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U.S. BUSINESS CONSULTANTS HAVE TAKEN AN INCREASED interest in the chemical industry, spurred by the many downsizing and business transformation projects that have taken place in the chemical sector in [...]

Context.A 10-arcmin region around the Hubble Deep Field (North) contains 92 radio sources brighter than 40 μJy which are well-resolved by MERLIN+VLA at 0$\farcs$2-2´´resolution (average size ~1´´). 55 of these have ChandraX-ray counterparts in the 2-Ms CDF(N) field including at least 17 with a hard X-ray photon index and high luminosity characteristic of a type-II (obscured) AGN. More than 70% of the radio sources have been classified as starbursts or AGN using radio morphologies, spectral indices and comparisons with optical appearance and rest-frame MIR emission. On this basis, starbursts outnumber radio AGN 3:1.

Previous economic analyses of liver transplantation have focused on the cost of the transplant and subsequent care. Accurate characterization of the pretransplant costs, indexed to severity of illness, is needed to assess the economic burden of liver disease. A novel data set linking Medicare claims with transplant registry data for 15 710 liver transplant recipients was used to determine average monthly waitlist spending (N = 249 434 waitlist months) using multivariable linear regression models to adjust for recipient characteristics including Model for End-Stage Liver Disease (MELD) score. Characteristics associated with higher spending included older age, female gender, hepatocellular carcinoma, diabetes, hypertension and increasing MELD score (p < 0.05 for all). Spending increased exponentially with severity of illness: expected monthly spending at a MELD score of 30 was 10 times higher than at MELD of 20 ($22 685 vs. $2030). Monthly spending within MELD strata also varied geographically. For candidates with a MELD score of 35, spending varied from $19 548 (region 10) to $36 099 (region 7). Regional variation in waitlist costs may reflect the impact of longer waiting times on greater pretransplant hospitalization rates among high MELD score patients. Reducing the number of high MELD waitlist patients through improved medical management and novel organ allocation systems could decrease total spending for end-stage liver care.

The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinum containing therapy. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal.

Retransplantation (RT) in Hepatitis C (HCV) patients remains controversial. Aims: To study trends in RT and evaluate the impact of HCV status in the context of a comprehensive recipient and donor risk assessment. The UNOS database between 1994 and October 2005 was utilized to analyze 46  982 LT and RT. Graft and patient survival along with patient and donor characteristics were compared for 2283 RT performed in HCV and non‐HCV patients during 1994–1997, 1998–2001 and 2002–October 2005. Overall HCV prevalence at RT increased from 36% in the initial period to 40.6% after 2002. In our study group, 1‐year patient and graft survival post‐RT improved over the same time intervals from 65.0% to 70.7% and 54.87% to 65.8%, respectively. HCV was only associated with decreased patient and graft survival with a retransplant (LT‐RT) interval (RI) >90 days. Independent predictors of mortality for RT with RI >90 days were patient age, MELD score >25, RI <1 year, warm ischemia time ≥75 min and donor age ≥60 (significant for HCV patients only). Outcomes of RT are improving, but can be optimized by weighing recipient factors, anticipation of operative factors and donor selection.

Variability is a key issue in the processing of biological materials, in this case the drying of hardwood timber. This paper reports measurements of variability of mechanical properties and correlations with basic density and diffusion coefficients, which are relevant to the drying of blackbutt, Eucalyptus pilularisSm, from Northern New South Wales. Specifically, radial, circumferential and height variations are reported for two regrowth blackbutt logs. Both blackbutt logs consisted of more than 80% heartwood, thus diffusion was considered as the main transport mechanism of moisture for modelling purposes.The modulus of elasticity for boards taken from two blackbutt trees increased from their green state to their kiln-dried state, generally by a factor of around two. An analysis of variance of wood samples from different parts of the two blackbutt logs showed that the variability of basic density, diffusion coefficient and most mechanical properties of timber, are significant in the radial direction, at a confidence level of at least 75%.Therefore, density and the microfibril angle are probably the actual sources of the variations of mechanical properties, since both parameters vary in the radial direction. Furthermore, from pith to bark, the diffusion coefficient and shrinkage decreased, while the basic density increased. A potential reason for this is that timber with high diffusion coefficients means that more moisture is lost per unit time because there is less wood (i.e. low basic density) to resist moisture transport, and less wood material means that the timber experiences more shrinkage.Strong correlations between the diffusion coefficient and the modulus of elasticity were also suggested using principal components analysis. The principal component accounted for 70% of the total amount of variation between the basic density, diffusion coefficient and green modulus of elasticity (perpendicular to the grain). From this, there is a strong possibility that the variabilities of the basic density, diffusion coefficient and green modulus of elasticity are correlated with each other.It is possible that high modulus of elasticity (whether it is longitudinal or green transverse to the grain) meant low diffusion coefficients, because of high basic density – i.e. more wood per unit volume possibly increased the stiffness of the timber. Such correlations may then be utilized to predict important drying parameters, such as the diffusion coefficient of a particular board prior to kiln-drying, by simply measuring the basic density, or using acoustic methods to measure the longitudinal modulus of elasticity. This parameter (longitudinal modulus of elasticity) is strongly correlated with the diffusion coefficient and basic density, because the principal component accounted for 98% of the total amount of variation between these parameters.

The use of allografts from donors with hepatitis B core antibody in liver transplantation (LT) is associated with the risk of de novohepatitis B virus (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and lamivudine alone or in combination has been reported. Yet, there are no standardized regimens and long‐term efficacy is not known. We report a case of a patient who underwent LT for alcoholic liver disease who received an allograft from a donor with Hepatitis B core antibody. The patient had no previous exposure to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface antibody present in serum before and 6 months after transplantation. Prophylaxis with short‐term HBIg (1 week) and indefinite lamivudine was given. De novoHBV infection developed more than 3 years after LT with a lamivudine‐resistant polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the risk of de novopost‐LT HBV infection in recipients of livers from hepatitis B core antibody positive donors. High risk were HBV naïve recipients, moderate risk recipients had isolated hepatitis B surface antibody (anti‐HBs) or hepatitis B core antibody (anti‐HBc), while low‐risk recipients had both anti‐HBs and anti‐HBc. We reviewed prophylaxis protocols reported in the literature and made recommendations for management.

With discrete states, several-atom Agn nanoclusters exhibit molecule-like behavior with strong visible fluorescence and robust optical properties. This new class of single-molecule fluorophores has been created and electrically contacted in thin films to produce the first electroluminescent single molecules. A direct reporter of nanoscale charge injection and transport through discrete energy levels, bright Agn electroluminescence has been harnessed to create single-molecule light-emitting diodes (LEDs) and optoelectronic logic gates and even to demonstrate full addition operations. These experiments utilizing the small size and quantum behavior of individual Ag nanoclusters usher in the new field of single-molecule optoelectronics.

Background: The comparative clinical effectiveness of new (reteplase, tenecteplase) vs. older (alteplase, streptokinase) thrombolytic agents in the treatment of acute myocardial infarction is uncertain.
Aim: To examine 30-35 day mortality and major adverse effects of thrombolytic agents in the treatment of acute myocardial infarction.
Design: Systematic review of randomized controlled trials comparing the clinical efficacy of included drug regimens.
Methods: We searched MEDLINE, EMBASE, Science Citation Index/Web of Science from 1980 to December 2001, and the Cochrane Library (2001, Issue 4). Reference lists of included studies and a number of medical journals were hand searched. Randomized controlled trials that compared any two of the included drugs provided to patients in the early stages of acute myocardial infarction, were included. Outcome measures included: mortality, bleeding, stroke, reinfarction, allergy and anaphylaxis.
Results: We found 14 studies, total study population 142 907. For available comparisons (all alteplase vs. streptokinase, reteplase vs. streptokinase or alteplase, tenecteplase vs. alteplase), meta-analysis showed no significant differences in mortality at 30-35 days. The GUSTO-I study showed an apparent benefit of accelerated alteplase over streptokinase, but its inclusion or exclusion made little difference. Total stroke and haemorrhagic stroke rates were lower for streptokinase than for all alteplase combined (total stroke, OR 1.29, 95%CI 1.13-1.46; haemorrhagic stroke OR 1.83, 95%CI 1.14-2.93).
Discussion: All thrombolytic drugs appear to be of similar efficacy in reducing mortality, and the apparent benefits of accelerated alteplase in GUSTO-I are consistent with this. Whether accelerated alteplase is sufficiently different from other regimens of administering alteplase to be excluded from a meta-analysis, and whether more weight should be placed on a meta-analysis than on a single trial, are matters for debate.

