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https://www.readbyqxmd.com/read/29222458/serendipity-and-strategy-in-rapid-innovation
#1
T M A Fink, M Reeves, R Palma, R S Farr
Innovation is to organizations what evolution is to organisms: it is how organizations adapt to environmental change and improve. Yet despite advances in our understanding of evolution, what drives innovation remains elusive. On the one hand, organizations invest heavily in systematic strategies to accelerate innovation. On the other, historical analysis and individual experience suggest that serendipity plays a significant role. To unify these perspectives, we analysed the mathematics of innovation as a search for designs across a universe of component building blocks...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174954/cell-milieu-significantly-affects-the-fate-of-aapoai-amyloidogenic-variants-predestination-or-serendipity
#2
Rosa Gaglione, Giovanni Smaldone, Rocco Di Girolamo, Renata Piccoli, Emilia Pedone, Angela Arciello
BACKGROUND: Specific apolipoprotein A-I variants are associated to severe hereditary amyloidoses. The organ distribution of AApoAI amyloidosis seems to depend on the position of the mutation, since mutations in residues from 1 to 75 are mainly associated to hepatic and renal amyloidosis, while mutations in residues from 173 to 178 are mostly responsible for cardiac, laryngeal, and cutaneous amyloidosis. Molecular bases of this tissue specificity are still poorly understood, but it is increasingly emerging that protein destabilization induced by amyloidogenic mutations is neither necessary nor sufficient for amyloidosis development...
November 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29163515/nanobody-based-delivery-systems-for-diagnosis-and-targeted-tumor-therapy
#3
REVIEW
Yaozhong Hu, Changxiao Liu, Serge Muyldermans
The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma's, monoclonal antibodies (mAbs) have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29154280/sisyphus-in-neverland
#4
Isidro Ferrer
The study of life and living organisms and the way in which these interact and organize to form social communities have been central to my career. I have been fascinated by biology, neurology, and neuropathology, but also by history, sociology, and art. Certain current historical, political, and social events, some occurring proximally but others affecting people in apparently distant places, have had an impact on me. Epicurus, Seneca, and Camus shared their philosophical positions which I learned from. Many scientists from various disciplines have been exciting sources of knowledge as well...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29095986/autobiography-series-from-there-to-here-a-crooked-trail-of-families-crossroads-serendipity-and-impatience
#5
James M Powers
No abstract text is available yet for this article.
October 31, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29094573/chance-serendipity-and-antiepileptic-drugs
#6
Karl Otto Nakken, Eylert Brodtkorb
No abstract text is available yet for this article.
October 31, 2017: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#7
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29052220/efficacy-from-strange-sources
#8
Lawrence Lesko
Reverse translation (RT) refers to perceptions and observations of clinical outcomes, both beneficial and harmful, that can lead to a hypothesis intended to identify a new use of a drug that is different than the original use. I provide a panoramic view of successes in RT from the historic discovery of penicillin to the contemporary development of CAR T therapies. I delineate the core principles of RT that shift discovery from serendipity to a systematic strategy based on target identification based on causal biology, pharmacodynamic biomarkers that recapitulates disease pathophysiology, confirmation of target engagement by clinical proof of concept studies, and optimal selection of dose and interval...
October 20, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29033605/onabotulinum-toxin-a-in-the-treatment-of-chronic-migraine-patient-selection-and-special-considerations
#9
REVIEW
Piero Barbanti, Patrizia Ferroni
Discovered by serendipity, onabotulinum toxin A (BoNT-A) is the only US Food and Drug Administration-approved treatment for the prevention of chronic migraine (CM), one of the most disabling and burdensome human conditions. Its efficacy, safety and tolerability, proved by the largest and longest migraine therapeutic trial (the Phase III Research Evaluating Migraine Prophylaxis Therapy program [PREEMPT]), have been replicated by various real-life studies also in the presence of medication overuse. The benefit of BoNT-A prophylaxis is likely due to its ability to counteract peripheral and central nociceptive sensitization through reversible chemical denervation of pericranial sensitive afferents...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28977688/digenic-inheritance-and-genetic-modifiers
#10
REVIEW
Constantinos Deltas
Digenic inheritance (DI) concerns pathologies with the simplest form of multigenic aetiology, implicating more than one gene (and perhaps the environment). True DI is when biallelic or even triallelic mutations in two distinct genes, in cis or in trans, are necessary and sufficient to cause pathology with a defined diagnosis. In true DI, a heterozygous mutation in each of two genes alone is not associated with a recognizable phenotype. Well-documented diseases with true DI are so far rare and follow non-Mendelian inheritance...
October 4, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28960281/serendipity-in-a-salt-marsh-detecting-frequent-sea-otter-haul-outs-in-a-marsh-ecosystem
#11
Ron Eby, Robert Scoles, Brent Bancroft Hughes, Kerstin Wasson
No abstract text is available yet for this article.
November 2017: Ecology
https://www.readbyqxmd.com/read/28922867/discoveries-of-the-structures-of-sialic-acid-and-cmp-sialic-acid-1957-1960-a-letter-from-saul-roseman
#12
Ronald L Schnaar, Yuan C Lee
Sialic acids have a special place in vertebrate glycobiology, where they constitute the dominant terminal saccharides on many cell surface glycans. From early studies that identified sialoglycans as receptors for important pathogens and toxins to more recent discoveries of sialic acid-binding proteins essential for immune system (and other) functions in humans, sialic acids and sialoglycans have become cornerstones in understanding vertebrate glycobiology and pathology. During a remarkable 3-year period in the late 1950s, a newly minted postdoctoral fellow (Donald G...
June 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28900272/from-malaria-to-cancer-computational-drug-repositioning-of-amodiaquine-using-plip-interaction-patterns
#13
Sebastian Salentin, Melissa F Adasme, Jörg C Heinrich, V Joachim Haupt, Simone Daminelli, Yixin Zhang, Michael Schroeder
Drug repositioning identifies new indications for known drugs. Here we report repositioning of the malaria drug amodiaquine as a potential anti-cancer agent. While most repositioning efforts emerge through serendipity, we have devised a computational approach, which exploits interaction patterns shared between compounds. As a test case, we took the anti-viral drug brivudine (BVDU), which also has anti-cancer activity, and defined ten interaction patterns using our tool PLIP. These patterns characterise BVDU's interaction with its target s...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889281/discovery-of-the-second-messenger-cyclic-di-gmp
#14
Ute Römling, Michael Y Galperin
The nearly ubiquitous bacterial second messenger cyclic di-GMP is involved in a multitude of fundamental physiological processes such as sessility/motility transition and the switch between the acute and chronic infection status, combined with cell cycle control. The discovery of cyclic di-GMP, though, has been an example par excellence of scientific serendipity. We recapitulate here its years-long discovery process as an activator of the cellulose synthase of the environmental bacterium Komagataeibacter xylinus and its consequences for follow-up research...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28856807/finding-serendipity
#15
Nipon Chattipakorn
No abstract text is available yet for this article.
September 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28854560/the-princes-of-serendip
#16
I K Moppett, S R Moonesinghe, M P Grocott
No abstract text is available yet for this article.
August 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28773088/4-2-6-4-and-3-2-6-3-terpyridines-the-conflict-between-well-defined-vectorial-properties-and-serendipity-in-the-assembly-of-1d-2d-and-3d-architectures
#17
Y Maximilian Klein, Alessandro Prescimone, Edwin C Constable, Catherine E Housecroft
A comparative investigation of the coordination assemblies formed between Co(NCS)₂ and two monotopic 4,2':6',4''-terpyridine (4,2':6',4"-tpy) ligands or two related ditopic ligands is reported. Crystals were grown by layering MeOH solutions of Co(NCS)₂ over a CHCl₃ or 1,2-C₆H₄Cl₂ solution of the respective ligand at room temperature. With 4'-(2-methylpyrimidin-5-yl)-4,2':6',4"-terpyridine (6), the 1D-coordination polymer {[Co₂(NCS)₄(MeOH)₄(6)₂]∙2MeOH∙8H₂O}n assembles with 6 coordinating only through the outer N-donors of the 4,2':6',4"-tpy unit; coordination by the MeOH solvent blocks two cobalt coordination sites preventing propagation in a higher-dimensional network...
June 30, 2017: Materials
https://www.readbyqxmd.com/read/28670453/novel-aspects-in-diagnostic-approach-to-respiratory-patients-is-it-the-time-for-a-new-semiotics
#18
Gino Soldati, Andrea Smargiassi, Alberto A Mariani, Riccardo Inchingolo
Medical approach to patients is a fundamental step to get the correct diagnosis. The aim of this paper is to analyze some aspects of the reasoning process inherent in medical diagnosis in our era. Pathologic signs (anamnestic data, symptoms, semiotics, laboratory and strumental findings) represent informative phenomena to be integrated for inferring a diagnosis. Thus, diagnosis begins with "signs" and finishes in a probability of disease. The abductive reasoning process is the generation of a hypothesis to explain one or more observations (signs) in order to decide between alternative explanations searching the best one...
2017: Multidisciplinary Respiratory Medicine
https://www.readbyqxmd.com/read/28653277/moving-beyond-serendipity-to-mechanism-driven-psychiatric-therapeutics
#19
EDITORIAL
Andrew A Pieper, Jay M Baraban
No abstract text is available yet for this article.
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28647023/how-i-became-a-clinician-scientist-in-dermatology-a-tale-of-serendipity-wise-mentors-and-a-good-pinch-of-tenacity
#20
EDITORIAL
Thomas Krieg
No abstract text is available yet for this article.
July 2017: Journal of Investigative Dermatology
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