A 23Na magic angle spinning nuclear magnetic resonance, XANES, and high-temperature X-ray diffraction study of NaUO3, Na4UO5, and Na2U2O7.

The valence state of uranium has been confirmed for the three sodium uranates NaU(V)O3/[Rn](5f(1)), Na4U(VI)O5/[Rn](5f(0)), and Na2U(VI)2O7/[Rn](5f(0)), using X-ray absorption near-edge structure (XANES) spectroscopy. Solid-state (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) measurements have been performed for the first time, yielding chemical shifts at -29.1 (NaUO3), 15.1 (Na4UO5), and -14.1 and -19 ppm (Na1 8-fold coordinated and Na2 7-fold coordinated in Na2U2O7), respectively. The [Rn]5f(1) electronic structure of uranium in NaUO3 causes a paramagnetic shift in comparison to Na4UO5 and Na2U2O7, where the electronic structure is [Rn]5f(0). A (23)Na multi quantum magic angle spinning (MQMAS) study on Na2U2O7 has confirmed a monoclinic rather than rhombohedral structure with evidence for two distinct Na sites. DFT calculations of the NMR parameters on the nonmagnetic compounds Na4UO5 and Na2U2O7 have permitted the differentiation between the two Na sites of the Na2U2O7 structure. The linear thermal expansion coefficients of all three compounds have been determined using high-temperature X-ray diffraction: αa = 22.7 × 10(-6) K(-1), αb = 12.9 × 10(-6) K(-1), αc = 16.2 × 10(-6) K(-1), and αvol = 52.8 × 10(-6) K(-1) for NaUO3 in the range 298-1273 K; αa = 37.1 × 10(-6) K(-1), αc = 6.2 × 10(-6) K(-1), and αvol = 81.8 × 10(-6) K(-1) for Na4UO5 in the range 298-1073 K; αa = 6.7 × 10(-6) K(-1), αb = 14.4 × 10(-6) K(-1), αc = 26.8 × 10(-6) K(-1), αß = -7.8 × 10(-6) K(-1), and αvol = -217.6 × 10(-6) K(-1) for Na2U2O7 in the range 298-573 K. The α to ß phase transition reported for the last compound above about 600 K was not observed in the present studies, either by high-temperature X-ray diffraction or by differential scanning calorimetry.

Coupling XRD, EXAFS, and 13C NMR to study the effect of the carbon stoichiometry on the local structure of UC(1±x).

A series of uranium carbide samples, prepared by arc melting with a C/U ratio ranging from 0.96 to 1.04, has been studied by X-ray diffraction (XRD), (13)C nuclear magnetic resonance (NMR), and extended X-ray absorption fine structure (EXAFS). XRD determines phase uniqueness and the increase of the lattice parameter versus the carbon content. In contrast, (13)C NMR detects the different carbon environments in the lattice and in this study, clearly identifies the presence of discrete peaks for carbon in the octahedral lattice site in UC and an additional peak associated with excess carbon in hyperstoichiometric samples. Two peaks associated with different levels of carbon deficiency are detected for all hypostoichiometric compositions. More than one carbon environment is always detected by (13)C NMR. This exemplifies the difficulty in obtaining a perfect stoichiometric uranium monocarbide UC(1.00). The (13)C MAS spectra of uranium carbides exhibit the effects resulting from the carbon content on both the broadening of the peaks and on the Knight shift. An abrupt spectral change occurs between hypo- and hyperstoichiometric samples. The results obtained by EXAFS highlight subtle differences between the different stoichiometries, and in the hyperstoichiometric samples, the EXAFS results are consistent with the excess carbon atoms being in the tetrahedral interstitial position.

The use of a multicellular in vitro model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal Bacteroides thetaiotaomicron.

