For Ludwigshafen am Bodensee, see Bodman-Ludwigshafen. Ludwigshafen am Rhein is a city in Rhineland-Palatinate, Germany, on the river Rhine, opposite Mannheim. With Mannheim and the surrounding region, it forms the Rhine Neckar Area. Known as an industrial city, Ludwigshafen is the home of chemical giant BASF and other companies. Among its cultural facilities are the Staatsphilharmonie Rheinland-Pfalz, it is the philosopher Ernst Bloch. The city is a global city with'sufficiency' status. In antiquity and Germanic tribes settled in the Rhine Neckar area. During the 1st century B. C. the Romans conquered the region, a Roman auxiliary fort was constructed near the present suburb of Rheingönheim. The Middle Ages saw the foundation of some of Ludwigshafen's future suburbs, including Oggersheim, Maudach and Mundenheim. Most of the area, remained swampland, with its development hindered by seasonal flooding of the Rhine; the Rhine Neckar region was part of the territory of the Prince-elector of the Kurpfalz, or Electorate of the Palatinate, one of the larger states within the Holy Roman Empire.
The foundation of the new capital of the Kurpfalz, was a decisive influence on the development of the area as a whole. Parallel to the foundation of Mannheim in 1606, a fortress was built by Frederick IV, Elector Palatine on the other side of the Rhine to protect the City of Mannheim, thus forming the nucleus of the City of Ludwigshafen itself. In the 17th century the region was devastated and depopulated during the Thirty Years' War, in King Louis XIV of France’s wars of conquest in the part of the century, it was only in the 18th century that the settlements around the Rheinschanze began to prosper, profiting from the proximity of the capital Mannheim. Oggersheim in particular gained some importance, after the construction of both a small palace serving as secondary residence for the Elector, the famous pilgrimage church, Wallfahrtskirche. For some weeks in 1782, the great German writer and playwright Friedrich Schiller lived in Oggersheim, on flight from his native Württemberg). War returned to the Ludwigshafen area with the armies of the French Revolution.
The palace at Oggersheim was burned down, Mannheim besieged several times, all the area west of the Rhine annexed by France from 1798 to 1813. The Electorate of the Palatinate was split up; the eastern bank of the Rhine with Mannheim and Heidelberg was given to Baden, while the western bank was granted to Bavaria, following the Wars of Liberation, in which the French were expelled. The Rhine had become a frontier and the Rheinschanze, cut off politically from Mannheim, lost its function as the neighbouring city's military bulwark. In 1808, during the French occupation, Carl Hornig of Mannheim purchased the fortress from the French authorities and turned it into a way station for passing river traffic; the Rheinschanze with its winter-proof harbour basin was used as trading post. Hornig died in 1819, but Johann Heinrich Scharpff, a businessman from Speyer, continued Hornig's plans, which were turned over to his son-in-law, Philipp Markus Lichtenberger, in 1830, their activities marked the beginning of the civilian use of the Rheinschanze.
The year 1844 was the official birth of Ludwigshafen, when Lichtenberger sold this property to the state of Bavaria, the military title of the fortress was removed. The Bavarian king, Ludwig I, set forth plans to rename the settlement after himself and to start construction of an urban area as a Bavarian rival to Mannheim on the opposite bank. During the failed German revolution of 1848 rebels captured Ludwigshafen, but they were bombarded from Mannheim, Prussian troops expelled the revolutionaries. On December 27, 1852, King Maximilian II granted Ludwigshafen am Rhein political freedom and as on November 8, 1859, the settlement gained city status. At its founding Ludwigshafen was still a modest settlement with just 1,500 inhabitants. Real growth began with industrialization, gained enormous momentum in Ludwigshafen due to its ideal transport facilities. In addition to its excellent position and harbor facilities on the Rhine, a railway connecting Ludwigshafen with the Saar coalfields was completed in 1849.
The year 1865 was an important date in the history of independent Ludwigshafen. After several discussions, BASF decided to move its factories from Mannheim to the Hemshof district, which belonged to Ludwigshafen. From on, the city's rapid growth and wealth were linked to BASF's success and its expansion into becoming one of the world's most important chemical companies. Ludwigshafen became home to several other growing chemical companies, including Friedrich Raschig GmbH, the Benckiser company, Giulini Brothers, Grünzweig&Hartmann AG, Knoll AG. With more jobs available, the population of Ludwigshafen increased rapidly. In 1899 the city was governing more than 62,000 residents; this population explosion looked quite “American” to contemporaries. The solution was the expansion of the municipal area and the incorporation of the two nearest villages and Mundenheim, in the years 1892 and 1899. In the area between the city centre and those two suburbs new quarters were built after modern urban development plans.
Vasile Goldiș Western University of Arad
„Vasile Goldiș” Western University of Arad is a private university located in Arad, Romania. The spiritual patron of the university is Vasile Goldiș, a prominent Romanian politician, publicist, member of the Romanian Academy and a key figure of the Union of Transylvania with Romania in 1918. Subsequent to the union he was a member of the Ion I. C. Brătianu, Artur Văitoianu and Alexandru Averescu cabinets and a deputy in the Romanian Parliament. After his withdrawal from politics he dedicated himself to cultural activities. Between 1923-1932 he was the president of the ASTRA society; the Vasile Goldiș Western University was founded in 1990 with only two faculties at the time: Law and Marketing and Computer Sciences. Subsequently, to the development of the university new faculties appeared completing the initial two. So in 1991 appeared the Faculty of Dentistry, the Faculty of Medicine in 1992, the Faculty of Physical Training and Sport in 1993. Nowadays the University has branches in Satu Mare, Baia Mare, Zalău, Marghita, Bistrița, Alba Iulia.
In 2017, the University had an approximate number of 6,000 students, enrolled in the classic 3 level programs of undergraduate and doctoral degrees. The University is a signatory of the 1999 Bologna Process Charter. Structure of the VGWU Faculty of Law Faculty of Economics, Information Technology and Engineering Faculty of Medicine Institute of Life Sciences Faculty of Pharmacy Faculty of Dentistry Faculty of Humanities, Physical Education and Sport Macea University Botanical GardenVGWU establishes itself on a yearly programme separated in two semesters and spring. Prof. PhD. Aurel Ardelean - President of “Vasile Goldiș” Western University of Arad Prof. PhD. Coralia A. Cotoraci - rector Prof. PhD. Petru Darau – deputy rector Prof. PhD. Anca Hermenean – deputy rector Associate Prof. PhD. Cristian Bente – deputy rector Associate Prof. PhD. Andrei Anghelina – deputy rector Associate Prof. PhD. Aristide Sorin Baschir - president of Senate The University is organized in 6 faculties and 2 departments incorporated into the faculty structure.
Auxiliary to the academic structure, the university developed a system of supporting structures for research and innovation. Official website
Super-resolution microscopy, in light microscopy, is a term that gathers several techniques, which allow images to be taken with a higher resolution than the one imposed by the diffraction limit. Due to the diffraction of light, the resolution in conventional light microscopy is limited, as stated by Ernst Abbe in 1873. In this context, a diffraction-limited microscope with numerical aperture N. A. and light with wavelength λ reaches a lateral resolution of d = λ/ - a similar formalism can be followed for the axial resolution. The resolution for a standard optical microscope in the visible light spectrum is about 200 nm laterally and 600 nm axially. Experimentally, the attained resolution can be measured from the full width at half maximum of the point spread function using images of point-like objects. Although the resolving power of a microscope is not well defined, it is considered that a super-resolution microscopy technique offers a resolution better than the one stipulated by Abbe. Super-resolution imaging techniques include single-molecule localization methods, photon tunneling microscopy as well as those that utilize the Pendry Superlens and near field scanning optical microscopy, the 4Pi Microscope, confocal microscope, or confocal microscopy aided with computational methods such as deconvolution or detector-based pixel reassignment, structured illumination microscopy technologies like SIM and SMI.
