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Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 micrograms/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 micrograms/kg on days -3, -1, and 1, or 0.6 micrograms/kg on days -1 and 1. G-CSF, 5 micrograms/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34(+) cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 10(6)/kg (range, 1.3 to 17.6) versus 0.8 x 10(6)/ kg (range, 0.3 to 4.2), P =.0003. The targeted minimum yield of 3 x 10(6) CD34(+) cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P =.001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P =.0001) and platelet recovery (day 9 v 10, P =.07) were accelerated, and fewer erythrocyte (3 v 4, P =.02) and platelet (4 v 5, P =.02) transfusions were needed compared with G-CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P.0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 microgram/kg. rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.

Wind tunnels utilize some of the largest drives in the world. The current NASA-NTF wind tunnel project, by replacing its aging fan drive system with a new adjustable speed drive (ASD) using a single 135000 HP synchronous motor, will employ the largest adjustable speed drive system in the world. High voltage DC transmission and traditional ASD technology, and utilization of large rotating machinery design and manufacturing techniques, makes this system possible.

A new concept for polymer surface modification is described that employs surface-active ω-functional block copolymers as additives to create polymers with smart sufaces. The block copolymers are composed of three components: a low surface energy block that causes the copolymer to segregate to the surface of the matrix homopolymer to which it is added, an anchor block that tethers the copolymer into that matrix, and a functional group located at the terminus of the surface-active block. The functional end group is selected to interact selectively with a complementary receptor on the target substrate. When the modified polymer surface and a substrate are placed in contact, adhesion is enhanced only if the functional end group senses an appropriate receptor on that substrate with which it can form the specific interaction. If a receptor is not present, the modified surface exhibits release properties. This class of copolymer additives can thereby be employed to create smart polymer surfaces with sel...

Summary We reported the case of an 85-year-old woman who presented with an acutely tender abdomen and underwent abdominal computed tomography (CT) scanning initially reported as showing diverticulitis. After failed conservative management, this patient was taken to theatre, and laparotomy revealed a punctate perforation of the ileum due to a 4 × 3 cm fish fin, which was removed through enterotomy. Retrospective analysis of the initial CT scans showed a foreign body consistent with that removed. This is the first case documented in the literature of perforation of bowel due to fish fin ingestion, as opposed to fish bone. It highlights firstly how common presentations may have an uncommon cause and secondly, how easily a small foreign body can be missed on CT scan. It also highlights and the importance of (i) eliciting a full history of eating habits in those presenting with abdominal pain and (ii) basing intervention on clinical findings. In this case report, we review the wider medical literature on perforation due to foreign body ingestion.

Radiation-induced mutants of groundnut cv. Spanish Improved showing distinct morphological differences and the parent were screened for RAPD variability. The analysis revealed characteristic band differences among the 12 mutants and the parent. The polymorphic RAPD bands were dominant in the F1 and segregated in a Mendelian fashion in the F2. The RAPD technique brought out greater genome variability than RFLP.

Blackgram (Vigna mungo L. Hepper) seeds contain two galactose-specific lectins, BGL-I and BGL-II. BGL-I was partially purified into two monomeric lectins which were designated as BGL-I-1 (94 kDa) and BGL-I-2 (89 kDa). BGL-II is a monomeric lectin of 83 kDA. The purified lectins were associated with galactosidase activities. BGL-I-1 and BGL-II were copurified with α-galactosidase activity while BGL-I-2 was largely associated with β-galactosidase activity. These lectins agglutinate trypsin treated rabbit erythrocytes, but not the human erythrocytes of A, B or O groups. They were stable between pH 3·5 and 7·5 for their agglutination. The lectins did not show any metalion requirement. They were inactivated at 50°C. The lectin activity was inhibited by D-galactose (0·1 mM). The Scatchard plots of galactose binding to these lectins are nonlinear and biphasic curves indicative of multiple binding sites. The data show that the monomeric lectins have both lectin and galactosidase activities suggestive of a bifunctional protein.

Aim: The aim of the study was to assess how adequately distal radial fracture reduction was reproduced and maintained with the distal volar radius anatomic DVR-A (Biomet, Inc) locking plate. Methods: We looked at a consecutive series of 111 patients treated with the DVR-A plate at our institution from 2007–2010. The preoperative, intra-operative, and postoperative films were reviewed. The AO and Frykman classification was recorded. The sagittal tilt, radial inclination, and radial length were measured on intra-operative X-rays and compared with final follow-up X-rays. The last recorded range of motion at follow-up and a functional assessment using the Disabilities of the Arm, Shoulder, and Hand (DASH) score was recorded. Results: At final follow-up a mean radial inclination of 22.22 degrees (11 to 38 degrees), radial height of 11.85 mm (6 to 18 mm), and sagittal tilt of 6.71 degrees volar (-9 to 19 degrees) was achieved. From initial post-operative films, to final follow-up X-rays there was a mean increase of 0.17 degrees in radial inclination, a mean loss of 0.36 mm radial height, and a mean loss of 2.17 degrees volar tilt. The mean extension was 46.8 degrees, flexion 48.3 degrees, pronation 77.4 degrees, supination 74.8 degrees, radial deviation 15.3 degrees and the ulnar deviation 19 degrees. The mean DASH score was 12.8 (0–68). Conclusion: The DVR-A plate achieved a highly satisfactory reduction of radial length and radial inclination, with a small loss of volar sagittal tilt at final follow-up. A good functional outcome was reported, with a satisfactory range of motion achieved. The DVR-A plate is a safe and effective treatment for unstable and intra-articular displaced distal radius fractures, particularly in younger patients, in the short term.

