Be Empowered! Take the \u27Scary\u27 out of Linked Data

The archives and library community has implemented linked data in recent years. Linked data empowers archivists to connect local data to a global audience using common identifiers and standards. However, due to the high level of institutional requirements that projects typically need with the high barrier of time and resources, many archivists have difficulty incorporating linked data practices into their daily descriptive work. The Dr. Jo Ann Rayfield Archives at Illinois State University’s Milner Library received the opportunity to digitize a segment of the expansive Ken-Way Studio Photograph Collection. The collection encompasses 120 linear feet and documents the history of Bloomington-Normal and the Central Illinois region. The Ken-Way Studio Digital Collection is a detailed photographic history of the development of national businesses in the Midwest. Many of the images in the digital collection feature the local and regional Central Illinois business community. Several companies held national significance, including Prairie Farms, Standard Oil, Admiral Corporation, and Nestle Beich. Because the collection was not physically processed, it allowed an opening to invest time to research and create original descriptive metadata, including linked data elements, to accompany individual images in the digital collection. To lower the barrier, Milner Library observed an incremental approach to contribute to the linked data environment and prepared descriptive metadata for future use/reuse

Junior doctors' experiences of managing patients with medically unexplained symptoms: a qualitative study

OBJECTIVES: To explore junior doctors' knowledge about and experiences of managing patients with medically unexplained symptoms (MUS) and to seek their recommendations for improved future training on this important topic about which they currently receive little education. DESIGN: Qualitative study using in-depth interviews analysed using the framework method. SETTING: Participants were recruited from three North Thames London hospitals within the UK. PARTICIPANTS: Twenty-two junior doctors undertaking the UK foundation two-year training programme (FY1/FY2). RESULTS: The junior doctors interviewed identified a significant gap in their training on the topic of MUS, particularly in relation to their awareness of the topic, the appropriate level of investigations, possible psychological comorbidities, the formulation of suitable explanations for patients' symptoms and longer term management strategies. Many junior doctors expressed feelings of anxiety, frustration and a self-perceived lack of competency in this area, and spoke of over-investigating patients or avoiding patient contact altogether due to the challenging nature of MUS and a difficulty in managing the accompanying uncertainty. They also identified the negative attitudes of some senior clinicians and potential role models towards patients with MUS as a factor contributing to their own attitudes and management choices. Most reported a need for more training during the foundation years, and recommended interactive case-based group discussions with a focus on providing meaningful explanations to patients for their symptoms. CONCLUSIONS: There is an urgent need to improve postgraduate training about the topics of MUS and avoiding over-investigation, as current training does not equip junior doctors with the necessary knowledge and skills to effectively and confidently manage patients in these areas. Training needs to focus on practical skill development to increase clinical knowledge in areas such as delivering suitable explanations, and to incorporate individual management strategies to help junior doctors tolerate the uncertainty associated with MUS

Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses

BACKGROUND: Vaccine efficacy depends significantly on the use of appropriate adjuvant(s) in the formulation. Phytol, a dietary diterpene alcohol, is similar in structure to naturally occurring isoprenoid adjuvants; but little is known of its adjuvanticity. In this report, we describe the relative safety and efficacy of phytol and its hydrogenated derivative PHIS-01 compared to commercial adjuvants. METHODS: We tested adjuvant properties using a formulation consisting of either a hapten, phthalate-conjugated to a protein, keyhole limpet hemocyanin (KLH), or ovalbumin (OVA) emulsified with the test adjuvants in mice without any surfactant. Humoral immunity was assessed in terms of titer, specificity, and isotypic profiles. The effect on cell-mediated immunity was studied by assaying the induction of either OVA- or B-lymphoma-specific cytotoxic T-lymphocyte (CTL) activity. RESULTS AND DISCUSSION: The phytol compounds, particularly PHIS-01, elicit increased titers of all major IgG subclasses, especially IgG2a. Unlike commercial adjuvants, both phytol compounds are capable of inducing specific cytotoxic effector T cell responses specific to both OVA and B-lymphoma tested. Phytols as adjuvants are also distinctive in that they provoke no adverse anti-DNA autoimmune response. Intraperitoneally administered phytol is comparable to complete Freund's adjuvant in toxicity in doses over 40 ug/mouse, but PHIS-01 has no such toxicity. CONCLUSION: These results and our ongoing studies on antibacterial immunity show that phytol and PHIS-01 are novel and effective adjuvants with little toxicity

Correction: Phytol-based novel adjuvants in vaccine formulation: 1. assessment of safety and efficacy during stimulation of humoral and cell-mediated immune responses

This is a correction article

Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

BACKGROUND: Adjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phytol and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against E. coli and S. aureus, and in terms of inflammatory cytokines. METHODS: Vaccines, consisting of heat-attenuated E. coli or S. aureus and either of the two phytol-based adjuvants or IFA, were tested in female BALB/c mice. The vaccines were administered intraperitoneally at 10-day intervals. The efficacy of the phytol and PHIS-01, as compared to IFA, was assessed by ELISA in terms of anti-bacterial antibody and inflammatory cytokines. We also examined the ability of the vaccines to induce specific protective immunity by challenging mice with different doses of live bacteria. RESULTS AND DISCUSSION: IFA, phytol, and PHIS-01 were equally efficient in evoking anti-E. coli antibody response and in providing protective immunity against live E. coli challenges. In contrast, the antibody response to S. aureus was significant when PHIS-01 was used as the adjuvant. However, in terms of the ability to induce protective immunity, phytol was most effective against S. aureus. Moreover, during challenges with live E. coli and S. aureus immune mice produced much less IL-6, the mediators of fatal septic shock syndromes. CONCLUSION: Our results show that vaccine formulations containing phytol and PHIS-01 as adjuvants confer a robust and protective immunity against both Gram-negative and Gram-positive bacteria without inducing adverse inflammatory cytokine due to IL-6

Macrophages in solid organ transplantation

Macrophages are highly plastic hematopoietic cells with diversified functions related to their anatomic location and differentiation states. A number of recent studies have examined the role of macrophages in solid organ transplantation. These studies show that macrophages can induce allograft injury but, conversely, can also promote tissue repair in ischemia-reperfusion injury and acute rejection. Therapeutic strategies that target macrophages to improve outcomes in solid organ transplant recipients are being examined in preclinical and clinical models. In this review, we discuss the role of macrophages in different types of injury and rejection, with a focus on macrophage-mediated tissue injury, specifically vascular injury, repair and remodeling. We also discuss emerging macrophage-centered therapeutic opportunities in solid organ transplantation

Functionalised metal nanoparticles as novel reagents for biomedical analysis.

This thesis describes a study of the synthesis and characterisation of a new family of cationic alkane-thiolate and -selenolate compounds bearing a phosphonium (or phosphine oxide) head group, and the applications as ligands for the stabilisation of gold nanoparticles. The ability of these cationic phosphonium gold nanoparticles as substrates for the detection of negatively charged biomolecules has also been explored. In chapter 1, topics concerning the synthesis of functionalised gold nanoparticles, their biorecognition properties, the application of these nanoparticles in the biomedical field and gold nanoparticles stabilised with phosphorus-containing ligands, are outlined in a literature review.Instrument details of the analytical methods employed to characterise all the compounds and nanoparticles obtained in the study are outlined in Chapter 2. The syntheses and structural characterisation by NMR, ESMS and X-ray crystallography of cationic phosphonium-containing ligands are described in Chapters 3 to 5. Chapter 3 contains the description of the synthesis of phosphonioalkylthiosulfate zwitterions. The synthesis of related phosphonioalkylselenide compounds is presented in Chapter 4, and Chapter 5 is concerned with the synthesis of phosphonioalkylthioacetate and related phosphine oxide ligands. In Chapter 6, the preparation of the cationic phosphonium-functionalised gold nanoparticles using the phosphonium-containing compounds as protecting ligands, in a two-phase liquid-liquid (DCM-H[2]O) and one phase (ethanol) systems, is described. This chapter also contains details of characterisation of these nanoparticles by NMR, XPS and TEM. The ability of the cationic phosphonium gold nanoparticles to interact with RNA and cDNA, and the potential of using these nanoparticles as biorecognition systems was investigated by the Biacore Surface Plasmon Resonance technique and this work is described in Chapter 7. Finally, a summary of conclusions and some suggestions for future work are presented in Chapter 8

Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

Nitrogen-containing-bisphosphonates (N-BPs) are widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance