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PURPOSE: The gender, age, lens culinaris agglutinin-reactive fraction of alphafetoprotein, alphafetoprotein, des-gamma-carboxyprothrombin (GALAD) score is a biomarker-based statistical model for the serologic diagnosis of hepatocellular carcinoma (HCC) that has been developed and validated using the case-control approach with a view to early detection. Performance has, however, been suboptimal in the first prospective studies which better reflect the real-world situation. In this article, we report the application of machine learning to a large, prospectively accrued, HCC surveillance data set. PATIENTS AND METHODS: Models were built on a cohort of 3,473 patients with chronic liver disease within a rigorous surveillance program between 1998 and 2014, during which 459 patients with HCC were detected. Two random forest (RF) models were trained. The first RF model uses the same variables as the original GALAD model (GALAD-RF); the second is based on routinely available clinical and laboratory features (RF-practical). For comparison, we evaluated a logistic regression GALAD model trained on this longitudinal prospective data set (termed GALAD-Ogaki). RESULTS: Models were evaluated using a repetitive cross-validation approach with the metrics averaged over 100 independent runs. As judged by area under the receiver operator curve (AUROC) and F1 score, the GALAD RF model significantly outperformed the original GALAD model. The RF-practical model also outperformed the original GALAD model in terms of both AUROC and F1 score, and both models outperformed the individual biomarkers. An online web application that implemented the GALAD-RF and RF-practical models is presented. CONCLUSION: RF-based models improve on the diagnostic performance of the original GALAD model in the setting of a standard HCC surveillance program. Further prospective validation studies are warranted using these models and could be expanded to offer prediction of risk of HCC development over defined periods of time. Machine learning is used to predict development of hepatocellular carcinoma in those with cirrhosis [ABSTRACT FROM AUTHOR]

To fully exploit ultra-short X-ray pulse durations routinely available at X-ray free-electron lasers to follow out-of-equilibrium dynamics, inherent arrival time fluctuations of the X-ray pulse with an external perturbing laser pulse need to be measured. In this work, two methods of arrival time measurement were compared to measure the arrival time jitter of hard X-ray pulses. The methods were photoelectron streaking by a THz field and a transient refractive index change of a semiconductor. The methods were validated by shot-to-shot correction of a pump-probe transient reflectivity measurement. An ultimate shot-to-shot full width at half-maximum error between the devices of 19.2 ± 0.1 fs was measured. [ABSTRACT FROM AUTHOR]

Why do criminal actors publicly display threatening messages? Studies of organized crime emphasize that criminal actors rely on clandestine networks of influence. Subtle or coded threats are an effective means of extending that influence, but publicizing these threats appears to undermine their chief advantage. We argue that publicized threats broadcast an imagined order, delineating who has a place in society under criminal control, and who does not. To demonstrate this argument, we construct a "grammar of threat" and use this to analyze public threats broadcast by four criminal actors: two groups in Colombia and two in Mexico. The analysis demonstrates that every group projects an order through their threats, but that the order imagined varies by group. Some orders are more clearly ideological; some are more localized or more expansive. These findings highlight the important role of communication—distinct from but often combined with violence—in criminal governance. [ABSTRACT FROM AUTHOR]

Summary: Equine primary hyperparathyroidism is rare compared with the condition in human medicine where it is often encountered and represents the most common explanation for hypercalcemia in the outpatient setting. Primary hyperparathyroidism results from a hyperfunctioning parathyroid gland and surgical treatment (parathyroidectomy) is typically curative. Successful surgical removal of a diseased parathyroid gland can be challenging in horses as both normal and hyperfunctioning glands are difficult to localise. Identification of surgical targets using ultrasonography and/or Technetium‐99 m sestimibi scintigraphy are useful for this purpose in both the human and equine contexts. However, these localisation approaches are not always effective. Moreover, not all patients are candidates for general anaesthesia and surgery and the costs associated with diagnostic localisation and parathyroidectomy may be prohibitive for some owners. This commentary presents information about primary hyperparathyroidism in the event that it is not treated and strives to review aspects of the disease when left untreated from the human medical context. [ABSTRACT FROM AUTHOR]

A 26‐year‐old mule gelding was evaluated for chronic weight loss and decreased appetite. The mule had been losing weight and intermittently hypophagic for approximately 7 months. Laboratory analysis of whole blood and plasma identified severe total hypercalcemia, marked hypophosphatemia, markedly increased parathyroid hormone concentration, and marked lymphocytosis. A sestimibi scan intended to identify parathyroid gland tissue was nondiagnostic. Results of flow cytometry and PCR for antigen receptor rearrangement (PARR) were consistent with a B cell lymphoproliferative disorder, likely chronic lymphocytic leukemia (CLL). Although not previously described concurrently, these conditions may sometimes arise together, complicating definition of the underlying mechanism for weight loss and hypercalcemia in aged equids. [ABSTRACT FROM AUTHOR]

The excited state photodynamics of isolated benzene have been studied in the nanosecond range by two-step photoionization through various vibrations of the lowest singlet state, with imaging photoelectron spectroscopy detection. Photoelectron spectra are measured as a function of pump–probe delay time, and their time evolution is successfully compared to a biexponential decay function without regard to a particular kinetic model. The only reasonable kinetic model with only two exponentials is the one that involves an intersystem crossing from S1 to T1, although that model has previously been called into question by high-resolution studies that failed to find any singlet–triplet perturbations in Zeeman studies of the S1 spectrum. That contradiction remains unresolved. [ABSTRACT FROM AUTHOR]

The 3′ untranslated regions (UTRs) of positive-strand RNA plant viruses commonly contain elements that promote viral replication and translation. The ~700 nt 3′UTR of umbravirus pea enation mosaic virus 2 (PEMV2) contains three 3′ cap-independent translation enhancers (3′CITEs), including one (PTE) found in members of several genera in the family Tombusviridae and another (the 3′TSS) found in numerous umbraviruses and several carmoviruses. In addition, three 3′ terminal replication elements are found in nearly every umbravirus and carmovirus. For this report, we have identified a set of three hairpins and a putative pseudoknot, collectively termed "Trio", that are exclusively found in a subset of umbraviruses and are located just upstream of the 3′TSS. Modification of these elements had no impact on viral translation in wheat germ extracts or in translation of luciferase reporter constructs in vivo. In contrast, Trio hairpins were critical for viral RNA accumulation in Arabidopsis thaliana protoplasts and for replication of a non-autonomously replicating replicon using a trans-replication system in Nicotiana benthamiana leaves. Trio and other 3′ terminal elements involved in viral replication are highly conserved in umbraviruses possessing different classes of upstream 3′CITEs, suggesting conservation of replication mechanisms among umbraviruses despite variation in mechanisms for translation enhancement. [ABSTRACT FROM AUTHOR]

Background and Aims: The aMAP score is a model that predicts risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. Its performance in a 'real world' surveillance setting has not yet been ascertained.Patients and Methods: We had access to a cohort of 3473 individuals enrolled in a rigorously implemented and prospectively accrued surveillance programme (patients undergoing regular ultrasound and biomarker examination between 1998 and 2021). During this period 445 had HCC detected. Of these, 77.8% had early stage disease (within Milan criteria), permitting potentially curative therapy to be implemented in nearly 70% of cases. We applied the recently developed aMAP score to classify patients according to their initial aMAP score in to low, medium and high-risk groups as proposed in the original publication. The performance of the aMAP score was assessed according to the concordance-index and calibration (i.e. agreement between observed and predicted risk). Allowance was made for competing causes of death.Results: The aMAP score achieved an overall C-index of 0.81 (95% CI: 0.79-0.82) consistent with the initial report and was unaffected by allowance for competing causes of death. Sub-group analysis showed that the results did not change significantly according to gender, or aetiology. However, aMAP discrimination was greater for younger individuals (versus older individuals), and also for individuals without cirrhosis. The HCC incidence rate was 0.98, 7.05 and 29.1 events per 1000 person-years in the low-, moderate- and high-risk aMAP groups, respectively.Conclusions: The results from this 'real-world' cohort demonstrate that risk stratification is a realistic prospect and that identification of a subgroup of chronic liver disease patients who have a very low risk of HCC is feasible. [ABSTRACT FROM AUTHOR]

Intrinsic fluorescence analysis is a sensitive technique to gain insight about aptamer-small molecule interactions. Employing fluorescence properties of the ligand, the binding affinities of the aptamer-ligand complex can be quantified in the nM to mM range with great accuracy and precision. Here, we present a detection method for aptamer-ligand binding analysis that is based on the inherent fluorescence of the ligand. Further, we discuss how to optimize and resolve some common experimental challenges. [ABSTRACT FROM AUTHOR]

The article informs that healthy lifestyle and health behavior change has always been a core element of family medicine. It is noted that number of medical schools throughout the nation are leading the way in lifestyle medicine training in medical education. it is noted that challenges and opportunities associated with integration of lifestyle medicine across undergraduate medicine education include lack of awareness of the efficacy of lifestyle medicine.

Purpose The 2020 Safe to Touch Consensus Conference on Hazardous Drug Surface Contamination was convened in order to gather subject matter experts in the field of hazardous drug (HD) handling to develop consensus statements regarding surface contamination monitoring for adoption by stakeholders in the drug supply chain, policy, and healthcare arenas. Summary The Safe to Touch conference convened virtually on September 22, 24, and 26, 2020. An expert panel of healthcare providers with experience in HD handling, monitoring, and research; pharmacy and nursing operations; and medication safety led the conference. An experienced audience of approximately 25 reaction panel members provided feedback to the panel via a preconference survey, during the conference, and at a postconference virtual town hall. Additionally, expert speakers presented on a range of issues, including the impact of HD surface contamination on health, current regulations and standards, surface contamination monitoring technologies, and variables impacting surface contamination testing. Conclusion At the end of the conference, the expert panel developed 11 consensus statements and corresponding recommendations that should be widely disseminated in order to educate individuals regarding the impact of HD surface contamination and increase the scope of HD surface contamination monitoring. Institutions involved in the handling of HDs should set short- and long-term goals for implementation of applicable consensus statements. [ABSTRACT FROM AUTHOR]

Naphthalene, anthracene, and phenanthrene are shown to have very long-lived triplet lifetimes when the isolated molecules are excited with nanosecond pulsed lasers resonant with the lowest singlet state. For naphthalene, triplet state populations are created only during the laser pulse, excluding the possibility of normal intersystem crossing at the one photon level, and all molecules have triplet lifetimes greater than hundreds of microseconds, similar to the behavior previously reported for phenylacetylene. Although containing 7-12 thousand cm-1 of vibrational energy, the triplet molecules have ionization thresholds appropriate to vibrationless T1 states. The laser power dependences (slopes of log-log power plots) of the excited singlet and triplet populations are about 0.7 for naphthalene and about 0.5 for anthracene. Kinetic modeling of the power dependences successfully reproduces the experimental results and suggests that the triplet formation mechanism involves an enhanced spin orbit coupling caused by sigma character in states at the 2-photon level. Symmetry adapted cluster-configuration interaction calculations produced excited state absorption spectra to provide guidance for estimating kinetic rates and the sigma character present in higher electronic states. It is concluded that higher excited state populations are significant when larger molecules are excited with pulsed lasers and need to be taken into account whenever discussing the molecular photodynamics. [ABSTRACT FROM AUTHOR]

Bacteremia resulting from dental surgery is increasingly recognized as a health risk, especially in older and immunocompromised patients. Dentistry-associated bacteremia can lead to remote infections, as exemplified by valvular endocarditis. Emerging evidence points to a novel role played by oral cavity commensals in the pathogenesis of diabetes, respiratory disease, cardiovascular disease, and adverse pregnancy outcomes. Whether dental extraction, a commonly undertaken procedure in old horses, causes bacteremia has not been reported extensively. In a prospective clinical study using next generation sequencing (based on bacterial 16S rRNA), the circulating blood microbiome was characterized before and at 1 h following extraction of incisor, canine or cheek teeth from 29 adult horses with dental disease. 16S rRNA gene sequencing results from the blood microbiome were compared with those from gingival swab samples obtained prior to extraction at the location of the diseased tooth. Bacteremia associated with translocated gingival commensals was demonstrated in horses undergoing exodontia and was, in some cases, still evident one hour post-operatively. [ABSTRACT FROM AUTHOR]

Whilst the benefit of direct‐acting antiviral agents (DAAs) in achieving sustained virological response (SVR) is now well‐accepted, their impact on liver function, particularly in relation to achievement of SVR, has not been well documented. We studied 2394 patients with chronic HCV infection, 1276 receiving DAAs and 1118 interferon‐based therapy. Liver function was assessed by the albumin‐bilirubin (ALBI) score or grade. Overall survival according to SVR status and baseline ALBI grade was examined. We also studied time to first decompensation according to ALBI grade, as well as longitudinal changes in ALBI score over time according to SVR. Among the patients receiving DAAs, 89% achieved SVR (Japan = 99%, UK = 78%). Amongst the decompensated patients in the UK cohort, three distinct risk groups according to ALBI grade at baseline were observed. The UK patients receiving DAAs, who had predominantly decompensated disease, showed clear evidence of improvement of liver function detectable within 2 years of the start of treatment, especially in those achieving SVR. These early changes in liver function were very similar to those observed in the first 2‐3 years after interferon‐based therapy. DAAs improve liver function especially in those with decompensated disease who achieve SVR. Experience with interferon‐based therapy suggests that failure to achieve SVR is associated with long‐term decline in liver function and, in contrast, patients who do achieve SVR can expect long‐term disease improvement and subsequent stabilization of liver function. Our initial analysis suggests that those receiving DAAs are likely, in the long term, to follow a similar course. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-lymphocyte ratio (NLR), a presumed measure of the balance between neutrophil-associated pro-tumour inflammation and lymphocyte-dependent antitumour immune function, has been suggested as a prognostic factor for several cancers, including hepatocellular carcinoma (HCC).Methods: In this study, a prospectively accrued cohort of 781 patients (493 HCC and 288 chronic liver disease (CLD) without HCC) were followed-up for more than 6 years. NLR levels between HCC and CLD patients were compared, and the effect of baseline NLR on overall survival amongst HCC patients was assessed via multivariable Cox regression analysis.Results: On entry into the study ('baseline'), there was no clinically significant difference in the NLR values between CLD and HCC patients. Amongst HCC patients, NLR levels closest to last visit/death were significantly higher compared to baseline. Multivariable Cox regression analysis showed that NLR was an independent prognostic factor, even after adjustment for the HCC stage.Conclusion: NLR is a significant independent factor influencing survival in HCC patients, hence offering an additional dimension in prognostic models. [ABSTRACT FROM AUTHOR]

Objective The goal of this study is to compare the performance of two assay methodologies for the measurement of fructosamine in canine serum and plasma. This study is not intended to validate either reagent, but to highlight differences between these reagents. Background Serum fructosamine is used clinically to examine average glucose level over a one to two week period. Determination of serum fructosamine can eliminate the necessity of multiple serum glucose measurements since it is not affected by short-term fluctuations in blood glucose levels. It is one of the most common alternatives used for assessment of glycemic control in diabetic patients. Methods A Nitroblue tetrazolium (NBT) fructosamine assay and a Fructosaminase™ fructosamine assay were tested for correlation, precision, stability, and interference for the measurement of fructosamine in canine serum and plasma. Results The NBT assay is more precise but low and intermediate fructosamine values were indistinguishable compared to the Fructosaminase ™ assay. High levels of lipid, hemolysis, or icterus may interfere significantly with both methodologies. Conclusions Both assays are useful for measuring serum and plasma fructosamine levels in canine samples but they do not correlate well and cannot be used interchangeably. Storage conditions, matrix used, (serum or plasma), and interference from lipemia, icterus, and hemolysis affect these assays differently. This highlights the need to interpret patient results carefully, particularly when they may come from multiple laboratories or clinics. [ABSTRACT FROM AUTHOR]

Nuclear Magnetic Resonance (NMR) Spectroscopy is a powerful technique for studying aptamer structure and function. Important information about ligand binding and how binding affects aptamer structure can be obtained relatively quickly using ¹H NMR spectra focused on the imino resonances. Here we summarise some practical information for preparing aptamer samples for NMR analysis, designing experiments, and interpreting results, with an emphasis on aptamer-small molecule interactions. [ABSTRACT FROM AUTHOR]

MS offers a flexible and precise alternative to traditional methods for allergen detection and quantitation. However, this flexibility also engenders many ways of acquiring information and translating it to simple, clear data useful to end-users. Currently, methods for performing data analysis for allergen detection by MS are unstandardized, and it is therefore difficult to compare different analytical methods. We identify three key components of data analysis: detection of positive signals, calibration, and signal integration. For each of these components, there are multiple pathways available for method developers. We discuss these alternative methods, giving examples from literature. Assuming that the end result of an allergen analysis should be clear, unambiguous, and understandable to all relevant stakeholders, we pay particular attention to the consequences of each choice to the analysis in question and, where appropriate, suggest best practices. We also identify data analysis criteria that should be clearly delineated in the reporting of a method. Establishment of community-wide standards for unambiguous reporting of data analysis workflows will improve the evaluation, comparability, and transferability of methods. [ABSTRACT FROM AUTHOR]

A method is described for the use of electronic structure and Franck-Condon factor programs in the calculation of the vibrational intensities in forbidden electronic transitions. Using the B 2B2-X 2B1 electronic transition of benzonitrile cation as a test case, transition moments were calculated using the symmetry adapted cluster/configuration interaction method at various points along the normal mode displacements of the molecule, from which transition moment derivatives were obtained. The transition moments were found to vary almost linearly with respect to the normal mode displacements. Using these, along with Franck-Condon factors, an expansion of the transition moment with respect to the normal coordinates provides a measure of vibrational intensities, including the effects of geometry change and Duschinsky rotation [Acta Physicochim. URSS 7, 551 (1937)]. Second order terms in the moment expansion are calculated, and it is determined that they must be included if the intensity of combination bands is to be properly obtained. [ABSTRACT FROM AUTHOR]

Photoinduced Rydberg ionization (PIRI) spectra of the second excited electronic state of benzonitrile cation were recorded via the origin and 6a1 and 6b1 vibrational levels of the cation ground electronic state. This B←X transition was verified to be a forbidden 2B2←2B1 transition with an origin at 17 225 cm-1 above the ground ionic state. By the use of vibronic coupling calculations, as well as symmetry analysis and comparison of the PIRI spectra via different ground vibrational levels, a nearly complete assignment of the vibrational structure was made, and the vibrational frequencies of the B 2B2 state of benzonitrile cation were obtained based on the assignments. Comparisons of the experimental spectra with simulations from the vibronic structure calculations are also used to validate the theoretical procedures used in the simulations. [ABSTRACT FROM AUTHOR]

Jahn-Teller (JT) coupling parameters can be simply derived from features of the potential energy surfaces of the JT active vibrational modes of a molecule subject to that effect. Potential energy curves representing cuts of D[SUB2h] symmetry have been calculated using density functional theory for each of the four active e[SUB2g] modes of benzene cation in each of the lowest three degenerate electronic states. From these curves and the vibrational frequencies, the JT coupling parameters can be found (vibrational numbering follows Wilson's notation, coupling parameters are in Moffit's notation). For the C[SUB6]H[SUP+,SUB6]+&Xtilde;[SUP2]E[SUB1g] state the largest JT coupling parameter is provided by mode 6 (D = 0.48), followed closely by mode 8 (0.30) and then mode 9 (0.10). Mode 7 provides almost no stabilization. For the [SUP2]E[SUB2g] state, calculated coupling parameters are very large, particularly for modes 8 (1.36) and 6 (0.93). Modes 7 (0.10) and 9 (0.07) are smaller but finite. For the &Dtilde;[SUP2]E[SUBlu] state, mode 6 has an impressive linear coupling parameter of 4.12, able to support several vibrations below the JT cusp. Indications of a substantial quadratic stabilization for that mode result in the possibility of a completely static distortion in that state. Similar, but not identical, results are obtained for C[SUB6]D[SUP+,SUB6] . [ABSTRACT FROM AUTHOR]

The vibrational structure seen in photoinduced Rydberg ionization spectra of the &Btilde;[SUP2]E[SUB2g] state of benzene cation (C[SUB6]H[SUP+,SUB6] and C[SUB6]D[SUP+,SUB6]) has been analyzed by fitting the vibrational patterns to energy levels derived from multimode Jahn-Teller calculations. Most of the structure can be ascribed to various combinations of modes 6 and 16, with minor contributions from 4, 17, and 18 (using Wilson's numbering convention). In qualitative agreement with parameters derived from electronic structure calculations, the linear coupling parameter for mode 6 is very large (D = 1.39 in C[SUB6]H[SUP+,SUB6] and 1.28 in + C[SUB6]D[SUB6] ). This raises questions about certain angular momentum selection rules in the classical Jahn-Teller model. [ABSTRACT FROM AUTHOR]

Describes the interaction between molecules of ethyl radical with small torsional barrier. Range of action between internal rotation and other normal modes of the molecule; Use of electronic structure calculations to estimate both the electronic and vibrational contributions to the barrier.

Reports the infrared spectrum measurements of ethyl radical carbon hydrogen[sub 2] out-of-plane rocking vibrational fundamental by transient diode laser absorption spectroscopy. Data providing information on the structure of and the barrier of internal rotation; Examination of how quantities change on vibrational excitation.

Food-derived bioactive peptides have gained attention for their role in preventing chronic diseases. Edible insects are viable sources of bioactive peptides owing to their high protein content and sustainable production. In this study, whole crickets ( Gryllodes sigillatus) were alcalase-hydrolyzed to a degree of hydrolysis (DH) ranging from 15 to 85%. Antioxidant activity, angiotensin converting enzyme (ACE), and dipeptidyl peptidase-4 (DPP-IV)- inhibition of the cricket protein hydrolysates (CPH) were evaluated before and after simulated gastrointestinal digestion (SGD). Antioxidant activity was similar among CPH, whereas ACE and DPP-IV inhibition was greater (p < 0.05) in CPH with 60–85% DH. Bioactivity improved after SGD. CPH allergenicity was evaluated using human shrimp-allergic sera. All sera positively reacted to tropomyosin in the unhydrolyzed cricket and CPH with 15–50% DH, whereas 60–85% DH showed no reactivity. In conclusion, CPH (60–85% DH) had the greatest bioactive potential and lowest reactivity to tropomyosin, compared with other CPH and the unhydrolyzed control. [ABSTRACT FROM AUTHOR]

The observation and analysis of the high resolution spectrum of the CH2 rocking fundamental of the ethyl radical, C2H5, at wavelengths close to 18.9 μm is reported. The band origin is found to be at 528.1 cm-1. The spectrum shows evidence for a very low barrier to internal rotation, or torsion, in this species. A simple model Hamiltonian, based on an assumed structure with G12 symmetry, qualitatively reproduces the observations and implies a torsional barrier of approximately 20 cm-1 in both the zero point and excited vibrational states. The Hamiltonian cannot reproduce the observations to the level of the experimental accuracy and the importance of several neglected terms is tested and discussed. The observed torsional splittings imply that, within the confines of the model, the a-inertial and internal rotation axes in the molecule are coincident to within 1°. In addition to their intrinsic interest, the spectra will be useful for future state resolved studies of the kinetics of chemical reactions involving the radical. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The pump–probe threshold ionization photoelectron spectra of pyrazine have been recorded using nine different vibrations of S1 as intermediate resonances. The extensive vibrational structure in these spectra of the ionic ground state have enabled the measurement of 12 of its vibrational frequencies and their assignments. Three new vibrational assignments of S1 are also made. MP2/6-31G* calculations of the vibrational frequencies of the neutral ground, S1, and the ionic ground state are compared with the experimental values, finding that certain vibrations of S1 and the ion which engage in extensive vibronic coupling are not properly determined by the calculated force field. Most vibrational frequencies are accurately reproduced, however. Variations in the complexity of the threshold ionization spectra with the level of S1 excitation indicate that internal vibrational relaxation is taking place at a very low energy in that state, possibly involving vibronic interactions and mixing with the triplet manifold. [ABSTRACT FROM AUTHOR]