An important issue for mobile ad hoc network is the routing protocol design. Due to frequent changes in the topology of the network this becomes a major technical challenge. Node failures and link breakages in the network may cause loss of the network resources. In this paper we proposed a method which, works in two phases, first is signal strength based AODV if this approach is not work then it switch to second phase means work like as normal AODV, In signal strength based AODV protocol measures signal strength between nodes and compare with RSSI threshold values if it is greater than threshold value then it is accepted for further processing otherwise it is discarded if it is not find any route between source and destination then it switch to normal AODV which select route on the basis of minimum hop count. The benefit of this scheme is by selecting a strong route to the destination we can increase the lifetime of the network. Simulation results show that IAODV has performance better than AODV routing protocol in terms of the metrics: Packets delivery ratio, throughput, Routing overhead.

An exploratory analytical and computational study of gasifying energetic liquid fuel droplets is presented. The liquid-fuel reaction, heating, and breakup are modelled and characterized. A spherically-symmetric geometry is considered, and the problem is described by considering a general formulation capable of resolving the solution domain consisting of a liquid-phase region, a bubbly two-phase region, and a gas-phase region. The transient, two-phase, governing equations are solved numerically for various values of the nondimensional rate constant, heat of decomposition, activation energy, number of bubbles per unit mass, and ratio of gas-phase to liquid-phase thermal conductivities.

Five CMS lines, Ogu12A, Ogu13A, Ogu14A, Ogu15A and Ogu16A were selected among fifteen lines after BC7 based on superior commercial, floral and seed setting traits. Line × Tester analysis was done by taking these five CMS lines as female parent with ten diverse lines of snowball cauliflower as testers. Data were recorded for 14 important vegetative and commercial traits. For days to 50% curd initiation and days to 50% curd maturity the CMS line Ogu15A exhibited significantly high GCA effect in negative direction (−14.52 and-14.38). For marketable curd weight and marketable curd yield significantly high GCA effects were recorded in the CMS line Ogu15A (0.11; 0.10) and Ogu13A (5.28; 4.75). Among the ten testers only two genotypes, Kt-2 and EC-162587 had significantly high GCA effect for marketable curd yield. Very high and significant SCA effect has been recorded in the combination Ogu16A × Kt-25 (20.25) and Ogu15A × Kt-2 (19.72) for marketable curd yield. The CMS line, Ogu15A was involved in the most of the heterotic combinations for earliness. Average heterosis was in desirable positive direction for 7 among 14 traits. The range of average heterosis for days to 50% curd maturity was-8.55 to 25.0% and it was-32.04 to 127.91% marketable curd yield. Ogu15A was involved in maximum number of combinations for earliness and higher productivity. Highest heterosis for marketable curd yield was recorded in the combination, Ogu15A × Kt-2 (127.91%), followed by Ogu14A × Sel-26 (90.90%) and Ogu15A × Sel-26 (86.18%). The CMS lines with better combiling ability are involved with most of the heterotic combinations for different traits thus can be used for development of F1 hybrids.

Hyperplastic dental follicles are very commonly seen associated with an impacted tooth. Multiple calcifying hyperplastic dental follicles (MCHDF), a term used for multiple unerupted teeth with abundant calcifications and rests of odontogenic epithelium in enlarged dental follicles is a rare entity. Varied pattern of calcifications have been observed in such follicles. We report one such case with four patterns of calcifications and odontogenic epithelium associated with bilaterally impacted canines.

We have developed an approximate technique, based on the principles of multi-mode Gaussian optics, for studying the behaviour of shaped off-axis mirrors. We describe a mirror as an inclined phase-transforming plane, where the phase transformation across the plane is determined by the depth of the mirror as a function of position. The scattering matrix is calculated in the usual way by evaluating the overlap integrals over some surface for which the amplitudes and phases of the incoming and outgoing fields are known; because, however, the modes are not orthogonal over the surface of interest, a system of linear equations has to be solved. We demonstrate the “thin-mirror” technique by studying the behaviour of paraboloidal and ellipsoidal mirros, and we show how the performance of measured and approximate surfaces can be assessed.

Thirty-six patients with post-traumatic brain abscess were managed over 18 years. They constituted 9.3% of all brain abscesses encountered during the same period. The head injury was associated with an external compound fracture in 20, internal compounding in three and was closed in 13 patients. The mean interval between the time of injury to presentation with an abscess was 113 days. This did not differ significantly in patients with closed and compound head injury, and amongst patients who had wound sepsis and with clean wounds after the injury. The occurrence of focal neurological deficit was more frequent in patients with a closed injury ( p0.05). Twenty patients underwent primary excision of the abscess with recurrence of the abscess in one patient. Of the 14 patients in whom the abscess was initially aspirated, eight patients required a subsequent excision. Excision was required in 18 patients (94.7%) with external compound injury, five (50%) of those with closed injury and in all patients with internally compound injuries. Two patients had 'coned' and died before they could be operated upon. The operative mortality in the absence of signs of herniation preoperatively was 12.5% in patients with compound injury and none among patients with closed head injury.

Contracture of the proximal interphalangeal joint after surgery to excise Dupuytren’s disease, despite release of the contributory structures within the finger, can be caused by flexor digitorum superficialis (FDS) contracture. We describe five cases where FDS contracture was released by intramuscular tenotomy in the distal forearm. Standard postoperative therapy for Dupuytren’s fasciectomy was used and clinical review showed improved finger extension with no loss of strength. We suggest that intramuscular tenotomy of FDS in the forearm can be used safely where indicated after excision of the Dupuytren’s disease.

This University of Massachusetts, Amherst project, "Fast Pyrolysis Oil Stabilization: An Integrated Catalytic and Membrane Approach for Improved Bio-oils" started on 1st February 2009 and finished on August 31st 2011. The project consisted following tasks: Task 1.0: Char Removal by Membrane Separation Technology The presence of char particles in the bio-oil causes problems in storage and end-use. Currently there is no well-established technology to remove char particles less than 10 micron in size. This study focused on the application of a liquid-phase microfiltration process to remove char particles from bio-oil down to slightly sub-micron levels. Tubular ceramic membranes of nominal pore sizes 0.5 and 0.8 AƒÂ‚A‚µm were employed to carry out the microfiltration, which was conducted in the cross-flow mode at temperatures ranging from 38 to 45 C and at three different trans-membrane pressures varying from 1 to 3 bars. The results demonstrated the removal of the major quantity of char particles with a significant reduction in overall ash content of the bio-oil. The results clearly showed that the cake formation mechanism of fouling is predominant in this process. Task 2.0 Acid Removal by Membrane Separation Technology The feasibility of removing small organic acids from the aqueous fraction of fastmore » pyrolysis bio-oils using nanofiltration (NF) and reverse osmosis (RO) membranes was studied. Experiments were carried out with a single solute solutions of acetic acid and glucose, binary solute solutions containing both acetic acid and glucose, and a model aqueous fraction of bio-oil (AFBO). Retention factors above 90% for glucose and below 0% for acetic acid were observed at feed pressures near 40 bar for single and binary solutions, so that their separation in the model AFBO was expected to be feasible. However, all of the membranes were irreversibly damaged when experiments were conducted with the model AFBO due to the presence of guaiacol in the feed solution. Experiments with model AFBO excluding guaiacol were also conducted. NF membranes showed retention factors of glucose greater than 80% and of acetic acid less than 15% when operated at transmembrane pressures near 60 bar. Task 3.0 Acid Removal by Catalytic Processing It was found that the TAN reduction in bio-oil was very difficult using low temperature hydrogenation in flow and batch reactors. Acetic acid is very resilient to hydrogenation and we could only achieve about 16% conversion for acetic acid. Although it was observed that acetic acid was not responsible for instability of aqueous fraction of bio-oil during ageing studies (described in task 5). The bimetallic catalyst PtRe/ceria-zirconia was found to be best catalyst because its ability to convert the acid functionality with low conversion to gas phase carbon. Hydrogenation of the whole bio-oil was carried out at 125AƒÂ‚A‚°C, 1450 psi over Ru/C catalyst in a flow reactor. Again, negligible acetic acid conversion was obtained in low temperature hydrogenation. Hydrogenation experiments with whole bio-oil were difficult to perform because of difficulty to pumping the high viscosity oil and reactor clogging. Task 4.0 Acid Removal using Ion Exchange Resins DOWEX M43 resin was used to carry out the neutralization of bio-oil using a packed bed column. The pH of the bio-oil increased from 2.43 to 3.7. The GC analysis of the samples showed that acetic acid was removed from the bio-oil during the neutralization and recovered in the methanol washing. But it was concluded that process would not be economical at large scale as it is extremely difficult to regenerate the resin once the bio-oil is passed over it. Task 5.0 Characterization of Upgraded Bio-oils We investigated the viscosity, microstructure, and chemical composition of bio-oils prepared by a fast pyrolysis approach, upon aging these fuels at 90AƒÂ‚A‚ÂoC for periods of several days. Our results suggest that the viscosity increase is not correlated with the acids or char present in the bio-oils. The viscosity increase is due to formation of high molecular weight polymeric species over time. Our work also suggests that hydrogenation of the samples is beneficial in eliminating the viscosity increase. Task 6.0 Commercialization Assessment Renewable Oil International LLC (ROI) was responsible for Task 6.0, AƒÂ‚A‚ÂœCommercialization Assessment.AƒÂ‚A‚ As part of this effort ROI focused on methods to reduce char carryover in the vapor stream from the fast pyrolysis reactor and residence time of the vapor in the reactor. Changes were made in the bio-oil recovery methodology and a reactor sweep gas used to reduce vapor residence time. Cyclones were placed in the vapor stream to reduce char particulate carryover. Microfiltration of the bio-oil was also researched to remove char particulate from the bio-oil. The capital cost for these improvements would be less than 2% of the total plant capital cost.« less

A comparison is presented of Sunyaev-Zeldovich measurements for 11 galaxy clusters as obtained by Planck and by the ground-based interferometer, the Arcminute Microkelvin Imager. Assuming a universal spherically-symmetric Generalised Navarro, Frenk and White (GNFW) model for the cluster gas pressure profile, we jointly constrain the integrated Compton-Y parameter (Y 500) and the scale radius (θ500) of each cluster. Our resulting constraints in the Y500-θ500 2D parameter space derived from the two instruments overlap significantly for eight of the clusters, although, overall, there is a tendency for AMI to find the Sunyaev-Zeldovich signal to be smaller in angular size and fainter than Planck. Significant discrepancies exist for the three remaining clusters in the sample, namely A1413, A1914, and the newly-discovered Planck cluster PLCKESZ G139.59+24.18. The robustness of the analysis of both the Planck and AMI data is demonstrated through the use of detailed simulations, which also discount confusion from residual point (radio) sources and from diffuse astrophysical foregrounds as possible explanations for the discrepancies found. For a subset of our cluster sample, we have investigated the dependence of our results on the assumed pressure profile by repeating the analysis adopting the best-fitting GNFW profile shape which best matches X-ray observations. Adopting the best-fitting profile shape from the X-ray data does not, in general, resolve the discrepancies found in this subset of five clusters. Though based on a small sample, our results suggest that the adopted GNFW model may not be sufficiently flexible to describe clusters universally. © ESO, 2013., The Planck Collaboration acknowledges the support of: ESA; CNES and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MICINN and JA (Spain); Tekes, AoF and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); and DEISA (EU).

In September 1995, a project was initiated to replace the existing drive line at NASA's most unique transonic wind tunnel, the National Transonic Facility (NTF), with a single 101 MW synchronous motor driven by a Load Commutated Inverter (LCI). This Adjustable Speed Drive (ASD) system also included a custom four-winding transformer, harmonic filter, exciter, switch gear, control system, and feeder cable. The complete system requirements and design details have previously been presented and published [1], as well as the commissioning and acceptance test results [2]. The NTF was returned to service in December 1997 with the new drive system powering the fan. Today, this installation still represents the world s largest horizontal single motor/drive combination. This paper describes some significant events that occurred with the drive system during the first 15 years of service. These noteworthy issues are analyzed and root causes presented. Improvements that have substantially increased the long term viability of the system are given.

Detached mungbean (Vigna radiata L.Wilczek) leaves were inoculated with a conidial suspension of a local isolate (TI-1) of the powdery mildew pathogen (Erysiphe polygoni DC) under controlled environment conditions. Based on the latent period and severity of the infection, a rating scale of 0-5 was used to classify the host pathogen interactions. Reactions 0, 1 and 2 were considered resistant and referred to as R0, R1 and R2 while 3, 4 and 5 were classified as susceptible (S). RUM lines (resistant to powdery mildew) and their derivatives are crossed with several susceptible (reaction types 3-5) genotypes and the inheritance of the resistance was studied in the F1, F2 and F3 generations. The results showed that powdery mildew resistance in mungbean is governed by two dominant genes designated as Pm-1 and Pm-2. When both Pm-1 and Pm-2 were present, an R0 reaction was observed after inoculation with TI-1. The resistant reaction was R1 when only Pm-1 was present and R2 in the presence of Pm-2. In the absence of both Pm-1 and Pm-2, susceptible reactions 3, 4 and 5 were observed.

Aspirated intracranial fluid, in the surgical management of intracranial sepsis, may not culture an organism due to the previous administration of antibiotics. We have sought to utilise polymerase chain reaction (PCR) to determine the cause of culture-negative sepsis and in monitoring response to therapy. This was a retrospective review of five cases of Streptococcus pneumoniae intracranial sepsis. Samples were analysed using real-time quantitative PCR targeting the pneumococcal lytA gene and the number of genome copies per microlitre of sample determined. Streptococcus pneumoniae sepsis was diagnosed by PCR in five culture-negative cases comprising: ventriculitis (×3), subdural empyema and meningitis. Serial serum inflammatory markers (CRP and WBC) and number of genome copies were graphically plotted over the duration of inpatient stay for cases requiring surgical drainage of recurrent collections or external ventricular drainage. A correlation was demonstrated between change in bacterial genomic load and serum inflammatory markers, reflecting similar changes in clinical state. This is the first report of the use of serial quantitative PCR in monitoring the course of intracranial sepsis secondary to S. pneumoniae. Further work is required to determine the precise relationship between serum inflammatory markers, clinical state and bacterial load: do changes in one precede the other? Furthermore, a threshold value for number of genome copies in cerebrospinal fluid/aspirate samples has yet to be defined.

Poly(lactide) – block – poly(ethylene oxide) – block – poly(lactide) [PLA–PEO–PLA] triblock copolymers are known to form physical hydrogels in water, due to the polymer’s amphiphilic architecture. Their biodegradability has made them attractive for use as soft tissue scaffolds and other biological applications such as drug delivery. In many cases, their mechanical properties have been poorly investigated and “rules” for tuning their stiffness are missing. Often the network junction points are only physical cross-links, not covalent, and in a highly aqueous environment, these hydrogels will absorb more water, transform from gel to sol, and lose the designed mechanical properties. New insights into the self-assembly of these materials have resulted in new PLA–PEO–PLA gels with novel structural and mechanical properties. Here, we summarize our recent efforts to understand these novel hydrogels and control their mechanical properties. This is highlighted by a new approach in which the system is allowed to self-assemble and then it is covalently cross-linked to capture this self-assembled architecture. This produces hydrogels with permanent cross-links and allows their mechanical properties to be studied in much more detail.

INTRODUCTIONFractures of the distal radius are common upper limb injuries, representing a substantial proportion of the trauma workload in orthopaedic units. With ever increasing advancements in implant technology, operative intervention is becoming more frequent. As growing numbers of surgeons are performing operative fixation of distal radial fractures, an accurate understanding of the relevant surgical anatomy is paramount. The flexor carpi radialis (FCR) tendon forms the cornerstone of the Henry approach to the volar cortex of the distal radius. A number of key neurovascular structures around the wrist are potentially at risk during this approach, especially when the FCR is mobilised and placed under retractors. METHODSIn order to clarify the safe margins of the FCR approach, ten fresh frozen human cadaver limbs were dissected. The location of the radial artery, the median nerve, the palmar cutaneous branch of the median nerve and the superficial branch nerve were measured with respect to the FCR tend...

This paper proposes a fuzzy approach to classify single-channel surface electromyography (SEMG) signals for multifunctional prosthesis control. In this approach three variables root mean square, standard deviation & variance were selected for the analysis. These three parameters gave best results for discriminating hand movements from time domain analysis using SEMG. As the frequency range of SEMG signal is specified to be from 0 Hz to 400 Hz, therefore the analysis was divided into three sections of frequencies as: low(250 Hz) and band pass (70-250 Hz). This is done to establish the frequency change in the three regions for specified selected output. The three parameters were used as input variables to fuzzy logic controller for discrimination of the hand movements i.e. whether the hand is closed or open. SEMG signal was taken from below elbow position using bipolar electrodes as this part was found to be more active during expansion and contraction of muscles. Out of the three parameters standard deviation gave best results for discriminating hand movements (opening and closing). Out of three filters, low pass filter gave the best results for discriminating opening and closing movements. Further, to develop precise control of the grip prosthetic, the work is extended to multilevel SEMG control. A grip-exerciser was used to calibrate the executed force and SEMG signal. The result was a fuzzy logic controller for the accurate grip force.

Most serpins inhibit serine and/or cysteine proteases, and their inhibitory activities are usually defined in vitro. However, the physiological protease targets of most serpins are unknown despite many years of research. This may be due to the rapid degradation of the inactive serpin:protease complexes and/or the conditions under which the serpin inhibits the protease. The model organism Caenorhabditis elegans is an ideal system for identifying protease targets due to powerful forward and reverse genetics, as well as the ease of creating transgenic animals. Using combinatorial approaches of genetics and biochemistry in C. elegans, the true in vivo protease targets of the endogenous serpins can be elucidated.

An analytical and numerical study of vaporization and combustion of an isolated liquid hydrocarbon droplet containing a single metal particle in its core is presented. The objective is to formulate a simplified vaporization model that can be used in spray combustion calculations. Further, the model is extended to include the combustion of the liquid fuel, so that ignition characteristics of the metal particle can be studied. The gas phase includes the effects of variable thermophysical properties and nonunitary Lewis number. The liquid phase includes the effects of transient heating and circulation. Results are presented for both a spherically symmetric configuration, and an axisymmetric case, where the liquid motion is analytically given. Calculations are made for both liquid vaporization without combustion and vaporization followed by combustion. The effects associated with varying solid loading are studied. The vaporization rates for a composite droplet are found to be close to those for a corresponding all-liquid droplet. Ignition times for the metal particle are found to depend on the solid mass loading, and can be several times larger than the liquid fuel burnout time. The heat transfer to the particle is convection dominated.

Despite the undeniable success of tyrosine kinase inhibitors (TKI) in treatment of Bcr-Abl-dependent leukemia, the issue of Bcr-Abl-positive stem cells that persist in the blood of patients with major molecular remission or complete molecular remission remains unresolved. Our data indicate that the frequency of BCR-ABL+CD34+CD38− cells was 1–2% in the blood of patients in remission.1 This is with agreement with clinical data showing that ~60% of patients relapse after TKI discontinuation.2 A subset of patients will achieve deep molecular remission, and in these patients TKI treatment will be discontinued. Forty to fifty percent of these patients will maintain treatment-free remission; however, BCR-ABL+ cells are still detectable.3 We believe that heterogeneity of leukemia stem cell (LSC) potential and immune/microenvironmental regulation allow these cells to be present even without the recurrence of leukemia. Co-culture with BM mesenchymal cells (MSC) enhances survival and maintenance of CML stem cells as assessed by in vitro analysis of CML CD34+CD38− cells or by engraftment of CML CD34+ cells in NSG mice.4 We found that the N-cadherin receptor plays an important role in MSC-mediated protection of CML stem cells from TKI. N-cadherin-mediated adhesion to MSC was associated with increased cytoplasmic N-cadherin–β-catenin complex formation, as well as enhanced β-catenin nuclear translocation and transcriptional activity. Increased exogenous Wnt-mediated β-catenin signaling played an important role in MSC-mediated protection of CML progenitors from TKI treatment. These results reveal novel mechanisms of CML LSC resistance to TKI treatment, and suggest new targets for treatment. We have also used an SCL-tTA /TRE-BCR-ABL transgenic mouse model based on targeted Bcr-Abl expression in murine hematopoietic stem cells (HSC) via a Tet-regulated SCL promoter to study CML stem cell regulation and targeting. In this model, withdrawal of tetracycline leads to BCR-ABL expression in murine HSC and development of a CML-like disorder with leukocytosis and splenomegaly.5 We have used this model to characterize the main features of the LSC. Long-term hematopoietic stem cell (LT-HSC) numbers were markedly reduced in the BM of BCR-ABL mice, but were increased in the spleen compared with controls. Long-term engrafting and leukemia-initiating capacity is restricted to BCR-ABL cells with LT-HSC phenotype. Cell cycling of BCR-ABL LT-HSC was increased compared to control mice. We observed that both reduced homing to the BM and enhanced egress from the BM to the spleen contribute to altered LT-HSC localization in BCR-ABL mice. However, we also found that there are altered chemokine and cytokine levels in the BM of BCR-ABL mice compared to control mice, and we confirmed that altered chemokine and cytokine expression in CML BM may persist after TKI treatment.6 CML LT-HSC demonstrated reduced homing and retention in the bone marrow (BM), related to decreased CXCL12 expression in CML BM, resulting from increased G-CSF production by leukemia cells. In transplantation experiments, we observed that CML stem cells had a competitive advantage in the CML BM microenvironment in comparison to normal LT-HSC. Leukemia-induced abnormalities in cytokine expression selectively suppressed normal stem cell growth and enhanced LSC growth in CML BM. This observation was confirmed in an in vitro setting, where CML stem cells had a growth advantage over the normal HSC upon growth in CML versus normal conditioned medium. Our data indicated that IL-1α, IL-1β, TNF-α, MIP-1α and MIP-1β contributed to enhanced growth of leukemic compared to normal stem cells. We are currently assessing whether inhibition of the major pro-inflammatory cytokine IL-1 can lead to reduced leukemia development and prolonged survival of CML mice, as well as target primary CML CD34+CD38−CD90+ cells. Our data show that maintenance of HSC depends on interaction with their niche, and these interactions become abnormal in the pathophysiology of leukemia and contribute to persistence of leukemic stem cells in the niche. Interestingly, in limiting dilution transplantation experiments, we have observed that Bcr-Abl+ LT-HSC have a heterogeneous leukemogenic capacity. In gene expression profiling we identified MPL as one of the genes that are differentially expressed in LT-HSC isolated from leukemic and non-leukemic mice. We are currently assessing the role of MPL in the leukemogenic potential of Bcr-Abl+ LT-HSC, and as a potential target for LSC-directed therapeutics.

An internal physiological ripening disorder, “spongy tissue”, affects about 30% of ‘Alphonso’ mangoes, the most popular Indian cultivar. Fruits show no external symptoms at harvest or on ripening but cutting reveals internal damage to the mesocarp which adversely affects fruit quality. Both fully grown green, unripe mangoes and ripe fruits show spongy tissue. A non-destructive x-ray inspection method has been developed to detect affected mangoes. X-ray photographs and x-ray images of fruits having spongy tissue show dark grey patches corresponding to internal cavities in contrast to light grey areas of healthy flesh. The method could be used for quality control for on-line detection and separation of mangoes having spongy tissue prior to packaging, by monitoring x-ray screen images.

This study investigates the effects of exposure to intermittent hypoxia on cardiovascular autonomic control and metabolic function in obese children with obstructive sleep apnea (OSA). Each subject underwent: (1) a polysomnography; (2) morning fasting blood samples and a subsequent FSIVGTT; (3) noninvasive measurement of respiration, arterial blood pressure, and heart rate during supine and standing postures. Assessment of adiposity was performed using a DEXA scan. From these measurements, we deduced the pertinent sleep parameters, Bergman minimal model parameters and the parameters characterizing a minimal model of cardiovascular variability. Results suggest that intermittent hypoxia in OSA contributes independently to insulin resistance and autonomic dysfunction in overweight children.

Currently there is no reliable diagnostic marker to distinguish between the subgroups of idiopathic inflammatory myopathies (IIMs), i.e. dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). Membrane attack complex (MAC) has been shown to be involved in the pathogenesis of dermatomyositis but its role as a diagnostic marker has not been evaluated.To assess the diagnostic utility of MAC deposition in distinguishing dermatomyositis from other neuromuscular disorders.Immunohistochemical detection of MAC deposition on endomysial microvessels was carried out on 127 muscle biopsies comprising of 21 cases of dermatomyositis, 42 other IIMs and 64 non-IIM neuromuscular diseases.MAC deposition showed a high sensitivity (80.9%) and specificity (85%) to differentiate DM from other IIMs. Its specificity was higher (98.4%) in discriminating DM from non-IIM muscular diseases and IIM from non-IIMs.MAC deposition can serve as a reliable marker to distinguish DM from other IIMs (i.e. PM and IBM) as well as from non-IIM diseases. It can also serve as a useful adjunct in diagnosis of IIMs when there is diagnostic dilemma with their morphologic similarities. These results provide further credence to the long-standing view that MAC-mediated capillary destruction is involved in the immunopathogenesis of DM.

An analytical and numerical study of combustion of an isolated liquid hydrocarbon and a liquid hydrocarbon droplet containing a metal particle is presented. The objective is to formulate a simplified combustion model, which accounts for the unsteady gas phase. Further, the model is extended to include an idealized configuration of metal slurry droplets in which a metal particle is enveloped by liquid hydrocarbon, so that ignition characteristics of the metal particles can be studied. The governing spherically symmetric, unsteady conservation equations are simplified using the Schvab-Zel'dovich and von Mises transformations. The liquid-solid phase includes the effect of transient heating. Results indicate that the burning rates for a composite droplet are close to those for a corresponding all-liquid droplet. It is found that in absence of forced convection, unless the ambient air is preheated to large temperatures comparable to the aluminum oxide melting point, the flame does not possess sufficie...

This prospective study investigated a cohort of 59 scaphoid waist fractures which were treated nonoperatively in a below-elbow plaster cast for 4 weeks and then underwent a Week 4 CT scan to assess displacement and progress to union. Forty-three were classed as undisplaced and 37 of these 43 were also classed as ‘united’. All the 37 undisplaced and ‘united’ fractures united with up to 8 weeks’ cast immobilisation, including 26 which were taken out of plaster at 4 weeks and mobilised. We conclude that scaphoid waist fractures which appear to be undisplaced and united on a week 4 CT scan will unite, and may not need to be immobilised in a plaster cast for more than 4 weeks. Such a treatment policy may reduce the period of disability and time off work associated with nonoperative treatment.

A 28-year-old woman presented to the A&E with acute severe bleeding from a caesarean section scar. Bleeding coincided with her menstruation and on that occasion, she had lost an estimated 500 ml of...

Hydrophobically modified alginate (HMA) was synthesized by an amide coupling reaction with alkyl amine (C8) at low pH. At and above a critical concentration, HMA forms reversible physical gel in aqueous media due to hydrophobic interactions. Unreacted guluronic units of alginate were further crosslinked with divalent cations, such as Ca2+, which resulted in a gel having elastic moduli ∼ 100 kPa. Interplay of the two different gelation mechanisms, hydrophobic association and chemical crosslinking, enables us to tune the mechanical properties of the system. Solubility of a model lipophilic drug (Sulindac) was found to be improved at least by a factor of 5 compared to neat polymer, presumably due to preferential uptake of the drugs by micelles formed by hydrophobic moiety. Controlled and extended release of sulindac was observed for upto 5–6 days, probably due to stronger crosslinked alginate units surrounding the drug loaded hydrophobic rich domains.

Poly(lactic acid)-poly(ethylene oxide)-poly(lactic acid) (PLA-PEO-PLA) triblock copolymer hydrogels are a promising biomaterial, with applications to drug delivery and cell scaffolds for tissue engineering. Using L-lactic acid gives PLLA-PEO-PLLA, which has stereoregular end blocks. The resulting system forms lamellae with hydrophobic semi crystalline domains of PLLA with hydrophilic domains of PEO connecting them. Gelation is achieved by raising the temperature of the polymer/water mixture, and this study focuses on the effect on the nano- and microscale structures of the gel that the gelation temperature has. By confocal microscopy, we determine the average particle size on the microscale increases from 2.3 µm to 3 µm from an increase in gelation temperature of 40°C to 80°C. Meanwhile, small angle x-ray scattering indicates that the nanoscale structures, the lamellae, are unchanged over the same range. This implies that an annealing effect is occurring. The lamellae align to a greater degree with a higher temperature, increasing the size of the semi-crystalline domains.

Research has shown how useful alginate, a natural polymer found in brown algae, is in drug delivery engineering. However, the addition of various substances that form gel networks with alginate improves the mechanical properties of the gels formed. This study examines how gels from alginate and cellulose behave mechanically to determine which cellulose shows the best improvement for future drug delivery research. Mechanical properties studied include swelling, gelation, and rheological characteristics. Hydrophobically enhanced ethyl hydroxyethyl cellulose (EHEC) with various degrees of polymerization was used in the study. Higher concentrations of cellulose in the mixture yielded more solid-like behavior from the alginate-EHEC gel networks. With the improvement of mechanical durability of drug encapsulation substances, longer lasting drug release can be used to reduce frequency of dosage per medication.

