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Using a combination of vibrational and chiroptical spectroscopy together with principal component analysis and a random forest algorithm, we have successfully distinguished patients with hepatocellular carcinoma from patients with cirrhosis.

Summary: None of the bio­markers studied so far in the HCC area has yielded higher sensitivity and specificity in the early-stage dia­gnosis than the liver ultrasonography examination. There is an urgent clinical need for establishing a laboratory marker for HCC that meets the requirements for high sensitivity and specificity for the screening and early dia­gnosis of at-risk patients. As a variety of pathological processes, including carcinogenesis, may cause changes in both the concentration and the structure and spatial arrangement of body bio­molecules, the spectroscopic analysis of blood-based derivatives appears to be an appropriate tool for the early detection thereof. In our research, the focus is on the identification of novel bio­markers in blood plasma, which would exhibit sufficient sensitivity and specificity to detect early and potentially curable HCC stages, and which would be potentially useful for routine screening of this disease in well-defined at-risk groups. For this purpose, we utilised a unique combination of two chiroptical methods – electronic circular dichroism (ECD) and Raman optical activity (ROA) – supplemented by non-polarised variants – infrared (IR) absorption and Raman spectroscopy. Methods: Blood plasma of 18 selected patients with liver cirrhosis, 8 of which also suffered from HCC, was analysed by a combination of ECD, ROA, IR and Raman spectroscopy. Results: The obtained spectral data were processed by a multivariate statistical evaluation using principal component analysis (PCA) and linear discriminant analysis (LDA). The visualisation of the LDA results showed the separation of the two monitored groups with only a slight overlap. Based on the spectral analysis within this preliminary study, sensitivity and specificity for the discrimination between cirrhotic individuals with and without HCC reached 88% and 90% after leave-one-out cross validation, respectively. The area under the ROC curve of 0.975 proved high reliability of the established model. Conclusion: Based on our findings, the combination of advanced spectroscopic methods for the analysis of blood plasma might be a promising tool in HCC dia­gnosis and potentially in the screening thereof. Key words: hepatocellular carcinoma – blood plasma – spectroscopy – cirrhosis

Stable picosecond supercontinuum generated in long crystals is an excellent means of seeding broadband, high-energy CPA systems. The generated output energy and spectrum can be almost three times as stable as the pump for a wide range of input pulse parameters. In this work, we show this is an intrinsic property for crystals longer than the filament and for a range of input energy values. We present a description of the stability mechanism in both the visible and infrared regions together with experimental data that support the theoretical explanation.

We measure parameters of a stable supercontinuum generated in long YAG crystal, driven by 3 ps pulses at 1030 nm and evaluate the impact of initial conditions on supercontinuum stability.

We present the design of a collinear femtosecond optical parametric amplification (OPA) system producing a tunable output at wavelengths between 1030 nm and 1080 nm from a Ti:Sapphire pump laser at a wavelength of 795 nm. Generation of a supercontinuum seed pulse is followed by one stage of amplification in Beta Barium Borate (BBO) and two stages of amplification in Potassium Titanyle Arsenate (KTA), resulting in a 225 μJ output pulse with a duration of 90 fs. The output of the system has been measured by self-referenced spectral interferometry to yield the complete spectrum and spectral phase of the pulse. When compared to KTP, the greater transparency of KTA in the spectral range from 3 - 4 μm allows for reduced idler absorption and enhanced gain from the OPA process when it is pumped by the fundamental frequency of a Ti:sapphire laser. In turn, the use of the Ti:sapphire fundamental at 795 nm as a pump improves the efficiency with which light can be converted to wavelengths between 1030 nm and 1080 nm and subsequently used to test components for Nd-based laser systems. This OPA system is operated at 1 kHz for diagnostic development and laser-induced damage threshold testing of optical components for the ELI-Beamlines project.

We present a stable supercontinuum (SC) generated in a bulk YAG crystal, pumped by 3 ps chirped pulses at 1030 nm. The SC is generated in a loose focus geometry in a 13 cm long YAG crystal, allowing for stable and robust single-filament generation. The SC energy stability exceeds that of the pump laser by almost a factor of 3. Additionally, we show that the SC spectrum has long-term stability and that the SC is coherent and compressible by compressing the portions of SC spectra close to the corresponding Fourier limit. This makes the picosecond-pulse-driven SC a suitable stable seed for OPCPA amplifiers.