Bacterial extracellular vesicles (BEVs) are increasingly seen as key signalling mediators between the gut microbiota and the host. Recent studies have provided evidence of BEVs ability to transmigrate across cellular barriers to elicit responses in other tissues, such as the central nervous system (CNS). Here we use a combination of single-, two- and three-cell culture systems to demonstrate the transmigration of Bacteroides thetaiotaomicron derived BEVs (Bt-BEVs) across gut epithelium and blood brain barrier (BBB) endothelium, and their subsequent acquisition and downstream effects in neuronal cells. Bt-BEVs were shown to traffic to the CNS in vivo after intravenous administration to mice, and in multi-cell in vitro culture systems to transmigrate across gut epithelial and BBB endothelial cell barriers, where they were acquired by both microglia and immature neuronal cells. No significant activation/inflammatory effects were induced in non-differentiated neurons, in contrast to that observed in microglia cells, although this was notably less than that induced by lipopolysaccharide (LPS). Overall, our findings provide evidence for transmigration of Bt-BEVs across gut-epithelial and BBB endothelial cell barriers in vivo and in vitro, and their downstream responses in neural cells. This study sheds light onto how commensal bacteria-derived BEV transport across the gut-brain axis and can be exploited for the development of targeted drug delivery.

Short-term physiological effects of a xenobiotic mixture on the freshwater mussel Elliptio complanata exposed to municipal effluents.

The aim of this study was to investigate the short-term effects of tertiary-treated municipal effluents on the freshwater mussel Elliptio complanata. Caged mussels were immersed during 2 weeks in a river located North of Montreal Island, upstream/downstream the outfall and in one reference site located at the beginning of the Rivière des Prairies. A selection of biomarkers was analyzed to depict changes on various physiological systems: general physiology (mussel viability, condition index and gonado-somatic index), immune status (hemocyte viability, cellularity, phagocytosis efficiency, NK-like cytotoxic activity and lysozyme activity), inflammation (cyclo-oxygenase activity), detoxification (glutathione-S-transferases activity) and vitellogenesis (alkali-labile phosphate level). The analysis of total and fecal coliform counts in water and of heterotrophic bacteria levels in mussel tissues showed that the bacteriological quality of the water strongly decreased from the reference site to the downstream site. This was correlated with a significant loss of weight and an increase of mussel mortality. Cellularity and phagocytosis efficiency were significantly increased in the downstream site compared to the reference site. Though not statistically significant, lysozyme activity was also increased. NK-like cytotoxicity, activity of the pro-inflammatory enzyme COX and the levels of ALP and MT were not significantly changed. Conversely, the municipal effluents induced a significant increase of GST activity in downstream site, indicating a stimulation of detoxification metabolism. Altogether, these results confirm that a short-term exposure to a mixture of bacterial and chemical compounds released by the wastewater treatment plant La Pinière induces adverse physiological effects in E. complanata, as observed with the modulation of immune response and induction of detoxification metabolism.

Tiny Earth: A Big Idea for STEM Education and Antibiotic Discovery.

The world faces two seemingly unrelated challenges-a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

Ultra-fast prompt gamma detection in single proton counting regime for range monitoring in particle therapy.

In order to fully exploit the ballistic potential of particle therapy, we propose an online range monitoring concept based on time-of-flight (TOF)-resolved prompt gamma (PG) detection in a single proton counting regime. In a proof of principle experiment, different types of monolithic scintillating gamma detectors are read in time coincidence with a diamond-based beam hodoscope, in order to build TOF spectra of PG generated in a target presenting an air cavity of variable thickness. Since the measurement was carried out at low beam currents (< 1 proton/bunch) it was possible to reach excellent coincidence time resolutions, of the order of 100 ps (σ). Our goal is to detect possible deviations of the proton range with respect to treatment planning within a few intense irradiation spots at the beginning of the session and then carry on the treatment at standard beam currents. The measurements were limited to 10 mm proton range shift. A Monte Carlo simulation study reproducing the experiment has shown that a 3 mm shift can be detected at 2σ by a single detector of ∼1.4 × 10-3 absolute detection efficiency within a single irradiation spot (∼108 protons) and an optimised experimental set-up.