The Steer-a-Year course is designed to provide classroom and hands-on experience, industry-student interaction, and student group problem-solving opportunities. It is a cooperative agreement between the Department of Animal Sciences and the Oregon Cattlemen's and Cattlewomen's Associations. Steers are donated to the program by beef producers, fed a high concentrate ration to a target BW and condition, and marketed as either carcass or retail beef. After feed and management expenses are deducted, the Department of Animal Sciences retains one-half of the profit to be used for beef facilities improvements, and the other half is distributed to the donor's choice of either the Oregon Cattlemen's or Cattlewomen's Association. Approximately 30 steers have been donated to the program annually each of the past eight years. The donor receives updates regarding steer performance during the feeding period and carcass data following harvest of the animal. Students and instructors feed and manage the steers. The instructor uses classroom time to provide information to enable students to make informed management decisions. Officers are elected from within the class each term. Student officers are responsible for ensuring that cattle are managed and fed appropriately, and they lead the class in writing and sending producer updates. An evolving facet of the program is processing and marketing. Steers are sold locally through the Clark Meat Science Center. Students are encouraged to participate in a separate course in which they process the steers into retail product. In this manner, students can be involved in procurement, management, processing, and marketing. The course is challenging for the instructor since it requires management of lecture material, cattle health and feeding, producer and employee rapport, and student participation to ensure annual success of the program in terms of student learning and public relations. The course is very well received by students, most of whom have labeled it as a great learning experience.

Thin AgO films are readily photoactivated at room temperature to produce dynamic, multicolored fluorescent Agn nanoclusters. Writing efficiencies were separately examined as functions of excitation wavelength, intensity, and environmental interactions. The effects of external conditions on written nanocluster fluorescence are interpreted in terms of a mechanistic understanding of fluorescent Agn nanocluster creation and subsequent spectral dynamics, illustrating the equilibrium between nanocluster creation and destruction.

Matriptase, a trypsin-like serine protease, which may be involved in tissue remodeling, cancer invasion, and metastasis. Potent and selective matriptase inhibitors not only would be useful pharmacological tools for further elucidation of the role of matriptase in these processes but also could have therapeutic potential for the treatment and/or prevention of cancers. We report herein the structure-based approach for the discovery of bis-benzamidines as a novel class of potent matriptase inhibitors. The lead compound, hexamidine (1), inhibits not only the proteolytic activity of matriptase, (Ki = 924 nM) but also of thrombin Ki = 224 nM). By testing several available analogues, we identified a new analogue (7) that has a Ki = 208 nM against matriptase and has only weak inhibitory activity against thrombin (Ki = 2670 nM), thus displaying a 13-fold selectivity toward matriptase. Our results demonstrated that structure-based database screening is effective in the discovery of matriptase inhibitors and that bis-benzamidines represent a class of promising matriptase inhibitors that can be used for further drug design studies. Finally, our study suggested that there is sufficient structural differences between matriptase and its closely related serine proteases, such as thrombin, for the design of potent and selective matriptase inhibitors.

Ever since Bishop and his co-workers discovered the c-myc gene in the late 1970s (Bishop 1982), voluminous literature has documented its central role in proliferation and malignant transformation of human and animal cells (Amati et al. 1998, Bouchard et al. 1998, Dang et al. 1999). Most, if not all, types of human malignancy have been reported to have amplification and/or overexpression of this gene, although the frequency of these alterations varies greatly among different reports (Nesbit et al. 1999). In 1992, researchers started to realize that aberrant expression of c-myc could cause apoptosis (Evan et al. 1992, Shi et al. 1992), although the phenomenon had actually been observed much earlier (Wurm et al. 1986). Studies in recent years have further shown that the c-myc gene regulates growth, both in the sense of cell size and in the context of tissue differentiation (Gandarillas & Watt 1997, Iritani & Eisenman 1999, Johnston et al. 1999, Schmidt 1999, Schuhmacher et al. 1999). Thus, it is now known that the c-myc gene participates in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis (Packham & Cleveland 1995, Hoffman & Liebermann 1998, Dang 1999, Dang et al. 1999, Elend & Eilers 1999, Prendergast 1999). How the c-Myc protein may be specifically directed to perform one, but not the others, of these functions is still obscure, despite the fact that the relevant literature has been accumulating at a fast pace in the past two decades. This review focuses on the profound roles of c-Myc in breast cancer and in the actions of the hormones that are eitologically related to breast cancer.

Surgical decompression of the spinal canal is presently accepted worldwide as the method of treatment for thoracolumbar burst fractures with neurological deficit in the belief that neurological recovery may be produced or enhanced. Our clinical and laboratory experience, however, indicates that the paralysis occurs at the moment of injury and is not related to the position of the fragments of the fracture on subsequent imaging. Since the preoperative geometry of the fracture may be of no relevance, our hypothesis, backed by more than two decades of operative experience, is that alteration of the canal by ‘surgical clearance’ does not affect the neurological outcome.We have reviewed the existing world literature in an attempt to find evidence-based justification for the variety of surgical procedures used in the management of these fractures. We retrieved 275 publications on the management of burst fractures of which 60 met minimal inclusion criteria and were analysed more closely. Only three papers were prospective studies; the remainder were retrospective descriptive analyses. None of the 60 articles included control groups. The design of nine studies was sufficiently similar to allow pooling of their results, which failed to establish a significant advantage of surgical over non-surgical treatment as regards neurological improvement. Significant complications were reported in 75% of papers, including neurological deterioration. Surgical treatment for burst fracture in the belief that neurological improvement can be achieved is not justified, although surgery may still occasionally be indicated for structural reasons. This information should not be withheld from the patients.

We report the observation of unidirectional plasmon propagation in metallic nanowires over distances >10 μm. Through control of the incident excitation wavelength and rod composition, we demonstrate the selective coupling of photons into the plasmon mode of a 20 nm diameter nanowire. This mode then propagates in a nonemissive fashion down the wire length before being emitted as an elastically scattered photon at the distal end. As expected from previous studies of plasmon excitation in nanoparticles and thin films, we observe a strong wavelength and material dependence of this phenomenon. This metal-dependent plasmon propagation is exploited to produce a wire through which plasmons propagate unidirectionally. A bimetallic wire with a sharp Au/Ag heterojunction is shown to display both wavelength dependence and unidirectionality with respect to plasmon propagation across the heterojunction. It is expected that these results will contribute to the growing interest in optical energy transport in molecular-level and nanoscale devices.

Unlike the GroEL homologs of eubacteria and mitochondria, oligomer preparations of the higher plant chloroplast chaperonin 60 (cpn60) consist of roughly equal amounts of two divergent subunits, alpha and beta. The functional significance of these isoforms, their structural organization into tetradecamers, and their interactions with the unique binary chloroplast chaperonin 10 (cpn10) have not been elucidated. Toward this goal, we have cloned the alpha and beta subunits of the ch-cpn60 of pea (Pisum sativum), expressed them individually in Escherichia coli, and subjected the purified monomers to in vitro reconstitution experiments. In the absence of other factors, neither subunit (alone or in combination) spontaneously assembles into a higher order structure. However, in the presence of MgATP, the beta subunits form tetradecamers in a cooperative reaction that is potentiated by cpn10. In contrast, alpha subunits only assemble in the presence of beta subunits. Although beta and alpha/beta 14-mers are indistinguishable by electron microscopy and can both assist protein folding, their specificities for cpn10 are entirely different. Similar to the authentic chloroplast protein, the reconstituted alpha/beta 14-mers are functionally compatible with bacterial, mitochondrial, and chloroplast cpn10. In contrast, the folding reaction mediated by the reconstituted beta 14-mers is only efficient with mitochondrial cpn10. The ability to reconstitute two types of functional oligomer in vitro provides a unique tool, which will allow us to investigate the mechanism of this unusual chaperonin system.

The gut microbiome orchestrates epithelial homeostasis and both local and remote immunological responses. Critical to these regulatory interactions are innate immune receptors termed Toll-like receptors (TLRs).

The enzyme serine palmitoyltransferase (SPT; EC 2.3.1.50), which catalyzes the first committed and rate-limiting step in sphingolipid synthesis, is up-regulated in the epidermis as part of the homeostatic repair in response to permeability barrier perturbation. Moreover, UVB exposure, which also perturbs the barrier, up-regulates sphingolipid synthesis, but the basis for this increase is not known. The recent isolation of cDNAs for SPT (i.e., LCB1 and LCB2) allow molecular regulation studies to be performed. Therefore, we determined whether UVB exposure alters mRNA, protein, or activity levels for SPT in cultured human keratinocytes (CHKs) as a mechanism for regulation of epidermal sphingolipid synthesis. In CHK, transcripts for both LCB1 (3.0 kb) and LCB2 (2.3 kb) are evident by Northern blot analysis, and UVB exposure (23 mJ/cm2) induces a delayed 1.8 to 3.3-fold increase in LCB2 mRNA levels (P < 0.01) 48 h after treatment versus non-irradiated control cells. In contrast, neither LCB1 nor a second LCB2 transcript (8.0 kb) changed significantly. Likewise, Lcb2 protein levels (by Western blot analysis), as well as SPT activity, increase in parallel with the increased LCB2 mRNA. Finally, incorporation of [14C]-acetate into sphingolipids was increased significantly 48 h after UVB treatment. Together, these results demonstrate that CHKs respond to UVB by increasing sphingolipid synthesis, primarily through increases in both LCB2 mRNA and protein levels, leading to increased SPT activity. These results demonstrate one mechanism (UVB) whereby SPT is regulated at the molecular level, and suggest further that epidermis up-regulates sphingolipid synthesis at both the mRNA and protein levels in response to UVB.

Matriptase, a trypsin-like serine protease with two potential regulatory modules (low density lipoprotein receptor and complement C1r/s domains), was initially purified from T-47D breast cancer cells. Given its plasma membrane localization, extracellular matrix-degrading activity, and expression by breast cancer cells, this protease may be involved in multiple aspects of breast tumor progression, including cancer invasion. In breast cancer cells, matriptase was detected mainly as an uncomplexed form; however, low levels of matriptase were detected in complexes. In striking contrast, only the complexed matriptase was detected in human milk. The complexed matriptase has now been purified. Amino acid sequences obtained from the matriptase-associated proteins reveal that they are fragments of a Kunitz-type serine protease inhibitor that was previously reported to be an inhibitor of the hepatocyte growth factor activator. In addition, matriptase and its complexes were detected in milk-derived, SV40 T-antigen-immortalized mammary luminal epithelial cell lines, but not in human foreskin fibroblasts or in HT-1080 fibrosarcoma cells. These results suggest that the milk-derived matriptase complexes are likely to be produced by the epithelial components of the lactating mammary gland in vivo and that the activity and function of matriptase may be differentially regulated by its cognate inhibitor, comparing breast cancer with the lactating mammary gland.

A major protease from human breast cancer cells was previously detected by gelatin zymography and proposed to play a role in breast cancer invasion and metastasis. To structurally characterize the enzyme, we isolated a cDNA encoding the protease. Analysis of the cDNA reveals three sequence motifs: a carboxyl-terminal region with similarity to the trypsin-like serine proteases, four tandem cysteine-rich repeats homologous to the low density lipoprotein receptor, and two copies of tandem repeats originally found in the complement subcomponents C1r and C1s. By comparison with other serine proteases, the active-site triad was identified as His-484, Asp-539, and Ser-633. The protease contains a characteristic Arg-Val-Val-Gly-Gly motif that may serve as a proteolytic activation site. The bottom of the substrate specificity pocket was identified to be Asp-627 by comparison with other trypsin-like serine proteases. In addition, this protease exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Thus, the protease is a mosaic protein with broad spectrum cleavage activity and two potential regulatory modules. Given its ability to degrade extracellular matrix and its trypsin-like activity, the name matriptase is proposed for the protease.

When the cyclic thioethers L = SCH2CH2CH2, SCH(Me)CH2, and SCH2CH2CH2CH2 were added to [(η⁵-C5H5)2Rh2(μ-CO)(μ-η²:η²-CF3C2CF3)] (1), the coordinative addition products [(η⁵-C5H5)2Rh2(CO)(μ-η¹:η¹-CF3C2CF3)L] (2a−c) were formed reversibly. When it is left in solution in the presence of excess ligand, the propylene sulfide complex 2b (L = SCH(Me)CH2) transforms to the bridging sulfido complex [(η⁵-C5H5)2Rh2{μ-η¹:η¹:η²-C(O)C(CF3)C(CF3)}(μ-S)] (3a). A similar reaction occurred, but to a lesser extent, with the trimethylene sulfide complex 2a (L = SCH2CH2CH2). Comparable decompositions do not occur with the tetrahydrothiophene complex 2a (L = SCH2CH2CH2CH2). The dimethylselenane complex [(η⁵-C5H5)2Rh2(CO)(μ-η¹:η¹-CF3C2CF3)(SeMe2)] (4a) was formed reversibly when SeMe2 was added to solutions of 1. The reactions of 1 with the organotelluranes L‘ = TeMe2 and TeEt2 gave solid addition products [(η⁵-C5H5)2Rh2(CO)(μ-η¹:η¹-CF3C2CF3)L‘] (4b,c), which remained intact when dissolved in polar solvents. No rearrangement products were formed when solutions of the tellurane addition products were kept for several days. The bridging sulfido complex 3a and the analogous complexes [(η⁵-C5H5)2Rh2{μ-η¹:η¹:η²-C(O)C(CF3)C(CF3)}(μ-E)] (3b, E = Se; 3c, E = Te) were obtained from the direct reaction between E and the complex 1. Addition of the cyclic tellurane TeCH2CH2CH2CH2 to 1 gave [(η⁵-C5H5)2Rh2(CO)(μ-η¹:η¹-CF3C2CF3)(TeCH2CH2CH2CH2)] (6), which underwent rapid intramolecular ligand scrambling in solution. The crystal and molecular structure of 6 was determined by X-ray crystallography.

Phosphaalkynes, P&tbd1;CR (R = Bu^t, 1-adamantyl), react rapidly with the dirhodium compound [Rh2(η⁵-C5H5)2(μ-CO)(μ-η²-CF3C&tbd1;CCF3)], affording the η⁴: η¹ mono(phosphacyclobutadienyl) complexes [Rh(η⁵-C5H5){μ-η⁴:η¹-PC3R(CF3)2}{Rh(CO)(η⁵-C5H5)}] (R = Bu^t, Ad). Reaction of one of these complexes (R = Bu^t) with [W(CO)5(THF)] leads to the novel, crystallographically characterized “flyover” compound [Rh2(η⁵-C5H5)2{μ-(1,2,4-η): (1,3,4-η)-PC3Bu^t(CF3)2}{W(CO)5}]. Both react with [Fe2(CO)9], affording the dirhodium phosphacyclobutenyl complexes [Rh2(η⁵-C5H5)2(CO){μ-η¹:η³-PC3R(CF3)2}{Fe(CO)4}] (R = Bu^t, Ad). Spectroscopic analysis suggests the last two complexes exist in two isomeric forms in solution. One complex (R = Ad) has been characterized by an X-ray diffraction study.

