Approximate resilience, monotonicity, and the complexity of agnostic learning

A function $f$ is $d$-resilient if all its Fourier coefficients of degree at most $d$ are zero, i.e., $f$ is uncorrelated with all low-degree parities. We study the notion of $\mathit{approximate}$ $\mathit{resilience}$ of Boolean functions, where we say that $f$ is $\alpha$-approximately $d$-resilient if $f$ is $\alpha$-close to a $[-1,1]$-valued $d$-resilient function in $\ell_1$ distance. We show that approximate resilience essentially characterizes the complexity of agnostic learning of a concept class $C$ over the uniform distribution. Roughly speaking, if all functions in a class $C$ are far from being $d$-resilient then $C$ can be learned agnostically in time $n^{O(d)}$ and conversely, if $C$ contains a function close to being $d$-resilient then agnostic learning of $C$ in the statistical query (SQ) framework of Kearns has complexity of at least $n^{\Omega(d)}$. This characterization is based on the duality between $\ell_1$ approximation by degree-$d$ polynomials and approximate $d$-resilience that we establish. In particular, it implies that $\ell_1$ approximation by low-degree polynomials, known to be sufficient for agnostic learning over product distributions, is in fact necessary. Focusing on monotone Boolean functions, we exhibit the existence of near-optimal $\alpha$-approximately $\widetilde{\Omega}(\alpha\sqrt{n})$-resilient monotone functions for all $\alpha>0$. Prior to our work, it was conceivable even that every monotone function is $\Omega(1)$-far from any $1$-resilient function. Furthermore, we construct simple, explicit monotone functions based on ${\sf Tribes}$ and ${\sf CycleRun}$ that are close to highly resilient functions. Our constructions are based on a fairly general resilience analysis and amplification. These structural results, together with the characterization, imply nearly optimal lower bounds for agnostic learning of monotone juntas

Non-Malleable Codes for Small-Depth Circuits

We construct efficient, unconditional non-malleable codes that are secure against tampering functions computed by small-depth circuits. For constant-depth circuits of polynomial size (i.e. $\mathsf{AC^0}$ tampering functions), our codes have codeword length $n = k^{1+o(1)}$ for a $k$-bit message. This is an exponential improvement of the previous best construction due to Chattopadhyay and Li (STOC 2017), which had codeword length $2^{O(\sqrt{k})}$. Our construction remains efficient for circuit depths as large as $\Theta(\log(n)/\log\log(n))$ (indeed, our codeword length remains $n\leq k^{1+\epsilon})$, and extending our result beyond this would require separating $\mathsf{P}$ from $\mathsf{NC^1}$. We obtain our codes via a new efficient non-malleable reduction from small-depth tampering to split-state tampering. A novel aspect of our work is the incorporation of techniques from unconditional derandomization into the framework of non-malleable reductions. In particular, a key ingredient in our analysis is a recent pseudorandom switching lemma of Trevisan and Xue (CCC 2013), a derandomization of the influential switching lemma from circuit complexity; the randomness-efficiency of this switching lemma translates into the rate-efficiency of our codes via our non-malleable reduction.Comment: 26 pages, 4 figure

The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects.

Genome instability is associated with tumorigenesis. Here, we identify a role for the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex (SWR-C), in preventing genome instability in the absence of the replication fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication-defective mrc1 mutation causes synergistic increases in gross chromosomal rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and hypersensitivity to replication stress. The double mutants have severe replication defects and accumulate aberrant replication intermediates. None of the individual mutations cause large increases in GCR rates; however, defects in MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication defects. We propose a model in which Htz1 deposition and retention in chromatin prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3 mutants from being converted to DNA double-strand breaks that trigger genome instability

Augmented Cardiopulmonary Baroreflex Sensitivity in Intradialytic Hypertension.

IntroductionEnd-stage renal disease (ESRD) patients with a paradoxical increase in blood pressure (BP) during hemodialysis (HD), termed intradialytic hypertension (ID-HTN), are at significantly increased risk for mortality and adverse cardiovascular events. ID-HTN affects up to 15% of all HD patients, and the pathophysiologic mechanisms remain unknown. We hypothesized that ESRD patients prone to ID-HTN have heightened volume-sensitive cardiopulmonary baroreflex sensitivity (BRS) that leads to exaggerated increases in sympathetic nervous system (SNS) activation during HD.MethodsWe studied ESRD patients on maintenance HD with ID-HTN (n = 10) and without ID-HTN (controls, n = 12) on an interdialytic day, 24 to 30 hours after their last HD session. We measured continuous muscle sympathetic nerve activity (MSNA), beat-to-beat arterial BP, and electrocardiography (ECG) at baseline, and during graded lower body negative pressure (LBNP). Low-dose LBNP isolates cardiopulmonary BRS, whereas higher doses allow assessment of physiologic responses to orthostatic stress.ResultsThe ID-HTN patients had significantly higher pre- and post-HD BP, and greater interdialytic fluid weight gain compared to controls. There was a significantly greater increase in MSNA burst incidence (P = 0.044) during graded LBNP in the ID-HTN group, suggesting heightened cardiopulmonary BRS. The ID-HTN group also had a trend toward increased diastolic BP response during LBNP, and had significantly greater increases in BP during the cold pressor test.ConclusionPatients with ID-HTN have augmented cardiopulmonary BRS that may contribute to increased SNS activation and BP response during HD