Photofragmentation of the chlorofluorocarbons, CF3Cl, CF2Cl2, and CFCl3, was investigated at 187, 125, and 118 nm using VUV harmonic generation techniques and (2+1) resonantly enhanced multiphoton ionization detection of ground Cl(2P3/20) and excited Cl*(2P1/20) state fragment atoms. Product translational energy and angular distributions were derived from Cl+ arrival time distributions obtained by time-of-flight mass spectrometry. Photolysis of CF3Cl at 125 and 118 nm takes place via the 4s(a1) and 4p(e) Rydberg states, respectively, and two primary fragmentation channels are observed. A ‘‘slow’’ channel with a most probable center-of-mass (c.m.) translational energy near zero is assigned to the production CF*3 radicals in the 2A’1, 2A‘2, and 1E’ electronically excited states. The second Cl/Cl* fragmentation channel has a c.m. translational energy distribution peaked at Etr≥1 eV and is tentatively assigned to a sequential dissociation process in which rapid C–Cl single bond rupture is followed by a secondary fragmentation of CF*3 to CF2+F. The time-of-flight (TOF) spectra for CF2Cl2 and CFCl3 following excitation at 125 and 118 nm suggest that concerted three-body fragmentation involving the loss of two Cl/Cl* atoms is the dominant dissociation process. By contrast, photolysis of CF2Cl2 and CFCl3 at 187 nm results in structured Cl+ arrival time distributions which are used to derive translational energy distributions and asymmetry parameters. Simulations of the TOF spectra suggest the presence of three Cl/Cl* fragment channels, with the highest energy channel clearly attributable to single C–Cl bond rupture leading to internally excited molecular fragments. The contribution of sequential and simultaneous two-Cl loss processes to the low translational energy channels is also discussed. [ABSTRACT FROM AUTHOR]

In (3+1) resonance enhanced multiphoton ionization photoelectron spectra (REMPI-PES) of CO2, photoionization competes with dissociation. In addition to direct photoionization, autoionization is possible through accidental resonances embedded in the continuum at the four-photon level. Photoabsorption from these long-lived autoionizing states leads to resonance enhanced above threshold absorption (REATA). REATA produces photoelectron terminations on the C state of CO2+. Previous experiments did not indicate whether the dissociation occurred at the three-photon level or four-photon level. REMPI-PES of CO2 via several Rydberg states have been collected at a number of laser intensities, and it was found that the photoelectron spectra terminating on each individual ionic state do not change over the range of experimentally available laser intensities. This indicates that the dissociation of CO2 occurs at the four-photon level. The long vibrational progressions in the PES indicate that the dominant ionization process is autoionization rather than direct ionization. Relative intensities of the X and C state components of the PES do change with intensity, confirming the C state assignment and its five-photon mechanism. [ABSTRACT FROM AUTHOR]

The structure of the multiphoton ionization spectra of carbon dioxide in the vicinity of 4f and 5f resonances is analyzed in detail. The rotational contour of the f complex is calculated using the frame transform method of Chang and Fano. It is found that only one electronic splitting constant k4f=7 cm-1 is needed to attain a reasonable approximation to the experimental spectrum. This would indicate that the Rydberg electron is relatively atomic-like and excluded from the core. It is also found that the dominant contribution to the three-photon excitation strength comes from the ΔΩ=3 path. The additional sharp structure to the blue of the 4f and 5f resonances is due to four-photon resonances with autoionization states belonging to Rydberg series converging on the A and B states of the ion. The unusual strength of these lines arises from a coincidence between the photon energy and the energy of B←X core transitions and the predissociation of the nearby bound resonances, which limits their strength. [ABSTRACT FROM AUTHOR]

The MPI spectra of CO2 were recorded in the range 275 to 338 nm in both a conventional MPI cell and a molecular beam apparatus. The polarization ratio of each MPI peak was measured in order to assign the symmetry of excited states. The 3pσu 1Πu and 3pσu 1Πu110 Rydberg states were observed, while the 3pπu 1Σ+u Rydberg state was missing, and a new Rydberg state, 3pπu 1Δu was observed at 333.03 and 333.70 nm. In the nf (n=4,5) Rydberg series, evidence was found of interaction with other nearby Rydberg states. A mass selected pure CO+2 ion signal was measured for the 3pπu 1Δu state, but both CO+ and CO+2 ion signals were detected for the other Rydberg states. Predissociation and fragmentation in MPI processes are discussed. Lower limit lifetimes for the observed Rydberg states of CO2 are given. [ABSTRACT FROM AUTHOR]

Two new (2+1) multiphoton ionization spectra of gerade Rydberg states of molecular iodine are observed in the 310.0–322.5 and the 285.5–295.5 nm ranges. These spectra were obtained in both a conventional MPI cell and in a TOF molecular beam apparatus. A long progression in the 310.0–322.5 nm range is suggested to be 2g(2Π3/2g)ndσg, having a band origin at 62 440 cm-1. Three progressions in the 285.5–295.5 nm range are suggested to be 2g, 1g, 0g(2Π3/2g)(n+1)dσg, having band origins at 68 335, 68 407, and 68 434 cm-1, respectively. The photodissociation behavior of molecular iodine in a MPI process is discussed. [ABSTRACT FROM AUTHOR]

Quantum yields and rates of intersystem crossing and internal conversion are obtained for the lowest excited singlet state of collisionless phenol. It is found that internal conversion is the dominant decay channel, even at the origin of S1, in contrast to previously studied molecules. Also, triplet lifetimes measured as a function of vibrational energy are an order of magnitude shorter than in other isoelectronic aromatics. Hydrogen bonding by water and in a dimer is found to lengthen the singlet lifetime and decrease the quantum yield of internal conversion. This behavior parallels the effects, in solution, of going from a nonpolar to a polar solvent, indicating that substantial solvation effects are caused by a single hydrogen bond. [ABSTRACT FROM AUTHOR]

While recent advances in culture-independent sequencing approaches have revitalized the field of microbiology, rapid collection and preservation of microbial DNA in samples like feces is critical to avoid degradation of target DNA via nuclease activity and proliferation of aerotolerant microbes. Common laboratory practices to ameliorate such changes rely on prompt freezing of samples or dispersion in nuclease-inhibiting reagents. As many of the microbial enzymes associated with nuclease activity and bacterial proliferation are hydrolases, prompt desiccation of samples offers an attractive alternative to freezing and liquid reagents for field collection of samples in remote areas. Herein, we evaluated the utility of a portable desiccant chamber with a rechargeable cartridge, for preservation of equine fecal samples for downstream microbial profiling via 16S rRNA amplicon sequencing. Controls included matched samples promptly frozen at −80 °C or left at room temperature for an equivalent period of time. While samples held at room temperature showed a significant reduction in richness and proliferation of several facultative anaerobes, desiccated samples showed minimal change from promptly frozen samples, with the exception of increased abundance of Acinetobacter spp. in desiccated samples relative to frozen samples. The data support the utility of portable desiccant chambers for the preservation of microbial field samples intended for downstream sequencing approaches. [ABSTRACT FROM AUTHOR]

The detection and quantitation of allergens as contaminants in foods using MS is challenging largely due to the requirement to detect proteins in complex, mixed, and often processed matrixes. Such methods necessarily rely on the use of proteotypic peptides as indicators of the presence and amount of allergenic foods. These peptides should represent the allergenic food in question in such a way that their use is both sensitive (no false-negatives) and specific (no false-positives). Choosing such peptides to represent food allergens is beset with issues, including, but not limited to, separated ingredients (e.g., casein and whey), extraction difficulties (particularly from thermally processed foods), and incomplete sequence information, as well as the more common issues associated with protein quantitation in biological samples. Here, we review the workflows that have been used to select peptide targets for food allergen detection. We describe the use and limitations of both in silico-based analyses and experimental methods relying on high-resolution MS. The variation in the way in which target selection is performed highlights a lack of standardization, even around the principles describing what the detection method should achieve. A lack of focus on the food matrixes to which the method will be applied is also apparent during the peptide target selection process. It is hoped that highlighting some of these issues will assist in the generation of MS-based allergen detection methods that will encourage uptake and use by the analytical community at large. [ABSTRACT FROM AUTHOR]

Isothermal titration calorimetry (ITC) is a powerful technique for studying binding interactions. From a single ITC experiment it is possible to quantify the affinity and thermodynamics of a binding event. Here, we outline an experimental approach for performing ITC experiments with a focus on aptamer-small molecule interactions. We also discuss some common problems that can be encountered and how to resolve these issues. [ABSTRACT FROM AUTHOR]

We explore the capability of the non-natural amino acid azidohomoalanine (AHA) as an IR label to sense relatively small structural changes in proteins with the help of 2D IR difference spectroscopy. To that end, we AHA-labeled an allosteric protein (the PDZ2 domain from human tyrosine-phosphatase 1E) and furthermore covalently linked it to an azobenzene-derived photoswitch as to mimic its conformational transition upon ligand binding. To determine the strengths and limitations of the AHA label, in total six mutants have been investigated with the label at sites with varying properties. Only one mutant revealed a measurable 2D IR difference signal. In contrast to the commonly observed frequency shifts that report on the degree of solvation, in this case we observe an intensity change. To understand this spectral response, we performed classical MD simulations, evaluating local contacts of the AHA labels to water molecules and protein side chains and calculating the vibrational frequency on the basis of an electrostatic model. Although these simulations revealed in part significant and complex changes of the number of intraprotein and water contacts upon trans-cis photoisomerization, they could not provide a clear explanation of why this one label would stick out. Subsequent quantum-chemistry calculations suggest that the response is the result of an electronic interaction involving charge transfer of the azido group with sulfonate groups from the photoswitch. To the best of our knowledge, such an effect has not been described before. [ABSTRACT FROM AUTHOR]

We tested a cross-race friendship picture book intervention under two conditions that aimed to facilitate the reduction of racial prejudice that children of two age groups ascribe to adults reading the book (communicators) and their own prejudice. White majority children, 113 kindergarteners (M = 5.97 years) and 103 second graders (M = 7.93 years) were randomly assigned to an ingroup (White) or outgroup (Black) communicator and skill training. They were pretested on racial attitudes they ascribed to their photographed communicator and then trained in reconciliation or classification. They heard four cross-race friend stories; then were retested on communicator attitudes, own attitudes and cognitive elaboration. Results indicated only second graders, and those able to reconcile differences in perspectives, predicted on the basis of their photo alone that outgroup communicators would hold positive attitudes toward Blacks. After communicators read the stories and explicitly stated their antibias attitude, reports changed among second graders who now rated both communicators as holding more positive Black attitudes. Second graders also held more positive Black attitudes themselves. Kindergarteners consistently assumed both ingroup and outgroup communicators were pro-White. Children elaborated more about the Black story characters when read to by an outgroup (Black) communicator. In conclusion, cross-race friend storybooks are a promising way to expose children to other racial groups and to antibias attitudes, under certain conditions. [ABSTRACT FROM AUTHOR]