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing.We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable ‘second hit’. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems.Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF.

Providing previously obscured positional and orientational information, a novel wide-field optical microscope capable of visualizing three-dimensional orientational dynamics of individual room temperature molecules has been developed. Utilizing a single detector, this facile method enables simultaneous observation of all molecular orientations without polarization optics. Such methods not only provide conclusive, nondestructive evidence of single molecule observation, but will also make single molecule orientational studies accessible to a wide range of researchers. Analysis of observed molecular emission patterns not only directly and noninvasively reveals true 3-D orientational dynamics of individual molecules, but also demonstrates that perceived molecular position is strongly dependent on orientation.

Utilizing noninvasive far- and near-field microscopy techniques, the dipole emission patterns of individual molecules have been directly visualized. By accurately modeling the imaging system upon introduction of specific aberrations, fits of simulated to observed molecular images have enabled true three-dimensional single-molecule orientation determinations at room temperature. Following emission pattern changes in time, this new imaging technique has enabled observation of individual molecule rotational motions within polymeric hosts. Such single-molecule orientational diffusion measurements cannot only probe nanoscale polymer dynamics, but should also lead to enhanced understandings of many materials and biological systems.

Twelve cases of wrist fusion for rheumatoid disease have been assessed pre and postoperatively in terms of symptoms, function, union, and complications. Improvement in hand function can be attributed to the provision of a painless stable wrist, and fusion in the straight position is in no way detrimental to personal hygiene. Delayed wound healing and pin migration are not uncommon complications but do not affect the end-results, which is radiological union from third metacarpal to radius—a definitive situation.

A study has been made of the fatigue behaviour of carbon/Kevlar-49/epoxy hybrid composites. Stress-life data have been obtained for both unidirectional and [(±45, 0, 0)2]s laminates in repeated tension and compression-tension cycling tests at various values of the stress (or R) ratio. Goodman (constant life) diagrams are presented for the unidirectional composites which indicate that the fatigue resistance of hybrid mixtures varies linearly with composition. The presence of the Aramid fibre, whose natural resistance to compression loads is suspect, does not appear to exert any unexpected damaging influence on the response of the hybrids either in tensile or tension-compression loading. This is also true of the behaviour of hybrid laminates containing plies at an angle to the main loading direction.

A study has been made of the fatigue behaviour in repeated tension of unidirectional and [(±45, 0, 0)2]s hybrid laminates composed of XAS carbon fibres and E-glass fibres in the same 913 epoxy resin. The ordinary mechanical properties of these composites are close to those predicted by simple, conventional models of hybrid behaviour. For the unidirectional materials, the fatigue stress for a given life is not a linear function of composition, showing a substantial positive deviation from the rule of mixtures. This behaviour closely mirrors that of unidirectional carbon-Kevlar hybrids reported in Part 1 of this work. In terms of strain-life comparisons, results for all hybrid compositions and plain carbon fibre reinforced plastic fall within a single scatter-band. These features are also reflected in the fatigue behaviour of the more complex hybrid laminate.

Summary Spontaneous lymphocyte activity has been measured over 24 weeks in rheumatoid arthritis patients who were receiving placebo, auranofin or gold sodium thiomalate (GST). The results suggest a relationship between a fall in lymphocyte activity and clinical improvement on GST. They also show that the patients with most active disease, as determined by the ESR, had normal levels of lymphocyte activity. We suggest that peripheral lymphocyte activity is secondary to immunological stimulation in the joint capsule, and is not directly related to disease activity. We conclude that spontaneous activity is probably an epiphenomenon and not related directly to disease activity or to disease prognosis.

Summary Most of the pharmaceuticals in clinical practice today for treatment of breast and other cancers are cytotoxic or cytostatic inhibitors of tumor growth. While this type of drug has found its place, along with surgery and radiotherapy, in treatment of disease, the breast cancer death rate has not decreased. This appears to be the result of rising incidence, resistance to therapy, and metastasis of the disease. Since distant metastasis (usually indicated by lymph node involvement) of breast cancer is related only indirectly to tumor size, it would appear that a concerted effort should be made to discover drugs which directly interfere with this complex process. Metastasis appears to depend upon tumor cell motility, dedifferen-tiation, local invasion, and angiogenesis. Significant progress has been recently made in the creation of new animal models of metastasis and in identifying several new drugs which may be suitable for clinical inhibition of this process. This article reviews current findings on anti-invasion/metastasis drugs with a focus on breast cancer.

Long-term (9–32 month) current meter records from the eastern North Atlantic (41°N–59°N) suggest that, remote from the influence of the Western Boundary Current, eddy kinetic energy (KE) at all depths is principally a function of wind stress and stratification, generated during the winter and early spring, propagating to abyssal depths and decaying to a minimum in late summer. Although this seasonal variation in KEhas not previously been described from the midlatitude ocean, some theoretical basis for it is presented.

The ECOPHYS model is an ecophysiological growth process model of juvenile poplar clones growing under near optimal conditions. The theoretical basis for the ECOPHYS model is that (1) individual leaves drive and control growth; (2) the microenvironment at the leaf exerts primary control of photosynthetic rates; (3) leaf orientation is a major determinant of that microenvironment, (4) photosynthates produced by leaves are allocated among meristematic and respiratory sinks: and (5) the plant's genome and microenvironment regulate photosynthate allocation. The major driving variables are solar radiation, temperature, and clonal morphological and physiological factors. The user can interact or override any or all of the input variables to examine the effects of such changes on photosynthetic production and growth. Verification and sensitivity analyses of ECOPHYS are presented and discussed. The use of ECOPHYS as a research tool is illustrated with several examples. Model potential and limitations are discussed.

Attempts to relate plant metabolic activity with developmental stage are often hindered by lack of an appropriate developmental index. Existing indices of morphological development are unsuitable for use with plants having a semideterminate, recurrently flushing pattern of growth as displayed by Quercus seedlings. We propose the following morphological index (QMI) to define the stages of Quercus seedling ontogeny: (1) radicle emergence; (2) epicotyl emergence from the soil; and (for each flush) (3) termination of elongation of the second internode, which corresponds with the period of most rapid stem elongation; (4) completion of elongation by all internodes, which corresponds with the period of most rapid leaf elongation; and (5) completion of elongation of the last leaf but one, which usually precedes closely the pause between one growth flush and another. The relationship between QMI and net photosynthesis by individual leaves of Quercus rubra L. seedlings was determined. Net photosynthesis increased with QMI during a flush, but at a particular QMI stage, generally decreased from one flush to the next.

LAC9 is a positive regulatory protein that controls transcription of the lactose-galactose regulon in Kluyveromyces lactis. LAC9 is homologous to the GAL4 protein of Saccharomyces cerevisiae. Both proteins have a single "zinc finger" which plays a role in DNA binding. We previously hypothesized (L. V. Wray, M. M. Witte, R. C. Dickson, and M. I. Riley, Mol. Cell. Biol. 7:1111-1121, 1987) that the DNA-binding domain of the LAC9 protein consisted of the zinc finger as well as a region of amino acids on the carboxyl-terminal side of the zinc finger. In this study we used oligonucleotide-directed mutagenesis to introduce 13 single-amino-acid changes into the proposed DNA-binding domain of the LAC9 protein. Variant LAC9 proteins carrying an amino acid substitution in any one of the four highly conserved Cys residues of the zinc finger had reduced DNA-binding activity, suggesting that each Cys is necessary for DNA binding. Three of four variant LAC9 proteins with amino acid substitutions located on the carboxyl-terminal side of the zinc finger had reduced DNA-binding activity. These results support our hypothesis that the DNA-binding domain of the LAC9 protein is composed of the zinc finger and the adjacent region on the carboxyl side of the zinc finger, a region that has the potential to form an alpha-helix. Finally, LAC9 proteins containing His residues substituted for the conserved Cys residues also had reduced DNA-binding activity, indicating that His residues are not equivalent to Cys residues, as had been previously thought.