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In this work, a new image guidance system and protocols for delivering image-guided radiotherapy (IGRT) on the Imaging and Medical Beamline (IMBL) at the ANSTO Australian Synchrotron are introduced. The image guidance methods used and the resulting accuracy of tumour alignment in in vivo experiments are often under-reported. Image guidance tasks are often complex, time-consuming and prone to errors. If unchecked, they may result in potential mis-treatments. We introduce SyncMRT, a software package that provides a simple, image guidance tool-kit for aligning samples to the synchrotron beam. We have demonstrated sub-millimetre alignment using SyncMRT and the small-animal irradiation platform (the DynamicMRT system) on the IMBL. SyncMRT has become the standard for carrying out IGRT treatments on the IMBL and has been used in all pre-clinical radiotherapy experiments since 2017. Further, we introduce two quality assurance (QA) protocols to synchrotron radiotherapy on the IMBL: the Winston-Lutz test and hidden target test. It is shown that the presented QA tests are appropriate for picking up geometrical setup errors and assessing the end-to-end accuracy of the image guidance process. Together, these tools make image guidance easier and provide a mechanism for reporting the geometric accuracy of synchrotron-based IGRT treatments. Importantly, this work is scalable to other delivery systems, and is in continual development to support the upcoming veterinary radiotherapy trials on the IMBL.

The CLIC study is investigating the technical feasibility of an electron-positron collider with high luminosity and a nominal centre-of-mass energy of 3 TeV. The predamping rings and damping rings (DRs) will produce ultra-low emittance beam with high bunch charge. To avoid beam emittance increase, the DR kicker systems must provide extremely stable field pulses during injection and extraction of bunches. The DR extraction kicker system consists of a stripline kicker and two pulse modulators. The present specification for the modulators calls for pulses with 160 ns or 900 ns flat-top duration of nominally ±12.5 kV and 305 A, with ripple of not more than ±0.02% (±2.5 V). In addition, there is a proposal to use the same modulators and striplines for dumping the beam, with ±17.5 kV stripline pulse voltage. An inductive adder is a very promising approach to meeting the CLIC DR extraction kicker specifications because analogue modulation methods can be applied to adjust the shape of the flat-top of the output waveform. Furthermore, the inductive adder can be operated with all or only a portion of the constant voltage layers triggered during the pulse, which allows two different operation modes: 12.5 kV for extraction of the beam and 17.5 kV for the beam dump. Recently, a 20-layer, 12.5/6.5 kV prototype inductive adder has been assembled at CERN and testing has commenced. The results of the initial tests and measurements are presented. The long-term goal is to also test the inductive adder with both operation modes.

The Dubinin-Astashov (DA) isotherm parameters for U, Pu, Sr and Np have been updated to include additional data obtained since the original derivation. The DA isotherms were modified to include a kinetic function derived by Rahn to describe sorbate loading from the beginning of sorption up to steady state. The final functions describe both kinetic and thermodynamic sorption.

We propose a novel method to measure the time-resolved momentum distribution and size of beams with very large momentum spread. To demonstrate the principle we apply the method to the beam at the end of a Compact Linear Collider decelerator, where conventional diagnostic methods are hampered by the large energy spread of the drive beam after up to 90% of its kinetic energy is converted into microwave power. Our method is based on sweeping the beam in a circular pattern to determine the momentum distribution and recording the beam size on a screen using optical transition radiation. We present an algorithm to extract the time-resolved momentum distribution. Furthermore, the beam size along the bunch train can be extracted from the image left on a screen by sweeping the beam linearly. We introduce the analysis technique and show simulation results that allow us to estimate the applicability. In addition, we present a conceptual design of the technical realization.

This study provided a first of a kind demonstration of the decontamination of High Level Radioactive Waste from the Savannah River Site using a continuous precipitation/adsorption process. Testing used a composite sample obtained from a number of waste tanks at the Savannah River Site. Preliminary batch processing experiments determined the efficacy of continuous process to precipitate sodium, potassium and cesium tetraphenylborate. The tetraphenylborate effectively removes cesium from solution. Researchers were also able to use the results of the batch experiments in design and prediction of the operation of the continuous process. This demonstration used two continuous reactors in series. This paper details the results obtained from batch tests with simulant and continuous decontamination of actual High Level Waste from the Savannah River Site.

This work studied the kinetics of copper-catalyzed decomposition of tetraphenylborate, triphenylborane, diphenylborinic acid and phenylboronic acid (NaTPB, 3PB, 2PB and 1PB, respectively) in aqueous alkaline solution over the temperature range of 25 to 70 degrees C. The statistically designed test matrices added copper sulfate to maximum concentrations of 10 mg/L. The relative rates of decomposition increase in the order of NaTPB 10-7 Mh-1) thermal hydrolysis of the phenylborate species occurs at 55 to 70 degrees C in alkaline (0.6-2.3 M OH-, 2-4.7 M Na+) solution with no added copper. The experiments suggest an important role for oxygen in copper-catalyzed phenylborate decomposition. NaTPB decomposes promptlymore » under anoxic conditions while 3PB, 2PB and 1PB decompose faster in aerobic solutions. Benzene and phenol form as the predominant end-products from alkaline copper catalysis in static systems sealed under air. Both 2PB and 1PB decompose with near equal rates and quantitatively produce phenol under flowing air-purge conditions at 25 to 60 degrees C. Mechanisms for copper-catalyzed phenylborate decomposition likely involve a redox process giving loss of a phenyl group from the phenylborate with reduction of cupric ion, or dephenylation by reduced cuprous ion involving a phenylated copper intermediate.« less

Simple collagen-like peptides comprising a repeat Gly-Pro-Hyp sequence are highly platelet-reactive when presented to platelets in triple-helical and polymeric form. This activity is not mediated by the platelet collagen receptor integrin alpha 2 beta 1. This may imply the existence of an intrinsic platelet reactivity associated with the collagen triple helix as such or perhaps that the Gly-Pro-Hyp sequence in collagen serves as a specific cell-recognition site. In our view this basic alpha 2 beta 1-independent reactivity is modulated by the presence in collagen of sequences that may either enhance or diminish the interaction with platelets. Inhibition studies with short linear peptides have allowed the tentative identification of sequences in collagen such as XPGEP(Q)GPX and D(N)GE(Q)X that may promote the activation of platelets and so enhance collagen-platelet interaction. Sequences serving as integrin alpha 2 beta 1-binding sites may also promote platelet reactivity by permitting interaction with the collagen receptor. Using triple-helical peptides based on the sequence of the platelet-reactive collagen type III fragment alpha 1(III)CB4, we have been able to locate an alpha 2 beta 1-binding site in collagen type III within a 30-mer sequence representing residues 508-537 of the alpha 1(III) constituent alpha-chain. Despite their alpha 2 beta 1-independent platelet reactivity, signalling by the (Gly-Pro-Hyp)n-based peptides shows many features in common with signalling by collagen fibers, including activation of p72SYK and p125FAK the latter of which has until now been considered a specific consequence of ligand binding to alpha 2 beta 1.

The aim of this investigation was to identify domains of collagen type I that can support platelet adhesion under flow conditions. Four cyanogen bromide (CB) fragments composing 87% of the collagen alpha 1(I)-chain were studied under static and flow conditions. Under static conditions, bovine and human collagen fragment alpha 1(I)CB3 induced aggregate formation, whereas alpha 1(I)CB7 and alpha 1(I)CB8 supported adhesion of dendritic and contact platelets. Bovine alpha 1(I)CB6 weakly supported platelet adhesion. At shear rate 300/s, collagen fragment alpha 1(I)CB3 strongly supported platelet adhesion, whereas lower platelet adhesion was observed to alpha 1(I)CB7 and alpha 1(I)CB8. The fragment alpha 1(I)CB6 did not support platelet adhesion under flow conditions. Adhesion to alpha 1(I)CB3 was completely inhibited by a low concentration (0.6 IgG microgram/mL) of anti-GPIa monoclonal antibody (MoAb), whereas this concentration of antibody partially inhibited adhesion to alpha 1(I)CB7 and alpha 1(I)CB8. At higher concentrations (3 micrograms/mL) the anti-glycoprotein Ia (GPIa) antibody completely inhibited adhesion to alpha 1(I)CB8 and further reduced adhesion to alpha 1(I)CB7. Platelet adhesion to alpha 1(I)CB3, alpha 1(I)CB7, and alpha 1(I)CB8 was strongly inhibited by an anti-GPIb MoAb. A MoAb against the GPIb-binding site of von Willebrand factor (vWF) strongly inhibited platelet adhesion to alpha 1(I)CB7 and alpha 1(I)CB8, whereas platelet adhesion to alpha 1(I)CB3 was not inhibited. We conclude that under flow conditions alpha 1(I)CB3, alpha 1(I)CB7, and alpha 1(I)CB8 support GPIa/IIa-dependent platelet adhesion. The GPIb-vWF interaction is important under flow conditions for adhesion to alpha 1(I)CB7 and alpha 1(I)CB8 and probably also to alpha 1(I)CB3.

Collagen fibres in suspension have been shown to inhibit adenylate cyclase in human platelet preparations. Direct inhibition by collagen fibres was observed when intact platelets were used, although secondary events such as ADP secretion or prostanoid formation were important contributors to the inhibition of adenylate cyclase after treatment of platelets with collagen. The nature of the direct inhibition caused by collagen has been investigated in platelet membrane preparations, with the following results. (1) Collagen fibres inhibit platelet membrane adenylate cyclase in a dose-dependent manner. (2) Inhibition of adenylate cyclase by thrombin, adrenaline or collagen fibres could be abolished in the presence of guanosine 5′-[beta-thio]diphosphate; half-maximal inhibition was obtained at about 100 microM for the inhibitory action of thrombin, and at about 500 microM for that of either adrenaline or collagen. (3) The action of each ligand was blocked to a similar extent by pertussis-toxin treatment of the platelet membranes. Taken together, these results indicate that the action of collagen, like that of thrombin and adrenaline, is G-protein-dependent. (4) inhibition of adenylate cyclase by collagen fibres was additive with that caused by adrenaline, but co-operative with that caused by thrombin, suggesting that inhibitory pathways exists for collagen and adrenaline which are distinct from, but interactive with, that for thrombin. (5) Modification of the collagen fibres by pepsin treatment attenuated the effects of collagen, whereas heat-denaturation of the collagen fibres completely abolished their effects. These data suggest that the effects of collagen are specific, and depend on the detailed structure of the collagen fibres.

Twenty patients who had a varus deformity of the foot secondary to spastic cerebral palsy had twenty-two operations involving combined split anterior tibial-tendon transfer and intramuscular lengthening of the posterior tibial tendon, with and without concomitant lengthening of the Achilles tendon. Preoperatively, all patients had had a dynamic varus deformity of the hindfoot and adduction of the forefoot in both the stance phase and the swing phase of gait. At an average follow-up of 6.2 years (range, 2.3 to 8.8 years), there were fourteen excellent, four good, and four poor clinical results. Two patients who had a fixed varus deformity of the hindfoot and one patient who had a very weak anterior tibial muscle had a poor result. We concluded that the combined procedure is effective for correction of a flexible varus deformity of the foot in patients who have spastic cerebral palsy.

At radiography, hyperplastic polyps classically appear as smooth, sessile elevations less than 5 mm in diameter. However, a retrospective review of double-contrast barium enema studies in 22 patients with 31 pathologically proved hyperplastic polyps revealed an average polyp size of 7.3 mm, with a range of 3-21 mm. Fifteen polyps (48%) were 2-5 mm, 12 (39%) were 6-10 mm, and four (13%) were greater than 10 mm in diameter. Twenty-nine polyps (94%) were sessile, and two polyps (6%) were pedunculated. Twenty-three polyps (74%) had a smooth contour, and eight polyps (26%) were lobulated. Twenty-six of the hyperplastic polyps (84%) were located in the rectosigmoid colon. If the radiologic criteria for an atypical hyperplastic polyp at double-contrast barium enema examination include size greater than 5 mm, lobulation, and/or pedunculation, 16 of the 31 hyperplastic polyps (52%) could be classified as atypical. Thus, radiologists should be aware that many hyperplastic polyps seen at double-contrast barium enema examination do not fit the classic description of a smooth, sessile elevation less than 5 mm in size but instead appear as larger, more lobulated lesions that are indistinguishable from adenomatous polyps.

