For years you have been telling us to read this, look at that , look what Wolfgang did in 2015!!! Wow very impressive in 2015!!! Now 2018, Bbbbhenny and we r at 24 pennies, ur boss has disappeared, and nobody knows what the fuk is going on!!! I dont want to hear from Wolf and his Gang!!! Where is Roger and his slam bam I got it in hand approach to being a ceo??? Ten years, 24 pennies, no personal support for his own company during its more crucial time! Has he given us his views on our results??? Good? Bad? Indifferent??? The bottom info you have given us is just more waste of our time, mindless drivel!! 24 pennies is reality! WE KNOW OUR SCIENCE IS GREAT, SOLID!! WHY ISNT HE SAYING THAT, WHY IS HE SILENT???? What are his plans for the new year??? I know , lets guess?? Ok my guess is he will fuk it all up like he has for the last 11 months!!! Any other guesses??? Love investing where the ceo encourages guessing rather than receiving solid information FROM THE FUKKIN GUY IN CHARGE!!!  Sad!!!!!! REALLY SAD! 




quote=bencro]TLT is clearly teaming up with the best.  Here's just another example.

Dr. Rueck's longtime collaborator, Wolfgang Becker, was able to come up with this amazing demonstration, with the same FLIM/PLIM technology that TLT will be presenting on:

BH News 2015-03

bh TCSPC Detects Mouse Behaviour

Cui et al. used a bh SPC150 TCSPC module in combination with a fibre-optical system to record Ca++ signals from the brain of mice performing an operant task. The fluorescence of a Ca++ sensor was excited and detected via fibre-optics implanted in the head of the mouse. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements and predicted the occurance of specific movements within 500 ms.


More at:  http://www.becker-hickl.de/bhnews.htm


By the way, Dr. Rueck and Dr. Wolfgang Becker will both lecture @Berkeley Univ. and Dr. Becker clearly has a huge credibility @Berkeley Univ.:

15th Annual Advanced Imaging Methods Workshop 
 

January 24-26, 2018 
Berkeley City Club 
Berkeley, CA


AIM is a full 3-day event with talks from internationally-renowned researchers from a wide variety of fields, including biology, chemistry, physics, engineering, and optics.

Past speakers have included 5 Nobel Laureates: Roger Tsien, WE Moerner, Stephen Hell, Eric Betzig, and Steven Chu. In addition to invited talks, AIM also includes a vendor show with demonstrations on-site, off-site visits to the CRL MIC and other campus facilities, as well as a popular poster session with beer and wine in the Julia Morgan Room at the Berkeley City Club. 

 

Organizing Committee


Holly Aaron, CRL Molecular Imaging Center, University of California, Berkeley
Wolfgang Becker, Becker-Hickl GmbH
Eric Betzig, Physics, University of California, Berkeley
Xavier Darzacq, Molecular and Cell Biology, University of California, Berkeley
Danielle Jorgens, Electron Microscope Lab, University of California, Berkeley
Markita Landry, Chemical and Biomolecular Engineering, University of California, Berkeley
Evan Miller, Chemistry and Molecular and Cell Biology, University of California, Berkeley
Jon Mulholland, Cell Sciences Imaging Facility, Stanford University
Laura Waller, Electrical Engineering and Computer Sciences, University of California, Berkeley

Speakers

Kimberly Beatty, Oregon Health & Science University
Wolfgang BeckerBecker-Hickl, Germany
Jeff Chan, University of Illinois, Urbana-Champaign
Laurent Cognet, Institute of Optics, University of Bordeaux, France
Emilia Entcheva, George Washington University
Thomas Gensch, Research Centre Juelich, Germany
Joseph Huff, Zeiss Microscopy
Jennifer Hunter, University of Rochester, New York
Na Ji, University of California, Berkeley
Sanjay Kumar, University of California, Berkeley
Markita Landry, University of California, Berkeley
Luke Lavis, Janelia Farms, Howard Hughes Medical Institute
Alex Lippert, Southern Methodist University, Dallas
Shalin Mehta, Chan-Zuckerberg Biohub, San Francisco
Yves Mely, University of Strasbourg, France
Ammasi Periasamy, University of Virginia, Charlottsville
Angelika Rueck, University of Ulm, Germany
Lydia Sauer, John A. Moran Eye Center, Salt Lake City
Patrick Schfer, Children's Hospital of Philadelphia
Martin Schnermann, National Institutes of Health
Marina Shirmanova, Nizhny Novgorod State Medical Academy, Russia
Michael Shribak, Marine Biological Laboratory
Melissa Skala, University of Wisconsin, Madison
Ben Smith, University of California, Berkeley
Lin Tian, University of California, Davis
Andreea Trache, Texas A&M University Health Science Center, College Station
Steven Vogel, Laboratory of Molecular Physiology, National Institutes of Health
Laura Waller, University of California, Berkeley
Horst Wallrabe, University of Virginia, Charlottesville
Tomasz Zal, MD Anderson, Houston




