bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet depletion in mice increases mortality after thermal injury
Authors: Fujimi Satoshi , MacConmara Malcolm P. , Maung Adrian A. , Zang Yan , Mannick John A. , Lederer James A. , Lapchak Peter H. 
Published: February 2006

AbstractPlatelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P < .001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P < .01) and neutrophils (P < .05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNFα (P < .001), IL-6 (P < .001), and MCP-1 (P < .05) were also elevated by 24 hours whereas levels of TGFβ1 were reduced between 24 and 36 hours following injury in platelet-depleted mice (P < .001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFβ1 modulate the systemic inflammatory response occurring after injury.
Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10
Authors: Zernecke Alma , Liehn Elisa A. , Gao Ji-Liang , Kuziel William A. , Murphy Philip M. , Weber Christian 
Published: February 2006

AbstractThe chemokine RANTES has been implicated in neointimal hyperplasia after arterial injury. We analyzed the differential role of the RANTES receptors CCR1 and CCR5 by genetic deletion in apolipoprotein E–deficient mice. Deficiency in CCR5 significantly reduced neointimal area after arterial wire injury, associated with a decrease in macrophages, CD3+ T lymphocytes, and CCR2+ cells. In contrast, CCR1 deficiency did not affect neointimal area or cell content. Deletion of CCR5 entailed an up-regulation of the anti-inflammatory cytokine interleukin 10 (IL-10) in neointimal smooth muscle cells, and its antibody blockade reversed effects in CCR5–/– mice. Conversely, proinflammatory interferon γ was increased in the neointima of CCR1–/– mice, and its blockade unmasked a reduction in macrophage recruitment. Our data indicate that CCR5 is more crucial than CCR1 for neointimal plaque formation, and that its attenuation in CCR5–/– mice is due to an atheroprotective immune response involving IL-10. This harbors important implications for targeting chemokine receptors in vascular remodeling.
BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate–treated patients with CML
Authors: Press Richard D. , Love Zac , Tronnes Ashlie A. , Yang Rui , Tran Thuan , Mongoue-Tchokote Solange , Mori Motomi , Mauro Michael J. , Deininger Michael W. , Druker Brian J. 
Published: February 2006

AbstractAlthough most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase–polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P < .001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.
Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma
Authors: Stewart Douglas A. , Bahlis Nizar , Valentine Karen , Balogh Alex , Savoie Lynn , Morris Donald G. , Jones Allan , Brown Chris , Russell James A. 
Published: February 2006

AbstractA single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m2, etoposide 800 mg/m2, Ara-C 1600 mg/m2, melphalan 140 mg/m2 (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.
SHIP deficiency enhances HSC proliferation and survival but compromises homing and repopulation
Authors: Desponts Caroline , Hazen Amy L. , Paraiso Kim H. T. , Kerr William G. 
Published: February 2006

AbstractThe SH2 domain–containing inositol 5′-phosphatase-1 (SHIP) has the potential to modulate multiple signaling pathways downstream of receptors that impact hematopoietic stem cell (HSC) biology. Therefore, we postulated that SHIP might play an important role in HSC homeostasis and function. Consistent with this hypothesis, HSC proliferation and numbers are increased in SHIP–/– mice. Despite expansion of the compartment, SHIP–/– HSCs exhibit reduced capacity for long-term repopulation. Interestingly, we observe that SHIP–/– stem/progenitor cells home inefficiently to bone marrow (BM), and consistent with this finding, have reduced surface levels of both CXCR4 and vascular cell adhesion marker-1 (VCAM-1). These studies demonstrate that SHIP is critical for normal HSC function, homeostasis, and homing.
A mathematical model for supplying air-cooling for a building using a packed bed
Authors: Marewo GT , Henwood DJ 
Published: February 2006

The cooling system at the Harare International School uses a packed bed system for storing the coldness of the night-time to be used later for day-time airconditioning. A two-phase mathematical model is described for the packed bed which includes heat dispersion in the fluid, and heat loss to the environment. This is in contrast to other studies, where at least one of these terms is neglected to simplify the mathematical model. A numerical method for obtaining a solution is proposed and implemented. Using measured inlet temperatures, the measured and predicted outlet temperatures of the bed show good trend agreement. The differences in detail are examined through sensitivity analyses for both the heat convection transfer and air velocity. It is apparent that adjusting these parameters can increase the agreement between the predicted and measured data. A parametric study for heat storage with various materials and bed sizes is given, which indicates how the code may be used as a tool for improving design and operational parameters. Practical application: A mathematical model of a packed bed is described; the bed is made up of fluid flowing over solid material with heat interchange between the two. The solid material is idealized as spheres and the fluid temperature is assumed uniform in a cross-section of the bed. The model includes heat interchange between the bed and its surrounding environment and allows for time varying fluid velocity. The input data is the inlet temperature to the bed, which may be measured. The comparison with measured data may be helpful to anyone attempting to develop and test a similar model. The sensitivity tests give an understanding of the significance of some of the parameters involved. The Appendix gives a mathematical statement of the problem and an outline of an approach to developing computer code for a numerical solution.
High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age
Authors: van Dijk Marije , Mulder Paul , Houdijk Mieke , Mulder Jaap , Noordam Kees , Odink Roelof J. , Rongen-Westerlaken Ciska , Voorhoeve Paul , Waelkens Johan , Stokvis-Brantsma Jet , Hokken-Koelega Anita 
Published: February 2006

Context: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks.
Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses.
Patients: Thirty-six prepubertal short SGA children were the subjects of this study.
Intervention: Subjects received 1 (group A) or 2 (group B) mg GH/m2·d.
Main Outcome Measures: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured.
Results: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P &lt; 0.009). In group B, maximum GH levels increased from 43.9–161 mU/liter (P &lt; 0.0002), and in group A, from 57.2–104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A.
Conclusion: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range.
Increased Activation of Nuclear Factor κB Triggers Inflammation and Insulin Resistance in Polycystic Ovary Syndrome
Authors: González Frank , Rote Neal S. , Minium Judi , Kirwan John P. 
Published: February 2006

Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS).
Objective: The purpose of this study was to determine the effects of hyperglycemia on nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS.
Design and Setting: This was a prospective controlled study conducted at an academic medical center.
Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese).
Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion.
Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P &lt; 0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. −14.1 ± 10.9, P &lt; 0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P &lt; 0.04) and plasma testosterone (r = 0.49; P &lt; 0.006) and correlated negatively with ISOGTT (r = 0.39; P &lt; 0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (−22.3 ± 3.2 and −17.0 ± 5.0 vs. 8.4 ± 11.8, P &lt; 0.02).
Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.
A Novel Thyroid Hormone Receptor-β Mutation That Fails to Bind Nuclear Receptor Corepressor in a Patient as an Apparent Cause of Severe, Predominantly Pituitary Resistance to Thyroid Hormone
Authors: Wu Sharon Y. , Cohen Ronald N. , Simsek Enver , Senses Dursun A. , Yar Nese E. , Grasberger Helmut , Noel Janet , Refetoff Samuel , Weiss Roy E. 
Published: February 2006

Context: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of variable tissue hyporesponsiveness to thyroid hormone (TH).Objective: We report a newborn who presented with severe RTH (Mkar) with serum TSH 1500 mU/liter and free T3 greater than 50 pm (normal 3.1–9.4) and free T4 25.3 pm (normal 12–22). We hypothesized that the RTH was due to reduced ligand binding and/or abnormal interaction with nuclear cofactors.Design: These were prospective in vivo and in vitro studies.Setting: The study was conducted at a tertiary care university hospital.Patients: Patients included a newborn child and two other subjects with RTH.Intervention: The effect of various TH-lowering agents in the subject with RTH was studied. In vitro studies including EMSA and mammalian two-hybrid assay as well as in vitro transfection studies were conducted.Main Outcome Measures: Sequencing of the TH receptor (TR)β and in vitro measurements of receptor-cofactor interaction were measured.Results: Sequencing of the TRβ demonstrated a de novo heterozygous mutation, 1590_1591insT, resulting in a frameshift producing a mutant TRβ (mutTR)-β with a 28-amino acid (aa) nonsense sequence and 2-amino acid carboxyl-terminal extension. The Mkar mutation was evaluated in comparison to three other TRβ frameshift mutations in the carboxyl terminus. EMSA demonstrated that the Mkar mutTRβ1 had impaired ability to recruit nuclear receptor corepressor but intact association with silencing mediator of retinoid and thyroid receptor (SMRT).Conclusion: Our data suggest that alterations in codons 436–453 in helix 11 result in significantly diminished association with nuclear receptor corepressor but not SMRT. This novel mutTRβ demonstrates nuclear corepressor specificity that results in severe predominantly pituitary RTH due to impaired release of SMRT.
Global positioning system-based vehicle control for automated parking
Authors: Zhu C , Rajamani R 
Published: February 2006

This paper addresses control system design for parking of an automated vehicle. The challenge in the control design task for parking arises from the fact that the vehicle constitutes an underactuated non-holonomic system. There are three generalized coordinates to be controlled but only two constrained control inputs. A control system designed to track a two-piece trajectory is developed with only some of the degrees of freedom being controlled in each piece of the trajectory. Constraints on the available parking space, the lateral distance available, and steering limits are taken into consideration in the trajectory design. The trajectory design and control system ensure that the vehicle can reach any desired final point with any desired final orientation. A major portion of the paper concentrates on experimental implementation of the control system. The experimental demonstration is carried out on a truck using a differential global positioning system (GPS) to sense the position of the vehicle. Experimental results show that the truck is able to maintain a spacing accuracy better than 40 cm in tracking the desired trajectory while being driven backwards.
Some aspects concerning the geometry of a hinged engine with a variable compression ratio
Authors: Clenci A , Descombes G , Podevin P , Hara V 
Published: February 2006

An improvement in automotive fuel consumption has been for many years the most important challenge in engine development. In a century of automotive spark ignition engine development, only two parameters were subject to automatic control: the air-fuel ratio and spark advance. Ever since, a wide range of technologies has been developed in order to improve fuel economy further. The following strategy was used: the identification of the sources of losses in the conventional spark ignition engine and then the attempt to reduce them one by one. The potential of these technologies needs to be evaluated by a cost and consumption benefit trade-off and all these, of course, without affecting the power level. In this context, the authors are about to develop a variable geometrical compression ratio engine, in order to overcome the main drawback of the spark ignition engine: the continuous variation of the real rate of compression, caused by the load control. The concept of the variable geometrical compression ratio (VCR) engine is the subject of a patent and consists of a hinged mechanism. It is an intrinsic, automatic self-regulation system with a fast response time and at the same time is a natural development of the classic engine. So far, two prototypes have been designed and tested. The paper presents some specific features regarding hinge position choice. The following are taken into consideration: the upper block rotational angle, added angle of the piston, tipping torque, and relative motion of the camshaft with respect to the crankshaft.
Computational study of the effects of the throat diameter of the piston bowl for the performance and emissions of a high-speed direct-injection diesel engine
Authors: Zhu Y , Zhao H 
Published: February 2006

The purpose of this study is to investigate computationally the effect of the bowl shape with different throat diameters associated with different re-entrant lips using an experimentally validated KIVA3V-based computational fluid dynamics (CFD) program. In order to investigate individually the effects of the throat diameter and the re-entrant lip shape with the minimum interactive effects on other parameters, the bowl pip height and width were changed in order to maintain the same bowl height and volume. Three bowls, namely the baseline bowl, a bowl with increased throat diameter with limited pip height, and a bowl with increased throat diameter with the same pip height as the baseline, were investigated at the three speeds 4000 r/min maximum power, 2000 r/min maximum torque with three injector protrusions and three injection timings, and 1600 r/min part-load with two EGR fraction and injection timings respectively. It was found that the bowl with larger throat diameter and high pip has the best air-fuel mixing of all three bowls.
Influence of hyaluronic acid on the time-dependent friction response of articular cartilage under different conditions
Authors: Bell C J , Ingham E , Fisher J 
Published: February 2006

Therapeutic lubricant injections of hyaluronic acid are a relatively recent treatment for osteoarthritis. Their efficacy however, in vivo has been subject to much debate. Frictional properties of cartilage-cartilage contacts under both static and dynamic loading conditions have been investigated, using healthy cartilage and cartilage with a physically disrupted surface, with and without the addition of a therapeutic lubricant, hyaluronic acid. Most of the cartilage friction models produced typical time-dependent loading curves, with a rise in static friction with loading time. For the dynamic loading conditions the rise in friction with loading time was dependent on the spatial (and time) variation in the load on the cartilage plate. For sliding distances of 4 mm or greater, when the cartilage plate was unloaded during sliding, the dynamic friction remained low whereas, with shorter sliding distances, the dynamic friction increased with increasing loading time. Static friction was higher than dynamic friction (under the same tribological conditions). The ‘damaged’ cartilage models produced higher friction than healthy cartilage under equivalent tribological conditions. It was shown that hyaluronic acid was an effective boundary lubricant for articular cartilage under static conditions with both healthy and damaged cartilage surfaces. Hyaluronic acid was less effective under dynamic conditions. However, these dynamic conditions had low friction values with the control lubricant because of the effectiveness of the intrinsic biphasic lubrication of the cartilage. It was only under the tribological conditions in which the cartilage friction was higher and rising with increasing loading time because of depletion of the intrinsic biphasic lubrication, that the role of hyaluronic acid as an effective therapeutic lubricant was demonstrated.
The biomechanics of abfraction
Authors: Rees J S 
Published: February 2006

The role of occlusal loading in the development of non-carious cervical lesions is becoming increasingly prominent. It is suggested that high occlusal loads result in large stress concentrations in the cervical region of the teeth. These stresses may be high enough to cause disruption of the bonds between the hydroxyapatite crystals, eventually resulting in the loss of cervical enamel. This article reviews the evidence to support the thesis that occlusal loading can contribute to the process of non-carious cervical tooth loss or abfraction. It also reviews the potential interactions between occlusal loading and erosion that may contribute to non-carious cervical tooth loss.