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau_mu = 2.197013(24) us, is in excellent agreement with the previous world average. The new world average tau_mu = 2.197019(21) us determines the Fermi constant G_F = 1.166371(6) x 10^-5 GeV^-2 (5 ppm). Additionally, the precision measurement of the positive muon lifetime is needed to determine the nucleon pseudoscalar coupling g_P., As published version (PRL, July 2007)

The DA isotherm parameters for U, Pu, Sr and Np have been updated to include additional data obtained since the original derivation. The DA isotherms were modified to include a kinetic function derived by Rahn to describe sorbate loading from the beginning of sorption up to equilibrium. The final functions describe both kinetic and thermodynamic sorption. We selected the Rahn function to describe radionuclide sorption because it originates from diffusion and absorption controlled sorption. An investigation of the thermal behavior of radionuclide sorption on MST as shown by this data revealed the sorption process is diffusion (or transport) controlled (in solution). Transport in solution can in theory be accelerated by vigorous mixing but the range of available mixing speed in the facility design will probably not be sufficient to markedly increase radionuclide sorption rate on MST from diffusion-controlled sorption. The laboratory studies included mixing energies hydraulically-scaled to match those of the Actinide Removal Process and these likely approximate the range of energies available in the Salt Waste Processing Facility.

This document presents work conducted in support of technical needs expressed, in part, by the Engineering, Procurement, and Construction Contractor for the Salt Waste Processing Facility (SWPF). The Department of Energy (DOE) requested that Savannah River National Laboratory (SRNL) analyze and characterize supernate waste from seven selected High Level Waste (HLW) tanks to allow: classification of feed to be sent to the SWPF; verification that SWPF processes will be able to meet Saltstone Waste Acceptance Criteria (WAC); and updating of the Waste Characterization System (WCS) database. This document provides characterization data of samples obtained from Tanks 13H, 30H, 37H, 39H, 45F, 46F, and 49H and discusses results. Characterization of the waste tank samples involved several treatments and analysis at various stages of sample processing. These analytical stages included as-received liquid, post-dilution to 6.44 M sodium (target), post-acid digestion, post-filtration (at 3 filtration pore sizes), and after cesium removal using ammonium molybdophosphate (AMP). All tanks will require cesium removal as well as treatment with Monosodium Titanate (MST) for {sup 90}Sr (Strontium) decontamination. A small filtration effect for 90Sr was observed for six of the seven tank wastes. No filtration effects were observed for Pu (Plutonium), Np (Neptunium), U (Uranium), or Tcmore » (Technetium); {sup 137}Cs (Cesium) concentration is ~E+09 pCi/mL for all the tank wastes. Tank 37H is significantly higher in {sup 90}Sr than the other six tanks. {sup 237}Np in the F-area tanks (45F and 46F) are at least 1 order of magnitude less than the H-Area tank wastes. The data indicate a constant ratio of {sup 99}Tc to Cs in the seven tank wastes. This indicates the Tc remains largely soluble in Savannah River Site (SRS) waste and partitions similarly with Cs. {sup 241}Am (Americium) concentration was low in the seven tank wastes. The majority of data were detection limit values, the largest being < 1.0E+04 pCi/mL. Measured values for Pu and U were generally well below solubility model predictions.« less

Pretreatment processes at the Savannah River Site will separate {sup 90}Sr, alpha-emitting and radionuclides (i.e., actinides) and {sup 137}Cs prior to disposal of the high-level nuclear waste. Separation of {sup 90}Sr and alpha-emitting radionuclides occurs by ion exchange/adsorption using an inorganic material, monosodium titanate (MST). Previously reported testing with simulants indicates that the MST exhibits high selectivity for strontium and actinides in high ionic strength and strongly alkaline salt solutions. This paper provides a summary of data acquired to measure the performance of MST to remove strontium and actinides from actual waste solutions. These tests evaluated the effects of ionic strength, mixing, elevated alpha activities, and multiple contacts of the waste with MST. Tests also provided confirmation that MST performs well at much larger laboratory scales (300-700 times larger) and exhibits little affinity for desorption of strontium and plutonium during washing.

Integrin alpha2beta1 is the major receptor for collagens in the human body, and the collagen-binding site on the alpha2 subunit von Willebrand factor A-type domain (vWFA domain) is now well defined. However, the biologically important conformational changes that are associated with collagen binding, and the means by which the vWFA domain is integrated into the whole integrin are not completely understood. We have raised monoclonal antibodies against recombinant alpha2 vWFA domain for use as probes of function. Three antibodies, JA202, JA215 and JA218, inhibited binding to collagen, collagen I C-propeptide and E-cadherin, demonstrating that their function is important for structurally diverse alpha2beta1 ligands. Cross-blocking studies grouped the epitopes into two clusters: (I) JA202, the inhibitory antibody, Gi9, and a non-inhibitory antibody, JA208; (II) JA215 and JA218. Both clusters were sensitive to events at the collagen binding site, as binding of Gi9, JA202, JA215 and JA218 were inhibited by collagen peptide, JA208 binding was enhanced by collagen peptide, and binding of JA202 was decreased after mutagenesis of the cation-binding residue Thr(221) to alanine. Binding of cluster I antibodies was inhibited by the anti-functional anti-beta1 antibody Mab13, and binding of Gi9 and JA218 to alpha2beta1 was inhibited by substituting Mn(2+) for Mg(2+), demonstrating that these antibodies were sensitive to changes initiated outside the vWFA domain. Mapping of epitopes showed that JA202 and Gi9 bound between residues 212-216, while JA208 bound between residues 199-216. We have therefore identified two epitope clusters with novel properties; i.e. they are intimately associated with the collagen-binding site, responsive to conformational changes at the collagen-binding site and sensitive to events initiated outside the vWFA domain.

We have determined the crystal structure of a complex between the I domain of integrin alpha2beta1 and a triple helical collagen peptide containing a critical GFOGER motif. Three loops on the upper surface of the I domain that coordinate a metal ion also engage the collagen, with a collagen glutamate completing the coordination sphere of the metal. Comparison with the unliganded I domain reveals a change in metal coordination linked to a reorganization of the upper surface that together create a complementary surface for binding collagen. Conformational changes propagate from the upper surface to the opposite pole of the domain, suggesting both a basis for affinity regulation and a pathway for signal transduction. The structural features observed here may represent a general mechanism for integrin-ligand recognition.

The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Cell growth inhibition and drug-induced inhibition of de novo thymidylate and purine biosynthesis were used as measures of the cellular effects of the drugs. CCRF-CEM:RC2Tomudex cells had11% of the FPGS activity of CCRF-CEM cells, whereas MTX uptake and TS activity were equivalent. In CCRF-CEM:RC2Tomudex cells, MTX polyglutamate formation was undetectable after exposure to 1 microM [3H]MTX for 24 h. After exposure to 0.1 microM raltitrexed, levels of total intracellular raltitrexed-derived material in CCRF-CEM:RC2Tomudex cells were 30- to 50-fold lower than in the CCRF-CEM cell line. CCRF-CEM: RC2Tomudex cells were1000-fold resistant to raltitrexed and 6-fold resistant to lometrexol but sensitive to MTX and nolatrexed when exposed to these antifolates for 96 h. After 6 h of exposure, CCRF-CEM cells retained sensitivity to MTX and raltitrexed but were less sensitive to lometrexol-mediated growth inhibition. In contrast, CCRF-CEM: RC2Tomudex cells were markedly insensitive to raltitrexed, lometrexol, and to a lesser degree, MTX. Simultaneous measurement of de novo thymidylate and purine biosynthesis revealed 90% inhibition of TS activity by 100 nM MTX in both cell lines, whereas inhibition of de novo purine synthesis was only observed in CCRF-CEM cells, and only after exposure to 1000 nM MTX. Ten nM raltitrexed induced90% inhibition of TS activity in CCRF-CEM cells, whereas in CCRF-CEM:RC2Tomudex cells, there was no evidence of inhibition after exposure to 1000 nM raltitrexed. These studies demonstrate that polyglutamation is a critical determinant of the cellular pharmacology of both raltitrexed and MTX, markedly influencing potency in the case of raltitrexed and locus of action in the case of MTX.

Seven overlapping peptides derived from the bovine alpha1(III)CB4 fragment of collagen III support static platelet adhesion, and an integrin alpha2beta1-recognition site has been assigned within this fragment to residues 522-528 of the collagen alpha1(III) chain; (25). In this study we found that two of the peptides, CB4(III)-6 and -7, were able to support platelet adhesion under flow conditions, whereas the other peptides showed either very little (CB4(III)-1 and -4) or no platelet adhesion at all (CB4(III)-2, -3 and -5). Using the recombinant leech anti-platelet protein (rLAPP), known to prevent both alpha2beta1 integrin- and von Willebrand factor (vWF)-binding to collagen, we observed almost complete inhibition of platelet adhesion to peptides CB4(III)-6 and -7. In solid-phase binding assays rLAPP bound to CB4(III)-6 and -7 and to CB4(III)-6/7, containing the peptide 6/7 overlap sequence, and not to any other peptide. Our results suggest that the overlap sequence GPP*GPRGGAGPP*GPEGGK (single-letter amino acid code, P* = hydroxyproline), corresponding to residues 523-540 of the alpha1(III) collagen chain, contains a binding site for rLAPP. Monoclonal antibodies (MoAbs) directed against the alpha2 subunit of integrin alpha2beta1 inhibited platelet adhesion to both CB4(III)-6 and -7 by about 50%, showing that the alpha2beta1-recognition site in this locality in alpha1(III)CB4 detected under static conditions is of sufficient affinity to withstand shear forces. Solid-phase binding studies indicated that vWF binds to CB4(III)-7 and to a lesser extent to CB4(III)-4. Furthermore, rLAPP competed with vWF in binding to CB4(III)-7. Our results indicate that residues 541-558 of the alpha1(III)-chain may contain one of the critical vWF-binding sites involved in the initial phase of platelet adhesion to collagen III. MoAbs against vWF (A1 and A3 domain) and glycoprotein (GP)Ib confirmed that vWF is involved in adhesion to CB4(III)-7 and showed that vWF is also involved in adhesion to CB4(III)-6 despite the absence of direct binding of vWF to the peptide. The existence of alpha2beta1-, vWF- and rLAPP-binding sites all in close proximity in alpha1(III)CB4 testifies to the importance of this locus in collagen III for its platelet reactivity.

We have previously reported that a triple-helical, collagen-related peptide (CRP; also known as CRP-XL) containing a glycine-proline-hydroxyproline (GPP*) repeat motif and cross-linked through cysteine residues at its N-terminus and C-terminus is a powerful stimulus of platelet aggregation and secretion through the surface receptor glycoprotein VI (GPVI). The activation of platelets is associated with tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase C gamma2 (PLCgamma2). We now report that the non-cross-linked backbone of CRP, monomeric CRP (mCRP), stimulates the tyrosine phosphorylation of Syk and PLCgamma2 in platelets and induces the weak secretion of [3H]5-hydroxytryptamine ([3H]5-HT) and aggregation. The action of mCRP does not seem to be due to spontaneous cross-linking, because alkylation of the cysteine residues leads to an increase in activity. The tripeptide backbone of CRP, GPP*10 (in which P* represents hydroxyproline) also stimulates platelet shape change and the weak tyrosine phosphorylation of Syk and PLCgamma2, but is unable to induce aggregation or secretion. The monomeric peptides partly inhibit the release of [3H]5-HT by CRP, suggesting that they are partial agonists of the collagen receptor GPVI. These results demonstrate that GPP* present as a repeat motif is sufficient to activate the platelet collagen receptor GPVI but that the cross-linking of monomers brings about an increase in activity.

The data obtained from the tests described in this document provide results for determining tank size for in the proposed Small-Tank Tetraphenylborate (STTP) facility.

A population-based study of pediatric cervical spine trauma in the Auckland region over 7 years starting in March 1989 identified 32 patients younger than 15 years of age who sustained a fracture, dislocation, or major ligamentous injury including SCIWORA (spinal cord injury without radiographic abnormality). Thirty-one percent had associated injuries and 53% had abnormal neurologic findings on presentation. Children younger than 10 years of age with cervical spine trauma more commonly sustained the injury in a motor vehicle accident and had a preponderance of injuries of the upper cervical spine. Children 10 years of age or older were more often injured during sport or recreational activity and the injuries followed a more typically adult pattern. Treatment included closed reduction in two patients and posterior open reduction and stabilization in eight patients (25%) with one of these also requiring decompression. All patients treated surgically had a very satisfactory outcome.

The chemical decomposition of aqueous alkaline solutions of sodium tetraphenylborate (NaTPB) has been investigated. The focus of the investigation is on the determination of additives and/or variables which influence NaTBP decomposition. This document describes work aimed at providing better understanding into the relationship of copper (II), solution temperature, and solution pH to NaTPB stability.

