Rapid creation and quantitative monitoring of high coverage shRNA libraries.

Short hairpin RNA libraries are limited by low efficacy of many shRNAs and by off-target effects, which give rise to false negatives and false positives, respectively. Here we present a strategy for rapidly creating expanded shRNA pools (approximately 30 shRNAs per gene) that are analyzed by deep sequencing (EXPAND). This approach enables identification of multiple effective target-specific shRNAs from a complex pool, allowing a rigorous statistical evaluation of true hits

Anomalous Noise in the Pseudogap Regime of YBa2_2Cu3_3O7−δ_{7-\delta}

An unusual noise component is found near and below about 250 K in the normal state of underdoped YBCO and Ca-YBCO films. This noise regime, unlike the more typical noise above 250 K, has features expected for a symmetry-breaking collective electronic state. These include large individual fluctuators, a magnetic sensitivity, and aging effects. A possible interpretation in terms of fluctuating charge nematic order is presented.Comment: 4 pages, 4 figure

Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats.

Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation. In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal's face. Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector. Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to about 30 °C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, thereby maintaining a role for TRPV1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat Trpv1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs and moles), supporting a close phylogenetic relationship with bats. These findings reveal a novel molecular mechanism for physiological tuning of thermosensory nerve fibres

Sparse random networks for communication-efficient federated learning

One main challenge in federated learning is the large communication cost of ex-changing weight updates from clients to the server at each round. While prior work has made great progress in compressing the weight updates through gradient compression methods, we propose a radically different approach that does not update the weights at all. Instead, our method freezes the weights at their initial random values and learns how to sparsify the random network for the best performance. To this end, the clients collaborate in training a stochastic binary mask to find the optimal sparse random network within the original one. At the end of the training, the final model is a sparse network with random weights – or a sub-network inside the dense random network. We show improvements in accuracy, communication (less than 1 bit per parameter (bpp)), convergence speed, and final model size (less than 1 bpp) over relevant baselines on MNIST, EMNIST, CIFAR- 10, and CIFAR-100 datasets, in the low bitrate regime

Coherent oscillations and incoherent tunnelling in one - dimensional asymmetric double - well potential

For a model 1d asymmetric double-well potential we calculated so-called survival probability (i.e. the probability for a particle initially localised in one well to remain there). We use a semiclassical (WKB) solution of Schroedinger equation. It is shown that behaviour essentially depends on transition probability, and on dimensionless parameter which is a ratio of characteristic frequencies for low energy non-linear in-well oscillations and inter wells tunnelling. For the potential describing a finite motion (double-well) one has always a regular behaviour. For the small value of the parameter there is well defined resonance pairs of levels and the survival probability has coherent oscillations related to resonance splitting. However for the large value of the parameter no oscillations at all for the survival probability, and there is almost an exponential decay with the characteristic time determined by Fermi golden rule. In this case one may not restrict oneself to only resonance pair levels. The number of perturbed by tunnelling levels grows proportionally to the value of this parameter (by other words instead of isolated pairs there appear the resonance regions containing the sets of strongly coupled levels). In the region of intermediate values of the parameter one has a crossover between both limiting cases, namely the exponential decay with subsequent long period recurrent behaviour.Comment: 19 pages, 7 figures, Revtex, revised version. Accepted to Phys. Rev.

Stem cells, cancer, and cancer stem cells

Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells'-rare cells with indefinite potential for self-renewal that drive tumorigenesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62862/1/414105a0.pd

IJED support for eating disorders research in the time of COVID‐19

This editorial reports on an anonymous survey question posed to eating disorders researchers about changes the International Journal of Eating Disorders (IJED) should implement to support the eating disorders research community affected by COVID‐19. The editorial accompanies an IJED article that details responses to the larger survey focusing more broadly on COVID‐19‐related research disruptions. Survey invitations were sent to editorial board members of eating disorders journals, members of eating disorder scientific organizations (e.g., Eating Disorders Research Society), and individuals who provided at least three IJED reviews in the prior 12 months. We reviewed the responses of 187 participants and identified three categories of changes that: (a) had already been implemented by the journal, (b) cannot be implemented because they fall outside the scope of IJED, or (c) will be implemented in coming weeks or months. The latter category includes publishing topical COVID‐19 papers, making some COVID‐19‐related content available open access, revising statistical guidelines, and issuing author guidance on reporting protocol changes caused by COVID‐19‐related disruptions. IJED recognizes the disruptive impacts that COVID‐19 has on all activities in our field, including clinical work, teaching, and advocacy, and is committed to supporting authors during this difficult time while striving to publish high‐quality research

Functional kernel estimators of conditional extreme quantiles

We address the estimation of "extreme" conditional quantiles i.e. when their order converges to one as the sample size increases. Conditions on the rate of convergence of their order to one are provided to obtain asymptotically Gaussian distributed kernel estimators. A Weissman-type estimator and kernel estimators of the conditional tail-index are derived, permitting to estimate extreme conditional quantiles of arbitrary order.Comment: arXiv admin note: text overlap with arXiv:1107.226

Developing a collaborative, humanistic interprofessional healthcare culture: a multi-site study

Introduction:Developing a collaborative, humanistic interprofessional healthcare culture requires optimal relational skills, respect, interpersonal cohesion, and role clarity. We developed a longitudinal curriculum to engender these skills and values in institutional leaders. We report results of a qualitative study at seven US-based academic health centers to identify participants’ learning. Methods:At each institution, participants from at least three different professions met in small group sessions twice-monthly over nine months. Sessions focused on relational capacities to enhance leadership and professionalism, and utilized critical reflection and experiential learning to promote teamwork, self-knowledge, communication skills, and address challenges encountered by a healthcare team. Participants completed reflective responses to open-ended questions asking what knowledge, insights, or skills they gained by working in this interprofessional group and applications of their learning. Five investigators analyzed the anonymized responses using the constant comparative method. Results:Overarching themes centered on relationships and the strength of the relational nature of the learning. We observed learning on three levels: a) Intrapersonal learning included self-awareness, mindfulness, and empathy for self that translated to reflections on application of these to teamwork and teaching; b) Interpersonal learning concerned relational skills and teaching about listening, understanding others’ perspectives, appreciation/respect for colleagues, and empathy for others; c) Systems level learning included teaching skills about resilience, conflict management, team dynamics and cultural norms, and appreciation of resources from interprofessional colleagues. Discussion:A curriculum focusing on humanistic teaching for leaders led to new insights and positive changes in relational perspectives. Learning occurred on multiple levels. Many learners reported revising previous assumptions, a marker for transformative learning. Humanistic faculty development can facilitate deep bonds between professions. &nbsp