Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzyme-Catalyzed Activation of Anticancer Prodrugs

The rationale for the development of prodrugs relies upon delivery of higher concentrations of a drug to target cells compared to administration of the drug itself. In the last decades, numerous prodrugs that are enzymatically activated into anti-cancer agents have been developed. This review describes the most important enzymes involved in prodrug activation notably with respect to tissue distribution, up-regulation in tumor cells and turnover rates. The following endogenous enzymes are discussed: aldehyde oxidase, amino acid oxidase, cytochrome P450 reductase, DT-diaphorase, cytochrome P450, tyrosinase, thymidylate synthase, thymidine phosphorylase, glutathione S-transferase, deoxycytidine kinase, carboxylesterase, alkaline phosphatase, β-glucuronidase and cysteine conjugate β-lyase. In relation to each of these enzymes, several prodrugs are discussed regarding organ- or tumor-selective activation of clinically relevant prodrugs of 5-fluorouracil, axazaphosphorines (cyclophosphamide, ifosfamide, and trofosfamide), paclitaxel, etoposide, anthracyclines (doxorubicin, daunorubicin, epirubicin), mercaptopurine, thioguanine, cisplatin, melphalan, and other important prodrugs such as menadione, mitomycin C, tirapazamine, 5-(aziridin-1-yl)-2,4-dinitrobenzamide, ganciclovir, irinotecan, dacarbazine, and amifostine. In addition to endogenous enzymes, a number of nonendogenous enzymes, used in antibody-, gene-, and virus-directed enzyme prodrug therapies, are described. It is concluded that the development of prodrugs has been relatively successful; however, all prodrugs lack a complete selectivity. Therefore, more work is needed to explore the differences between tumor and nontumor cells and to develop optimal substrates in terms of substrate affinity and enzyme turnover rates for prodrug-activating enzymes resulting in more rapid and selective cleavage of the prodrug inside the tumor cells.
Critical illness in pregnancy: An overview

Objectives:To provide an overview of the critical illnesses that afflict the pregnant patient. Design:A comprehensive review of the literature was performed with Pubmed Medline using medical subject headings of pregnancy, critical care, epidemiology, prognostic score, dyspnea, fever, and jaundice. Results:Although pregnant women constitute a small number of admissions to an intensive care unit, they pose a challenge to the health care team. The physiological changes that occur in pregnancy stress and limit the compensatory response required to adapt to a superimposed acute illness. Although a number of conditions are uniquely associated with pregnancy, other medical conditions may complicate the course of pregnancy. The pregnant state also increases susceptibility to a number of illnesses. In this overview, we reviewed the epidemiology and different clinical presentations of critical illness in a pregnant patient. Conclusions:The critically ill pregnant patient presents a challenge to the critical care physician due to unique physiology and specific medical disorders in this population.
The relationship between safety-seeking, self-authenticity, self-esteem, and relatedness in social anxiety

Cognitive models of Social Anxiety Disorder (SAD) emphasize the role of safety behaviours in maintaining the negative sense of self hypothesized to be at the core of SAD. The social psychology literature contains theories regarding the self that might enrich clinical cognitive models by addressing the interplay between aspects of self and social functioning. The first theory pertains to authenticity: being able to engage in self-congruent behaviours is associated with better social functioning and self-esteem. The second pertains to the contribution of social belonging to self-esteem. My goal in this dissertation was to examine the links between safetyseeking, authenticity, relatedness, and self-esteem suggested by an integration of these theories. In Study 1, individuals seeking treatment for SAD participated in an experiment designed to manipulate use of safety behaviours in laboratory-based social interactions (N = 93). Consistent with study predictions, reduction in safety behaviours was related to increase in selfauthenticity. Additionally, increased authenticity mediated the relationship between condition and enhanced interpersonal functioning (i.e., prosocial behaviour and perceived partner reaction). In Study 2, structural equation modeling was used to evaluate two potential models of the interrelationships between safety behaviours, authenticity, relatedness, and self-esteem in a nonclinical sample (N = 279): (a) a “self-protection model,” based on the hypothesis that less reliance on safety behaviours would be linked to greater self-authenticity, which, in turn, would be linked to stronger relatedness and self-esteem, or (b) a “relatedness model” in which relatedness was hypothesized to be linked to higher self-esteem, which was linked to less safetyseeking behaviour and, thereby, greater authenticity. Results found preliminary support for both models.
trans Activity of the Norovirus Camberwell Proteinase and Cleavage of the N-Terminal Protein Encoded by ORF1

ABSTRACT The virus-encoded proteinase of Camberwell virus, a genogroup 2 norovirus, was synthesized in Escherichia coli. The purified proteinase had correct N and C termini and showed trans activity in cell-free assays. trans activity was also demonstrated in COS cells transfected with constructs encoding either the proteinase or a proteinase-polymerase fusion. The N-terminal protein of ORF1 was cleaved in COS cells, possibly at the site E194/S.
Evaluation of a low cost reverse transcriptase assay for plasma HIV-1 viral load monitoring.

