Quantum chemical methods have been intensively applied to study the pyrolytic conversion of glucose into hydroxymethylfurfural (HMF) and furfural (FF). Herein, we collect the most relevant mechanistic proposals from the recent literature and organize them into a single reaction network. All the transition structures (TSs) and intermediates are characterized using highly accurate ab initio methods and the possible reaction pathways are assessed in terms of the Gibbs energies of the TSs and intermediates with respect to β-glucopyranose, selecting a 2D ideal-gas standard state at 773 K to represent the pyrolysis conditions. Several pathways can lead to the formation of both HMF and FF passing through rate-determining TSs that have ΔG‡ values of ~49-50 kcal/mol. Both water-assisted mechanisms and nonspecific environmental effects have a minor impact on the Gibbs energy profiles. We find that the HMF → FF + CH2O fragmentation has a small ΔrxnG value and an accessible ΔG‡ barrier. Our computational results, which are in consonance with the kinetic parameters derived from lumped models, the results of isotopic labeling experiments and the reported HMF/FF molecular ratios, could be useful for modeling studies including on nonequilibrium kinetic effects that may render more information about product yields and the relevance of the various pathways.

Angiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (FF) during folliculogenesis is clinically significant and important for in vitro fertilization. This study aims to identify the key angiogenic factors in FF for predicting oocyte maturity during in vitro fertilization.
Forty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, > 18 mm; one mid-antral follicle, < 14 mm) were collected without flushing during oocyte retrieval. In total, 80 FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in FF were analyzed via Luminex high-performance assays. Recorded patient data included antral follicle count, anti-müllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH/LH/E2/P4, trigger day E2/LH/P4, and retrieval day E2/LH/P4 were measured by chemiluminescence assay.
Ten angiogenic factors were highly expressed in FF: eotaxin, Gro-α, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-α and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p < 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.
Our findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro fertilization.

In this study, we have designed and explored a new series of non-fullerene acceptors for possible applications in organic solar cells. We have designed four molecules named as APH1 to APH4 after end-capped modification of recently synthesized Y6-Se-4Cl molecule. Density functional theory and time dependent-density functional theory have been employed for computing geometric and photovoltaic parameters of the designed molecules. Designed molecules have displayed high values of fill factor and FF%. Further, high mobility of electrons and holes between metal electrodes are also noted for designed molecules. Good values of open circuit voltage enhance the power conversion efficiency in the APH1-APH4. Frontier molecular orbitals analysis and excitation energy values suggested easy transportation of charges between molecular orbitals. Moreover, red-shifting in the absorption spectrum with high oscillating strength is also noted in APH1 to APH4 as compared to reference molecules. Results of different opto-electronic and photovoltaic parameters recommended that APH1 to APH4 are effective contributors for the development of high performance organic solar cells.

All-small-molecule acceptors (ASMAs) are considered as well-defined molecular structures with good sustainability and processability. Although these acceptor molecules did not exhibit high power conversion efficiency (PCE) as compared to polymer solar cells, a lot of research is yet to be focused on the development of ASMAs. In this report, a new series of ASMAs (ZMY1 to ZMY5) has been designed by end-capped alteration of recently synthesized ZR-Si4 molecule (PCE = 10.10%). Photovoltaic, optoelectronic and geometric parameters of the newly designed molecules have been investigated through DFT and TD-DFT approaches. Additionally, power conversion efficiency along with fill factor (FF) percentage has been computed for the designed molecules. Enhanced open circuit voltage (Voc) allows PCE at around 18.25 % which is better than the experimentally synthesized ZR-Si4 molecule. Additionally, the high mobility of electrons and hole between metal electrodes also suggested that the designed molecules are effective candidates for the development of efficient organic solar cell (OSC) applications.