The stability of excess amounts of sodium tetraphenylborate (NaTPB) in the In-Tank Precipitation (ITP) facility depends on a number of variables. Concentration of palladium, initial benzene, and sodium ion as well as temperature provide the best opportunities for controlling the decomposition rate. This study examined the influence of these four variable on the reactivity of palladium-catalyzed sodium tetraphenylborate decomposition. Also, single effects tests investigated the reactivity of simulants with continuous stirring and nitrogen ventilation, with very high benzene concentrations, under washed sodium concentrations, with very high palladium concentrations, and with minimal quantities of excess NaTPB.

A series of twelve tests examined benzene generation rates with radioactive materials simulating the planned Batches 2 through 4 that complete Cycle 1 for the In-Tank Precipitation (ITP) facility.

Simple collagen-related peptides (CRPs) containing a repeat Gly-Pro-Hyp sequence are highly potent platelet agonists. Like collagen, they must exhibit tertiary (triple-helical) and quaternary (polymeric) structure to activate platelets. Platelet signaling events induced by the peptides are the same as most of those induced by collagen. The peptides do not recognize the alpha 2 beta 1 integrin. To identify the signaling receptor involved, we have evaluated the response to the CRP, Gly-Lys-Hyp(Gly-Pro-Hyp)10-Gly-Lys-Hyp-Gly of platelets with defined functional deficiencies. These studies exclude a primary recognition role for CD36, von Willebrand factor (vWF), or glycoprotein (GP) IIb/IIIa. Thus, both CD36 and vWF-deficient platelets exhibited normal aggregation, normal fibrinogen binding, and normal expression of CD62 and CD63, measured by flow cytometry, in response to the peptide, and there was normal expression of CD62 and CD63 on thrombasthenic platelets. In contrast, GPVI-deficient platelets were totally unresponsive to the peptide, indicating that this receptor recognizes the Gly-Pro-Hyp sequence in collagen. GPVI-deficient platelets showed some fibrinogen binding in response to collagen but failed to aggregate and to express CD62 and CD63. Collagen, but not CRP-XL, contains binding sites for alpha 2 beta 1. Therefore, it is possible that collagen still induces some signaling via alpha 2 beta 1, leading to activation of GPIIb/IIIa. Our findings are consistent with a two-site, two-step model of collagen interaction with platelets involving recognition of specific sequences in collagen by an adhesive receptor such as alpha 2 beta 1 to arrest platelets under flow and subsequent recognition of another specific collagen sequence by an activatory receptor, namely GPVI.

At the Savannah River Site, the In-Tank Precipitation process uses sodium tetraphenylborate to decontaminate soluble waste by precipitating cesium-137.

The platelet-reactive collagen III-derived fragment alpha1(III)CB4 has been synthesized as seven overlapping peptides, each as a homotrimeric triple-helical species covalently linked at the C terminus. Additional Gly-Pro-Hyp triplets were introduced at each end of the peptide sequence to ensure a stable triple-helical conformation at 20 degrees C, the temperature at which cell reactivity was measured. A Cys-containing triplet was included at each end to allow intermolecular cross-linking. All seven peptides in triple-helical, cross-linked form were able to cause platelet aggregation. Peptide 6, the most reactive species, was more aggregatory than collagen fibers. Platelet adhesion occurred to all peptides immobilized on plastic in monomeric form. Adhesion was integrin alpha2beta1-independent except in the case of peptide 6, adhesion to which was partially reduced by anti-integrin alpha2beta1 monoclonal antibodies. The presence of an alpha2beta1 recognition site in peptide 6 was confirmed using HT 1080 cells, which express alpha2beta1 as their major or sole collagen receptor. HT 1080 adhesion to both peptide 6 and collagen was strongly inhibited by anti-integrin alpha2beta1 monoclonal antibodies. These cells did not adhere to any of the other peptides. Comparison of the structure of peptide 6 with that of adjacent peptides indicates that the sequence Gly-Gly-Pro-Hyp-Gly-Pro-Arg, residues 522-528 of the collagen alpha1(III) chain, represents the minimum structure required for the recognition of alpha2beta1. Our findings support the view that the collagen triple helix possesses an intrinsic platelet reactivity that can be expressed independently of integrin alpha2beta1 and the precise level of which is governed by the exact nature of the primary sequence. Sequences such as those recognizing alpha2beta1 may potentiate the activity, whereas others may have the opposite effect.

