Understanding the roles of glia and circulating leukocytes in neurodegenerative diseases
Tay, Tuan Leng; Locatelli, Giuseppe; Constantin, Gabriela; Yong, V. Wee
↧
Understanding the roles of glia and circulating leukocytes in neurodegenerative diseases
↧
EbbRT: a framework for building per-application library operating systems
EbbRT: a framework for building per-application library operating systems
Krieger, O.
Keeton, Kimberly; Roscoe, Timothy
General purpose operating systems sacrifice per-application performance in order to preserve generality.
On the other hand, substantial effort is required to customize or construct an operating system to meet the needs of an application. This paper describes the design and implementation of the Elastic Building Block Runtime (EbbRT), a framework for building per-application library operating systems. EbbRT reduces the effort required to construct and maintain library operating systems without hindering the degree of specialization required for high performance. We combine several techniques in order to achieve this, including a distributed OS architecture, a low-overhead component model, a lightweight event-driven runtime, and many language level primitives. EbbRT is able to simultaneously enable performance specialization, support for a broad range of
applications, and ease the burden of systems development.
An EbbRT prototype demonstrates the degree of customization made possible by our framework approach.
In an evaluation of memcached, EbbRT and is able to attain 2:08 higher throughput than Linux. The node.js runtime, ported to EbbRT, demonstrates the broad applicability and ease of development enabled by our approach
↧
↧
Towards general-purpose neural network computing
Towards general-purpose neural network computing
Eldridge, S.; Waterland, A.; Seltzer, M.; Appavoo, Jonathan; Joshi, Ajay
↧
On facility location problem in the local differential privacy model
On facility location problem in the local differential privacy model
Cohen-Addad, Vincent; Esencayi, Yunus; Fan, Chenglin; Gaboardi, Marco; Li, Shi; Wang, Di
In this paper we study the uncapacitated facility location problem in the model of differential privacy (DP) with uniform facility cost. Specifically, we first show that, under the hierarchically well-separated tree (HST) metrics and the super-set output setting that was introduced in [8], there is an ∊-DP algorithm that achieves an O (¹/∊) expected multiplicative) approximation ratio; this implies an O( ^log n/_∊) approximation ratio for the general metric case, where n is the size of the input metric. These bounds improve the best-known results given by [8]. In particular, our
approximation ratio for HST-metrics is independent of n, and the ratio for general metrics is independent of the aspect ratio of the input metric.
On the negative side, we show that the approximation ratio of any ∊-DP algorithm is lower bounded by Ω (1/√∊), even for instances on HST metrics with uniform facility cost, under the super-set output setting. The lower bound shows that the dependence of the approximation ratio for HST metrics on ∊ can not be removed or greatly improved.
Our novel methods and techniques for both the upper and lower bound may find additional applications.
↧
Equilibrium information in credence goods; Oslo Metropolitan University seminar presentation
Equilibrium information in credence goods; Oslo Metropolitan University seminar presentation
Ma, Ching-To; Liu, Ting
↧
↧
The Bruce effect: representational stability and memory formation in the accessory olfactory bulb of the female mouse
The Bruce effect: representational stability and memory formation in the accessory olfactory bulb of the female mouse
Yoles-Frenkel, Michal; Shea, Stephen D.; Davison, Ian G.; Ben-Shaul, Yoram
In the Bruce effect, a mated female mouse becomes resistant to the pregnancy-blocking effect of the stud. Various lines of evidence suggest that this form of behavioral imprinting results from reduced sensitivity of the female's accessory olfactory bulb (AOB) to the stud's chemosignals. However, the AOB's combinatorial code implies that diminishing responses to one individual will distort representations of other stimuli. Here, we record extracellular responses of AOB neurons in mated and unmated female mice while presenting urine stimuli from the stud and from other sources. We find that, while initial sensory responses in the AOB (within a timescale required to guide social interactions) remain stable, responses to extended stimulation (as required for eliciting the pregnancy block) display selective attenuation of stud-responsive neurons. Such temporal disassociation could allow attenuation of slow-acting endocrine processes in a stimulus-specific manner without compromising ongoing representations that guide behavior.
↧
Rapid changes in synaptic strength after mild traumatic brain injury
Rapid changes in synaptic strength after mild traumatic brain injury
Witkowski, Ellen D.; Gao, Yuan; Gavsyuk, Alexander F.; Maor, Ido; DeWalt, Gloria J.; Eldred, William D.; Mizrahi, Adi; Davison, Ian G.