There are two major groups of methods for functional super-resolution microscopy: Deterministic super-resolution: The most used emitters in biological microscopy, show a nonlinear response to excitation, this nonlinear response can be exploited to enhance resolution. These methods include STED, GSD, RESOLFT and SSIM. Stochastic super-resolution: The chemical complexity of many molecular light sources gives them a complex temporal behavior, which can be used to make several close-by fluorophores emit light at separate times and thereby become resolvable in time; these methods include Super-resolution optical fluctuation imaging and all single-molecule localization methods such as SPDM, SPDMphymod, PALM, FPALM, STORM and dSTORM. On October 8, 2014, the Nobel Prize in Chemistry was awarded to Eric Betzig, W. E. Moerner and Stefan Hell for "the development of super-resolved fluorescence microscopy," which brings "optical microscopy into the nanodimension". In 1978, the first theoretical ideas had been developed to break the Abbe limit using a 4Pi microscope as a confocal laser scanning fluorescence microscope where the light is focused ideally from all sides to a common focus, used to scan the object by'point-by-point' excitation combined with'point-by-point' detection.
Some of the following information was gathered from a chemistry blog's review of sub-diffraction microscopy techniques Part I and Part II. For a review, see reference. In 1986, the super-resolution optical microscope based on stimulated emission was patented by Okhonin. NORM microscopy is a method of optical near-field acquisition by a far-field microscope through the observation of nanoparticles' Brownian motion in an immersion liquid. NORM utilizes object surface scanning by stochastically moving nanoparticles. Through the microscope, nanoparticles look like symmetric round spots; the spot width is equivalent to the point spread function and is defined by the microscope resolution. Lateral coordinates of the given particle can be evaluated with a precision much higher than the resolution of the microscope. By collecting the information from many frames one can map out the near field intensity distribution across the whole field of view of the microscope. In comparison with NSOM and ANSOM this method does not require any special equipment for tip positioning and has a large field of view and a depth of focus.
Due to the large number of scanning "sensors" one can get shorter time of image acquisition. A 4Pi microscope is a laser scanning fluorescence microscope with an improved axial resolution; the typical value of 500–700 nm can be improved to 100–150 nm, which corresponds to an spherical focal spot with 5–7 times less volume than that of standard confocal microscopy. The improvement in resolution is achieved by using two opposing objective lenses, both of which are focused to the same geometrical location; the difference in optical path length through each of the two objective lenses is aligned to be minimal. By this, molecules residing in the common focal area of both objectives can be illuminated coherently from both sides and the reflected or emitted light can be collected coherently, i.e. coherent superposition of emitted light on the detector is possible. The solid angle Ω, used for illumination and detection is increased and approaches the ideal case. In this case the sample is detected from all sides simultaneously.
Up to now, the best quality in a 4Pi microscope was reached in conjunction with the STED principle in fixed cells and RESOLFT microscopy with switchable proteins in living cells. There is the wide-field structured-illumination approach. SI enhances spatial resolution by collecting information from frequency space outside the observable region; this process is done in reciprocal space: The Fourier transform of an SI image contains superimposed additional information from different areas of reciprocal space.
Stimulated emission depletion microscopy is one of the techniques that make up super-resolution microscopy. It creates super-resolution images by the selective deactivation of fluorophores, minimising the area of illumination at the focal point, thus enhancing the achievable resolution for a given system, it was developed by Stefan W. Hell and Jan Wichmann in 1994, was first experimentally demonstrated by Hell and Thomas Klar in 1999. Hell was awarded the Nobel Prize in Chemistry in 2014 for its development. In 1986, V. A. Okhonin had patented the STED idea; this patent was unknown to Hell and Wichmann in 1994. STED microscopy is one of several types of super resolution microscopy techniques that have been developed to bypass the diffraction limit of light microscopy to increase resolution. STED is a deterministic functional technique that exploits the non-linear response of fluorophores used to label biological samples in order to achieve an improvement in resolution, to say STED allows for images to be taken at resolutions below the diffraction limit.
This differs from the stochastic functional techniques such as Photoactivated localization microscopy and stochastic optical reconstruction microscopy as these methods use mathematical models to reconstruct a sub diffraction limit from many sets of diffraction limited images. In traditional microscopy, the resolution that can be obtained is limited by the diffraction of light. Ernst Abbe developed an equation to describe this limit; the equation is: D = λ 2 N A where D is the diffraction limit, λ is the wavelength of the light, NA is the numerical aperture, or the refractive index of the medium multiplied by the sine of the angle of incidence. This diffraction limit is the standard; because STED selectively deactivates the fluorescence, it can achieve resolution better than traditional confocal microscopy. Normal fluorescence occurs by exciting an electron from the ground state into an excited electronic state of a different fundamental energy level which, after relaxing back to the ground state, emits a photon by dropping from S1 to a vibrational energy level on S0.
STED interrupts this process. The excited electron is forced to relax into a higher vibration state than the fluorescence transition would enter, causing the photon to be released to be red-shifted as shown in the image to the right; because the electron is going to a higher vibrational state, the energy difference of the two states is lower than the normal fluorescence difference. This lowering of energy raises the wavelength, causes the photon to be shifted farther into the red end of the spectrum; this shift differentiates the two types of photons, allows the stimulated photon to be ignored. To force this alternative emission to occur, an incident photon must strike the fluorophore; this need to be struck by an incident photon has two implications for STED. First, the number of incident photons directly impacts the efficiency of this emission, secondly, with sufficiently large numbers of photons fluorescence can be suppressed. To achieve the large number of incident photons needed to suppress fluorescence, the laser used to generate the photons must be of a high intensity.
This high intensity laser can lead to the issue of photobleaching the fluorophore. Photobleaching is the name for the destruction of fluorophores by high intensity light. STED functions by depleting fluorescence in specific regions of the sample while leaving a center focal spot active to emit fluorescence; this focal area can be engineered by altering the properties of the pupil plane of the objective lens. The most common early example of these diffractive optical elements, or DOEs, is a torus shape used in two-dimensional lateral confinement shown below; the red zone is depleted. This DOE is generated by a circular polarization of the depletion laser, combined with a helical phase ramp; the lateral resolution of this DOE is between 30 and 80 nm. However, values down to 2.4 nm have been reported. Using different DOEs, axial resolution on the order of 100 nm has been demonstrated. A modified Abbe’s equation describes this sub diffraction resolution as: D = λ 2 n sin α 1 + I I sat Where n is the refractive index of the medium, I is the intracavity intensity and Isat is the saturation intensity.
To optimize the effectiveness of STED, the destructive interference in the center of the focal spot needs to be as close to perfect as possible. That imposes certain constraints on the optics. Early on in the development of STED, the number of dyes that could be used in the process was limited. Rhodamine B was named in the first theoretical description of STED; as a result, the first dyes used were laser emitting in the red spectrum. To allow for STED analysis of biological systems, the dyes and laser sources must be tailored to the system; this desire for better analysis of these systems has led to living cell STED and multicolor STED, but it has demanded more and more advanced dyes and excitation systems to accommodate the increased functionality. One such advancement was t
Confocal microscopy, most confocal laser scanning microscopy or laser confocal scanning microscopy, is an optical imaging technique for increasing optical resolution and contrast of a micrograph by means of using a spatial pinhole to block out-of-focus light in image formation. Capturing multiple two-dimensional images at different depths in a sample enables the reconstruction of three-dimensional structures within an object; this technique is used extensively in the scientific and industrial communities and typical applications are in life sciences, semiconductor inspection and materials science. Light travels through the sample under a conventional microscope as far into the specimen as it can penetrate, while a confocal microscope only focuses a smaller beam of light at one narrow depth level at a time; the CLSM achieves a controlled and limited depth of focus. The principle of confocal imaging was patented in 1957 by Marvin Minsky and aims to overcome some limitations of traditional wide-field fluorescence microscopes.
In a conventional fluorescence microscope, the entire specimen is flooded evenly in light from a light source. All parts of the specimen in the optical path are excited at the same time and the resulting fluorescence is detected by the microscope's photodetector or camera including a large unfocused background part. In contrast, a confocal microscope uses point illumination and a pinhole in an optically conjugate plane in front of the detector to eliminate out-of-focus signal – the name "confocal" stems from this configuration; as only light produced by fluorescence close to the focal plane can be detected, the image's optical resolution in the sample depth direction, is much better than that of wide-field microscopes. However, as much of the light from sample fluorescence is blocked at the pinhole, this increased resolution is at the cost of decreased signal intensity – so long exposures are required. To offset this drop in signal after the pinhole, the light intensity is detected by a sensitive detector a photomultiplier tube or avalanche photodiode, transforming the light signal into an electrical one, recorded by a computer.
As only one point in the sample is illuminated at a time, 2D or 3D imaging requires scanning over a regular raster in the specimen. The beam is scanned across the sample in the horizontal plane by using one or more oscillating mirrors; this scanning method has a low reaction latency and the scan speed can be varied. Slower scans provide a better signal-to-noise ratio, resulting in better contrast and higher resolution; the achievable thickness of the focal plane is defined by the wavelength of the used light divided by the numerical aperture of the objective lens, but by the optical properties of the specimen. The thin optical sectioning possible makes these types of microscopes good at 3D imaging and surface profiling of samples. Successive slices make up a'z-stack' which can either be processed by certain software to create a 3D image, or it is merged into a 2D stack. Confocal microscopy provides the capacity for direct, serial optical sectioning of intact, living specimens with a minimum of sample preparation as well as a marginal improvement in lateral resolution.
Biological samples are treated with fluorescent dyes to make selected objects visible. However, the actual dye concentration can be low to minimize the disturbance of biological systems: some instruments can track single fluorescent molecules. Transgenic techniques can create organisms that produce their own fluorescent chimeric molecules. Confocal microscopes work on the principle of point excitation in the specimen and point detection of the resulting fluorescent signal. A pinhole at the detector provides a physical barrier. Only the in-focus, or central spot of the airy disk, is recorded. Raster scanning the specimen one point at a time permits thin optical sections to be collected by changing the z-focus; the resulting images can be stacked to produce a 3D image of the specimen. Four types of confocal microscopes are commercially available: Confocal laser scanning microscopes use multiple mirrors to scan the laser across the sample and "descan" the image across a fixed pinhole and detector.
Spinning-disk confocal microscopes use a series of moving pinholes on a disc to scan spots of light. Since a series of pinholes scans an area in parallel, each pinhole is allowed to hover over a specific area for a longer amount of time thereby reducing the excitation energy needed to illuminate a sample when compared to laser scanning microscopes. Decreased excitation energy reduces phototoxicity and photobleaching of a sample making it the preferred system for imaging live cells or organisms. Microlens enhanced or dual spinning-disk confocal microscopes work under the same principles as spinning-disk confocal microscopes except a second spinning-disk containing micro-lenses is placed before the spinning-disk containing the pinholes; every pinhole has an associated microlens. The micro-lenses act to capture a broad band of light and focus it into each pinhole increasing the amount of light directed into each pinhole and reducing the amount of light blocked by the spinning-disk. Microlens enhanced confocal mi
Heidelberg University Faculty of Physics and Astronomy
The Faculty of Physics and Astronomy is one of twelve faculties at the University of Heidelberg. It comprises the Kirchhoff Institute of Physics, the Institute of Physics, Theoretical Physics, Environmental Physics and Theoretical Astrophysics; the Kirchhoff-Institut für Physik, built in 2002, is a research institute located in Heidelberg, Germany. It shares faculty with the astronomy departments at the University of Heidelberg; the institute is named after Gustav Kirchhoff, who collaborated in Heidelberg in 1854 with Robert Bunsen in spectroscopic work. The scope of its research is broad. Many projects exist, from low temperature physics and neuronal information processing to surface physics. Facilities include a cleanroom, an ASIC laboratory, an experimental hall and, as it is serves undergraduates, there are 2 auditoriums with a capacity of over 300 people, several seminar rooms and a CIP pool. Current director is Prof. Dr. Markus Oberthaler. Research Interests Biophysics Complex Quantum Systems condensed matter systems at ultra-low temperatures and matter waves.
Particle Physics calorimetry and trigger processor development for the ATLAS and H1 particle detectors. Technical Computer Science The Institute of Environmental Physics was founded in 1975, its current director is Prof. Dr. Norbert Frank. Research Interests Atmosphere and Remote Sensing, Radiative Transfer and Solar Energy Deposition Terrestrial Systems, Water Flow, Solute Transport and Permafrost Aquatic Systems and Paleoclimate, Limnology Small-Scale Air-Sea Interaction, Image Processing Atmospheric Aerosols and Climate The Zentrum für Astronomie der Universität Heidelberg was founded in 2005 and is an association of three research institutes: the Astronomical Calculation Institute, the Institute of Theoretical Astrophysics and the Landessternwarte Heidelberg-Königstuhl; the Astromomisches Rechen-Institut is part of the Center of Astronomy of the University of Heidelberg. Before it was a research institute for astrometry and stellar dynamics belonging to the state of Baden-Württemberg, it is the most important international institution for astronomical data calculations.