________________________

Jan. 27, 2018:


Two-photon luminescence lifetime imaging microscopy (LIM) to follow up cell metabolism and oxygen consumption during theranostic applications 

(Invited Paper) 

Paper 10498-9

Author(s): Angelika C. Rueck, Jasmin Breymayer, Univ. Ulm (Germany); Lothar D. Lilge, Univ. Health Network (Canada), Univ. of Toronto (Canada); Arkadii Mandel, Theralase Technologies, Inc. (Canada); P. Schfer, Bjorn von Einem, Christine A. F. von Arnim, Sviatlana Kalinina, Univ. Ulm (Germany) 

Hide Abstract
A common property during tumor development is a switch between oxidative phosphorylation and glycolysis. The impact of this switch for theranostic applications could be significant. Interestingly altered metabolism could be correlated with a change in the fluorescence lifetimes of NAD(P)H and FAD. Besides, oxygen consumption has to be taken into account in order to understand treatment responses. For this, correlated imaging of phosphorescence and fluorescence lifetime parameters has been investigated and used to observe metabolic markers simultaneously with oxygen tension. Examples will be presented with respect to phosphorescent photosensitizers used in PDT of tumours and diagnosis of Alzheimers related disease.



 2016 Aug;9(8):800-11. doi: 10.1002/jbio.201500297. Epub 2016 Mar 15.

Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping.

Author information

1
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany. sviatlana.kalinina@uni-ulm.de.
2
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany.
3
Zentrum biomedizinische Forschung (ZBF), Ulm University, Institute of Neurology, Helmholtzstr. 8/1, 89081, Ulm, Germany.
4
Institut fr Ansthesiologische Pathophysiologie und Verfahrensentwicklung, Universittsklinikum Ulm, Helmholtzstr. 8/1, 89081, Ulm, Germany.
5
Becker & Hickl GmbH, Nahmitzer Damm 30, 12277, Berlin, Germany.
6
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany. angelika.rueck@uni-ulm.de.

Abstract

Cellular responses to oxygen tension have been studied extensively. Oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescence sensor. The simultaneous usage of FLIM of coenzymes as NAD(P)H and FAD(+) and PLIM of oxygen sensors could provide information aboutcorrelation of metabolic pathways and oxygen tension. We investigated correlative NAD(P)H-FLIM and oxygen sensing-PLIM for simultaneously analyzing cell metabolism and oxygen tension. Cell metabolism and pO2 were observed under different hypoxic conditions in squamous carcinoma cell cultures and in complex ex vivo systems. Increased hypoxia induced an increase of the phosphorescence lifetime of Ru(BPY)3 and in most cases a decrease in the lifetime of NAD(P)H which is in agreement to the expected decrease of the protein-bound NAD(P)H during hypoxiaOxygen was modulated directly in the mitochondrial membrane. Blocking of complex III and accumulation of oxygen could be observed by both the decrease of the phosphorescence lifetime of Ru(BPY)3 and a reduction of the lifetime of NAD(P)H which was a clear indication of acute changes in the redox state of the cells. For the first time simultaneous FLIM/PLIM has been shown to be able to visualize intracellular oxygen tension together with a change from oxidative to glycolytic phenotype.




________________________

Given this:

Session 3:
Metabolism/NADH/FAD.Tryptophan II
Sunday 28 January 2018
1:30 PM - 4:00 PM

