scholarly journals Light transport and amplification for a proof-of-principle experiment of Optical Stochastic Cooling

2018 ◽  
Author(s):  
Matthew Benjamin Andorf
Keyword(s):  
Light Transport ◽  
Optical Stochastic Cooling ◽  
Proof Of Principle

Zellersatztherapie beim Morbus Parkinson

2005 ◽  
Vol 24 (01) ◽  
pp. 36-40
Author(s):  
A. Storch ◽  
J. Schwarz
Keyword(s):  
Morbus Parkinson ◽  
Kontrollierte Studien ◽  
Proof Of Principle

ZusammenfassungDer Ersatz dopaminerger Neurone bei Patienten mit Morbus Parkinson bleibt eine attraktive Behandlungsstrategie. Die Implantation von embryonalem Mittelhirngewebe war die erste Therapie, die nicht nur den »Proof-of-Principle« in Tierversuchen lieferte, sondern auch Eingang in klinische Applikationen fand. 1987 wurde zunächst eine Reihe von kleinen offenen Studien mit sorgfältiger Patientenselektion gestartet, die sehr ermutigende Ergebnisse bei zumindest einem Teil der Patienten erbrachten. In den vergangenen Jahren wurden in den USA zwei doppelblinde, kontrollierte Studien abgeschlossen, deren Resultate eher enttäuschend blieben, da die primären Endpunkte (Besserung der Parkinson-Symptomatik im Off) keine signifikanten Unterschiede zeigten. Zudem wurden in beiden Studien 12 Stunden nach L-Dopa-Einnahme Dyskinesien beobachtet. Die Ursachen dieser unterschiedlichen Ergebnisse könnten in der Variabilität des Gewebes, relevanten Immunreaktionen und ungleichmäßiger Dopaminausschüttung im Striatum liegen. Zudem legen die ethischen Probleme bei der Gewinnung des Gewebes die Notwendigkeit anderer, besser standardisierter Gewebe nahe. Derzeit scheint es möglich, dass alternativ sowohl aus embryonalen als auch neuralen Stammzellen, vielleicht sogar aus körpereigenen mesenchymalen Stammzellen dopaminerge Neurone generiert werden könnten. Diese Zellen können über einen langen Zeitraum expandiert, ausreichend standardisiert und charakterisiert werden.

Skin Chromophore Estimation from Mobile Selfie Images using Constrained Independent Component Analysis

2020 ◽  
Vol 2020 (14) ◽  
pp. 357-1-357-6
Author(s):  
Luisa F. Polanía ◽  
Raja Bala ◽  
Ankur Purwar ◽  
Paul Matts ◽  
Martin Maltz
Keyword(s):  
Independent Component Analysis ◽  
Spectral Reflectance ◽  
Source Separation ◽  
Principal Component ◽  
Component Analysis ◽  
Previous Method ◽  
Independent Component ◽  
Light Transport ◽  
Camera Model ◽  
Constrained Independent Component Analysis

Human skin is made up of two primary chromophores: melanin, the pigment in the epidermis giving skin its color; and hemoglobin, the pigment in the red blood cells of the vascular network within the dermis. The relative concentrations of these chromophores provide a vital indicator for skin health and appearance. We present a technique to automatically estimate chromophore maps from RGB images of human faces captured with mobile devices such as smartphones. The ultimate goal is to provide a diagnostic aid for individuals to monitor and improve the quality of their facial skin. A previous method approaches the problem as one of blind source separation, and applies Independent Component Analysis (ICA) in camera RGB space to estimate the chromophores. We extend this technique in two important ways. First we observe that models for light transport in skin call for source separation to be performed in log spectral reflectance coordinates rather than in RGB. Thus we transform camera RGB to a spectral reflectance space prior to applying ICA. This process involves the use of a linear camera model and Principal Component Analysis to represent skin spectral reflectance as a lowdimensional manifold. The camera model requires knowledge of the incident illuminant, which we obtain via a novel technique that uses the human lip as a calibration object. Second, we address an inherent limitation with ICA that the ordering of the separated signals is random and ambiguous. We incorporate a domain-specific prior model for human chromophore spectra as a constraint in solving ICA. Results on a dataset of mobile camera images show high quality and unambiguous recovery of chromophores.

