Long period fiber grating for biosensing: an improved design methodology to enhance add-layer sensitivity

We present our theoretical study on the design of LPFG sensor where its add-layer sensitivity is enhanced. addlayer sensitivity quantifies the sensitivity of the sensor to the changes taking place within few tens of nanometers around the receptor molecules. Two different methodologies: the use of dual overlay layer and tailoring of the intermodal separation between two cladding modes, have been used to enhance the add-layer sensitivity. Using coupled mode analysis we compute several examples to carry out a detailed comparative analysis between the results obtained, focusing on the cladding mode near mode transition.This work was supported by Council of Scientific Research (CSIR), India during the 12th Five Year Plan. Project Nos. ESC-0102 and ESC-0110. The author I. D. Villar thankfully acknowledge the support of the Spanish Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (TEC2016-78047-R) and the Government of Navarre through the project with reference 2017/PI044

Sensitivity Analysis of Sidelobes of the Lowest Order Cladding Mode of Long Period Fiber Gratings at Turn Around Point

A new methodology to enhance the sensitivity of a long period fiber grating sensor (LPFG) at the Turn Around Point (TAP) is here presented. The LPFG sensor has been fabricated by etching the fiber up to 20.4 mu m, until the sidelobes of dispersed LP0,2 cladding mode appeared near TAP in aqueous medium. The dual peak sensitivity of the sidelobes was found to be 16,044 nm/SRIU (surrounding refractive index units) in the RI range from 1.333 to 1.3335

Wnt signaling in triple negative breast cancer is associated with metastasis

Background Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies. Methods We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease. Results The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/β-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from β-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/β-catenin classifier had a greater risk of lung and brain, but not bone metastases. Conclusion These data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways

Down’s Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship

Down’s syndrome (DS), the most common genetic cause of significant intellectual disability in children and adults is caused by the trisomy of either all or a part of human chromosome 21 (HSA21). Patients with DS mostly suffer from characteristic tumor types. Although individual patients of DS are at a higher risk for acute leukemia and testicular cancers, other types of solid tumors including breast cancers are mostly uncommon and have significantly lower-than-expected age-adjusted incidence rates. Except for an increased risk of retinoblastomas, and lymphomas, the risk of developing solid tumors has been found to be lower in both children and adults, and breast cancer was found to be almost absent (Hasle H., The Lancet Oncology, 2001). A study conducted in the United States found only one death when 11.65 were expected (Scholl T et al., Dev Med Child Neurol. 1982). A recent study examined mammogram reports of women with DS treated in the largest medical facility specifically serving adults with DS in the United States. It was found that only 0.7% women with DS had been diagnosed with breast cancers (Chicoine B et al., Intellect Dev Disabil. 2015). Here we describe a case of breast cancer in a 25-year-old patient with DS. The disease was presented as lymph node positive carcinoma with alterations of tumor suppressor genes characteristic to the triple negative breast cancer subtype. Comprehensive Genomic Profiling (CGP) revealed a wild-type status for BRCA1. The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as characteristically found in triple-negative breast cancers. The VUS (Variance of Unknown Significance) alteration(s) were identified in ASXL1 (L1395V), NTRK1 (G18E), DDR2 (I159T), RUNX1 (amplification), ERG (amplification), SOX2 (T26A), FAM123B (G1031D), and HNF1A (A301T). Bonafide cancer-related genes of chromosome 21 amplified in the patient’s tumor are RUNX1 and ERG genes. After the completion of the radiation, the patient was placed on everolimus which was based on the result of her CGP report. Thus, post-mastectomy radiation therapy was completed with a recommendation for everolimus for one year. During the time of writing of this report, no metastatic lesions were identified. The patient currently has no evidence of disease

(Un)Making Citizens: Bordering Regimes, Colonialism, and Security in South Asia

In 2019, India stripped close to 2 million people of their citizenship when the National Register of Citizens—meant to identify ‘genuine Indian citizens’—was implemented in the state of Assam. Policies of denationalization—or citizenship stripping—are not new in South Asia. As millions of people confront the possibility of statelessness, I ask: How do citizens come to be legally defined as foreigners? I employ the concept of securitized belonging to show that citizenship is increasingly withheld from or denied to those who are objects of security or seen as a threat to state stability and endurance. Securitized belonging provides a useful framework to understand why states wish to list, track, and surveil their citizens in order to ensure their ongoing loyalty while simultaneously providing a justification to deprive of citizenship those individuals or groups who are perceived as a threat to the state. Securitized belonging simultaneously makes and unmakes citizens. The dominant scholarship on citizenship and security emphasize the role of state capacity, but without a deep investigation into the historical—specifically, imperial—construction and marginalization of certain groups as criminals, minorities, or outsiders. In British India, the colonial administration made very specific efforts—from anthropological investigations into colonized societies and to laws that criminalized specific tribal groups—to order Indian society and institutionalize certain laws, practices, and ideas. Using extensive archival evidence, my research shows that the insecurities about imperial control were central to colonial migration control and in policing or punishing crime. These insecurities created sticky notions about who could or could not be “genuinely” Indian that then became entrenched in laws, the state apparatus, and even in social attitudes that targeted them for exclusion. In doing this research, I take seriously the call to examine colonial histories of bordering, migration control, and social ordering by scholars of postcolonial citizenship. My work challenges the long-held assumptions in the literature that tend to fetishize European (or Western) ideas, designs, and institutions as original blueprints or yardsticks for liberal abstractions yet to be realised in the non-Western world

Precision Medicine in Solid Tumors: How Far We Traveled So Far?

The future of disease management in solid tumors will rely heavily on how effectively we understand precision medicine and how successfully we can deliver personalized medicine [...

Precision Medicine in Solid Tumors: How Far We Traveled So Far?

The future of disease management in solid tumors will rely heavily on how effectively we understand precision medicine and how successfully we can deliver personalized medicine [...

Targeted Neoadjuvant Therapies in HR+/HER2−Breast Cancers: Challenges for Improving pCR

A strong association of pCR (pathological complete response) with disease-free survival or overall survival is clinically desirable. The association of pCR with disease-free survival or overall survival in ER+/HER2−breast cancers following neoadjuvant systemic therapy (NAT) or neoadjuvant endocrine therapy (NET) is relatively low as compared to the other two subtypes of breast cancers, namely triple-negative and HER2+ amplified. On the bright side, a neoadjuvant model offers a potential opportunity to explore the efficacy of novel therapies and the associated genomic alterations, thus providing a rare personalized insight into the tumor’s biology and the tumor cells’ response to the drug. Several decades of research have taught us that the disease’s biology is a critical factor determining the tumor cells’ response to any therapy and hence the final outcome of the disease. Here we propose two scenarios wherein apoptosis can be induced in ER+/HER2− breast cancers expressing wild type TP53 and RB genes following combinations of BCL2 inhibitor, MDM2 inhibitor, and cell-cycle inhibitor. The suggested combinations are contextual and based on the current understanding of the cell signaling in the ER+/HER2− breast cancers. The two combinations of drugs are (1) BCL2 inhibitor plus a cell-cycle inhibitor, which can prime the tumor cells for apoptosis, and (2) BCL2 inhibitor plus an MDM2 inhibitor

Therapeutic Strategies for Metastatic Triple-Negative Breast Cancers: From Negative to Positive

Metastatic triple-negative breast cancer (TNBC) is a distinct and immensely complex form of breast cancer. Among all subtypes of breast cancers, TNBC has a comparatively high rate of relapse, a high rate of distant metastasis, and poor overall survival after standard chemotherapy. Chemotherapy regimens are an essential component of the management of this estrogen receptor-negative, progesterone receptor-negative, and epidermal growth factor receptor2 negative subtype of breast cancers. Chemotherapy is critical for preventing the recurrence of the disease and for achieving long-term survival. Currently, a couple of agents are approved for the management of this disease, including chemotherapy like eribulin, targeted therapy like PARP inhibitor, as well as an antibody-drug conjugate (ADC) to target TROP2. Like many other metastatic cancers, immune checkpoint inhibitors (ICIs) have also been approved for TNBC patients with PD-L1 positive tumors and high tumor mutational burden. In this review article, we discuss these newly approved and promising novel agents that may change the therapeutic landscape for advanced/metastatic TNBC patients

RAC1 Takes the Lead in Solid Tumors

Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents