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An attempt was made to determine the sports-specific coordination abilities necessary for goalball player for productive performance. The features of their manifestation were revealed taking into account the complete or partial visual deprivation of athletes, as well as the features of physical and technical fitness in goalball. Recommendations are given on the selection of means and methods for developing the ability to react, rebuild, orient and differentiate the parameters of goalball players’ movements during the training process.

The paper describes ways of physical training of mountain skiers with upper limbs injuries at the initial stage, options for strength, speed and aerobic training, as well as the means of developing flexibility and coordination abilities. Within the framework of stage control in the form of motor tests recommended by the Federal Standard of Sports Training, the assessment of the effectiveness of the development of physical fitness of the mountain skiers with musculoskeletal system tumors from the experimental group was carried out.

Background Crohn’s disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the pituitary-hypophysis-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX) impacts their inflammatory process. Methods Circulating inflammatory markers (IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-18, IL-23, and IL-33) and a wide range of psychological parameters were measured before (T1) and after (T2) COBMINDEX in CD patients. Inflammatory parameters were also compared to age- and sex-matched healthy controls (HCs) at T1, and to wait-list CD patients (at T1 and T2) who were followed for 3 months but did not receive COMBINDEX. Psychological symptoms were assessed by two questionnaires: the Perceived Stress Scale PSS4, and the Brief Symptom Inventory of psychological distress with Global Severity Index GSI. Statistical significance was assessed using Spearman correlation. Results CD patients (N=100, mean age 33.6 ± 13 years, 69% female, Harvey-Bradshaw Index mean 31± 55) exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by higher serum levels of interleukin (IL)-6 (mean 4.084± 8.4) and IL-18 (mean 302.09± 286) shown in Figure 1. Notably, IL-18 levels correlated with a higher stress score and a lower wellbeing score in CD patients (Figure 2). COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 (0.32, p Conclusion Our results show that CD patients have a characteristic immunological profile that correlates with psychological stress and disease activity, and predicts COBMINDEX outcomes. We suggest that COBMINDEX induces stress resilience in CD patients, which not only impacts their well-being, but also their disease-associated inflammatory process.

Double-walled orbital fractures involving the floor and medial wall are commonly encountered in instances of significant midface trauma. Operative intervention is indicated in the presence of persistent diplopia, significant enophthalmos, or muscle entrapment. Surgical repair of these injuries may be challenging due to large fracture sizes or loss of bony supports. The transconjunctival and transcaruncular approaches have been popularized to reconstruct isolated floor and medial wall fractures, respectively. However, surgical approaches for fractures involving both these walls have not been well described in the literature. In this technical note, we detail a combined transcaruncular-transconjunctival approach that is safe, effective, and aesthetically sensitive.

This paper provides a synopsis of discussions related to biomedical engineering core curricula that occurred at the Fourth BME Education Summit held at Case Western Reserve University in Cleveland, Ohio in May 2019. This summit was organized by the Council of Chairs of Bioengineering and Biomedical Engineering, and participants included over 300 faculty members from 100+ accredited undergraduate programs. This discussion focused on six key questions: QI: Is there a core curriculum, and if so, what are its components? QII: How does our purported core curriculum prepare students for careers, particularly in industry? QIII: How does design distinguish BME/BIOE graduates from other engineers? QIV: What is the state of engineering analysis and systems-level modeling in BME/BIOE curricula? QV: What is the role of data science in BME/BIOE undergraduate education? QVI: What core experimental skills are required for BME/BIOE undergrads? s. Indeed, BME/BIOI core curricula exists and has matured to emphasize interdisciplinary topics such as physiology, instrumentation, mechanics, computer programming, and mathematical modeling. Departments demonstrate their own identities by highlighting discipline-specific sub-specialties. In addition to technical competence, Industry partners most highly value our students' capacity for problem solving and communication. As such, BME/BIOE curricula includes open-ended projects that address unmet patient and clinician needs as primary methods to prepare graduates for careers in industry. Culminating senior design experiences distinguish BME/BIOE graduates through their development of client-centered engineering solutions to healthcare problems. Finally, the overall BME/BIOE curriculum is not stagnant-it is clear that data science will become an ever-important element of our students' training and that new methods to enhance student engagement will be of pedagogical importance as we embark on the next decade.

Purpose/objective(s) Locoregional control remains an issue in women with multi-node positive estrogen receptor-positive (ER+) breast cancer and many women with triple-negative breast cancer (TNBC). There is growing evidence that CDK4/6 inhibition (CDK4/6i) sensitizes breast cancer cells to ionizing radiation (RT) by suppressing the DNA damage response, but the role of RB is currently unclear. We sought to understand the role of RB and the implications of RB loss in ER+ and TNBC. Materials/methods Clonogenic survival assays were used to calculate radiosensitivity and calculate enhancement ratios (rER). Cellular viability was quantified 72 hours after drug addition to calculate half-maximal inhibitory concentrations (IC50s). Phospho- and total RB expression levels were assessed by immunoblotting. DNA repair was assessed with γH2AX and RAD51 immunofluorescence. GFP-based plasmid reporter systems were used to assess homologous recombination (HR) and non-homologous end joining (NHEJ) competency. Isogenic RB1 knockout cells were generated with CRISPR-Cas9, and siRNA was used for transient RB1 knockdown. G1 cell cycle arrest was quantified using propidium iodide-based flow cytometry. In vivo efficacy of CDK4/6 inhibition + RT was assessed using MDA-MB-231 xenografts. Results Four TNBC cell lines with intact RB expression were radiosensitized (rER 1.08 - 2.22) after CDK4/6i with palbociclib, ribociclib, or abemaciclib, but two RB null TNBC models were not radiosensitized with combination treatment (rER: 0.84 - 1.00). In ER+ and TNBC cell lines, response to CDK4/6i + RT was accurately predicted by the presence or absence of RB protein, and higher RB expression led to increased radiosensitization of breast cancer cell lines at lower doses. In addition, pRB expression decreased in wild type TNBC cell lines treated with CDK4/6i + RT. HR was suppressed with CDK4/6i in RB wild type - but not mutant - cell lines. NHEJ efficiency in RB wild type TNBC was unchanged with CDK4/6i. Genetic knockdown of RB1 led to the loss of radiosensitization in ER+ and TNBC cell lines (rER: 0.84 - 1.13) as well as a decrease in sensitivity to CDK4/6i monotherapy. Parental and Cas9 control TNBC cells arrested in G1 24 hours after CDK4/6i and remained arrested at 48 hours, but RB1 CRISPR TNBC cells did not arrest after drug treatment. In a TNBC xenograft model with wild type RB expression (MDA-MB-231), CDK4/6i + RT led to significant radiosensitization in vivo and delayed time to tumor doubling. Conclusion RB loss mitigates CDK4/6 inhibitor-mediated radiosensitization of both ER+ and TNBC cells. Loss of RB expression prevents CDK4/6i-mediated radiosensitization, suggesting that RB expression may be a valuable clinical biomarker to predict efficacy of CDK4/6i + RT in future clinical trials. Our data also provide the preclinical rationale for CDK4/6i with RT not just in ER+ BC, but also in women with TNBC that express RB.

