Role of Thermal Equilibrium Dynamics in Atomic Motion during Nonthermal Laser-Induced Melting.

This study shows that initial atomic velocities as given by thermodynamics play an important role in the dynamics of phase transitions. We tracked the atomic motion during nonthermal laser-induced melting of InSb at different initial temperatures. The ultrafast atomic motion following bond breaking can in general be governed by two mechanisms: the random velocity of each atom at the time of bond breaking (inertial model), and the forces acting on the atoms after bond breaking. The melting dynamics was found to follow the inertial model over a wide temperature range.

Attosecond pulse walk-off in high-order harmonic generation.

We study the influence of the generation conditions on the group delay of attosecond pulses in high-order harmonic generation in gases. The group delay relative to the fundamental field is found to decrease with increasing gas pressure in the generation cell, reflecting a temporal walk-off due to the dispersive properties of the nonlinear medium. This effect is well reproduced using an on-axis phase-matching model of high-order harmonic generation in an absorbing gas.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

AIM: Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. METHODS AND RESULTS: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (ß coefficient -0.404, p = 0.002), and a decrease in LASct (%) (ß coefficient -0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). CONCLUSIONS: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease.

Decreased left atrial function in obesity patients without known cardiovascular disease.

Obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF). We hypothesized that assessment of left atrial (LA) strain may be useful to reveal precursors of HFpEF in obesity patients. Echocardiograms of obesity patients without known cardiovascular disease who underwent bariatric surgery, and echocardiograms of age- and gender matched controls were analyzed. The echocardiogram was repeated 1 year after bariatric surgery. LA reservoir strain (LASr), LA conduit strain (LAScd), and LA contractile strain (LASct) were measured. 77 Obesity patients were compared with 46 non-obese controls. Obesity patients showed a significantly decreased LA function compared with non-obese individuals (LASr 32.2% ± 8.8% vs. 39.6% ± 10.8%, p < 0.001; LAScd 20.1% ± 7.5% vs. 24.9% ± 8.3%, p = 0.001; LASct 12.1% ± 3.6% vs. 14.5% ± 5.5%, p = 0.005). There was no difference in prevalence of diastolic dysfunction between the obesity group and controls (9.1% vs. 2.2%, p = 0.139). One year after bariatric surgery, LASr improved (32.1% ± 8.9% vs. 34.2% ± 8.7%, p = 0.048). In the multivariable linear regression analysis, BMI was associated with LASr, LAScd, and LASct (ß = - 0.34, CI - 0.54 to - 0.13; ß = - 0.22, CI - 0.38 to - 0.06; ß = - 0.10, CI - 0.20 to - 0.004). Obesity patients without known cardiovascular disease have impairment in all phases of LA function. LA dysfunction in obesity may be an early sign of cardiac disease and may be a predictor for developing HFpEF. LASr improved 1 year after bariatric surgery, indicating potential reversibility of LA function in obesity.

Palaeoceanographic implications of genetic variation in living North Atlantic Neogloboquadrina pachyderma.

The shells of the planktonic foraminifer Neogloboquadrina pachyderma have become a classical tool for reconstructing glacial-interglacial climate conditions in the North Atlantic Ocean. Palaeoceanographers utilize its left- and right-coiling variants, which exhibit a distinctive reciprocal temperature and water mass related shift in faunal abundance both at present and in late Quaternary sediments. Recently discovered cryptic genetic diversity in planktonic foraminifers now poses significant questions for these studies. Here we report genetic evidence demonstrating that the apparent 'single species' shell-based records of right-coiling N. pachyderma used in palaeoceanographic reconstructions contain an alternation in species as environmental factors change. This is reflected in a species-dependent incremental shift in right-coiling N. pachyderma shell calcite delta18O between the Last Glacial Maximum and full Holocene conditions. Guided by the percentage dextral coiling ratio, our findings enhance the use of delta18O records of right-coiling N. pachyderma for future study. They also highlight the need to genetically investigate other important morphospecies to refine their accuracy and reliability as palaeoceanographic proxies.

Repetitive non-thermal melting as a timing monitor for femtosecond pump/probe X-ray experiments.

Time-resolved optical pump/X-ray probe experiments are often used to study structural dynamics. To ensure high temporal resolution, it is necessary to monitor the timing between the X-ray pulses and the laser pulses. The transition from a crystalline solid material to a disordered state in a non-thermal melting process can be used as a reliable timing monitor. We have performed a study of the non-thermal melting of InSb in single-shot mode, where we varied the sample temperature in order to determine the conditions required for repetitive melting. We show how experimental conditions affect the feasibility of such a timing tool.

Relevance of aquatic environments for hominins: a case study from Trinil (Java, Indonesia).

Knowledge about dietary niche is key to understanding hominin evolution, since diet influences body proportions, brain size, cognition, and habitat preference. In this study we provide ecological context for the current debate on modernity (or not) of aquatic resource exploitation by hominins. We use the Homo erectus site of Trinil as a case study to investigate how research questions on possible dietary relevance of aquatic environments can be addressed. Faunal and geochemical analysis of aquatic fossils from Trinil Hauptknochenschicht (HK) fauna demonstrate that Trinil at approximately 1.5Ma contained near-coastal rivers, lakes, swamp forests, lagoons, and marshes with minor marine influence, laterally grading into grasslands. Trinil HK environments yielded at least eleven edible mollusc species and four edible fish species that could be procured with no or minimal technology. We demonstrate that, from an ecological point of view, the default assumption should be that omnivorous hominins in coastal habitats with catchable aquatic fauna could have consumed aquatic resources. The hypothesis of aquatic exploitation can be tested with taphonomic analysis of aquatic fossils associated with hominin fossils. We show that midden-like characteristics of large bivalve shell assemblages containing Pseudodon and Elongaria from Trinil HK indicate deliberate collection by a selective agent, possibly hominin.

Tripeptide structure of bursin, a selective B-cell-differentiating hormone of the bursa of fabricius.

Differentiation of lymphoid precursor cells in a variety of species is induced by polypeptide hormones such as thymopoietin for T cells and bursin for B cells. In the present experiments, bursin isolated from the bursa of Fabricius of chicken was found to induce the phenotypic differentiation of mammalian and avian B precursor cells but not of T precursor cells in vitro. Similarly, bursin increased cyclic guanosine monophosphate in cells of the human B-cell line Daudi but not in cells of the human T-cell line CEM. These inducing properties of bursin are the reverse of the inducing properties of thymopoietin produced by the thymus and are appropriate to a physiological B-cell-inducing hormone. A tripeptide sequence (lysyl-histidyl-glycyl-amide) was determined for bursin and confirmed by synthesizing this proposed structure and demonstrating chemical identity of the natural and synthetic peptides. Similarity of biological action was indicated in induction assays by elevation of cyclic adenosine monophosphate and guanosine monophosphate in Daudi B cells but not in CEM T cells.

Human CD4 binds immunoglobulins.

T cell glycoprotein CD4 binds to class II major histocompatibility molecules and to the human immunodeficiency virus (HIV) envelope protein gp120. Recombinant CD4 (rCD4) bound to polyclonal immunoglobulin (Ig) and 39 of 50 (78%) human myeloma proteins. This binding depended on the Fab and not the Fc portion of Ig and was independent of the light chain. Soluble rCD4, HIV gp120, and sulfated dextrans inhibited the CD4-Ig interaction. With the use of a panel of synthetic peptides, the region critical for binding to Ig was localized to amino acids 21 to 38 of the first extracellular domain of CD4. CD4-bound antibody (Ab) complexed with antigen approximately 100 times better than Ab alone. This activity may contribute to the Ab-mediated enhancement of cellular HIV interaction that appears to depend on a trimolecular complex of HIV, antibodies to gp120, and CD4.

Communication: Demonstration of a 20 ps X-ray switch based on a photoacoustic transducer.

We have studied an X-ray switch based on a gold coated indium antimonide crystal using time-resolved X-ray diffraction and demonstrated that the switch could reduce the pulse duration of a 100 ps X-ray pulse down to 20 ps with a peak reflectivity of 8%. We have used a dynamical diffraction code to predict the performance of the switch, which was then confirmed experimentally. The experiment was carried out at the FemtoMAX beamline at the short-pulse facility of the MAX IV laboratory. The performance and limitation of the switch are discussed in terms of acoustic transport properties between the two materials and the electron transport properties of gold.

Photoionization in the time and frequency domain.

Ultrafast processes in matter, such as the electron emission after light absorption, can now be studied using ultrashort light pulses of attosecond duration (10-18 seconds) in the extreme ultraviolet spectral range. The lack of spectral resolution due to the use of short light pulses has raised issues in the interpretation of the experimental results and the comparison with theoretical calculations. We determine photoionization time delays in neon atoms over a 40-electron volt energy range with an interferometric technique combining high temporal and spectral resolution. We spectrally disentangle direct ionization from ionization with shake-up, in which a second electron is left in an excited state, and obtain excellent agreement with theoretical calculations, thereby solving a puzzle raised by 7-year-old measurements.

Spectral phase measurement of a Fano resonance using tunable attosecond pulses.

Electron dynamics induced by resonant absorption of light is of fundamental importance in nature and has been the subject of countless studies in many scientific areas. Above the ionization threshold of atomic or molecular systems, the presence of discrete states leads to autoionization, which is an interference between two quantum paths: direct ionization and excitation of the discrete state coupled to the continuum. Traditionally studied with synchrotron radiation, the probability for autoionization exhibits a universal Fano intensity profile as a function of excitation energy. However, without additional phase information, the full temporal dynamics cannot be recovered. Here we use tunable attosecond pulses combined with weak infrared radiation in an interferometric setup to measure not only the intensity but also the phase variation of the photoionization amplitude across an autoionization resonance in argon. The phase variation can be used as a fingerprint of the interactions between the discrete state and the ionization continua, indicating a new route towards monitoring electron correlations in time.

Amino-terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity.

BACKGROUND: Erythropoietin (EPO), the hormone involved in red blood cell production, activates its receptor by binding to the receptor's extracellular domain and presumably dimerizing two receptor monomers to initiate signal transduction. EPO-mimetic peptides, such as EMP1, also bind and activate the receptor by dimerization. These mimetic peptides are not as potent as EPO, however. The crystal structure of the EPO receptor (EBP) bound to EMP1 reveals the formation of a complex consisting of two peptides bound to two receptors, so we sought to improve the biological activity of EPO-mimetic peptides by constructing covalent dimers of EMP1 and other peptide mimetics linked by polyethylene glycol (PEG). RESULTS: The potency of the PEG-dimerized EPO peptide mimetics both in vitro and in vivo was improved up to 1,000-fold compared to the corresponding peptide monomers. The dimers were constructed using peptide monomers which have only one reactive amine per molecule, allowing us to conclude that the increase in potency can be attributed to a structure in which two peptides are linked through their respective amino termini to the difunctional PEG molecule. In addition, an inactive peptide was converted into a weak agonist by PEG-induced dimerization. CONCLUSIONS: The potency of previously isolated peptides that are modest agonists of the EPO receptor was dramatically increased by PEG-induced dimerization. The EPO receptor is thought to be dimerized during activation, so our results are consistent with the proposed 2:2 receptor : peptide stoichiometry. The conversion of an inactive peptide into an agonist further supports the idea that dimerization can mediate receptor activation.

Technetium-99m-labeled hydrazino nicotinamide derivatized chemotactic peptide analogs for imaging focal sites of bacterial infection.

We synthesized and evaluated four hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analogs: For-NleLFK-HYNIC (HP1), For-MLFK-HYNIC (HP2), For-MLFNH(CH2)6NH-HYNIC (HP3), and For-MLF-(D)-K-HYNIC (HP4), for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 99mTc via a glucoheptonate co-ligand and their biodistribution determined in rats (n = 6/time point) at 5, 30, 60 and 120 min after injection. Localization of the peptides at sites of deep thigh Escherichia coli infection was determined by radioactivity measurements on excised tissues in rats (n = 6/time point) and rabbits as well as scintillation camera imaging in rabbits (n = 6). All peptides maintained biological activity (EC50s for O2 production by human PMNs: 12-500 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMNs (EC50s for binding: 0.12-40 nM). After incubation with 99mTc-glucoheptonate, radiolabeled peptides were isolated by HPLC at specific activities of > 10,000 mCi/microM. Technetium-99m-labeled peptides retained receptor binding with EC50s < 10 nM. Blood clearance of all four peptides was rapid. Biodistributions of the individual peptides were similar, with low levels of accumulation in most normal tissues. In rats, all of the peptides concentrated at the infection sites (T/B ratio: 2.5-3:1) within 1 hr of injection. In rabbits, outstanding images of the infection sites were obtained, with T/B ratios of > 20:1 at 15 hr after injection. This study demonstrates that 99mTc-labeled chemotactic peptide analogs are effective agents for the external imaging of focal sites of infection.

Imaging focal sites of bacterial infection in rats with indium-111-labeled chemotactic peptide analogs.

Four DTPA-derivatized chemotactic peptide analogs: ForNleLFNleYK-DTPA (P1), ForMLFNH(CH2)6NH-DTPA (P2), ForNleLFK(NH2)-DTPA (P3), and ForNleLFK-DTPA (P4), were synthesized and evaluated for in vitro bioactivity and receptor binding. The peptides were radiolabeled with 111In by transchelation and their biodistribution determined in rats at 5, 30, 60 and 120 min after injection. Localization at sites of infection was determined by scintillation camera imaging in animals with deep-thigh infection due to Escherichia coli. Images were recorded from 5 min to 2 hr after injection. All peptides maintained biologic activity (EC50 for O2-production by human PMN's: 3-150 nM) and the ability to bind to the oligopeptide chemoattractant receptor on human PMN's (EC50 for binding: 7.5-50 nM); biologic activity and receptor binding were highly correlated (r = 0.99). For all the peptides, blood clearance was rapid (half-lives: 21.5, 33.1, 31.6, and 28.7 min for P1, P2, P3, and P4, respectively). Biodistributions of the individual peptides were similar with low levels of accumulation in the heart, lung, liver, spleen, and gastrointestinal tract. In the kidney, P1 had much greater accumulation than other organs. All peptides yielded high quality images of the infection sites within 1 hr of injection. This study demonstrates that 111In-labeled chemotactic peptide analogs were effective agents for the external imaging of focal sites of infection.

In vivo bioactivity and biodistribution of chemotactic peptide analogs in nonhuman primates.

The dose dependence of the effect of chemotactic peptide on peripheral leukocyte levels was measured in normal Rhesus monkeys. A 99mTc-labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analog was used to study biodistribution and inflammation imaging in Rhesus monkeys. In normal animals the studies demonstrated that chemotactic peptide induced a clear dose-dependent reduction in peripheral leukocyte levels. The decrease in leukocyte number occurred almost immediately after injection and rapidly returned to baseline. Significant effects on differential WBC count, blood pressure, pulse rate or respiration rate were not detected. The lowest dose of peptide tested (10 ng/kg) had minimal effect on leukocyte level. The HYNIC derivatized peptide was prepared in excellent yield and purity, had biological activity similar to the native peptide and was readily labeled at specific activity of > 20,000 mCi/mumole. When approximately 0.5 mCi (< 2.0 ng/kg) of radiolabeled peptide was injected in monkeys with focal sites of mild sterile inflammation, a pattern of biodistribution similar to radiolabeled WBCs was observed and reductions in leukocyte levels were not detected. At 3 hr after injection, the site of inflammation was readily apparent with a target-to-background ratio of approximately 3:1. These studies demonstrate that radiolabeled chemotactic peptide analogs are effective agents for imaging sites of inflammation in monkeys. By radiolabeling at high specific activity, the effect of these reagents on peripheral leukocyte levels can be avoided.

Biologically active analogs of thymopentin with enhanced enzymatic stability.

Thymopentin, a synthetic pentapeptide fragment of thymopoietin (residues 32-36, Arg-Lys-Asp-Val-Tyr) is biologically active but susceptible to proteolytic digestion. Analogs were synthesized and studied for biological activity and susceptibility to peptidases. Amino acid changes were incorporated at positions known to not affect activity adversely and N-terminal acetylation and C-terminal amidation were used to increase resistance to proteolytic degradation by exopeptidases. Ac-Pro2-TP5-NH2 and Aib2-TP5-NH2 retained activity and were shown to exhibit a high degree of stability when incubated in human serum.

Cooperativity of thymopoietin 32-36 (the active site) and thymopoietin 38-45 in receptor binding.

Thymopoietin is a 49 amino acid polypeptide hormone of the thymus whose biological activity is reproduced by the synthetic pentapeptide thymopentin, corresponding to amino acids 32-36. Thymopentin requires the addition of an octapeptide corresponding to thymopoietin 38-45 for full competition with native thymopoietin in a radioreceptor assay with receptor derived from the human T-cell line CEM. Thus thymopoietin appears to bind to its receptor on T-cells by two regions (32-36 and 38-45). Thymopentin alone is biologically active and induces elevations of intracellular cyclic GMP. Whilst occupancy of the adjacent site by thymopoietin 37-45 does not of itself cause an elevation of intracellular cyclic GMP this peptide is not biologically silent as it does enhance the potency of thymopentin.

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P

The role of autologous blood transfusion in adolescents undergoing spinal surgery.

STUDY DESIGN: A prospective study of 147 consecutive patients undergoing spinal surgery who were analyzed for response to an effect of an offered autologous blood program. OBJECTIVES: Analysis of the impact of the autologous program within a comprehensive blood conservation philosophy toward the reduction in the use of homologous blood. METHODS: Each patient was prescreened by the autologous program for inclusions and ability. Physical parameters were recorded as were predonation and postdonation hemoglobin levels. The volume of each donation and the number of autologous and homologous units transfused and total operating blood loss were recorded as were complications during donation and transfusion. RESULTS: One hundred sixteen of the original one hundred forty-seven patients participated in the program and donated between 150 and 1900 ml of blood during the preoperative period. Of these, 35 patients weighed 45 kg or less. Diagnoses included 97 cases of idiopathic scoliosis and the remainder had spinal deformities of other causes. Of the entire group, 13 patients (11%) received homologous blood transfusion, 7 of these patients had diagnoses other than idiopathic scoliosis. CONCLUSIONS: In this study of 116 patients, 89% of the spinal surgeries were successfully completed using only autologous blood. This compared favorably with a historical control group in which 60% of the patients required homologous blood transfusion. It is concluded that the use of autologous blood donation combined with other blood conservation techniques has significantly lessened the need for homologous transfusion.