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UNLABELLED: This study reports on a numerical investigation of transport behavior of indoor airflow and size-dependent particulate matter (PM) in multi-room buildings. An indoor size-dependent PM transport approach, combining the Eulerian large-eddy simulation of turbulent flow with the Lagrangian particle trajectory tracking, was developed to investigate indoor airflow pattern and PM1/PM2.5/PM10 removal efficiency in naturally ventilated multi-room buildings. A displacement ventilation with a measured indoor PM10 profile in Taipei Metropolis as the initial condition was carried out to characterize spatial and temporal variations of indoor PM1/PM2.5/PM10 removal behavior. The effects of indoor airflow pattern on particle transport mechanisms, e.g., deposition, suspension, migration and escape, were analyzed. Two comparison scenarios, which considered the effects of no indoor partition and different air change rate, respectively, were also conducted. In comparison with the effectiveness of PM1/PM2.5/PM10 removal, the simulated results showed that coarse particles were easier to be removed out of the building than fine particles. Natural ventilation was not an effective way to remove fine particles such as PM1 and PM2.5 in a multi-room building. Indoor partitions can impede 12% of the mean streamwise velocities and significantly increase 30-50% turbulence intensities. However, indoor partitions increased particle deposition and decreased particle escape. As a result of the two opposite particle removal mechanisms, i.e., deposition and escape, the impact of indoor partitions on PM1/PM2.5/PM10 removal behavior was not as significant as the results of airflow velocities. PRACTICAL IMPLICATIONS: This work developed a computational fluid dynamics technique to investigate indoor airflow patterns and PM1/PM2.5/PM10 removal ability in ventilated multi-room buildings. The results of this paper can help to identify adequate PM1/PM2.5/PM10 cleaning procedure and provide useful size-dependent PM control strategy in multi-room buildings.

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The rat forelimb compression model has been used widely to study bone response to mechanical loading. We used strain gages to assess load sharing between the ulna and radius in the forelimb of adult Fisher rats. We used histology and peripheral quantitative computed tomography (pQCT) to quantify ulnar bone formation 12 days after in vivo fatigue loading. Lastly, we developed a finite element model of the ulna to predict the pattern of surface strains during compression. Our findings indicate that at the mid-shaft the ulna carries 65% of the applied compressive force on the forelimb. We observed large variations in fatigue-induced bone formation over the circumference and length of the ulna. Bone formation was greatest 1-2 mm distal to the mid-shaft. At the mid-shaft, we observed woven bone formation that was greatest medially. Finite element analysis indicated a strain pattern consistent with a compression-bending loading mode, with the greatest strains occurring in compression on the medial surface and lesser tensile strains occurring laterally. A peak strain of -5190 microepsilon (for 13.3N forelimb compression) occurred 1-2 mm distal to the mid-shaft. The pattern of bone formation in the longitudinal direction was highly correlated to the predicted peak compressive axial strains at seven cross-sections (r2 = 0.89, p = 0.014). The in-plane pattern of bone formation was poorly correlated to the predicted magnitude of axial strain at 51 periosteal locations (r2 = 0.21, p < 0.001), because the least bone formation was observed where tensile strains were highest. These findings indicate that the magnitude of bone formation after fatigue loading is greatest in regions of high compressive strain.

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The anabolic effect of mechanical loading on bone tissue is modulated by loading frequency. The objective of this study was to characterize the new bone formation on the periosteal and endocortical surfaces of the ulnar diaphysis in adult, female rats in response to controlled dynamic loading and to examine the interactions between strain magnitude, loading frequency, and bone formation rate (BFR/BS) for frequencies ranging from 1 to 10 Hz. Cyclic, compressive loading was applied to the ulnas of 60 adult, female rats divided into 12 loading groups. Loading was applied for 360 cycles/day with peak loads ranging from 4.3 to 18N at frequencies of 1, 5, and 10 Hz. After 2 weeks of loading, bone formation on the periosteal and endocortical surfaces of the ulna was quantified using double-label histomorphometry on transverse sections obtained at the middiaphysis. Periosteal bone formation increased in a dose-response manner with peak load at each of the three loading frequencies tested. Loading frequency significantly affected the x intercepts and slopes of the peak strain versus BFR/BS (p < 0.001) and peak strain versus mineralizing surface (MS/BS; p < 0.001) curves. Periosteal osteogenesis was best predicted by a mathematical model that assumed: (1) bone cells are activated by fluid shear stresses and (2) that stiffness of the bone cells and the extracellular matrix near the cells increases at higher loading frequencies because of viscoelasticity. Consequently, mechanotransduction appears to involve a complex interaction between extracellular fluid forces and cellular mechanics.

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To test the hypothesis that factors associated with bone strength (i.e., volumetric bone mineral density [vBMD], geometry, and microstructure) have heritable components, we exploited the 12 BXH recombinant inbred (RI) strains of mice derived from C57BL/6J (B6; low bone mass) and C3H/HeJ (C3H; high bone mass) progenitor strains. The femurs and lumbar vertebrae from each BXH RI strain were characterized for phenotypes of vBMD, microstructural, biomechanical, and geometrical properties. Methods included bending (femur) and compression (vertebra) testing, peripheral quantitative computed tomography (pQCT), and microcomputed tomography (microCT). Segregation patterns of femoral and vertebral biomechanical properties among the BXH RI strains suggested polygenic regulation. Femoral biomechanical properties were strongly associated with femoral width in the anteroposterior (AP) direction and cortical thickness--geometric properties with complex genetic regulation. Vertebral vBMD and biomechanical properties measured in BXH RI strains showed a greater variability than either B6 or C3H progenitors, suggesting both progenitor strains have independent subsets of genes that yield similar vBMD and strength. The microCT and pQCT data suggested that the distribution of vertebral mineral into cortical and trabecular compartments is regulated genetically. Although the B6 and C3H progenitors had similar vertebral strength, their vertebral structures were markedly different: B6 had good trabecular bone structure and modest cortical bone mineral content (BMC), whereas C3H had high cortical BMC combined with a deficiency in trabecular structure. These structural traits segregated independently in the BXH RI strains. Finally, vertebral strength was not correlated consistently with femoral strength among the BXH RI strains, suggesting genetic regulation of bone strength is site specific.

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Bone tissue responds to elevated mechanical loading with increased bone formation, which is triggered either directly or indirectly by the mechanical strain engendered in the bone tissue. Previous studies have shown that mechanical strain magnitude must surpass a threshold before bone formation is initiated. The objective of this study was to estimate the strain thresholds at three different locations along the ulna of adult rats. We hypothesized that the strain threshold would be greater in regions of the ulna habitually subjected to larger mechanical strains. New bone formation was measured on the periosteal and endocortical surfaces of the ulnar diaphysis in adult female rats exposed to controlled dynamic loading. Axial, compressive loading was applied daily at five different magnitudes for a period of 2 weeks. Bone formation rate (BFR) was measured, using double-label histomorphometry at the ulnar middiaphysis and at locations 3 mm proximal and 3 mm distal to the middiaphysis. Loading induced lamellar bone formation on the periosteal surface that was greater at the distal ulnar location and lower at the proximal location when compared with the middiaphysis. Likewise, peak strains on the periosteal surface were greatest distally and less proximally. There was a significant dose-response relationship between peak strain magnitude and periosteal new bone formation when the mechanically induced strain surpassed a threshold. The strain threshold varied from 1343 microstrain (mu strain) proximally to 2284 mu strain at the midshaft to 3074 mu strain distally. Unlike the periosteal response to mechanical loading, there was not a clear dose-response relationship between applied load and bone formation on the endocortical surface. Endocortical strains were estimated to be < 20% of periosteal strains and may not have been sufficient to initiate a bone formation response. Our results show that the osteogenic response on the periosteal surface of the ulna depends on peak strain level once a strain threshold is surpassed. The threshold strain is largest distally, where locomotor bone strains are typically higher and smallest proximally where locomotor bone strains are lower.

