Jamming of Nano-Ellipsoids in a Microsphere: A Quantitative Analysis of Packing Fraction by Small-Angle Scattering.

The packing of particles is ubiquitous, and it is of fundamental importance, particularly in materials science in the nanometric length scale. It becomes more intriguing when constituent particles deviate from spherical symmetry owing to the inherent complexity in quantifying their positional and rotational correlation. For quantitative estimation of packing fraction, it requires a thorough analysis of the positional correlation of jammed particles. This article adopts a novel approach for determination of the packing fraction of strongly correlated nano-ellipsoids in a microsphere using small-angle scattering. The method has been elucidated through a quantitative analysis of structural correlation of nano-hematite ellipsoids in 3D micrometric granules, which are realized using rapid evaporative assembly. Owing to the deviation from spherical symmetry, the conventional analysis of scattering data fails to interpret the actual packing fraction of the anisotropic particles. The structural correlation gets smeared out because of orientation distribution among the packed anisotropic particles, which leads to an anomaly in the estimation of packing fraction using the conventional analysis approach. It is illustrated that consideration of an interparticle distance distribution function of the correlated nano-ellipsoids becomes indispensable in determining their packing fraction.

Deregulation of H19 is associated with cervical carcinoma.

CACX is one of the most common cancer affecting women world-wide. Here, expression microarray analysis revealed 8 over-expressed transcribed pseudogenes (GBP1P1, HLA-DRB6, HLA-H, SLC6A10P, NAPSB, KRT16P2, PTTG3P and RNF126P1), down-regulated 7 lincRNAs (H19, MIR100HG, MEG3, DIO3OS, HOXA11-AS, CD27-AS1 and EPB41L4A-AS) and 6 snoRNAs (SNORD97, SNORD3A, SNORD3C, SNORD3D, SNORA12 and SCARNA9) as DEncGs (log2 fold-change ≥ ±1.0) in CACX. Consequently, down-regulation of lincRNA MEG3 and over-expression of pseudogenes, GBP1P1 and PTTG3P in the microarray analysis were found concordant with the real-time quantitative PCR results upon validation. Then, Ingenuity® Pathway analysis (IPA®) analysis with deregulated DEncGs identified functionally important gene, H19. Further, validation (n = 52) of expression confirmed frequent downregulation of H19 with significant association with its deletion (LOH) and promoter methylation (n = 128) in CACX. Moreover, clinicopathological analysis found Indian CACX patients (n = 26) with alterations of H19 by deletion or, promoter methylation with concomitant low expression have poor prognosis.

Patterning of colloids into spirals via confined drying.

Drying of complex fluids is a fascinating subject of interest to several growing fields, for example, forensic science, lithography, printing and coating technologies. In this article, we report that the drying of charge stabilized colloidal dispersions between two parallel plates is a route to intriguing self-assembly patterns. We show that when the dispersions are dried in parallel plate confinement, particles deposit as spiral patterns after the complete evaporation of the solvent irrespective of the confinement spacing. The formation of such patterns is understood by analyzing the underlying three phase contact line dynamics during the drying process. Compared to the usual discrete stick-slip motion of the contact line, typically observed in several drying configurations, in the parallel plate drying configuration, the contact line is found to exhibit continuous stick-slip motion. The de-pinning of the contact line is found to occur only locally and is observed to propagate in both clockwise and anticlockwise directions, leading to the patterning of colloids as spirals. Furthermore, we show that while the number of turns in the spiral deposit is influenced by the dispersion volume and particle concentration, the spiral patterns form irrespective of the shape of the particles in the dispersion.

Reply to "Comment on 'Patterns in Drying Drops Dictated by Curvature-Driven Particle Transport'".

Hodges and Tangparitkul (Hodges, C. S.; Tangparitkul, S. M. Langmuir 2019, 35, doi: 10.1021/acs.langmuir.9b01442) in their Comment on "Patterns in Drying Drops Dictated by Curvature Driven Particle Transport" argue that the coffee-eye deposits in dried pendant drops can also be formed if the particles or particle clusters in the drying drop are large enough to sediment during the course of evaporation. In our reply to this comment, we compare these two different mechanisms, namely, gravity settling and curvature-driven interfacial migration of particles in the drying particle-laden drops, with an aim towards placing them in a correct perspective.

Influence of the drying configuration on the patterning of ellipsoids - concentric rings and concentric cracks.

Evaporation of colloidal dispersions leading to patterning of particles is a simple and elegant route for controlling the self-assembly of particles on a solid surface. In this article, we demonstrate that the configuration in which a colloidal dispersion is dried greatly influences the patterning of particles on a solid surface after complete evaporation of the solvent. Evaporation experiments are carried out using well-characterized stable aqueous dispersions of hematite ellipsoids and polystyrene spheres. The drying of particle laden sessile drops always give a "coffee-ring" deposit irrespective of the particle concentration. At a particle concentration ≥0.3 wt% circular cracks appear in the annular region of the coffee-ring deposit owing to the ordered arrangement of ellipsoids. In stark contrast, the deposits formed by drying the dispersion of ellipsoids in the sphere-on-plate configuration show a transition from "concentric rings" to "concentric cracks" in the micro-structure of the particulate film with an increase in the concentration of particles. Further, our experimental findings reveal that long-range circular cracks and long-range assemblies of particles can be achieved by drying of the dispersion in the sphere-on-plate configuration. While the nature of patterns - that is - coffee-rings and concentric rings - is independent of the shape of the particles, a strikingly different crack morphology is shown to be dictated by the shape of the particles in the dispersion. The results presented show that the drying of colloidal dispersions in the sphere-on-plate configuration enables the fabrication of a long range ordered assembly of particles over an area as large as few square millimeters.

IGF2 is Deregulated During the Development of Uterine Cervical Carcinoma in Indian Patients.

Uterine cervical carcinoma (CACX) is one of the leading causes of deaths in Indian women. Chromosomal alterations including 11p15.5 locus were reported in CACX. Consequently, we strived for the first time to understand the molecular status of the candidate gene Insulin-like growth factor 2, IGF2 (11p15.5) in Indian CACX patients (n = 128). DNA copy number (CN) analysis using CGH-SNP analysis showed no genetic alteration and it was further validated by comparison with publicly available CN datasets. But promoter hypo-methylation during the progression of CACX was observed and also found to be concordant with publicly available DNA methylation datasets. Interestingly, we found diverse expression of IGF2 transcript in both normal cervical epithelium (NCE) and CACX tumors. Similar heterogeneous expression pattern was seen in publicly available expression datasets as well. Finally, protein expression analysis in NCE showed concordance with transcript expression but tumors showed frequent low expression. Log-rank test showed a difference (p-value = 0.057) in overall survival between cases with and without alteration for IGF2 in Indian CACX patients. Collectively, our study proposes that regulation of IGF2 expression in NCE appeared to be multifaceted and deregulation during the development of CACX resulted in the differential expression.

Patterns in Drying Drops Dictated by Curvature-Driven Particle Transport.

Patterns generated by controlled evaporation of droplets containing colloids are dictated by internally generated flows. This advective particle transport is crucial to the efficacy of printing and coating processes and is also an elegant route to the self-assembly of particles. We propose a novel particle transport route, which involves adsorption of particles to the interface and subsequent curvature-driven migration of the particles along the interface. This interface-mediated transport can be exploited to control the distribution of particles in the dried patterns, which we experimentally elucidate by achieving gravity-induced drop shape changes. Our experiments demonstrate that the interplay between the bulk and the interfacial transport leads to strikingly different patterns: while dried aqueous sessile drops of colloidal dispersions produce well known "coffee-rings", dried pendant drops lead to "coffee-eyes". We support our experimental findings using scaling arguments. In previous studies, the effect of gravity-induced change in drop shape on the patterns formed in drying drops has been neglected. However, we show that the structure of the patterns formed by the colloidal particles after solvent evaporation is markedly different when the drops are deformed by gravity.

Integrative genomic and network analysis identified novel genes associated with the development of advanced cervical squamous cell carcinoma.

BACKGROUND: CSCC is one of the most common cancer affecting women globally. Though it is caused by the infection of hrHPV but long latency period for malignant outcome in only a subset of hrHPV infected women indicates involvement of additional alterations, primarily CNVs. Here, we showed how CNVs played a crucial role in development of advanced tumors (stage III/IV) in Indian patients. METHODS: Initially, high-resolution CGH-SNP microarray analysis pointed out frequent CNVs followed by significantly altered genes. After comparison with TCGA dataset, expressions of the genes were checked in three CSCC datasets to identify key genes followed by Ingenuity® Pathway analysis. Then node effect property analysis was applied on the constructed PPI network to rank the key proteins. Finally, validations in independent samples were performed. RESULTS: For the first time, frequent chromosomal amplifications at 3q13.13-3q29, 1p36.11-1p31.1, 1q21.1-1q44 and 5p15.33-5p12 followed by common deletions at 11q14.1-11q25, 2q34-2q37.3, 4p16.3-4p12 and 13q13.3-13q14.3 were identified in Indian CSCC patients. Integrative analysis found 78 key genes including several novel ones, which were mostly associated with 'Cancer' and may regulate DNA repair and metabolic pathways. Analysis showed PARP1 and ATR were among the top ranking protein interactors. CONCLUSIONS: Frequent amplification and over-expression of ATR and PARP1 were further confirmed in cervical lesions, indicating their association with poor prognosis of advanced CSCC patients. GENERAL SIGNIFICANCE: Our novel approach identified precise CNVs along with several novel genes within these loci and showed that PARP1 and ATR, having biologically significant interactions, may be involved in development of advanced CSCC.

Inactivation of PTCH1 is associated with the development of cervical carcinoma: clinical and prognostic implication.

The aim of this study was to analyze the alterations of PTCH1 (deletion/promoter methylation/mutation/expression) during the development of cervical cancer (CACX). For this purpose, deletion/methylation of PTCH1 were analyzed in HPV16 positive exfoliated asymptomatic cervical swabs (n = 74), cervical intraepithelial neoplasia (CIN) (n = 32), CACX (n = 174) samples, and two CACX cell lines. The deletion of PTCH1 increased significantly from CIN (11.5%) to stage I/II (42%) and comparable in stage III/IV (46%). Low frequency (14-16%) of PTCH1 methylation was seen in the asymptomatic exfoliated cervical cells and in the normal epithelium adjacent to the tumor followed by a significant increase in CIN (31%) to stage I/II (57%) and comparable in stage III/IV (58%). The overall alterations (deletion/methylation) of PTCH1 significantly increased from CIN (34%) to stage I/II (70%) and comparable in stage III/IV (69%). Interestingly, in the normal epithelium, methylation of PTCH1 was high in basal/parabasal layers (83%), followed by decrease in the spinous layer (33 %), and showed significant inverse correlation with its expression. Reduced expression of PTCH1 seen in tumors showed a significant association with its alterations (deletion/methylation). The expression pattern of PTCH1 showed an inverse correlation with the nuclear expression of GLI1 in the normal epithelium as well as in the tumors. High nuclear expression of HPV16, E6, and E7 were seen in basal/parabasal layers of the normal epithelium and also in tumors. The PTCH1 alterations (deletion and/or methylation) in tumors and its methylation in adjacent normal epithelium were associated with poor prognosis of patients. Thus, our data suggests that activation of the Hedgehog pathway due to PTCH1 inactivation along with HPV infection is important in CACX development.

Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.

PURPOSE: Cervical Squamous Cell Carcinoma (CSCC) is one of the significant causes of cancer deaths among women. Distinct genetic and epigenetic-altered loci, including chromosomal 11p15.5-15.4, have been identified. CDKN1C (Cyclin-Dependent Kinase Inhibitor 1C, p57KIP2), a member of the CIP/KIP family of cyclin-dependent kinase inhibitors (CDKIs), located at 11p15.4, is a putative tumor suppressor. Apart from transcriptional control, S-Phase Kinase Associated Protein 2 (SKP2), an oncogenic E3 ubiquitin ligase, regulates the protein turnover of CDKN1C. But the molecular status of CDKN1C in CSCC and the underlying mechanistic underpinnings have yet to be explored. METHODS: TCGA and other publicly available datasets were analyzed to evaluate the expression of CDKN1C and SKP2. The expression (transcript/protein) was validated in independent CSCC tumors (n = 155). Copy number alteration and promoter methylation were correlated with the expression. Finally, in vitro functional validation was performed. RESULTS: CDKN1C was down-regulated, and SKP2 was up-regulated at the transcript and protein levels in CSCC tumors and the SiHa cell line. Notably, promoter methylation (50%) was associated with the downregulation of the CDKN1C transcript. However, high expression of SKP2 was found to be associated with the decreased expression of CDKN1C protein. Independent treatments with 5-aza-dC, MG132, and SKP2i (SKPin C1) in SiHa cells led to an enhanced expression of CDKN1C protein, validating the mechanism of down-regulation in CSCC. CONCLUSION: Collectively, CDKN1C was down-regulated due to the synergistic effect of promoter hyper-methylation and SKP2 over-expression in CSCC tumors, paving the way for further studies of its role in the pathogenesis of the disease.

Alterations of RASSF1A in premalignant cervical lesions: clinical and prognostic significance.

This study aimed to understand the importance of RASSF1A and CACNA2D2, located in chromosomal 3p21.31 region, in the development of uterine cervical carcinoma (CACX). To this end, firstly the expression (RNA) profiles of RASSF1A and CACNA2D2 were screened in primary cervical carcinoma (CACX) samples which indicated highly reduced expression for both genes. Thereafter alterations (deletion/methylation) of these genes were analyzed in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN, deletion was observed only for RASSF1A (26%), whereas methylation was in the following order: RASSF1A (35%) > CACNA2D2 (9%). However, in CACX their deletion frequencies were the same (50%) and methylation frequencies were comparable RASSF1A (33%), CACNA2D2 (27%). The reduced expression and molecular alterations of these genes were concordant. Overall alterations of RASSF1A showed association with CIN lesions and CACNA2D2 with disease progression from CIN → stage I/II. Interestingly, alterations of these genes showed significant association in CACX suggesting possible functional synergism during tumor progression. Alterations of RASSF1A and CACNA2D2 predicted poor prognosis for the patients. Moreover, RASSF1A alterations along with multiparity (≥5 yr) and early sexual debut (<19 yr) were determinants of worse prognosis. Our data suggests the association of RASSF1A and CACNA2D2 in cervical carcinogenesis and its importance in early diagnosis and prognosis of the tumor.

Prevalence of human papillomavirus in women without cervical cancer: a population-based study in Eastern India.

Despite the high incidence of cervical cancer, population-based data on prevalence of human papillomavirus (HPV) are limited in India. This study aimed to evaluate the prevalence of any HPV type and type-specific prevalence of HPV 16/18 in women without cervical cancer. HPV viral load was measured and correlated with cytologic abnormalities of the cervix. A total of 2501 women between 25 and 65 years of age and without cervical cancer were screened by pap smear cytology. HPV DNA was detected from cervical scrapes by nested polymerase chain reaction. Detection of HPV 16/18 was carried out by polymerase chain reaction using type-specific primers and was confirmed by Southern hybridization. Viral load was determined by absolute real-time polymerase chain reaction. Population prevalence of any HPV was found to be 9.9%. The risk of HPV infection was higher in women aged 25 to 34 years (odds ratio, 1.11), in married women below 20 years of age (odds ratio, 1.80), and in women with parity ≥4 (odds ratio, 1.04). Prevalence of HPV 18 (1.4%) was greater than that of HPV 16 (0.6%) in the overall screened population. High-grade squamous intraepithelial lesion cytology was more frequent in women infected with HPV 16 than in those infected with HPV 18 and other types. A gradual increase in HPV copy numbers was associated with progressive cytologic severity. In this study, HPV prevalence is comparable to HPV prevalence reported by other studies among Indian and Asian women. Although the prevalence of HPV 18 was more than that of HPV 16, type 16 infection was associated with higher oncogenicity.

PTPRJ is downregulated in cervical squamous cell carcinoma.

Squamous cell carcinoma of the uterine cervix (CSCC) is one of the leading causes of death in Indian women. Protein tyrosine phosphatase receptor (PTPR) type J (also known as DEP1) is a recently reported tumour suppressor receptor phosphatase. Critical molecular analysis of PTPRJ/DEP1 (11p11.2) has not performed in CSCC to date. Here, we observed frequent downregulation of cancer samples (n=31) at the transcriptional level. Immunohistochemistry revealed concordant low expression of PTPRJ protein with a few samples showing intermediate expression. To probe for the cause of such downregulation of the gene in CSCC (n=155), we analysed the copy number and promoter methylation of PTPRJ. The genetic locus showed deletion (14.8%) and the promoter showed methylation (33.5%) of PTPRJ. To the best of our knowledge, for the first time we explored the molecular status of PTPRJ although we observed no statistically significant association with the prognosis of Indian CSCC patients (n=76). However, we observed enhanced expression of PTPRJ protein levels that contributes to effective cisplatin chemotherapy in the SiHa cell line. Thus, the present study paves the way for further research into the plausible mechanisms of downregulation of PTPRJ in cervical cancer.

Inactivation of CHEK1 and EI24 is associated with the development of invasive cervical carcinoma: clinical and prognostic implications.

To understand the importance of frequent deletion of chromosomal 11q23.3-24.3 region in cervical carcinogenesis, alterations (deletion/methylation/mutation/expression) of the candidate genes LOH11CR2A, EI24 and CHEK1 located in the region were analyzed in 29 cervical intraepithelial neoplasia (CIN), 112 cervical carcinoma (CACX) samples and two CACX cell lines. The deletion frequency of these genes was low in CIN than in CACX [CIN: CHEK1: 28%, EI24: 21%, LOH11CR2A: 15% and CACX: CHEK1: 51%, EI24: 41%, LOH11CR2A: 36%]. Similar trend was seen in promoter methylation of these genes [CIN: CHEK1: 10%, EI24: 3%, LOH11CR2A: 3% and CACX: CHEK1: 55%, EI24: 31%, LOH11CR2A: 14%]. Mutations of the genes are a rare event. Overall alterations (deletion and methylation) of CHEK1 and EI24 were associated with progression of CACX. Quantitative mRNA expression analysis showed reduced expression of the three genes in concordance to their molecular alterations. A shorter isoform of CHEK1 lacking exon 8, hence impaired in substrate binding capacity, was found in two samples. Immunohistochemical analysis showed nuclear expression of Chek1, p-Chek1 and Ei24 in tumor tissues, whereas the cell lines exhibited both nuclear and cytoplasmic expression of Chek1 and Ei24, as is also evident from Western blot analysis suggesting differential localization of the proteins. Alterations of CHEK1 and EI24 coupled with tumor stage and early sexual debut (≤ 19 years) predicted worst prognosis. Thus, our data suggest that inactivation of EI24 and CHEK1 through two independent mechanisms contributes to the development of CACX.

Alterations of ATM and CADM1 in chromosomal 11q22.3-23.2 region are associated with the development of invasive cervical carcinoma.

To understand the importance of chr11q22.3-23.2 region in the development of cervical cancer, we have studied the genetic and epigenetic alterations of the candidate genes ATM, PPP2R1B, SDHD and CADM1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma (CACX) samples. Our study revealed low expression and high alterations (methylation/deletion) (55-59%) of ATM and CADM1 genes along with poor patient outcome. The alterations of ATM and CADM1 are associated with the progression of tumor from CIN to Stage I/II, thus implying their role in early invasiveness. The two genes, PPP2R1B and SDHD, lying in between ATM and CADM1, have low frequency of alterations, and majority of the alterations are in CACX samples, indicating that their alterations might be associated with disease progression. Expressions (mRNA/protein) of the genes showed concordance with their molecular alterations. Significant co-alteration of ATM and CADM1 points to their synergic action for the development of CACX. Mutation is, however, a rare phenomenon for inactivation of ATM. Association between the alteration of ATM and CHEK1 and poor survival of the patients having co-alterations of ATM and CHEK1 points to the DNA damage response pathway disruption in development of CACX. Thus, our data suggest that inactivation of ATM-CHEK1-associated DNA damage response pathway and CADM1-associated signaling network might have an important role in the development of CACX.

Genetic and epigenetic changes of HPV16 in cervical cancer differentially regulate E6/E7 expression and associate with disease progression.

OBJECTIVE: The study was aimed at understanding the complex interactions of genetic and epigenetic events in expression of HPV16 E6/E7 and progression of cervical carcinoma. For this, expression of E6/E7 was done in 36 samples, along with the physical status, methylation and LCR sequence variations. Later, the genetic and epigenetic studies were extended to 239 samples to find out the association of these factors with progression of cervical cancer. METHODS: E6/E7 expression was quantified by real-time PCR. Physical status of HPV16 was determined by mutiplex-PCR of whole E2 ORF using overlapping primers and E6 ORF and validated by real-time PCR. Methylation status of P97 promoter/enhancer was analyzed by methylation sensitive restriction analysis (MSRA). Viral lineage and variations in LCR was ascertained by sequencing LCR/E6/E7 ORFs. RESULTS: Samples with episomal unmethylated virus showed comparatively high expression of E6/E7 than episomal methylated, integrated unmethylated and integrated methylated forms of HPV16. Variations in the LCR, particularly in the binding sites of negatively regulating transcription factors, also contribute to high expression of E6/E7. The integrated form significantly increases with decrease of episomal form during tumor progression. Methylation of the promoter/enhancer gradually decreased with tumor progression and is inversely correlated to integration. Two novel variants were observed in E6 gene in European- and North-American-1-lineages. Log-rank test revealed better prognosis of the patients with episomal methylated HPV16 compared to the other forms. CONCLUSION: Our results show higher expression of E6/E7 in samples with episomal unmethylated virus having sequence variations in LCR.

RBSP3 is frequently altered in premalignant cervical lesions: clinical and prognostic significance.

To understand the importance of frequent deletion of 3p22.3 in cervical carcinogenesis, alterations (deletion/methylation/expression) of the candidate genes STAC, MLH1, ITGA9, and RBSP3, located in the region, were analyzed in 24 cervical intraepithelial neoplasia (CIN) and 137 uterine cervical carcinoma (CACX) samples. In CIN, RBSP3 deletion (48%) and methylation (26%) were high compared with the other genes (4-9%). In CACX, alterations of these genes were as follows: deletion: STAC (54%) > MLH1 (46%) > RBSP3 (45%) > ITGA9 (41%), methylation: RBSP3 (25%) > ITGA9 (24%) > STAC (19%) > MLH1 (13%). Overall, alterations of RBSP3 showed association with CIN, whereas for STAC and MLH1, this frequency increased significantly from CIN --> Stage I/II and for ITGA9 from CIN --> Stage I/II and also from Stage I/II --> Stage III/IV. Quantitative mRNA expression analysis showed differential reduced expression of these genes in CACX concordant to their molecular alterations. The more active RBSP3B splice variant was underexpressed in CACX. RB1 was infrequently deleted in CACX. Concordance was seen between (i) inactivation of RBSP3 and intense p-RB1 nuclear immunostaining and (ii) low/absence of MLH1 expression and its molecular alterations in CACX. In normal cervical epithelium, p-RB1 immunostaining was low in differentiated cells, whereas MLH1 staining was seen in both nucleus and cytoplasm irrespective of differentiation stage. Alterations of the genes were significantly associated with poor prognosis. High parity (>or=5)/early sexual debut (

Amplification of CyclinL1 in uterine cervical carcinoma has prognostic implications.

The chromosomal 3q25.31 region was consistently amplified in primary cancer of cervix (CACX). CyclinL1 is a candidate gene of this region and already have been implicated as an oncogene in head and neck cancers. In this study, we aimed to investigate the involvement of CyclinL1 in cervical carcinogenesis and for this purpose its copy number variation (CNV) was studied in 23 cervical intraepithelial neoplasia (CIN) and 110 CACX samples. In CIN lesions CyclinL1 was not amplified; however, the amplification frequency was 16% (9/56) in stage I/II tumors which remained comparable during subsequent stages of tumorigenesis. This implied association of CyclinL1 amplification with development of early invasiveness. Quantitation of mRNA expression revealed 2.6 ± 1.53-fold overexpression of this gene in primary CACX. The amplification/copy number gain of CyclinL1 and its mRNA profile were concordant, in tumors. Immunohistochemical (IHC) analysis in primary CACX, cell lines: SiHa and HeLa revealed intense nuclear expression of cyclinL1, which was further confirmed by Western blot in the cell lines. However 47% (7/15) CACX samples expressed high/intermediate level of cyclin L1. Kaplan-Meier survival analysis indicated CyclinL1 amplification as a determinant of poor patient outcome. Tumor radio-resistance developed as a consequence of CyclinL1 amplification. Cox multivariate analysis revealed that multiparous (≥5) CACX patients with amplified CyclinL1 locus along with advanced tumor stage (III/IV) had worst prognosis. Our data suggest importance of CyclinL1 in cervical carcinogenesis with its associated pathways viz: pre-mRNA splicing, cell-cycle regulation (G0/G1 and G2/M) being potential targets of therapeutic interventions in CACX.

Cracks in dried deposits of hematite ellipsoids: Interplay between magnetic and hydrodynamic torques.

The orientation and morphology of cracks in coffee-ring like particulate deposit obtained by drying sessile drops containing anisotropic magnetic particles strongly depends on the magnitude of the applied magnetic field and its direction. This opens up the possibility of tuning the micro-structure of cracks via suitable manipulation of magnetic and hydrodynamic torques on the particles which has potential applications in nano-fabrication and field driven self-assembly. We report a systematic study of magnetic field driven self-assembly of hematite ellipsoids in sessile drops dried on solid substrates and resulting crack patterns. The experiments are carried out over a wide range of applied magnetic field strength (|B→|) varying from 0 to 400G and ellipsoids of two different aspect ratios. Dried coffee-ring deposits of ellipsoids in absence of the external applied magnetic field and at low field strength, |B→|≤20G exhibit circular cracks. However, at |B→|⩾30G, the cracks are observed to be linear and perpendicular to the direction of the applied magnetic field. Random cracks are observed in the intermediate field range of 20G<|B→|<30G. Thus our experiments reveal that there exists a critical magnetic field at which the orientation of cracks change from circular to linear. The knowledge of the critical field is exploited to measure the hydrodynamic torque experienced by nano-ellipsoids and fluid velocities during evaporation, which are challenging to measure experimentally.

Phylogenetic analysis of Human papillomavirus 16 variants isolated from Indian Breast cancer patients showed difference in genetic diversity with that of cervical cancer isolates.

The genetic variations of HPV16 in Breast Cancer (BC) are not well studied unlike HPV16 in Cervical Cancer (CACX). In this study, the genetic variations of HPV16 in BC were compared with HPV16 in CACX. In sequencing analysis of LCR, E6 and E7 regions of HPV16 in BC and CACX the A lineage was seen to be 64.2% and 66.6% respectively. The other lineages showed differential frequency in BC and CACX. The mutation frequency index of the regions in BC and CACX was in the following order: LCR>E6>E7. However, the inter-patient genetic diversity in LCR and E6/E7 regions was high in BC than CACX. The LCR region showed more variations than the E6/E7 region in BC. Apart from some common variations, some unique tissue specific variants in LCR and E6/E7 region were seen in BC and in CACX. Besides the selection of some common variants in both BC and CACX, some unique variants in BC (D98Y; 395 G>T) and CACX (R48W; 245 G>T) were observed. The 7521 G>A variant of LCR showed association with Luminal B subtype of BC and progression of CACX. Whereas, 145 G>T (Q14H) and 335 C>T (H78Y) variants of E6 showed association with either early invasiveness of BC and/or poor outcome of the patients. Thus, this study indicates that there may be a difference in the genetic variation of HPV16 in BC and in CACX.