Long-Axis Spinning of an Optically Levitated Particle: A Levitated Spinning Top.

An elongated object can be rotated around one of its short axes, like a propeller, or around its long axis, like a spinning top. Using optically levitated nanoparticles, short-axis rotation and libration have been systematically investigated in several recent studies. Notably, short-axis rotational degrees of freedom have been cooled to millikelvin temperatures and driven into gigahertz rotational speeds. However, controlled long-axis spinning has so far remained an unrealized goal. Here, we demonstrate controlled long-axis spinning of an optically levitated nanodumbbell with spinning rates exceeding 1 GHz. We show that the damping rate in high vacuum can be as low as a few millihertz. Our results open up applications in inertial torque sensing and studies of rotational quantum interference.

Controlling Optomechanical Libration with the Degree of Polarization.

Control of the potential energy and free evolution lie at the heart of levitodynamics as key requirements for sensing, wave function expansion, and mechanical squeezing protocols. Here, we experimentally demonstrate versatile control over the optical potential governing the libration motion of a levitated anisotropic nanoparticle. This control is achieved by introducing the degree of polarization as a new tool for rotational levitodynamics. We demonstrate thermally driven free rotation of a levitated anisotropic scatterer around its short axis and we use the rotational degrees of freedom to probe the local spin of a strongly focused laser beam.

Stimulated scintillation emission depletion X-ray imaging.

X-ray microtomography is a widely applied tool for noninvasive structure investigations. The related detectors are usually based on a scintillator screen for the fast in situ conversion of an X-ray image into an optical image. Spatial resolution of the latter is fundamentally diffraction limited. In this work, we introduce stimulated scintillation emission depletion (SSED) X-ray imaging where, similar to stimulated emission depletion (STED) microscopy, a depletion beam is applied to the scintillator screen to overcome the diffraction limit. The requirements for the X-ray source, the X-ray flux, the scintillator screen, and the STED beam were evaluated. Fundamental spatial resolution limits due to the spread of absorbed X-ray energy were estimated with Monte Carlo simulations. The SSED proof-of-concept experiments demonstrated 1) depletion of X-ray excited scintillation, 2) partial confinement of scintillating regions to sub-diffraction sized volumes, and 3) improvement of the imaging contrast by applying SSED.

STED properties of Ce3+, Tb3+, and Eu3+ doped inorganic scintillators.

Scintillator-based X-ray imaging is a powerful technique for noninvasive real-space microscopic structural investigation such as synchrotron-based computed tomography. The resolution of an optical image formed by scintillation emission is fundamentally diffraction limited. To overcome this limit, stimulated scintillation emission depletion (SSED) X-ray imaging, based on stimulated emission depletion (STED) microscopy, has been recently developed. This technique imposes new requirements on the scintillator material: efficient de-excitation by the STED-laser and negligible STED-laser excited luminescence. In this work, luminescence depletion was measured in several commonly-used Ce3+, Tb3+, and Eu3+ - doped scintillators using various STED lasers. The depletion of Tb3+ and Eu3+ via 4f-4f transitions was more efficient (Ps = 8…19 mW) than Ce3+ depletion via 5d-4f transitions (Ps = 43…45 mW). Main origins of STED-laser excited luminescence were one- and two-photon excitation, and scintillator impurities. LSO:Tb scintillator and a 628 nm cw STED-laser is the most promising combination for SSED satisfying the above-mentioned requirements.

Protein synthesis inhibitors of natural origin for CML therapy: semisynthetic homoharringtonine (Omacetaxine mepesuccinate).

Omacetaxine mepesuccinate is a drug approved in 2014 by FDA for the use in CML therapy in patients resistant to at least two thymidine kinase inhibitors (TKIs). It possesses unique mechanism of anticancer activity that is principally different from mechanism of activity of TKIs. Omacetaxine mepesuccinate inhibits protein translation through prevention of the initial elongation step of protein synthesis and its use benefits CML patients possessing the BCR-ABL oncogene. Because of the superior activity of Omacetaxine in patients who became resistant to therapy with TKIs, FDA decided on the accelerated approval of this drug taking its consideration not only its activity as such but also a favorable benefit-to-risk profile in patients included into clinical studies.