Background Crohn’s disease (CD) is associated with psychological stress and alteration of gut microbiota as compared to healthy individuals. Previous work has reported imbalances in CD patients across four major bacterial phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. We aimed to determine the effect on gut microbiota of a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX), a psychological intervention shown to improve the wellbeing and inflammatory state of CD patients. Methods Microbial analysis of stool samples, circulating inflammatory markers and a wide range of psychological parameters related to stress, well-being and daily activities were measured and compared among 25 CD patients before (T1) and after (T2) COBMINDEX, and 25 matched CD wait-list controls at the corresponding time-points T1 and T2. Stool DNA extracts were subjected to 16S amplicon sequencing (Illumina) and analysed for taxonomical abundance, alpha and beta diversity using the QIIME2 pipeline and correlated with inflammatory and clinical parameters. Results Microbial alpha diversity among all CD patients at T1 significantly correlated to the 3 key cytokines: IL-10 (p=0.04, correlation=0.48), INFg (p=0.02, correlation=0.53), and INFa (p=0.02, correlation=0.51). At T2, while beta diversity was significantly increased in the COBMINDEX group (p=0.03), it was significantly decreased (p=0.0001) among the wait-list controls (Figure 1). Furthermore, compared with the wait-list controls, changes in inflammatory and clinical markers such as INFg, TNFa, IL-6, calprotectin and CRP, occurring following COBMINDEX, were accompanied by changes in the 4 main phyla including Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria (Figure 2). Lastly, changes in a variety of unique taxa, not previously implicated in CD, were also associated with changes in inflammatory and clinical markers such as INFg, TNFa, IL-6, calprotectin and CRP in the COBMINDEX but not in wait-list controls (Figure 2). Conclusion Our results show that microbial diversity is connected to the inflammatory profile of CD patients, and is significantly altered by COBMINDEX. Moreover, changes in the 4 main phyla that are known to be different among CD patients are linked to changes in various inflammatory markers, demonstrating the microbial-inflammatory relationship among CD patients. Lastly, we found that changes in the abundancies of 7 taxa, hitherto untied to CD in the literature, correlate with inflammatory markers, hinting at new microbial targets in CD.

The optical performance of the human cornea under intraocular pressure (IOP) is the result of complex material properties and their interactions. The measurement of the numerous material parameters that define this material behavior may be key in the refinement of patient-specific models. The goal of this study was to investigate the relative contribution of these parameters to the biomechanical and optical responses of human cornea predicted by a widely accepted anisotropic hyperelastic finite element model, with regional variations in the alignment of fibers. Design of experiments methods were used to quantify the relative importance of material properties including matrix stiffness, fiber stiffness, fiber nonlinearity and fiber dispersion under physiological IOP. Our sensitivity results showed that corneal apical displacement was influenced nearly evenly by matrix stiffness, fiber stiffness and nonlinearity. However, the variations in corneal optical aberrations (refractive power and spherical aberration) were primarily dependent on the value of the matrix stiffness. The optical aberrations predicted by variations in this material parameter were sufficiently large to predict clinically important changes in retinal image quality. Therefore, well-characterized individual variations in matrix stiffness could be critical in cornea modeling in order to reliably predict optical behavior under different IOPs or after corneal surgery.

The system of intercropping maize with other plant species has been a common practice for several years, but its use has been increasingly mainly to improve the quality of soil physical properties of no-tillage system. The objective of this study was to investigate the effect of intercropping using different cover plants on the physical properties of soil and the productivity of maize. Field experiments were conducted on the property of Mr. Arno Paulo Deimling, located in Linha Sao Joao, in the municipality of Quatro Pontes-PR. The experiment was carried out using a randomized complete block design, with four treatments and five repetitions. The treatments were winter maize intercropped with Urochloa brizantha, Urochloa ruziziensis or black oats (Avena strigosa), and maize sown in monoculture. In winter period, the production of maize used for silage and the production of dry matter from cover crops were assessed. The physical properties of soil samples were also investigated. Cover crops did not influence the productivity of winter maize used for silage, but it promoted improvements in soil macroporosity. The cover crops promoted improvements in the macroporosity of the soil and reduction at soil penetration resistance, particularly in the area planted with U. brisantha, demonstrating its potential in improving water infiltration and soil aeration. Key words: Direct seeding system, green manures, macroporosity, soil penetration resistance, conservationist system.

We present a simplified analysis suitable for a beginners' course in quantum mechanics of a recently presented model of positional decoherence in a gas of scatterers. As such, no reference is made to the density matrix formalism, many body theory, or even operator algebra. We only make use of the properties of quantum states and the position and momentum wavefunctions, which students typically encounter in a first quantum mechanics course.

Purpose The spatial distribution of collagen fibril dispersion has a significant impact on both corneal biomechanical and optical behaviors. The goal of this study was to demonstrate a novel method to characterize collagen fibril dispersion using intraocular pressure (IOP)-induced changes in corneal optical aberrations for individualized finite-element (FE) modeling. Methods The method was tested through both numerical simulations and ex vivo experiments. Inflation tests were simulated in FE models with three assumed patterns of collagen fibril dispersion and experimentally on three rhesus monkey corneas. Geometry, matrix stiffness, and the IOP-induced changes in wavefront aberrations were measured, and the collagen fibril dispersion was characterized. An individualized corneal model with customized collagen fibril dispersion was developed, and the estimated optical aberrations were compared with the measured data. Results For the theoretical investigations, three assumed distributions of fibril dispersion were all successfully characterized. The estimated optical aberrations closely matched the measured data, with average root-mean-square (RMS) differences of 0.29, 0.24, and 0.10 µm for the three patterns, respectively. The overall features of the IOP-induced changes in optical aberrations were estimated for two ex vivo monkey corneas, with average RMS differences of 0.57 and 0.43 µm. Characterization of the fibril dispersion in the third cornea might have been affected by corneal hydration, resulting in an increased RMS difference, 0.8 µm. Conclusions A more advanced corneal model with individualized distribution of collagen fibril dispersion can be developed and used to improve our ability to understand both biomechanical and optical behaviors of the cornea.

