EMaP: Explainable AI with Manifold-based Perturbations

In the last few years, many explanation methods based on the perturbations of input data have been introduced to improve our understanding of decisions made by black-box models. The goal of this work is to introduce a novel perturbation scheme so that more faithful and robust explanations can be obtained. Our study focuses on the impact of perturbing directions on the data topology. We show that perturbing along the orthogonal directions of the input manifold better preserves the data topology, both in the worst-case analysis of the discrete Gromov-Hausdorff distance and in the average-case analysis via persistent homology. From those results, we introduce EMaP algorithm, realizing the orthogonal perturbation scheme. Our experiments show that EMaP not only improves the explainers' performance but also helps them overcome a recently-developed attack against perturbation-based methods.Comment: 29 page

Exploration of cloud computing late start LDRD #149630 : Raincoat. v. 2.1.

This report contains documentation from an interoperability study conducted under the Late Start LDRD 149630, Exploration of Cloud Computing. A small late-start LDRD from last year resulted in a study (Raincoat) on using Virtual Private Networks (VPNs) to enhance security in a hybrid cloud environment. Raincoat initially explored the use of OpenVPN on IPv4 and demonstrates that it is possible to secure the communication channel between two small 'test' clouds (a few nodes each) at New Mexico Tech and Sandia. We extended the Raincoat study to add IPSec support via Vyatta routers, to interface with a public cloud (Amazon Elastic Compute Cloud (EC2)), and to be significantly more scalable than the previous iteration. The study contributed to our understanding of interoperability in a hybrid cloud

Internally Controlled, Generic Real-Time PCR for Quantification and Multiplex Real-Time PCR with Serotype-Specific Probes for Serotyping of Dengue Virus Infections

Dengue has become a global public health problem and a sensitive diagnostic test for early phase detection can be life saving. An internally controlled, generic real-time PCR was developed and validated by testing serial dilutions of a DENV positive control RNA in the presence of a fixed amount of IC with results showing a good linearity (R2 = 0.9967) and a LOD of at least 1.95 × 104 copies/mL. Application of the generic PCR on 136 patient samples revealed a sensitivity of 95.8% and specificity of 100%. A newly developed multiplex real-time PCR with serotype-specific probes allowed the serotyping of DENV for 80 out of 92 (87%) generic real-time PCR positive patients. Combined these real-time PCRs offer a convenient diagnostic tool for the sensitive and specific quantification of DENV in clinical specimens with the possibility for serotyping

Combination Antifungal Therapy for Cryptococcal Meningitis

Background Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. Methods We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. Results A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. Conclusions Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Las políticas de reequilibro territorial e innovación institucional en Madrid, 2015-2019

Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional. El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia.Lograr un mejor reparto de los recursos materiales es una tarea inseparable de una transformación institucional dirigida a un mejor reparto del poder y de la capacidad de decisión. Es preciso reconfigurar las instituciones para redefinir la relación entre estas y la ciudadanía. El espacio de cooperación entre las instituciones públicas y la sociedad civil organizada es un terreno privilegiado para lograr esa reconfiguración institucional.El Fondo de Reequilibrio Territorial se concibe como un primer paso en ese complejo camino y se relaciona con el proceso de descentralización y con el concepto de cooperación público-social. Debe entenderse en relación con otros desarrollos institucionales, como el Consejo Coordinador de los Distritos o los Foros Locales. Una tarea de estas características no puede realizarse desde un solo espacio institucional y en un solo mandato, pero en todo caso debe hacerse contando con la firme voluntad y dirección política del equipo de gobierno que quiera desempeñarla. El gobierno es una herramienta formidable para emprender un proceso de reequilibrio territorial, pero aun cuando no hay en el mismo voluntad política en este sentido existen posibilidades para estimular o condicionar la voluntad del equipo de gobierno: articular un amplio pacto entre los actores políticos, sociales, económicos, académicos, etc. que ponga la cuestión en el centro de la agenda política y eleve hasta lo impagable el coste político de seguir dando la espalda a una cuestión crucial para el futuro de la democracia

Contributions of lean mass and fat mass to bone mineral density: a study in postmenopausal women

<p>Abstract</p> <p>Background</p> <p>The relative contribution of lean and fat to the determination of bone mineral density (BMD) in postmenopausal women is a contentious issue. The present study was undertaken to test the hypothesis that lean mass is a better determinant of BMD than fat mass.</p> <p>Methods</p> <p>This cross-sectional study involved 210 postmenopausal women of Vietnamese background, aged between 50 and 85 years, who were randomly sampled from various districts in Ho Chi Minh City (Vietnam). Whole body scans, femoral neck, and lumbar spine BMD were measured by DXA (QDR 4500, Hologic Inc., Waltham, MA). Lean mass (LM) and fat mass (FM) were derived from the whole body scan. Furthermore, lean mass index (LMi) and fat mass index (FMi) were calculated as ratio of LM or FM to body height in metre squared (m²).</p> <p>Results</p> <p>In multiple linear regression analysis, both LM and FM were independent and significant predictors of BMD at the spine and femoral neck. Age, lean mass and fat mass collectively explained 33% variance of lumbar spine and 38% variance of femoral neck BMD. Replacing LM and FM by LMi and LMi did not alter the result. In both analyses, the influence of LM or LMi was greater than FM and FMi. Simulation analysis suggested that a study with 1000 individuals has a 78% chance of finding the significant effects of both LM and FM, and a 22% chance of finding LM alone significant, and zero chance of finding the effect of fat mass alone.</p> <p>Conclusions</p> <p>These data suggest that both lean mass and fat mass are important determinants of BMD. For a given body size -- measured either by lean mass or height --women with greater fat mass have greater BMD.</p

ZEB1 Links p63 and p73 in a Novel Neuronal Survival Pathway Rapidly Induced in Response to Cortical Ischemia

Background: Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/ pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage. Methodology/Principal Findings: We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/ differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia. Employing histological, tissue culture, and molecular biological read-outs, we show that this novel pro-survival response, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. We show further that this phylogenetically conserved pathway is induced as well in the human cortex subjected to episodes of clinically relevant stroke. Conclusions/Significance: The data presented here provide the first evidence that ZEB1 induction is part of a protective response by neurons to ischemia. The stroke-induced increase in ZEB1 mRNA and protein levels in cortical neurons is both developmentally and phylogenetically conserved and may therefore be part of a fundamental cellular response to thi