Bipedial Locomotion Up Sandy Slopes: Systematic Experiments Using Zero Moment Point Methods

Bipedal robotic locomotion in granular media presents a unique set of challenges at the intersection of granular physics and robotic locomotion. In this paper, we perform a systematic experimental study in which biped robotic gaits for traversing a sandy slope are empirically designed using Zero Moment Point (ZMP) methods. We are able to implement gaits that allow our 7 degree-of-freedom planar walking robot to ascend slopes with inclines up to 10°. Firstly, we identify a given set of kinematic parameters that meet the ZMP stability criterion for uphill walking at a given angle. We then find that further relating the step lengths and center of mass heights to specific slope angles through an interpolated fit allows for significantly improved success rates when ascending a sandy slope. Our results provide increased insight into the design, sensitivity and robustness of gaits on granular material, and the kinematic changes necessary for stable locomotion on complex media

Coexpression of Two Functional Odor Receptors in One Neuron

SummaryOne of the most fundamental tenets in the field of olfaction is that each olfactory receptor neuron (ORN) expresses a single odorant receptor. However, the one receptor-one neuron principle is difficult to establish rigorously. Here we construct a receptor-to-neuron map for an entire olfactory organ in Drosophila and find that two receptor genes are coexpressed in one class of ORN. Both receptors are functional in an in vivo expression system, they are only 16% identical in amino acid sequence, and the genes that encode them are unlinked. Most importantly, their coexpression has been conserved for >45 million years. Expression of multiple odor receptors in a cell provides an additional degree of freedom for odor coding

Targeting Fatty Acid Reprogramming Suppresses CARM1-expressing Ovarian Cancer

The arginine methyltransferase CARM1 exhibits high expression levels in several human cancers, with the trend also observed in ovarian cancer. However, therapeutic approaches targeting tumors that overexpress CARM1 have not been explored. Cancer cells exploit metabolic reprogramming such as fatty acids for their survival. Here we report that CARM1 promotes monounsaturated fatty acid synthesis and fatty acid reprogramming represents a metabolic vulnerability for CARM1-expressing ovarian cancer. CARM1 promotes the expression of genes encoding rate-limiting enzymes of de novo fatty acid metabolism such as acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FASN). In addition, CARM1 upregulates stearoyl-CoA desaturase 1 (SCD1) that produces monounsaturated fatty acid by desaturation. Thus, CARM1 enhances de novo fatty acids synthesis which was subsequently utilized for synthesis of monounsaturated fatty acids. Consequently, inhibition of SCD1 suppresses the growth of ovarian cancer cells in a CARM1 status-dependent manner, which was rescued by the addition of monounsaturated fatty acids. Consistently, CARM1-expressing cells were more tolerant to the addition of saturated fatty acids. Indeed, SCD1 inhibition demonstrated efficacy against ovarian cancer in both orthotopic xenograft and syngeneic mouse models in a CARM1-dependent manner. In summary, our data show that CARM1 reprograms fatty acid metabolism and targeting SCD1 through pharmacological inhibition can serve as a potent therapeutic approach for CARM1-expressing ovarian cancers. Significance: CARM1 reprograms fatty acid metabolism transcriptionally to support ovarian cancer growth by producing monounsaturated fatty acids, supporting SCD1 inhibition as a rational strategy for treating CARM1-expressing ovarian cancer

Bipedial Locomotion Up Sandy Slopes: Systematic Experiments Using Zero Moment Point Methods

Bipedal robotic locomotion in granular media presents a unique set of challenges at the intersection of granular physics and robotic locomotion. In this paper, we perform a systematic experimental study in which biped robotic gaits for traversing a sandy slope are empirically designed using Zero Moment Point (ZMP) methods. We are able to implement gaits that allow our 7 degree-of-freedom planar walking robot to ascend slopes with inclines up to 10°. Firstly, we identify a given set of kinematic parameters that meet the ZMP stability criterion for uphill walking at a given angle. We then find that further relating the step lengths and center of mass heights to specific slope angles through an interpolated fit allows for significantly improved success rates when ascending a sandy slope. Our results provide increased insight into the design, sensitivity and robustness of gaits on granular material, and the kinematic changes necessary for stable locomotion on complex media

Physician communication styles in initial consultations for hematological cancer

Objective To characterize practices in subspecialist physicians’ communication styles, and their potential effects on shared decision-making, in second-opinion consultations. Methods Theme-oriented discourse analysis of 20 second-opinion consultations with subspecialist hematologist-oncologists. Results Physicians frequently “broadcasted” information about the disease, treatment options, relevant research, and prognostic information in extended, often-uninterrupted monologues. Their communicative styles had one of two implications: conveying options without offering specific recommendations, or recommending one without incorporating patients’ goals and values into the decision. Some physicians, however, used techniques that encouraged patient participation. Conclusions Broadcasting may be a suboptimal method of conveying complex treatment information in order to support shared decision-making. Interventions could teach techniques that encourage patient participation. Practice Implications Techniques such as open-ended questions, affirmations of patients’ expressions, and pauses to check for patient understanding can mitigate the effects of broadcasting and could be used to promote shared decision-making in information-dense subspecialist consultations.Other Research Uni

Targeting the Mevalonate Pathway Suppresses ARID1A-Inactivated Cancers by Promoting Pyroptosis

ARID1A, encoding a subunit of the SWI/SNF complex, is mutated in ∼50% of clear cell ovarian carcinoma (OCCC) cases. Here we show that inhibition of the mevalonate pathway synergizes with immune checkpoint blockade (ICB) by driving inflammasome-regulated immunomodulating pyroptosis in ARID1A-inactivated OCCCs. SWI/SNF inactivation downregulates the rate-limiting enzymes in the mevalonate pathway such as HMGCR and HMGCS1, which creates a dependence on the residual activity of the pathway in ARID1A-inactivated cells. Inhibitors of the mevalonate pathway such as simvastatin suppresses the growth of ARID1A mutant, but not wild-type, OCCCs. In addition, simvastatin synergizes with anti-PD-L1 antibody in a genetic OCCC mouse model driven by conditional Arid1a inactivation and in a humanized immunocompetent ARID1A mutant patient-derived OCCC mouse model. Our data indicate that inhibition of the mevalonate pathway simultaneously suppresses tumor cell growth and boosts antitumor immunity by promoting pyroptosis, which synergizes with ICB in suppressing ARID1A-mutated cancers

Carbon budget of the Harvard Forest Long- Term Ecological Research site: pattern, process, and response to global change

How, where, and why carbon (C) moves into and out of an ecosystem through time are long- standing questions in biogeochemistry. Here, we bring together hundreds of thousands of C- cycle observations at the Harvard Forest in central Massachusetts, USA, a mid- latitude landscape dominated by 80- 120- yr- old closed- canopy forests. These data answered four questions: (1) where and how much C is presently stored in dominant forest types; (2) what are current rates of C accrual and loss; (3) what biotic and abiotic factors contribute to variability in these rates; and (4) how has climate change affected the forest- s C cycle? Harvard Forest is an active C sink resulting from forest regrowth following land abandonment. Soil and tree biomass comprise nearly equal portions of existing C stocks. Net primary production (NPP) averaged 680- 750 g C·m- 2·yr- 1; belowground NPP contributed 38- 47% of the total, but with large uncertainty. Mineral soil C measured in the same inventory plots in 1992 and 2013 was too heterogeneous to detect change in soil- C pools; however, radiocarbon data suggest a small but persistent sink of 10- 30 g C·m- 2·yr- 1. Net ecosystem production (NEP) in hardwood stands averaged ~300 g C·m- 2·yr- 1. NEP in hemlock- dominated forests averaged ~450 g C·m- 2·yr- 1 until infestation by the hemlock woolly adelgid turned these stands into a net C source. Since 2000, NPP has increased by 26%. For the period 1992- 2015, NEP increased 93%. The increase in mean annual temperature and growing season length alone accounted for ~30% of the increase in productivity. Interannual variations in GPP and NEP were also correlated with increases in red oak biomass, forest leaf area, and canopy- scale light- use efficiency. Compared to long- term global change experiments at the Harvard Forest, the C sink in regrowing biomass equaled or exceeded C cycle modifications imposed by soil warming, N saturation, and hemlock removal. Results of this synthesis and comparison to simulation models suggest that forests across the region are likely to accrue C for decades to come but may be disrupted if the frequency or severity of biotic and abiotic disturbances increases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/3/ecm1423_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/2/ecm1423-sup-0001-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163495/1/ecm1423.pd

National Mass Drug Administration Costs for Lymphatic Filariasis Elimination

Lymphatic filariasis (LF), commonly known as elephantiasis, is a profoundly disfiguring parasitic disease caused by thread-like nematode worms. This disease can often be disabling, thus reducing the potential productivity of the affected individuals. The WHO places the number of people at risk in 83 countries at 1.307 billion. This study was undertaken in seven countries—Burkina Faso, Ghana, Egypt, Tanzania, the Philippines, the Dominican Republic, and Haiti—using a common protocol to determine the costs of mass drug administration (MDA) programs to interrupt transmission of infection with LF, because there is lack of sufficient information about the costs of these programs. The results demonstrate that LF MDA is affordable and relatively inexpensive when compared to other public health programs. In the context of initiatives for integrating programs for the control and elimination of neglected tropical diseases, this study adds specifically to the relatively scarce body of information about the costs of MDA programs for LF. It also adds to the general knowledge about the application of methods that can be used to estimate the costs and cost-effectiveness of an integrated approach