Xenikoudakis et al. report a partial mitochondrial genome of the extinct giant beaver Castoroides and estimate the origin of aquatic behavior in beavers to approximately 20 million years. This time estimate coincides with the extinction of terrestrial beavers and raises the question whether the two events had a common cause.

Several factors are believed to contribute to patellofemoral joint function throughout knee flexion including patellofemoral (PF) kinematics, contact, and bone morphology. However, data evaluating the PF joint in this highly flexed state have been limited. Therefore, the purpose of this study was to evaluate patellofemoral contact and alignment in low (0°), moderate (60°), and deep (140°) knee flexion, and then correlate these parameters to each other, as well as to femoral morphology.Sagittal magnetic resonance images were acquired on 14 healthy female adult knees (RSRB approved) using a 1.5 T scanner with the knee in full extension, mid-flexion, and deep flexion. The patellofemoral cartilage contact area, lateral contact displacement (LCD), cartilage thickness, and lateral patellar displacement (LPD) throughout flexion were defined. Intra- and inter-rater repeatability measures were determined. Correlations between patellofemoral contact parameters, alignment, and sulcus morphology were calculated.Measurement repeatability ICCs ranged from 0.94 to 0.99. Patellofemoral cartilage contact area and thickness, LCD, and LPD were statistically different throughout all levels of flexion (p0.001). The cartilage contact area was correlated to LPD, cartilage thickness, sulcus angle, and epicondylar width (r=0.47-0.72, p0.05).This study provides a comprehensive analysis of the patellofemoral joint throughout its range of motion.This study agrees with past studies that investigated patellofemoral measures at a single flexion angle, and provides new insights into the relationship between patellofemoral contact and alignment at multiple flexion angles.The study provides a detailed analysis of the patellofemoral joint in vivo, and demonstrates the feasibility of using standard clinical magnetic resonance imaging scanners to image the knee joint in deep flexion.

Meniscal implants have been developed in an attempt to provide pain relief and prevent pathological degeneration of articular cartilage. However, as yet there has been no systematic and comprehensive analysis of the effects of the meniscal design variables on meniscal function across a wide patient population, and there are no clear design criteria to ensure the functional performance of candidate meniscal implants. Our aim was to develop a statistically-augmented, experimentally-validated, computational platform to assess the effect of meniscal properties and patient variables on knee joint contact mechanics during the activity of walking. Our analysis used Finite Element Models (FEMs) that represented the geometry, kinematics as based on simulated gait and contact mechanics of three laboratory tested human cadaveric knees. The FEMs were subsequently programmed to represent prescribed meniscal variables (circumferential and radial/axial moduli - Ecm, Erm, stiffness of the meniscal attachments - Slpma, Slamp) and patient variables (varus/valgus alignment – VVA, and articular cartilage modulus - Ec). The contact mechanics data generated from the FEM runs were used as training data to a statistical interpolator which estimated joint contact data for untested configurations of input variables. Our data suggested that while Ecm and Erm of a meniscus are critical in determining knee joint mechanics in early and late stance (peak 1 and peak 3 of the gait cycle), for some knees that have greater laxity in the mid-stance phase of gait, the stiffness of the articular cartilage, Ec, can influence force distribution across the tibial plateau. We found that the medial meniscus plays a dominant load-carrying role in the early stance phase and less so in late stance, while the lateral meniscus distributes load throughout gait. Joint contact mechanics in the medial compartment are more sensitive to Ecm than those in the lateral compartment. Finally, throughout stance, varus-valgus alignment can overwhelm these relationships while the stiffness of meniscal attachments in the range studied have minimal effects on the knee joint mechanics. In summary, our statistically-augmented, computational platform allowed us to study how meniscal implant design variables (which can be controlled at the time of manufacture or implantation) interact with patient variables (which can be set in FEMs but cannot controlled in patient studies) to affect joint contact mechanics during the activity of simulated walking.

22q11.2 deletion syndrome (22q11DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by extensive phenotypic variability. Penetrance of signs, including congenital heart, craniofacial, and neurobehavioral abnormalities, varies widely and is not well correlated with genotype. The three-dimensional structure of the genome may help explain some of this variability. The physical interaction profile of a given gene locus with other genetic elements, such as enhancers and co-regulated genes, contributes to its regulation. Thus, it is possible that regulatory interactions with elements outside the deletion region are disrupted in the disease state and modulate the resulting spectrum of symptoms. COMT, a gene within the commonly deleted ~3 Mb region has been implicated as a contributor to the neurological features frequently found in 22q11DS patients. We used this locus as bait in a 4C-seq experiment to investigate genome-wide interaction profiles in B lymphocyte and fibroblast cell lines derived from both 22q11DS and unaffected individuals. All normal B lymphocyte lines displayed local, conserved chromatin looping interactions with regions that are lost in atypical and distal deletions, which may mediate similarities between typical, atypical, and distal 22q11 deletion phenotypes. There are also distinct clusterings of cis interactions based on disease state. We identified regions of differential trans interactions present in normal, and lost in deletion-carrying, B lymphocyte cell lines. This data suggests that hemizygous chromosomal deletions such as 22q11DS can have widespread effects on chromatin organization, and may contribute to the inherent phenotypic variability.

A monoclonal antibody, MAb vpg15, inhibits feline immunodeficiency virus (FIV) infection in tissue culture. The antibody is directed to a determinant of the feline cell surface marker, CD9, implying that CD9 may serve as a viral receptor or coreceptor in this system. In cells expressing CD9, MAb vpg15 markedly delayed acute virus infection in terms of reverse transcriptase activity detected in cell culture supernatants. This effect was evident if the antibody was added before, immediately after, or 24 h after virus infection. Binding experiments showed that MAb vpg15 did not block virus binding to the cells. PCR analyses at various intervals postinfection also indicated that MAb vpg15 did not block virus uptake, reverse transcription of viral RNA, or integration into host cell DNA. Multiply spliced mRNAs were detected up to 24 h postinfection in both control and MAb vpg15-treated cells. However, viral mRNAs were markedly diminished in MAb vpg15-treated cells after this time, consistent with a failure of the FIV infection to spread in the cell culture. Treatment of chronically infected cells with MAb vpg15 also caused a sharp diminution in viral particle production, while viral mRNA levels were the same in both untreated and MAb-treated infected cells. Analyses of intracellular and extracellular levels of virus-associated antigens showed an enhanced accumulation of intracellular p24. These findings are consistent with the interpretation that MAb vpg15 acts at a posttranscriptional stage by interfering with the assembly and/or release of virus from the cell.

