Presence Of Amplification Research Articles

Soret Effect on Mixed Convection of Casson Fluid Flow in Presence of Porous Media in a Porous Channel

The purpose is to investigate the impact of Soret on free and mixed convective Casson fluid flow in presence of amplification in a porous channel with magnetic field is carried out analytically. The obtained are coupled PDEs are highly nonlinear and are converted to an ODEs by similarity transformation and further solved by using perturbation technique to obtain velocity, concentration and temperature equations of the physical system. The influence of non-dimensional parameters such as Prandtl number Pr, Schmidt number Sc, thermal buoyancy parameter λ, Reynolds number R, chemical reaction rate γ, concentration buoyancy parameter N, Darcy number Da, Casson fluid parameter β, Hartmann number M2 , Soret effect Sr on velocity, thickness of fluid and heat have been discussed with graphs. The few important computational outcomes reveal that the Soret effect Sr enriches the concentration, fluid flow and temperature of fluid whereas Casson fluid parameter β diminishes the profiles. The earlier work and present work have been compared in the absence of Soret effect and is establishes to be good contract.

Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma?

Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). PIK3CA gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 tumors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor (r = −0.243) and positive correlation with a 5-year survival (r = 0.235). The number of copies of the PIK3CA gene was associated with the tumor grading (r = 0.208). The present study shows that loss of PTEN protein and the grading (p = 0.040), distant metastases (p = 0.033), smoking (p = 0.016), and alcohol abuse (p = 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival (p = 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results.

CCND1 and FGFR1 gene amplifications are associated with reduced benefit from aromatase inhibitors in metastatic breast cancer.

Endocrine therapy is a mainstay for the treatment of hormone receptor-positive breast cancer (BC); however, only a fraction of patients experience a pronounced response to antagonists of estrogen signaling. There is a need to identify predictors for efficacy of this treatment. This study included 138 patients with newly diagnosed metastatic BC, who received upfront endocrine therapy. Archival biopsy specimens were tested for CCND1 and FGFR1 gene amplification and mRNA expression by PCR-based methods. CCND1 and FGFR1 amplification was detected in 24 (17.9%) and 28 (20.9%) of 134 evaluable cases, respectively; 9 carcinomas had concurrent alterations of these two genes. Presence of amplification in at least one locus was more common in tumors of higher grade (p = 0.018) and was associated with higher Ki-67 proliferation index (p = 0.036). CCND1 gene amplification was associated with shorter progression-free survival (PFS) in patients receiving aromatase inhibitors (AI) [16.0months vs. 32.4months, HR = 3.16 (95% CI 1.26-7.93), p = 0.014]. FGFR1 status did not significantly affect PFS of AI-treated women; however, objective response to AI was observed less frequently in FGFR1-amplified BC as compared to cases with normal FGFR1 copy number [2/15 (13.3%) vs. 22/46 (47.8%), p = 0.031]. Meanwhile, CCND1/FGFR1 gene status did not influence the outcome of tamoxifen-treated patients. Presence of CCND1 and/or FGFR1 amplification is associated with worse outcomes of AI therapy in patients with metastatic BC.

Mie Scatter and Interfacial Tension Based Real-Time Quantification of Colloidal Emulsion Nucleic Acid Amplification.

This work demonstrates for the first time rapid, real-time Mie scatter sensing of colloidal emulsion nucleic acid amplification directly from emulsion droplets. Loop-mediated isothermal amplification is used in this study, and, to our knowledge, has not previously been used in a colloidal emulsion platform. Interfacial tension values (γ) associated with bulk protein adsorption and denaturation at the oil-water interface exhibit characteristic changes in the absence or presence of amplification. In the presence of target and amplicon, emulsions maintain a constant 300-400 nm diameter, whereas emulsions formed with no target control show a rapid decrease in droplet diameter to <100 nm over the first 20 min of incubation. This method is validated using whole bacteria (Staphylococcus aureus MSSA and Escherichia coli O157:H7) and whole virus (Potato virus Y and Zika virus) samples suspended in water, buffer, or serum-like matrices. Short-term formation of colloidal emulsion is quantified via 60° scatter monitoring, where the initial slope of scattering intensity is utilized to confirm target amplification in less than 5 min. The unique benefits of this method render it more cost-effective and field-deployable than existing methods, while being adaptable to a multitude of targets, sample matrices, and nucleic acid amplification tests.

PROGNOSTIC SIGNIFICANCE OF REARRANGEMENTS OF EML4-ALK IN PATIENTS WITH STAGE TI-II ADENOCARCINOMA IN THE RELATIONSHIP WITH SOME CLINICAL AND MORPHOLOGICAL PARAMETERS

The purpose of the study: determination of ALK gene status (mutation) in patients with stage TI-II adenocarcinoma in the relationship with survival, stage, size, metastases in bronchopulmonary lymph nodes and the amplification of Her2/Neu. Materials. 98 stage I-II adenocarcinoma patients. Cases with a mutation in ALK account for 20 (4.8% without randomization). There was used the immunohistochemical method and in situ hybridization. Results. The survival rate of adenocarcinoma patients with metastases in the lymph nodes was lower than in cases without metastases: 8.3 ± 7.8% and 40.9 ± 13% respectively. None of patients with a mutation ALK lived up to 9 years in contrast to the cases without mutations (37.4 ± 12.6%). In the presence of amplification of the Her2 gene survival rate in adenocarcinoma patients was lower if compared to cases without amplification (p = 0.02). Correlation between ALK mutation and amplification of Her2 with increased N is not revealed. Thus, an independent criterion of the prognosis for cases with of stage I-II lung adenocarcinoma is the N index (χ2 = 9.6, p = 0.001). The rate of mutation of ALK was lower, but had the second largest impact on the prognosis (χ2 = 7.7, p = 0.005).

DIAGNOSTIC CAPABILITIES OF DIGITAL FLUOROGRAPHY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The purpose of the study – to examine the capabilities of the method of digital chest fluorography in diagnosis of chronic obstructive pulmonary disease (COPD) of different stages. By chest digital fluorography 247 patients with clinically diagnosed COPD stage I–III were examined. The average age of the patients was (55.3  1.7) years (16 to 88 years), forced expiration volume for the first second (FEV1) was (59.17  16.28) %. It was shown that for patients with COPD stage I most characteristic radiographic symptom was emphysema of the lung in the upper regions (26 (48%) of 54 patients); the mean values of the inspiratory lung optical density (ILOD) ranged from (703.48  2.15) to (807.47  5.61) optical density units (ODU), the expiratory lung optical density (ELOD) – from (786.05  6.15) to (830.23  4.71) ODU. For patients with COPD stage II the most common radiographic sign was the presence of amplification and deformation pulmonary pattern (95 (89%) of 107 patients); the mean values of ILOD ranged from (646.20  4.94) to (791.38  2.81) ODU, ELOD – from (677.34  9.91) to (813.91  3.29) ODU. Patients with COPD stage III were characterized by a combination of amplification and deformation pulmonary pattern (77 (90%) of 86 patients) with lung emphysema (51 (59%) of 86 patients); the mean values of the inspiratory lung optical density ranged from (765.93  16.4) to (863.37  15.83) ODU, expiratory lung optical density – from (826.80  11.64) to (881.37  4.29) ODU. Thus, we concluded that the method of digital chest fluorography, possessing low dose burden to the patient, can detect the characteristic radiological symptoms and determine the stage of the disease up to the values of the lung optical density in patients with COPD.

HER2 testing in esophageal adenocarcinoma (EAC) using parallel tissue-based methods.

2 Background: Testing for HER2 in EAC has become routine given its ability to predict benefit from HER2-targeted therapy. HER2 protein analysis by immunohistochemistry (IHC) is more rapid and generally less expensive than assessment of gene amplification by fluorescence in situ hybridization (FISH). However, the accuracy of IHC for predicting HER2 amplification has not been examined in a large EAC cohort. Methods: Surgical EAC specimens were examined from 675 patients who underwent curative resection at a single institution without preoperative therapy. Tumors were located in the esophagus (47%) or gastroesophageal junction (53%); most were node-positive (73%). Every tumor was evaluated by IHC in parallel with FISH in a blinded manner using FDA-approved assays. A consensus IHC score was determined by 2 pathologists using tumor-specific criteria (negative, 0 or 1+; equivocal, 2+; positive, 3+). Gene amplification by FISH was defined as a HER2/CEP17ratio ≥ 2. Results: HER2 amplification was detected in 89% of IHC 3+ cases, 13% of IHC 2+ cases, and 4% of IHC 0-1+ cases (Table). Accordingly, using FISH as the reference standard, the positive predictive value (PPV) of a positive IHC test (3+) was 89% (79/89 [95% CI 82%-95%]), and the negative predictive value of a negative IHC test (0-1+) was 96% (401/417 [94%-98%]). Importantly, the PPV of an equivocal IHC score (2+) for detecting HER2 amplification was 13% (22/169 [8%-18%]). Conclusions: In the largest study to date comparing HER2 testing methods in EAC, a negative IHC result (0 or 1+) nearly excludes the presence of gene amplification by FISH. Whereas a positive IHC result (3+) strongly predicts for the presence of amplification, an equivocal IHC result (2+) is a weak predictor. These findings in EAC support a HER2 testing algorithm where IHC is used for initial screening and FISH testing is restricted to cases with equivocal IHC results. [Table: see text]

Nonlinear Shannon Limit in Pseudolinear Coherent Systems

In this paper, we develop a general first-order perturbation theory of the propagation of a signal in an optical fiber in the presence of amplification and Kerr nonlinearity, valid for arbitrary pulse shapes. We obtain a general expression of the sampled signal after optical filtering, coherent detection, and optimal sampling. We include intrachannel and as well as interchannel nonlinear effects. We obtain simplified expressions in the case in which the accumulated dispersion is high (equivalent to the far-field limit in paraxial optics). This general theory is applied in detail to the special case of spectral-efficient sinc pulses. This exercise shows that the characteristics of the neighboring wavelength-division multiplexed channels are essential in determining the nonlinear impairments.

Immunohistochemical Overexpression of Platelet-Derived Growth Factor Receptor–Beta (PDGFR-β) is Associated With PDGFRB Gene Copy Number Gain in Sarcomatoid Non–Small-Cell Lung Cancer

IntroductionSarcomatoid non-small cell lung cancer (NSCLC) is an uncommon histologic variant that has not been molecularly well-characterized. We hypothesized that the PDGF-B/PDGF-Rβ pathway may be dysregulated in sarcomatoid lung cancer. MethodsWe conducted immunohistochemical (IHC) and gene copy number gain studies of PDGF-B/PDGFR-β on archived surgically resected specimens, 43 sarcomatoid NSCLCs and 42 control NSCLCs that were age, gender and stage-matched. Biomarkers were correlated to patient demographics, tumor characteristics, and survival. ResultsSarcomatoid tumors had higher PDGFR-β IHC expression than control NSCLC (median score 2.69 vs. 1.93; P < 0.0001). No difference was seen between the two groups of PDGF-B IHC expression; and neither PDGF-B nor PDGFR-β IHC levels correlated with gender, age, clinical or pathologic TNM status, or overall survival. PDGFRB gene copy number was evaluated by FISH using three ways: presence of amplification, gene copy number gain, and gene copy ratio between tumor and normal tissue. PDGFRB gene copy number gain was associated with sarcomatoid histology (P = 0.006), lower clinical and pathologic T-stage (P = 0.07, P = 0.048), and higher pathologic N-stage (P = 0.013). Sarcomatoid NSCLC patients (P = 0.006) and female patients (P = 0.03) had higher gene copy ratios above 1.83. Higher PDGFR-β IHC expression in tumor cells was associated with gene copy number gain (P = 0.021) and higher gene copy ratio status (P = 0.005). ConclusionThis is the first study to demonstrate high PDGFR-β IHC expression and gene copy number gain in sarcomatoid NSCLC tumors and suggests that further studies are warranted to determine whether PDGFR-β is a feasible therapeutic target in this population.

Use of the ErbB2/CEP17 ratio to predict prognosis and response to trastuzumab-based therapy in the metastatic breast cancer setting

11110 Background: Despite patient selection based upon detection of Her-2/neu overexpression by immunohistochemistry (IHC) and/or presence of amplification of the Her-2/neu-encoding erbB2 oncogene measured by FISH, response to trastuzumab-based therapy is only achieved in a subset of patients with Her-2/neu overexpressing breast carcinomas. Exact quantification of erbB2 copy-number relative to chromosome 17 (CEP17) (ErbB2/CEP17 ratio “R”) probably adds further important predictive information. Methods: Clinical data of 137 patients receiving trastuzumab based treatment for Her-2/neu overexpressing (IHC) metastatic breast cancer were analysed. ErbB2/CEP17 ratio (R) was determined by quantitative FISH analysis in original tumor tissue using Vysis PathVysion DNA-based FISH technology. Results: ErbB2/CEP17 (R) provided additional predictive value for progression free survival (PFS) and time to first metastasis (TTM), but not for overall survival (OS) (all from start of trastuzumab containing treatment). The following cutoffs of Her-2/neu were identified: group A: 0–2.2 R (TTM: 49.8; OS: 6.7; PFS: 6.2); group B: 2.2- 6 R (TTM: 26.2; OS: 5.3; PFS: 9.3); group C: &gt;6 CN (TTM: 20.1; OS: 3.9; PFS: 13.7) Kaplan-Maier analysis showed significant longer TTM for group A (p&lt;0.01 vs. B/C), significant longer PFS for group C (p&lt;0.01 vs. A/B). Significant differences in complete response (B/C: 16.9% vs C:44.4%), partial response (B/C: 20.2% vs. C: 33.3%) and progressive disease (B/C: 27% vs. 11.1%) were noted. No significant difference in overall survival between the groups was seen. Conclusions: ErbB/CEP17 R provides important prognostic information and, in metastatic patients, allows one to better predict response to trastuzumab-based treatment than the widely used binary classification of ErbB2 amplification that is based on a cut-off at a copy number of &gt;2.2. No significant financial relationships to disclose.

Amplification of solitary optical waves in fibers with positive group velocity dispersion

Abstract Solitary optical waves with characteristic red frequency shift have been numerically identified in fibers with positive group velocity dispersion in the presence of amplification by semiconductor amplifiers. Influence of the Henry factor, the net gain, gain saturation characteristics, and frequency modulation on the frequency shift of the observed solitary optical waves has been examined. Normalized pulse energy as a function of the gain saturation characteristics has been studied.

HER-2 Is an Independent Prognostic Factor in Endometrial Cancer: Association With Outcome in a Large Cohort of Surgically Staged Patients

To evaluate HER-2 expression and amplification in a large cohort of endometrial cancer with complete surgical staging and outcome data. A tissue microarray was constructed of 483 patients with endometrial cancer of diverse histologic type and stage and tested for HER-2 expression and amplification using current standards of practice. There was outcome data for 83% of all patients and 81% with complete surgical staging. Both expression and amplification of HER-2 was associated with high-grade (P = .0001) and high stage (P = .0001) endometrial cancer. The highest rate of HER-2 expression and amplification was seen in serous carcinoma (43% and 29%), while grade 1 endometrioid adenocarcinoma showed the lowest levels (3% and 1%). For all histologic types, the rate of HER-2 expression and amplification was remarkably different (P < .0001) for grade 3 cancers (31% and 15%) versus grade 2 (7% and 3%) and grade 1 cancers (3% and 1%), with similar results for endometrioid type (P < .0001). Both HER-2 expression and amplification correlated with disease-specific survival and progression-free survival in univariate analyses. By multivariate analysis HER-2 expression in the presence of amplification (P = .012) correlated with overall survival, but not expression in the absence of amplification. Overall survival was significantly shorter (P = .0001) in patients who overexpressed (median, 5.2 years) and/or showed amplification of HER-2 (median, 3.5 years) versus those that did not (median of all cases, 13 years). Our results would suggest that HER-2 is an important oncogene in high grade and stage endometrial cancer, but plays only a minor role in the much more common low grade and stage tumors that encompass the majority of clinical practice.

HER-2/neu evaluation in breast cancer are we there yet?

The HER-2/neu oncogene is located on chromosome 17q and encodes a transmembrane glycoprotein with intracellular tyrosine kinase activity. Several studies have shown an association of HER-2 gene amplification or protein overexpression with prognosis and predictor of therapeutic response. Most important, the presence of amplification or overexpression is the basis of eligibility for trastuzumab therapy. However, there are several methods of determining HER-2 status, each measuring a different aspect such as DNA content, gene copy number, protein expression, expression of RNA, and circulating HER-2 extracellular domain protein. There is no consensus with regard to the optimal test for HER-2 assessment. This review examines the various methods used in an attempt to define the most accurate and reliable test. The most widely used assays are immunohistochemical analysis and fluorescence in situ hybridization (FISH), which measure protein expression and gene amplification, respectively. Based on current data, FISH is the most accurate and reproducible test with a better correlation with prognosis and response to therapy.

Amplification and photonic band gaps for eigenmodes in two-dimensional photonic crystals with active media

The behavior of eigenmodes near the first low-frequency band gap of a two-dimensional squarearray photonic crystal in the presence of amplification has been studied in detail using an approximate analytic solution for the mode dispersion characteristics. A qualitative analysis of the complex propagation constants was conducted for various directions in the crystal, and the frequency regions corresponding to amplification and absence of transmission due to interference-induced wave damping were identified. The enhancement of amplification in a two-dimensional photonic crystal was estimated.

C-erb-b2/int-2 amplification appears faster in breast-cancer patients receiving second-line endocrine treatment.

We have examined the appearance of c-erb-b2 and int-2 amplification in 2 different groups of breast-cancer patients. The groups differed with regard to their clinical status in that one group was receiving first-line endocrine treatment (tamoxifen) whereas the second was receiving second-line endocrine treatment (after failing on tamoxifen). The latter group of patients showed clinicallya a more advanced disease (higher frequency of stage-IV as compared to stage-III disease). Consecutive tumor samples were obtained using fine-needle biopsies from individual tumor lesions of each patient every second or third month. Median time from diagnosis to the last biopsy for patients receiving tamoxifen was 25 months and, for patients receiving second-line treatment, 55 months. The presence of amplification was determined using semi-quantificative PCR. We found that both genes developed amplification during tumor progression. The appearance of amplification was more pronounced in the clinically more advanced patients receiving second-line treatment (p = 0.018).

Demonstration of gene-amplification by PCR in archival paraffin-embedded breast cancer tissue

The polymerase chain reaction (PCR) is a powerful tool to examine genetic alterations in tumor samples. We describe a simple, rapid, nonisotopic PCR method to semi-quantitatively determine the number of gene copies in human formalin-fixed paraffin-embedded tissue. The procedure is exemplified by analysis of 15 years old breast cancer samples to determine the presence of amplification of c-erb-B2. The samples were obtained from routine specimens kept in pathological archives. Patients with amplified samples showed a poor prognosis, both for recurrences and death in breast cancer.

Molecular studies of the fragile X syndrome.

We have studied families segregating for the fragile X syndrome for the presence of amplification of the CGG repeat sequence adjacent to the HpaII Tiny Fragment (HTF) island in the FMR-1 gene. We demonstrate that 138/143 fragile X positive, mentally retarded males show a characteristic smear of fragments corresponding to somatic variation in the amplification of the CGG sequence. In 7/8 normal transmitting males (NTM's), we show that there is a small amplification of sequence but no evidence for somatic variation. Defined mutated fragments in the size range found in NTM's are seen in daughters of NTM's. The daughters of these female carriers show either a defined fragment in the NTM size range, a defined larger fragment or a heterogeneous pattern of fragments. In the latter 2 cases the clinical phenotype of the females cannot easily be predicted, presumably because of variable X inactivation. In some families, the observed DNA genotype does not correlate with the phenotype; in others we demonstrate the occurrence of individuals with a mosaic DNA genotype. The implications of these data for diagnosis of the disease are discussed.

Optical characteristics of devices with coupled waveguides utilizing semiconductor heterostructures

An analysis is made of the laws governing the propagation of optical radiation in a semiconductor heterostructure with coupled waveguides in the presence of amplification or absorption. A method is developed for the calculation of the transfer functions describing the operation of various systems (optical amplifier, photodetector, laser) using similar structures. The influence of the spread of the parameters of the waveguide layers on the operating characteristics of these systems is assessed.

Gene amplification in human neuroblastomas: Basic mechanisms and clinical implications

Extrachromosomal double minutes (DM) and homogeneously staining regions (HSR) of metaphase chromosomes have been reported frequently in human neuroblastomas and tumor derived cell lines. We and other investigators have determined that virtually all DM- and HSR-bearing neuroblastoma cell lines have multiple copies of the oncogene N-myc. Circumstantial evidence suggests that the extrachromosomal DM may be the level at which amplification takes place, with subsequent linear integration into HSR. Indeed, DM may represent circular molecules. The global organization and fine structure of the amplified sequences remains to be determined, but the unit of amplification is probably between 2 × 10 5 and 2 × 10 6 base pairs (bp). In some cases, the process of amplification may involve somatic recombination with distant DNA segments. We have determined that N-myc amplification is a common finding in primary neuroblastomas from untreated patients. We identified N-myc amplification, ranging from 3- to 300-fold, in 34 of 89 cases (38%). N-myc amplification is found almost exclusively in tumors from patients with advanced stages of disease (stages III and IV, p < 0.01). In addition, the presence of amplification is highly correlated with rapid tumor progression ( p < 0.001). Thus, amplification of the N-myc oncogene is a new intrastage prognostic factor, and N-myc amplification appears to play an important role in determining disease progression.