Functional fetal nigral grafts in a patient with Parkinson's disease: chemoanatomic, ultrastructural, and metabolic studies.

A patient with Parkinson's disease received bilateral fetal human nigral implants from six donors aged 6.5 to 9 weeks post-conception. Eighteen months following a post-operative clinical course characterized by marked improvement in clinical function, this patient died from events unrelated to the grafting procedure. Post-mortem histological analyses revealed the presence of viable grafts in all 12 implant sites, each containing a heterogeneous population of neurons and glia. Approximately 210,146 implanted tyrosine hydroxylase-immunoreactive (TH-ir) neurons were found. A greater number of TH-ir grafted neurons were observed in the right (128,162) than the left (81,905) putamen. Grafted TH-ir neurons were organized in an organotypic fashion. These cells provided extensive TH-ir and dopamine transporter-ir innervation to the host striatum which occurred in a patch-matrix fashion. Quantitative evaluations revealed that fetal nigral grafts reinnervated 53% and 28% of the post-commissural putamen on the right and left side, respectively. Grafts on the left side innervated a lesser area of the striatum, but optical density measurements were similar on both sides. There was no evidence that the implants induced sprouting of host TH-ir systems. Electron microscopic analyses revealed axo-dendritic and occasional axo-axonic synapses between graft and host. In contrast, axo-somatic synapses were not observed. In situ hybridization for TH mRNA revealed intensely hybridized grafted neurons which far exceeded TH mRNA expression within residual host nigral cells. In addition, gamma-amino butyric acid (GABA)-ergic neurons were observed within the graft that formed a dense local neuropil which was confined to the implant site. Serotonergic neurons were not observed within the graft. Cytochrome oxidase activity was increased bilaterally within the grafted post-commissural putamen, suggesting increased metabolic activity. In this regard, a doubling of cytochrome oxidase activity was observed within the grafted post-commissural putamen bilaterally relative to the non-grafted anterior putamen. The grafts were hypovascular relative to the surrounding striatum and host substantia nigra. Blood vessels within the graft stained intensely for GLUT-1, suggesting that this marker of blood--brain barrier function is present within human nigral allografts. Taken together, these data indicate that fetal nigral neurons can survive transplantation, functionally reinnervate the host putamen, establish synaptic contacts with host neurons, and sustain many of the morphological and functional characteristics of normal nigral neurons following grafting into a patient with PD.

Thrombus imaging using technetium-99m-labeled high-potency GPIIb/IIIa receptor antagonists. Chemistry and initial biological studies.

Platelet-specific compounds which are radiolabeled with gamma-emitting radionuclides may be particularly useful for the noninvasive in vivo detection of thrombi. The synthesis of peptides which are potent inhibitors of platelet aggregation and which contain a chelator for the radionuclide technetium-99m are described. The target compounds were designed such that stable, oxotechnetium(V) species could be prepared where the site of metal coordination was well defined. A strategy was employed where the pharmacophore-Arg-Gly-Asp-(RGD), or RGD mimetic, was constrained in a ring which was formed by the S-alkylation of a cysteine residue with an N-terminal chloroacetyl group. Binding affinities were enhanced by the replacement of arginine with the arginine mimetics S-(3-aminopropyl)cysteine and 4-amidinophenylalanine. Further enhancements could be obtained by the synthesis of oligomers which contained two or more rings containing receptor binding regions. The increase in binding affinity seen was more than that expected from a simple stoichiometric increase of pharmacophore. The most potent compounds described had IC50s of approximately 0.03 microM for the inhibition of human platelet aggregation. Two of the more potent peptides (P280 and P748) were labeled with technetium-99m and assessed in a canine thrombosis model. The 99m Tc complexes of the peptides prepared in this work hold promise as thrombus imaging agents due to their high receptor binding affinity, ease of preparation, and expected rapid pharmacokinetics.

Somatostatin receptor-binding peptides labeled with technetium-99m: chemistry and initial biological studies.

The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (Ki's in the 0.25 - 10 nM range) compared favorably with [DTPA]octreotide (Ki = 1.6 nM), which, as the indium-111 complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a Ki's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The 99m Tc-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.

Influence of cardiac functional capacity on gender differences in maximal oxygen uptake in children.

OBJECTIVE: To examine the role of gender differences in cardiac functional capacity in explaining higher mean values for maximal oxygen uptake (VO(2)max) in boys than in girls. DESIGN: Comparative group exercise testing. SETTING: Pediatric exercise testing laboratory. SUBJECTS: Twenty-five prepubertal boys (mean [+/- SD] age, 12 +/- 0.4 years) and 24 premenarcheal girls (mean age, 11.7 +/- 0.5 years). INTERVENTIONS: Maximal incremental upright cycle exercise. MEASUREMENTS AND RESULTS: Mean values for VO(2)max were the following: boys, 47.2 +/- 6.1 mL/kg/min; and girls, 40.4 +/- 5.8 mL/kg/min (16.8% difference; p < 0.05). The average maximal stroke index with Doppler echocardiography was 62 +/- 9 mL/m(2) for boys and 55 +/- 9 mL/m(2) for girls (12.7% difference; p < 0.05). No significant gender differences were seen in maximal heart rate or arterial venous oxygen difference. When VO(2)max and maximal stroke volume (SV) were expressed relative to lean body mass, gender differences declined but persisted, falling to 6.2% and 5.2%, respectively. CONCLUSIONS: These findings indicate that differences in SV as well as in body composition contribute to gender-related variations in VO(2)max during childhood. Whether this reflects small gender differences in relative heart size or dynamic factors influencing ventricular preload and contractility during exercise is unknown.

Interplay of self-doping and disorder in epitaxial Bi2Sr2Ca(n-1)Cu(n)O(2n+4+x) (n = 1,2) thin films under heavy-Ion irradiation

We propose a novel mechanism for the modification of T(c) in Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4+x) epitaxial thin films (2212 and 2201) under energetic heavy-ion irradiation. By irradiating films with various oxygen content, we show from the temperature dependence of the resistance that irradiation always produces a doping effect superimposed on the damage caused to the sample. The effect is larger in 2201 than in 2212 thin films. The T(c) decrease observed by irradiating optimally doped films is partially due to this doping effect. Irradiation of semiconducting samples restores metallic superconducting behavior.

One-mile run performance and cardiovascular fitness in children.

BACKGROUND: Endurance run tests are administered in schools to assess cardiovascular fitness, defined in the laboratory as maximum oxygen consumption. OBJECTIVE: To examine the validity of this concept, assessing the influences of body fat and maximum values of oxygen consumption per unit time, stroke volume, heart rate, and arteriovenous oxygen difference on 1-mile (1.6-km) run time in healthy sixth-grade boys. STUDY DESIGN: Subjects were 36 boys with a mean (SD) age of 12.2 (0.5) years. The relationship was examined between body fat content (estimated by skinfold measurements) and maximum oxygen consumption per kilogram and cardiac variables (during maximum cycle testing) with 1-mile run velocity. RESULTS: Body fat content and maximum oxygen consumption per kilogram (independent of body fat) accounted for 31% and 28% of the variance in run velocity, respectively. Stroke volume was the only component of maximum oxygen consumption that related to run performance. CONCLUSIONS: These findings suggest that cardiovascular fitness and body fat content contribute equally to 1-mile run time in healthy boys and together account for only 60% of the variance in performance on this endurance fitness test. Consequently, 1-mile run performance in children may not serve as a strong indicator of cardiovascular fitness.

Background urinary 1-hydroxypyrene levels in non-occupationally exposed individuals in the Province of Québec, Canada, and comparison with its excretion in workers exposed to PAH mixtures.

The urinary excretion of 1-hydroxypyrene (1-OHP) was measured in two reference groups of non-occupationally exposed individuals and in four groups of workers. Two of these groups were exposed to what were considered to be low levels of polycyclic aromatic hydrocarbons (PAH) on the basis that even post-shift 1-OHP excretion values were low (< 2 mumol/mol creatinine). Therefore, urine samples were collected from these workers after a period of > 60 h without occupational exposure which should yield values approaching background levels. Pooling these results with those of the reference groups yielded a total of 140 individuals having a mean (geometric) excretion of 0.08 mumol/mol creatinine and 5th, 50th and 95th percentiles of 0.02, 0.09 and 0.32 mumol/mol creatinine. The mean (geometric) excretion in the 95 nonsmokers and 45 smokers of this pool was 0.07 and 0.12 mumol/mol creatinine, respectively (one-tailed Student t-test, P < 0.001). Both this background excretion and the contribution of smoking appeared small in comparison with the excretion levels observed in some groups of exposed workers. Indeed, creosote workers described in this report had a geometric mean (range) excretion of 1.63 (0.18-10.47) mumol/mol creatinine during their working week. It is concluded that, for the biological monitoring of workers exposed to PAH, urinary 1-OHP appears to be a useful bioindicator for which background environmental contamination or smoking habits can be neglected in most cases.

Correction of postburn syndactyly: an analysis of children with introduction of the VM-plasty and postoperative pressure inserts.

An analysis of 190 operations for correction of postburn syndactyly in children showed that none of the procedures commonly used was entirely satisfactory because of partial recurrence of the lesion or less than optimal cosmetic results. Complete correction of the dorsal slant was a particular problem. Because of this, a new operation, designated the VM-plasty, was devised specifically for correction of postburn syndactyly, and this procedure was evaluated in 24 deformities. Our experience suggests that incision of the web with simple closure, simple YV-plasties, and simple or complex Z-plasties should not be used for postburn correction of webs 2, 3, and 4. The five-flap technique of Rousso and, occasionally, Z-plasties are suitable for correction of simple webs of the thumb space, and rotational flaps are suitable in some instances for correction of webs 2, 3 and 4. However, the VM-plasty now appears to be preferable in all instances of volar or dorsal webs where there is no limitation of the back of the hand at or distal to the metacarpophalangeal joints with the fist clenched. Contractures limiting the clenched fist usually require a graft to achieve complete anatomic correction. An adjunctive procedure of graded interdigital pressure inserts was evaluated following the correction of 28 webs and appeared to prevent the appearance of hypertrophic scar formation with improved cosmetic appearance and preservation of the dorsal slant.

Surgical correction of postburn flexion contractures of the fingers in children.

One-hundred forty-eight operative procedures for flexion contractures of the finger(s) following burn injury in children have been studied in detail with follow-up from 6 months to 8 years. Intramedullary K-wires, used for 53 procedures where a graft was done, were associated with a significantly worse long-term result, and graft take was not improved by using K-wires. Length of time between burn injury and reconstruction, age at time of operation, the use of full-thickness versus partial-thickness grafts, and the digit involved had an apparent effect on final result. The use of postoperative topical steroids could not be evaluated adequately in this study. The preferred operative techniques for this condition are discussed.

Origen intraorbitario de las arterias etmoidales: estudio anatómico / Intraorbital origin of the ethmoidal arteries: anatomical study