Little is known about knee-specific factors that influence contact mechanics. Finite Element (FE) models offer a powerful tool to study contact mechanics, but there often exists ambiguity in the exact values of the inputs (e.g., tissue properties), which can result in a range of output values. Our objective was to quantify the reduction in the range of output values (defined herein as "uncertainty") from FE models of the human knee joint when known pre-defined values are used for clinically measurable inputs. To achieve this goal, we applied a statistically augmented FE approach to three human cadaveric knees for which full geometric and kinematic data were available. Two sets of conditions were simulated: All model inputs, clinically measurable or not, were varied to represent a "normal" patient population (Condition 1); subsets of clinically measurable variable inputs were fixed at specific values (called "patient derived inputs," or PDIs) while the other variables were varied over "normal" values (Condition 2). We found that by fixing body mass index and the anterior-posterior position of the meniscal-bony insertion points, model output uncertainty was reduced by one- to three-fifths. The magnitude of uncertainty reduction was strongly influenced by the individual knee. It was observed that knees with great anterior-posterior translation during gait had greater reductions in uncertainty when PDIs were used. This study represents the first step in developing FE models of the human knee joint based on inputs that can be derived from patients in a clinical setting. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2233-2242, 2017.

The integral form of Ampere’s law applied to an infinitely long solenoid gives a good first approximation to the magnetic field of finite air-cored solenoids with length L to width w ratios (aspect ratios) significantly greater than 1. It is less well known that this approximation requires much larger aspect ratios to be applicable to solenoids whose relative core permeability μr is much greater than that of the surrounding medium. An exact expression is derived for the magnetic field and inductance of a linear permeable core spheroidal solenoid, and an inequality is obtained for the validity of the infinite solenoid approximation. It is demonstrated that the magnetic field and inductance of a spheroidal solenoid with a linear core approximate well with those of a cylindrical solenoid of the same length and width.

The structure of a colored intermediate commonly formed in the oxidation of p-aminophenol at low pH is established by analysis of H NMR and UV/vis spectra, kinetics, and molecular modeling, following a new method for synthesizing the dye in high concentrations. The chromogen is shown to consist of two compounds with absorption maxima at 540-560 and 375-385 nm. The 2,6-dimethyl and 3,5-dimethyl analogues of p-aminophenol are found to undergo N- rather than C-substitution under similar conditions.

Interruption of suppressive highly active antiretroviral therapy (HAART) in HIV-infected patients leads to increased HIV replication and viral rebound in peripheral blood. Effects of therapy interruption on gut-associated lymphoid tissue (GALT) have not been well investigated. We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 + T cells in peripheral blood was observed, while gut mucosal CD4 + T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Sequence analysis of rebound virus suggested that GALT was not the major contributor to the postinterruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants. Our data suggest an early establishment and persistence of viral reservoirs in GALT with minimal diversity. Early detection of and therapy for HIV infection may be beneficial in controlling viral evolution and limiting establishment of diverse viral reservoirs in the mucosal compartment.

Despite the remarkable healing potential of long bone fractures, traumatic injuries that result in critical defects require challenging reconstructive limb sparing surgery. While devitalized allografts are the gold standard for these procedures, they are prone to failure due to their limited osseointegration with the host. Thus, the quest for adjuvants to enhance allograft healing remains a priority for this unmet clinical need. To address this, we investigated the effects of daily systemic injections of 40 μg/kg teriparatide (recombinant human parathyroid hormone) on the healing of devitalized allografts used to reconstruct critical femoral defects (4mm) in C57Bl/6 mice. The femurs were evaluated at 4 and 6 weeks using micro CT, histology, and torsion testing. Our findings demonstrated that teriparatide induced prolonged cartilage formation at the graft-host junction at 4 weeks, which led to enhanced trabeculated bone callus formation and remarkable graft-host integration at 6-weeks. Moreover, we observed a significant 2-fold increase in normalized callus volume (1.04 ± 0.3 vs. 0.54 ± 0.14 mm³/mm; p < 0.005), and Union Ratio (0.28 ± 0.07 vs. 0.13 ± 0.09; p < 0.005), compared to saline treated controls at 6-weeks. Teriparatide treatment significantly increased the torsional rigidity (1175 ± 311 versus 585 ± 408 N.mm²) and yield torque (10.5 ± 4.2 versus 6.8 ± 5.5 N.mm) compared to controls. Interestingly, the Union Ratio correlated significantly with the yield torque and torsional rigidity (R²=0.59 and R²=0.77, p < 0.001, respectively). These results illustrate the remarkable potential of teriparatide as an adjuvant therapy for allograft repair in a mouse model of massive femoral defect reconstruction, and warrant further investigation in a larger animal model at longer time intervals to justify future clinical trials for PTH therapy in limb sparing reconstructive procedures.

Purpose To study the use of an interleaved water-fat (IWF) sequence with a custom-made radiofrequency (RF) coil for high-resolution imaging of arthritic finger joints. Materials and Methods High-resolution finger magnetic resonance imaging (MRI) was performed using a custom-made dedicated RF receiver coil and an IWF sequence. A phantom, a cadaver finger specimen, and the fingers of two normal controls and six arthritic subjects were imaged with a resolution of 156 × 156 × 600 μm. The appearance of anatomic structures on the IWF images were compared with images acquired with a regular sequence. The images were reviewed by two musculoskeletal radiologists for the depiction of anatomical structures and for the presence of abnormalities. Results The high-resolution images revealed detailed structures of the finger joints not detectable using typical clinical resolution. The IWF sequence gave more realistic depiction of subchondral bone thickness, and avoided false bone erosions displayed in the regular sequence. It also allowed better visualization of ligaments and tendons. Conclusion This pilot study shows the feasibility and the potential usefulness of high-resolution IWF imaging for finger joint evaluation. This technique may be useful for the diagnosis and treatment assessment of arthritis, and for the study of joint disease pathogenesis. J. Magn. Reson. Imaging 2011;33:245–251. © 2010 Wiley-Liss, Inc.