Palliative transarterial chemoembolization is indicated for patients with stage B hepatocellular carcinoma (HCC) based on the Barcelona Clinic Liver Cancer classification (BCLC). As this is a very wide and heterogenous group of patients, the ART score was designed to better differentiate these patients and to guide the decision for a second transarterial chemoembolization cycle.The goal of the study is to prove that the ART score is appropriate to define subgroups within the stage BCLC-B HCC group with significantly better or worse overall survival (OS) after repeated transarterial chemoembolization. A combined retrospective and prospective study was performed of the OS of patients with stage BCLC-B HCC that were monitored and treated at the Internal Medicine Clinic of the First Faculty of Medicine, Charles University in Prague and the Central Military Hospital Prague. An analysis of the survival curve using the Kaplan-Meier method was performed using the R software package.The median OS of the entire patient group was 18 months (95% CI 12-33). The median OS of patients with a favorable ART score was 33 months (95% CI 12-33) compared to 12 months (95% CI 6-18) for patients with an unfavorable ART score. The difference in OS in the subgroups differentiated by ART score was statistically significant (p0.01). Due to the significant difference in OS of patients differentiated by ART score, the currently recommended guidelines for the treatment of patients with stage BCLC-B hepatocellular carcinoma should be revised.

A Compact Yb:YAG thin-disk regenerative amplifier utilizing a chirped volume Bragg grating (CVBG) as a pump source for anOPCPA amplifier at ELI-Beamlines is demonstrated. As a compact and stable stretcher, a chirped fiber Bragg grating (CFBG) followed by a CVBG is used. After amplification to 24 mJ, pulses are compressed to 2 ps in the CVBG and a short grating compressor; this allows the system to be compact while avoiding the SPM which comes from highly compressed pulses within the CVBG. The compact setup fits into a box 1200x600 mm 2 large, which includes the regenerative amplifier, grating compressor, and second harmonic assembly.

Chromophytes are an important group of microorganisms that contribute significantly to the carbon cycle on Earth. Their photosynthetic capacity depends on efficiency of the light-harvesting system that differs in pigment composition from that of green plants and other groups of algae. Here we employ femtosecond transient absorption spectroscopy to study energy transfer pathways in the main light-harvesting complex of Xanthonema debile, denoted XLH, which contains four carotenoids--diadinoxanthin, heteroxanthin, diatoxanthin, and vaucheriaxanthin--and Chl-a. Overall carotenoid-to-chlorophyll energy transfer efficiency is about 60%, but energy transfer pathways are excitation wavelength dependent. Energy transfer from the carotenoid S(2) state is active after excitation at both 490 nm (maximum of carotenoid absorption) and 510 nm (red edge of carotenoid absorption), but this channel is significantly more efficient after 510 nm excitation. Concerning the energy transfer pathway from the S(1) state, XLH contains two groups of carotenoids: those that have the S(1) route active (~25%) and those having the S(1) pathway silent. For a fraction of carotenoids that transfer energy via the S(1) channel, energy transfer is observed after both excitation wavelengths, though energy transfer times are different, yielding 3.4 ps (490 nm excitation) and 1.5 ps (510 nm excitation). This corresponds to efficiencies of the S(1) channel of ~85% that is rather unusual for a donor-acceptor pair consisting of a noncarbonyl carotenoid and Chl-a. Moreover, major carotenoids in XLH, diadinoxanthin and diatoxanthin, have their S(1) energies in solution lower than the energy of the acceptor state, Q(y) state of Chl-a. Thus, binding of these carotenoids to XLH must tune their S(1) energy to allow for efficient energy transfer. Besides the light-harvesting function, carotenoids in XLH also have photoprotective role; they quench Chl-a triplets via triplet-triplet energy transfer from Chl-a to carotenoid.

ELI-Beamlines will be a high-energy, repetition-rate laser pillar of the ELI (Extreme Light Infrastructure) project. It will be an international facility for both academic and applied research, slated to provide user capability since the beginning of 2016. The main objective of the ELI-Beamlines Project is delivery of ultra-short high-energy pulses for the generation and applications of high-brightness X-ray sources and accelerated particles. The laser system will be delivering pulses with length ranging between 10 and 150 fs and will provide high-energy petawatt and 10-PW peak powers. For high-field physics experiments it will be able to provide focused intensities attaining 1024 Wcm-2, while this value can be upgraded in a later phase without the need to upgrade the building infrastructure. In this paper we describe the overall conception and layout of the designed ELI-Beamlines facility, and review some essential elements of the design.