Traumatic brain injury (TBI) affects millions of Americans annually, but effective treatments remain inadequate due to our poor understanding of how injury impacts neural function. Data are particularly limited for mild, closed-skull TBI, which forms the majority of human cases, and for acute injury phases, when trauma effects and compensatory responses appear highly dynamic. Here we use a mouse model of mild TBI to characterize injury-induced synaptic dysfunction, and examine its progression over the hours to days after trauma. Mild injury consistently caused both locomotor deficits and localized neuroinflammation in piriform and entorhinal cortices, along with reduced olfactory discrimination ability. Using whole-cell recordings to characterize synaptic input onto piriform pyramidal neurons, we found moderate effects on excitatory or inhibitory synaptic function at 48 h after TBI and robust increase in excitatory inputs in slices prepared 1 h after injury. Excitatory increases predominated over inhibitory effects, suggesting that loss of excitatory-inhibitory balance is a common feature of both mild and severe TBI. Our data indicate that mild injury drives rapidly evolving alterations in neural function in the hours following injury, highlighting the need to better characterize the interplay between the primary trauma responses and compensatory effects during this early time period.
↧
Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
Dorsolateral septum somatostatin interneurons gate mobility to calibrate context-specific behavioral fear responses
Besnard, Antoine; Gao, Yuan; Kim, Michael TaeWoo; Twarkowski, Hannah; Reed, Alexander Keith; Langberg, Tomer; Feng, Wendy; Xu, Xiangmin; Saur, Dieter; Zweifel, Larry S.; Davison, Ian; Sahay, Amar
Adaptive fear responses to external threats rely upon efficient relay of computations underlying contextual encoding to subcortical circuits. Brain-wide analysis of highly coactivated ensembles following contextual fear discrimination identified the dorsolateral septum (DLS) as a relay of the dentate gyrus-CA3 circuit. Retrograde monosynaptic tracing and electrophysiological whole-cell recordings demonstrated that DLS somatostatin-expressing interneurons (SST-INs) receive direct CA3 inputs. Longitudinal in vivo calcium imaging of DLS SST-INs in awake, behaving mice identified a stable population of footshock-responsive SST-INs during contextual conditioning whose activity tracked and predicted non-freezing epochs during subsequent recall in the training context but not in a similar, neutral context or open field. Optogenetic attenuation or stimulation of DLS SST-INs bidirectionally modulated conditioned fear responses and recruited proximal and distal subcortical targets. Together, these observations suggest a role for a potentially hard-wired DLS SST-IN subpopulation as arbiters of mobility that calibrate context-appropriate behavioral fear responses.
↧
Dark radiation from neutrino mixing after Big Bang Nucleosynthesis
Dark radiation from neutrino mixing after Big Bang Nucleosynthesis
Schmaltz, Martin; Joseph, Melissa; Aloni, Daniel; Weiner, Neal
↧
↧
A step in understanding the S8 tension
A step in understanding the S8 tension
Schmaltz, Martin; Joseph, Melissa; Aloni, Daniel; Weiner, Neal; Sivarajan, Eashwar
↧
Cosmology intertwined: a review of the particle physics, astrophysics, and cosmology associated with the cosmological tensions and anomalies
Cosmology intertwined: a review of the particle physics, astrophysics, and cosmology associated with the cosmological tensions and anomalies
Abdalla, Elcio; Abellán, Guillermo Franco; Aboubrahim, Amin; Agnello, Adriano; Akarsu, Özgür; Akrami, Yashar; Alestas, George; Aloni, Daniel; Amendola, Luca; Anchordoqui, Luis A.; Anderson, Richard I.; Arendse, Nikki; Asgari, Marika; Ballardini, Mario; Barger, Vernon; Basilakos, Spyros; Batista, Ronaldo C.; Battistelli, Elia S.; Battye, Richard; Benetti, Micol; Benisty, David; Berlin, Asher; de Bernardis, Paolo; Berti, Emanuele; Bidenko, Bohdan; Birrer, Simon; Blakeslee, John P.; Boddy, Kimberly K.; Bom, Clecio R.; Bonilla, Alexander; Borghi, Nicola; Bouchet, François R.; Braglia, Matteo; Buchert, Thomas; Buckley-Geer, Elizabeth; Calabrese, Erminia; Caldwell, Robert R.; Camarena, David; Capozziello, Salvatore; Casertano, Stefano; Chen, Geoff C.-F.; Chluba, Jens; Chen, Angela; Chen, Hsin-Yu; Chudaykin, Anton; Cicoli, Michele; Copi, Craig J.; Courbin, Fred; Cyr-Racine, Francis-Yan; Czerny, Bożena; Dainotti, Maria; D'Amico, Guido; Davis, Anne-Christine; de Cruz Pérez, Javier; de Haro, Jaume; Delabrouille, Jacques; Denton, Peter B.; Dhawan, Suhail; Dienes, Keith R.; Di Valentino, Eleonora; Du, Pu; Eckert, Dominique; Escamilla-Rivera, Celia; Ferté, Agnès; Finelli, Fabio; Fosalba, Pablo; Freedman, Wendy L.; Frusciante, Noemi; Gaztañaga, Enrique; Giarè, William; Giusarma, Elena; Gómez-Valent, Adrià; Handley, Will; Harrison, Ian; Hart, Luke; Hazra, Dhiraj Kumar; Heavens, Alan; Heinesen, Asta; Hildebrandt, Hendrik; Hill, J. Colin; Hogg, Natalie B.; Holz, Daniel E.; Hooper, Deanna C.; Hosseininejad, Nikoo; Huterer, Dragan; Ishak, Mustapha; Ivanov, Mikhail M.; Jaffe, Andrew H.; Jang, In Sung; Jedamzik, Karsten; Jimenez, Raul; Joseph, Melissa; Joudaki, Shahab; Kamionkowski, Marc; Karwal, Tanvi; Kazantzidis, Lavrentios; Keeley, Ryan E.; Klasen, Michael; Komatsu, Eiichiro; Koopmans, Léon V.E.; Kumar, Suresh; Lamagna, Luca; Lazkoz, Ruth; Lee, Chung-Chi; Lesgourgues, Julien; Levi Said, Jackson; Lewis, Tiffany R.; L'Huillier, Benjamin; Lucca, Matteo; Maartens, Roy; Macri, Lucas M.; Marfatia, Danny; Marra, Valerio; Martins, Carlos JAP; Masi, Silvia; Matarrese, Sabino; Mazumdar, Arindam; Melchiorri, Alessandro; Mena, Olga; Mersini-Houghton, Laura; Mertens, James; Milaković, Dinko; Minami, Yuto; Miranda, Vivian; Moreno-Pulido, Cristian; Moresco, Michele; Mota, David F.; Mottola, Emil; Mozzon, Simone; Muir, Jessica; Mukherjee, Ankan; Mukherjee, Suvodip; Naselsky, Pavel; Nath, Pran; Nesseris, Savvas; Niedermann, Florian; Notari, Alessio; Nunes, Rafael C.; Ó Colgáin, Eoin; Owens, Kayla A.; Özülker, Emre; Pace, Francesco; Paliathanasis, Andronikos; Palmese, Antonella; Pan, Supriya; Paoletti, Daniela; Perez Bergliaffa, Santiago E.; Perivolaropoulos, Leandros; Pesce, Dominic W.; Pettorino, Valeria; Philcox, Oliver H.E.; Pogosian, Levon; Poulin, Vivian; Poulot, Gaspard; Raveri, Marco; Reid, Mark J.; Renzi, Fabrizio; Riess, Adam G.; Sabla, Vivian I.; Salucci, Paolo; Salzano, Vincenzo; Saridakis, Emmanuel N.; Sathyaprakash, Bangalore S.; Schmaltz, Martin; Schöneberg, Nils; Scolnic, Dan; Sen, Anjan A.; Sehgal, Neelima; Shafieloo, Arman; Sheikh-Jabbari, M.M.; Silk, Joseph; Silvestri, Alessandra; Skara, Foteini; Sloth, Martin S.; Soares-Santos, Marcelle; Solà Peracaula, Joan; Songsheng, Yu-Yang; Soriano, Jorge F.; Staicova, Denitsa; Starkman, Glenn D.; Szapudi, István; Teixeira, Elsa M.; Thomas, Brooks; Treu, Tommaso; Trott, Emery; van de Bruck, Carsten; Vazquez, J. Alberto; Verde, Licia; Visinelli, Luca; Wang, Deng; Wang, Jian-Min; Wang, Shao-Jiang; Watkins, Richard; Watson, Scott; Webb, John K.; Weiner, Neal; Weltman, Amanda; Witte, Samuel J.; Wojtak, Radosław; Yadav, Anil Kumar; Yang, Weiqiang; Zhao, Gong-Bo; Zumalacárregui, Miguel
↧
Response: expert or intellectual? Other views of legal and medical expertise
Response: expert or intellectual? Other views of legal and medical expertise
Uden, James
Bubb, Claire; Peachin, Michael
↧
Sublinear-time computation in the presence of online erasures
Sublinear-time computation in the presence of online erasures
Kalemaj, Iden; Raskhodnikova, Sofya; Varma, Nithin
We initiate the study of sublinear-time algorithms that access their input via an online adversarial
erasure oracle. After answering each query to the input object, such an oracle can erase t input values.
