Bringing Clean Energy to the Base of the Pyramid: The Interplay of Business Models, Technology, and Local Context

Social enterprises are providing affordable energy and environmentally sustainable energy to a small but growing percentage of the four billion people living on less than $2,000/year. Santa Clara University’s Global Social Benefit Incubator (GSBITM) has worked with over 60 of these enterprises and profiled them on its Energy Map website. Based on this direct experience and associated research, the authors conclude that it is the interplay among innovative business models, quality technologies tailored to localized energy markets, and appropriate interfacing with local ecosystems that allows social enterprises to go to scale. This conclusion is supported by a review of prominent enterprises including Shindulai, Solar Sister, Angaza Design, Potential Energy, Selco, Husk Power Systems, and Practical Action

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

A constitutive description of the anisotropic response of the fascia lata

In this paper we propose a constitutive model to analyze in-plane extension of goat fascia lata. We first perform a histological analysis of the fascia that shows a well-organized bi-layered arrangement of undulated collagen fascicles oriented along two well defined directions. To develop a model consistent with the tissue structure we identify the absolute and relative thickness of each layer and the orientation of the preferred directions. New data are presented showing the mechanical response in uniaxial and planar biaxial extension. The paper proposes a constitutive relation to describe the mechanical response. We provide a summary of the main ingredients of the nonlinear theory of elasticity and introduce a suitable strain-energy function to describe the anisotropic response of the fascia. We validate the model by showing good fit of the numerical results and the experimental data. Comments are included about differences and analogies between goat fascia lata and the human iliotibial band.Organismic and Evolutionary Biolog

Nodular bilateral amygdala degeneration in demented individuals

Among more than 2050 brains in our Alzheimer disease brain banks we came across three brains with well demarcated indurated white-yellow nodules in the amygdalas. Microscopically, these nodules were composed of numerous lipid-laden macrophages located in the central region surrounded by an eosinophilic hyaline-like material with minimal reactive gliosis in the periphery. Neurons within these lesions had a normal appearance but were moderately decreased in number. Beta-amyloid, tau and alpha-synuclein immunostaining revealed no abnormal deposits within the nodules. The three patients had long histories of dementia (one linked to a presenilin-1 mutation). The neuropathological diagnoses were Alzheimer disease in two of them and an unclassified tauopathy with argyrophilic grains in the third

The human iliotibial band is specialized for elastic energy storage compared with the chimp fascia lata

This study examines whether the human iliotibial band (ITB) is specialized for elastic energy storage relative to the chimpanzee fascialata (FL). To quantify the energy storage potential of these structures, we created computer models of human and chimpanzee lower limbs based on detailed anatomical dissections. We characterized the geometry andforce–length properties of the FL,tensorfascia lata (TFL) and gluteus maximus (GMax) in four chimpanzee cadavers based on measurements of muscle architecture and moment arms about the hip and knee. We used the chimp model to estimate the forces and corresponding strains in the chimp FL during bipedal walking, and compared these data with analogous estimates from a model of the human ITB, accounting for differences in body mass and lower extremity posture. We estimate that the human ITB stores 15- to 20- times more elastic energy per unit body mass and stride than the chimp FL during bipedal walking. Because chimps walk with persistent hip flexion, the TFL and portions of GMax that insert on the FL undergo smaller excursions (origin to insertion) than muscles that insert on the human ITB. Also, because a smaller fraction of GMax inserts on the chimp FL than on the human ITB, and thus its mass-normalized physiological cross-sectional area is about three times less in chimps, the chimp FL probably transmits smaller muscle forces. These data provide new evidence that the human ITB is anatomically derived compared with the chimp FL and potentially contributes to locomotor economy during bipedal locomotion.Human Evolutionary Biolog

Vitamin D status in female military personnel during combat training

Vitamin D is an essential nutrient for maintaining bone health. Recent data suggest that vitamin D and calcium supplementation might affect stress fracture incidence in military personnel. Although stress fracture is a health risk for military personnel during training, no study has investigated changes in vitamin D status in Soldiers during United States (US) Army basic combat training (BCT). This longitudinal study aimed to determine the effects of BCT on 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) levels in female Soldiers. Serum 25(OH)D and PTH were assessed in 74 fasted Soldier volunteers before and after an 8-week BCT course conducted between August and October in Columbia, South Carolina. In the total study population, 25(OH)D levels decreased (mean ± SD) from 72.9 ± 30.0 to 63.3 ± 19.8 nmol/L (P < 0.05) and PTH levels increased from 36.2 ± 15.8 to 47.5 ± 21.2 pg/mL (P < 0.05) during BCT. Ethnicity affected changes in vitamin D status (ethnicity-by-time interaction, P < 0.05); 25(OH)D decreased (P < 0.05) in both Hispanic and non-Hispanic whites, but did not change in non-Hispanic blacks. Ethnicity did not affect BCT-induced changes in PTH. These data indicate that vitamin D status in female Soldiers may decline during military training in the late summer and early autumn months in the Southeastern US. Future studies should strive to determine the impact of military clothing and seasonality on vitamin D status, as well as the functional impact of declining vitamin D status on bone health

Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.

Molecular chaperones such as Hsp40 and Hsp70 hold the androgen receptor (AR) in an inactive conformation. They are released in the presence of androgens, enabling transactivation and causing the receptor to become aggregation-prone. Here we show that these molecular chaperones recognize a region of the AR N-terminal domain (NTD), including a FQNLF motif, that interacts with the AR ligand-binding domain (LBD) upon activation. This suggests that competition between molecular chaperones and the LBD for the FQNLF motif regulates AR activation. We also show that, while the free NTD oligomerizes, binding to Hsp70 increases its solubility. Stabilizing the NTD-Hsp70 interaction with small molecules reduces AR aggregation and promotes its degradation in cellular and mouse models of the neuromuscular disorder spinal bulbar muscular atrophy. These results help resolve the mechanisms by which molecular chaperones regulate the balance between AR aggregation, activation and quality control

C9 ORF 72 expansion in a family with bipolar disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98405/1/bdi12063.pd

Diagnostic Potential of Imaging Flow Cytometry

Imaging flow cytometry (IFC) captures multichannel images of hundreds of thousands of single cells within minutes. IFC is seeing a paradigm shift from low- to high-information-content analysis, driven partly by deep learning algorithms. We predict a wealth of applications with potential translation into clinical practice

Directional Differences in the Biaxial Material Properties of Fascia Lata and the Implications for Fascia Function

Fascia is a highly organized collagenous tissue that is ubiquitous in the body, but whose function is not well understood. Because fascia has a sheet-like structure attaching to muscles and bones at multiple sites, it is exposed to different states of multi- or biaxial strain. In order to measure how biaxial strain affects fascia material behavior, planar biaxial tests with strain control were performed on longitudinal and transversely oriented samples of goat fascia lata (FL). Cruciform samples were cycled to multiple strain levels while the perpendicular direction was held at a constant strain. Structural differences among FL layers were examined using histology and SEM. Results show that FL stiffness, hysteresis, and strain energy density are greater in the longitudinal vs. transverse direction. Increased stiffness in the longitudinal layer is likely due to its greater thickness and greater average fibril diameter compared to the transverse layer(s). Perpendicular strain did not affect FL material behavior. Differential loading in the longitudinal vs. transverse directions may lead to structural changes, enhancing the ability of the longitudinal FL to transmit force, store energy, or stabilize the limb during locomotion. The relative compliance of the transverse fibers may allow expansion of underlying muscles when they contract.Organismic and Evolutionary Biolog