We evaluated a low cost manual reverse transcriptase assay (ExaVir Load V.1 and V.2; Cavidi Tech AB) against commercially available HIV RNA assays that quantify viral load to assess its suitability for use in resource-constrained settings. Frozen plasma samples previously tested for RNA by RT-PCR (Roche Diagnostics) and bDNA (Bayer Diagnostics) were retested for RT activity. Text sequence obtained from HIV genotype analysis was submitted to the Stanford HIV Resistance Database V.3. 9 and were examined for resistant virus. Detectable RT was present in 98% of samples (V.1; n=127) and in 95% of samples (V.2; n=69) with RNA >10,000 and >1,000 copies/ml respectively. Positive association was found between the log10 RNA copies/ml and log10 RT copies/ml equivalents variables using Pearson's correlation (V.1: r=0.89, n=189; V.2: r=0.89, n=85). The RT activity over time closely followed the trend for RNA levels in samples from 10 HIV seropositive patients with progressive disease. A strong association between RT and RNA was also found with paired samples from 19 patients taken at initiation or change of antiretroviral therapy and again within 2 months. Current (n=40) or no (n=119) exposure to efavirenz therapy had no effect on RT assay performance despite efavirenz binding tightly to the RT enzyme. Samples that demonstrated resistance to the non-nucleoside RT inhibitors (n=112) had a decrease in RT of 0.20 log10 indicating a possible decrease in RT fitness. The RT assay showed good association with current molecular assays, and V.2 is sufficiently sensitive for monitoring HIV viral load in resource-constrained settings.
LIQUID CONSUMPTION

This article proposes a theoretical framework for examining recent anti-consumerist practices. It argues that such practices are important in terms not only of the political sentiments and collective concerns they mobilize, for the broader life-projects, or identity constructions they entail. Drawing on Zygmunt Bauman's thesis on ‘liquid modernity’, a theory of ‘liquid consumption’ is used to argue that many anti-consumerist practices and sensibilities shape personal identities by appealing to a decommodified sociability, yet this sociability is more often the rhetorical production of anti-consumerist discourses, and hence not capable of reinforcing the identity projects they aim to consolidate. Examples of this effect are described in the discourses of Feng Shui and the Slow Food movement.
The anatomical variation of the circulus arteriosus cerebri in a cadaver cohort representing the population dynamics of the Western Cape

Abstract The literature revealed a connection between the variations of the Circulus arteriosus cerebri (CAC) and cerebrovascular disease, ischemia, stroke, aneurysms and atherosclerosis. The diameters of the vessels forming the CAC have been classified into 22 types by previous authors. The aim of this study was to assess the variation of the CAC (diameter, length and anomalies) in a cadaver cohort representing the population of the Western Cape. Thirty-nine subjects (female n = 11, male n = 28) who had died of causes unrelated to brain trauma, were obtained from Stellenbosch University. Additionally, a pilot study was done on 20 specimens. The CAC were removed and fixed for three weeks in 10% buffered formaldehyde. Digital images were taken and the vessels were measured using Adobe Creative Suite 5: Extended edition (Photoshop). The normal diameter (type 1) was observed in 41% of specimens and type 4 (hypoplastic posterior communicating artery) was observed in 23.1%. One case (bilateral hypoplastic posterior communicating arteries and a hypoplastic right posterior cerebral artery) was classified as “other”, since it could not be classified into the 22 types. Additional variations included duplication (17.9%) and one point fusion (15.4%) of the anterior communicating artery. Studies have shown that about half of a healthy population have a typical CAC (normal diameter and no anomalies). In the present study the prevalence of a typical CAC was only 15.4%. Studies can only be compared if the same definitions for variations are used. The knowledge of these variations is important in endarterectomy, stenting head and neck surgery and angiography.
The evolution of ultracompact x-ray binaries

Context. Ultracompact X-ray binaries (UCXBs) typically consist of a white dwarf donor and a neutron star or black hole accretor. The evolution of UCXBs and very low mass ratio binaries in general is poorly understood. In particular, the dynamical behavior of an accretion disk extending to a large radius (relative to the orbit) is unclear. Aims. We investigate the evolution of UCXBs in order to learn for which mass ratios and accretor types these systems can exist, and if they do, what are their orbital and neutron star spin periods, mass transfer rates and evolutionary timescales. Methods. We compute tracks of a binary containing a Roche-lobe overflowing helium white dwarf in which mass transfer is driven by gravitational wave emission. For different assumptions concerning accretion disk behavior we calculate for which system parameters dynamical instability, thermal-viscous disk instability or the propeller effect emerge. The significance of these processes during the evolution of an UCXB is considered. Results. At the onset of mass transfer, the survival of the UCXB is determined by how efficiently the accretor can eject matter in the case of a super-Eddington mass transfer rate. At later times, the evolution of systems strongly depends on the binary’s capacity to return angular momentum from the disk to the orbit. We find that this feedback mechanism most likely remains effective even at very low mass ratio. In the case of steady mass transfer, the propeller effect can stop accretion onto recycled neutron stars completely at as ufficiently low mass transfer rate, based on energy considerations. However, mass transfer will likely be non-steady because disk instability allows for accretion of some of the transferred matter. Together, the propeller effect and disk instability cause the low mass ratio UCXBs to be visible a small fraction of the time at most, thereby explaining the lack of observations of such systems. Conclusions. Most likely UCXBs avoid late-time dynamically unstable mass loss from the donor and continue to evolve as the age of the Universe allows. This implies the existence of a large population of low mass ratio binaries with orbital periods ∼70‐80 min, unless some other mechanism has destroyed these binaries. Even though none have been discovered yet, black hole UCXBs could also exist, at orbital periods of typically 100‐110 min.
The Quantum Theory of the Dielectric Constant of Hydrogen Chloride and Similar Gases.

The quantum theory of diatomic dipoles. —Using the treatment of Pauli, an expression for the dielectric constant of a diatomic dipole gas is obtained, in which half-quantum numbers are used. It is shown that for cases of practical interest the approximation suggested by Pauli is not valid; hence numerical values of the temperature-function C have been calculated and tabulated. Application to experimental measurements. —The theory has been applied in the interpretation of Zahn's measurements of the dielectric constants of the hydrogen halides. The electric moments of molecules of hydrogen chloride, bromide, and iodide were found to be 0.3316, 0.252, and 0.146×10^-18 cgsu respectively; i.e., only about one-third of the values given on the basis of the classical theory. Moreover, the values 0.00077 and 0.00102 for 4πN0α for hydrogen chloride and bromide, in which α is the coefficient of induced polarization, are shown to be in better agreement with measurements of indices of refraction than are the classical theory values. A discussion is given of possible inaccuracies in the theory, of the choice of quantum numbers, and of the possibility of weak quantization.
Transmission of West Nile Virus Through Human Breast Milk Seems to Be Rare

INTRODUCTION.In September 2002, possible transmission of West Nile virus via human milk was reported for the first time. METHODS.Since 2003, the Centers for Disease Control and Prevention collected reports of maternal or infant West Nile virus illness during the breastfeeding period. All of the reported instances were reviewed. In addition, milk samples from women infected during pregnancy were tested for West Nile virus RNA and West Nile virus–specific antibodies. RESULTS.Six infants were reported to have breastfed from mothers with West Nile virus fever. Five of the 6 infants had no illness or detectable antibodies to West Nile virus in serum after onset of maternal illness. One infant who was not tested and developed a rash was otherwise well 1 week after onset of maternal illness. In addition, 2 infants were reported to have developed West Nile virus illness while breastfeeding; preceding maternal illness was not documented. Two breastfed infants whose mothers acquired West Nile virus fever in the last week of pregnancy developed West Nile virus–specific antibodies; both infant infections could have been congenitally acquired. Of 45 milk samples from women infected with West Nile virus during pregnancy, 2 had West Nile virus RNA, and 14 had immunoglobin M antibodies to West Nile virus. CONCLUSIONS.Of 10 reported instances since 2003 of maternal or infant West Nile virus illness while breastfeeding, transmission of West Nile virus through human milk could neither be ruled out nor confirmed for 5 cases; in 5 others, serologic tests indicated no vertical transmission. Transmission of West Nile virus through breastfeeding seems to be rare, but more information is needed.
Rumination and avoidance as mediators of the relationship between self-compassion and depression in adolescents

Background This study sought to investigate the mediating effects of rumination and cognitivebehavioural avoidance in the relationship between self-compassion and depression amongst adolescents. Method Ninety nonclinical adolescents completed self-report measures of self-compassion, depressive symptomatology, rumination (reflection and brooding subtypes) and cognitive-behavioural avoidance. Results Results showed that for the relationship between self-compassion and depression, brooding rumination, reflective rumination and total cognitive-behavioural avoidance emerged as significant mediators. Additionally, brooding rumination and cognitivebehavioural avoidance were collectively found to mediate the relationship between self-compassion and depressive symptoms. Conclusion These findings extend previous research from adult samples and suggest that selfcompassion buffers against depressive symptoms by reducing unproductive repetitive thinking and avoidant coping in adolescents. This has important implications for promoting resilience amongst adolescents and helping both the prevention and treatment of adolescent depression.
On the performance of non-orthogonal multiple access in visible light communication

In this paper, the performance of non-orthogonal multiple access (NOMA) is characterized in a downlink visible light communication (VLC) system. Analytical expressions of the system performance are derived for two separate scenarios. In the scenario of achieving guaranteed quality of service (QoS), the outage probability of each user is studied and the effect of power allocation coefficients on the system coverage probability is investigated. In the scenario of providing opportunistic best-effort service, system ergodic sum rate is formulated based on a fixed power allocation (FPA) strategy. Both simulation and analytical results demonstrate that, in the first scenario, the maximum coverage probability can be achieved through the exhaustive search (ES) method to find the optimum set of power allocation coefficients. In the second scenario, it is shown that unlike orthogonal multiple access (OMA) techniques, NOMA can achieve a higher system capacity for a larger number of users. Also, the performance of NOMA can be further enhanced by choosing LEDs with a suitable semi-angle. When compared with OMA, NOMA can increase the system capacity by 125% if LEDs with 30° semi-angle are used.
An Augmented Primal-Dual Method for Linear Conic Programs

We propose a new iterative approach for solving linear programs over convex cones. Assuming that Slater's condition is satisfied, the conic problem is transformed to the minimization of a convex differentiable function in the primal-dual space. This function shows similarities with the augmented Lagrangian function and is called “augmented primal-dual function” or “apd-function”. The evaluation of the function and its derivative is cheap if the projection of a given point onto the cone can be computed cheaply, and if the projection of a given point onto the affine subspace defining the primal problem can be computed cheaply. For the special case of a semidefinite program, a certain regularization of the apd-function is analyzed. Numerical examples minimizing the apd-function with a conjugate gradient method illustrate the potential of the approach.
Eudragit S100 entrapped insulin microspheres for oral delivery

The purpose of this research was to investigate whether Eudragit S100 microspheres have the potential to serve as an oral carrier for peptide drugs like insulin. Microspheres were prepared using water-in oil-in water emulsion solvent evaporation technique with polysorbate 20 as a dispersing agent in the internal aqueous phase and polyvinyl alcohol (PVA)/polyvinyl pyrrolidone as a stabilizer in the external aqueous phase. The use of smaller internal aqueous-phase volume (50 μL) and external aqueous-phase volume (25 mL) containing PVA in the manufacturing process resulted in maximum encapsulation efficiency (81.8%±0.9%). PVA-stabilized microspheres having maximum drug encapsulation released 2.5% insulin at pH 1.0 in 2 hours. In phosphate buffer (pH 7.4), microspheres showed an initial burst release of 22% in 1 hour with an additional 28% release in the next 5 hours. The smaller the volumes of internal and external aqueous phase, the lower the initial burst release. The release of drug from microspheres followed Higuchi kinetics. Scanning electron microscopy of PVA-stabilized microspheres demonstrated spherical particles with smooth surface, and laser diffractometry revealed a mena particle size of 32.51±20 μm. Oral administration of PVA stabilized microspheres in normal albino rabbits (equivalent to 6.6 IU insulin/kg of animal weight) demonstrated a 24% reduction in blood glucose level, with maximum plasma glucose reduction of 76±3.0% in 2 hours and effect continuing up to 6 hours. The area under the percentage glucose reduction-time curve was 93.75%. Thus, our results indicate that Eudragit S100 microspheres on oral administration can protect insulin from proteolytic degradation in the gastrointestinal tract and produce hypoglycemic effect.
Report on carcinogens monograph on 1-bromopropane.

The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in experimental animals to humans.
Does Scotland ‘like’ This? Social Media Use by Political Parties and Candidates in Scotland during the 2010 UK General Election Campaign

This paper reports the results of a study which investigated the use of social media by political parties and candidates in Scotland as part of their campaign for election to the UK Parliament in 2010. The study consisted of an analysis of the content of the social media sites belonging to parties and candidates standing in the 59 Scottish constituencies. During the fiveweek campaign period preceding the election date of 6 May 2010, the content of 81 Twitter accounts, 78 Facebook pages and 44 blogs was analysed in order to identify the ways in which political actors provided information to, and interacted with, potential voters. While parties and candidates appeared relatively keen to be seen embracing social media, they were used primarily for the one-way flow of information to the electorate. There was little direct, two-way engagement, and a general reluctance to respond to ˜difficult policy questions or critical comments posted by the public. The information provided also frequently lacked any meaningful policy comment. The followers, ˜friends and ˜likers of these sites seemed to be largely family, friends and associates of the candidates, or party members and activists. Thus, the political actors appeared to be simply ˜preaching to the converted rather than providing opportunities for objective debate with the wider electorate.