| 1. |
- Adler, Andrew F., et al.
(författare)
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hESC-Derived Dopaminergic Transplants Integrate into Basal Ganglia Circuitry in a Preclinical Model of Parkinson's Disease
- 2019
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:13, s. 5-3473
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Tidskriftsartikel (refereegranskat)abstract
- Cell replacement is currently being explored as a therapeutic approach for neurodegenerative disease. Using stem cells as a source, transplantable progenitors can now be generated under conditions compliant with clinical application in patients. In this study, we elucidate factors controlling target-appropriate innervation and circuitry integration of human embryonic stem cell (hESC)-derived grafts after transplantation to the adult brain. We show that cell-intrinsic factors determine graft-derived axonal innervation, whereas synaptic inputs from host neurons primarily reflect the graft location. Furthermore, we provide evidence that hESC-derived dopaminergic grafts transplanted in a long-term preclinical rat model of Parkinson's disease (PD) receive synaptic input from subtypes of host cortical, striatal, and pallidal neurons that are known to regulate the function of endogenous nigral dopamine neurons. This refined understanding of how graft neurons integrate with host circuitry will be important for the design of clinical stem-cell-based replacement therapies for PD, as well as for other neurodegenerative diseases. Adler et al. graft hESC-derived dopaminergic progenitors into a rat model of Parkinson's disease. They find grafts correctly innervate host targets and receive appropriate synaptic input after intranigral and intrastriatal placement. Furthermore, the same host neurons projecting toward endogenous dopamine neurons are found to also connect to the grafts.
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| 2. |
- Allen, Marie, et al.
(författare)
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Origin of the U87MG glioma cell line : Good news and bad news
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:354
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Tidskriftsartikel (refereegranskat)abstract
- Human tumor-derived cell lines are indispensable tools for basic and translational oncology. They have an infinite life span and are easy to handle and scalable, and results can be obtained with high reproducibility. However, a tumor-derived cell line may not be authentic to the tumor of origin. Two major questions emerge: Have the identity of the donor and the actual tumor origin of the cell line been accurately determined? To what extent does the cell line reflect the phenotype of the tumor type of origin? The importance of these questions is greatest in translational research. We have examined these questions using genetic profiling and transcriptome analysis in human glioma cell lines. We find that the DNA profile of the widely used glioma cell line U87MG is different from that of the original cells and that it is likely to be a bona fide human glioblastoma cell line of unknown origin.
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| 3. |
- Andersen, J, et al.
(författare)
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Communication: THz absorption spectrum of the CO2-H2O complex: Observation and assignment of intermolecular van der Waals vibrations.
- 2014
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 140:9
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Tidskriftsartikel (refereegranskat)abstract
- Terahertz absorption spectra have been recorded for the weakly bound CO2-H2O complex embedded in cryogenic neon matrices at 2.8 K. The three high-frequency van der Waals vibrational transitions associated with out-of-plane wagging, in-plane rocking, and torsional motion of the isotopic H2O subunit have been assigned and provide crucial observables for benchmark theoretical descriptions of this systems' flat intermolecular potential energy surface. A (semi)-empirical value for the zero-point energy of 273 ± 15 cm(-1) from the class of intermolecular van der Waals vibrations is proposed and the combination with high-level quantum chemical calculations provides a value of 726 ± 15 cm(-1) for the dissociation energy D0.
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| 4. |
- Andersson, Åke, et al.
(författare)
-
Coherent synchrotron radiation in the far infrared from a 1-mm electron bunch
- 2000
-
Ingår i: Optical Engineering. - : SPIE-Intl Soc Optical Eng. - 0091-3286. ; 39:12, s. 3099-3105
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Tidskriftsartikel (refereegranskat)abstract
- The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber-screening effects have so far blocked observation of coherent radiation from a conventional radiation beamline. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent far-infrared emission observed from such a bunch. The paper discusses the origin of coherent synchrotron radiation for Gaussian and non-Gaussian electron bunches, and the procedure used to generate such bunches. The emission was characterized using the infrared beamline at MAX-I, including an interferometer, a liquid-helium-cooled bolometer detector, waveguide high-pass filters, and a conductive-grid polarization filter. The intensity of the coherent radiation is greater by a factor of 2×103 to 6×103 than normal incoherent synchrotron radiation, and is seen between 8 and 22 cm-1.
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| 5. |
- Andersson, Åke, et al.
(författare)
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Observation of coherent synchrotron radiation from a 1 mm electron bunch at the MAX-I storage ring
- 1999
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 1996-756X. ; 3775, s. 77-87
-
Tidskriftsartikel (refereegranskat)abstract
- The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber- screening effects have so-far blocked observation of coherent radiation from a conventional radiation beam line. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent emission phenomena observed from such a bunch at the infrared beam line attached to the MAX-I ring.The coherent generation of synchrotron radiation by an electron storage ring is predicted for wavelengths equal to or longer than the electron bunch length. With typical bunch lengths of approximately 1 cm, diffraction and chamber- screening effects have so-far blocked observation of coherent radiation from a conventional radiation beam line. In the low-energy, second-generation light source MAX-I, the magnet lattice has been tuned to a small momentum compaction factor, allowing rms bunch lengths as short as 1 mm. Here we report the coherent emission phenomena observed from such a bunch at the infrared beam line attached to the MAX-I ring.
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| 6. |
- Birtele, Marcella, et al.