The University of Massachusetts Amherst Institute for Cellular Engineering (ICE) has developed a novel interdisciplinary graduate training program in cellular engineering, the NSF-funded ICE IGERT program. Engineering cellular form and function is the basis for many ventures in the biomedical and biotechnology industries in Massachusetts and across the U.S., including design of bioremediation processes for contaminated site cleanup, generation of artificial organs and tissues, and production of biologic pharmaceuticals. Students focus in one of three interrelated cellular engineering thrust areas: 1) Applied Systems Biology, 2) Cell Delivery and 3) Protein Engineering. Key features of the program include a unifying course to train both life scientists and engineers/physical scientists in the fundamentals of cellular engineering, hands-on laboratory modules on state-of-the-art techniques, a weekly research seminar series with mentoring component, and formal professional development activities including team-building and ethics. This IGERT is unique in that the leadership is all-female and the faculty participants are 45% female and 15% non-white, and we recruit diverse students through collaboration with the Northeast Alliance for Graduate Education and the Professoriate (NEAGEP) program. The primary outcome of this novel training program is establishment of a well-trained diverse workforce in state-of-the art technologies that is poised to be leaders in cellular engineering both in academia and industry.

Emulsions are usually generated in high-pressure homogenization chambers. The flow field is these units are typically highly turbulent and chaotic, and mechanisms for drop formation under these conditions are not well understood. In this paper, we have applied the PBE modeling approach to droplet break-up in a high pressure homogenizer using mechanistic functions for breakage rate. We have compared our modeling results to experimental data that we have obtained on a model oil-in-water emulsion. In principle, once these functions are known, the PBE approach can be used in a predictive manner to aid in the selection of process and product variables that will lead to the desired drop size distribution. This was verified for a number of test cases by changing product properties and homogenizing conditions. We observed that the population balance model did a reasonably good job of predicting the drop size distribution and therefore look promising. For cases where the model fails, we discuss strategies for improving predictions for these types of systems.

The goals of the REU on Cellular Engineering at the University of Massachusetts Amherst are to engage undergraduate students in cross-disciplinary research at the interface of life sciences and engineering/physical sciences and to increase the number and diversity of domestic students pursuing advanced degrees and careers in bioengineering and related fields. Our program distinguishes itself through a high level of faculty and institutional commitment to undergraduate research, larger scale collaborative research activities, and dedication to underrepresented populations. Unique aspects include: (i) a campus-wide “REU network” and collaboration with NEAGEP to promote recruiting of underrepresented students; (ii) close interactions between participants, graduate students, and faculty other than mentors through regular research seminars; (iii) a Professional Development seminar that includes training in interdisciplinary team-building, ethics, mentoring, and career skills; and (iv) promotion of relationships between REU and graduate students through interactions with the ICE IGERT and CBI programs. To date, 21 students have participated, including 12 from underrepresented groups (57%): 9 women (43%), 4 minorities (19%) and one disabled student (4.8%). Nine participants were eligible to enter graduate school in Fall 2008, and of these seven (77%) are in PhD programs related to cellular engineering, including two women and one disabled student.

A one-dimensional computational analysis is performed to investigate the liquid-fueled combustion instability. The governing gas-phase equations in an Eulerian frame are solved using an implicit scheme based on the implicit continuous-fluid Eulerian (ICE) method. The liquid-phase equations in a Lagrangian frame are solved using the Effective Conductivity Model. Dirichlet boundary conditions are imposed at the combustor inlet, with a time-dependent inlet gas velocity. Neumann boundary conditions with the short-nozzle approximation are employed at the outlet. Spray characteristics, mixture ratio profiles, and combustor geometry are amongst the parameters studied. Both stable and unstable modes of combustor operation are found. Under certain conditions, limited cycle behavior of pressure, temperature, and velocity oscillations is obtained. The frequency of oscillation is approximately the fundamental resonant frequency of a chamber with one closed end and one open end, and is independent of the forcing function frequency. Large-scale temperature or entropy waves convected with the gas velocity are seen for some cases. The parameter domains of stable/unstable combustor operation have been plotted. Vaporization is rate controlling and the ratio of the period of oscillation to droplet heating time and the ratio of residence time to droplet heating time emerge as important parameters.

ABA triblock copolymers in solvents selective for the midblock are known to form associative micellar gels. We have modified the structure and rheology of ABA triblock copolymer gels comprising poly(lactide)−poly(ethylene oxide)−poly(lactide) (PLA−PEO−PLA) through addition of a clay nanoparticle, laponite. Addition of laponite particles resulted in additional junction points in the gel via adsorption of the PEO corona chains onto the clay surfaces. Rheological measurements showed that this strategy led to a significant enhancement of the gel elastic modulus with small amounts of nanoparticles. Further characterization using small-angle X-ray scattering and dynamic light scattering confirmed that nanoparticles increase the intermicellar attraction and result in aggregation of PLA−PEO−PLA micelles.

Extensor Carpi Radialis Longus (ECRL) avulsion is a rare injury which follows resisted wrist hyperflexion. Treatment of this condition with open reduction and internal fixation is not previously described in the literature, and treatment with plaster immobilisation or k-wire fixation requires a prolonged period of immobilisation. We believe that open reduction and internal fixation of these fractures with early mobilisation will result in the best possible wrist function. We describe a sign to raise the index of suspicion for this injury: a palpable bone lump on the dorsum of the hand in the presence of wrist extensor pain or weakness after wrist hyperflexion injury is a sign of wrist extensor avulsion.