Session Chair:  
Elena V. Zagaynova, Nizhny Novgorod State Medical Academy (Russian Federation)
Two-photon luminescence lifetime imaging microscopy (LIM) to follow up cell metabolism and oxygen consumption during theranostic applications (Invited Paper) 
Paper 10498-9
Author(s): Angelika C. Rueck, Jasmin Breymayer, Univ. Ulm (Germany); Lothar D. Lilge, Univ. Health Network (Canada), Univ. of Toronto (Canada); Arkadii Mandel, TheralaseTechnologies, Inc. (Canada); P. Schfer, Bjorn von Einem, Christine A. F. von Arnim, Sviatlana Kalinina, Univ. Ulm (Germany) 
Hide Abstract
A common property during tumor development is a switch between oxidative phosphorylation and glycolysis. The impact of this switch for theranostic applications could be significant. Interestingly altered metabolism could be correlated with a change in the fluorescence lifetimes of NAD(P)H and FAD. Besides, oxygen consumption has to be taken into account in order to understand treatment responses. For this, correlated imaging of phosphorescence and fluorescence lifetime parameters has been investigated and used to observe metabolic markers simultaneously with oxygen tensionExamples will be presented with respect to phosphorescent photosensitizers used in PDT of tumours and diagnosis of Alzheimers related disease.
Here's a bit more on that:


2017:

Simultaneous Phosphorescence and Fluorescence Lifetime ...



Simultaneous Phosphorescence and Fluorescence Lifetime Imaging by Multi-Dimensional TCSPC and Multi-Pulse Excitation

Wolfgang Becker, Vladislav Shcheslavskiy, and Angelika Rck.

Abstract TCSPC FLIM/PLIM is based on a multi-dimensional time-correlated single-photon counting process. The sample is scanned by a highfrequency-pulsed laser beam which is additionally modulated on/off synchronously with the pixels of the scan. FLIM is obtained by building up the distribution of the photons over the scanning coordinates and the times of the photons in the excitation pulse sequence, PLIM is obtained by building up the photon distribution over the scanning coordinates and the photon times in the modulation period. FLIM and PLIM data are thus obtained simultaneously within the same imaging process. Since the technique uses not only one but many excitation pulses for every phosphorescence signal period the sensitivity is much higher than for techniques that excite with a single pulse only. TCSPC FLIM/PLIM works both with onephoton and two-photon excitation, does not require a reduction of the laser pulse repetition rate by a pulse picker, and eliminates the need of high pulse energy for phosphorescence excitation.


...

2.5 Applications

2.5.1 Oxygen Sensing 


Oxygen sensing by PLIM has become a hot topic in biomedical microscopy, see [5–10]. Until recently, phosphorescence imaging has mainly been performed by gated camera techniques. The disadvantage of the camera is that does not suppress out-of-focus light and lateral and longitudinal scatterin. A camera is therefore not a good solution for deep-tissue imaging. PLIM by the technique described here solves these problems by confocal and two-photon laser scanning microscopy, and, additionally, yields FLIM and PLIM simultaneously. An increasing number of publications therefore aims at the use of PLIM for oxygen sensing in cells and tissue.

...

2.5.2 Simultaneous Recording of pO2 and NAD(P)H Images


... As can be seen from Fig. 2.7 the ruthenium dye binds to the constituents of the cells. The phosphorescence lifetime of bound and unbound dye can be different. Moreover, quenching phenomena are at least in part diffusion-controlled. The quenching rate - and thus the sensitivity to oxygen - more or less depends on the oxygen diffusion constant. The diffusion constant may be different inside the cells and outside, and in different compartments of the cells

...


Fig. 2.7 FLIM and PLIM images of SCC-4 cells stained with (2,2′-bipyridyl) dichlororuthenium (II) hexahydrate. FLIM shown left, PLIM shown right. Zeiss LSM 780 NLO with PLIM option, bh Simple-Tau 152 FLIM/PLIM system, 2-photon excitation at 750 nm

...


___________________

From this:

Simultaneous Phosphorescence and Fluorescence Lifetime Imaging by Multi-Dimensional TCSPC and Multi-Pulse Excitation

done by:

Contact:
Wolfgang Becker

Becker & Hickl GmbH
Berlin, Germany
becker@becker-hickl.com

We know that:

Wolfgang Becker is a partner of Dr. Rueck. 

Proof #1

Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping
 
Sviatlana Kalinina1,*, Jasmin Breymayer1, Patrick Schfer2, Enrico Calzia3, Vladislav Shcheslavskiy4, Wolfgang Becker4 and Angelika Rck1,*
Version of Record online: 15 MAR 2016



Proof #2

Angelika Rck visualises the dance of molecules

Oct. 25, 2010 - Angelika Rck first became interested in time-resolved methods when she got to know Wolfgang Becker, head of a small Berlin-based company, whom she met at a congress several years ago. "The best thing that ever happened to me was coming into contact with Becker's small company," said Rck.