(författare)
-
Single-cell transcriptional and functional analysis of dopaminergic neurons in organoid-like cultures derived from human fetal midbrain
- 2022
-
Ingår i: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 149:23
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Tidskriftsartikel (refereegranskat)abstract
- Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells (PSCs) for application in disease modeling, diagnostics, drug screening, and cell-based therapies for Parkinson's Disease (PD). An increased understanding of the timing and molecular mechanisms promoting the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from PSCs. Here, we used droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach revealed that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons, which can be used to guide stem cell-based therapies and disease modeling approaches in PD.
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| 7. |
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| 8. |
- Cancer, Matko, et al.
(författare)
-
BET and Aurora Kinase A inhibitors synergize against MYCN-positive human glioblastoma cells
- 2019
-
Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients usually undergo surgery followed by aggressive radio- and chemotherapy with the alkylating agent temozolomide (TMZ). Still, median survival is only 12-15 months after diagnosis. Many human cancers including GBMs demonstrate addiction to MYC transcription factor signaling and can become susceptible to inhibition of MYC downstream genes. JQ1 is an effective inhibitor of BET Bromodomains, a class of epigenetic readers regulating expression of downstream MYC targets. Here, we show that BET inhibition decreases viability of patient-derived GBM cell lines. We propose a distinct expression signature of MYCN-elevated GBM cells that correlates with significant sensitivity to BET inhibition. In tumors showing JQ1 sensitivity, we found enrichment of pathways regulating cell cycle, DNA damage response and repair. As DNA repair leads to acquired chemoresistance to TMZ, JQ1 treatment in combination with TMZ synergistically inhibited proliferation of MYCN-elevated cells. Bioinformatic analyses further showed that the expression of MYCN correlates with Aurora Kinase A levels and Aurora Kinase inhibitors indeed showed synergistic efficacy in combination with BET inhibition. Collectively, our data suggest that BET inhibitors could potentiate the efficacy of either TMZ or Aurora Kinase inhibitors in GBM treatment.
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| 9. |
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| 10. |
- Cardoso, Tiago, et al.
(författare)
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Target-specific forebrain projections and appropriate synaptic inputs of hESC-derived dopamine neurons grafted to the midbrain of parkinsonian rats
- 2018
-
Ingår i: Journal of Comparative Neurology. - 0021-9967. ; 526:13, s. 2133-2146
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are a promising unlimited source of cells for cell replacement therapy in Parkinson's disease (PD). A number of studies have demonstrated functionality of DA neurons originating from hESCs when grafted to the striatum of rodent and non-human primate models of PD. However, several questions remain in regard to their axonal outgrowth potential and capacity to integrate into host circuitry. Here, ventral midbrain (VM) patterned hESC-derived progenitors were grafted into the midbrain of 6-hydroxydopamine-lesioned rats, and analyzed at 6, 18, and 24weeks for a time-course evaluation of specificity and extent of graft-derived fiber outgrowth as well as potential for functional recovery. To investigate synaptic integration of the transplanted cells, we used rabies-based monosynaptic tracing to reveal the origin and extent of host presynaptic inputs to grafts at 6 weeks. The results reveal the capacity of grafted neurons to extend axonal projections toward appropriate forebrain target structures progressively over 24weeks. The timing and extent of graft-derived dopaminergic fibers innervating the dorsolateral striatum matched reduction in amphetamine-induced rotational asymmetry in the animals where recovery could be observed. Monosynaptic tracing demonstrated that grafted cells integrate with host circuitry 6 weeks after transplantation, in a manner that is comparable with endogenous midbrain connectivity. Thus, we demonstrate that VM patterned hESC-derived progenitors grafted to midbrain have the capacity to extensively innervate appropriate forebrain targets, integrate into the host circuitry and that functional recovery can be achieved when grafting fetal or hESC-derived DA neurons to the midbrain.
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| 11. |
- Ceponkus, J, et al.
(författare)
-
A simple model for the water o-H-2 complex
- 2006
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 124:2
-
Tidskriftsartikel (refereegranskat)abstract
- The infrared spectrum of the complex between o-H-2 and H2O, D2O, or HDO, isolated in a matrix of solid p-H-2, has been studied between 20 and 4500 cm(-1). In addition the infrared spectrum of the complex between p-D-2 and H2O in solid o-D-2 has been studied. The spectral shifts are interpreted as the result of the quadrupole-dipole interaction between hydrogen and water. (c) 2006 American Institute of Physics.
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| 12. |
- Ceponkus, J, et al.
(författare)
-
Acceptor switching and axial rotation of the water dimer in matrices, observed by infrared spectroscopy.
- 2010
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 133:7
-
Tidskriftsartikel (refereegranskat)abstract
- Several isotopologues of the water dimer have been studied in different matrices (Ne, Ar, Kr, and p-H(2)) at very low temperatures. A fine structure, which is more or less matrix independent and very similar for different intramolecular fundamentals of the same isotopologic dimer, is present on the high wavenumber side of the main component. The bound OD (OH) stretches of the donor have temperature dependent components. The fine structure and temperature dependency is interpreted as evidence for acceptor switching and rotation of the water dimer around its O-O axis in the matrices studied here. The slow nuclear spin equilibration in H(2)O inhibits the thermal equilibration between the acceptor switching states in H(2)O-DOH and H(2)O-DOD. The condensed environment slows down the acceptor switching rate compared to the gas phase. The antisymmetric stretch of the proton acceptor is assigned by combining information from different matrices with the rotation-acceptor switching model.
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| 13. |
- Ceponkus, J, et al.
(författare)
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Complex Formation of Small Molecules during Isolation in Low Temperature Matrices: Water Dimers in p-H-2 and Ne Matrices
- 2010
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 114:25, s. 6829-6831
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Tidskriftsartikel (refereegranskat)abstract
- The concentrations of water dimer are compared in Ne and p-H-2 matrices at low temperatures, using infrared spectroscopy. Additional data are given for o-D-2 and Ar matrices. For a given monomer concentration, the dimer concentration is significantly higher in solid Ne (or Ar) than in solid p-H-2. In p-H-2, the dimer concentration is only slightly higher than expected for a random distribution of water in the matrix. The dimer concentration in o-D-2 matrices is intermediate between p-H-2 and noble gas matrices. This strongly suggests that most dimers form on the surface of the growing matrix, and not as the result of diffusion in the bulk of the matrix.
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| 14. |
- Ceponkus, Justinas, et al.
(författare)
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Far-Infrared Band Strengths in the Water Dimer: Experiments and Calculations.
- 2008
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 112:17, s. 3921-3926
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Tidskriftsartikel (refereegranskat)abstract
- Most fundamentals modes of the water dimer have been experimentally determined, and the frequencies have been measured in either neon or parahydrogen matrices. The band strengths of all intramolecular and most intermolecular fundamentals of the water dimer have been measured. The results are further corroborated by comparison with the corresponding data for the fully deuterated water dimer. DFT calculations of the mode frequencies and band strength are in qualitative agreement with the experimental observations.
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| 15. |
- Ceponkus, J, et al.
(författare)
-
Intermolecular vibrations of different isotopologs of the water dimer: Experiments and density functional theory calculations.
- 2008
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 129:19
-
Tidskriftsartikel (refereegranskat)abstract
- Far infrared spectra of seven different isotopologs of the water dimer have been measured in neon matrices at 2.8 K. The experiments are interpreted with the aid of density functional theory calculations, in particular the calculated harmonic isotopic shifts were utilized. All six intermolecular vibrational modes of the water dimer and the fully deuterated water dimer are assigned based the isotopic shifts induced. 31 of a total of 42 intermolecular fundamental modes of the seven different H, D, and (18)O containing water dimers have been experimentally observed and assigned accordingly. The overall agreement between the calculations and the experiments of all isotopologs results in a complete and consistent description of these modes.
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| 16. |
- Ceponkus, Justinas, et al.
(författare)
-
Intermolecular vibrations of the water trimer, a matrix isolation study
- 2005
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 109:35, s. 7859-7864
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Tidskriftsartikel (refereegranskat)abstract
- Infrared spectra from 25 to 4000 cm(-1) have been recorded of water (H2O, D2O and (H2O)-O-18) matrix isolated in neon, argon, and krypton matrices. Intermolecular absorption bands of different isotopologues of the water trimer and tetramer have been assigned from concentration dependencies and diffusion behavior, using the well-known mid-infrared trimer and tetramer absorption bands as measures of the trimer and tetramer concentrations. The results are compared to ab initio calculations.
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| 17. |
- Ceponkus, J, et al.
(författare)
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Observations of Host Guest Interactions Specific to Molecular Matrices: Water Monomers and Dimers in Hydrogen Matrices.
- 2011
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Ingår i: Journal of physical chemistry. A. - : American Chemical Society (ACS). - 1520-5215 .- 1089-5639. ; 115:27, s. 7921-7927
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Tidskriftsartikel (refereegranskat)abstract
- Water monomers and dimers have been studied at low temperatures in matrices of solid p-H(2), o-D(2), n-H(2), and n-D(2) using infrared spectroscopy. Our data demonstrate interaction mechanisms between host matrix and guest molecules that are different from the ones observed in atomic noble gas matrices. Notably both guest/host rotational-rotational interaction and matrix induced modifications of the guest libration modes are observed. We also show that different types of interaction influence the relaxation times of some of guest modes. Water rotates freely in p-H(2) and o-D(2) but librates in n-H(2) and n-D(2). Rotational relaxation is faster in o-D(2) than in p-H(2) and faster in p-H(2) than in Ne. This is attributed to interactions between water rotation and matrix molecule rotation in p-H(2) and o-D(2). In n-H(2) and n-D(2), a strong water libration band is observed in the far-infrared, and strong water monomer vibration bands have libration satellites. Water dimer bands, close to matrix rotation bands, are perturbed by the matrix motions. The H-bonded isomer H(2)O-HOD rapidly converts to the D-bonded form H(2)O-DOH in p-H(2) and in o-D(2) but slowly in n-H(2) and n-D(2).
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| 18. |
- Ceponkus, J, et al.
(författare)
-
On the structure of the matrix isolated water trimer.
- 2011
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 134:6
-
Tidskriftsartikel (refereegranskat)abstract
- Infrared spectra of partially deuterated water trimers have been investigated. It is found that HDO(H(2)O)(2) has a single, bound OD stretching fundamental, (HDO)(2)H(2)O two bound OD stretches. (HDO)(3) has a single, bound OD stretch and (H(2)O)(3) has a pair of bound OH stretches. Ab initio and discrete Fourier transform (DFT) calculations predict that the water trimer has C(1) symmetry with six different, isoenergetic minima. These calculations consequently give three numerically different OD stretches for HDO(H(2)O)(2), six for (HDO)(2)H(2)O, three for (HDO)(3), and three bound OH stretches for (H(2)O)(3). The connection between the observations and the pseudorotation of the trimer is discussed with the help of Wales' pseudorotation model. It is found that pseudorotation is sufficiently fast to average the effective symmetry of the A(3) trimer to C(3h) and to eliminate the difference between the different ab initio minima for A(2)B. The only exception is (H(2)O)(3) where the splitting between the different bound OH stretches is largest. Here a doublet is observed due to incomplete averaging. DFT calculations indicate that the D-bonded form of HDO(H(2)O)(2) is between 50 and 60 cm(-1) more stable than the H-bonded form. The energy difference is determined by differences in zero point vibration energy of intermolecular librations of the two forms. Attempts to measure the energy difference indicate that the energy difference is larger, of the order of 100 cm(-1).
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| 19. |
- Ceponkus, J, et al.
(författare)
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Rotation of Water in Solid Parahydrogen and Orthodeuterium.
- 2010
-
Ingår i: Journal of physical chemistry. A. - : American Chemical Society (ACS). - 1520-5215 .- 1089-5639. ; 114, s. 12979-12985
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Tidskriftsartikel (refereegranskat)abstract
- The far-infrared spectra of solid orthodeuterium and solid normal deuterium are presented and compared to the corresponding spectra of solid parahydrogen and solid normal hydrogen. Spectra of water in orthodeuterium are compared to spectra of water in parahydrogen. The water rotation constants in orthodeuterium are approximately 80% of the rotation constants of water in parahydrogen. The S(0)(0) band of orthodeuterium gets a strong satellite in the presence of water. The position and width of the satellite depends on the isotopic composition of the water present. If there is a corresponding satellite in parahydrogen it is weak and closer to the S(0)(0) band of the matrix. The conclusion of the paper is that interaction between guest rotation and the rotation of matrix molecules must be taken into account to explain the reduction of the rotation constants in orthodeuterium.
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| 20. |
- Ceponkus, J., et al.
(författare)
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Structure and dynamics of small water clusters, trapped in inert matrices
- 2013
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 581, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- Recent matrix isolation (p-H-2, Ne, Ar, Kr) studies of water clusters made in Lund are reviewed. Gas phase positions of water cluster bands are estimated from matrix data. Intermolecular spectra of several isotopomers of the water dimer have been obtained, and approximate band strengths have been measured. Acceptor switching of the water dimer has been observed in matrices. A few intermolecular vibrations of (H2O)(3), (D2O)(3), (H2O)(4), and (D2O)(4) have been measured. The pseudorotation of the water trimer is not quenched in matrices, and pentamer pseudorotation appears to be fast as well. Spectra of partially deuterated water tetramers support a rigid cyclic tetramer structure. The hydrogen rotation in p-H-2 may interfere with guest vibrations at frequencies near the J = 2 <- J = 0 band of solid parahydrogen. (C) 2013 Elsevier B.V. All rights reserved.
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| 21. |
- Ceponkus, J., et al.
(författare)
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The coupling between translation and rotation for monomeric water in noble gas matrices.
- 2013
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 138:24
-
Tidskriftsartikel (refereegranskat)abstract
- The rotation of water in noble gas matrices has been studied. It is shown that the rotation-translation coupling model of Friedmann and Kimel predicts rotation line spacings, which are close to the experimental observations for H2O, D2O, and HDO, when gas phase rotation constants are used. The model gives intensity estimates in reasonable agreement with the observations for the local oscillator bands, which accompany the rotation spectrum. It also predicts the intensity variations in the bending region of H2O between neon, argon, and krypton matrices.
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| 22. |
- Ceponkus, Justinas, et al.
(författare)
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Water dimer in solid neon. Far-infrared spectrum
- 2004
-
Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 108:31, s. 6499-6502
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Tidskriftsartikel (refereegranskat)abstract
- Infrared spectra of water and deuterated water isolated in neon matrices have been recorded between 20 and 5000 cm(-1). The water concentration has been varied between very low concentrations with only monomers present up to concentrations where pentamers and possibly hexamers are present in significant amounts. The concentration dependencies of the observed absorption bands have been used to assign the dimer spectrum. The matrices studied were on the order of 1 mm thick, which has made it simpler to vary concentrations in a manner which discriminates between higher aggregates. It has also made it possible to avoid the baseline problems which appear when the matrices are only slightly thicker than the wavelengths in the far-infrared part of the spectrum.
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| 23. |
- Ceponkus, J., et al.
(författare)
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Water Tetramer, Pentamer, and Hexamer in Inert Matrices
- 2012
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Ingår i: The Journal of Physical Chemistry Part A: Molecules, Spectroscopy, Kinetics, Environment and General Theory. - : American Chemical Society (ACS). - 1520-5215. ; 116:20, s. 4842-4850
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Tidskriftsartikel (refereegranskat)abstract
- The infrared spectrum of water, isolated in inert matrices, has been studied in the interval from 60 to 4000 cm(-1). Experiments with partially deuterated water combined with DFT (density functional theory) calculations have been used to investigate the structure of matrix-isolated water tetramer. A few, strong intermolecular fundamentals of the water tetramer have been observed. Mid-infrared bands due to deuterated pentamers and hexamers have been observed and are used to discuss the assignments of these water clusters.
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| 24. |
- Dalmo, Erika, et al.
(författare)
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Growth-Inhibitory Activity of Bone Morphogenetic Protein 4 in Human Glioblastoma Cell Lines Is Heterogeneous and Dependent on Reduced SOX2 Expression
- 2020
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Ingår i: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 18:7, s. 981-991
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme continues to have a dismal prognosis. Even though detailed information on the genetic aberrations in cell signaling and cell-cycle checkpoint control is available, no effective targeted treatment has been developed. Despite the advanced molecular defects, glioblastoma cells may have remnants of normal growth-inhibitory pathways, such as the bone morphogenetic protein (BMP) signaling pathway. We have evaluated the growth-inhibitory effect of BMP4 across a broad spectrum of patient samples, using a panel of 40 human glioblastoma initiating cell (GIC) cultures. A wide range of responsiveness was observed. BMP4 sensitivity was positively correlated with a proneural mRNA expression profile, high SOX2 activity, and BMP4-dependent upregulation of genes associated with inhibition of the MAPK pathway, as demonstrated by gene set enrichment analysis. BMP4 response in sensitive cells was mediated by the canonical BMP receptor pathway involving SMAD1/5/9 phosphorylation and SMAD4 expression. SOX2 was consistently downregulated in BMP4-treated cells. Forced expression of SOX2 attenuated the BMP4 sensitivity including a reduced upregulation of MAPK-inhibitory genes, implying a functional relationship between SOX2 downregulation and sensitivity. The results show an extensive heterogeneity in BMP4 responsiveness among GICs and identify a BMP4-sensitive subgroup, in which SOX2 is a mediator of the response.
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| 25. |
- Dalmo, Erika, et al.
(författare)
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Targeting SOX2 in glioblastoma cells reveals heterogeneity in SOX2 dependency
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Glioblastoma (GBM) is a lethal disease with no curative treatment. SOX2 is a stem cell transcription factor which is widely expressed across human GBM tumors. Downregulation of SOX2 inhibits tumor formation and its depletion leads to a complete stop of cell proliferation. Despite its known important role in GBM, there is a lack of SOX2 overexpression studies in human GBM cells cultured under stem cell conditions. Previous work in our lab suggests that SOX2 levels need to be precisely maintained for GBM cells to thrive. In this project, we have investigated how altered SOX2 expression affects primary human GBM lines. We found that elevated SOX2 expression inhibited proliferation in a dose-dependent manner in three out of four GBM cell lines. Global gene expression in the resistant line was shifted towards that of the proliferation-inhibited lines upon SOX2 induction. However, SOX2 induction also led to an increase in a GBM stem cell injury response phenotype, which was not present in proliferation-inhibited lines. Furthermore, CRISPR/Cas9-mediated SOX2 knockout revealed a SOX2 independence in the resistant cell line, where SOX2-negative cells could be propagated both in vitro and in vivo.
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| 26. |
- Darmanis, Spyros, et al.
(författare)
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Simultaneous Multiplexed Measurement of RNA and Proteins in Single Cells
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 14:2, s. 380-389
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Tidskriftsartikel (refereegranskat)abstract
- Significant advances have been made in methods to analyze genomes and transcriptomes of single cells, but to fully define cell states, proteins must also be accessed as central actors defining a cell's phenotype. Methods currently used to analyze endogenous protein expression in single cells are limited in specificity, throughput, or multiplex capability. Here, we present an approach to simultaneously and specifically interrogate large sets of protein and RNA targets in lysates from individual cells, enabling investigations of cell functions and responses. We applied our method to investigate the effects of BMP4, an experimental therapeutic agent, on early-passage glioblastoma cell cultures. We uncovered significant heterogeneity in responses to treatment at levels of RNA and protein, with a subset of cells reacting in a distinct manner to BMP4. Moreover, we found overall poor correlation between protein and RNA at the level of single cells, with proteins more accurately defining responses to treatment.
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| 27. |
- Engdahl, Anders, et al.
(författare)
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A 1 : 1 complex between a hydroxyl radical and ozone
- 2005
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 122:12
-
Tidskriftsartikel (refereegranskat)abstract
- A hydrogen bonded complex between a hydroxyl radical and ozone has been found in argon matrices at 9 K. The shift of the OH stretch (-12.6 cm(-1)) indicates that this complex is somewhat weaker than the OH-CO complex (-21.8 cm(-1), D-0<= 430 cm(-1), 1.2 kcal/mol).
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| 28. |
- Engdahl, Anders, et al.
(författare)
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Axial motion of water hydrogen halide and water halogen complexes in argon matrices
- 1986
-
Ingår i: The Journal of chemical physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 84:4, s. 1981-1987
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Tidskriftsartikel (refereegranskat)abstract
- The infrared spectra of the water (H2O, HDO, D2O) complexes with HCl, HBr, HI Cl2, Br2, and I2 have been studied in argon matrices in the 11 to 25 K interval. In all cases, water acts as a lone-pair donor. The hydrogen halide complexes are effectively planar and rotate around the axis through the heavy atoms. For the water halogen complexes, the results are less clear, but a similar rotation, coupled to low wave number bending motions, seems possible.
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| 29. |
- Engdahl, Anders, et al.
(författare)
-
Hydrogen iodide in argon matrices
- 1986
-
Ingår i: Journal of Physical Chemistry. - : American Chemical Society (ACS). - 0022-3654 .- 1541-5740. ; 90:23, s. 6118-6121
-
Tidskriftsartikel (refereegranskat)abstract
- The infrared spectra of HI and DI in argon matrices have been studied in the 11-25 K interval. The effects of concentration changes and of impurities have been investigated. Dimer and trimer bands have been assigned, as well as bands due to binary complexes with water, hydrogen bromide, hydrogen chloride, and atomic and molecular iodine.
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| 30. |
- Engdahl, Anders, et al.
(författare)
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On the relative stabilities of H- And D-bonded water dimers
- 1987
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Ingår i: The Journal of chemical physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 86:4, s. 1819-1823
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Tidskriftsartikel (refereegranskat)abstract
- The infrared spectra of water dimers formed from H2O, D 2O, and HDO in krypton matrices have been recorded. Thermal equilibria between H- and D-bonded dimers have been studied. D bonding is preferred, and H-bonded dimers are approximately 60 cm-1 less stable than D-bonded dimers. The energy difference seems to be due to the higher value of the intermolecular out-of-plane H-bond shear vibration compared to the corresponding D-bond vibration.
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| 31. |
- Engdahl, Anders, et al.
(författare)
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Structure of the bromovinyl radical : A matrix isolation study
- 1985
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Ingår i: Journal of the Chemical Society, Perkin Transactions 2. - 1472-779X. ; :11, s. 1747-1750
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Tidskriftsartikel (refereegranskat)abstract
- The bromovinyl radical has been prepared by the reaction of bromine atoms with acetylene in an argon matrix at 17 K and its i.r. spectrum has been studied. The spectrum of C2HDBr• shows the presence of two isomers, indicating that the radical has an unsymmetric structure.
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| 32. |
- Engdahl, Anders, et al.
(författare)
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The Binary Complex Between Hydrogen Peroxide and Ozone: A Matrix Isolation Study.
- 2003
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Ingår i: Chemical Physics. - 0301-0104. ; 293:2, s. 203-209
-
Tidskriftsartikel (refereegranskat)abstract
- The interaction between hydrogen peroxide and ozone has been studied in argon matrices using infrared spectroscopy. The spectra show that hydrogen peroxide forms a weak hydrogen bond to one of the end oxygens of ozone. A comparison is made with other ozone complexes.
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| 33. |
- Engdahl, Anders, et al.
(författare)
-
The HOOH-HOO complex. A matrix isolation study
- 2004
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084. ; 6:4, s. 730-734
-
Tidskriftsartikel (refereegranskat)abstract
- The peroxy radical forms a cyclic complex with hydrogen peroxide, with both entities acting as hydrogen bond donors and as hydrogen bond acceptors. The strength of the complex is very similar to that of the hydrogen peroxide dimer.
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| 34. |
- Engdahl, Anders, et al.
(författare)
-
The vibrational spectrum of H2O3.
- 2002
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 295:5554, s. 482-483
-
Tidskriftsartikel (refereegranskat)abstract
- This report presents positive infrared spectroscopic identification of H2O3, a higher oxide of hydrogen of importance for the understanding of the chain formation ability of atomic oxygen and a possible intermediate in hydrogen oxygen radical chemistry. All fundamental vibrations of H2O3, isolated in an argon matrix, have been observed. In addition, several bands of HDO3, D2O3, and H2(16)O2(18)O have been measured. One particular mode, the antisymetric O-O stretch at 776 cm-1, should be observable even in the presence of high water concentrations.
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| 35. |
- Engdahl, Anders, et al.
(författare)
-
The water dimer in a too tight matrix cage
- 2002
-
Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 4:11, s. 2140-2143
-
Tidskriftsartikel (refereegranskat)abstract
- When an argon matrix containing hydrogen peroxide dimer is irradiated with 266 nm radiation from a YAG laser, water forms. Some of it is formed as monomer but the main part is formed as dimer. The photogenerated water dimer is formed together with an oxygen molecule in the cage of the parent hydrogen peroxide dimer and the dimer bands are shifted from their normal positions indicating that the cage severely perturbs the product structure.
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| 36. |
- Engdahl, Anders, et al.
(författare)
-
The water-hydroxyl radical complex: A matrix isolation study.
- 2003
-
Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 118:17, s. 7797-7802
-
Tidskriftsartikel (refereegranskat)abstract
- The water–hydroxyl radical complex was prepared by irradiating peroxy radicals in hydrogen-doped argon matrices. The low water content of the matrices made it possible to observe the fundamental bands of the complexed water molecule. The experimental results are compared with the results from ab initio calculations. The complex rotates around the O–O axis in the matrix. ©2003 American Institute of Physics.
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| 37. |
- Engdahl, Anders, et al.
(författare)
-
Water-olefin complexes. : A matrix isolation study
- 1986
-
Ingår i: Journal of Physical Chemistry. - : American Chemical Society (ACS). - 0022-3654 .- 1541-5740. ; 90:21, s. 4982-4987
-
Tidskriftsartikel (refereegranskat)abstract
- The infrared spectra of the H2O, HDO, and D2O complexes with ethylene, propene, cis-2-butene, trans-2-butene, 2-methylpropene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, 1,3-butadiene, benzene, and naphthalene have been recorded at temperatures from 11 to 20 K. Interaction energies have been estimated. HDO prefers to form a deuterium bond to the unsaturated molecule; however, small amounts of the hydrogen-bonded forms are present in thermal equilibrium with the deuterium-bonded forms. The energy difference between the hydrogen-bonded and deuterium-bonded forms has been estimated for most of the complexes.
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| 38. |
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| 39. |
- Hegelund, F, et al.
(författare)
-
High-Resolution Infrared and Microwave Study of the n20 and n21 Levels near 300 cm-1 in 1,2,4-Triazine.
- 2003
-
Ingår i: Journal of Molecular Spectroscopy. - 0022-2852. ; 217:1, s. 9-18
-
Tidskriftsartikel (refereegranskat)abstract
- The gas phase far-IR spectrum of the small nu, Greek20 (A″, 367.88 cm−1) and small nu, Greek21 (A″, 311.28 cm−1) bands of 1,2,4-triazine, a five membered ring having the point group Cs, has been studied at a resolution ranging from 0.002 to 0.003 cm−1. From the MW spectrum 58 transitions in the small nu, Greek20 level and 64 in the small nu, Greek21 level have been assigned. The small nu, Greek20 and small nu, Greek21 modes which are due to non-planar motions of the ring system are found to be nearly unperturbed. From a simultaneous analysis of IR and MW transitions band centers, rotational constants, and the quartic centrifugal distortion constants ΔJ, ΔJK, ΔK, small delta, GreekJ, and small delta, GreekK have been obtained using the Watson Hamiltonian, A-reduction, IIIr-representation.
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| 40. |
- Hermida-Ramón, Jose Manuel, et al.
(författare)
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On the influence of the basis set superposition error on calculated vibrational frequencies
- 2003
-
Ingår i: Theoretical Chemistry Accounts. - : Springer Science and Business Media LLC. - 1432-881X. ; 110:3, s. 190-195
-
Tidskriftsartikel (refereegranskat)abstract
- The relation between the so called basis set superposition error and intramolecular vibrational frequencies calculated at the Hartree Fock SCF level of approximation was investigated. A linear conformation of HF dimer was chosen as test system for the investigation. It was found that the direct basis set superposition error for the studied system is rather small. It was further found that the shifts are mainly determined by the geometry parameters of the system
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| 41. |
- Hoban, Deirdre B, et al.
(författare)
-
Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD
- 2020
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 117:26, s. 15209-15220
-
Tidskriftsartikel (refereegranskat)abstract
- Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better recapitulates the main disease features, obtained by coinjection of preformed human α-synuclein (α-syn) fibrils and adeno-associated virus (AAV) expressing human wild-type α-syn unilaterally into the rat substantia nigra (SN). This model gives rise to DA neuron dysfunction and progressive loss of DA neurons from the SN and terminals in the striatum, accompanied by extensive α-syn pathology and a prominent inflammatory response, making it an interesting and relevant model in which to examine long-term function and integrity of transplanted neurons in a PD-like brain. We transplanted DA neurons derived from human embryonic stem cells (hESCs) into the striatum and assessed their survival, growth, and function over 6 to 18 wk. We show that the transplanted cells, even in the presence of ongoing pathology, are capable of innervating the DA-depleted striatum. However, on closer examination of the grafts, we found evidence of α-syn pathology in the form of inclusions of phosphorylated α-syn in a small fraction of the grafted DA neurons, indicating host-to-graft transfer of α-syn pathology, a phenomenon that has previously been observed in PD patients receiving fetal tissue grafts but has not been possible to demonstrate and study in toxin-based animal models.
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| 42. |
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| 43. |
- Ilkhanizadeh, Shirin, et al.
(författare)
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Live Detection of Neural Progenitors and Glioblastoma Cells by an Oligothiophene Derivative
- 2023
-
Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 6:9, s. 3790-3797
-
Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
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| 44. |
- Kaffes, Ioannis, et al.
(författare)
-
Human Mesenchymal glioblastomas are characterized by an increased immune cell presence compared to Proneural and Classical tumors
- 2019
-
Ingår i: Oncoimmunology. - : TAYLOR & FRANCIS INC. - 2162-4011 .- 2162-402X. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults, with a median survival of 14.6 months. Recent efforts have focused on identifying clinically relevant subgroups to improve our understanding of pathogenetic mechanisms and patient stratification. Concurrently, the role of immune cells in the tumor microenvironment has received increasing attention, especially T cells and tumor-associated macrophages (TAM). The latter are a mixed population of activated brain-resident microglia and infiltrating monocytes/monocyte-derived macrophages, both of which express ionized calcium-binding adapter molecule 1 (IBA1). This study investigated differences in immune cell subpopulations among distinct transcriptional subtypes of GBM. Human GBM samples were molecularly characterized and assigned to Proneural, Mesenchymal or Classical subtypes as defined by NanoString nCounter Technology. Subsequently, we performed and analyzed automated immunohistochemical stainings for TAM as well as specific T cell populations. The Mesenchymal subtype of GBM showed the highest presence of TAM, CD8(+), CD3(+) and FOXP3(+) T cells, as compared to Proneural and Classical subtypes. High expression levels of the TAM-related gene AIF1, which encodes the TAM-specific protein IBA1, correlated with a worse prognosis in Proneural GBM, but conferred a survival benefit in Mesenchymal tumors. We used our data to construct a mathematical model that could reliably identify Mesenchymal GBM with high sensitivity using a combination of the aforementioned cell-specific IHC markers. In conclusion, we demonstrated that molecularly distinct GBM subtypes are characterized by profound differences in the composition of their immune microenvironment, which could potentially help to identify tumors amenable to immunotherapy.
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| 45. |
- Kirkeby, Agnete, et al.
(författare)
-
Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
- 2023
-
Ingår i: Cell Stem Cell. - 1934-5909. ; 30:10, s. 1299-1314
-
Tidskriftsartikel (refereegranskat)abstract
- Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
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| 46. |
- Kitambi, Satish Srinivas, et al.
(författare)
-
Vulnerability of Glioblastoma Cells to Catastrophic Vacuolization and Death Induced by a Small Molecule
- 2014
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 157:2, s. 313-328
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer with marginal life expectancy. Based on the assumption that GBM cells gain functions not necessarily involved in the cancerous process, patient-derived glioblastoma cells (GCs) were screened to identify cellular processes amenable for development of targeted treatments. The quinine-derivative NSC13316 reliably and selectively compromised viability. Synthetic chemical expansion reveals delicate structure-activity relationship and analogs with increased potency, termed Vacquinols. Vacquinols stimulate death by membrane ruffling, cell rounding, massive macropinocytic vacuole accumulation, ATP depletion, and cytoplasmic membrane rupture of GCs. The MAP kinase MKK4, identified by a shRNA screen, represents a critical signaling node. Vacquinol-1 displays excellent in vivo pharmacokinetics and brain exposure, attenuates disease progression, and prolongs survival in a GBM animal model. These results identify a vulnerability to massive vacuolization that can be targeted by small molecules and point to the possible exploitation of this process in the design of anticancer therapies.
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| 47. |
- Larsen, R. Wugt, et al.
(författare)
-
High-resolution infrared study of collisionally cooled trans-1,2-dichloroethylene
- 2007
-
Ingår i: Journal of Molecular Spectroscopy. - : Elsevier BV. - 0022-2852. ; 243:1, s. 99-102
-
Tidskriftsartikel (refereegranskat)abstract
- A recently constructed long-path enclosive flow cooling apparatus is employed to obtain the Fourier transform gas-phase infrared absorption spectrum of natural isotopic trans-1,2-dichloroethylene with a resolution of 0.00190 cm(-1) in the 800-1000 cm(-1) spectral region. The rotational structure of the out-of-plane CH flapping fundamental has been analyzed for the isotopic analogues Cl-35(2) and (ClCl)-Cl-35-Cl-37 using the Watson A-reduced Hamiltonian model and I-r-representation. A ground-state combination difference analysis for the (ClCl)-Cl-35-Cl-37 isotopomer based on 1402 assigned transitions belonging to the v(6) band yields a band origin of 897.94493(10) cm(-1) and values for the ground-state rotational constants: A(0) = 1.7466454(44) cm(-1), B-0 = 0.05019643(82) cm(-1) and C-0 = 0.04877977(82) cm(-1) together with quartic centrifugal distortion constants. The red-shift of 0.00444(10) cm(-1) observed for the v(6) band origin of (ClCl)-Cl-35-Cl-37 relative to the Cl-35(2), band origin is now consistent with the Rayleigh rule. (c) 2007 Elsevier Inc. All rights reserved.
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| 48. |
- Larsson, Ida, et al.
(författare)
-
Modeling glioblastoma heterogeneity as a dynamic network of cell states
- 2021
-
Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 17:9
-
Tidskriftsartikel (refereegranskat)abstract
- Tumor cell heterogeneity is a crucial characteristic of malignant brain tumors and underpins phenomena such as therapy resistance and tumor recurrence. Advances in single-cell analysis have enabled the delineation of distinct cellular states of brain tumor cells, but the time-dependent changes in such states remain poorly understood. Here, we construct quantitative models of the time-dependent transcriptional variation of patient-derived glioblastoma (GBM) cells. We build the models by sampling and profiling barcoded GBM cells and their progeny over the course of 3 weeks and by fitting a mathematical model to estimate changes in GBM cell states and their growth rates. Our model suggests a hierarchical yet plastic organization of GBM, where the rates and patterns of cell state switching are partly patient-specific. Therapeutic interventions produce complex dynamic effects, including inhibition of specific states and altered differentiation. Our method provides a general strategy to uncover time-dependent changes in cancer cells and offers a way to evaluate and predict how therapy affects cell state composition.
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| 49. |
- Mikulskiene, Birute, et al.
(författare)
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On the stability of the hydrogen chloride complexes with ethylene and acetylene. A high resolution gas phase and ab initio study
- 2003
-
Ingår i: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. - 1386-1425. ; 59:4, s. 733-741
-
Tidskriftsartikel (refereegranskat)abstract
- The temperature dependencies of the intensities of the HCl stretching bands of the hydrogen chloride complexes with acetylene and ethylene have been used to obtain estimates of the dissociation enthalpies of the two complexes. Quantum chemical calculations on the Hartree Fock and DFT/B3LYP levels of theory have been combined with experimental data to give estimates of the intensities of the HCl stretching vibration in the two complexes.
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| 50. |
- Nelander, B., et al.
(författare)
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Optically active low-temperature inversion stabilised 1,2-dithiane by photolysis with circularly polarised light
- 1974
-
Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614. ; 28:3, s. 384-386
-
Tidskriftsartikel (refereegranskat)abstract
- Optically active 1,2-dithiane has been produced in a hydrocarbon g ass at 77 K by photolysis with circularly polarised light. Its CD spectrum (above 270 nm) consists of a single symmetric component coinciding with the position of the low energy absorption band. The possibility of using the method to study any per se chiral but at room temperature statistically optically inactive molecule is stressed. A relation yielding Δϵ is presented.
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