Advances in biomaterial fabrication have introduced numerous innovations in designing scaffolds for bone tissue engineering. Often, the focus has been on fabricating scaffolds with high and interconnected porosity that would allow for cellular seeding and tissue ingrowth. However, such scaffolds typically lack the mechanical strength to sustain in vivo ambulatory stresses in models of load bearing cortical bone reconstruction. In this study, we investigated the microstructural and mechanical properties of dense PLA and PLA/beta-TCP (85:15) scaffolds fabricated using a rapid volume expansion phase separation technique, which embeds uncoated beta-TCP particles within the porous polymer. PLA scaffolds had a volumetric porosity in the range of 30 – 40%. With the embedding of beta-TCP mineral particles, the porosity of the scaffolds was reduced in half while the ultimate compressive and torsional strength were significantly increased. We also investigated the properties of the scaffolds as delivery vehicles for growth factors and gene delivery vectors in vitro and in vivo. The low surface porosity resulted in sub optimal retention efficiency of the growth factors, and burst release kinetics reflecting surface coating rather than volumetric entrapment, regardless of the scaffold used. When loaded with BMP2 and VEGF and implanted in the quadriceps muscle, PLA/beta-TCP scaffolds did not induce ectopic mineralization but induced a significant 1.8 fold increase in neo vessel formation. In conclusion, dense PLA/beta-TCP scaffolds can be engineered with enhanced mechanical properties and potentially be exploited for localized therapeutic factor delivery.

Our objective was to characterize variations in mechanical knee alignment, tibial torsion, tibial width, and ACL laxity measurements between Japanese and Caucasian populations in the healthy, young adult knee joint. Seventy young adult subjects participated in this study, including 23 Japanese and 47 Caucasian subjects. Coronal magnetic resonance images of the hip, knee, and ankle were acquired for analysis. Japanese subjects had a significantly higher (p = 0.04) varus alignment (1.64 ± 0.43° standard error) than Caucasians (0.55 ± 0.33°), while women exhibited a more valgus alignment (0.16 ± 0.52°) than men (0.94 ± 0.42°, p = 0.04). Significant differences were found in tibial torsion and ACL laxity (p < 0.01) between ethnicities, with Japanese exhibiting lower tibial torsion (33.4 ± 10.0°) and higher ACL laxity (7.5 ± 0.4 mm) measurements compared to Caucasians (38.9 ± 9.5° and 5.7 ± 0.3 mm, respectively). Significant differences between genders were found in hip-knee-ankle alignment (p = 0.04), tibial width (p < 0.0001), and ACL laxity (p < 0.01) measurements. Measurements were reliable between observers and for repeated positioning. Our study provides new insight into anatomical and geometric differences in the knee joint between Japanese and Caucasians, as well as between females and males. Further consideration of these results may improve development of implants to accommodate for these differences, and understanding of characteristics leading to increased prevalence of knee OA in certain populations. The use of magnetic resonance imaging to obtain these measurements also allows soft tissue structure characterization without exposure to ionizing radiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Phylogenetic relationships among birds of prey in the subfamily Buteoninae are not fully established but are of particular interest because the Buteoninae constitute one of the largest accipitrid subgroups and include multiple species of conservation concern. Genera previously included within the Buteoninae are Buteo, Leucopternis, Buteogallus, Harpyhaliaetus, Busarellus, Parabuteo, Geranoaetus, Geranospiza, Ictinia, Rostrhamus, Kaupifalco, and Butastur. We analyzed representatives from all buteonine genera and most non-Buteo (i.e., "sub-buteo") species with >3,000 bases of nuclear and mitochondrial DNA and found non-monophyly for the nominal genera Buteo, Buteogallus, and Leucopternis. The Old World Lizard Buzzard (Kaupifalco monogrammicus) is not closely related to buteonine taxa but is sister to goshawks in the genera Melierax, Micronisus, and Urotriorchis. Another Old World genus, Butastur, is sister to the clade including all other buteonine genera mentioned above. Investigation of several "...

The purpose of this study was to clarify meniscal displacement and cartilage-meniscus contact behavior in a full extension position and a deep knee flexion position. We also studied whether the meniscal translation pattern correlated with the tibiofemoral cartilage contact kinematics. Magnetic resonance (MR) images were acquired at both positions for 10 subjects using a conventional MR scanner. Subjects achieved a flexion angle averaging 139 degrees +/- 3 degrees. Both medial and lateral menisci translated posteriorly on the tibial plateau during deep knee flexion. The posterior translation of the lateral meniscus (8.2 +/- 3.2 mm) was greater than the medial (3.3 +/- 1.5 mm). This difference was correlated with the difference in tibiofemoral contact kinematics between medial and lateral compartments. Contact areas in deep flexion were approximately 75% those at full extension. In addition, the percentage of area in contact with menisci increased significantly due to deep flexion. Our results related to meniscal translation and tibio-menisco-femoral contact in deep knee flexion, in combination with information about force and pressure in the knee, may lead to a better understanding of the mechanism of meniscal degeneration and osteoarthritis associated with prolonged kneeling and squatting.

Purpose: The androgen receptor (AR) harbors a polymorphic CAG repeat sequence in exon 1, coding for a polyglutamine tract whose length inversely correlates with AR transactivation function. AIB1, an AR coactivator, expresses a similar polymorphic glutamine sequence within the carboxyl-terminal coding region. We hypothesized that genotypic variations in the androgen-signaling pathway promote aggressive epithelial ovarian cancer biology, and sought to examine the effect of AIB1 genotype on clinical outcome. Experimental Design: Genotype analysis of the AIB1 CAG repeat region was done on 89 patients with epithelial ovarian cancer. Medical records were reviewed for clinicopathologic factors and survival. Data were examined using the χ2 test and Kaplan-Meier survival and Cox regression analyses. Results: We identified four AIB1 genotypes, with glutamine codon lengths of 26, 28, 29, and 30. Patients with a short AIB1 genotype (with ≤28 CAG repeats) showed statistically shorter time to disease recurrence compared to those with a long genotype (≥29 CAG repeats; 15.0 versus 30.0 months; P = 0.01). Patients with short AIB1 also showed decreased overall survival (57.0 months) compared to those with a long genotype (median survival not yet reached; P = 0.02). When controlling for established prognostic factors, multivariate analysis identified the presence of a short AIB1 genotype as an independent poor prognostic factor for overall survival (P = 0.05). Conclusions: These data suggest that short AIB1 genotypes may promote aggressive malignant phenotypes of epithelial ovarian cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2919–22)