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Twenty fresh frozen hand specimens from cadavers were studied. Physiologic levels of extrinsic muscle loads were applied to the extrinsic flexor tendons of the index finger to simulate tip pinch of the finger on a fixed plate. The acute effects of transection of the radial collateral ligament and accessory radial collateral ligament (radial collateral ligament complex) with and without transection of the dorsal capsule and volar plate on the position of the proximal phalanx with respect to the metacarpal bone of the index finger were investigated. The acute effects of reconstruction of the radial collateral ligament, for each of two different surgical techniques, on the position of the proximal phalanx also were investigated. The spatial positions of the metacarpal bone and proximal phalanx were measured with a six-degree-of-freedom digitizing system for flexion angles from 0 degrees to 90 degrees in increments of 15 degrees. Transection of the radial collateral ligament complex resulted in significant increases in ulnar deviation (adduction) of the proximal phalanx and in volar translation. Additional transection of the dorsal capsule and volar plate caused significant increases in ulnar deviation, pronation, volar translation, and ulnar shift. The first surgical technique, one traditionally used to reconstruct the metacarpophalangeal joint of the thumb, failed to return the three-dimensional position of the proximal phalanx on the metacarpal head of the index finger to normal. The second surgical technique, based on anatomy, returned the position of the proximal phalanx to levels not statistically different from normal for most flexion angles.

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The inbred strains of mice C57BL/6J (B6) and C3H/HeJ (C3H) have very different femoral peak bone densities and may serve as models for studying the genetic regulation of bone mass. Our objective was to further define the bone biomechanics and microstructure of these two inbred strains. Microarchitecture of the proximal femur, femoral midshaft, and lumbar vertebrae were evaluated in three dimensions using microcomputed tomography (microCT) with an isotropic voxel size of 17 microm. Mineralization of the distal femur was determined using quantitative back-scatter electron (BSE) imaging. MicroCT images suggested that C3H mice had thicker femoral and vertebral cortices compared with B6. The C3H bone tissue also was more highly mineralized. However, C3H mice had few trabeculae in the vertebral bodies, femoral neck, and greater trochanter. The trabecular number (Tb.N) in the C3H vertebral bodies was about half of that in B6 vertebrae (2.8(-1) +/- 0.1 mm(-1) vs. 5.1(-1) +/- 0.2 mm(-1); p < 0.0001). The thick, more highly mineralized femoral cortex of C3H mice resulted in greater bending strength of the femoral diaphysis (62.1 +/- 1.2N vs. 27.4 +/- 0.5N, p < 0.0001). In contrast, strengths of the lumbar vertebra were not significantly different between inbred strains (p = 0.5), presumably because the thicker cortices were combined with inferior trabecular structure in the vertebrae of C3H mice. These results indicate that C3H mice benefit from alleles that enhance femoral strength but paradoxically are deficient in trabecular bone structure in the lumbar vertebrae.

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Injuries to the ulnar collateral ligament (UCL) of the metacarpophalangeal joint of the thumb are common and may result in functional instability of the joint. Eight cadaveric hands were studied. Physiologic levels of muscle loads were applied to the extrinsic flexor tendon of the thumb to simulate tip pinch of the thumb. We investigated the effects of transection of the UCL and accessory UCL (UCL complex) with and without transection of the dorsal capsule and volar plate and of reconstruction of the UCL, for 2 surgical techniques, on the position of the proximal phalanx with respect to the thumb metacarpal. The spatial positions of the metacarpal and proximal phalanx were measured with a 6 degrees of freedom digitizing system for flexion angles from 0 degrees to 60 degrees in 15 degrees increments. Transection of the UCL complex, dorsal capsule, and volar plate (ulnar capsuloligamentous structures) of the metacarpophalangeal joint did not affect radioulnar deviation or radioulnar shift, but did produce significant increases in supination by 8 degrees and volar translation by 2 mm at 45 degrees and 60 degrees compared with those found for the intact joint. The UCL was reconstructed with a tendon graft using the autogenous extensor digiti quinti. The first surgical technique, a traditional technique, and the second surgical technique, a technique based on anatomy, returned the position of the proximal phalanx on the metacarpal head to normal, with the exceptions of volar translation of the proximal phalanx at 60 degrees and trends toward abnormal supination of the proximal phalanx for flexion angels of 45 degrees and 60 degrees.

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Studies of the adaptive skeletal response to mechanical loading require appropriate animal models. Two new approaches involve the nonsurgical application of loads to either the ulna or tibia of rats. Both of these approaches require the loading of bone through adjacent soft tissues, and thus the tissue viscoelasticity might affect the way load is transferred to the bone. The objective of this study was to characterize the mechanical strain in the rat tibia or ulna during applied loading at different frequencies. For the rat ulna model, loading was applied to the ulnae of four adult, female rats as a haversine waveform at frequencies of 1, 2, 5, 10, and 20 Hz and peak loads of 5, 10, 15, and 20 N. Mechanical strain was measured on the medial and lateral ulnar surfaces using single element strain gauges. For the rat tibia model, four-point bending loads were applied to the right tibiae of seven rats at frequencies of 0.5, 1, 2, 5, 10, and 20 Hz and peak loads of 30, 40, 50, and 60 N. Mechanical strain was measured on the lateral tibial surface at 5 mm proximal to the tibiofibular junction. We found that peak strains were linearly proportional to applied load, but decreased logarithmically as loading frequency was increased, indicating a significant viscoelastic effect in the soft tissues surrounding the ulnocarpal joint and in the soft tissues surrounding the tibia shaft. The viscoelastic response of the ulna and tibia tends to "filter out" high-frequency loading components and, as a result, the rat loading systems act as a low-pass filter. Consequently, any experiment designed to test the effect of loading frequency on bone formation in the rat ulna and tibia should employ progressively larger loads at higher loading frequencies to guarantee a consistent peak strain magnitude in the bone. The filtering effect of the ulna loading system is illustrated by an analysis of the strain waveforms from the recent study by Mosley and Lanyon (Bone 23:313-318; 1998) that was designed to evaluate the effect of strain rate on bone formation.

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In the past, there has been a plausible hypothesis that anterior cruciate ligament graft placement at isometric sites, such that the tibial and femoral attachment sites remain equidistant from each other throughout knee range of motion, would increase the likelihood of a satisfactory outcome. For a given tibial placement we wanted to determine whether placing the graft on the average of the most isometric femoral line, a fixed distance from the outlet of the intercondylar notch, would return normal laxity to all knees. The three-dimensional kinematics of seven cadaveric knees were measured for angles from full extension to 90 degrees of flexion at 15 degrees increments. Physiologic levels of quadriceps muscle forces were applied to the intact knee, after transection of the anterior cruciate ligament, and after ligament reconstruction with a patellar tendon graft. On average, the reconstruction was found to return anterior-posterior translation, internal-external rotation, and varus-valgus rotation to levels not significantly different from those of the intact knee. However, the ranges of the translation and rotations were large. Placing the graft on the average most isometric femoral line did not restore knee laxity to normal in all knees. This supports the need to customize graft placement in each knee at the time of surgery.

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Mechanical stimulation of bone induces new bone formation in vivo and increases the metabolic activity and gene expression of osteoblasts in culture. We investigated the role of the actin cytoskeleton and actin-membrane interactions in the transmission of mechanical signals leading to altered gene expression in cultured MC3T3-E1 osteoblasts. Application of fluid shear to osteoblasts caused reorganization of actin filaments into contractile stress fibers and involved recruitment of beta1-integrins and alpha-actinin to focal adhesions. Fluid shear also increased expression of two proteins linked to mechanotransduction in vivo, cyclooxygenase-2 (COX-2) and the early response gene product c-fos. Inhibition of actin stress fiber development by treatment of cells with cytochalasin D, by expression of a dominant negative form of the small GTPase Rho, or by microinjection into cells of a proteolytic fragment of alpha-actinin that inhibits alpha-actinin-mediated anchoring of actin filaments to integrins at the plasma membrane each blocked fluid-shear-induced gene expression in osteoblasts. We conclude that fluid shear-induced mechanical signaling in osteoblasts leads to increased expression of COX-2 and c-Fos through a mechanism that involves reorganization of the actin cytoskeleton. Thus Rho-mediated stress fiber formation and the alpha-actinin-dependent anchorage of stress fibers to integrins in focal adhesions may promote fluid shear-induced metabolic changes in bone cells.

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Patellofemoral pain may be associated with anterior cruciate ligament deficiency or may occur after anterior cruciate ligament reconstruction. We investigated the effects of the removal and reconstruction of the anterior cruciate ligament on the kinematics of the tibiofemoral and patellofemoral joints during physiologic levels of quadriceps muscle loads in seven cadaveric knees. A bone-patellar tendon-bone graft was used for intraarticular reconstruction of the anterior cruciate ligament. The spatial positions of the tibiofemoral and patellofemoral joints were measured between 0 degrees and 90 degrees of knee flexion in 15 degrees increments with a six degree-of-freedom digitizing system. Excision of the anterior cruciate ligament resulted in statistically significant increases in anterior tibial translation between 0 degrees and 90 degrees and valgus tibial rotation between 30 degrees and 90 degrees; intraarticular reconstruction returned these to levels not significantly different from those of the intact knee. Excision of the anterior cruciate ligament resulted in significant increases in lateral patellar tilt, ranging from 6.3 degrees to 9.0 degrees between full extension and 90 degrees of knee flexion, and in lateral patellar shift, ranging from 2.9 mm at 15 degrees of knee flexion to 5.9 mm at 90 degrees; intraarticular reconstruction returned these to levels not significantly different from those of the intact knee. Neither removal nor reconstruction of the anterior cruciate ligament significantly affected tibial internal-external rotation, patellar flexion, patellar mediolateral rotation, patellar anteroposterior translation, or patellar proximodistal translation.

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The relationships between the lengths of the ligaments and kinematics of the knee and quadriceps load, for low to physiologic levels of quadriceps loads, have not previously been studied. We investigated the effects of increasing levels of quadriceps force, necessary to balance increasing levels of externally applied flexion moments, on the kinematics of the tibiofemoral joint and on the separation distances between insertions of selected fibers of the major ligaments of the knee in twelve cadavera. Static measurements were made using a six-degree-of-freedom digitizer for flexion angles ranging from 0 to 120 deg in 15 deg increments. Quadriceps generated extension of the knee was performed by applying loads to the quadriceps tendon to equilibrate each of four magnitudes of external flexion moments equivalent to 8.33, 16.67, 25.00, and 33.33 percent of values previously reported for maximum isometric extension moments. The magnitude of quadriceps force increased linearly (p < 0.0001) as external flexion moment increased throughout the entire range of flexion. Anterior translation, internal rotation, and abduction of the tibia increased linearly (p < 0.0001, p < 0.001, p < 0.001) as external flexion moment and, hence, quadriceps load increased. For the fibers studied, the anterior cruciate ligament (p < 0.0076), posterior cruciate ligament (p < 0.0001), and medial collateral ligament (p < 0.0383) lengthened linearly while the lateral collateral ligament (p < 0.0124) shortened linearly as quadriceps load increased. Based on these results for low to physiologic levels of quadriceps loads, it is reasonable to assume that the ligament lengths or knee kinematics expected with higher quadriceps loads can be extrapolated.

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The synthesis of structural analogs and the process of drug discovery have evolved dramatically through recent advances in solid-phase synthesis reagents and automated screening systems. As molecular diversity strategies emerge, the need for automated target-based selection of lead candidates becomes equally important. Multidimensional automated chromatographic techniques coupled to electrospray ionization mass spectrometry facilitate the selection process and provide maximum characterization information in a single screening run. The capture of tightly bound affinity leads by target biomolecules, followed by subsequent release and high-resolution separation with sensitive detection, significantly reduces the time required to identify and characterize lead compounds. This automated multidimensional chromatographic approach coupled with mass spectrometry, Selectronics, was used with several organic and natural libraries to demonstrate an automated target-based screening technique to select for high-affinity binders as potential lead compounds.

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We modeled an intraarticular anterior cruciate ligament graft and investigated the effects of attachment orientation and twist of the graft on its isometry during quadriceps muscle loading. Physiologic levels of quadriceps muscle loads were applied to 15 intact cadaveric knees. We measured the changes in distance between points on the tibia and femur for knee flexion angles between 0 degree and 120 degrees using a three-dimensional digitizer. Selected points on the tibia and femur, representing graft attachment sites, allowed us to model the graft as a broad band. Distance was used to approximate graft fiber length. A 180 degrees twist in the graft significantly reduced the maximal range of changes in distance when the graft was attached in the anteroposterior direction. Range is defined as the difference between the largest and smallest changes in distance among the fibers of the graft for a given angle of flexion. This reduction enhanced isometry among the fibers of the graft. Enhanced isometry would be expected to enhance load sharing among these fibers, thereby increasing the overall strength of the graft. For a graft 10 mm wide and 4 mm thick, the dimensions of a typical patellar tendon graft, the best overall isometry was found when the breadth of the graft was attached to the tibia in the mediolateral direction, to the femur along the most isometric line, and with a 180 degrees twist in the graft.

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We investigated the changes in distance between Gerdy's tubercle on the tibia and points on the posterior two thirds of the lateral surface of the lateral femoral condyle and adjacent lateral femoral shaft in 15 cadaveric knees. A three-dimensional digitizer was used to quantify motion of the knee during flexion ranging from full extension to 120 degrees of flexion. Four load states were applied: internal, external, and neutral rotation, and quadriceps muscles loads based on one third of values in the literature for maximal isometric quadriceps muscles moments. The femoral location most isometric to Gerdy's tubercle was found to be strongly influenced by the load state. A 1.0 cm wide iliotibial band tenodesis was modelled by five straight lines arising from Gerdy's tubercle and attaching to a simulated washer at the junction of the lateral femoral condyle and shaft. Using this model and the motion data obtained from the cadavers, we investigated the effects of quadriceps muscles loading and external rotation of the knee on changes in the distances between these tibial and femoral attachments for each of the five lines. A 180 degrees twist modelled into the tenodesis significantly reduced the range of changes in distance (difference between the largest and smallest changes in distance among the lines for a given angle of flexion) for both of these load states. Therefore, a 180 degrees twist in the tenodesis can enhance isometry among the fibers of the tenodesis. This implies that a 180 degrees twist can enhance load sharing among the fibers of the tenodesis and, therefore, enhance the overall strength of the tenodesis.

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The object of this study is to determine the effect of tibial rotations on the three-dimensional patello-femoral motions and contact areas during a physiological loading condition, the knee-extension exercise. A commercially available device, the 3-SPACE digitizer and tracker system, was used to collect the motion data, utilizing cadaveric human lower limbs as well as the geometric measurements describing the articular surfaces at the patello-femoral joint. It was found that tibial rotations caused statistically significant differences, at the 0.05 level, in patellar tilt, patellar rotation and patellar medial-lateral shift. It was also found that while the magnitude of the total contact area at a given knee flexion angle did not change significantly with tibial rotations, medial and lateral components of the total contact areas were affected by tibial rotations. Medical femoral contact areas increased with internal tibial rotations at all flexion angles; lateral femoral contact areas increased with external tibial rotations at all flexion angles. This correlates well with the kinematic data since it was found that the patella shifted medially with internal tibial rotations at all flexion angles, and titled more medially near full-extension causing an increase in the medial contact areas and a decrease in the lateral contact areas.

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