TY - JOUR
AB - Mosaic Analysis with Double Markers (MADM) is a method for generating genetically mosaic mice, in which sibling mutant and wild-type cells are labeled with different fluorescent markers. It is a powerful tool that enables analysis of gene function at the single cell level in vivo. It requires transgenic cassettes to be located between the centromere and the mutation in the gene of interest on the same chromosome. Here we compare procedures for introduction of MADM cassettes into new loci in the mouse genome, and describe new approaches for expanding the utility of MADM. We show that: 1) Targeted homologous recombination outperforms random transgenesis in generation of reliably expressed MADM cassettes, 2) MADM cassettes in new genomic loci need to be validated for biallelic and ubiquitous expression, 3) Recombination between MADM cassettes on different chromosomes can be used to study reciprocal chromosomal deletions/duplications, and 4) MADM can be modified to permit transgene expression by combining it with a binary expression system. The advances described in this study expand current, and enable new and more versatile applications of MADM.
AU - Tasic, Bosiljka
AU - Miyamichi, Kazunari
AU - Simon Hippenmeyer
AU - Dani, Vardhan S.
AU - Zeng, H.
AU - Joo, William
AU - Zong, Hui
AU - Chen-Tsai, Yanru
AU - Luo, Liqun
ID - 2262
IS - 3
JF - PLoS One
TI - Extensions of MADM (Mosaic Analysis with Double Markers) in Mice
VL - 7
ER -
TY - JOUR
AB - Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.
AU - Liang, Huixuan
AU - Hippenmeyer, Simon
AU - Ghashghaei, H.
ID - 2263
IS - 12
JF - Biology open
TI - A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
VL - 1
ER -
TY - CONF
AB - Capturing real-world objects with laser-scanning technology has become an everyday task. Recently, the acquisition of dynamic scenes at interactive frame rates has become feasible. A high-quality visualization of the resulting point cloud stream would require a per-frame reconstruction of object surfaces. Unfortunately, reconstruction computations are still too time-consuming to be applied interactively. In this paper we present a local surface reconstruction and visualization technique that provides interactive feedback for reasonably sized point clouds, while achieving high image quality. Our method is performed entirely on the GPU and in screen pace, exploiting the efficiency of the common rasterization pipeline. The approach is very general, as no assumption is made about point connectivity or sampling density. This naturally allows combining the outputs of multiple scanners in a single visualization, which is useful for many virtual and augmented reality applications.
AU - Preiner, Reinhold
AU - Jeschke, Stefan
AU - Wimmer, Michael
ID - 2267
TI - Auto splats: Dynamic point cloud visualization on the GPU
ER -
TY - CONF
AB - This paper presents an analytic formulation for anti-aliased sampling of 2D polygons and 3D polyhedra. Our framework allows the exact evaluation of the convolution integral with a linear function defined on the polytopes. The filter is a spherically symmetric polynomial of any order, supporting approximations to refined variants such as the Mitchell-Netravali filter family. This enables high-quality rasterization of triangles and tetrahedra with linearly interpolated vertex values to regular and non-regular grids. A closed form solution of the convolution is presented and an efficient implementation on the GPU using DirectX and CUDA C is described.
AU - Thomas Auzinger
AU - Guthe, Michael
AU - Stefan Jeschke
ID - 2268
IS - 121
TI - Analytic anti-aliasing of linear functions on polytopes
VL - 31
ER -
TY - JOUR
AB - We introduce propagation models (PMs), a formalism able to express several kinds of equations that describe the behavior of biochemical reaction networks. Furthermore, we introduce the propagation abstract data type (PADT), which separates concerns regarding different numerical algorithms for the transient analysis of biochemical reaction networks from concerns regarding their implementation, thus allowing for portable and efficient solutions. The state of a propagation abstract data type is given by a vector that assigns mass values to a set of nodes, and its (next) operator propagates mass values through this set of nodes. We propose an approximate implementation of the (next) operator, based on threshold abstraction, which propagates only "significant" mass values and thus achieves a compromise between efficiency and accuracy. Finally, we give three use cases for propagation models: the chemical master equation (CME), the reaction rate equation (RRE), and a hybrid method that combines these two equations. These three applications use propagation models in order to propagate probabilities and/or expected values and variances of the model's variables.
AU - Henzinger, Thomas A
AU - Mateescu, Maria
ID - 2302
IS - 2
JF - IEEE ACM Transactions on Computational Biology and Bioinformatics
TI - The propagation approach for computing biochemical reaction networks
VL - 10
ER -
TY - JOUR
AB - The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders.
