Neoplastic transformation of porcine mammary epithelial cells in vitro and tumor formation in vivo.

BackgroundThe mammary glands of pigs share many functional and morphological similarities with the breasts of humans, raising the potential of their utility for research into the mechanisms underlying normal mammary function and breast carcinogenesis. Here we sought to establish a model for the efficient manipulation and transformation of porcine mammary epithelial cells (pMEC) in vitro and tumor growth in vivo.MethodsWe utilized a vector encoding the red florescent protein tdTomato to transduce populations of pMEC from Yorkshire -Hampshire crossbred female pigs in vitro and in vivo. Populations of primary pMEC were then separated by FACS using markers to distinguish epithelial cells (CD140a-) from stromal cells (CD140a+), with or without further enrichment for basal and luminal progenitor cells (CD49f+). These separated pMEC populations were transduced by lentivirus encoding murine polyomavirus T antigens (Tag) and tdTomato and engrafted to orthotopic or ectopic sites in immunodeficient NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ (NSG) mice.ResultsWe demonstrated that lentivirus effectively transduces pMEC in vitro and in vivo. We further established that lentivirus can be used for oncogenic-transformation of pMEC ex vivo for generating mammary tumors in vivo. Oncogenic transformation was confirmed in vitro by anchorage-independent growth, increased cell proliferation, and expression of CDKN2A, cyclin A2 and p53 alongside decreased phosphorylation of Rb. Moreover, Tag-transformed CD140a- and CD140a-CD49f + pMECs developed site-specific tumors of differing histopathologies in vivo.ConclusionsHerein we establish a model for the transduction and oncogenic transformation of pMEC. This is the first report describing a porcine model of mammary epithelial cell tumorigenesis that can be applied to the study of human breast cancers

Numerical solution of the Lyapunov equation by approximate power iteration

AbstractWe present the approximate power iteration (API) algorithm for the computation of the dominant invariant subspace of the solution X of large-order Lyapunov equations AX + XAT + Q = 0 without first computing the matrix X itself. The API algorithm is an iterative procedure that uses Krylov subspace bases in computing estimates of matrix-vector products Xv in a power iteration sequence. Application of the API algorithm requires that A + AT < 0; numberical experiments indicate that, if the matrix X admits a good low-rank solution, then API provides an orthogonal basis of a subspace that closely approximates the dominant X-invariant subspace of corresponding dimension. Analytical convergence results are also presented

Platonov and a Reproch against Karataev Philosophy: Do Moral Principles Undermine Bolshevist Revolution?

The article is a study of Andrei Platonov’s ethical principles’ evolution and of the reasons for his writings’ victimization by the Soviet critics and authorities.В статье анализируется эволюция морально-этических принципов А. Платонова и причин нападок на его творчество со стороны советских критиков и властей

Compliance with wearing a thoracolumbar orthosis in nonoperative treatment of osteoporotic vertebral fractures: A prospective sensor-controlled study

BACKGROUND CONTEXT Hyperextension orthoses (HOs) for non-operative treatment of osteoporotic vertebral fractures (OVFs) are widely prescribed. However, the compliance, how much an HO is worn after it has been prescribed, is widely unknown. PURPOSE This study was performed to assess the wearing time of HOs for OVFs in a prospective blinded, sensor-controlled manner. STUDY DESIGN / SETTING A prospective, single blinded observational study was performed. PATIENT SAMPLE This study prospectively included 18 patients who were treated non-operatively with an HO for OVFs. OUTCOME MEASURES The true wearing time was measured using a hidden temperature-based sensor. The patients were invited to return for regular follow-up every 2 weeks for 6 weeks, at which time clinical evaluation (including a visual analog scale for pain and the Oswestry disability questionnaire) and radiographs of the spine were performed. METHODS Full compliance was defined as a wearing time of 15 hours per day. Correlation between compliance and demographic differences, patient reported outcomes and radiographic changes of the vertebral structures were calculated. RESULTS The mean HO wearing time was 5.5±3.3 hours (37%±22% compliance). Female patients used the HO significantly longer per day than did male patients (6.5±3.2 vs 2.9±2.0 hours, p=.039). Age and body mass index had no influence on wearing behavior. CONCLUSIONS Overall, compliance with wearing HOs is poor and shows great variability with significant gender-dependency but not associated with BMI, age, or pain-level. Further studies are required to confirm our results that the wearing time does not have an influence on kyphotic progression of the osteoporotic fractured segment, nor on clinical outcome at short term. LEVEL OF EVIDENCE I

A Note on Monotonically Metacompact Spaces

We show that any metacompact Moore space is monotonically metacompact and use that result to characterize monotone metacompactness in certain generalized ordered (GO)spaces. We show, for example, that a generalized ordered space with a sigma-closed-discrete dense subset is metrizable if and only if it is monotonically (countably) metacompact, that a monotonically (countably) metacompact GO-space is hereditarily paracompact, and that a locally countably compact GO-space is metrizable if and only if it is monotonically (countably) metacompact. We give an example of a non-metrizable LOTS that is monotonically metacompact, thereby answering a question posed by S. G. Popvassilev. We also give consistent examples showing that if there is a Souslin line, then there is one Souslin line that is monotonically countable metacompact, and another Souslin line that is not monotonically countably metacompact

Influence of Bone Morphology on In Vivo Tibio-Femoral Kinematics in Healthy Knees during Gait Activities

An improved understanding of the relationships between bone morphology and in vivo tibio-femoral kinematics potentially enhances functional outcomes in patients with knee disorders. The aim of this study was to quantify the influence of femoral and tibial bony morphology on tibio-femoral kinematics throughout complete gait cycles in healthy subjects. Twenty-six volunteers underwent clinical examination, radiographic assessment, and dynamic video-fluoroscopy during level walking, downhill walking, and stair descent. Femoral computer-tomography (CT) measurements included medial condylar (MC) and lateral condylar (LC) width, MC and LC flexion circle, and lateral femoral condyle index (LFCI). Tibial CT measurements included both medial (MTP) and lateral tibial plateau (LTP) slopes, depths, lengths, and widths. The influence of bony morphology on tibial internal/external rotation and anteroposterior (AP)-translation of the lateral and medial compartments were analyzed in a multiple regression model. An increase in tibial internal/external rotation could be demonstrated with decreasing MC width β: -0.30 (95% CI: -0.58 to -0.03) (p = 0.03) during the loaded stance phase of level walking. An increased lateral AP-translation occurred with both a smaller LC flexion circle β: -0.16 (95% CI: -0.28 to -0.05) (p = 0.007) and a deeper MTP β: 0.90 (95% CI: 0.23 to 1.56) (p = 0.01) during the loaded stance phase of level walking. The identified relationship between in vivo tibio-femoral kinematics and bone morphology supports a customized approach and individual assessment of these factors in patients with knee disorders and potentially enhances functional outcomes in anterior cruciate ligament injuries and total knee arthroplasty

Tibial internal rotation in combined anterior cruciate ligament and high-grade anterolateral ligament injury and its influence on ACL length

BACKGROUND Assessment of combined anterolateral ligament (ALL) and anterior cruciate ligament (ACL) injury remains challenging but of high importance as the ALL is a contributing stabilizer of tibial internal rotation. The effect of preoperative static tibial internal rotation on ACL -length remains unknown. The aim of the study was analyze the effect of tibial internal rotation on ACL length in single-bundle ACL reconstructions and to quantify tibial internal rotation in combined ACL and ALL injuries. METHODS The effect of tibial internal rotation on ACL length was computed in a three-dimensional (3D) model of 10 healthy knees with 5° increments of tibial internal rotation from 0 to 30° resulting in 70 simulations. For each step ACL length was measured. ALL injury severity was graded by a blinded musculoskeletal radiologist in a retrospective analysis of 61 patients who underwent single-bundle ACL reconstruction. Preoperative tibial internal rotation was measured in magnetic resonance imaging (MRI) and its diagnostic performance was analyzed. RESULTS ACL length linearly increased 0.7 ± 0.1 mm (2.1 ± 0.5% of initial length) per 5° of tibial internal rotation from 0 to 30° in each patient. Seventeen patients (27.9%) had an intact ALL (grade 0), 10 (16.4%) a grade 1, 21 (34.4%) a grade 2 and 13 (21.3%) a grade 3 injury of the ALL. Patients with a combined ACL and ALL injury grade 3 had a median static tibial internal rotation of 8.8° (interquartile range (IQR): 8.3) compared to 5.6° (IQR: 6.6) in patients with an ALL injury (grade 0-2) (p = 0.03). A cut-off > 13.3° of tibial internal rotation predicted a high-grade ALL injury with a specificity of 92%, a sensitivity of 30%; area under the curve (AUC) 0.70 (95% CI: 0.54-0.85) (p = 0.03) and an accuracy of 79%. CONCLUSION ACL length linearly increases with tibial internal rotation from 0 to 30°. A combined ACL and high-grade ALL injury was associated with greater preoperative tibial internal rotation. This potentially contributes to unintentional graft laxity in ACL reconstructed patients, in particular with concomitant high-grade ALL tears. STUDY DESIGN Cohort study; Level of evidence, 3