Our goal is to understand the complexity of basic computational tasks in extremely adversarial
situations, where the algorithm’s access to data is blocked during the execution of the algorithm in
response to its actions. Specifically, we focus on property testing in the model with online erasures.
We show that two fundamental properties of functions, linearity and quadraticity, can be tested
for constant t with asymptotically the same complexity as in the standard property testing model.
For linearity testing, we prove tight bounds in terms of t, showing that the query complexity isΘ(log t). In contrast to linearity and quadraticity, some other properties, including sortedness and
the Lipschitz property of sequences, cannot be tested at all, even for t = 1. Our investigation leads to
a deeper understanding of the structure of violations of linearity and other widely studied properties.
↧
↧
Predictors of self-perceived stigma in Parkinson’s disease
Predictors of self-perceived stigma in Parkinson’s disease
Salazar, Robert D.; Weizenbaum, Emma; Ellis, Terry D.; Earhart, G.M.; Ford, M.P.; Dibble, L.E.; Cronin-Golomb, Alice
OBJECTIVE: The burden of PD extends beyond physical limitations and includes significant psychosocial adjustments as individuals undergo changes to their self-perception and how others perceive them. There is limited quantitative evidence of the factors that contribute to self-perceived stigma, which we addressed in the present study.
METHODS: In 362 individuals with PD (157 women, 205 men), self-perceived stigma was measured by the four-item stigma subscale of the Parkinson's Disease Questionnaire (PDQ-39). Hierarchical linear modeling was used to assess predictors of stigma including demographics (age, gender) and disease characteristics: duration, stage (Hoehn & Yahr Scale), motor severity (Unified Parkinson's Disease Rating Scale, UPDRS, Part 3), activities of daily living (UPDRS Part 2), and depression (Geriatric Depression Scale). Predictor variables were chosen based on their significant correlations with the stigma subscale. Further analyses were conducted for men and women separately.
RESULTS: For the total sample, the full model accounted for 14% of the variance in stigma perception (p < .001). Younger age and higher depression scores were the only significant predictors (both p < .001). This pattern was also seen for the men in the sample. For the women, only depression was a significant predictor. Depression mediated the relation between stigma and activities of daily living.
CONCLUSIONS: Younger age (men) and depression (men and women) were the primary predictors of self-perceived stigma in PD. Disease characteristics (motor and ADL) did not contribute to stigma perception. Depression is a potential treatment target for self-perceived stigma in PD.
↧
Derivedness index for estimating degree of phenotypic evolution of embryos: a study of comparative transcriptomic analyses of chordates and echinoderms
Derivedness index for estimating degree of phenotypic evolution of embryos: a study of comparative transcriptomic analyses of chordates and echinoderms
Leong, Jason Cheok Kuan; Li, Yongxin; Uesaka, Masahiro; Uchida, Yui; Omori, Akihito; Hao, Meng; Wan, Wenting; Dong, Yang; Ren, Yandong; Zhang, Si; Zeng, Tao; Wang, Fayou; Chen, Luonan; Wessel, Gary; Livingston, Brian T.; Bradham, Cynthia; Wang, Wen; Irie, Naoki
Species retaining ancestral features, such as species called living fossils, are often regarded as less derived than their sister groups, but such discussions are usually based on qualitative enumeration of conserved traits. This approach creates a major barrier, especially when quantifying the degree of phenotypic evolution or degree of derivedness, since it focuses only on commonly shared traits, and newly acquired or lost traits are often overlooked. To provide a potential solution to this problem, especially for inter-species comparison of gene expression profiles, we propose a new method named "derivedness index" to quantify the degree of derivedness. In contrast to the conservation-based approach, which deals with expressions of commonly shared genes among species being compared, the derivedness index also considers those that were potentially lost or duplicated during evolution. By applying our method, we found that the gene expression profiles of penta-radial phases in echinoderm tended to be more highly derived than those of the bilateral phase. However, our results suggest that echinoderms may not have experienced much larger modifications to their developmental systems than chordates, at least at the transcriptomic level. In vertebrates, we found that the mid-embryonic and organogenesis stages were generally less derived than the earlier or later stages, indicating that the conserved phylotypic period is also less derived. We also found genes that potentially explain less derivedness, such as Hox genes. Finally, we highlight technical concerns that may influence the measured transcriptomic derivedness, such as read depth and library preparation protocols, for further improvement of our method through future studies. We anticipate that this index will serve as a quantitative guide in the search for constrained developmental phases or processes.