Escape dynamics of active particles in multistable potentials.

Rare transitions between long-lived metastable states underlie a great variety of physical, chemical and biological processes. Our quantitative understanding of reactive mechanisms has been driven forward by the insights of transition state theory and in particular by Kramers' dynamical framework. Its predictions, however, do not apply to systems that feature non-conservative forces or correlated noise histories. An important class of such systems are active particles, prominent in both biology and nanotechnology. Here, we study the active escape dynamics of a silica nanoparticle trapped in a bistable potential. We introduce activity by applying an engineered stochastic force that emulates self-propulsion. Our experiments, supported by a theoretical analysis, reveal the existence of an optimal correlation time that maximises the transition rate. We discuss the origins of this active turnover, reminiscent of the much celebrated Kramers turnover. Our work establishes a versatile experimental platform to study single particle dynamics in non-equilibrium settings.

Levitodynamics: Levitation and control of microscopic objects in vacuum.

The control of levitated nano- and micro-objects in vacuum­which capitalizes on scientific achievements in the fields of atomic physics, control theory, and optomechanics­is of considerable interest. The ability to couple the motion of levitated systems to internal degrees of freedom, as well as to external forces and systems, provides opportunities for science and technology. Attractive research directions, ranging from fundamental quantum physics to commercial sensors, have been unlocked by the many recent experimental achievements, including motional ground-state cooling of an optically levitated nanoparticle. Here we review the status, challenges, and prospects of levitodynamics, the multidisciplinary research area devoted to understanding, controlling, and using levitated nano- and micro-objects in vacuum.

Selenium as a chemoprotective anti-cancer agent: reality or wishful thinking?

It is generally accepted that selenium (Se) plays an important role in maintaining equilibrium of a healthy organism. It also participates in processes related to carcinogenesis such as inhibition of tumor formation and regression. Scientific data accumulated so far using experimental animal models and from clinical studies devoted to investigating the effects of Se confirm strong relationship or correlation between Se supplementation and tumor frequency of prostate, lungs, liver and colon. However, details of mechanisms of action of Se in modulation of carcinogenesis and cancer prevention are not yet fully elucidated. It is not clear yet whether Se deficiency itself is a cancer risk factor or whether it helps an already present cancer to progress. Additionally, the effects of other factors such as age, gender, life style, geographic location, comorbidities and use of drugs, are not clear. Despite the fact that some positive results were obtained with Se supplementation, it is necessary to verify these findings in more controlled experimental models including clinical studies. At the present time, data related to Se supplementation are not convincing enough as to allow general recommendation for using Se as an effective agent for chemoprevention of cancer. The goal of this minireview is to highlight present level of understanding of Se biological and prospects of its future clinical use. Information regarding Se, its effectiveness in various experimental models and in clinical tests, including combinations with other bioactive agents and anticancer drugs, is evaluated and summarized.

Morphology and distribution of granulomatous inflammation in freshwater ornamental fish infected with mycobacteria.

Mycobacteriosis in fish is a chronic progressive ubiquitous disease caused by Mycobacterium marinum, M. gordonae and M. fortuitum in most cases. The aim of this study was to describe the morphology and distribution of lesions in 322 freshwater ornamental fish across 36 species. Granulomatous inflammation was diagnosed by gross examination and histopathology testing in 188 fish (58.4%); acid-fast rods (AFR) were determined in only 96 (51.1%) fish from 19 species after Ziehl-Neelsen staining. The most often affected organs with AFR were the kidney (81.2%), digestive tract (54.1%), liver (48.2%), spleen (45.9%) and skin (21.2%); sporadically, AFR were found in the branchiae (9.4%) and gonads (4.7%). In 14 randomly selected fish originating from four different fish tanks, the distribution of mycobacterial infection was studied by culture examination of the skin, gills, muscle tissue, digestive tract, liver, spleen and kidney. In 12 fish, the species M. marinum, M. gordonae, M. fortuitum, M. triviale, and M. avium subsp. hominissuis (serotypes 6 and 8 and genotype IS901- and IS1245+) were detected; mixed infection caused by different mycobacterial species was documented in five of them.

