Assessing the potential for U.S. utility green bonds

EXECUTIVE SUMMARY: Bonds are the largest single class of financial instrument across the world’s financial markets. Recently, a subclass of these bonds, called green bonds, has emerged in the market place. Green bonds are a type of bond whose proceeds may be used only for certain approved “green” investments. In exchange for agreeing to invest only in such projects, the bond issuer obtains some value greater than they would obtain from traditional financing, and are therefore encouraged to finance and undertake a greater number of green projects. This unique value may not be recognized in traditional financial accounting. Of course, like any other capital-raising investment, green bonds enable their issuer to finance a new project that should increase (or at least maintain) its revenues, profits, and cash flow. The utility sector was the second largest issuer of green bonds in 2017, accounting for $26.2 billion dollars’ worth of green bond issuance globally. These were primarily issued to finance renewable energy projects, a class of projects that makes the utility sector one of the most logical for deployment of green bonds. While choosing to issue green bonds does not seem to have any price advantage over regular bonds in the market, green bonds can provide other benefits. These benefits may include reputation effects, better treatment in secondary markets, and other intangibles (See Table ES1)

Affine insertion and Pieri rules for the affine Grassmannian

We study combinatorial aspects of the Schubert calculus of the affine Grassmannian Gr associated with SL(n,C). Our main results are: 1) Pieri rules for the Schubert bases of H^*(Gr) and H_*(Gr), which expresses the product of a special Schubert class and an arbitrary Schubert class in terms of Schubert classes. 2) A new combinatorial definition for k-Schur functions, which represent the Schubert basis of H_*(Gr). 3) A combinatorial interpretation of the pairing between homology and cohomology of the affine Grassmannian. These results are obtained by interpreting the Schubert bases of Gr combinatorially as generating functions of objects we call strong and weak tableaux, which are respectively defined using the strong and weak orders on the affine symmetric group. We define a bijection called affine insertion, generalizing the Robinson-Schensted Knuth correspondence, which sends certain biwords to pairs of tableaux of the same shape, one strong and one weak. Affine insertion offers a duality between the weak and strong orders which does not seem to have been noticed previously. Our cohomology Pieri rule conjecturally extends to the affine flag manifold, and we give a series of related combinatorial conjectures.Comment: 98 page

Direct Inhibition of T-Cell Responses by the Cryptococcus Capsular Polysaccharide Glucuronoxylomannan

The major virulence factor of the pathogenic fungi Cryptococcus neoformans and C. gattii is the capsule. Glucuronoxylomannan (GXM), the major component of the capsule, is a high-molecular-weight polysaccharide that is shed during cryptococcosis and can persist in patients after successful antifungal therapy. Due to the importance of T cells in the anticryptococcal response, we studied the effect of GXM on the ability of dendritic cells (DCs) to initiate a T-cell response. GXM inhibited the activation of cryptococcal mannoprotein-specific hybridoma T cells and the proliferation of OVA-specific OT-II T cells when murine bone marrow-derived DCs were used as antigen-presenting cells. Inhibition of OT-II T-cell proliferation was observed when either OVA protein or OVA323-339 peptide was used as antigen, indicating GXM did not merely prevent antigen uptake or processing. We found that DCs internalize GXM progressively over time; however, the suppressive effect did not require DCs, as GXM directly inhibited T-cell proliferation induced by anti-CD3 antibody, concanavalin A, or phorbol-12-myristate-13-acetate/ionomycin. Analysis of T-cell viability revealed that the reduced proliferation in the presence of GXM was not the result of increased cell death. GXM isolated from each of the four major cryptococcal serotypes inhibited the proliferation of human peripheral blood mononuclear cells stimulated with tetanus toxoid. Thus, we have defined a new mechanism by which GXM can impart virulence: direct inhibition of T-cell proliferation. In patients with cryptococcosis, this could impair optimal cell-mediated immune responses, thereby contributing to the persistence of cryptococcal infections. SynopsisInfections due to the pathogenic yeast Cryptococcus are a significant cause of morbidity and mortality in persons with impaired T-cell functions, particularly those with AIDS. The major virulence factor of Cryptococcus is its capsule, which is composed primarily of the polysaccharide glucuronoxylomannan (GXM). The capsule not only surrounds the organism but also is shed during cryptococcosis. GXM is taken up by macrophages in vitro and in vivo; however, little is known about the interaction between GXM and dendritic cells, which are the most potent cells capable of activating T cells. Because of the importance of T cells in the anticryptococcal response, the authors investigated the effect of GXM on the ability of dendritic cells to initiate a T-cell response. They found the polysaccharide was internalized by dendritic cells and inhibited antigen-specific T-cell responses. Furthermore, GXM had a direct, inhibitory effect on T-cell proliferation, independent of the effect on dendritic cells. These findings may help explain the persistence of cryptococcal infections and suggest that GXM could be therapeutic in situations where suppression of T-cell responses is desired.National Institutes of Health (R01 AI25780, R01 AI066087, R01 AI37532

Cryptococcus neoformans chitin synthase 3 plays a critical role in dampening host inflammatory responses

Cryptococcus neoformans is the most common disseminated fungal pathogen in AIDS patients, resulting in ∼200,000 deaths each year. There is a pressing need for new treatments for this infection, as current antifungal therapy is hampered by toxicity and/or the inability of the host’s immune system to aid in resolution of the disease. An ideal target for new therapies is the fungal cell wall. The cryptococcal cell wall is different from the cell walls of many other pathogenic fungi in that it contains chitosan. Strains that have decreased chitosan are less pathogenic and strains that are deficient in chitosan are avirulent and can induce protective responses. In this study, we investigated the host responses to a chs3Δ strain, a chitosan-deficient strain, and found that mice inoculated with the chs3Δ strain all died within 36 h and that death was associated with an aberrant hyperinflammatory immune response driven by neutrophils, indicating that chitosan is critical in modulating the immune response to Cryptococcus.Cryptococcus neoformans infections are significant causes of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. One of the main interfaces between the fungus and the host is the fungal cell wall. The cryptococcal cell wall is unusual among human-pathogenic fungi in that the chitin is predominantly deacetylated to chitosan. Chitosan-deficient strains of C. neoformans were found to be avirulent and rapidly cleared from the murine lung. Moreover, infection with a chitosan-deficient C. neoformans strain lacking three chitin deacetylases (cda1Δcda2Δcda3Δ) was found to confer protective immunity to a subsequent challenge with a virulent wild-type counterpart. In addition to the chitin deacetylases, it was previously shown that chitin synthase 3 (Chs3) is also essential for chitin deacetylase-mediated formation of chitosan. Mice inoculated with the chs3Δ strain at a dose previously shown to induce protection with the cda1Δcda2Δcda3Δ strain die within 36 h after installation of the organism. Mortality was not dependent on viable fungi, as mice inoculated with a heat-killed preparation of the chs3Δ strain died at the same rate as mice inoculated with a live chs3Δ strain, suggesting that the rapid onset of death was host mediated, likely caused by an overexuberant immune response. Histology, cytokine profiling, and flow cytometry indicate a massive neutrophil influx in the mice inoculated with the chs3Δ strain. Mice depleted of neutrophils survived chs3Δ inoculation, indicating that death was neutrophil mediated. Altogether, these studies lead us to conclude that Chs3, along with chitosan, plays critical roles in dampening cryptococcus-induced host inflammatory responses

Impact of Covid-19 on the Italian and American Healthcare Systems : A Comparative Assessment

This report aims to examine and assess the impact of the COVID-19 global pandemic on the healthcare systems of the United States of America and Italy; two of the most heavily affected nations. Using data from December 2019 to January 2021, several consultations, and policy reviews, we identify risks and notable areas of issue in each nations’ approach to combating the virus. We focus our report particularly on the health policies and the governmental structures in place that contributed to each nations’ initial method of alleviating the impact of COVID-19. Our report compares the two healthcare systems and proposes a list of mitigation strategies for each respective country to consider implementing in order to alleviate the risks and impact of future pandemics and systemic consequences

kk-Schur functions and affine Schubert calculus

This book is an exposition of the current state of research of affine Schubert calculus and $k$-Schur functions. This text is based on a series of lectures given at a workshop titled "Affine Schubert Calculus" that took place in July 2010 at the Fields Institute in Toronto, Ontario. The story of this research is told in three parts: 1. Primer on $k$-Schur Functions 2. Stanley symmetric functions and Peterson algebras 3. Affine Schubert calculusComment: 213 pages; conference website: http://www.fields.utoronto.ca/programs/scientific/10-11/schubert/, updates and corrections since v1. This material is based upon work supported by the National Science Foundation under Grant No. DMS-065264

Genome-Wide Transposon Screen of a Pseudomonas syringae mexB Mutant Reveals the Substrates of Efflux Transporters.

Bacteria express numerous efflux transporters that confer resistance to diverse toxicants present in their environment. Due to a high level of functional redundancy of these transporters, it is difficult to identify those that are of most importance in conferring resistance to specific compounds. The resistance-nodulation-division (RND) protein family is one such example of redundant transporters that are widespread among Gram-negative bacteria. Within this family, the MexAB-OprM protein complex is highly expressed and conserved among Pseudomonas species. We exposed barcoded transposon mutant libraries in isogenic wild-type and ΔmexB backgrounds in P. syringae B728a to diverse toxic compounds in vitro to identify mutants with increased susceptibility to these compounds. Mutants with mutations in genes encoding both known and novel redundant transporters but with partially overlapping substrate specificities were observed in a ΔmexB background. Psyr_0228, an uncharacterized member of the major facilitator superfamily of transporters, preferentially contributes to tolerance of acridine orange and acriflavine. Another transporter located in the inner membrane, Psyr_0541, contributes to tolerance of acriflavine and berberine. The presence of multiple redundant, genomically encoded efflux transporters appears to enable bacterial strains to tolerate a diversity of environmental toxins. This genome-wide screen performed in a hypersusceptible mutant strain revealed numerous transporters that would otherwise be dispensable under these conditions. Bacterial strains such as P. syringae that likely encounter diverse toxins in their environment, such as in association with many different plant species, probably benefit from possessing multiple redundant transporters that enable versatility with respect to toleration of novel toxicants.IMPORTANCE Bacteria use protein pumps to remove toxic compounds from the cell interior, enabling survival in diverse environments. These protein pumps can be highly redundant, making their targeted examination difficult. In this study, we exposed mutant populations of Pseudomonas syringae to diverse toxicants to identify pumps that contributed to survival in those conditions. In parallel, we examined pump redundancy by testing mutants of a population lacking the primary efflux transporter responsible for toxin tolerance. We identified partial substrate overlap for redundant transporters, as well as several pumps that appeared more substrate specific. For bacteria that are found in diverse environments, having multiple, partially redundant efflux pumps likely allows flexibility in habitat colonization

A Systematic Review of Measurement Instruments to Assess Cognition and Language Development at 24 Months of Age, for Use in Effectiveness Trials of Nurse-Home Visitation Programs

This systematic review evaluates cognitive and language measurement instruments for use at 24 months of age in effectiveness trials of nurse-home visitation programs. In particular, this review aims to identify and recommend potential instruments for the British Columbia Healthy Connections Project, a scientific evaluation of the Nurse Family Partnership, a nurse-home visitation program, in Canada. Although there is an overlap in child cognitive and language development in young children, the extent of the overlap is unclear, and hence it is recommended that instruments designed to separately assess cognition and language be used if feasible. A general search of potential instruments was completed, in addition to searches pertaining to instruments that have been used in home visitation interventions designed to improve language and cognition in young children. Detailed components are reported for 6 instruments: the Bayley Scales of Infant and Toddler Development –Third Edition (Bayley-III), the Battelle Developmental Inventory –Second Edition (BDI-2), the Preschool Language Scale –Fifth Edition (PLS-5), the MacArthur-Bates Communicative Development Inventory (CDI), the Language Development Survey (LDS), and the Language Use Inventory for Young Children (LUI). All 6 instruments were considered as acceptable for reliability and validity (r > 0.70). Although the Bayley-III is considered the gold standard, without adequate resources and planning, it presents challenges in training and administration. The BDI-2 is a suitable substitute for the Bayley-III in lower resource situations. More research is required to draw conclusions on the reliability and validity of the PLS-5. Selection between the CDI, LDS, and LUI depends on what aspect of language development is to be evaluated. Child cognitive and language instruments administered at 24 months of age have limitations in their predictive validity and use in populations speaking English as a second language. Further research and longitudinal studies in these areas are warranted

Risk factors for oral HPV persistence and HPV-associated cancer

Background: Persistent human papillomavirus (HPV) infection is a well-known cause of cervical and anogenital cancers. In the past decade, oral HPV infection was established as a cause of oropharyngeal squamous cell carcinoma (OPSCC), but risk factors for oral HPV persistence are poorly understood. Increasing HPV-associated OPSCC has been reported in several Western countries, predominantly in younger white men. Trends in Asian populations have not been well-described, but may differ since the epidemiology of HPV-associated cancers varies by age, sex, geography and race/ethnicity. Objectives: We aimed to investigate potential factors associated with oral HPV persistence, including 1) serum cytokines, 2a) recreational drug use and 2b) medication use. We also explored: 3) the epidemiology of OPSCC and other potentially HPV-associated cancers in Singapore, a Southeast Asian country. Methods: For aims 1 and 2, participants were enrolled in the “Persistence of Oral Papillomavirus Study” (POPS), a U.S.-based cohort study. Oral rinse samples were collected semi-annually for HPV DNA testing. Blood samples were collected for cytokine testing. Drug and medication use were assessed via questionnaire. For aim 3, the epidemiology of potentially HPV-associated cancers in Singapore was described, using cancer registry data. Data were analyzed using Wei-Lin-Weissfeld regression (aims 1&2) and Joinpoint regression (aim 3). Results: From 2010 to 2014, 1,666 participants were enrolled in POPS. Oral HPV prevalence was 36% and median time to clearance was 6.3 months. Higher TNF-α concentration was associated with decreased oral HPV clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95%CI=0.34-0.79) and women (aHR=0.76, 95%CI=0.55-1.04), p-interaction=0.049. Cocaine use (aHR=0.60, 95%CI=0.41-0.88) and antipsychotic medication use (aHR=0.75, 95%CI=0.57-0.99) were also each associated with reduced clearance. In Singapore, OPSCC incidence increased in both genders (men 1993-2012, annual percentage change [APC]=1.9%, p<0.001; women 1968-2012, APC=2.0%, p=0.01), in contrast to non-oropharyngeal head and neck cancers. The incidence of HPV-associated cancers varied by ethnicity. Conclusions: Some immunomodulatory agents, including high serum TNF-α, cocaine, and antipsychotic medication may reduce oral HPV clearance. Similar to trends in other countries, OPSCC incidence increased in Singapore in recent years, suggesting the epidemiologic shift in head and neck cancers is not just occurring in the West