Edgar Dobriban, William Leeb, Amit Singer.

Source: The Annals of Statistics, Volume 48, Number 1, 491--513.

Abstract:
We consider the linearly transformed spiked model , where the observations $Y_{i}$ are noisy linear transforms of unobserved signals of interest $X_{i}$: egin{equation*}Y_{i}=A_{i}X_{i}+varepsilon_{i},end{equation*} for $i=1,ldots ,n$. The transform matrices $A_{i}$ are also observed. We model the unobserved signals (or regression coefficients) $X_{i}$ as vectors lying on an unknown low-dimensional space. Given only $Y_{i}$ and $A_{i}$ how should we predict or recover their values? The naive approach of performing regression for each observation separately is inaccurate due to the large noise level. Instead, we develop optimal methods for predicting $X_{i}$ by “borrowing strength” across the different samples. Our linear empirical Bayes methods scale to large datasets and rely on weak moment assumptions. We show that this model has wide-ranging applications in signal processing, deconvolution, cryo-electron microscopy, and missing data with noise. For missing data, we show in simulations that our methods are more robust to noise and to unequal sampling than well-known matrix completion methods.

Dimitris Bertsimas, Bart Van Parys.

Source: The Annals of Statistics, Volume 48, Number 1, 300--323.

Abstract:
We present a novel binary convex reformulation of the sparse regression problem that constitutes a new duality perspective. We devise a new cutting plane method and provide evidence that it can solve to provable optimality the sparse regression problem for sample sizes $n$ and number of regressors $p$ in the 100,000s, that is, two orders of magnitude better than the current state of the art, in seconds. The ability to solve the problem for very high dimensions allows us to observe new phase transition phenomena. Contrary to traditional complexity theory which suggests that the difficulty of a problem increases with problem size, the sparse regression problem has the property that as the number of samples $n$ increases the problem becomes easier in that the solution recovers 100% of the true signal, and our approach solves the problem extremely fast (in fact faster than Lasso), while for small number of samples $n$, our approach takes a larger amount of time to solve the problem, but importantly the optimal solution provides a statistically more relevant regressor. We argue that our exact sparse regression approach presents a superior alternative over heuristic methods available at present.

Emmanuel J. Candès, Pragya Sur.

Source: The Annals of Statistics, Volume 48, Number 1, 27--42.

Abstract:
This paper rigorously establishes that the existence of the maximum likelihood estimate (MLE) in high-dimensional logistic regression models with Gaussian covariates undergoes a sharp “phase transition.” We introduce an explicit boundary curve $h_{mathrm{MLE}}$, parameterized by two scalars measuring the overall magnitude of the unknown sequence of regression coefficients, with the following property: in the limit of large sample sizes $n$ and number of features $p$ proportioned in such a way that $p/n ightarrow kappa $, we show that if the problem is sufficiently high dimensional in the sense that $kappa >h_{mathrm{MLE}}$, then the MLE does not exist with probability one. Conversely, if $kappa <h_{mathrm{MLE}}$, the MLE asymptotically exists with probability one.

Wei-Kuo Chen.

Source: The Annals of Statistics, Volume 47, Number 5, 2734--2756.

Abstract:
We consider the problem of detecting a deformation from a symmetric Gaussian random $p$-tensor $(pgeq3)$ with a rank-one spike sampled from the Rademacher prior. Recently, in Lesieur et al. (Barbier, Krzakala, Macris, Miolane and Zdeborová (2017)), it was proved that there exists a critical threshold $eta_{p}$ so that when the signal-to-noise ratio exceeds $eta_{p}$, one can distinguish the spiked and unspiked tensors and weakly recover the prior via the minimal mean-square-error method. On the other side, Perry, Wein and Bandeira (Perry, Wein and Bandeira (2017)) proved that there exists a $eta_{p}'<eta_{p}$ such that any statistical hypothesis test cannot distinguish these two tensors, in the sense that their total variation distance asymptotically vanishes, when the signa-to-noise ratio is less than $eta_{p}'$. In this work, we show that $eta_{p}$ is indeed the critical threshold that strictly separates the distinguishability and indistinguishability between the two tensors under the total variation distance. Our approach is based on a subtle analysis of the high temperature behavior of the pure $p$-spin model with Ising spin, arising initially from the field of spin glasses. In particular, we identify the signal-to-noise criticality $eta_{p}$ as the critical temperature, distinguishing the high and low temperature behavior, of the Ising pure $p$-spin mean-field spin glass model.

Chih-Yuan Hsu, Yi-Hau Chen, Ruoh-Rong Yu, Tsung-Wei Hung.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 160--177.

Abstract:
Workers in Taiwan overall have been suffering from long-lasting wage stagnation since the mid-1990s. In particular, there seems to be little mobility for the wages of Taiwanese workers to transit across wage quantile groups. It is of interest to see if certain groups of workers, such as female, lower educated and younger generation workers, suffer from the problem more seriously than the others. This work tries to apply a systematic statistical approach to study this issue, based on the longitudinal data from the Panel Study of Family Dynamics (PSFD) survey conducted in Taiwan since 1999. We propose the quantile transition regression model, generalizing recent methodology for quantile association, to assess the wage status transition with respect to the marginal wage quantiles over time as well as the effects of certain demographic and job factors on the wage status transition. Estimation of the model can be based on the composite likelihoods utilizing the binary, or ordinal-data information regarding the quantile transition, with the associated asymptotic theory established. A goodness-of-fit procedure for the proposed model is developed. The performances of the estimation and the goodness-of-fit procedures for the quantile transition model are illustrated through simulations. The application of the proposed methodology to the PSFD survey data suggests that female, private-sector workers with higher age and education below postgraduate level suffer from more severe wage status stagnation than the others.

Peter Bank, Yan Dolinsky.

Source: Bernoulli, Volume 26, Number 3, 2176--2201.

Abstract:
We prove a scaling limit theorem for the super-replication cost of options in a Cox–Ross–Rubinstein binomial model with transient price impact. The correct scaling turns out to keep the market depth parameter constant while resilience over fixed periods of time grows in inverse proportion with the duration between trading times. For vanilla options, the scaling limit is found to coincide with the one obtained by PDE-methods in ( Math. Finance 22 (2012) 250–276) for models with purely temporary price impact. These models are a special case of our framework and so our probabilistic scaling limit argument allows one to expand the scope of the scaling limit result to path-dependent options.

Michael Jauch, Peter D. Hoff, David B. Dunson.

Source: Bernoulli, Volume 26, Number 2, 1560--1586.

Abstract:
Random orthogonal matrices play an important role in probability and statistics, arising in multivariate analysis, directional statistics, and models of physical systems, among other areas. Calculations involving random orthogonal matrices are complicated by their constrained support. Accordingly, we parametrize the Stiefel and Grassmann manifolds, represented as subsets of orthogonal matrices, in terms of Euclidean parameters using the Cayley transform. We derive the necessary Jacobian terms for change of variables formulas. Given a density defined on the Stiefel or Grassmann manifold, these allow us to specify the corresponding density for the Euclidean parameters, and vice versa. As an application, we present a Markov chain Monte Carlo approach to simulating from distributions on the Stiefel and Grassmann manifolds. Finally, we establish that the Euclidean parameters corresponding to a uniform orthogonal matrix can be approximated asymptotically by independent normals. This result contributes to the growing literature on normal approximations to the entries of random orthogonal matrices or transformations thereof.

Reaction and analysis from Fox News contributor Byron York and former Florida Attorney General Pam Bondi.

Brian Zingg
Apr 15, 2020; 40:3250-3267
Systems/Circuits

Hedok Lee
Aug 5, 2015; 35:11034-11044
Neurobiology of Disease

Georg S. Kranz
Nov 12, 2014; 34:15466-15475
Systems/Circuits

John D. Cahoy
Jan 2, 2008; 28:264-278
Cellular

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Benjamin Meyer
Jul 3, 2019; 39:5326-5335
Systems/Circuits

Zhengui Xia
Sep 1, 1996; 16:5425-5436
Articles

Lennart Mucke
Jun 1, 2000; 20:4050-4058
Cellular

John D. Cahoy
Jan 2, 2008; 28:264-278
Cellular

Ye Zhang
Sep 3, 2014; 34:11929-11947
Cellular

Revealing the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) exhibits anterograde transneuronal transport, however, the synaptic specificity of this spread and its broad application within a diverse set of circuits remains to be explored. Here, using anatomic, functional, and molecular approaches, we provide evidence for the preferential transport of AAV1 to postsynaptically connected neurons and reveal its spread is strongly dependent on synaptic transmitter release. In addition to glutamatergic pathways, AAV1 also spreads through GABAergic synapses to both excitatory and inhibitory cell types. We observed little or no transport, however, through neuromodulatory projections (e.g., serotonergic, cholinergic, and noradrenergic). In addition, we found that AAV1 can be transported through long-distance descending projections from various brain regions to effectively transduce spinal cord neurons. Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be applied within a wide variety of pathways to categorize neurons according to their input sources, morphology, and molecular identities. These properties make AAV1 a promising anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain, although its capacity for retrograde transport currently limits its use to unidirectional circuits.

