Evaluation of thermal pattern distributions in racehorse saddles using infrared thermography

The impact of a rider’s and saddle’s mass on saddle thermal pattern distribution was evalu ated using infrared thermography (IRT). Eighteen racehorses were ridden by four riders with their own saddle. Images of the saddle panels were captured at each of six thermographic examinations. On each image, six regions of interest (ROIs) were marked on the saddle panels. The mean temperature for each ROI was extracted. To evaluate the influence of load on saddle fit, 4 indicators were used: ΔTmax (difference between the mean temperature of the warmest and coolest ROI); standard deviation of the mean temperature of the six ROIs; right/left; bridging/rocking and front/back thermal pattern indicator. Incorrect saddle fit was found in 25 measurements (23.1%) with ΔTmax greater than 2˚C. The relationships between rider and saddle fit as well as saddle fit and horse were significant (p<0.001). An average ΔTmax in rider A was significantly higher than in other riders (p<0.001). The right/left thermal pattern differed significantly from the optimal value for riders A and B; while the bridging/rocking thermal pattern differed significantly from this value for riders A, C and D (p<0.05). Front saddle thermal pattern was most frequent for rider A (41.5%), whereas back saddle thermal pattern was most frequent for rider C (85.7%). Measurement of the mean temperature in 6 ROIs on saddle panels after training was helpful in assessing the influence of rider and saddle mass on saddle fit. IRT offered a non-invasive, rapid and simple method for assessing load on thermal pattern distribution in race saddles.info:eu-repo/semantics/publishedVersio

Single Nucleotide Polymorphism in the LDHA Gene as a Potential Marker for the Racing Performance of Pigeons

The objective of the present study was to investigate the relationship between the g.2582481G>A, g.2583935G>A and g.2584057C>T single nucleotide polymorphisms (SNPs) within the lactate dehydrogenase A gene (LDHA) coding for lactate dehydrogenase isoform A and the racing performance of homing pigeons. As a measure of racing performance, we used the mean values of ace points won by individual birds during the whole season. The estimated heritability of the racing performance of pigeons was relatively low (h2=0.0596; SE=0.0249). The analysis performed for all race reports together showed that the factors such as gender, weather conditions at the start and at the end of the race affect the analyzed trait. Of the 3 single nucleotide polymorphisms, only the effect of the g.2582481G>A genotype on the performance of racing pigeons was significant. Statistical analysis indicated the difference in the value of ace points between the animals of GG and GA genotypes for the g.2582481G>A SNP. The study showed that the genotype homozygous for g.2582481A is linked to the highest mean value of ace points. Consequently, the relationship between the genotype for g.2582481G>A and the racing performance was shown

Dystocia in Friesian cows and its effects on postpartum reproductive performance and milk production

A total of 1,243 records for 585 dairy Friesian cows from 1997–2004 were used to study the factors affecting dystocia and its effects on reproductive performance and milk production. The overall incidence of dystocia was 6.9%. The percentage of dystocia decreased with increasing live body weight, age, and parity of cows (P < 0.05); however, it increased with increasing birth weight of calves (P < 0.05). The highest percentage of dystocia was detected in winter season, but the least percentage was in summer season (P < 0.05). The percentage of incidence of dystocia was significantly (P < 0.05) higher with winter feeding compared to summer ration (8.2% vs. 5.1%). The percentage of incidence of dystocia was significantly (P < 0.05) higher with twinning than single calving (15.5% vs. 6.5%), while not significantly affected by the sex of born calves. Incidence of dystocia had adverse effects on reproductive performance and milk yield. The service interval, service period, days open, and calving interval were significantly (P < 0.05) longer in cows afflicted with dystocia compared to normal cows. The conception rate was lower (P < 0.05), but the number of service per conception was higher (P < 0.05) in cows afflicted with dystocia compared to normal cows (60.5% vs. 73.0% and 3.4 vs. 2.7, respectively). Average daily milk yield was lower (P < 0.05) by 1 kg for cows with incidence of dystocia compared to normal cows

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

BCR-ABL1-independent PI3Kinase activation causing imatinib-resistance

<p>Abstract</p> <p>Background</p> <p>The <it>BCR-ABL1 </it>translocation occurs in chronic myeloid leukemia (CML) and in 25% of cases with acute lymphoblastic leukemia (ALL). The advent of tyrosine kinase inhibitors (TKI) has fundamentally changed the treatment of CML. However, TKI are not equally effective for treating ALL. Furthermore, <it>de novo </it>or <it>secondary </it>TKI-resistance is a significant problem in CML. We screened a panel of <it>BCR-ABL1 </it>positive ALL and CML cell lines to find models for imatinib-resistance.</p> <p>Results</p> <p>Five of 19 <it>BCR-ABL1 </it>positive cell lines were resistant to imatinib-induced apoptosis (KCL-22, MHH-TALL1, NALM-1, SD-1, SUP-B15). None of the resistant cell lines carried mutations in the kinase domain of <it>BCR-ABL1 </it>and all showed resistance to second generation TKI, nilotinib or dasatinib. STAT5, ERK1/2 and the ribosomal S6 protein (RPS6) are <it>BCR-ABL1 </it>downstream effectors, and all three proteins are dephosphorylated by imatinib in sensitive cell lines. TKI-resistant phosphorylation of RPS6, but responsiveness as regards JAK/STAT5 and ERK1/2 signalling were characteristic for resistant cell lines. PI3K pathway inhibitors effected dephosphorylation of RPS6 in imatinib-resistant cell lines suggesting that an oncogene other than <it>BCR-ABL1 </it>might be responsible for activation of the PI3K/AKT1/mTOR pathway, which would explain the TKI resistance of these cells. We show that the TKI-resistant cell line KCL-22 carries a PI3Kα E545G mutation, a site critical for the constitutive activation of the PI3K/AKT1 pathway. Apoptosis in TKI-resistant cells could be induced by inhibition of AKT1, but not of mTOR.</p> <p>Conclusion</p> <p>We introduce five Philadelphia-chromosome positive cell lines as TKI-resistance models. None of these cell lines carries mutations in the kinase domain of <it>BCR-ABL1 </it>or other molecular aberrations previously indicted in the context of imatinib-resistance. These cell lines are unique as they dephosphorylate ERK1/2 and STAT5 after treatment with imatinib, while PI3K/AKT1/mTOR activity remains unaffected. Inhibition of AKT1 leads to apoptosis in the imatinib-resistant cell lines. In conclusion, Ph+ cell lines show a form of imatinib-resistance attributable to constitutive activation of the PI3K/AKT1 pathway. Mutations in <it>PIK3CA</it>, as observed in cell line KCL-22, or PI3K activating oncogenes may undelie TKI-resistance in these cell lines.</p

Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

<p>Abstract</p> <p>Background</p> <p>Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples.</p> <p>Methods</p> <p>We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated <it>CD44 </it>was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of <it>CD44 </it>and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry.</p> <p>Results</p> <p>On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that <it>CD44 </it>was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: <it>CD44 </it>was not methylated in MCL patients (0/11) whereas <it>CD44 </it>was frequently hypermethylated in BL patients (18/29). In cell lines with <it>CD44 </it>hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of <it>CD44</it>. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44⁺lymphoma cells. <it>CD44 </it>hypermethylated, CD44^-lymphoma cell lines were consistently resistant towards anti-CD44 induced apoptosis.</p> <p>Conclusion</p> <p>Our data show that <it>CD44 </it>is epigenetically regulated in lymphoma and undergoes <it>de novo </it>methylation in distinct lymphoma subtypes like BL. Thus <it>CD44 </it>may be a promising new epigenetic marker for diagnosis and a potential therapeutic target for the treatment of specific lymphoma subtypes.</p

Detekcja jałówek z trudnymi porodami za pomocą sztucznych sieci neuronowych z uwzględnieniem genotypów ERalfaBGLI, ERalfa-SNABI i CYP19-PVUII

The aim of this study was to detect heifers with dystocia using artificial neural networks (ANN). A total of 531 calving records of Holstein-Friesian heifers of Black-and-White strain and 8 diagnostic variables were used. The output variable was the class of calving difficulty: difficult or easy. Perceptrons with one (MLP1) and two (MLP2) hidden layers and radial basis function (RBF) networks were investigated. The root mean square error and the structure of selected ANN (number of neurons in the input, hidden and output layers) were 0.22, 10-4-1; 0.25, 10-17-17-1 and 0.19, 10-25-1 for MLP1, MLP2 and RBF, respectively. The percentage of correctly recognized heifers with difficult and easy calvings and that of correctly diagnosed heifers from both categories for the training and validation sets were approx. 90%. The same values for the test set were 75-83%, 82–88% and 82–86%, respectively. In both cases, no significant differences in these proportions were found. The following variables contributed most to the detection of heifers with dystocia: gestation length, BCS index, CYP19-PvuII and ERα-BglI genotypes and percentage of HF genes in heifer’s genotype.Celem niniejszej pracy była detekcja jałówek z trudnymi porodami przy użyciu sztucznych sieci neuronowych (SSN).Wykorzystano w tym celu dane o 531 wycieleniach jałówek rasy polskiej holsztyńsko-fryzyjskiej odmiany czarno-białej oraz 8 zmiennych diagnostycznych. Zmienną wyjściową była klasa trudności porodu: trudny lub łatwy. Analizowano perceptrony z jedną (MLP1) i dwoma (MLP2) warstwami ukrytymi oraz sieci o radialnych funkcjach bazowych (RBF). Pierwiastek błędu średniokwadratowego oraz struktura wybranych SSN (liczba neuronów w warstwach wejściowej, ukrytej i wyjściowej) były następujące: 0,22, 10-4-1; 0,25, 10-17-17-1 i 0,19, 10-25-1 odpowiednio dla MLP1, MLP2 i RBF. Odsetek prawidłowo rozpoznanych jałówek z trudnymi i łatwymi porodami oraz odsetek prawidłowo zdiagnozowanych jałówek z obu kategorii dla zbioru uczącego i walidacyjnego wynosiły ok. 90%.Wartości te dla zbioru testowego wynosiły odpowiednio: 75–83%, 82–88% i 82–86%. W obu przypadkach nie stwierdzono istotnych statystycznie różnic między tymi proporcjami. Następujące zmienne miały największy wkład w detekcję jałówek z trudnymi porodami: długość ciąży, indeks BCS, genotypy CYP19-PvuII i ERα-BglI oraz procentowy udział genow hf w genotypie jałówki

Effect of process parameters on the condition of the wire electrode in WEDM of Ti6Al4V

Conventional machining of titanium alloy Ti6Al4V cause high temperature and rapid wear of tool which makes him hardly suitable for machining by machine cutting. The presented experimental study was carried out on a modern wire EDM Sodick AQ327L. Three types of the wire were used. Investigated were the effects of such input parameters as the pulse width and the time between two pulses on the output parameters such as area cutting efficiency, workpiece surface roughness and wear rate of the electrode. The resulting relationships were determined using the conventional regression analysis and neural networks. The results were checked for goodness of fit

Analysis of the wire electrical discharge machinability of roots of steam turbine blades

This paper presents method for the unconventional machining of the blades of steam turbines. Blade material as steel X12Cr13 was chosen into the investigation. Blade failures in gas turbine engines often lead to loss of all downstream stages and can have a dramatic effect on the availability of the turbine engines.. Conventional machining of the roots of steam turbine blades causes high temperature and rapid wear of tool which makes machining expensive WEDM is currently regarded among the most popular non-conventional machining. WEDM allows treatment of hard, brittle materials and composite, irrespective of their structure (thin-wall components) and mechanical properties. Submitted work is an analysis of potential impact on the received thickness of heat affected zone by appropriate heat treatment of material prior to WEDM. Such action is intended to eliminate or reduce the initiating impact of any microcracks on the formation of surface defects on the turbine blades roots during operation. The aim of the article is to replace the traditional methods of machining the blades roots by WEDM and thus the elimination of problems such as the need to monitor the tool wear. The presented experimental study was carried out on a modern wire EDM Sodick AQ327L. Investigated were the effects of WEDM of X12Cr13 steel as the Heat Affected Zone, the micro-fractures and surface roughness parameters