The Astronomisches Rechen-Institut is responsible among other things for the Gliese catalog of nearby stars, the fundamental catalog FK5 and FK6 and the annual published Apparent places, a high precision catalog with pre-calculated positions for over 3 thousand stars for each day. The ARI was founded in 1700 in Berlin-Dahlem by Gottfried Kirch, it has its origin from the catalog patent application in this time by Frederick I of Prussia, who introduced a monopoly on publishing star catalogs in Prussia. In 1945 the Institute was moved by the occupying force nearer to their headquarters in Heidelberg. Since January 1, 2005 it has been integrated into the Center of Astronomy and as of today is not limited to publishing star catalogs but has a wide research scope; the Institute of Theoretical Astrophysics was founded in 1976. Research Interest Cosmology, Gravitational lensing and Galaxy groups and clusters Star formation, interstellar turbulences and development of galactic gas clouds Planet formation, through gravitation collapse of interstellar molecular gas clouds Accretion discs, theory of accretion discs and mass loss from discs
RESOLFT, an acronym for REversible Saturable OpticaL Fluorescence Transitions, denotes a group of optical microscopy techniques with high resolution. Using standard far field visible light optics a resolution far below the diffraction limit down to molecular scales can be obtained. With conventional microscopy techniques, it is not possible to distinguish features that are located at distances less than about half the wavelength used; this diffraction limit is based on the wave nature of light. In conventional microscopes the limit is determined by the used wavelength and the numerical aperture of the optical system; the RESOLFT concept surmounts this limit by temporarily switching the molecules to a state in which they cannot send a signal upon illumination. This concept is different from for example electron microscopy where instead the used wavelength is much smaller. RESOLFT microscopy is an optical microscopy with high resolution that can image details in samples that cannot be imaged with conventional or confocal microscopy.
Within RESOLFT the principle of STED microscopy and GSD microscopy are generalized. Structures that are too close to each other to be distinguished are read out sequentially. Within this framework all methods can be explained which operate on molecules that have at least two distinguishable states, where reservible switching between the two states is possible, where at least one such transition can be optically induced. In most cases fluorescent markers are used, where one state, bright, that is, generates a fluoresence signal, the other state is dark, gives no signal. One transition between them can be induced by light; the sample is illuminated inhomogeneously with the illumination intensity at one position being small. Only at this place are the molecules never in the dark state B and remain in the bright state A; the area where molecules are in the bright state can be made small by increasing the transition light intensity. Any signal detected is thus known to come only from molecules in the small area around the illumination intensity minimum.
A high resolution image can be constructed by scanning the sample, i.e. shifting the illumination profile across the surface. The transition back from B to A can be either driven by light of another wavelength; the molecules have to be switchable several times in order to be present in state A or B at different times during scanning the sample. The method works if the bright and the dark state are reversed, one obtains a negative image. Despite the diffraction-limit the area where molecules reside in state A can be made arbitrarily small. One has to illuminate the sample inhomogeneously so that an isolated zero intensity point is created; this can be achieved e.g. by interference. At low intensities most marker molecules are in the bright state, if the intensity is above, most markers are in the dark state. Upon weak illumination we see that the area is quite large where the illumination is so low that most molecules reside in state A; the shape of the illumination profile does not need to be altered.
Increasing the illumination brightness results in a smaller area where the intensity is below the amount for efficient switching to the dark state. The area where molecules can reside in state A is diminished; the signal during a following readout originates from a small spot and one can obtain sharp images. In the RESOLFT concept the resolution can be approximated by Δ d = λ π ⋅ n ⋅ I I s a t, whereby I s a t is the characteristic intensity required for saturating the transition, I denotes the intensity applied. If the minima are produced by focusing optics with a numerical aperture N A = n sin α, the minimal distance at which two identical objects can be discerned is Δ d = λ 2 n ⋅ sin α ⋅ 1 + I I s a t which can be regarded as an extension of Abbe’s equation; the diffraction-unlimited nature of the RESOLFT family of concepts is reflected by the fact that the minimal resolvable distance Δ d can be continuously decreased by increasing ς = I I s a t. Hence the quest for nanoscale resolution comes down to maximizing this quantity.
This is possible by increasing I or by lowering I s a t. Different processes are used when switching the molecular states. However, all have in common that a