bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzyme replacement therapy and beyond—in memoriam Roscoe O. Brady, M.D. (1923–2016)
Authors: Ries Markus 
Published: March 2017

AbstractLysosomal storage disorders are strong candidates for the development of specific innovative therapies. The discovery of enzyme deficiencies is an important milestone in understanding the underlying cause of disease. Being able to replace the first missing enzyme in a lysosomal storage required three decades of dedicated research. Successful drug development for lysosomal storage disorders was fostered by the U.S. Orphan Drug Act. Various optimization strategies have the potential to overcome the current limitations of enzyme replacement therapies. In addition, substrate reduction therapies are an alternative approach to treat lysosomal storage disorders, chemical chaperones enhance residual enzyme activity, and small molecules can facilitate substrate transport through subcellular compartments. Bone‐marrow derived multipotent stem cells and gene therapies have received FDA orphan drug designation status. The science of small clinical trials played an essential role: non‐neurological endpoints, biomarker, and regulatory alignment are key factors in successful drug development for lysosomal storage disorders. Being able to treat brain disease is the next frontier. This review is dedicated to the memory of Roscoe O. Brady, an early pioneer in the research of lysosomal storage diseases.
Reasons for Declining Preconception Expanded Carrier Screening Using Genome Sequencing
Authors: Gilmore Marian J. , Schneider Jennifer , Davis James V. , Kauffman Tia L. , Leo Michael C. , Bergen Kellene , Reiss Jacob A. , Himes Patricia , Morris Elissa , Young Carol , McMullen Carmit , Wilfond Benjamin S. , Goddard Katrina A.B. 
Published: March 2017

AbstractGenomic carrier screening can identify more disease‐associated variants than existing carrier screening methodologies, but its utility from patients’ perspective is not yet established. A randomized controlled trial for preconception genomic carrier screening provided an opportunity to understand patients’ decisions about whether to accept or decline testing. We administered a survey to potential genomic carrier screening recipients who declined participation (N = 240) to evaluate their reasons for doing so. Two thirds of women declined participation. We identified major themes describing reasons these individuals declined to participate; the most common were time limitation, lack of interest, not wanting to know the information, and potential cause of worry or anxiety. Most women eligible for genomic carrier screening indicated that their reasons for opting out were due to logistical issues rather than opposing the rationale for testing. As expanded carrier screening and genomic sequencing become a more routine part of clinical care, it is anticipated there will be variable uptake from individuals for this testing. Thus, the advancement of clinical carrier screening from single genes, to expanded screening panels, to an exome‐ or genome‐wide platform, will require approaches that respect individual choice to receive genetic testing for reproductive risk assessment.
A PDE approach to some asymptotic problems concerning random differential equations with small noise intensities
Authors: Ishii H. , Evans L.C. 
Published: March 2017

We illustrate the effectiveness of viscosity solution methods for Hamilton–Jacobi PDE by demonstrating a new approach to a method of W. Fleming ([10], [11]) for proving WKB-type representations. We present new proofs of three examples, due originally to Ventcel-Freidlin, Varadhan, and Fleming.

Résumé
On étudie, par une méthode issue de la théorie des équations aux dérivées partielles, certains problèmes asymptotiques concernant les équations différentielles stochastiques, quand l’intensité du bruit tend vers zéro. La méthode employée est celle des solutions de viscosité pour les équations de Hamilton–Jacobi. Ceci permet une approche nouvelle de la méthode de Fleming ([10], [11]) pour établir des représentations du type WKB. On donne des démonstrations nouvelles de trois exemples, dus à Ventcel-Freidlin, Varadhan et Fleming.
Remarques sur des résultats d’existence pour les équations de Hamilton-Jacobi du premier ordre
Authors: Barles G. 
Published: March 2017

We complement some existence results obtained previously by P. L. Lions for first-order Hamilton Jacobi Equations. These results rely on the notion of viscosity solution.

Résumé
Nous complétons certains résultats d’existence obtenus antérieurement par P. L. Lions pour les équations de Hamilton Jacobi du premier ordre. Ces résultats sont basés sur la notion de solution de viscosité.
Problème de Cauchy pour des systèmes hyperboliques semi‐linéaires
Authors: Bachelot Alain 
Published: March 2017

We resolve the global Cauchy problem for systems of Schroedinger and Klein–Gordon equations without conserved energy, and for not very regular data. We also obtain local solutions for coupled Dirac–Klein–Gordon equations having quadratic non linearities generalizing the Yukawa interaction.

Résumé
On résout le problème de Cauchy global pour des systèmes d’équations de Schroedinger et de Klein–Gordon sans conservation d’énergie et avec des données initiales peu régulières. On obtient également des solutions locales pour des systèmes de Dirac–Klein–Gordon avec non linéarités quadratiques généralisant l’interaction de Yukawa.
Existence results for first order Hamilton Jacobi equations
Authors: Barles G. 
Published: March 2017

We prove existence results for the classical first-order Hamilton Jacobi Equations. These results rely on the notion of viscosity solution and they are obtained under the same assumptions as the uniqueness optimal results for bounded, uniformly continuous solutions.

Résumé
On démontre des résultats d’existence pour les équations classiques de Hamilton Jacobi du premier ordre. Ces résultats sont basés sur la notion de solution de viscosité et sont obtenus sous les mêmes hypothèses que les résultats optimaux d’unicité pour les solutions bornées uniformément continues.
Bifurcation and multiplicity results for nonlinear elliptic problems involving critical Sobolev exponents
Authors: Cerami Giovanna , Fortunato Donato , Struwe Michaël 
Published: March 2017

In this paper we study the existence of nontrivial solutions for the boundary value problem

\left\{
\begin{align*}
−\:\Delta u\:−\:\lambda u\:−\:u\left|u\right|^{2^{⁎}\:−\:2}\: &= \:0\:\: && \mathrm{in}\:\:\Omega \\
u \: &= \: 0 && \mathrm{on}\:∂\Omega \\
\end{align*}
\right.

when

Ω⊂R^n

is a bounded domain,

n⩾ 3

,

2^{⁎}\: = \:\frac{2n}{n−2}

is the critical exponent for the Sobolev embedding

\mathrm{H}_{0}^{1}(\Omega ) \subset \mathrm{L}^{p}(\Omega )

,

λ

is a real parameter.

We prove that there is bifurcation from any eigenvalue

λ_j

of

− Δ

and we give an estimate of the left neighbourhoods

]\lambda _{j}^{⁎},\lambda _j]

of

λ_j

,

j\in N

, in which the bifurcation branch can be extended. Moreover we prove that, if

\lambda \in{]\lambda_j^{⁎},\lambda_j[}

, the number of nontrivial solutions is at least twice the multiplicity of

λ_j

.

The same kind of results holds also when

Ω

is a compact Riemannian manifold of dimension

n ⩾ 3

, without boundary and

Δ

is the relative Laplace–Beltrami operator.

Résumé
Dans cet article, nous étudions l’existence de solutions non triviales pour le problème aux limites

\left\{
\begin{align*}
−\:\Delta u\:−\:\lambda u\:−\:u\left|u\right|^{2^{⁎}\:−\:2}\: &= \:0\:\: && \mathrm{in}\:\:\Omega \\
u \: &= \: 0 && \mathrm{on}\:∂\Omega \\
\end{align*}
\right.

où

Ω⊂R^n

est un domaine borné,

n⩾ 3

,

2^{⁎}\: = \:\frac{2n}{n−2}

est l’exposant critique pour le plongement de Sobolev

\mathrm{H}_{0}^{1}(\Omega ) \subset \mathrm{L}^{p}(\Omega )

,

λ

est un paramètre réel.

Nous démontrons que toute valeur propre

λ_j

de

− Δ

est une valeur de bifurcation, et nous donnons une estimation des voisinages

]\lambda _{j}^{⁎},\lambda _j]

de

λ_j

où existent des solutions non triviales. Nous montrons en outre que le nombre de celles-ci est au moins le double de la multiplicité de

λ_j

.

On ales mêmes résultats quand Ω est une variété riemannienne compacte de dimension

n ≧ 3

, et

Δ

l’opérateur de Laplace–Beltrami.
Uniqueness and non-existence of metrics with prescribed Ricci curvature
Authors: DeTurck Dennis M. , Koiso Norihito 
Published: March 2017

We investigate whether the Ricci tensor uniquely determines the Riemannian structure, and we give conditions that a doubly covariant tensor has to satisfy in order to be the Ricci tensor for some Riemannian structure.

Résumé
Nous cherchons si le tenseur de Ricci détermine la structure riemannienne, et nous donnons des conditions que doit satisfaire un tenseur deux fois covariant pour être le tenseur de Ricci d’une certaine structure riemannienne.
Closed geodesics for the Jacobi metric and periodic solutions of prescribed energy of natural Hamiltonian systems
Authors: Benci V. 
Published: March 2017

We prove that the Hamiltonian system

\begin{cases}
\.{p}\: = \:−\frac{∂\mathrm{V}}{∂q} \\
\.{q}\: = \:p
\end{cases}
\qquad p,\:q \in \mathrm{R}^{n};\ \mathrm{V} \in \mathrm{C}^{2}\left(\mathrm{R}^{n}\right)

has at least one periodic solution of energy

h

, provided that the set

\{q \in \mathrm R^n | \mathrm V(q) ⩽ h\}

is compact.

Résumé
Nous démontrons que le système hamiltonien

\begin{cases}
\.{p}\: = \:−\frac{∂\mathrm{V}}{∂q} \\
\.{q}\: = \:p
\end{cases}
\qquad p,\:q \in \mathrm{R}^{n};\ \mathrm{V} \in \mathrm{C}^{2}\left(\mathrm{R}^{n}\right)

a au moins une solution périodique d’énergie

h

, pourvu que l’ensemble

\{q \in \mathrm R^n | \mathrm V(q) ⩽ h\}

soit compact.
A homotopy method for solving an equation of the type $− Δu = F(u)$
Authors: Witomski P. , Devys Christophe , Morel Jean-Michel 
Published: March 2017

We describe a homotopy algorithm for solving the equation

− Δu = F(u)

. To this end, we define a pseudo-inverse and a pseudo-determinant with sufficient regularity properties, for operators of Laplacian type.

Résumé

On décrit une méthode d’homotopie pour résoudre l’équation

− Δu = F(u)

. Dans ce but, on définit pour les opérateurs du type Laplacien un pseudo-inverse et un pseudo-déterminant munis des propriétés de régularité nécessaires.
Multiple orbits for Hamiltonian systems on starshaped surfaces with symmetries
Authors: Girardi Mario 
Published: March 2017

This paper deals with the existence of periodic solutions of Hamiltonian system with

N

degrees of freedom, on a given energy surface. The surface is supposed to be symmetric and starshaped with respect to the origin. We show that any such surface carries at least one symmetric periodic solution and we give a sufficient condition on the surface for the existence of

N

such solutions.

Résumé

Dans ce travail nous considérons l’existence de solutions périodiques de systèmes hamiltoniens à

N

degrés de liberté sur une surface d’énergie donnée que nous supposons symétrique et étoilée par rapport à l’origine. Nous montrons que toute surface de ce type admet au moins une solution périodique et symétrique, et nous donnons une condition suffisante pour l’existence de

N

telles solutions.
The concentration-compactness principle in the Calculus of Variations. The locally compact case, part 1.
Authors: Lions P.L. 
Published: March 2017

We present here a new method for solving minimization problems in unbounded domains. We first derive a general principle showing the equivalence between the compactness of all minimizing sequences and some strict sub-additivity conditions. The proof is based upon a compactness lemma obtained with the help of the notion of concentration function of a measure. We give various applications to problems arising in Mathematical Physics.

Résumé
Nous présentons ici une méthode nouvelle de résolution des problèmes de minimisation dans des domaines non bornés. Nous commençons par établir un principe général montrant l’équivalence entre la compacité de toutes les suites minimisantes et certaines conditions de sous-additivité stricte. La démonstration s’appuie sur un lemme de compacité obtenu à l’aide de la notion de fonction de concentration d’une mesure. Nous donnons diverses applications à des problèmes de physique mathématique.
Large-scale heterogeneous service systems with general packing constraints
Authors: Stolyar A. L. 
Published: March 2017

Abstract
A service system with multiple types of customers, arriving according to Poisson processes, is considered. The system is heterogeneous in that the servers can also be of multiple types. Each customer has an independent, exponentially distributed service time, with the mean determined by its type. Multiple customers (possibly of different types) can be placed for service into one server, subject to `packing' constraints, which depend on the server type. Service times of different customers are independent, even if served simultaneously by the same server. The large-scale asymptotic regime is considered such that the customer arrival rates grow to ∞. We consider two variants of the model. For the infinite-server model, we prove asymptotic optimality of the greedy random (GRAND) algorithm in the sense of minimizing the weighted (by type) number of occupied servers in steady state. (This version of GRAND generalizes that introduced by Stolyar and Zhong (2015) for homogeneous systems, with all servers of the same type.) We then introduce a natural extension of the GRAND algorithm for finite-server systems with blocking. Assuming subcritical system load, we prove existence, uniqueness, and local stability of the large-scale system equilibrium point such that no blocking occurs. This result strongly suggests a conjecture that the steady-state blocking probability under the algorithm vanishes in the large-scale limit.
Generalized Markov branching trees
Authors: Crane Harry 
Published: March 2017

AbstractMotivated by the gene tree/species tree problem from statistical phylogenetics, we extend the class of Markov branching trees to a parametric family of distributions on fragmentation trees that satisfies ageneralized Markov branching property. The main theorems establish important statistical properties of this model, specifically necessary and sufficient conditions under which a family of trees can be constructed consistently as sample size grows. We also consider the question of attaching random edge lengths to these trees.
Impulse control and expected suprema
Authors: Christensen Sören , Salminen Paavo 
Published: March 2017

Abstract
We consider a class of impulse control problems for general underlying strong Markov processes on the real line, which allows for an explicit solution. The optimal impulse times are shown to be of a threshold type and the optimal threshold is characterised as a solution of a (typically nonlinear) equation. The main ingredient we use is a representation result for excessive functions in terms of expected suprema.
The influence of föhn winds on Glacial Lake Washburn and palaeotemperatures in the McMurdo Dry Valleys, Antarctica, during the Last Glacial Maximum
Authors: Obryk M.K. , Doran P.T. , Waddington E.D. , Mckay C.P. 
Published: March 2017

AbstractLarge glacial lakes, including Glacial Lake Washburn, were present in the McMurdo Dry Valleys, Antarctica, during the Last Glacial Maximum (LGM) despite a colder and drier climate. To address the mechanism capable of generating enough meltwater to sustain these large lakes, a conceptual model was developed based on the warming potential of infrequent contemporary föhn winds. The model suggests that föhn winds were capable of generating enough meltwater to sustain large glacial lakes during the LGM by increasing degree days above freezing (DDAF) and prolonging the melt season. A present-day relationship between infrequent summer föhn winds and DDAF was established. It is assumed that the Taylor Dome ice core record represents large-scale palaeoclimatic variations for the McMurdo Dry Valleys region. This analysis suggests that because of the warming influence of the more frequent föhn winds, summer DDAF in the McMurdo Dry Valleys during the LGM were equivalent to present-day values, but this enhanced summer signal is not preserved in the annually averaged ice core temperature record.
The role of adaptive immunity as an ecological filter on the gut microbiota in zebrafish
Authors: Stagaman Keaton , Burns Adam R , Guillemin Karen , Bohannan Brendan J M 
Published: March 2017

Abstract
All animals live in intimate association with communities of microbes, collectively referred to as their microbiota. Certain host traits can influence which microbial taxa comprise the microbiota. One potentially important trait in vertebrate animals is the adaptive immune system, which has been hypothesized to act as an ecological filter, promoting the presence of some microbial taxa over others. Here we surveyed the intestinal microbiota of 68 wild-type zebrafish, with functional adaptive immunity, and 61 rag1− zebrafish, lacking functional B- and T-cell receptors, to test the role of adaptive immunity as an ecological filter on the intestinal microbiota. In addition, we tested the robustness of adaptive immunity’s filtering effects to host–host interaction by comparing the microbiota of fish populations segregated by genotype to those containing both genotypes. The presence of adaptive immunity individualized the gut microbiota and decreased the contributions of neutral processes to gut microbiota assembly. Although mixing genotypes led to increased phylogenetic diversity in each, there was no significant effect of adaptive immunity on gut microbiota composition in either housing condition. Interestingly, the most robust effect on microbiota composition was co-housing within a tank. In all, these results suggest that adaptive immunity has a role as an ecological filter of the zebrafish gut microbiota, but it can be overwhelmed by other factors, including transmission of microbes among hosts.
High resolution analysis of tropical forest fragmentation and its impact on the global carbon cycle
Authors: Brinck Katharina , Fischer Rico , Groeneveld Jürgen , Lehmann Sebastian , Dantas De Paula Mateus , Pütz Sandro , Sexton Joseph O. , Song Danxia , Huth Andreas 
Published: March 2017

AbstractDeforestation in the tropics is not only responsible for direct carbon emissions but also extends the forest edge wherein trees suffer increased mortality. Here we combine high-resolution (30 m) satellite maps of forest cover with estimates of the edge effect and show that 19% of the remaining area of tropical forests lies within 100 m of a forest edge. The tropics house around 50 million forest fragments and the length of the world’s tropical forest edges sums to nearly 50 million km. Edge effects in tropical forests have caused an additional 10.3 Gt (2.1–14.4 Gt) of carbon emissions, which translates into 0.34 Gt per year and represents 31% of the currently estimated annual carbon releases due to tropical deforestation. Fragmentation substantially augments carbon emissions from tropical forests and must be taken into account when analysing the role of vegetation in the global carbon cycle.
New cofactors and inhibitors for a DNA-cleaving DNAzyme: superoxide anion and hydrogen peroxide mediated an oxidative cleavage process
Authors: Sun Yanhong , Ma Rulong , Wang Shijin , Li Guiying , Sheng Yongjie , Rui Hongyue , Zhang Jin , Xu Jiacui , Jiang Dazhi 
Published: March 2017

AbstractHerein, we investigated the effects of new cofactors and inhibitors on an oxidative cleavage of DNA catalysis, known as a pistol-like DNAzyme (PLDz), to discuss its catalytic mechanism. PLDz performed its catalytic activity in the presence of ascorbic acid (AA), in which Cu2+ promoted, whereas Fe2+ significantly inhibited the catalytic function. Since Fe2+/AA-generated hydroxyl radicals are efficient on DNA damage, implying that oxidative cleavage of PLDz had no relation with hydroxyl radical. Subsequently, we used Fe2+/H2O2 and Cu2+/H2O2 to identify the role of hydroxyl radicals in PLDz catalysis. Data showed that PLDz lost its activity with Fe2+/H2O2, but exhibited significant cleavage with Cu2+/H2O2. Because Fe2+/H2O2 and Cu2+/H2O2 are popular reagents to generate hydroxyl radicals and the latter also produces superoxide anions, we excluded the possibility that hydroxyl radical participated in oxidative cleavage and confirmed that superoxide anion was involved in PLDz catalysis. Moreover, pyrogallol, riboflavin and hypoxanthine/xanthine oxidase with superoxide anion and hydrogen peroxide generation also induced self-cleavage of PLDz, where catalase inhibited but superoxide dismutase promoted the catalysis, suggesting that hydrogen peroxide played an essential role in PLDz catalysis. Therefore, we proposed a catalytic mechanism of PLDz in which superoxide anion and hydrogen peroxide mediated an oxidative cleavage process.
2D hybrid analysis: Approach for building three-dimensional atomic model by electron microscopy image matching
Authors: Matsumoto Atsushi , Miyazaki Naoyuki , Takagi Junichi , Iwasaki Kenji 
Published: March 2017

AbstractIn this study, we develop an approach termed “2D hybrid analysis” for building atomic models by image matching from electron microscopy (EM) images of biological molecules. The key advantage is that it is applicable to flexible molecules, which are difficult to analyze by 3DEM approach. In the proposed approach, first, a lot of atomic models with different conformations are built by computer simulation. Then, simulated EM images are built from each atomic model. Finally, they are compared with the experimental EM image. Two kinds of models are used as simulated EM images: the negative stain model and the simple projection model. Although the former is more realistic, the latter is adopted to perform faster computations. The use of the negative stain model enables decomposition of the averaged EM images into multiple projection images, each of which originated from a different conformation or orientation. We apply this approach to the EM images of integrin to obtain the distribution of the conformations, from which the pathway of the conformational change of the protein is deduced.
A Steep-Slope Transistor Combining Phase-Change and Band-to-Band-Tunneling to Achieve a sub-Unity Body Factor
Authors: Vitale Wolfgang A. , Casu Emanuele A. , Biswas Arnab , Rosca Teodor , Alper Cem , Krammer Anna , Luong Gia V. , Zhao Qing-T. , Mantl Siegfried , Schüler Andreas , Ionescu A. M. 
Published: March 2017

AbstractSteep-slope transistors allow to scale down the supply voltage and the energy per computed bit of information as compared to conventional field-effect transistors (FETs), due to their sub-60 mV/decade subthreshold swing at room temperature. Currently pursued approaches to achieve such a subthermionic subthreshold swing consist in alternative carrier injection mechanisms, like quantum mechanical band-to-band tunneling (BTBT) in Tunnel FETs or abrupt phase-change in metal-insulator transition (MIT) devices. The strengths of the BTBT and MIT have been combined in a hybrid device architecture called phase-change tunnel FET (PC-TFET), in which the abrupt MIT in vanadium dioxide (VO2) lowers the subthreshold swing of strained-silicon nanowire TFETs. In this work, we demonstrate that the principle underlying the low swing in the PC-TFET relates to a sub-unity body factor achieved by an internal differential gate voltage amplification. We study the effect of temperature on the switching ratio and the swing of the PC-TFET, reporting values as low as 4.0 mV/decade at 25 °C, 7.8 mV/decade at 45 °C. We discuss how the unique characteristics of the PC-TFET open new perspectives, beyond FETs and other steep-slope transistors, for low power electronics, analog circuits and neuromorphic computing.