The application of proteomics to fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) human tissues is an important development spurred on by requests from stakeholder groups in clinical fields. One objective is to complement current diagnostic methods with new specific molecular information. An important goal is to achieve adequate and consistent protein recovery across and within large-scale studies. Here, we describe development of several protocols incorporating mass spectrometry compatible detergents, including Rapigest, PPS, and ProteaseMax. Methods were applied on 4 and 15 μm thick FF tissues, and 4 μm thick FFPE tissues. We evaluated sensitivity and repeatability of the methods and found that the protocol containing Rapigest enabled detection of 630 proteins from FF tissue of 1 mm2 and 15 μm thick, whereas 498 and 297 proteins were detected with the protocols containing ProteaseMax and PPS, respectively. Surprisingly, PPS-containing buffer showed good extraction of the proteins from 4 μm thick FFPE tissue with the average of 270 protein identifications (1 mm2), similar to the results on 4 μm thick FF. Moreover, we found that temperature increases during incubation with urea on 4 μm thick FF tissue revealed a decrease in the number of identified proteins and increase in the number of the carbamylated peptides.

OBJECTIVE: This study investigated the use of high spatial resolution solid-state detectors (DUO and Octa) combined with an inclinometer for machine-based quality assurance (QA) of Volumetric Modulated Arc Therapy (VMAT) with flattened and flattening filter-free beams.
METHODS: The proposed system was inserted in the accessory tray of the gantry head of a Varian 21iX Clinac and a Truebeam linear accelerator. Mutual dependence of the dose rate (DR) and gantry speed (GS) was assessed using the standard Varian customer acceptance plan (CAP). The multi-leaf collimator (MLC) leaf speed was evaluated under static gantry conditions in directions parallel and orthogonal to gravity as well as under dynamic gantry conditions. Measurements were compared to machine log files.
RESULTS: DR and GS as a function of gantry angle were reconstructed using the DUO/inclinometer and in agreement to within 1% with the machine log files in the sectors of constant DR and GS. The MLC leaf speeds agreed with the nominal speeds and those extracted from the machine log files to within 0.03 cm s-1 . The effect of gravity on the leaf motion was only observed when the leaves traveled faster than the nominal maximum velocity stated by the vendor. Under dynamic gantry conditions, MLC leaf speeds ranging between 0.33 and 1.42 cm s-1 were evaluated. Comparing the average MLC leaf speeds with the machine log files found differences between 0.9% and 5.7%, with the largest discrepancy occurring under conditions of fastest leaf velocity, lowest DR and lowest detector signal.
CONCLUSIONS: The investigation on the use of solid-state detectors in combination with an inclinometer has demonstrated the capability to provide efficient and independent verification of DR, GS, and MLC leaf speed during dynamic VMAT delivery. Good agreement with machine log files suggests the detector/inclinometer system is a useful tool for machine-specific VMAT QA.

The self-assembly of short aromatic peptides and peptide derivatives into a variety of different nano- and microstructures (fibrillar gels, crystals, spheres, plates) is a promising route toward the creation of bio-compatible materials with often unexpected and useful properties. Furthermore, such simple self-assembling systems have been proposed as model systems for the self-assembly of longer peptides, a process that can be linked to biological function and malfunction. Much effort has been made in the last 15 years to explore the space of peptide sequences, chemical modifications and solvent conditions in order to maximise the diversity of assembly morphologies and properties. However, quantitative studies of the corresponding mechanisms of, and driving forces for, peptide self-assembly have remained relatively scarce until recently. In this chapter we review the current state of understanding of the thermodynamic driving forces and self-assembly mechanisms of short aromatic peptides into supramolecular structures. We will focus on experimental studies of the assembly process and our perspective will be centered around diphenylalanine (FF), a key motif of the amyloid β sequence and a paradigmatic self-assembly building block. Our main focus is the basic physical chemistry and key structural aspects of such systems, and we will also compare the mechanism of dipeptide aggregation with that of longer peptide sequences into amyloid fibrils, with discussion on how these mechanisms may be revealed through detailed analysis of growth kinetics, thermodynamics and other fundamental properties of the aggregation process.

