Khalid A. Al-Ghamdi

Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid

BackgroundFollicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases.MethodsBRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was a p-value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level.ResultsExpression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2), neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate receptor interacting protein 1 (GRIP1). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions for a number of differentially expressed molecules including vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR), SMAD family member 9 (SMAD9), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and RXRG.ConclusionsThis is one of the first studies using whole-transcript expression arrays to compare expression profiles between FVPTCs and FAs. A set of differentially expressed genes has been identified that contains valuable candidate genes to differentiate both histopathologically related tumor types on the molecular level.

BRAF mutations in thyroid tumors from an ethnically diverse group

BackgroundThe molecular etiology of thyroid carcinoma (TC) and other thyroid diseases which may present malignant precursor lesions is not fully explored yet. The purpose of this study was to estimate frequency, type and clinicopathological value of BRAF exon 15 mutations in different types of cancerous and non-cancerous thyroid lesions originating in an ethnically diverse population.MethodsBRAF exon 15 was sequenced in 381 cases of thyroid lesions including Hashimoto´s thyroiditis, nodular goiters, hyperplastic nodules, follicular adenomas (FA), papillary TC (PTC), follicular variant PTC (FVPTC), microcarcinomas of PTC (micro PTC; tumor size ≤ 1 cm), follicular TC (FTC), and non-well differentiated TC (non-WDTC).ResultsWe identified BRAF mutations in one of 69 FA, 72 of 115 (63%) PTC, seven of 42 (17%) FVPTC, 10 of 56 (18%) micro PTC, one of 17 (6%) FTC, and one of eight (13%) non-WDTC. Most of the cases showed the common V600E mutation. One case each of PTC, FVPTC, and FTC harbored a K601E mutation. A novel BRAF mutation was identified in a FA leading to deletion of threonine at codon 599 (p.T599del). A rare 3-base pair insertion was detected in a stage III PTC resulting in duplication of threonine at codon 599 (p.T599dup). Patients with PTC harboring no BRAF mutation (BRAFwt) were on average younger than those with a BRAF mutation (BRAFmut) in the PTC (36.6 years vs. 43.8 years). Older age (≥ 45 years) in patients with PTC was significantly associated with tumor size ≥ 4 cm (P = 0.018), vessel invasion (P = 0.004), and distant metastasis (P = 0.001). Lymph node (LN) involvement in PTC significantly correlated with tumor size (P = 0.044), and vessel invasion (P = 0.013). Of notice, taken the whole TC group, family history of thyroid disease positively correlated with capsular invasion (P = 0.025).ConclusionsOlder age is manifold associated with unfavorable tumor markers in our series. The K601E identified in a PTC, FVPTC, and FTC seems to be more distributed among different histological types of TC than previously thought. The T599del is a yet undescribed mutation and the rare T599dup has not been reported as a mutation in PTC so far.

The pillowing tendency of materials in single-point incremental forming: Experimental and finite element analyses

The pillow is a defect that adversely affects the geometrical accuracy as well as the formability in single-point incremental forming. With a main objective to control this defect, the effects of mechanical properties of material on pillowing are examined in this work. To identify the mechanical property that significantly affects pillowing, single-point incremental forming tests are conducted using a variety of materials (i.e. 11). It is found that a property (i.e. area reduction at tensile fracture) that controls the formability of a material in single-point incremental forming does not have any significant effect on its pillowing tendency. Interestingly, hardening exponent (i.e. a property that has controlling influence on the stretch-ability of material) appears to be the most influential property that determines the pillowing tendency of sheet metals in single-point incremental forming. Furthermore, the pillowing tendency of a material decreases with the decrease in this particular property. This, according to finite element analysis, occurs because strain localization around the tool/sheet contact correspondingly increases. To select and rank materials with respect to the pillowing behavior, a formula describing the property–pillowing relationship is proposed. As a secondary objective, the correlation between pillowing and forming depth is also investigated in this work. It is shown that initially the pillow progresses as the forming depth increases. However, after forming has been carried out to a certain depth, the pillow begins to regress, most likely due to strain hardening of sheet metal. In conclusion, it is suggested to lower the hardening exponent of sheet metals in order to control pillowing in single-point incremental forming.

Forming Parameters and Forming Defects in Incremental Forming Process: Part B

Single point incremental forming (SPIF), at present, is suffering from defects. With an aim to enhance understanding on their development to control them methodically, FE analyses by varying four parameters are performed in the present study. It is found that, while deforming sheet, stresses develop in the bottom of part. The SPIF defects are in fact outgrowth of these stresses. More precisely, the ratio of vertical- to horizontal-stress is a principal factor that controls (or causes) defects. The development of wall defect depends on the stress ratio in the tool/blank contact (zone A), while that of pillow defect depends on the stress ratio both in the tool/blank contact (zone A) as well as in the center of parts bottom (zone B). Moreover, the magnitude and nature (tension or compression) of the stress ratio, subject to the type of parameter, varies as a parameter is varied. These variations in the stress state in turn affect the defects growth (or size). It is concluded that the stress ratio both in zone A and in zone B needs to be simultaneously controlled so as to overcome the SPIF defects.

Effect of BRAF mutational status on expression profiles in conventional papillary thyroid carcinomas

BackgroundWhereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs.MethodsMicroarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15.ResultsWe identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set.ConclusionsThe expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect important canonical pathways. The identified gene set adds to our understanding of the tumor biology of BRAFwt and BRAFmut PTCs and contains genes/biomarkers of interest.

SPIF of Cu/Steel Clad Sheet: Annealing Effect on Bond Force and Formability

Clad sheet metals offer a better combination of different properties than a monolithic sheet does. In the present study, the formability of a cold bonded Cu/Steel clad sheet was investigated in single point incremental forming (SPIF). In order to relieve deformation stresses, the sheet was annealed over a range of temperature and time. It was found that the sheet ductility increases as the annealing temperature increases, and as a result the formability increases. On the other hand, the bond force at the interface of constituent sheets was observed to decrease with the increasing of temperature. Moreover, the annealing time was found to have no significant effect both on the formability and bond force. Therefore, performing annealing for low times can satisfactorily serve the purpose. The most appropriate annealing temperature for maximizing the formability was 700°C, because higher temperature was noticed to cause severe delamination of Cu layer, thus deteriorating the clad sheet. As a promising aspect of the study, there was no delamination of laminates during forming till the maximum achievable angle. The correlations presented herein study can act as guideline for the users. This study is the first report of its nature.

Machinability comparison of AISI 4340 and Ti-6Al-4V under cryogenic and hybrid cooling environments: A knowledge engineering approach

Efficient removal of heat from the deformation zones in machining of difficult-to-cut materials is vital for attaining viability with respect to cost and productivity. The recently embraced heat removal and lubrication methods include applications of cryogenic fluids and minimum quantity of lubrication. This article presents an experimental investigation, complemented with a fuzzy modeling approach, for comparing the efficacies of using various combinations of CO2 snow and minimum quantity of lubrication in machining two tempers each of AISI 4340 and Ti-6Al-4V. In addition, cutting speed and feed rate are also included as predictor parameters, and their effects on tool damage, machining forces, and specific cutting energy consumption are evaluated. A total of 144 experimental runs are performed for developing the fuzzy knowledge–based model, and additional 20 experiments are conducted for testing its prediction accuracy. The model is also made capable of suggesting optimal settings of the cutting parameters and the most appropriate choice of cooling against various combinations of the objectives. In a nutshell, the cooling option of applying CO2 snow at the rake and flank faces of the tool proved beneficial for machining the titanium alloy while the option of using CO2 snow at the flank face and minimum quantity of lubrication at the rake face outshone the others in the case of the alloy steel. This article claims novelty with regard to machinability comparison of AISI 4340 and Ti-6Al-4V, application of cryogenic cooling to machining of hardened steels, investigation of hybrid cooling (CO2 snow plus minimum quantity of lubrication), and intelligent modeling of cryogenic machining of AISI 4340 and Ti-6Al-4V combined.

Role of climatic factors in the seasonal abundance of Aedes aegypti L. and dengue fever cases in Jeddah province of Saudi Arabia.

Fluctuation in the climatic factors influences not only the human health but also affect the abundance of disease vectors as well as infectious diseases. In the present study an attempt has been made to establish the relationship between Aedes mosquito abundance, dengue fever cases and prevailing climatic factors in the western region of Saudi Arabia. The role of Relative humidity is well established in the abundance of mosquito vector. But the role of temperature & rainfall is unpredictable in this area of study.

Relationships Between Specific Gravities and Higher Heating Values of Petroleum Components

The aim of this study was to estimate mathematical relationships between higher heating value (HHV) and specific gravity of petroleum fuels. The HHV is an important property defining the energy content of petroleum related fuels. The specific gravities of petroleum fuels generally range from 0.56 to 0.92 (based on the specific gravity of pure water is 1 at 15.6°C). There is high regression between specific gravity and HHVs for petroleum fuels. An increase in specific gravity from 0.56 to 0.92 for petroleum fuels decreases the HHVs from 50.4 to 41.6 and the decreases are highly regular. The HHV (MJ/kg) of the petroleum sample as a function of the specific gravity of petroleum constituent can be calculated from: For aliphatics and alicyclics HHV = –21.63SG + 62.88 For aromatics HHV = –2.67SG + 39.23 According to the two equations, higher heating value of petroleum is a function of the specific gravity of petroleum constituent. The HHVs (MJ/kg) of the crude oil samples as a function of carbon (C), hydrogen (H), oxygen (O), nitrogen (N), and sulfur (S) can be calculated from the following equation: HHV = 31.6(C) + 142.3(H) + 30.8(S) – 15.4(O) – 14.5(N)

Force Variations with Defects and a Force-based Strategy to Control Defects in SPIF

The control of defects and forces is, respectively, necessary to produce robust components and to preserve machine tool and energy. In the present work, the variations in forces with the evolution of various SPIF (single point incremental forming) defects are studied by employing the pyramid geometry. It is found that the forming force increases as the size of pillow and wall defects increases, and contrarily decreases as the size of corner-fold increases. Further, to carry out defect-free forming, the corner requires more force than the straight-wall of pyramid (i.e., F cr > F sw). This fact appears in the form of spikes corresponding to corner location in the force curve. Therefore, online monitoring of the force curve is proposed as a strategy to control defects in SPIF. Finally, following the condition F cr > F sw, force models describing the defect–force–parameter relationship are developed. These models will help the users to simultaneously predict and optimize the force as well as defects.