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Amir Rosenfeld, John K Tsotsos
Given an existing trained neural network, it is often desirable to learn new capabilities without hindering performance of those already learned. Existing approaches either learn sub-optimal solutions, require joint training, or incur a substantial increment in the number of parameters for each added domain, typically as many as the original network. We propose a method called Deep Adaptation Modules (DAM) that constrains newly learned filters to be linear combinations of existing ones. DAMs precisely preserve performance on the original domain, require a fraction (typically 13%, dependent on network architecture) of the number of parameters compared to standard fine-tuning procedures and converge in less cycles of training to a comparable or better level of performance...
November 30, 2018: IEEE Transactions on Pattern Analysis and Machine Intelligence
Clare V Logan, Jennie E Murray, David A Parry, Andrea Robertson, Roberto Bellelli, Žygimantė Tarnauskaitė, Rachel Challis, Louise Cleal, Valerie Borel, Adeline Fluteau, Javier Santoyo-Lopez, Tim Aitman, Inês Barroso, Donald Basel, Louise S Bicknell, Himanshu Goel, Hao Hu, Chad Huff, Michele Hutchison, Caroline Joyce, Rachel Knox, Amy E Lacroix, Sylvie Langlois, Shawn McCandless, Julie McCarrier, Kay A Metcalfe, Rose Morrissey, Nuala Murphy, Irène Netchine, Susan M O'Connell, Ann Haskins Olney, Nandina Paria, Jill A Rosenfeld, Mark Sherlock, Erin Syverson, Perrin C White, Carol Wise, Yao Yu, Margaret Zacharin, Indraneel Banerjee, Martin Reijns, Michael B Bober, Robert K Semple, Simon J Boulton, Jonathan J Rios, Andrew P Jackson
During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C...
November 23, 2018: American Journal of Human Genetics
Bobby G Ng, Jill A Rosenfeld, Lisa Emrick, Mahim Jain, Lindsay C Burrage, Brendan Lee, William J Craigen, David R Bearden, Brett H Graham, Hudson H Freeze
FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. Although it is essential for fucose salvage, this pathway is thought to make only a minor contribution to the total amount of GDP-fucose. A second pathway, the major de novo pathway, involves conversion of GDP-mannose to GDP-fucose. Here we describe two unrelated individuals who have pathogenic variants in FUK and who presented with severe developmental delays, encephalopathy, intractable seizures, and hypotonia...
November 21, 2018: American Journal of Human Genetics
Oded Sagiv, Elkanah Rosenfeld, Elinor Kalderon, Tamar Brutman Barazani, Ofira Zloto, Uriel Martinowitz, Guy J Ben Simon, Isaac Zilinsky
OBJECTIVE: Postoperative ecchymoses or hematomas can prolong healing from surgery, and a search for locally administered agents that decrease bleeding is warranted. The objective of this study is to evaluate whether preoperative subcutaneous injection of tranexamic acid (TXA) reduces intra- and postoperative bleeding or ecchymoses in skin-only upper eyelid blepharoplasty surgery. DESIGN: This is a prospective randomized, double-blind, controlled study. PARTICIPANTS: We included 34 consecutive patients who were referred to an upper eyelid blepharoplasty surgery in our institution...
December 2018: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
Megan E Cunningham, Eric H Rosenfeld, Huirong Zhu, Bindi J Naik-Mathuria, Robert T Russell, Adam M Vogel
BACKGROUND: Massive transfusion protocols with balanced blood product ratios have been associated with improved outcomes in adult trauma. The impact on pediatric trauma is unclear. MATERIAL AND METHODS: A retrospective review of the Pediatric Trauma Quality Improvement Program data set was performed using data from January 2015 to December 2016. Trauma patient's ≤ 18 y of age, who received red blood cells (RBCs) and were massively transfused were included. Children with burns, dead on arrival, and nonsurvivable injuries were excluded...
January 2019: Journal of Surgical Research
Shannon Rego, Orit Dagan-Rosenfeld, Wenyu Zhou, M Reza Sailani, Patricia Limcaoco, Elizabeth Colbert, Monika Avina, Jessica Wheeler, Colleen Craig, Denis Salins, Hannes L Rost, Jessilyn Dunn, Tracey McLaughlin, Lars M Steinmetz, Jonathan A Bernstein, Michael P Snyder
Exome sequencing is increasingly utilized in both clinical and non-clinical settings, but little is known about its utility in healthy individuals. Most previous studies on this topic have examined a small subset of genes known to be implicated in human disease and/or have used automated pipelines to assess pathogenicity of known variants. In order to determine the frequency of both medically actionable and non-actionable but medically relevant exome findings in the general population we assessed the exomes of 70 participants who have been extensively characterized over the past several years as part of a longitudinal integrated multi-omics profiling study...