Mechanism of near-field Raman enhancement in one-dimensional systems.

We develop a theory of near-field Raman enhancement in one-dimensional systems, and report supporting experimental results for carbon nanotubes. The enhancement is established by a laser-irradiated nanoplasmonic structure acting as an optical antenna. The near-field Raman intensity is inversely proportional to the 10th power of the separation between the enhancing structure and the one-dimensional system. Experimental data obtained from single-wall carbon nanotubes indicate that the Raman enhancement process is not significantly influenced by the specific phonon eigenvector, and is mainly defined by the properties of the nanoplasmonic structure.

Tip-enhanced near-field optical microscopy of carbon nanotubes.

We review recent experimental studies on single-walled carbon nanotubes on substrates using tip-enhanced near-field optical microscopy (TENOM). High-resolution optical and topographic imaging with sub 15 nm spatial resolution is shown to provide novel insights into the spectroscopic properties of these nanoscale materials. In the case of semiconducting nanotubes, the simultaneous observation of Raman scattering and photoluminescence (PL) is possible, enabling a direct correlation between vibrational and electronic properties on the nanoscale. So far, applications of TENOM have focused on the spectroscopy of localized phonon modes, local band energy renormalizations induced by charge carrier doping, the environmental sensitivity of nanotube PL, and inter-nanotube energy transfer. At the end of this review we discuss the remaining limitations and challenges in this field.

Cytarabine conjugates with biologically active molecules and their potential anticancer activity.

The presented review article deals with various conjugates of arabinosylcytosine (araC). This powerful drug that is routinely used in therapy of hematological malignancies has some shortcomings, which limit its use and therapeutic effects. These are low lipophilicity, low stability to degrading enzymes and need for biological activation through phosphorylation. Conjugating araC to another molecule is done with the intention of increasing araC stability and lipophilicity and possibly avoiding rate-limiting araC phosphorylation. An attachment of that another molecule, possessing its own biological activity, may result in formation of a conjugated molecule with new biological activities and better therapeutic potential. The review deals with various araC conjugates formed at the positions N(4), 2, 2', 3' and 5'. Biological activities and differences from araC of compounds formed by conjugation are also discussed.

[Treatment of trochanteric fractures by percutaneous compression plate]. / Osetrení trochanterických zlomenin PC.C.P. dlahou.

PURPOSE OF THE STUDY: To present a new type of percutaneous compression plate (PCP) for a minimally invasive method of treating trochanteric hip fractures. MATERIAL: Between September 2004 and December 2006, a total of 66 patients with hip fractures were treated by minimally invasive percutaneous osteosynthesis involving a PCP. The average age of the patients was 74.5 years (range, 27-95 years). The fractures were classified as pertrochanteric (AO31, A1.1-A2.3) in 73%, femoral neck fracture (AO31, B2) in 20%, and intertrochanteric fracture (AO31, A3.1) in 7% of the patients. METHODS: Reduction was performed under conduction or general anaesthesia on a traction table, using an X-ray image intensifier system. Reduction and intra-operative temporary stabilisation of the fracture was facilitated by a posterior reduction device. Access was gained and a PCP was inserted through two incisions at the lateral side of the proximal femur. RESULTS: The patients were followed up for at least 6 months. Radiographic union was found on average at 3 months post-operatively. No pseudoarthrosis or implant failure was recorded. At 6-month follow-up, 81% of the patients were able to walk without walking aid or with one walking cane only. Two crutches were used by 8% of the patients.To walk without help was impossible for 11% of the patients whose mobility had already been limited before the injury. DISCUSSION: PCP osteosynthesis for trochanteric fractures is a novel minimally invasive approach providing a better treatment of the fracture. Compared to dynamic hip screw osteosynthesis used before, PCP allows for earlier weight bearing and noticeably reduces blood loss. Implant construction as well as post-operative controlled impaction of the fracture minimize the risk of osteosynthesis failure. The simple instrumentation construction enables us to reduce operative time. CONCLUSIONS: The percutaneous compression plate is a contribution to minimally invasive osteosynthesis of trochanteric fractures. An increase in rotational stability of the implant due to its biaxial telescopic construction allows for earlier weight-bearing of the extremity, thus facilitating the patient's earlier return to everyday life activities. It also reduces operative trauma, blood loss and post-operative complications.