Chlorosomes, the light-harvesting antennae of green photosynthetic bacteria, are based on large aggregates of bacteriochlorophyll molecules. Aggregates with similar properties to those in chlorosomes can also be prepared in vitro. Several agents were shown to induce aggregation of bacteriochlorophyll c in aqueous environments, including certain lipids, carotenes, and quinones. A key distinguishing feature of bacteriochlorophyll c aggregates, both in vitro and in chlorosomes, is a large (>60 nm) red shift of their Qy absorption band compared with that of the monomers. In this study, we investigate the self-assembly of bacteriochlorophyll c with the xanthophyll astaxanthin, which leads to the formation of a new type of complexes. Our results indicate that, due to its specific structure, astaxanthin molecules competes with bacteriochlorophylls for the bonds involved in the aggregation, thus preventing the formation of any significant red shift compared with pure bacteriochlorophyll c in aqueous buffer. A strong interaction between both the types of pigments in the developed assemblies, is manifested by a rather efficient (~40%) excitation energy transfer from astaxanthin to bacteriochlorophyll c, as revealed by fluorescence excitation spectroscopy. Results of transient absorption spectroscopy show that the energy transfer is very fast (, This study was supported by the Czech Ministry of Education, Youth and Sports (projects MSM0021620835, MSM6007665808, AV0Z50510513), Czech Science Foundation (projects 206/09/0375, 202/09/H041, 202/09/1330), and Spanish Ministry of Science and Innovation (AVCR-CSIC joint project 2008CZ0004).

Effects of introducing a carbonyl group and its position in the conjugated system of carotenoids were studied by means of femtosecond time-resolved spectroscopy. We have compared four naturally occurring carotenoids with comparable structures, beta-carotene, echinenone, canthaxanthin and rhodoxanthin, which differ in the number and position of conjugated carbonyl group(s). The S(1) lifetime is systematically shorter upon increasing the number of the conjugated C=O groups, yielding 9.3 ps (for beta-carotene, no C=O group), 6.2 ps (echinenone, one C=O group), 4.5 ps (canthaxanthin, two C=O groups), and 1.1 ps (rhodoxanthin, two C=O groups in s-trans configuration). Except for slight polarity-induced broadening of absorption and transient absorption spectra, no other polarity effects, such as shortening of the S(1) lifetimes or transient features attributable to intramolecular charge transfer (ICT) state bands, were observed. The absence of these polarity-induced features is explained as due to the long conjugated chain (no lifetime shortening), and the symmetrical position of the carbonyl groups (no ICT bands). On the other hand, all carotenoids exhibit the characteristic spectral band attributed to the S* state, and for the two longest carotenoids, canthaxanthin and rhodoxanthin, decay of the S* state is markedly longer than that of the S(1) state. Moreover, it is shown that the S* state is preferentially populated for a specific subset of ground state conformations, underlining the importance of carotenoid conformation in S* state formation.

Excited-state properties of aryl carotenoids, important components of light harvesting antennae of green sulfur bacteria, have been studied by femtosecond transient absorption spectroscopy. To explore effects of the conjugated aryl group, we have studied a series of aryl carotenoids with conjugated phi-ring, chlorobactene, β-isorenieratene and isorenieratene, and compared them with their non-aryl counterparts γ-carotene and β-carotene, which contain β-ring. Changing β-ring to phi-ring did not reveal any changes in absorption spectra, indicating negligible effect of the phi-ring on the effective conjugation length. This observation is further supported by the carotenoid S1 lifetimes. In n-hexane, the S1 lifetime of chlorobactene having one phi-ring is 6.7 ps, while the S1 lifetime of the β-ring analog, γ-carotene is 5.4 ps. The same effect is observed for the series β-carotene (two β-rings), β-isorenieratene (one β- and one phi-ring) and isorenieratene (two phi-rings) whose S1 lifetimes in n-hexane are 8.2, 10.3 and 12.7 ps, respectively. The systematically longer lifetimes of aryl carotenoids show that the additional conjugated C=C bonds at the -ring do not contribute to the conjugation length. The S1 lifetimes of aryl carotenoids were slightly shortened in benzene, indicating π–π stacking interaction between the phi-ring and benzene., This research was supported by grants from the Czech Ministry of Education (MSM6007665808, MSM0021620835 and AV0Z50510513), and the Grant Agency of the Czech Academy of Sciences (IAA608170604). JBA thanks the Spanish Ministry of Science and Innovation (Ref. BF2007-68107-C02-02/BMC) and the AVCR-CSIC joint program(Ref. 2008CZ0004) for financial support.

A simple and compact scheme for synchronization of the pump and signal pulses for short-pulse OPCPA is demonstrated. Relative timing jitter of 17 fs RMS is achieved (1% of the pump pulse duration) and the system remains locked for hours. The scheme uses a balanced optical cross correlator to detect relative delays between the pump and signal pulses and can be operated with just 10's of μJ of pump energy and pJ-level signal energies.