Tissues and biofluids are important sources of information used for the detection of diseases and decisions on patient therapies. There are several accepted methods for preservation of tissues, among which the most popular are fresh-frozen and formalin-fixed paraffin embedded methods. Depending on the preservation method and the amount of sample available, various specific protocols are available for tissue processing for subsequent proteomic analysis. Protocols are tailored to answer various biological questions, and as such vary in lysis and digestion conditions, as well as duration. The existence of diverse tissue-sample protocols has led to confusion in how to choose the best protocol for a given tissue and made it difficult to compare results across sample types. Here, we summarize procedures used for tissue processing for subsequent bottom-up proteomic analysis. Furthermore, we compare protocols for their variations in the composition of lysis buffers, digestion procedures, and purification steps. For example, reports have shown that lysis buffer composition plays an important role in the profile of extracted proteins: the most common are tris(hydroxymethyl)aminomethane, radioimmunoprecipitation assay, and ammonium bicarbonate buffers. Although, trypsin is the most commonly used enzyme for proteolysis, in some protocols it is supplemented with Lys-C and/or chymotrypsin, which will often lead to an increase in proteome coverage. Data show that the selection of the lysis procedure might need to be tissue-specific to produce distinct protocols for individual tissue types. Finally, selection of the procedures is also influenced by the amount of sample available, which range from biopsies or the size of a few dozen of mm2 obtained with laser capture microdissection to much larger amounts that weight several milligrams.

While zebrafish embryos in the first five days after fertilization are clear and amenable to optical analysis, older juveniles and adults are not, due to pigmentation development and tissue growth. Thus other imaging methods are needed to image adult specimens. NMR is a versatile tool for studies of biological systems and has been successfully used for in vivo zebrafish microscopy. In this work we use NMR microscopy (MRM) for assessment of zebrafish specimens, which includes imaging of formalin fixed (FF), formalin fixed and paraffin embedded (FFPE), fresh (unfixed), and FF gadolinium doped specimens. To delineate the size and shape of various organs we concentrated on 3D MRM. We have shown that at 7 T a 3D NMR image can be obtained with isotropic resolution of 50 μm/pxl within 10 min and 25 μm/pxl within 4 h. Also, we have analyzed sources of contrast and have found that in FF specimens the best contrast is obtained by T1 weighting (3D FLASH, 3D FISP), whereas in FFPE specimens T2 weighting (3D RARE) is the best. We highlight an approach to perform segmentation of the organs in order to study morphological changes associated with mutations. The broader implication of this work is development of NMR methodology for high contrast and high resolution serial imaging and automated analysis of morphology of various zebrafish mutants.

Background: Recently we have upgraded our Varian Clinac 2100CD with a 6MV FFF beam, this upgrade being the first of its kind in our country. Even though the dosimetric characteristics of FFF beams have been reported both in experimental and Monte Carlo studies, application in planning and delivery is complex. The aim of this study was to validate the commissioning of upgraded FFF beams dosimetrically using AAPM TG-119 bench mark plans for VMAT and to make a comparison with IMRT plans for both flattened filtered and FFF beams. Materials and Methods: AAPM TG-119 proposes a set of test clinical cases for testing the accuracy of IMRT planning and delivery systems. For these clinical cases we generated four treatment plans using IMRT FF, IMRT FFF, VMAT FF and VMAT FFF on a Varian Clinac 2100CD machine equipped with a millennium 120 MLC in Eclipse treatment planning system. Dose prescription and planning objectives were set according to the TG-119 goals and plans were scored based on planning objectives. Plans were compared using dose coverage, the conformity index and the homogeneity index. Point doses were measured at points recommended by TG-119 using a CC13 ion chamber. Planar dosimetry was accomplished using Imatrix and gamma evaluation was conducted using Omnipro IMRT software. Results: Dose distributions of FFF beam based plans were comparable to FF plans for both IMRT and VMAT. Our planning results matched TG-119 planning results. Measured point doses were within ±2% of planned doses and planar dosimetry gamma values were <1 for >95% of data points for all plans. Conclusion: We found a reduction of 40% treatment time for FFF against FF beams for sliding window IMRT. Upgraded FFF beams were in good agreement with TG-119 benchmark plans and goals.