Ultrafast photochemical reactions are initiated by vibronic transitions from the reactant ground state to the excited potential energy surface, directly populating excited-state vibrational modes. The primary photochemical reaction of vision, the isomerization of retinal in the protein rhodopsin, is known to be a vibrationally coherent reaction, but the Franck–Condon factors responsible for initiating the process have been difficult to resolve with conventional time-resolved spectroscopies. Here we employ experimental and theoretical 2D photon echo spectroscopy to directly resolve for the first time the Franck–Condon factors that initiate isomerization on the excited potential energy surface and track the reaction dynamics. The spectral dynamics reveal vibrationally coherent isomerization occurring on the fastest possible time scale, that of a single period of the local torsional reaction coordinate. We successfully model this process as coherent wavepacket motion through a conical intersection on a ∼30 fs time scale, confirming the reaction coordinate as a local torsional coordinate with a frequency of ∼570 cm–1. As a result of spectral features being spread out along two frequency coordinates, we unambiguously assign reactant and product states following passage through the conical intersection, which reveal the key vibronic transitions that initiate the vibrationally coherent photochemistry of vision. [ABSTRACT FROM AUTHOR]

To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5= cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the Turnip crinkle virus (TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both in vitro and in vivo. An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2=-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing. Analysis of the IRES region in vitro by use of both the TCV gRNA and reporter constructs did not reveal any sequence-specific elements but rather suggested that an overall lack of structure was an important feature for IRES activity. The CP IRES is A-rich, independent of orientation, and strongly conserved among viruses in the same genus. The IRES was dependent on eIF4G, but not eIF4E, for activity. Low levels of CP accumulated in vivo in the absence of detectable TCV subgenomic RNAs, strongly suggesting that the IRES was active in the gRNA in vivo. Since the TCV CP also serves as the viral silencing suppressor, early translation of the CP from the viral gRNA is likely important for countering host defenses. Cellular mRNA IRES also lack extensive RNA structures or sequence conservation, suggesting that this viral IRES and cellular IRES may have similar strategies for internal translation initiation. [ABSTRACT FROM AUTHOR]

Background: Variation in survival in hepatocellular carcinoma (HCC) has been attributed to different aetiologies or disease stages at presentation. While international guidelines recommend surveillance of high-risk groups to permit early diagnosis and curative treatment, the evidence that surveillance decreases disease-specific mortality is weak.Methods: We compared HCC survival figures from Japan (n=1174) and Hong Kong (n=1675) over similar time periods (Japan 2000-2013, Hong Kong, China 2003-2014). The former has an intensive national surveillance programme, while the latter has none. We also analysed changes in survival in Japan over a 50-year period including data from before and after institution of a national HCC surveillance programme.Results: In Japan, over 75% of cases are currently detected by surveillance, whereas in Hong Kong <20% of cases are detected presymptomatically. Median survival was 52 months in Japan and 17.8 months in Hong Kong; this survival advantage persisted after allowance for lead-time bias. Sixty-two per cent of Japanese patients had early disease at diagnosis and 63% received curative treatment. The comparable figures for Hong Kong were 31.7% and 44.1%, respectively. These differences could not be accounted for by disease aetiology, and patients in Hong Kong who were detected at an early stage had a similar survival to the analogous patients in Japan.Conclusions: The variation in survival is largely accounted for by stage at diagnosis, which in turn relates to the intensity of surveillance programmes and the consequent variation in curative therapeutic options. [ABSTRACT FROM AUTHOR]

Horses are exquisitely sensitive to non-specific gastrointestinal disturbances as well as systemic and extraintestinal conditions related to gut health, yet minimal data are available regarding the composition of the microbiota present in the equine stomach, small intestine, and cecum and their relation to fecal microbiota. Moreover, there is minimal information regarding the concordance of the luminal and mucosal microbial communities throughout the equine gut. Illumina-based 16S rRNA gene amplicon sequencing of the luminal and mucosal microbiota present in seven regions of the gastrointestinal tract of nine healthy adult horses revealed a distinct compositional divide between the small and large intestines. This disparity in composition was more pronounced within the luminal contents, but was also detected within mucosal populations. Moreover, the uniformity of the gut microbiota was much higher in the cecum and colon relative to that in the stomach, jejunum and ileum, despite a significantly higher number of unique sequences detected in the colon. Collectively, the current data suggest that while colonic samples (a proxy for feces) may provide a reasonable profile of the luminal contents of the healthy equine large intestine, they are not informative with regard to the contents of the stomach or small intestine. In contrast to the distinct difference between the highly variable upper gastrointestinal tract microbiota and relatively uniform large bowel microbiota present within the lumen, these data also demonstrate a regional continuity present in mucosal microbial communities throughout the length of the equine gut. [ABSTRACT FROM AUTHOR]

The developement of a new mass selective method is reported for the determination of the optical spectra of molecular ions and for the production of state selected ions.(AIP) [ABSTRACT FROM AUTHOR]