Miracle-dz/UniFAR-FTUs huggingface dataset:
Galactose-conjugated photosensitizers for targeted cancer photodynamic therapy

The combination of a photosensitizing molecule (Photosensitizer, PS) and light to induce toxicity by Reactive Oxygen Species (ROS) production is very attractive in the treatment of cancer by Photodynamic Therapy (PDT). Unfortunately, the PSs used in clinic for the treatment of cancer have low cancer selectivity and poor water solubility. The success of new PDT agents in cancer treatment requires a strong collaboration between chemists for the synthesis of the porphyrinoid molecule and conjugation with a cancer-targeting motif, physicists for the development of appropriate light irradiation devices, biochemists for understanding cellular responses, and clinicians for the clinical studies. In this study, we have combined the knowledge of chemists and biochemists to develop new PSs by conjugating them with specific galactose motifs to be used in the treatment of cancer by PDT. These new galactose-PSs were designed for a specific target such as a galactose-binding protein overexpressed in cancer cells, and their photophysical properties evaluated. We have tested the photo-chemical and –physical properties of the new PSs and their photodynamic potential in different biological models. Chapter I of this dissertation presents a brief introduction to the use of PDT in the treatment of cancer and the potential of galactose-PSs in PDT. Chapter II reports the synthesis of water-soluble porphyrinoids attached to dendritic units of galactose or to galactose through carbon-3. In Chapter III, HT-1376 and UMUC-3 bladder cancer cells growing as monolayers were used to determine the uptake and photodynamic potential of a phthalocyanine conjugated with galactodendritic units (PcGal16). The galactose-binding proteins galectin-1 and GLUT1 demonstrated to be involved in the uptake and further phototoxicity of PcGal16 by bladder cancer cells. The role of caveolaeand clathrin-mediated endocytosis in the internalization of PcGal16 by bladder cancer cells is reported in Chapter IV. Cellular studies revealed that interfering with endocytic pathways led to increased phototoxicity in HT-1376 cancer cells resistant to PDT. Chapter V describes the in vitro and in vivo photodynamic properties of a porphyrin conjugated with dendritic units of galactose (PorGal8). PorGal8 uptake and PDT-induced cytotoxicity were higher in UM-UC-3 compared to HT1376 bladder cancer cells. These differences were correlated with the levels of galectin-1 protein expression and cytoskeleton alterations. PorGal8 accumulated in UM-UC-3 xenograft tumors and induced tumor ablation after PDT. Chapter VI discussed the potential of a repeated PDT treatment to increase in vitro and in vivo phototoxicity with a galactodendritic chlorin (ChlGal8) in HT-1376 cells resistant to PDT. Chapter VII reports the potential of a porphyrin conjugated with C3-galactose (Por-C3-Gal4) in monolayers and spheroid cultures of HCT-116 colon cancer cells, MCF-7 breast cancer cells, UM-UC-3 bladder cancer cells and HeLa cervical cancer cells.
Sex, size, and prey caloric value affect diet specialization and consumption of an invasive prey by a native predator

Abstract Escaping the control of natural enemies is thought to heavily influence the establishment success and impact of non-native species. Here, we examined how the profitability of alternative prey in combination with the presence of a competitor and predator aggressive behavior explain individual differences in diet specialization and the consumption of the invasive green porcelain crab Petrolisthes armatus by the native mud crab predator Panopeus herbstii. Results from bomb calorimetry estimates show that invasive P. armatus has high caloric value relative to alternative native prey. Laboratory assays indicated that specialization and consumption of invasive P. armatus was mostly exhibited by large, female P. herbstii, but the presence of a competitor and predator aggressiveness did not influence diet and the consumption of P. armatus. Thus, intrinsic factors (e.g., sex and body size) seem to explain consumption of P. armatus and dietary specialization in P. herbstii, more generally. Although there are still many predator individuals that do not consume P. armatus, the proportion of individuals that have begun to specialize on P. armatus suggests that for some, it has become more profitable relative to alternative native prey. Given the high caloric value of P. armatus, we suggest that it is likely that differences in the cost of its consumption, including attack, capture, and handling times relative to alternative prey, determine its net profitability to individual predators.
Exploring the role of team environment in building project performance

Design and construction projects incorporate stakeholders from many different organizations, often with conflicting goals, overlapping responsibilities and differing areas of expertise. With an increasing interest in improving the ‘integration’ and collaboration on construction projects, there is a need for empirical research to understand the contributions of project team interactions to project-level performance. The purpose of this paper is to explore the correlations between several indicators of the collaborative team environment and traditional measures of project success. With the assistance of an industry advisory board, a survey questionnaire was developed to collect detailed information for recently completed building projects in the United States. The questionnaire was distributed via mailing lists, conferences and industry contacts to reach a diverse set of respondents. Using this large data set of 124 projects, bivariate Spearman rho correlation coefficients are calculated and reported. Significant correlations suggest the role of on-time communication in reducing construction cost growth, higher team chemistry in reducing overall schedule growth and larger administrative burdens in increasing construction cost growth and final unit cost. Multicollinearity among the measures of team environment suggests the presence of latent variables and need for future multivariate analyses.
Artificial insemination in dogs

Artificial insemination is the process by which spermatozoa are placed into the reproductive tract of a female for the purpose of impregnation using means other than natural mating. This chapter looks at semen collection; semen examination; semen dilution and artificial insemination dose; freezing of semen; international movement of canine semen; timing of the insemination; insemination techniques; regulations, ethics and practice.
Investigations into the protective effects of the Multiple Myeloma Bone Marrow Microenvironment

Multiple Myeloma (MM) is the second most common haematological cancer in the Western World, accounting for approximately 10% of all newly diagnosed blood cancers each year. Despite the recent advancements in its treatment, MM remains incurable. This is partly due to the protective niche in which it inhabits – the bone marrow microenvironment (BMM). MM cells have been shown to `re-program’ other cell populations within this milieu to produce the growth factors needed for its own development. These factors initiate pro-survival pathways within MM cells, including the phosphatidylinositol 3-kinase (PI3K) pathway. The PI3K catalytic isoforms p110δ and p110γ are known to be specifically enriched by the haematopoietic system, providing a highly precise therapeutic target. In this thesis, the PI3K pathway was shown to be activated in response to both the BMM and IL-6 alone. Both p110δ/p110γ were found to be highly expressed in MM and were implicated in MM growth, survival and migration. p110γ only knockdown within human MM cell lines caused a significant reduction in MM adhesion to fibronectin. In vivo, xenograft models showed that knockdown of either of these isoforms in the human MM cell line U266 increased overall survival (OS), as did dual inhibition of p110δ and p110γ (via the drug IPI-145). Cytokine array analysis of MM primary cells revealed extremely high levels of extracellular Macrophage Migratory Inhibitory Factor (MIF), a known stimulator of the PI3K pathway. Knockdown of MM cell MIF resulted in significantly increased OS and reduced tumour burden in secondary sites. MIF was found to stimulate the production of IL-6/8 from bone marrow stromal cells, and c-Myc was implicated in the regulation of this process. Taken together, the data presented here demonstrates that PI3K signalling is beneficial to MM disease progression. MM-derived MIF increases the availability of IL-6 within the BMM, causing activation of the PI3K pathway. Therapies targeting the PI3K isoforms or MIF (alongside conventional MM therapeutics) could therefore benefit MM patient treatment, and warrants clinical investigation.
SPR-measuredkinetics of PROTAC ternary complexes influence target degradation rate

Bifunctional degrader molecules, known as proteolysis-targeting chimeras (PROTACs), function by recruiting a target to an E3 ligase, via a target:PROTAC:ligase ternary complex. Despite the importance of this key intermediate species, no method to monitor ternary complex kinetics has been reported, and it remains to be addressed how this might impact on the kinetics of protein degradation. Here, we develop an SPR-based assay to quantify the stability of PROTAC-induced ternary complexes by measuring for the first time the kinetics of their formation and dissociation. We benchmark our assay using four PROTACs that target the bromodomains (BDs) of BET proteins Brd2, Brd3 and Brd4 to the E3 ligase VHL. We reveal marked differences in ternary complex off-rates for different PROTACs that form either cooperative or non-cooperative complexes. The positively cooperative degrader MZ1 forms comparatively stable and long-lived ternary complexes with eitherBrd4BD2 or Brd2BD2 and VHL. Equivalent complexes with Brd3BD2 are destabilized due toa single amino acid difference (Glu/Gly swap) present in the bromodomain. We observe that this difference in ternary complex dissociative half-life correlates to a greater initial rate of intracellular degradation of Brd2 and Brd4 relative to Brd3. These findings establish a novel assay to measure the kinetics of PROTAC ternary complexes and elucidate the important kinetic parameters that drive effective target degradation.
Fabrication and nuclear reactor tests of ultra-thin 3D silicon neutron detectors with a boron carbide converter

We describe the design, fabrication process and characterization of a thermal neutron detector based on ultra-thin silicon PIN diodes with 3D electrodes and a 10B4C neutron converter layer. The sensors were fabricated on SOI silicon with an active thickness of 20 μm which allows for a low gamma sensitivity, while the 3D structure of the electrodes results in a lower capacitance that in the equivalent planar sensor. The 2.7 μm 10B4C converter layer was deposited through RF magnetron sputtering on a whole silicon wafer, opening the path for mass-production. The detectors were tested in a thermal neutron beam at the nuclear reactor at the Instituto Superior Técnico in Lisbon and their intrinsic detection efficiency for themal neutrons and the gamma sensitivity as a function of the energy threshold were obtained.
Factors associated with dental caries in children aged 4-6 years old

ABSTRACT Dental caries is one of the dental health problems. Dental caries are formed because there was leftover food that sticks to the teeth, which eventually lead to tooth calcification. Impact, teeth become brittle, hollow, even broken.Dental caries experience a loss of power to make a child chewing and digestive disruption, which resulted in growth of less than the maximum. This study aims to determine the relationship of parents’ behavior towards the maintenance of dental health of children (feeding habits sweet, sticky and drinking milk, teeth maintenance, inspection tooth and mouth) with dental caries in the TK R.A Bustanussholihin in Balun village Turi District of Lamongan. This study Analytics whose data is collected with a cross sectional sample of kindergarten children aged 4–6 years with a total sample of 49 children. The collection of primary data through interviews parents TK R.A Bustanussholihin student using questionnaires and secondary data obtained from the agency are in the region of the profile data TK R.A Bustanussholihin in Balun Village of Turi District of Lamongan. This study used a correlation coefficient of contingency. Based on the results of the contingency coefficient correlation test showed that the factors that have a strong relationship is the habit of feeding the sweet, sticky, and drink milk with a value of P = 0.504. While the factors that have a weak link is the habit of maintaining dental hygiene habits of children and child oral examination . From this study it can be concluded that there is a relationship or a strong correlation between feeding habits sweet, sticky and drinking milk with the incidence of dental caries in children aged 4–6. So as to prevent dental caries severity we need to hold counseling on feeding sweet, soft and gooey on the effect of dental caries as well as how it should be formula feeding or breast milk to the child to prevent rampant caries. Keywords: dental caries, sweetened food, children aged 4–6 years
The Role of Seaweed Antimicrobials in Selection for Antibiotic Resistance

Page 2 List of Tables. Page 6 List of Figures. Page 7 List of Supplementary data. Page 8 Acknowledgements. Page 9 Chapter 1: General Introduction. Page 10 1.1 Brief History of Antibiotics. Page 10 1.2 The Antimicrobial Resistance Epidemic. Page 11 1.3 Mechanisms of Resistance. Page 12 1.4 Selective Pressures for Antimicrobial Resistance. Page 13 1.5 Natural Antimicrobials. Page 15 1.6 Seaweed as a Model. Page 15 1.7 Seaweed-Associated Bacterial Communities. Page 16 1.8 Local Adaptation. Page 18 1.9 Cross-resistance. Page 19 1.10 Natural Antimicrobial Resistance. Page 19 1.11 Aims and Objectives. Page 20 Chapter 2: Culture-based Characterisation of Seaweed-Associated Bacteria and Their Resistance Profiles. Page 21 2.
The Incidence Of Rule Changes On Physiological Characteristics Of Male And Female Canoe Slalom Paddlers: A 14-Year Longitudinal Study.