November 28, 2018: Cold Spring Harbor Molecular Case Studies
Louis S Prahl, Patrick F Bangasser, Lauren E Stopfer, Mahya Hemmat, Forest M White, Steven S Rosenfeld, David J Odde
Microtubule-targeting agents (MTAs) are widely used chemotherapy drugs capable of disrupting microtubule-dependent cellular functions, such as division and migration. We show that two clinically approved MTAs, paclitaxel and vinblastine, each suppress stiffness-sensitive migration and polarization characteristic of human glioma cells on compliant hydrogels. MTAs influence microtubule dynamics and cell traction forces by nearly opposite mechanisms, the latter of which can be explained by a combination of changes in myosin motor and adhesion clutch number...
November 27, 2018: Cell Reports
Akshara Narayan Menon, Emily Rosenfeld, C Adam Brush
In an increasingly globalized world, countries face infectious disease threats and public health emergencies that transcend borders, making health security of paramount importance. Legal frameworks, at both the international and national levels, can empower governments to strengthen public health and preparedness systems to better detect and respond to infectious disease threats and public health emergencies. The development of the International Health Regulations (IHR) (2005) and the Global Health Security Agenda (GHSA), and the resulting Joint External Evaluation (JEE), are examples of coordinated global efforts to build capacity to prevent, detect, and respond to the international spread of disease...
2018: Health Security
Ronit Rosenfeld, Anat Zvi, Eitan Winter, Ronen Hope, Ofir Israeli, Ohad Mazor, Gur Yaari
Recombinant antibodies serve as therapeutic molecules for a broad range of applications. High affinity antibodies are typically isolated following an active and effective immunization. Human-like antibodies may be obtained from immunized nonhuman primates (NHP), such as rhesus macaque, when immunized human origin is not available. For the isolation of such antibodies, strategies like phage and yeast display, are employed. These strategies are primarily based on the amplification of the rearranged variable (V) regions coded by mRNA, obtained from lymphatic source of immunized animals...
November 22, 2018: Journal of Immunological Methods
E Debrot, L Tran, L Chartier, D Bolst, S Guatelli, C Vandevoorde, E de Kock, P Beukes, J Symons, J Nieto-Camero, D A Prokopovich, S Chiriotti, A Parisi, M De Saint-Hubert, F Vanhavere, J Slabbert, A B Rosenfeld
With more patients receiving external beam radiation therapy with protons, it becomes increasingly important to refine the clinical understanding of the relative biological effectiveness (RBE) for dose delivered during treatment. Treatment planning systems used in clinics typically implement a constant RBE of 1.1 for proton fields irrespective of their highly heterogeneous linear energy transfer (LET). Quality assurance tools that can measure beam characteristics and quantify or be indicative of biological outcomes become necessary in the transition towards more sophisticated RBE weighted treatment planning and for verification of the Monte Carlo and analytical based models they use...
November 23, 2018: Physics in Medicine and Biology
Cheryl S Rosenfeld, Paul S Cooke
Estrogen binding to estrogen receptors (ESR) triggers signaling cascades within cells. Historically, a major emphasis has been characterizing estrogen-induced genomic actions resulting from binding to nuclear estrogen receptor 1 (nESR1). However, recent evidence indicates the first receptors estrogens encounter as they enter a cell, membrane ESR1 (mESR1), also play crucial roles. Membrane and nuclear ESR are derived from the same transcripts but the former are directed to the membrane via palmitoylation. Binding and activation of mESR1 leads to rapid fluctuations in cAMP and Ca+2 and stimulation of protein kinase pathways...
November 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Elie H Motulsky, Fang Zheng, Yingying Shi, Giovanni Gregori, Philip J Rosenfeld
BACKGROUND AND OBJECTIVE: Swept-source optical coherence tomography angiography (SS-OCTA) and different boundary-specific segmentation strategies were used to distinguish type 1 macular neovascularization (MNV) from type 2 MNV in eyes with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: Eyes with exudative AMD were enrolled in a prospective study. Segmentation strategies included a slab from the outer retina (OR) to the choriocapillaris (CC) for the entire MNV, a slab from the retinal pigment epithelium (RPE) to the CC for the type 1 MNV, and a slab from the OR to the RPE for the type 2 MNV...
November 1, 2018: Ophthalmic Surgery, Lasers & Imaging Retina
Sharon Yunger, Pinhas Kafri, Liat Rosenfeld, Eliraz Greenberg, Noa Kinor, Yuval Garini, Yaron Shav-Tal
Imaging of transcription by quantitative fluorescence-based techniques allows the examination of gene expression kinetics in single cells. Using a cell system for the in vivo visualization of mammalian mRNA transcriptional kinetics at single-gene resolution during the cell cycle, we previously demonstrated a reduction in transcription levels after replication. This phenomenon has been described as a homeostasis mechanism that buffers mRNA transcription levels with respect to the cell cycle stage and the number of transcribing alleles...
October 2018: Life science alliance
Victoria J Vieira-Potter, Tzu-Wen L Cross, Kelly S Swanson, Saurav J Sarma, Zhentian Lei, Lloyd W Sumner, Cheryl S Rosenfeld
Phytoestrogens are plant-derived compounds found in a variety of foods, most notably, soy. These compounds have been shown to improve immuno-metabolic health, yet mechanisms remain uncertain. We demonstrated previously that dietary phytoestrogen-rich soy (SOY) rescued metabolic dysfunction/inflammation following ovariectomy (OVX) in female rats; we also noted remarkable shifts in gut microbiota in SOY vs control diet-fed rats. Importantly, specific bacteria that significantly increased in those fed the SOY correlated positively with several favorable host metabolic parameters...
November 15, 2018: Scientific Reports
William Koven, Enric Gisbert, Oriya Nixon, Mikhail M Solovyev, Aviad Gaon, Guy Allon, Iris Meiri-Ashkenazi, Amos Tandler, Hanna Rosenfeld
A study comprised of two trials determined the effects of water turbidity produced by live microalgae and inert clay particles on the larval rearing of grey mullet (Mugil cephalus). Trial 1 evaluated the effect of microalgae produced water turbidity on grey mullet larval performance and digestive tract (DT) enzyme ontogeny. Two microalgae (Nannochloropsis oculata and Isochrysis galbana) water turbidity levels (0.76 and 1.20 NTU, respectively) and a non-microalgae control (0.26 NTU) were investigated on 2 to 23 dph grey mullet larvae...
November 12, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Katharina Blumchen, Valerie Trendelenburg, Frank Ahrens, Armin Gruebl, Eckard Hamelmann, Gesine Hansen, Andrea Heinzmann, Katja Nemat, Thomas Holzhauser, Martin Roeder, Leonard Rosenfeld, Oliver Hartmann, Bodo Niggemann, Kirsten Beyer
BACKGROUND: Only two, small placebo-controlled trials on peanut- oral immunotherapy (OIT) have been published. OBJECTIVE: We examined the efficacy, safety, immunological parameters, quality of life (QoL) and burden of treatment (BoT) of low-dose peanut- OIT in a multicenter, double-blind, randomized placebo-controlled trial. METHODS: 62 children aged 3-17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut-OIT with a maintenance dose of 125-250 mg peanut protein or placebo...
November 10, 2018: Journal of Allergy and Clinical Immunology in Practice
Levi Madden, James Archer, Enbang Li, Dean Wilkinson, Anatoly Rosenfeld
Convolutional neural network (CNN) type artificial intelligences were trained to estimate the Cerenkov radiation present in the temporal response of a LINAC irradiated scintillator-fiber optic dosimeter. The CNN estimate of Cerenkov radiation is subtracted from the combined scintillation and Cerenkov radiation temporal response of the irradiated scintillator-fiber optic dosimeter, giving the sole scintillation signal, which is proportional to the scintillator dose. The CNN measured scintillator dose was compared to the background subtraction measured scintillator dose and ionisation chamber measured dose...
November 9, 2018: Physics in Medicine and Biology
Sahar Rosenfeld, Daniele Porretta, Eyal Rahav, Valentina Mastrantonio, Claire Duchet, Leon Blaustein
No abstract text is available yet for this article.
December 2018: Journal of Vector Ecology: Journal of the Society for Vector Ecology
Florent Mouliere, Dineika Chandrananda, Anna M Piskorz, Elizabeth K Moore, James Morris, Lise Barlebo Ahlborn, Richard Mair, Teodora Goranova, Francesco Marass, Katrin Heider, Jonathan C M Wan, Anna Supernat, Irena Hudecova, Ioannis Gounaris, Susana Ros, Mercedes Jimenez-Linan, Javier Garcia-Corbacho, Keval Patel, Olga Østrup, Suzanne Murphy, Matthew D Eldridge, Davina Gale, Grant D Stewart, Johanna Burge, Wendy N Cooper, Michiel S van der Heijden, Charles E Massie, Colin Watts, Pippa Corrie, Simon Pacey, Kevin M Brindle, Richard D Baird, Morten Mau-Sørensen, Christine A Parkinson, Christopher G Smith, James D Brenton, Nitzan Rosenfeld
Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0...
November 7, 2018: Science Translational Medicine
Florent Mouliere, Richard Mair, Dineika Chandrananda, Francesco Marass, Christopher G Smith, Jing Su, James Morris, Colin Watts, Kevin M Brindle, Nitzan Rosenfeld
Glioma is difficult to detect or characterize using current liquid biopsy approaches. Detection of cell-free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole-genome sequencing (sWGS, at a coverage of < 0.4×) of cell-free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor...
November 6, 2018: EMBO Molecular Medicine
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