A bit more on his expertise:

Wolfgang Becker is specialist in time-resolved optical detection techniques. ... He started to develop multi-dimensional TCSPC techniques in 1989, and is the originator of the TCSPC FLIM technique that is now widely used in laser scanning microscopes. 

He lectures at Berkeley Univ. (California), just like Dr. Rueck.
Proof: Events
 
Here's his web site:

Becker & Hickl: Technology Leader in Photon Counting - News
 
and his recent work:

2016: http://www.flim.ws/wp-content/uploads/2016/03/2_Becker.pdf

BH News 2016-11

BH TCSPC Systems Record FLIM with Sutter MOM Microscopes

The Sutter Instrument MOM microscope is a modular platform for fluorerscence imaging deep within live samples. It uses multi-photon excitation by a titanium-sapphire laser in combination with non-descanned detection. Due to its pulsed excitation source and its high modularity the MOM system can easily be combined with the bh TCSPC FLIM systems. Up to four FLIM detectors can be attached to the system. The signals are processed in up to four entirely parallel TCSPC FLIM channels. Due to the parallel system architecture, high photon count rates and short acquisition times can be achieved. Multiphoton excitation and non-descanned detection make the system especially useful for FLIM of live cells and tissues. FLIM data can be recorded with up to 1024x1024 pixels and 1024 time channels per pixel. Typical applications are metabolic imaging by recording the fluorescence of NADH and FAD, protein interaction experiments by FLIM-FRET techniques, and ion concentration measurements with environment-sensitive fluorescent dyes.



______________________

bencro - (12/23/2017 4:44:16 PM) 

RE:Reversing of the Warburg effect done with Dr. Rueck

Yep!  It all adds up.  Connecting the dots ...

Dr. Rueck's expertise is the scientific rigor that TLT neded to change perceptions on this latest breakthrough.


That's why we can read this from the Nov. 30 press release:
 
Arkady Mandel, MD, Ph.D., D.Sc., Chief Scientific Officer, Theralase stated that, “One of the key strategies of our scientific team’s Theralase® CLT preclinical development program is to break down preconceived notions pertaining to CLT with new scientific, preclinical and clinical knowledge of how Theralase® CLT works so effectively on tissues: including, discoveries of previously unknown therapeutic pathways, such as mitochondria independent cellular signalling mechanisms. This enables our scientific team to build strategies to re-shape the use of Theralase® CLT from its existing therapeutic market and launch it into the oncology market, as a stand-alone therapy or to be used in conjunction with other anti-cancer treatments.
 
 
Roger Dumoulin-White, P.Eng., President and CEO, Theralase stated, “The latest research from Dr. Mandel and his scientific team opens up new potential distribution possibilities for both the Therapeutic Laser Therapy (“TLT”) division and the Photo Dynamic Therapy (“PDT”) division. Theralase will focus ontranslating this preclinical research into clinical protocols that could be readily deployed in the clinic by healthcare practitioners to pre-treat patients suffering with various cancer conditions with a goal of increasing the efficacy of their present anti-cancer treatments, lowering any associated side effects and increasing their overall QOL.”
 
__________________

bencro - (12/23/2017 4:27:46 PM) 

Reversing of the Warburg effect done with Dr. Rueck

The Jan. 27 presentation is the next step after having pre-clinically demonstrated the concept with the help of Dr. Rueck.   And that's clearly the demonstration of the reversing of the Warburg effect! 



When you read this from the Nov. 27 press release:


Theralase has announced that its Theralase® therapeutic laser technology platform has been proven preclinically to render cancer cells more susceptible to cancer destruction by Photo Dynamic Therapy (“PDT”), by reversing the Warburg Effect.

One of the hallmarks of cancer cells is a change in cellular metabolism from mitochondrial respiration (the production of Adenosine TriPhosphate (“ATP”)) that relies on oxygen consumption to glycolysis, an oxygen independent process.

Cancer cells systematically modify their metabolism to promote their: growth, survival, proliferation and long-term maintenance, without the need for molecular oxygen, thus making them difficult to destroy by traditional means.

This common feature, amongst cancer cells, of a modified metabolism, is demonstrated by an increase in glucose (blood sugar) uptake and an increase in lactate production. This phenomenon was originally described by Dr. Otto Warburg at the turn of the 19th century, where he was awarded the Nobel prize in physiology or medicine for his work, and has subsequently been suitably named as the “Warburg Effect.