Redirecting the immune response towards immunoprotective domains of a DNABII protein resolves experimental otitis media.

The chronicity and recurrence of many bacterial diseases is largely attributable to the presence of a biofilm, and eradication of these structures is confounded by an extracellular DNA-rich matrix. DNABII proteins, including integration host factor (IHF), are critical components of the matrix formed by all human pathogens tested to date. Whereas the natural adaptive immune response to IHF is against non-protective epitopes within the carboxyl-terminal region, antibodies against the DNA-binding "tips" induce biofilm collapse. We designed a "tip-chimer" immunogen to mimic the DNA-binding regions within the α-subunit and ß-subunit of IHF from nontypeable Haemophilus influenzae (IHFNTHi). Re-direction of the natural adaptive immune response toward immunoprotective domains disrupted NTHi biofilms in vitro and in an experimental model of otitis media. Our data support the rational design of a powerful therapeutic approach, and also that of a DNABII-directed vaccine antigen that would avoid augmentation of any pre-existing natural, but nonprotective, immune response.

Near-field amplitude and phase recovery using phase-shifting interferometry.

Scattering-type scanning near-field optical microscopy has allowed for investigation of light-matter interaction of a large variety of samples with excellent spatial resolution. Light incident on a metallic probe experiences an amplitude and phase change on scattering, which is dependent on optical sample properties. We implement phase-shifting interferometry to extract amplitude and phase information from an interferometric near-field scattering system, and compare recorded optical images with theoretical predictions. The results demonstrate our ability to measure, with nanoscale resolution, amplitude and phase distributions of optical fields on sample surfaces. The here-introduced phase-shifting method is considerably simpler than heterodyne methods and less sensitive to errors than the two-step homodyne method.

alpha-Lipoic acid: the potential for use in cancer therapy.

This review deals with alpha-lipoic acid (LA) from the point of its chemical and biological characteristics affecting enzymatic activities that are part of cellular biochemical processes in normal and cancer cells. This includes attributes of LA that are related to its ability to act as a free-radicals scavenger and also as a radical generator. LA is discussed in the light of its physico-chemical features, toxicity, biochemical bases of LA biological activities, and mechanisms of action. Additionally, it is discussed how these properties of LA are reflected by results of in vivo experiments with cancer cells and in experimental cancer chemotherapy. Finally, the results of LA use in human cancer chemotherapy and as chemopreventive agent are discussed in the light of LA future inclusion into chemotherapeutic protocols.

Effects of subchronic nitrite exposure on rainbow trout (Oncorhynchus mykiss).

Subchronic toxicity of nitrite in rainbow trout (Oncorhynchus mykiss; mean mass ± S.D., 18.9 ± 1.3g) was assessed in a 28-day trial. The influence of nitrite on fish mortality, growth rate, haematology, blood biochemistry, and gill histology was observed. Survival was not affected by exposures up to 1 mg l(-1) NO(2)(-) (at 10 mg l(-1) Cl(-)). On the basis of growth rate inhibition data, the values of NOEC (28 d LC(0)) and LOEC (28 d LC(10)) were estimated at 0.01 and 0.2 mg l(-1) NO(2)(-), respectively. At 0.01 mg l(-1) NO(2)(-) (the lowest concentration tested), there was segmental hyperplasia of the respiratory epithelium of secondary lamellae and elevated glucose and decreased potassium. Elevated nitrite concentrations were found in blood plasma of fish exposed to concentrations of 1.0 mg l(-1) NO(2)(-) and higher, and in muscle tissue at the highest concentration 3.0 mg l(-1) NO(2)(-). Plasma and muscle nitrite levels were lower than those in the ambient water in all experimental groups.