RESUMEN Introducción: Ramas de la arteria oftálmica contribuyen a la irrigación de diversos territorios de la fosa nasal y de los senos paranasales. Objetivo: El objetivo de nuestro estudio es describir las arterias etmoidales desde su origen intraorbitario, y su relación con las estructuras musculares y nerviosas. Material y Método: Se realizó un estudio anatómico endoscópico en 20 fosas nasales y órbitas de diez cadáveres. Resultados: La disección del plano muscular permitió definir dos espacios de entrada a la órbita. Un primer espacio entre el músculo recto inferior y músculo recto medial (área 1) y otro entre el músculo recto medial y músculo oblicuo superior (área 2). En el área 1, la arteria oftálmica discurrió superior al nervio óptico en el 90%. La arteria etmoidal anterior se observó en todos los casos inferior al músculo oblicuo superior. En el área 2, la arteria etmoidal posterior, se localizó en todos los casos superior al músculo oblicuo superior. No se identificó la arteria etmoidal media en ningún caso. El origen de la arteria supraorbitaria se identificó entre las dos arterias etmoidales. Conclusión: La comprensión anatómica del origen intraorbitario de la arteria oftálmica permite el abordaje de determinada patología intraorbitaria compleja a través de la pared medial de la órbita.

ABSTRACT Introduction: Branches of the ophthalmic artery contribute to the irrigation of various territories of the nasal cavity and paranasal sinuses. Aim: The aim of our study is to describe the intraorbital course of the ethmoidal arteries and their relationship with the muscular and nervous structures. Material and method: We performed twenty nasal cavities and orbital dissections in ten adults cadaveric heads. Results: The dissection of the muscular orbital wall allowed defining two surgical orbital corridors, between the inferior rectus and the medial rectus muscles (area 1) and between the medial rectus and the superior oblique muscles (area 2). In area 1, the ophthalmic artery crosses over the optic nerve in 90% of the cases. The anterior ethmoidal artery was observed inferior to the superior oblique muscle. In area 2, the posterior ethmoidal artery was located superior to the superior oblique muscle in all cavities. No middle ethmoidal artery was identified. The origin of the supraorbital artery was found between the two ethmoidal arteries. Conclusions: The anatomical understanding of the intraorbital origin of the arteries of the ophthalmic artery allows perform two surgical approaches through the media orbital wall.

A nuclear magnetic resonance spectrometer concept for hermetically sealed magic angle spinning investigations on highly toxic, radiotoxic, or air sensitive materials.

A concept to integrate a commercial high-resolution, magic angle spinning nuclear magnetic resonance (MAS-NMR) probe capable of very rapid rotation rates (70 kHz) in a hermetically sealed enclosure for the study of highly radiotoxic materials has been developed and successfully demonstrated. The concept centres on a conventional wide bore (89 mm) solid-state NMR magnet operating with industry standard 54 mm diameter probes designed for narrow bore magnets. Rotor insertion and probe tuning take place within a hermetically enclosed glovebox, which extends into the bore of the magnet, in the space between the probe and the magnet shim system. Oxygen-17 MAS-NMR measurements demonstrate the possibility of obtaining high quality spectra from small sample masses (~10 mg) of highly radiotoxic material and the need for high spinning speeds to improve the spectral resolution when working with actinides. The large paramagnetic susceptibility arising from actinide paramagnetism in (Th(1-x)U(x))O2 solid solutions gives rise to extensive spinning sidebands and poor resolution at 15 kHz, which is dramatically improved at 55 kHz. The first (17)O MAS-NMR measurements on NpO(2+x) samples spinning at 55 kHz are also reported. The glovebox approach developed here for radiotoxic materials can be easily adapted to work with other hazardous or even air sensitive materials.

Microbe-induced lymphocyte blastogenesis enhancement after preculture.

The in vitro blastogenic response of human peripheral blood mononuclear cells to Fusobacterium nucleatum and other oral microorganisms was enhanced if the peripheral blood mononuclear cells were cultured for 24 h at 37 degrees C prior to the addition of stimulant. The enhancement which occurred at optimal and supraoptimal concentrations of F. nucleatum (10 to 100 micrograms/ml) was detected after a preculture period of as little as 2 h. The blastogenic response was a result of T-cell proliferation, and enhancement occurred independently of monocytes. Suppressor activity was induced by culturing fresh lymphocytes for 24 h in the presence of supraoptimal concentrations of F. nucleatum. The enhancement phenomenon occurred independently of the prostaglandin effects on lymphocyte blastogenesis and was not abrogated by treatment with indomethacin.