The impact of drug use and race on school performance was investigated. Data were collected retrospectively from a sample of 100 students in Grades 9 through 12, using a questionnaire devised by the authors. Most recent grades in English, mathematics, social studies, and science, and percentile scores on the mathematics portion of a recent Metropolitan Achievement Test, constituted achievement. Sufficient data were obtained for 38 students (11 black, 18 white, and 9 Latino). Results included significant main effects for both race (p.05) and user status (p.05). An interaction of race and user status was suggested. While black users and nonusers did not differ across academic areas, large differences for the two other ethnic groups emerged.

This report provides a qualitative and semiquantitative description of the chemical reaction that decomposed the excess sodium tetraphenylborate in Tank 48H during November and December 1995.

Synthetic collagen-like peptides, of general structure [Gly-Pro-HyP]n, adopt the triple-helical structure which is essential for the platelet-reactivity of native collagens. These peptides are potent activators of platelets, stimulating platelet aggregation at much lower dose than collagen fibres, but, unlike collagen fibres, they are not recognised by the integrin alpha 2 beta 1. We have examined the ability of the synthetic peptides to activate the various signalling pathways which regulate human platelet function. The peptides are potent activators of Ca2+ mobilisation and of protein kinase C, and they stimulate tyrosine phosphorylation of some substrates preferentially. However, in contrast with native type I collagen fibres, they are unable to inhibit platelet adenylate cyclase. This suggests a mode of action for the synthetic peptides which substantially overlaps, but which is not entirely identical with, that of native collagen.

Simple collagen-like peptides comprising a repeat Gly-Pro-Hyp sequence are highly platelet-reactive when presented to platelets in triple-helical and polymeric form. This activity is not mediated by the platelet collagen receptor integrin alpha 2 beta 1. This may imply the existence of an intrinsic platelet reactivity associated with the collagen triple helix as such or perhaps that the Gly-Pro-Hyp sequence in collagen serves as a specific cell-recognition site. In our view this basic alpha 2 beta 1-independent reactivity is modulated by the presence in collagen of sequences that may either enhance or diminish the interaction with platelets. Inhibition studies with short linear peptides have allowed the tentative identification of sequences in collagen such as XPGEP(Q)GPX and D(N)GE(Q)X that may promote the activation of platelets and so enhance collagen-platelet interaction. Sequences serving as integrin alpha 2 beta 1-binding sites may also promote platelet reactivity by permitting interaction with the collagen receptor. Using triple-helical peptides based on the sequence of the platelet-reactive collagen type III fragment alpha 1(III)CB4, we have been able to locate an alpha 2 beta 1-binding site in collagen type III within a 30-mer sequence representing residues 508-537 of the alpha 1(III) constituent alpha-chain. Despite their alpha 2 beta 1-independent platelet reactivity, signalling by the (Gly-Pro-Hyp)n-based peptides shows many features in common with signalling by collagen fibers, including activation of p72SYK and p125FAK the latter of which has until now been considered a specific consequence of ligand binding to alpha 2 beta 1.

We have investigated the effects of the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, on [3H]arachidonic acid release from human platelets. Both tyrosine kinase inhibitors blocked, in a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosine kinase inhibitors occurred early in the arachidonate release time course. Both genistein and methyl 2,5-dihydroxycinnamate also inhibited tyrosine phosphorylation in platelets. The inhibitors were specific in that they did not affect protein kinase C activity, ATP levels or mobilization of Ca2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A2 in platelets stimulated by the physiological ligands, thrombin and collagen.

e19672 Background: Childhood brain tumor survivors fatigue more easily and are more sedentary than same age peers. Cancer treatments can impair balance and coordination. Few studies have attempted ...

Twenty patients who had a varus deformity of the foot secondary to spastic cerebral palsy had twenty-two operations involving combined split anterior tibial-tendon transfer and intramuscular lengthening of the posterior tibial tendon, with and without concomitant lengthening of the Achilles tendon. Preoperatively, all patients had had a dynamic varus deformity of the hindfoot and adduction of the forefoot in both the stance phase and the swing phase of gait. At an average follow-up of 6.2 years (range, 2.3 to 8.8 years), there were fourteen excellent, four good, and four poor clinical results. Two patients who had a fixed varus deformity of the hindfoot and one patient who had a very weak anterior tibial muscle had a poor result. We concluded that the combined procedure is effective for correction of a flexible varus deformity of the foot in patients who have spastic cerebral palsy.