In vitro and in vivo antileukemic effect of novel dimers consisting of 5-fluorodeoxyuridine and arabinofuranosylcytosine.

Various amphiphilic heterodinucleoside phosphates containing 1-beta-D-arabinofuranosylcytosine (ara-C) and 5- fluorodeoxyuridine (5-FdUrd) have recently been synthesized in order to increase the efficacy of ara-C and 5-FdUrd. Employing growth inhibition and growth recovery assays, we evaluated the in vitro effects of four of these dimers (No. 2, 2A, 3, 10) in L1210 and P388D1 murine leukemia cells. Although ara-C and 5-FdUrd appeared equimolar in all dimers, their contribution to the cytotoxicity of these agents was different. Thus, the liberation of ara-C and 5-FdUrd from their dimeric origin and their subsequent metabolic activation had a different course. In another set of experiments, we examined the in vivo effects of these agents in mice. The dimer with the highest cytotoxicity in vitro exerted the lowest acute toxicity and yielded the lowest therapeutic effect in vivo. The obtained data indicate that dimers with slower liberation of ara-C and 5-FdUrd were less cytotoxic, but prolonged liberation of both antimetabolites protected them from inactivation and extended the time period of therapeutic action. Some of the dimers exceeded the synergistic effects yielded by simultaneous application of both ara-C and 5-FdUrd. The significantly higher therapeutic potential of these new antitumor agents indicates that further studies are warranted.

Effects of deltamethrin on rainbow trout (Oncorhynchus mykiss).

The aim of this study was to assess the effect of deltamethrin on rainbow trout (Oncorhynchus mykiss). Control and experimental group of fish were exposed to Decis EW 50 pesticide preparation (active substance 50g/l of deltamethrin). The acute semistatical toxicity test lasting 96h was performed on rainbow trout juveniles. The 96hLC(50) value of Decis EW 50 was 0.02mg/l. Examination of haematological and biochemical profile and histological tissue examination was performed on 1-2-year-old rainbow trout after 96h of exposure to Decis EW 50 in a concentration of 0.02mg/l. The experimental group showed significantly lower values (p<0.05) of plasma glucose, alanine aminotransferase, cholinesterase and significantly higher (p<0.05) values of erythrocyte count, haemoglobin content, haematocrit and plasma total protein, albumins, ammonia, aspartate aminotransferase, creatinekinase and calcium compared to the control group. The deltamethrin-based Decis EW 50 pesticide preparation was classified among substances strongly toxic for fish.

[Genotype-disease association and possibility to reveal environmentally modifiable disease causes: the use of mendelian randomization principle]. / Asociace genotypu s nemocí a odhalování jejich prostredím ovlivnitelných prícin: vyuzití principu mendelovské randomizace.

Though the methodology and designs of epidemiological studies and analyses of medical databases have improved, associations between modifiable exposures and the disease in observational epidemiological studies remain partly biased. Mendelian randomization principle, which is the random distribution of parental genes to offspring in meiosis during gametogeneis and at conception, represents a chance for methodology of evaluation of the causal relations between the external cause and the disease. The use of this principle assumes the association between the disease and the genetic polymorphism which reflects the biological relation between the suspected exposure and the disease, and is generally less prone to the phenomenon of confounding and reverse causation that can impair the interpretation of results in conventional observational studies. Authors describe explanatory options of the Mendelian randomization principle using examples in folic acid--homocysteine--coronary heart disease, and isothiocyanate versus lung carcinoma. Though the use of Mendelian randomization principle has its limitations, it offers new possibilities to test causal relations and clearly shows that means invested into the Human genome project can contribute to the understanding and prevention of adverse effects of modifiable exposure to the human health.