Blood Glucose Forecasting using LSTM Variants under the Context of Open Source Artificial Pancreas System

High accuracy of blood glucose prediction over the long term is essential for preventative diabetes management. The emerging closed-loop insulin delivery system such as the artificial pancreas system (APS) provides opportunities for improved glycaemic control for patients with type 1 diabetes. Existing blood glucose studies are proven effective only within 30 minutes but the accuracy deteriorates drastically when the prediction horizon increases to 45 minutes and 60 minutes. Deep learning, especially for long short term memory (LSTM) and its variants have recently been applied in various areas to achieve state-of-the-art results in tasks with complex time series data. In this study, we present deep LSTM based models that are capable of forecasting long term blood glucose levels with improved prediction and clinical accuracy. We evaluate our approach using 20 cases(878,000 glucose values) from Open Source Artificial Pancreas System (OpenAPS). On 30-minutes and 45-minutes prediction, our Stacked-LSTM achieved the best performance with Root-Mean-Square-Error (RMSE) marks 11.96 & 15.81 and Clark-Grid-ZoneA marks 0.887 & 0.784. In terms of 60-minutes prediction, our ConvLSTM has the best performance with RMSE = 19.6 and Clark-Grid-ZoneA=0.714. Our models outperform existing methods in both prediction and clinical accuracy. This research can hopefully support patients with type 1 diabetes to better manage their behavior in a more preventative way and can be used in future real APS context

Ethnicity and age as factors in sildenafil treatment of erectile dysfunction

IntroductionSildenafil has been evaluated in >16 000 men with erectile dysfunction (ED) in doubleâ blind, placeboâ controlled trials.AimTo assess efficacy and safety of sildenafil in ED by ethnicity (white, black Asian) and age (â ¤45, 46â 60, â ¥61 years).MethodsData were pooled from 38 doubleâ blind, placeboâ controlled, flexibleâ dose trials. Most had starting sildenafil doses of 50 mg once daily, ~1 hour before sexual activity, with adjustment to 100 or 25 mg as needed.Main Outcome MeasuresChange from baseline in International Index of Erectile Function erectile function (IIEFâ EF) domain score assessed with analysis of covariance and a Global Assessment Question (GAQ; â Did the treatment improve your erections?â ) at endpoint assessed with logistic regression analysis.Results4120 and 3714 men received sildenafil and placebo, respectively (2740 and 2671 White; 407 and 385 Black; 973 and 658 Asian). For sildenafil vs. placebo groups, overall treatment differences for IIEFâ EF domain and GAQ were significant for each ethnic and age group (P<.0001); significant treatmentâ byâ ethnicity and treatmentâ byâ age interactions were also observed for change in IIEFâ EF domain scores (P<.05), with differences significantly greater for White vs. Black (P<.0001), White vs. Asian (P=.0163), and Asian vs. Black (P=.0036) men. A significant treatmentâ byâ ethnicity interaction was observed for GAQ (P=.0004). The OR comparison for GAQ was significantly greater (P=.0001) with sildenafil vs. placebo in White (OR=11.2) or Asian (OR=12.4) men vs. Black men (OR=5.1). Adverseâ event rates were generally similar, with some age variations.ConclusionsSildenafil is effective and wellâ tolerated regardless of ethnicity or age; however, treatment effects can vary.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137386/1/ijcp12945_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137386/2/ijcp12945.pd

bNAber: database of broadly neutralizing HIV antibodies.

The discovery of broadly neutralizing antibodies (bNAbs) has provided an enormous impetus to the HIV vaccine research and to entire immunology. The bNAber database at http://bNAber.org provides open, user-friendly access to detailed data on the rapidly growing list of HIV bNAbs, including neutralization profiles, sequences and three-dimensional structures (when available). It also provides an extensive list of visualization and analysis tools, such as heatmaps to analyse neutralization data as well as structure and sequence viewers to correlate bNAbs properties with structural and sequence features of individual antibodies. The goal of the bNAber database is to enable researchers in this field to easily compare and analyse available information on bNAbs thereby supporting efforts to design an effective vaccine for HIV/AIDS. The bNAber database not only provides easy access to data that currently is scattered in the Supplementary Materials sections of individual papers, but also contributes to the development of general standards of data that have to be presented with the discovery of new bNAbs and a universal mechanism of how such data can be shared