestations and pathology of adult T-cell leukemia/lymphoma associated with human T-lymphotropic virus type 1

The human T-cell lymphotropic virus type 1 (HTLV-1), endemic in defined geographical areas around the world, is recognized as the etiologic agent of adult T-cell leukemia/lymphoma (ATL), or HTLV-1. ATL is a rare adult onset T-cell malignancy that is characterized by the presence of ATL flower cells with T-cell markers, HTLV-1 antibodies in the serum, and monoclonal integration of HTLV-1 provirus in affected cells. Ocular manifestations associated with HTLV-1 virus infection have been reported and include HTLV-1 uveitis and keratoconjunctivitis sicca, but reports of ocular involvement in ATL are exceedingly rare. This article describes the ocular manifestations and pathology of ATL. We also report for the first time a case of a 34-year-old male with systemic ATL and prominent atypical lymphoid cell infiltration in the choroid. To our knowledge, this is the first report defining prominent choroidal involvement as a distinct ocular manifestation of ATL. ATL may masquerade as a variety of other conditions, and molecular techniques involving microdissection and PCR have proven to be critical diagnostic tools. International collaboration will be needed to better understand the presentation and diagnosis of this rare malignancy

Human Papillomavirus Vaccine Uptake After a Tailored, Online Educational Intervention for Female University Students: A Randomized Controlled Trial

Background: Educational interventions may be a strategy to increase human papillomavirus (HPV) vaccination among female university students, but studies to date have shown mixed results. This study evaluated the effect of MeFirst, an individually tailored, online educational intervention, on HPV vaccine-related knowledge, vaccination intention, and uptake among previously unvaccinated female university students. Methods: All female students aged 18?26 years who reported being unvaccinated against HPV at a midwestern university were invited via email to enroll. Participants completed an online survey that assessed baseline HPV vaccine-related knowledge, attitudes and vaccination intention. Participants (n?=?661) were then randomized to receive either an educational website automatically tailored to their baseline survey responses (MeFirst intervention) or a standard CDC information factsheet on HPV vaccine (control). Vaccine uptake and repeat knowledge and attitude measures were assessed with online surveys 3 months following the intervention and analyzed using logistic regression models. Results: HPV vaccine uptake was similar in both the MeFirst and control groups at 3 months following the intervention (p?=?0.98). Three months after the intervention, the proportion of participants with high knowledge regarding HPV vaccination increased from baseline (32% to 50%; p?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140136/1/jwh.2015.5251.pd

LTMG: a novel statistical modeling of transcriptional expression states in single-cell RNA-Seq data

A key challenge in modeling single-cell RNA-seq data is to capture the diversity of gene expression states regulated by different transcriptional regulatory inputs across individual cells, which is further complicated by largely observed zero and low expressions. We developed a left truncated mixture Gaussian (LTMG) model, from the kinetic relationships of the transcriptional regulatory inputs, mRNA metabolism and abundance in single cells. LTMG infers the expression multi-modalities across single cells, meanwhile, the dropouts and low expressions are treated as left truncated. We demonstrated that LTMG has significantly better goodness of fitting on an extensive number of scRNA-seq data, comparing to three other state-of-the-art models. Our biological assumption of the low non-zero expressions, rationality of the multimodality setting, and the capability of LTMG in extracting expression states specific to cell types or functions, are validated on independent experimental data sets. A differential gene expression test and a co-regulation module identification method are further developed. We experimentally validated that our differential expression test has higher sensitivity and specificity, compared with other five popular methods. The co-regulation analysis is capable of retrieving gene co-regulation modules corresponding to perturbed transcriptional regulations. A user-friendly R package with all the analysis power is available at https://github.com/zy26/LTMGSCA

Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy

Background: Diabetic nephropathy (DN) is a major complication of diabetes and the main cause of end-stage renal disease. Extracellular vesicles (EVs) are small cell-derived vesicles that can alter disease progression by microRNA (miRNA) transfer. Methods: In this study, we aimed to characterize the cellular origin and miRNA content of EVs in plasma samples of type 2 diabetes patients at various stages of DN. Type 2 diabetes patients were classified in three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. The concentration and cellular origin of plasma EVs were measured by flow cytometry. A total of 752 EV miRNAs were profiled in 18 subjects and differentially expressed miRNAs were validated. Results: Diabetic patients with microalbuminuria and/or macroalbuminuria showed elevated concentrations of total EVs and EVs from endothelial cells, platelets, leucocytes and erythrocytes compared with diabetic controls. miR-99a-5p was upregulated in macroalbuminuric patients compared with normoalbuminuric and microalbuminuric patients. Transfection of miR-99a-5p in cultured human podocytes downregulated mammalian target of rapamycin (mTOR) protein expression and downregulated the podocyte injury marker vimentin. Conclusions: Type 2 diabetes patients with microalbuminuria and macroalbuminuria display differential EV profiles. miR-99a-5p expression is elevated in EVs from macroalbuminuria and mTOR is its validated mRNA target

A fast-degrading thiol–acrylate based hydrogel for cranial regeneration

Successful regeneration of the cranium in patients suffering from cranial bone defects is an integral step to restore craniofacial function. However, restoration of craniofacial structure has been challenging due to its complex geometry, limited donor site availability, and poor graft integration. To address these problems, we investigated the use of a thiol–acrylate hydrogel as a cell carrier to facilitate cranial regeneration. Thiol–acrylate hydrogels were formulated with 5–15 wt% poly(ethylene glycol)-diacrylate (PEGDA) and 1–9 mm dithiothreitol (DTT). The degradation rate, swelling ratio, and shear modulus of the resulting hydrogel were first characterized. Then, pre-osteoblast-like cells (MC3T3-E1) were encapsulated in the hydrogel and cultured for up to 21 d. Our results demonstrate that compared to samples formulated from 15 wt% PEGDA, 5 wt% PEGDA samples showed lower storage modulus at day 10 (0.7 kPa versus 8.3 kPa), 62.7% higher in weight change after soaking for 10 d. While the 5 wt% PEGDA group showed an 85% weight loss between day 10 and 21, the 15 wt% PEGDA group showed a 5% weight gain in the same time period. Cell viability with 15 wt% PEGDA and 5 mm DTT hydrogel decreased by 41.3% compared to 5 wt% PEGDA and 5mM DTT gel at day 7. However, histological analysis of cells after 21 d in culture revealed that they had pericellular mineral deposition indicating that the cells were differentiating into osteoblasts lineage in all experimental groups. This study shows that thiol–acrylate hydrogels can be tailored to achieve different degradation rates, in order to enhance cell viability and differentiation. Thus, the findings of this study provide a fundamental understanding for the application of thiol–acrylate hydrogels in cranial bone regeneration

Harmonizing national abortion and pregnancy prevention laws and policies for sexual violence survivors with the Maputo Protocol

In April 2016, the Population Council, the World Health Organization (WHO), and the International Consortium for Emergency Contraception (ICEC) convened a three-day regional technical meeting aimed at helping participating countries meet their obligations under the Maputo Protocol to protect and promote the reproductive health rights of women and girls, with a special emphasis on survivors of sexual and intimate partner violence. Participants included representatives from six countries in sub-Saharan Africa—Botswana, Ethiopia, Kenya, Malawi, Rwanda, and Zambia—as well as international and regional experts on reproductive health, law, and human rights. Presentations and discussions focused primarily on the prevention and management of pregnancy in the context of sexual violence and intimate partner violence, as well as the broader requirements of Maputo relating to emergency contraception and safe abortion services. The regional meeting was the first activity in a joint project of technical assistance by the Population Council, WHO and ICEC, aimed at strengthening access to emergency contraception and safe abortion for survivors of sexual violence within the context of comprehensive post-rape care