31 men and 22 women elite french canoe slalom paddlers were screened on a yearly basis using various tests. Anthropometric measurements included height (cm), weight (kg) and body composition using skinfold measurements (Durnin & Womersley, 1969). Maximal oxygen consumption (VO2max) and ventilatory threshold (VT) was assessed using an incremental exercise test on a Monark arm ergometer until volitional exhaustion and a 6s all-out force-velocity test to determine maximal power with the upper limbs. • Decrease in standing height in men and women related to a lowering of center of mass possibly allowing increased agility in the gates (Hunter, 2009).
Effects of Dietary Probiotic, Prebiotic and Enzyme Mixture Supplementation on Performance, Carcase, Organ, Ileal pH and Viscosity of Broilers

Amac: D eneme, probiyotik, prebiyotik ve enzimin etlik piliclerde performans, karkas, organlar, bagirsak pH’i ve viskozitesi uzerine tek basina ve kombine etkilerini belirlemek amaciyla yurutulmustur. Materyal ve Metot: Bir gunluk yasta 700 adet erkek Ross-308 etlik civciv, bireysel olarak tartilmis ve her bolmede 25 civciv olacak sekilde 28 gruba dagitilarak 0-42. gunler arasinda barindirilmistir. Denemede kullanilan katki maddeleri disinda benzer besin madde profiline sahip ve kullanilan yem katki maddesinin tek basina (1 g/kg) veya kombine sekilde (0.5 g/kg+0.5 g/kg) ilave edildigi yedi adet baslatma ve buyutme yemi formulasyonu olusturulmustur. Yemler, katki maddesi icermeyen (kontrol), prebiyotik, enzim, probiyotik+prebiyotik, probiyotik+enzim ve prebiyotik+enzim icerecek sekilde hazirlanmistir. Bulgular: Probiyotik, probiyotik+prebiyotik ve probiyotik+enzim ilavesi 42. gun canli agirligini onemli derecede artirmistir (P 0.05). Yem katkisi ilavesinin bagirsak pH’i ve viskozitesi uzerine onemli bir etkisi belirlenmistir. Kontrol grubu ile karsilastirildiginda deneme katkilarinin ilavesi ile bagirsak pH’i ve viskozitesi azalmistir. Sonuc: Probiyotikler, prebiyotikler ve enzimler arasindaki sinerjik etkiler daha fazla arastirilmali, pratikte uygun kombinasyonlar ve seviyeler belirlenmelidir
Seasonal variation of the phytoplankton community in tuna farms in Bahía de la Paz, southern Gulf of California, Mexico

The phytoplankton community of tuna farms in Bahía de La Paz, southern Baja California, Mexico was studied. Samples were taken from tuna farms near San Juan de la Costa, Rancheros del Mar and from a station in El Mogote, away from the influence of these farms. Water samples were collected monthly (June 2006-May 2007) with a van Dorn bottle at different depths in San Juan de la Costa (0, 25 and 50 m), Rancheros del Mar (0, 15 and 30 m) and El Mogote (0 m) to measure temperature, dissolved oxygen, inorganic nutrients, and chlorophyll-a and to determine phytoplankton composition and abundance. The index of simple dominance, Shannon-Weaver diversity, and Pielou evenness were estimated. The water column was stratified from June to September (~27.5°C) and mixed from October to May (~18.5°C). Nutrient concentrations at the three sampling sites did not increase significantly. Nanophytoplankton dominated, followed by microplanktonic diatoms, and the highest diatom abundance occurred during the warm period. The phytoplankton community was more diverse in San Juan de la Costa than in Rancheros del Mar. In the latter, a superficial bloom of the cyanobacterium Trichodesmium erythraeum (1630×10 cel L) occurred in September, and in San Juan de la Costa the diatom Pseudo-nitzschia fraudulenta reached the highest abundance (183.8×10 cel L) in July.
Using stem cells to model MERTK deficient retinis pigmentosa

Inherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of cellular material to study. This research used fibroblast-derived induced pluripotent stem cells (iPSC) to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. The patient phenotype, fibroblasts, iPSC and RPE were fully characterised at the DNA, RNA, protein and functional levels and compared to a control. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and based on this, the MERTK-RPE cells were subsequently treated with two translational read-through inducing drugs to investigate potential restoration of expression of the affected gene and production of a full-length protein. One of the drugs was able to reinstate phagocytosis of labelled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis, drug screening potential and treatments for these rare and blinding disorders.
HCV Lymphotropism and Its Pathogenic Significance

Hepatitis C virus (HCV) is not only a hepatotropic but also a lymphotropic virus. Infection of the immune system appears to be a natural propensity of HCV and, as the accumulated data indicate, a common characteristic of both symptomatic and clinically silent but molecularly evident infection known as occult infection. The ability of HCV to infect cells of the immune system is consistent with a significantly greater prevalence of certain lym - phoproliferative disorders in HCV-infected patients, such as mixed cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. This chapter recapitulates the approaches used to detect HCV and its replication within lymphoid cells, features of HCV compartmentalization in the lymphatic system and in different types of immune cells, and the cell culture models developed to study HCV lymphotropism. In addition, the characteristics of the molecules recently identified as those specifically mediating HCV entry leading to virus replication in B and T lymphocytes, which are distinct from those involved in virus entry to hepatocytes, are presented. Finally, the biological impact of HCV lymphotro- pism on the function of immune cells, virus persistence, and immune cell proliferation and lymphomagenesis is summarized. entiation toward the Th1 lineage, as well as inhibited Molt-4 T-cell proliferation while enhanc-ing their CD95 (Fas)-mediated apoptosis [68]. A study from our group showed that naturally occurring, patient-derived HCV inhibited the proliferation of primary CD4 + , but not CD8 + T cells, without augmenting cell death [72]. Interestingly, the results also suggested that just an exposure to authentic HCV in the absence of molecularly evident viral replication might be sufficient to inhibit CD4 + T-cell proliferation. It has also been shown that HCV core protein is capable of the transcriptional activation of the IL-2 promoter in T cells [97] and could modulate T-cell responses by inducing spontaneous and T-cell receptor (TCR)-mediated oscillations of calcium ions [98]. Others demonstrated that HCV core protein upregulated the expression of anergy-related genes in Jurkat T cells stably expressing this protein, and this coincided with the activation of nuclear factor of activated T cells (NFAT) and suppression of the IL-2 promoter [99]. In addition, it was reported that the direct binding of HCV core protein to complement receptor, gC1qR, on CD4 + and CD8 + T cells upregulated the expression of programmed death-1 (PD-1). This was accompanied by the dysregulation of T-cell activation, proliferation, and apoptosis [100]. These alterations were restored by blocking the engagement of the PD-1 and programmed death ligand-1 (PDL-1) pathway.
Neurological manifestations of severe acute respiratory syndrome coronavirus 2—a controversy ‘gone viral’

Abstract Severe acute respiratory syndrome coronavirus 2 first appeared in December 2019 in Wuhan, China, and developed into a worldwide pandemic within the following 3 months causing severe bilateral pneumonia (coronavirus disease 2019) with in part fatal outcomes. After first experiences and tentative strategies to face this new disease, several cases were published describing severe acute respiratory syndrome coronavirus 2 infection related to the onset of neurological complaints and diseases such as, for instance, anosmia, stroke or meningoencephalitis. Of note, there is still a controversy about whether or not there is a causative relation between severe acute respiratory syndrome coronavirus 2 and these neurological conditions. Other concerns, however, seem to be relevant as well. This includes not only the reluctance of patients with acute neurological complaints to report to the emergency department for fear of contracting severe acute respiratory syndrome coronavirus 2 but also the ethical and practical implications for neurology patients in everyday clinical routine. This paper aims to provide an overview of the currently available evidence for the occurrence of severe acute respiratory syndrome coronavirus 2 in the central and peripheral nervous system and the neurological diseases potentially involving this virus.