Optimization of Simple and Inexpensive Paper-Based Assay for Lead

The Environmental Protection Agency (EPA) guidelines state that lead is a toxic metal that humans should not be exposed to in any amount. Due to corrosion of water pipes, lead can enter drinking water and be consumed by millions of people. As a group, we decided to reduce this issue by creating a simple and inexpensive paper-based test to detect lead(II) in water. The signal for this test results from encapsulating a phenanthroline-based probe in synthesized polymer nanoparticles. This test will display a colorimetric change, turning from yellow to bright orange if lead(II) is present in the water system. In an attempt to optimize the response of the test, different variables were adjusted to analyze the nanoparticles’ effectiveness. In this work, polymer type, polymer concentration, solvent, probe concentration, and synthetic method were explored and the optimal method for lead(II) detection was determined. Future directions for our research include focusing on the selectivity of the test to confirm it does not respond to other metals, such as copper and zinc, and optimizing the attachment of the nanoparticles to the test strip itself

Electromagnetically Induced Transparency (EIT) aided cooling of strontium atoms

The presence of ultra-narrow inter-combination spectroscopic lines in alkaline earth elements places them as promising candidates for optical atomic clocks, quantum computation, and for probing fundmental physics. Doppler cooling of these atoms is typically achieved through two subsequent stages: the initial cooling is on the 1s0-1p1 transition followed by cooling using the narrow-line 1s0-3p1 transition. However, due to significantly lower linewidth of the second stage cooling transition, efficient transfer of atoms into the second stage becomes technically challenging. The velocity distribution of the atoms after the first stage of cooling is too broad for atoms to be captured efficiently in the second stage cooling. As a result, the capture efficiency of atoms into the second stage Magneto-Optical Trap is low, even if the linewidth of the second stage cooling laser is artificially broadened.Comment: 7 pages, 3 figure

How Online Communities of People With Long-Term Conditions Function and Evolve: Network Analysis of the Structure and Dynamics of the Asthma UK and British Lung Foundation Online Communities.

BACKGROUND: Self-management support can improve health and reduce health care utilization by people with long-term conditions. Online communities for people with long-term conditions have the potential to influence health, usage of health care resources, and facilitate illness self-management. Only recently, however, has evidence been reported on how such communities function and evolve, and how they support self-management of long-term conditions in practice. OBJECTIVE: The aim of this study is to gain a better understanding of the mechanisms underlying online self-management support systems by analyzing the structure and dynamics of the networks connecting users who write posts over time. METHODS: We conducted a longitudinal network analysis of anonymized data from 2 patients' online communities from the United Kingdom: the Asthma UK and the British Lung Foundation (BLF) communities in 2006-2016 and 2012-2016, respectively. RESULTS: The number of users and activity grew steadily over time, reaching 3345 users and 32,780 posts in the Asthma UK community, and 19,837 users and 875,151 posts in the BLF community. People who wrote posts in the Asthma UK forum tended to write at an interval of 1-20 days and six months, while those in the BLF community wrote at an interval of two days. In both communities, most pairs of users could reach one another either directly or indirectly through other users. Those who wrote a disproportionally large number of posts (the superusers) represented 1% of the overall population of both Asthma UK and BLF communities and accounted for 32% and 49% of the posts, respectively. Sensitivity analysis showed that the removal of superusers would cause the communities to collapse. Thus, interactions were held together by very few superusers, who posted frequently and regularly, 65% of them at least every 1.7 days in the BLF community and 70% every 3.1 days in the Asthma UK community. Their posting activity indirectly facilitated tie formation between other users. Superusers were a constantly available resource, with a mean of 80 and 20 superusers active at any one time in the BLF and Asthma UK communities, respectively. Over time, the more active users became, the more likely they were to reply to other users' posts rather than to write new ones, shifting from a help-seeking to a help-giving role. This might suggest that superusers were more likely to provide than to seek advice. CONCLUSIONS: In this study, we uncover key structural properties related to the way users interact and sustain online health communities. Superusers' engagement plays a fundamental sustaining role and deserves research attention. Further studies are needed to explore network determinants of the effectiveness of online engagement concerning health-related outcomes. In resource-constrained health care systems, scaling up online communities may offer a potentially accessible, wide-reaching and cost-effective intervention facilitating greater levels of self-management

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Chemical intervention in plant sugar signalling increases yield and resilience

The pressing global issue of food insecurity due to population growth, diminishing land and variable climate can only be addressed in agriculture by improving both maximum crop yield potential and resilience. Genetic modification is one potential solution, but has yet to achieve worldwide acceptance, particularly for crops such as wheat. Trehalose-6-phosphate (T6P), a central sugar signal in plants, regulates sucrose use and allocation, underpinning crop growth and development. Here we show that application of a chemical intervention strategy directly modulates T6P levels in planta. Plant-permeable analogues of T6P were designed and constructed based on a ‘signalling-precursor’ concept for permeability, ready uptake and sunlight-triggered release of T6P in planta. We show that chemical intervention in a potent sugar signal increases grain yield, whereas application to vegetative tissue improves recovery and resurrection from drought. This technology offers a means to combine increases in yield with crop stress resilience. Given the generality of the T6P pathway in plants and other small-molecule signals in biology, these studies suggest that suitable synthetic exogenous small-molecule signal precursors can be used to directly enhance plant performance and perhaps other organism function

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (Fludarabine/busulfan=166, Fludarabine/melphalan=327) and 379 using MAC (Fludarabine/busulfan=247, Busulfan/cyclophosphamide=132). In multivariable analysis with RIC, Fludarabine/melphalan was associated with inferior overall survival (HR 1.80, 95% CI 1.15-2.81, p=0.009), higher early non-relapse mortality (HR 1.81, 95% CI 1.12-2.91, p=0.01) and higher acute graft versus host disease (GVHD) (grade II-IV- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade III-IV HR 2.21, 95%CI 1.28-3.83, p=0.004) compared to Fludarabine/busulfan. In the MAC setting, Busulfan/cyclophosphamide was associated with a higher acute GVHD (grade II-IV HR 2.33, 95% CI 1.67-3.25, p\u3c0.001; grade III-IV HR 2.31, 95% CI 1.52-3.52, p\u3c0.001) and inferior GVHD-free relapse-free survival (GRFS) (HR 1.94, 95% CI 1.49-2.53, p\u3c0.001) as compared to Fludarabine/busulfan. Hence, our study suggests that Fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GVHD) and MAC (lower acute GVHD and better GRFS) in myelofibrosis

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

HIV-1 Populations in Semen Arise through Multiple Mechanisms

HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus