The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by ...pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.
Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial in the literature. The 2012 WHO classification of breast ...cancer categorizes neuroendocrine carcinomas into three morphologically distinct subtypes: well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. We aimed to gain insight into the clinical, morphologic, phenotypic, and molecular features of 47 neuroendocrine breast carcinomas. Targeted next-generation sequencing by an AmpliSeq 22 cancer gene hotspot panel and the Prosigna assay were performed on 42/47 and 35/47 cases, respectively. Average age at diagnosis was 69 years. All tumors were estrogen receptor-positive and the large majority expressed progesterone receptor (89%), GATA3 (98%), FOXA1 (96%), and CK8/18 (98%). There was an almost equal distribution of luminal A (52%) and B (48%) carcinomas. Almost half of the cohort (49%) displayed a high risk of recurrence score with the Prosigna test. Patients with a neuroendocrine carcinoma had a shorter disease-free survival compared with those affected by carcinomas of no special type matched for age, size, grade, and estrogen receptor status. No significant differences were observed in terms of overall survival. Stratification of neuroendocrine carcinomas using the 2012 WHO criteria did not reveal statistically significant differences among the distinct categories (well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation), in terms of either progression-free or overall survival. Our targeted sequencing analysis found three cases (7%) harboring a PIK3CA mutation, and in three other cases (7%) TP53 mutations were detected. This study showed that neuroendocrine breast carcinoma is a distinct subtype of luminal carcinoma with a low rate of PIK3CA mutations and with an aggressive clinical behavior. An accurate identification of neuroendocrine differentiation may be useful to better tailor patient adjuvant therapy within luminal carcinomas.
The development of new biomarkers for ovarian cancer is clearly necessary for the improved detection and monitoring of the disease. Surface enhanced laser desorption and ionization time‐of‐flight ...mass spectrometry (SELDI‐TOF‐MS) can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was, then, to identify potential diagnostic serological biomarkers for ovarian cancer. We performed protein expression difference analyses of 45 serum samples using SELDI protein chip array. Forty‐five sera obtained from ovarian cancer patients (n = 35) and normal healthy females (n = 10), were profiled on the surface of SELDI protein chip. The candidate biomarkers were purified by CM‐Sepharose, and their N‐terminal amino sequence was determined. The amounts of hemoglobin (Hb) in cancer patient's sera versus that of normal sera were measured by ELISA. Nine sera proteins that were found to be significantly differentially expressed (P < 0.05) between the sera of ovarian cancer patients and that of normal healthy females were selected using the WCX2 array. The most distinctive polypeptide peaks detected in the ovarian cancer samples were at 15.1 and 15.8 kDa and these two peaks were identified as the hemoglobin‐alpha (Hb‐α) and ‐beta (Hb‐β) chain, respectively. ELISA indicated that the sensitivity for intact Hb level was 77% in sera obtained from ovarian cancer patients, as compared with normal healthy female sera. In conclusion, two ovarian cancer biomarker proteins were discovered and identified as Hb‐α and Hb‐β. Hb levels were significantly different in ovarian cancer serum samples and those obtained from normal healthy females, as determined by ELISA. Additional studies are required to further validate Hb‐α and Hb‐β biomarkers. (Cancer Sci 2005; 96: 197–201)
We report on a electrothermally actuated Fabry-Perot wavelength tunable filter with a high tuning efficiency by using surface micromachining. To prevent a current flowing through the mirror, a ...Wheatstone bridge structure is introduced. Because the full wafer is monolithically grown and the electrodes are formed in a single step, the fabrication processes is simple and reproducible. As the current flows through the two parallel thermal actuators, the top mirror moves away from the bottom mirror so that a sticking problem does not occur. The maximum voltage for the 69-nm wavelength tuning by using a 5.2-mum-thick filter structure is only 1.7 V and the high tuning efficiency of ~75 nm/mW is achieved.
Screening in cervical cancer is progressing to find out candidate genes and proteins, which may work as biological markers and play a role in tumor progression. We examined the protein expression ...patterns of squamous cell carcinoma (SCC) tissues from Korean women using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometer.
Normal cervix and SCC tissues were solubilized and 2-DE was performed using the pH 3–10 linear IPG strips of 17 cm length and silver stained. Protein expression was evaluated using PDQuest 2-D software™. The differentially expressed protein spots were identified with MALDI-TOF mass spectrometer and the peptide mass spectra identification was performed using Mascot program searching the Swiss-prot or NCBInr databases.
A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins were down-regulated. Among the proteins identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, α-enolase, squamous cell carcinoma antigen 1 and 2, glutathione
S-transferase, apolipoprotein a1) were previously known proteins involved in tumor and 21 proteins were newly identified in this study.
2-DE offers total protein expression profiles of SCC tissues and further characterization of proteins that are differentially expressed will give a chance to identify tumor-specific diagnostic markers for SCC.
Despite receiving much attention as a biodegradable substitute for conventional non-biodegradable plastics, the commercial use of polyhydroxybutyrate (PHB) remains limited because of its high ...production cost. In order to reduce the recovery/purification cost, which forms over half of the total production cost, we have developed a new cultivation method which enables spontaneous liberation of PHB by modulation of the initial inoculum size and the medium composition in recombinant
Escherichia coli harboring
Alcaligenes eutrophus phbCAB genes. In flask cultivation using a low cell inoculum and 2x LB medium containing 21% glucose, autolysis of 80.2% as well as yields of 85.2 g/l of PHB and a PHB content of 99.0% (w/w) were obtained. The glucose conversion rate was 0.43. The strategies developed in this study can minimize complex and unfavorable efforts required for efficient recovery/purification processes, thereby enabling biodegradable plastic to be produced by the recombinant
E. coli so as to compete with conventional non-biodegradable plastic.
Using a genome-wide array-based comparative genomic hybridization (array-CGH), DNA copy number changes in uterine leiomyosarcoma were analyzed.
We analyzed 4 cases of uterine leiomyoma and 7 cases of ...uterine leiomyosarcoma. The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted. Array-based CGH and fluorescence in situ hybridization (FISH) were carried out with Genome database (Gene Ontology).
Uterine leiomyoma showed no genetic alterations, while all of 7 cases of uterine leiomyosarcoma showed specific gains and losses. The percentage of average gains and losses were 4.86% and 15.1%, respectively. The regions of high level of gain were 7q36.3, 7q33–q35, 12q13–12q15, and 12q23.3. And the regions of homozygous loss were 1p21.1, 2p22.2, 6p11.2, 9p21.1, 9p21.3, 9p22.1, 14q32.33, and 14q32.33 qter. There were no recurrent regions of gain, but recurrent regions of loss were 1p21.1–p21.2, 1p22.3–p31.1, 9p21.2–p22.2, 10q25–q25.2, 11q24.2–q25, 13q12–q12.13, 14q31.1–q31.3, 14q32.32–q32.33, 15q11–q12, 15q13–q14, 18q12.1–q12.2, 18q22.1–q22.3, 20p12.1, and 21q22.12–q22.13. In the high level of gain regions, BAC clones encoded
HMGIC,
SAS,
MDM2,
TIM1 genes. Frequently gained BAC clone-encoded genes were
TIM1,
PDGFR-β,
REC Q4,
VAV2,
FGF4,
KLK2,
PNUTL1,
GDNF,
FLG,
EXT1,
WISP1,
HER-2, and
SOX18. The genes encoded by frequently lost BAC clones were
LEU1,
ERCC5,
THBS1,
DCC,
MBD2,
SCCA1,
FVT1,
CYB5, and
ETS2/E2. A subset of cellular processes from each gene was clustered by Gene Ontology database.
Using array-CGH, chromosomal aberrations related to uterine leiomyosarcoma were identified. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.
Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the ...heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49 × 10(-9) (1.15, 1.10-1.20), 1.45 × 10(-8) (1.13, 1.08-1.18), and 7.14 × 10(-7) (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.
Numerous studies have attempted to pinpoint certain traits of rice varieties linked with great ratooning ability that may be used in cultural practice. However, both genetic and environmental ...variables affect rice's capacity for ratooning. We are able to measure the innovative ratooning ability that affects the decline in ratoon yield using the agronomic features of the main crop and ratoon rice in our global database for a meta‐analysis, drawn from 51 experiments in 14 countries. We discovered that changes in cultivar yield and maturity features, cropping location, and nitrogen fertilizer treatment may all affect a plant's capacity to tiller. On the other hand, the growth duration ratoon ability was less responsive to variations in cultivars and cropping location. We also found that ratooning changes the plant architecture for yield generation from bigger spikelets with fewer panicles to fewer spikelets (dropping 48%) with larger panicles (increasing 19%). We came to the conclusion based on our research that the decreased yield in ratoon crops may be caused by fast ear emergence and aggressive tillering, which negatively influence stem elongation, panicle differentiation, and a lack of nutrition, resulting in fewer spikelets (panicle−1). The present data are thoroughly summarized and analyzed in this research, which also clarifies the lack of knowledge around the characteristics that affect ratoon rice crop production.
Core Ideas
A comprehensive global quantitative analysis was conducted to assess the ratoon rice's ratooning ability.
The tillering–ratooning ability was found to be influenced by variations in genetic and environmental factors.
Genetic and environmental variables may have little effect on ratoon crop growth duration.
The plant architecture shifts from large spikelets in the main crop to large panicles in the ratoon crop.
The accelerated ear emergence could have a detrimental impact on stem elongation during panicle differentiation.
Force sensing is an essential requirement for dexterous robot manipulation. We describe composite robot end-effectors that incorporate optical fibers for accurate force sensing and estimation of ...contact locations. The design is inspired by the sensors in arthropod exoskeletons that allow them to detect contacts and loads on their limbs. In this paper, we present a fabrication process that allows us to create hollow multimaterial structures with embedded fibers and the results of experiments to characterize the sensors and controlling contact forces in a system involving an industrial robot and a two-fingered dexterous hand. We also briefly describe the optical-interrogation method used to measure multiple sensors along a single fiber at kilohertz rates for closed-loop force control.
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