The Warburg Effect describes cancer cells that are characterized by their decreased mitochondrial respiration, increased glycolysis (production of ATP without the use of molecular oxygen) and excessive lactate production.

Post treatment analysis of both of these cancer cell lines demonstrated a 20% decrease in the glycolysis rate (measured by a decrease in lactate production) and a 20% increase in mitochondrial respiration, leading to a shift in their metabolism (from cancerous to normal), indicating a reversal of the aptly named, Warburg Effect.



... it seems to be with this below (Dr. Rueck technology) that they were able to confirm reversing the Warbug effect ... when you focus on glycolytic oxygen tensionmitochondrial and that specially that Ru(PBY) is pretty much our PDC.


Sherri Mcfarland of Acadia University, Wolfville with expertise in Chemistry ... The bis-heteroleptic complex [Ru(bpy)2(ippy)]2+ (1), where bpy=2,2'-bipyridine and ippy=2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT)


Jan. 27, 2018:


Two-photon luminescence lifetime imaging microscopy (LIM) to follow up cell metabolism and oxygen consumption during theranostic applications 

(Invited Paper) 

Paper 10498-9

Author(s): Angelika C. Rueck, Jasmin Breymayer, Univ. Ulm (Germany); Lothar D. Lilge, Univ. Health Network (Canada), Univ. of Toronto (Canada); Arkadii Mandel, Theralase Technologies, Inc. (Canada); P. Schfer, Bjorn von Einem, Christine A. F. von Arnim, Sviatlana Kalinina, Univ. Ulm (Germany) 

Hide Abstract
A common property during tumor development is a switch between oxidative phosphorylation and glycolysis. The impact of this switch for theranostic applications could be significant. Interestingly altered metabolism could be correlated with a change in the fluorescence lifetimes of NAD(P)H and FAD. Besides, oxygen consumption has to be taken into account in order to understand treatment responses. For this, correlated imaging of phosphorescence and fluorescence lifetime parameters has been investigated and used to observe metabolic markers simultaneously with oxygen tension. Examples will be presented with respect to phosphorescent photosensitizers used in PDT of tumours and diagnosis of Alzheimers related disease.



 2016 Aug;9(8):800-11. doi: 10.1002/jbio.201500297. Epub 2016 Mar 15.

Correlative NAD(P)H-FLIM and oxygen sensing-PLIM for metabolic mapping.

Author information

1
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany. sviatlana.kalinina@uni-ulm.de.
2
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany.
3
Zentrum biomedizinische Forschung (ZBF), Ulm University, Institute of Neurology, Helmholtzstr. 8/1, 89081, Ulm, Germany.
4
Institut fr Ansthesiologische Pathophysiologie und Verfahrensentwicklung, Universittsklinikum Ulm, Helmholtzstr. 8/1, 89081, Ulm, Germany.
5
Becker & Hickl GmbH, Nahmitzer Damm 30, 12277, Berlin, Germany.
6
Ulm University, Core Facility Confocal and Multiphoton Microscopy, N24, Albert Einstein Allee 11, 89081, Ulm, Germany. angelika.rueck@uni-ulm.de.

Abstract

Cellular responses to oxygen tension have been studied extensively. Oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescence sensor. The simultaneous usage of FLIM of coenzymes as NAD(P)H and FAD(+) and PLIM of oxygen sensors could provide information aboutcorrelation of metabolic pathways and oxygen tension. We investigated correlative NAD(P)H-FLIM and oxygen sensing-PLIM for simultaneously analyzing cell metabolism and oxygen tension. Cell metabolism and pO2 were observed under different hypoxic conditions in squamous carcinoma cell cultures and in complex ex vivo systems. Increased hypoxia induced an increase of the phosphorescence lifetime of Ru(BPY)3 and in most cases a decrease in the lifetime of NAD(P)H which is in agreement to the expected decrease of the protein-bound NAD(P)H during hypoxiaOxygen was modulated directly in the mitochondrial membrane. Blocking of complex III and accumulation of oxygen could be observed by both the decrease of the phosphorescence lifetime of Ru(BPY)3 and a reduction of the lifetime of NAD(P)H which was a clear indication of acute changes in the redox state of the cells. For the first time simultaneous FLIM/PLIM has been shown to be able to visualize intracellular oxygen tension together with a change from oxidative to glycolytic phenotype.


http://www.becker-hickl.de/bhnews.htm[/quote]