The stress-activated protein kinase, c-Jun N-terminal kinase (JNK), has been implicated in the process of cardiac hypertrophy and apoptosis, yet the specific roles of JNK in heart failure are unclear. To determine the effects of JNK activation in intact heart, we established transgenic animals using a Cre/loxP-mediated gene switch approach to achieve targeted expression of an upstream activator, mitogen-activated protein kinase kinase 7 (D) (MKK7D), in ventricular myocytes. MKK7D expression led to significant JNK activation, robust induction of the fetal gene program, and contractile dysfunction. The animals died approximately 7 weeks after birth with signs of congestive heart failure. Doppler mode echocardiography revealed a marked stiffening of JNK-activated hearts that was associated with the remodeling of specific extracellular matrix components. Gene expression analysis of MKK7D hearts revealed up-regulation of transforming growth factor beta signaling, offering a potential molecular mechanism underlying changes in extracellular matrix composition. In addition, we demonstrated that JNK activation led to specific loss of connexin 43 protein and gap junctions without affecting the expression or localization of other key intercalated disc proteins. This specific and localized gap junction remodeling resulted in significant slowing of ventricular electrical conduction in JNK-activated hearts. These results represent the first characterization of JNK-mediated cardiac pathology in vivo and support an important role for JNK signaling in specific aspects of cardiac remodeling in the pathogenesis of cardiac disease.

Case report.To describe the knee kinematics and moments of a giving-way trial of a subject with an anterior-cruciate-ligament- (ACL) deficient knee relative to his non-giving-way trials and to healthy subjects during a step-down task.Episodes of giving way are believed to damage joint structures, therefore treatments aim to prevent giving-way episodes, yet few studies document giving-way events.The giving-way trial experienced by a 32-year-old male subject with ACL deficiency during a step-down task was compared to his non-giving-way trials (n = 5) and data from healthy subjects (n = 20). Position data collected at 60 Hz were combined with anthropometric data and ground reaction force data collected at 300 Hz to estimate knee displacement and 3-dimensional angles and net joint moments.The knee joint displacement was higher during the giving-way trial: from 4% to 32% of stance, reaching 9.0 mm at 18% of stance as compared to 1.6 +/- 0.7 mm for the non-giving-way trials. After 4% of stance, the knee flexion angle of the giving-way trial was 6.6 degrees higher than the non-giving-way trials and was associated with a higher knee extension moment. The knee frontal plane moment was near neutral during early stance of the giving-way trial in contrast to the non-giving way and healthy subjects which demonstrated a knee abduction moment.The response of this subject to the giving-way event suggests that higher knee flexion angles may enhance knee stability and, in reaction to the giving-way event, that knee extension moment may increase.

Analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. However, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43). Methods: High-resolution optical mapping was used to record action potentials from 256 sites, simultaneously, on the ventricular surface of Langendorff perfused hearts from 15 heterozygous (Cx43+/−) and 8 wildtype (Cx43+/+) mice (controls). A sensitive method for measuring epicardial conduction velocity was developed to minimize confounding influences of subepicardial breakthrough and virtual electrode effects. Results: Epicardial conduction velocity was significantly slower (23 to 35%, P

Time for primary review 28 days. Sudden cardiac death occurs with unacceptably high incidence in patients with ischemic heart disease and cardiomyopathy. As Zipes and Wellens [1] have emphasized, sudden death arises from highly variable interactions between anatomic and/or functional myocardial substrates, transient initiating events and cellular/tissue arrhythmia mechanisms. In our view, a key strategy for developing mechanistic insights into sudden death is to first define the role of individual factors (including specific gene products) that contribute to arrhythmias, and to then understand how these factors interact to cause sudden death. One of the most common disease settings leading to sudden cardiac death is the acute coronary syndromes. Acute ischemia is marked by alterations in cell metabolism, cell signaling, intercellular communication and electrical impulse propagation [2]. These changes produce a cascade of events that are adaptive in the sense that mechanisms are activated to mitigate injury, forestall cell death and isolate irreversibly injured myocytes from their viable neighbors, but also maladaptive in that they can create a substrate that supports the initiation and maintenance of malignant ventricular arrhythmias. Among the electrophysiologically relevant changes that occur rapidly after the onset of ischemia are reductions in tissue pH, increases in interstitial K+ and intracellular Ca2+ concentrations and changes in active and passive membrane properties, all of which interact in a complex milieu to slow conduction, alter excitability and refractoriness, promote electrical uncoupling, and generate spontaneous electrical activity [1–4]. In this review, we focus on the specific role of diminished intercellular electrical coupling in the pathogenesis of lethal arrhythmias induced by acute ischemia. Until recently, it has been difficult to isolate the contribution of diminished coupling per se to arrhythmogenesis in the complex setting of acute ischemia. However, the advent of techniques to manipulate gene expression and characterize cardiac …

Abstract —Electrical uncoupling at gap junctions during acute myocardial ischemia contributes to conduction abnormalities and reentrant arrhythmias. Increased levels of intracellular Ca 2+ and H + and accumulation of amphipathic lipid metabolites during ischemia promote uncoupling, but other mechanisms may play a role. We tested the hypothesis that uncoupling induced by acute ischemia is associated with changes in phosphorylation of the major cardiac gap junction protein, connexin43 (Cx43). Adult rat hearts perfused on a Langendorff apparatus were subjected to ischemia or ischemia/reperfusion. Changes in coupling were monitored by measuring whole-tissue resistance. Changes in the amount and distribution of phosphorylated and nonphosphorylated isoforms of Cx43 were measured by immunoblotting and confocal immunofluorescence microscopy using isoform-specific antibodies. In control hearts, virtually all Cx43 identified immunohistochemically at apparent intercellular junctions was phosphorylated. During ischemia, however, Cx43 underwent progressive dephosphorylation with a time course similar to that of electrical uncoupling. The total amount of Cx43 did not change, but progressive reduction in total Cx43 immunofluorescent signal and concomitant accumulation of nonphosphorylated Cx43 signal occurred at sites of intercellular junctions. Functional recovery during reperfusion was associated with increased levels of phosphorylated Cx43. These observations suggest that uncoupling induced by ischemia is associated with dephosphorylation of Cx43, accumulation of nonphosphorylated Cx43 within gap junctions, and translocation of Cx43 from gap junctions into intracellular pools.

Background —Myocardial ischemia causes profound changes in both active membrane currents and passive electrical properties. Because these complex changes develop and progress concomitantly, it has not been possible to elucidate the relative contributions of any one component to arrhythmogenesis induced by acute ischemia. Cx43+/− mice express 50% of the normal level of connexin43 (Cx43), the major ventricular electrical coupling protein, but are otherwise identical to wild-type (Cx43+/+) mice. Comparison of arrhythmogenesis in Cx43+/− and +/+ mice can provide insights into the role of changes in electrical coupling as an independent variable in the complex setting of acute ischemia. Methods and Results —Acute ischemia was induced in isolated perfused mouse hearts by occlusion of the left anterior descending coronary artery. Spontaneous ventricular tachyarrhythmias (VT) occurred in more than twice as many Cx43+/− hearts than Cx43+/+ hearts. VT was induced in nearly 3 times as many Cx43+/− hearts. Multiple runs and prolonged runs of spontaneous VT were more frequent in Cx43+/− hearts. Onset of the first run of VT occurred significantly earlier in Cx43+/− hearts. Premature ventricular beats were also more frequent in Cx43+/− hearts. The size of the hypoperfused region was equivalent in both groups. Conclusions —Reduced expression of Cx43 accelerates the onset and increases the incidence, frequency, and duration of ventricular tachyarrhythmias after coronary artery occlusion. Thus diminished electrical coupling per se plays a critical role in arrhythmogenesis induced by acute ischemia.

We present a phylogeny of all booted eagles (38 extant and one extinct species) based on analysis of published sequences from seven loci. We find molecular support for five major clades within the booted eagles: Nisaetus (10 species), Spizaetus (4 species), Clanga (3 species), Hieraaetus (6 species) and Aquila (11 species), requiring generic changes for 14 taxa. Additionally, we recommend that the Long-crested Eagle (Lophaetus occipitalis) and the Black Eagle (Ictinaetus malaiensis) remain in their monotypic genera, due to their distinctive morphology. We apply the recently resurrected genus Clanga for the spotted eagles (previously Aquila spp.) to resolve the paraphyly of the genus Aquila such that the clade including the Booted Eagle (H. pennatus), Little Eagle (H. morphnoides), Pygmy Eagle (H. weiskei), Ayres’s Eagle (H. ayresii) and Wahlberg’s Eagle (H. wahlbergi) can remain in the genus Hieraaetus. The Rufous-bellied Eagle should be retained in the genus Lophotriorchis. For consistency in English names, we recommend that the term “hawk-eagles” be used only for the species in the genera Nisaetus and Spizaetus. We suggest following new or modified English names: Cassin’s Eagle (Aquila africana), Bonaparte’s Eagle (A. spilogaster), Ayres’s Eagle (Hieraaetus ayresii), and Black-and-chestnut Hawk-Eagle (Spizaetus isidori). Molecular phylogeny, morphology, Nisaetus, Spizaetus, Clanga, Hieraaetus, Aquila, Oroaetus, Spizastur, Lophotriorchis © 2017 Magnolia Press. Licensed under a Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0

Gene transcription can be regulated by remote enhancer regions through chromosome looping either in cis or in trans. Cancer cells are characterized by wholesale changes in long-range gene interactions, but the role that these long-range interactions play in cancer progression and metastasis is not well understood. In this study, we used IGFBP3, a gene involved in breast cancer pathogenesis, as bait in a 4C-seq experiment comparing normal breast cells (HMEC) with two breast cancer cell lines (MCF7, an ER positive cell line, and MDA-MB-231, a triple negative cell line). The IGFBP3 long-range interaction profile was substantially altered in breast cancer. Many interactions seen in normal breast cells are lost and novel interactions appear in cancer lines. We found that in HMEC, the breast carcinoma amplified sequence gene family (BCAS) 1–4 were among the top 10 most significantly enriched regions of interaction with IGFBP3. 3D-FISH analysis indicated that the translocation-prone BCAS genes, which are located on chromosomes 1, 17, and 20, are in close physical proximity with IGFBP3 and each other in normal breast cells. We also found that epidermal growth factor receptor (EGFR), a gene implicated in tumorigenesis, interacts significantly with IGFBP3 and that this interaction may play a role in their regulation. Breakpoint analysis suggests that when an IGFBP3 interacting region undergoes a translocation an additional interaction detectable by 4C is gained. Overall, our data from multiple lines of evidence suggest an important role for long-range chromosomal interactions in the pathogenesis of cancer.

Specific pathogen-free cats were infected with the Maryland strain of FIV (FIV-MD) for the purpose of assessing the effects of FIV infection on the central nervous system (CNS). Two separate studies were performed, involving a total of 13 infected cats and six age-matched, sham-inoculated controls. All animals infected with FIV-MD seroconverted by 8 weeks post-infection and virus was recovered from peripheral blood mononuclear cells of all infected cats. All of the infected animals had lower absolute CD4+ cells counts and decreased CD4+/CD8+ ratios. Virus was recovered from the cerebrospinal fluid (CSF) of certain infected individuals, and antiviral antibody and pleocytosis were evident in the CSF of the majority of infected cats. Additionally, virus was recovered from tissue explants from the cerebellum, midbrain and brainstem of one sacrificed FIV+ cat. Specific neurological changes included anisocoria, delayed righting reflex and delayed pupillary reflex, as well as delayed visual and auditory evoked potentials, and marked alterations in sleep patterns similar to those reported for human immunodeficiency virus (HIV)-positive individuals. Histological evaluation revealed the presence of perivascular cuffing and glial nodules in FIV-infected cats. These results indicate that FIV causes an acute neurological disease that closely resembles the early neurological effects of HIV infection in humans and should serve well as an animal model for lentivirus-induced CNS disease.

Summary Evolutionary theory has gained tremendous insight from studies of adaptive radiations. High rates of speciation, morphological divergence, and hybridization, combined with low sequence variability, however, have prevented phylogenetic reconstruction for many radiations. The Hawaiian honeycreepers are an exceptional adaptive radiation, with high phenotypic diversity and speciation that occurred within the geologically constrained setting of the Hawaiian Islands. Here we analyze a new data set of 13 nuclear loci and pyrosequencing of mitochondrial genomes that resolves the Hawaiian honeycreeper phylogeny. We show that they are a sister taxon to Eurasian rosefinches ( Carpodacus ) and probably came to Hawaii from Asia. We use island ages to calibrate DNA substitution rates, which vary substantially among gene regions, and calculate divergence times, showing that the radiation began roughly when the oldest of the current large Hawaiian Islands (Kauai and Niihau) formed, ∼5.7 million years ago (mya). We show that most of the lineages that gave rise to distinctive morphologies diverged after Oahu emerged (4.0–3.7 mya) but before the formation of Maui and adjacent islands (2.4–1.9 mya). Thus, the formation of Oahu, and subsequent cycles of colonization and speciation between Kauai and Oahu, played key roles in generating the morphological diversity of the extant honeycreepers.

Whole knee joint MR image datasets were used to compare the performance of geometric trabecular bone features and advanced machine learning techniques in predicting biomechanical strength properties measured on the corresponding ex vivo specimens. Changes of trabecular bone structure throughout the proximal tibia are indicative of several musculoskeletal disorders involving changes in the bone quality and the surrounding soft tissue. Recent studies have shown that MR imaging also allows non-invasive 3-D characterization of bone microstructure. Sophisticated features like the scaling index method (SIM) can estimate local structural and geometric properties of the trabecular bone and may improve the ability of MR imaging to determine local bone quality in vivo. A set of 67 bone cubes was extracted from knee specimens and their biomechanical strength estimated by the yield stress (YS) [in MPa] was determined through mechanical testing. The regional apparent bone volume fraction (BVF) and SIM derived features were calculated for each bone cube. A linear multiregression analysis (MultiReg) and a optimized support vector regression (SVR) algorithm were used to predict the YS from the image features. The prediction accuracy was measured by the root mean square error (RMSE) for each image feature on independent test sets. The best prediction result with the lowest prediction error of RMSE = 1.021 MPa was obtained with a combination of BVF and SIM features and by using SVR. The prediction accuracy with only SIM features and SVR (RMSE = 1.023 MPa) was still significantly better than BVF alone and MultiReg (RMSE = 1.073 MPa). The current study demonstrates that the combination of sophisticated bone structure features and supervised learning techniques can improve MR-based determination of trabecular bone quality.

Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to produce a rapid stimulation of breast cancer cell proliferation and motility which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase (TK) inhibitor molecules that have the potential to bind selectively to the KGFR. The present study evaluated the biological activity of 57 of these KGFR TK inhibitor compounds on breast cancer cells.These compounds were tested for their ability to inhibit KGF-mediated breast cancer cell proliferation in MCF-7 breast cancer cells. Furthermore, the effects of the most effective proliferation inhibitors were examined on Erk signaling and on the relative density of cell membrane KGFR.It was observed that 27 of the 57 compounds tested produced a 20% or greater reduction in KGF-mediated proliferation; while five compounds produced greater than 50% inhibition. In addition, the most potent inhibitors also reduced Erk signaling and cell membrane density of the KGFR.The compounds examined appear to be selective KGFR inhibitors which inhibit KGF-mediated activity and reduce the expression of KGFR on cancer cells. These results may lead to the development of a novel class of anticancer agents for the prevention of metastatic cancer progression.

In vivo studies have suggested Caucasians achieve lower average knee flexion than non-Western populations. Some previous studies have also suggested gender may influence condylar AP translation and axial rotation, while others report an absence of such an influence.We determined whether different ethnic and gender groups residing in the United States had different knee translations and rotations.Three-dimensional knee rotations and translations were determined for 72 healthy subjects (24 Caucasian men, 24 Caucasian women, 13 Japanese men, 11 Japanese women) from full extension to maximum flexion using a fluoroscopic technique, under in vivo, weightbearing conditions.Although we observed substantial variability in all groups, small differences between groups were found, especially in deep flexion. Japanese women and men and Caucasian women achieved higher maximum flexion (153°, 151°, and 152°, respectively) than Caucasian men (146°). External rotation was higher for these three groups than for Caucasian men. The medial condyle remained more anterior for Caucasian women and all Japanese subjects than for Caucasian men, possibly leading to greater axial rotation and flexion, observed for these three groups.We identified small differences in maximum flexion between genders and ethnic groups. While no differences were identified in the lateral condyle translation, the medial condyle remained more stationary and more anterior for the groups that achieved highest (and similar) maximum flexion. Therefore, it may be important for future implant designs to incorporate these characteristics, such that only the lateral condyle experiences greater posterior femoral rollback, while the medial condyle remains more stationary throughout flexion.

The nonprimate lentiviruses feline immunodeficiency virus, equine infectious anemia virus, visna virus, and caprine encephalitis virus contain a gene segment in the polymerase gene that is lacking in the primate lentiviruses. A related sequence has been noted in other retroviruses, most notably the type D retroviruses. Computer searches have indicated a relatedness between this unique gene segment, termed proteaselike element and elements of both the aspartate proteinase and the dUTPase enzyme families. In this report, we show that members of both nonprimate lentiviruses and type D retroviruses possess dUTPase activity and present a formal demonstration that in feline immunodeficiency virus, the activity is encoded by the proteaselike element.

Cigarette smoking (CS) is associated with a variety of human pathologies including cardiovascular disease and cancer. Human monocytes are prevalent in oral and respiratory mucosa and may be affected by exposure to CS, which induces oxidative stress. As a result, up-regulation of nuclear factor-kappaB (NF-kappaB) may occur. Our aims were to analyze a possible regulatory effect of CS on NF-kappaB activity in human monocytes. Human monocyte cell lines were exposed to CS in vitro. Our findings show that in vitro exposure to CS did not affect viability of human monocytes and was associated with increased production and secretion of IL-8 and up-regulation of certain C-C chemokines. Inhibition of NF-kappaB with curcumin or parthenolide resulted in a decrease of IL-8 secretion. CS also impaired the differentiation of monocytes. However, induced secretion of IL-8 from differentiated monocytes was not impaired. Our results indicate that exposure to CS stimulates pro-inflammatory activity of human monocytes through the activation of NF-kappaB pathway and also interferes with monocyte differentiation, which could play a role in the carcinogenic effects of cigarette smoking.

The spatial coherence of the seismograms observed at a narrow-aperture array on hard rock sites in the Adirondack Mountains is approximately exp(− cf Δ x ) , where c about 0.67 km −1 Hz −1 , f is frequency and Δx is the distance between array elements. Vertical, radial, and transverse components were quite coherent over the aperture of the array (> 100 m ), indicating that the transverse motion of the compressional wave is a property of relatively large (10 6 m 3 ) volumes of rock, and not just an anomaly caused by a malfunctioning instrument, poor instrument-rock coupling, or outcrop-scale effects. The spatial coherence is approximately independent of component, epicentral azimuth and range, and whether P- or S- wave coda is being considered, at least for propagation distances between 5 and 170 km . The travel time of the seismic waves can be modelled by s simple, three layer model, but such a model produces an unacceptably small amount of coda. The introduction of thin vertically stratified velocity heterogeneities leads to significant coda, but the scale length of spatial coherence of this coda is an order of magnitude greater than is observed. A model of scattering from an ensemble of point scatters randomly placed in the shallow crust is capable for reproducing the observed coherence data, including its functional dependence on the quantity, fΔx.