SIGNIFICANCE STATEMENT The discovery of anterograde transneuronal spread of AAV1 generates great promise for its application as a unique tool for manipulating input-defined cell populations and mapping their outputs. However, several outstanding questions remain for anterograde transsynaptic approaches in the field: (1) whether AAV1 spreads exclusively or specifically to synaptically connected neurons, and (2) how broad its application could be in various types of neural circuits in the brain. This study provides several lines of evidence in terms of anatomy, functional innervation, and underlying mechanisms, to strongly support that AAV1 anterograde transneuronal spread is highly synapse specific. In addition, several potentially important applications of transsynaptic AAV1 in probing neural circuits are described.

Despite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) are derived from the same progenitors that give rise to ARH neurons. However, the mechanism whereby common neuronal precursors subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elusive. We hypothesize that POMC and NPY/AgRP cell fates are specified and maintained by distinct intrinsic factors. In search of them, we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice. Moreover, cell-type-specific transcriptomic analyses revealed transcription regulators that are selectively enriched in either population, but whose developmental functions are unknown in these neurons. Among them, we found the expression of the PR domain-containing factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons. To study the role of Prdm12 in vivo, we developed and characterized a floxed Prdm12 allele. Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expression as well as early-onset obesity in mice of either sex that recapitulates symptoms of human POMC deficiency. Interestingly, however, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Pomc expression or energy balance. Collectively, these findings establish a critical role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis. Finally, the combination of cell-type-specific genomic and genetic analyses provides a means to dissect cellular and functional diversity in the hypothalamus whose neurodevelopment remains poorly studied.

SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypothalamic progenitors but have opposing effects on food intake. We profiled the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypothalamus to decipher the transcriptional codes behind the versus orexigenic neuron identity. Our analyses revealed 29 transcription regulators that are selectively enriched in one of the two populations. We generated new mouse genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in developing and adult POMC neurons. Our studies establish a previously unrecognized role for Prdm12 in the anorexigenic neuron identity and suggest that it acts developmentally to program body weight homeostasis.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

Did you know that cash transfer (CT) programmes in countries of the sub-Saharan Africa actually have a significant impact? In Malawi, these programmes helped families invest in agricultural equipment and livestock to produce their own food and reduce levels of negative coping strategies, like begging and school drop-outs. In Kenya, secondary school attendance rose by 9 percent and access to [...]

Cash transfer programmes – regular money payments to poor households - aim to reduce poverty, promote sustainable livelihoods and increase production in the developing world. During the past decade, an increasing number of governments in sub-Saharan Africa have launched cash transfer programmes that target the most vulnerable groups, including subsistence farmers, people with disabilities and HIV/AIDS, as well as families [...]

  We can’t really talk about the planet’s most pressing environmental problems without talking about food systems. And by food systems, we also mean the agriculture that it takes to support them: farming, fisheries, forestry and the value chains that provide food and fiber for our daily lives. 

New research hints at how different environments impact animal behavior and the spread of infection

Matilda McCrear was just 2 when she was captured and brought to Alabama on the "Clotilda"

Governments around the world grapple with how to deliver important guidelines on minimizing the spread of COVID-19

The most commonly used method for production of recombinant adeno-associated virus (rAAVs) in research laboratories is by transient triple transfection of 293 cells with AAV cis and trans plasmids and an adenovirus helper plasmid. This protocol describes the processes required to prepare the transfected cell suspension for virus purification.

Artists from Michigan and around the world are painting 50 murals in Flint to refocus the city's image on art rather than the lead-tainted water crisis.

TransLink is suspending the service reductions it planned for later this month and is rescinding layoff notices to around 1,500 employees.

“The timing couldn’t have been worse for refugees from Syria passing through Macedonia.” An OM worker shares about conditions in a Macedonian refugee transit camp.

Lindsay Forsyth Brochu thought by now she'd have the double-lung transplant she's been waiting for. But she had the misfortune being put on the waitlist the day after most surgeries were suspended in Ontario due to COVID-19.

The Coldwater band is calling for federal intervention after Trans Mountain announced it was changing the way it would study the aquifer the First Nation relies on for its drinking water.

An Albanian man's heart is forever changed after suffering a heart attack and meeting Jesus in his recuperation.

The general field of quantitative biology has advanced significantly on the back of recent improvements in both sequencing technology and proteomics methods. The development of high-throughput, short-read sequencing has revolutionized RNA-based expression studies, while improvements in proteomics methods have enabled quantitative studies to attain better resolution. Here we introduce methods to undertake global analyses of gene expression through RNA and protein quantification in Xenopus embryos and tissues.

Learn how to use a transparent background to add your renders on top of an existing image or background.

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A woman and her husband accept the Lord after hearing the gospel from an OM team visiting the island of Sante Marie.

Despite knowing very little about the Androy region, OMers Fara and Herimanina went willingly and have seen God at work.

The impact of baseball as an outreach tool is growing far beyond the first teams that began nine years ago in Érd.