Enantioselective Multi-Component Cyclopropane Synthesis Enabled by Cu-Catalyzed Cyclopropene Carbometallation with Organoboron Reagent

2018 ◽  
Author(s):  
Zhanyu Li ◽  
Mengru Zhang ◽  
Yu Zhang ◽  
Shuang Liu ◽  
Jinbo Zhao ◽  
...  
Keyword(s):  
Carbon Source ◽  
Stereoselective Synthesis ◽  
Organometallic Reagents ◽  
Preliminary Results ◽  
Quaternary Center ◽  
Chiral Centers ◽  
Substituted Cyclopropanes ◽  
Proof Of Principle

Deployment of organoboron in lieu of the strongly basic <br>organometallic reagents as carbon source in Cu-catalyzed <br>cyclopropene carbometallation opens unprecedented three-<br>component reactivity for stereoselective synthesis of poly-substituted cyclopropanes. A proof-of-principle demonstration of this novel carbometallation strategy is presented herein for a highly convergent access to poly-substituted aminocyclopropane framework via <br>carboamination. Preliminary results on asymmetric desymmetrization with commercial bisphosphine ligands attained high levels of enantioselection, offering a straightforward access to enantioenriched aminocyclopropanes bearing all-three chiral centers, including an all-carbon quaternary center. This strategy may underpin a host of novel synthetic protocols for poly-substituted cyclopropanes. <br>

Covalent-Fragment Screening of Brd4 Identifies a Ligandable Site Orthogonal to the Acetyl-Lysine Binding Sites

2019 ◽  
Author(s):  
Michael Olp ◽  
Daniel Sprague ◽  
Stefan Kathman ◽  
Ziyang Xu ◽  
Alexandar Statsyuk ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Binding Site ◽  
Binding Sites ◽  
Computational Prediction ◽  
Chemical Probes ◽  
Computational Docking ◽  
Fragment Screening ◽  
Covalent Inhibitors ◽  
Bet Protein ◽  
Proof Of Principle

<p>Brd4, a member of the bromodomain and extraterminal domain (BET) family, has emerged as a promising epigenetic target in cancer and inflammatory disorders. All reported BET family ligands bind within the bromodomain acetyl-lysine binding sites and competitively inhibit BET protein interaction with acetylated chromatin. Alternative chemical probes that act orthogonally to the highly-conserved acetyl-lysine binding sites may exhibit selectivity within the BET family and avoid recently reported toxicity in clinical trials of BET bromodomain inhibitors. Here, we report the first identification of a ligandable site on a bromodomain outside the acetyl-lysine binding site. Inspired by our computational prediction of hotspots adjacent to non-homologous cysteine residues within the <i>C</i>-terminal Brd4 bromodomain (Brd4-BD2), we performed a mid-throughput mass spectrometry screen to identify cysteine-reactive fragments that covalently and selectively modify Brd4. Subsequent mass spectrometry, NMR and computational docking analyses of electrophilic fragment hits revealed a novel ligandable site near Cys356 that is unique to Brd4 among all human bromodomains. This site is orthogonal to the Brd4-BD2 acetyl-lysine binding site as Cys356 modification did not impact binding of the pan-BET bromodomain inhibitor JQ1 in fluorescence polarization assays. Finally, we tethered covalent fragments to JQ1 and performed NanoBRET assays to provide proof of principle that this orthogonal site can be covalently targeted in intact human cells. Overall, we demonstrate the potential of targeting sites orthogonal to bromodomain acetyl-lysine binding sites to develop bivalent and covalent inhibitors that displace Brd4 from chromatin.</p>

Sign in / Sign up

Export Citation Format

Share Document