↧
The developmental transcriptome for Lytechinus variegatus exhibits temporally punctuated gene expression changes
The developmental transcriptome for Lytechinus variegatus exhibits temporally punctuated gene expression changes
Hogan, John D.; Keenan, Jessica L.; Luo, Lingqi; Ibn-Salem, Jonas; Lamba, Arjun; Schatzberg, Daphne; Piacentino, Michael L.; Zuch, Daniel T.; Core, Amanda B.; Blumberg, Carolyn; Timmermann, Bernd; Grau, José Horacio; Speranza, Emily; Andrade-Navarro, Miguel A.; Irie, Naoki; Poustka, Albert J.; Bradham, Cynthia A.
Embryonic development is arguably the most complex process an organism undergoes during its lifetime, and understanding this complexity is best approached with a systems-level perspective. The sea urchin has become a highly valuable model organism for understanding developmental specification, morphogenesis, and evolution. As a non-chordate deuterostome, the sea urchin occupies an important evolutionary niche between protostomes and vertebrates. Lytechinus variegatus (Lv) is an Atlantic species that has been well studied, and which has provided important insights into signal transduction, patterning, and morphogenetic changes during embryonic and larval development. The Pacific species, Strongylocentrotus purpuratus (Sp), is another well-studied sea urchin, particularly for gene regulatory networks (GRNs) and cis-regulatory analyses. A well-annotated genome and transcriptome for Sp are available, but similar resources have not been developed for Lv. Here, we provide an analysis of the Lv transcriptome at 11 timepoints during embryonic and larval development. Temporal analysis suggests that the gene regulatory networks that underlie specification are well-conserved among sea urchin species. We show that the major transitions in variation of embryonic transcription divide the developmental time series into four distinct, temporally sequential phases. Our work shows that sea urchin development occurs via sequential intervals of relatively stable gene expression states that are punctuated by abrupt transitions.
↧
ICAT: a novel algorithm to robustly identify cell states following perturbations in single cell transcriptomes
ICAT: a novel algorithm to robustly identify cell states following perturbations in single cell transcriptomes
Hawkins, Dakota Y.; Zuch, Daniel T.; Huth, James; Rodriguez-Sastre, Nahomie; McCutcheon, Kelley R.; Glick, Abigail; Lion, Alexandra T.; Thomas, Christopher F.; Descoteaux, Abigail E.; Johnson, W. Evan; Bradham, Cynthia A.
↧
↧
Voltage-gated sodium channel activity mediates sea urchin larval skeletal patterning through spatial regulation of Wnt5 expression
Voltage-gated sodium channel activity mediates sea urchin larval skeletal patterning through spatial regulation of Wnt5 expression
Thomas, Christopher F.; Hawkins, Dakota Y.; Skidanova, Viktoriya; Marrujo, Simone R.; Gibson, Janay; Ye, Ziqing; Bradham, Cynthia A.
↧
Polychrome labeling reveals skeletal triradiate and elongation dynamics and abnormalities in patterning cue-perturbed embryos
Polychrome labeling reveals skeletal triradiate and elongation dynamics and abnormalities in patterning cue-perturbed embryos
Descoteaux, Abigail E.; Zuch, Daniel T.; Bradham, Cynthia A.
↧
Ethanol exposure perturbs sea urchin development and disrupts developmental timing
Ethanol exposure perturbs sea urchin development and disrupts developmental timing
Rodríguez-Sastre, Nahomie; Shapiro, Nicholas; Hawkins, Dakota Y.; Lion, Alexandra T.; Peyreau, Monique; Correa, Andrea E.; Dionne, Kristin; Bradham, Cynthia A.
Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal
alcohol syndrome (FAS). Our results show that sea urchin embryos treated with ethanol similarly
show broad skeletal patterning defects, potentially analogous to the defects associated with FAS.
The sea urchin larval skeleton is a simple patterning system that involves only two cell types: the
primary mesenchymal cells (PMCs) that secrete the calcium carbonate skeleton and the
ectodermal cells that provide migratory, positional, and differentiation cues for the PMCs.
Perturbations in RA biosynthesis and Hh signaling pathways are thought to be causal for the
FAS phenotype in vertebrates. Surprisingly, our results indicate that these pathways are not
functionally relevant for the teratogenic effects of ethanol in developing sea urchins. We found
that developmental morphology as well as the expression of ectodermal and PMC genes was
delayed by ethanol exposure. Temporal transcriptome analysis revealed significant impacts of
ethanol on signaling and metabolic gene expression, and a disruption in the timing of GRN gene
expression that includes both delayed and precocious gene expression throughout the
specification network. We conclude that the skeletal patterning perturbations in ethanol-treated
embryos likely arise from a loss of temporal synchrony within and between the instructive and
responsive tissues.
↧