AU - Dixon-Salazar, Tracy J
AU - Silhavy, Jennifer L
AU - Udpa, Nitin
AU - Schroth, Jana
AU - Bielas, Stephanie L
AU - Schaffer, Ashleigh E
AU - Olvera, Jesus
AU - Bafna, Vineet K
AU - Zaki, Maha S
AU - Abdel-Salam, Ghada M
AU - Mansour, Lobna A
AU - Selim, Laila A
AU - Abdel-Hadi, Sawsan S
AU - Marzouki, Naima
AU - Ben-Omran, Tawfeg I
AU - Al-Saana, Nouriya A
AU - Sönmez, Fatma M
AU - Celep, Figen
AU - Azam, Matloob
AU - Hill, Kiley J
AU - Collazo, Adrienne
AU - Fenstermaker, Ali G
AU - Gaia Novarino
AU - Akizu, Naiara
AU - Garimella, Kiran V
AU - Sougnez, Carrie L
AU - Russ, Carsten
AU - Gabriel, Stacey B
AU - Gleeson, Joseph G
ID - 2313
IS - 138
JF - Science Translational Medicine
TI - Exome sequencing can improve diagnosis and alter patient management
VL - 4
ER -
TY - JOUR
AB - Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.
AU - Gaia Novarino
AU - El-Fishawy, Paul
AU - Kayserili, Hülya
AU - Meguid, Nagwa A
AU - Scott, Eric M
AU - Schroth, Jana
AU - Silhavy, Jennifer L
AU - Kara, Majdi
AU - Khalil, Rehab O
AU - Ben-Omran, Tawfeg I
AU - Ercan-Sencicek, Adife G
AU - Hashish, Adel F
AU - Sanders, Stephan J
AU - Gupta, Abha R
AU - Hashem, Hebatalla S
AU - Matern, Dietrich
AU - Gabriel, Stacey B
AU - Sweetman, Lawrence
AU - Rahimi, Yasmeen
AU - Harris, Robert A
AU - State, Matthew W
AU - Gleeson, Joseph G
ID - 2314
IS - 6105
JF - Science
TI - Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy
VL - 338
ER -
TY - CONF
AB - We summarize our recent results on the ground state energy of multi-polaron systems. In particular, we discuss stability and existence of the thermodynamic limit, and we discuss the absence of binding in the case of large Coulomb repulsion and the corresponding binding-unbinding transition. We also consider the Pekar-Tomasevich approximation to the ground state energy and we study radial symmetry of the ground state density.
AU - Frank, Rupert L
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Thomas, Lawrence E
ID - 2316
TI - Ground state properties of multi-polaron systems
ER -
TY - CONF
AB - We present a summary of our recent rigorous derivation of the celebrated Ginzburg-Landau (GL) theory, starting from the microscopic Bardeen-Cooper-Schrieffer (BCS) model. Close to the critical temperature, GL arises as an effective theory on the macroscopic scale. The relevant scaling limit is semiclassical in nature, and semiclassical analysis, with minimal regularity assumptions, plays an important part in our proof.
AU - Frank, Rupert L
AU - Hainzl, Christian
AU - Robert Seiringer
AU - Solovej, Jan P
ID - 2317
TI - Microscopic derivation of the Ginzburg-Landau model
ER -
TY - JOUR
AB - We show that bosons interacting via pair potentials with negative scattering length form bound states for a suitable number of particles. In other words, the absence of many-particle bound states of any kind implies the non-negativity of the scattering length of the interaction potential.
AU - Seiringer, Robert
ID - 2318
IS - 3
JF - Journal of Spectral Theory
TI - Absence of bound states implies non-negativity of the scattering length
VL - 2
ER -
TY - JOUR
AB - The Manin conjecture is established for Châtelet surfaces over Q aris-ing as minimal proper smooth models of the surface Y 2 + Z 2 = f(X) in A 3 Q, where f ∈ Z[X] is a totally reducible polynomial of degree 3 without repeated roots. These surfaces do not satisfy weak approximation.
AU - de la Bretèche, Régis
AU - Timothy Browning
AU - Peyre, Emmanuel
ID - 237
IS - 1
JF - Annals of Mathematics
TI - On Manin's conjecture for a family of Châtelet surfaces
VL - 175
ER -
TY - JOUR
AB - For given positive integers a, b, q we investigate the density of solutions (x, y) ∈ Z2 to congruences ax + by2 ≡ 0 mod q.
AU - Baier, Stephan
AU - Timothy Browning
ID - 238
IS - 2
JF - Functiones et Approximatio, Commentarii Mathematici
TI - Inhomogeneous quadratic congruences
VL - 47
ER -
TY - JOUR
AB - We study the BCS gap equation for a Fermi gas with unequal population of spin-up and spin-down states. For cosh (δ μ/T) ≤ 2, with T the temperature and δμ the chemical potential difference, the question of existence of non-trivial solutions can be reduced to spectral properties of a linear operator, similar to the unpolarized case studied previously in [Frank, R. L., Hainzl, C., Naboko, S., and Seiringer, R., J., Geom. Anal.17, 559-567 (2007)10.1007/BF02937429; Hainzl, C., Hamza, E., Seiringer, R., and Solovej, J. P., Commun., Math. Phys.281, 349-367 (2008)10.1007/s00220-008-0489-2; and Hainzl, C. and Seiringer, R., Phys. Rev. B77, 184517-110 435 (2008)]10.1103/PhysRevB.77.184517. For cosh (δ μ/T) > 2 the phase diagram is more complicated, however. We derive upper and lower bounds for the critical temperature, and study their behavior in the small coupling limit.
AU - Freiji, Abraham
AU - Hainzl, Christian
AU - Robert Seiringer
ID - 2394
IS - 1
JF - Journal of Mathematical Physics
TI - The gap equation for spin-polarized fermions
VL - 53
ER -
TY - JOUR
AB - We give the first rigorous derivation of the celebrated Ginzburg-Landau (GL) theory, starting from the microscopic Bardeen-Cooper-Schrieffer (BCS) model. Close to the critical temperature, GL arises as an effective theory on the macroscopic scale. The relevant scaling limit is semiclassical in nature, and semiclassical analysis, with minimal regularity assumptions, plays an important part in our proof.
AU - Frank, Rupert L
AU - Hainzl, Christian
AU - Robert Seiringer
AU - Solovej, Jan P
ID - 2395
IS - 3
JF - Journal of the American Mathematical Society
TI - Microscopic derivation of Ginzburg-Landau theory
VL - 25
ER -
TY - JOUR
AB - A positive temperature analogue of the scattering length of a potential V can be defined via integrating the difference of the heat kernels of -Δ and, with Δ the Laplacian. An upper bound on this quantity is a crucial input in the derivation of a bound on the critical temperature of a dilute Bose gas (Seiringer and Ueltschi in Phys Rev B 80:014502, 2009). In (Seiringer and Ueltschi in Phys Rev B 80:014502, 2009), a bound was given in the case of finite range potentials and sufficiently low temperature. In this paper, we improve the bound and extend it to potentials of infinite range.
AU - Landon, Benjamin
AU - Robert Seiringer
ID - 2396
IS - 3
JF - Letters in Mathematical Physics
TI - The scattering length at positive temperature
VL - 100
ER -
TY - JOUR
AB - We consider the low-density limit of a Fermi gas in the BCS approximation. We show that if the interaction potential allows for a two-particle bound state, the system at zero temperature is well approximated by the Gross-Pitaevskii functional, describing a Bose-Einstein condensate of fermion pairs.
AU - Hainzl, Christian
AU - Robert Seiringer
ID - 2397
IS - 2
JF - Letters in Mathematical Physics
TI - Low density limit of BCS theory and Bose-Einstein condensation of Fermion pairs
VL - 100
ER -
TY - GEN
AB - We extend the mathematical theory of quantum hypothesis testing to the general W*-algebraic setting and explore its relation with recent developments in non-equilibrium quantum statistical mechanics. In particular, we relate the large deviation principle for the full counting statistics of entropy flow to quantum hypothesis testing of the arrow of time.
AU - Jakšić, Vojkan
AU - Ogata, Yoshiko
AU - Pillet, Claude A
AU - Robert Seiringer
ID - 2398
IS - 6
T2 - Reviews in Mathematical Physics
TI - Quantum hypothesis testing and non-equilibrium statistical mechanics
VL - 24
ER -
TY - CHAP
AB - Bose–Einstein condensation (BEC) in cold atomic gases was first achieved experimentally in 1995 [1, 6]. After initial failed attempts with spin-polarized atomic hydrogen, the first successful demonstrations of this phenomenon used gases of rubidium and sodium atoms, respectively. Since then there has been a surge of activity in this field, with ingenious experiments putting forth more and more astonishing results about the behavior of matter at very cold temperatures.
AU - Robert Seiringer
ED - Rivasseau, Vincent
ED - Robert Seiringer
ED - Solovej, Jan P
ED - Spencer, Thomas
ID - 2399
T2 - Quantum Many Body Systems
TI - Cold quantum gases and bose einstein condensation
VL - 2051
ER -
TY - JOUR
AB - We investigate the frequency of positive squareful numbers x, y, z≤B for which x+y=z and present a conjecture concerning its asymptotic behavior.
AU - Timothy Browning
AU - Valckenborgh, K Van
ID - 240
IS - 2
JF - Experimental Mathematics
TI - Sums of three squareful numbers
VL - 21
ER -
TY - JOUR
AB - If the polaron coupling constant α is large enough, bipolarons or multi-polarons will form. When passing through the critical α c from above, does the radius of the system simply get arbitrarily large or does it reach a maximum and then explode? We prove that it is always the latter. We also prove the analogous statement for the Pekar-Tomasevich (PT) approximation to the energy, in which case there is a solution to the PT equation at α c. Similarly, we show that the same phenomenon occurs for atoms, e. g., helium, at the critical value of the nuclear charge. Our proofs rely only on energy estimates, not on a detailed analysis of the Schrödinger equation, and are very general. They use the fact that the Coulomb repulsion decays like 1/r, while 'uncertainty principle' localization energies decay more rapidly, as 1/r 2.
AU - Frank, Rupert L
AU - Lieb, Élliott H
AU - Robert Seiringer
ID - 2400
IS - 2
JF - Communications in Mathematical Physics
TI - Binding of polarons and atoms at threshold
VL - 313
ER -