Fracture of high-density polyethylene used for bleach bottles

High-density polyethylene (HDPE) can be blow-molded and used for the production of bottles for aggressive products. These products can interact both chemically and physically with the polymer constituting these containers, leading to a decrease in the performance of the material and undermining the structural integrity of the component. A fracture mechanics approach was adopted to evaluate the Environmental Stress Cracking Resistance (ESCR) of two HDPE commercial grades used for bleach containers; two different solutions, with and without sodium hypochlorite (the main ingredient of commercial bleach solutions), were considered as aggressive environments. Size effects were studied using different test configurations and loading histories in air. The correlation between the stress intensity factor and the initiation time was found. A clear effect of the aggressive solutions on the fracture resistance of the two HDPEs was observed, irrespective of the presence of sodium hypochlorite; the effect therefore has to be ascribed to other bleach components

Identification of novel androgen-responsive genes by sequencing of LongSAGE libraries

<p>Abstract</p> <p>Background</p> <p>The development and maintenance of the prostate is dependent on androgens and the androgen receptor. The androgen pathway continues to be important in prostate cancer. Here, we evaluated the transcriptome of prostate cancer cells in response to androgen using long serial analysis of gene expression (LongSAGE) libraries.</p> <p>Results</p> <p>There were 131 tags (87 genes) that displayed statistically significant (p ≤ 0.001) differences in expression in response to androgen. Many of the genes identified by LongSAGE (35/87) have not been previously reported to change expression in the direction or sense observed. In regulatory regions of the promoter and/or enhancer regions of some of these genes there are confirmed or potential androgen response elements (AREs). The expression trends of 24 novel genes were validated using quantitative real time-polymerase chain reaction (qRT-PCR). These genes were: <it>ARL6IP5, BLVRB, C19orf48, C1orf122, C6orf66, CAMK2N1, CCNI, DERA, ERRFI1, GLUL, GOLPH3, HM13, HSP90B1, MANEA, NANS, NIPSNAP3A, SLC41A1, SOD1, SVIP, TAOK3, TCP1, TMEM66, USP33</it>, and <it>VTA1</it>. The physiological relevance of these expression trends was evaluated <it>in vivo </it>using the LNCaP Hollow Fibre model. Novel androgen-responsive genes identified here participate in protein synthesis and trafficking, response to oxidative stress, transcription, proliferation, apoptosis, and differentiation.</p> <p>Conclusion</p> <p>These processes may represent the molecular mechanisms of androgen-dependency of the prostate. Genes that participate in these pathways may be targets for therapies or biomarkers of prostate cancer.</p

Tracking of Normal and Malignant Progenitor Cell Cycle Transit in a Defined Niche.

While implicated in therapeutic resistance, malignant progenitor cell cycle kinetics have been difficult to quantify in real-time. We developed an efficient lentiviral bicistronic fluorescent, ubiquitination-based cell cycle indicator reporter (Fucci2BL) to image live single progenitors on a defined niche coupled with cell cycle gene expression analysis. We have identified key differences in cell cycle regulatory gene expression and transit times between normal and chronic myeloid leukemia progenitors that may inform cancer stem cell eradication strategies

High-throughput sequencing: a failure mode analysis

BACKGROUND: Basic manufacturing principles are becoming increasingly important in high-throughput sequencing facilities where there is a constant drive to increase quality, increase efficiency, and decrease operating costs. While high-throughput centres report failure rates typically on the order of 10%, the causes of sporadic sequencing failures are seldom analyzed in detail and have not, in the past, been formally reported. RESULTS: Here we report the results of a failure mode analysis of our production sequencing facility based on detailed evaluation of 9,216 ESTs generated from two cDNA libraries. Two categories of failures are described; process-related failures (failures due to equipment or sample handling) and template-related failures (failures that are revealed by close inspection of electropherograms and are likely due to properties of the template DNA sequence itself). CONCLUSIONS: Preventative action based on a detailed understanding of failure modes is likely to improve the performance of other production sequencing pipelines

Sequence biases in large scale gene expression profiling data

We present the results of a simple, statistical assay that measures the G+C content sensitivity bias of gene expression experiments without the requirement of a duplicate experiment. We analyse five gene expression profiling methods: Affymetrix GeneChip, Long Serial Analysis of Gene Expression (LongSAGE), LongSAGELite, ‘Classic’ Massively Parallel Signature Sequencing (MPSS) and ‘Signature’ MPSS. We demonstrate the methods have systematic and random errors leading to a different G+C content sensitivity. The relationship between this experimental error and the G+C content of the probe set or tag that identifies each gene influences whether the gene is detected and, if detected, the level of gene expression measured. LongSAGE has the least bias, while Signature MPSS shows a strong bias to G+C rich tags and Affymetrix data show different bias depending on the data processing method (MAS 5.0, RMA or GC-RMA). The bias in the Affymetrix data primarily impacts genes expressed at lower levels. Despite the larger sampling of the MPSS library, SAGE identifies significantly more genes (60% more RefSeq genes in a single comparison)

Identification of transcripts with enriched expression in the developing and adult pancreas

The expression profile of different developmental stages of the murine pancreas and predictions of transcription factor interactions, provides a framework for pancreas regulatory networks and development

The effect of posterior tibial slope on simulated laxity tests in cruciate-retaining TKA

INTRODUCTION: Tibial slope can affect the outcomes of Total Knee Arthroplasty (TKA). More posterior slope potentially helps releasing a too tight flexion gap and it is generally associated with a wider range of post-operative knee flexion. However, the mechanism by which tibial slope affects the function of TKA during dynamic activities of daily living is rather complex and not well documented. The aim of this study was to investigate the effect of tibial slope on the kinematics of the tibiofemoral (TF) contact point, quadriceps muscle forces, and patellofemoral (PF) joint contact forces during squat. In addition, we studied the effect of anterior tibial cortex-referencing (ACR) versus center of tibial plateau-referencing (CPR), as two possible techniques to obtain the desired degree of tibial slope. METHODS: A previously validated musculoskeletal model of a 86-year-old male subject, having a cruciate-retaining (CR) TKA prosthesis, was used to simulate a squat activity [1]. Motion-capture data were input to a motion optimization algorithm to find the full body kinematics. Quadriceps muscle forces were then calculated using inverse-dynamics. The kinematics of the TF contact point and PF joint contact forces were simultaneously calculated using force-dependent kinematics. A baseline case with 0° tibial slope was simulated, plus four additional cases with anterior (-3°), and posterior (+3°, +6°, +9°) tibial slope using the ACR technique (Fig. 1a), and four using the CPR technique (Fig. 1b). RESULTS: Compared to the baseline, more posterior tibial slope with ACR technique resulted in a larger excursion of the TF contact point, which shifted to a more anterior position, on the lateral side, and a more posterior position, on the medial side, in extension (Fig. 2). With the CPR technique, the contact point in extension shifted gradually more posterior on both sides with more posterior slope, and in flexion it shifted gradually more posterior mainly on the lateral side. The peak quadriceps force decreased on average by 1.7 and 1.2 % BW per degree of more posterior slope, with the ACR and CPR techniques, respectively. However, due to the different relative position of patella and femur, the peak PF contact force was mainly reduced by increasing the posterior slope with the CPR technique (-3.9 % BW/degree), rather than with the ACR technique (-1.5 % BW/degree) (Fig. 3). DISCUSSION: Increasing the tibial slope using the ACR technique produced large changes in the TF kinematics: the pattern of the contact point became more unstable, with a larger AP movement observed on the lateral side, denoting increased anterior-posterior laxity. On the other hand, variations of tibial slope with CPR technique resulted in more stable TF kinematics, more posterior position of the TF contact point, and a greater reduction of the PF contact forces. It is advisable to pre-plan the desired amount of tibial slope and execute it using the CPR technique. The surgeon should be very careful applying too much tibial slope with the ACR technique in CR-TKA, as it may have devastating effects on the TF kinematics, laxity and PF forces. SIGNIFICANCE: This study provides new insights into the effect of variation of tibial slope in TKA using different surgical techniques, which were not documented before, and used a highly controlled and parameterized study design and dynamic loading conditions. Orthopedic surgeons can directly use these results as an indication for the clinical practice. The presented tool can also be very useful for educational/medical training purposes

The effect of tibial slope on the biomechanics of cruciate-retaining TKA:a musculoskeletal simulation study

INTRODUCTION: Tibial slope can affect the outcomes of Total Knee Arthroplasty (TKA). More posterior slope potentially helps releasing a too tight flexion gap and it is generally associated with a wider range of post-operative knee flexion. However, the mechanism by which tibial slope affects the function of TKA during dynamic activities of daily living is rather complex and not well documented. The aim of this study was to investigate the effect of tibial slope on the kinematics of the tibiofemoral (TF) contact point, quadriceps muscle forces, and patellofemoral (PF) joint contact forces during squat. In addition, we studied the effect of anterior tibial cortex-referencing (ACR) versus center of tibial plateau-referencing (CPR), as two possible techniques to obtain the desired degree of tibial slope. METHODS: A previously validated musculoskeletal model of a 86-year-old male subject, having a cruciate-retaining (CR) TKA prosthesis, was used to simulate a squat activity [1]. Motion-capture data were input to a motion optimization algorithm to find the full body kinematics. Quadriceps muscle forces were then calculated using inverse-dynamics. The kinematics of the TF contact point and PF joint contact forces were simultaneously calculated using force-dependent kinematics. A baseline case with 0° tibial slope was simulated, plus four additional cases with anterior (-3°), and posterior (+3°, +6°, +9°) tibial slope using the ACR technique (Fig. 1a), and four using the CPR technique (Fig. 1b). RESULTS: Compared to the baseline, more posterior tibial slope with ACR technique resulted in a larger excursion of the TF contact point, which shifted to a more anterior position, on the lateral side, and a more posterior position, on the medial side, in extension (Fig. 2). With the CPR technique, the contact point in extension shifted gradually more posterior on both sides with more posterior slope, and in flexion it shifted gradually more posterior mainly on the lateral side. The peak quadriceps force decreased on average by 1.7 and 1.2 % BW per degree of more posterior slope, with the ACR and CPR techniques, respectively. However, due to the different relative position of patella and femur, the peak PF contact force was mainly reduced by increasing the posterior slope with the CPR technique (-3.9 % BW/degree), rather than with the ACR technique (-1.5 % BW/degree) (Fig. 3). DISCUSSION: Increasing the tibial slope using the ACR technique produced large changes in the TF kinematics: the pattern of the contact point became more unstable, with a larger AP movement observed on the lateral side, denoting increased anterior-posterior laxity. On the other hand, variations of tibial slope with CPR technique resulted in more stable TF kinematics, more posterior position of the TF contact point, and a greater reduction of the PF contact forces. It is advisable to pre-plan the desired amount of tibial slope and execute it using the CPR technique. The surgeon should be very careful applying too much tibial slope with the ACR technique in CR-TKA, as it may have devastating effects on the TF kinematics, laxity and PF forces. SIGNIFICANCE: This study provides new insights into the effect of variation of tibial slope in TKA using different surgical techniques, which were not documented before, and used a highly controlled and parameterized study design and dynamic loading conditions. Orthopedic surgeons can directly use these results as an indication for the clinical practice. The presented tool can also be very useful for educational/medical training purposes. REFERENCES: [1] Marra MA, Vanheule V, Fluit R, et al. A Subject-Specific Musculoskeletal Modeling Framework to Predict In Vivo Mechanics of Total Knee Arthroplasty. ASME. J Biomech Eng. 2015;137(2):020904-020904-12 ACKNOWLEDGEMENTS: The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 323091 awarded to N. Verdonschot