Miracle-dz/UniFAR-FTUs huggingface dataset:
Flow cytometry study of the role of superoxide anion and hydrogen peroxide in cellular photodestruction with 5‐aminolevulinic acid‐induced protoporphyrin IX

Flow cytometry was used to investigate the participation of reactive oxygen species, other than singlet oxygen, in the cytotoxic effect of photodynamic therapy (PDT) with 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) in vitro in A‐431 squamous cell carcinoma (SCC) cells and human skin fibroblasts (HSF). We used propidium iodide to determine cellular cytotoxicity, hydroethidine to measure intracellular superoxide anion (O2−) and dihydrorhodamine 123 to assess intracellular hydrogen peroxide (H2O2) content. Our data support the importance of the incubation time with ALA in the selectivity of PDT with ALA against SCC cells, inducing minimum damage on normal HSF. Photoradiation mortality curves of the response of these cell lines to ALA‐induced PpIX photosensitization correlated with the extent of photosensitizer accumulation. Intracellular O2− production correlated with cell death, increasing both in a light dose‐dependent fashion in ALA treated cells. This correlation was not observed with H2O2‐intracellular production. These results suggest the effectiveness of PDT with ALA in vitro in SCC, the significant participation of O2− in its phototoxic mechanism, and the usefulness of flow cytometry in the study of the cytotoxic effect of ALA‐induced PpIX PDT.
Developing a broad categorisation scheme to describe risk factors for mental illness, for use in prevention policy and planning

Objectives: The prevention of mental illness involves identifying and modifying those characteristics and exposures of an individual that threaten their mental health – commonly referred to as risk factors. Existing categorisations of risk factors for mental illness are either limited in their scope or oversimplified in their description. As part of a large mental health workforce and service planning project, we set out to develop a more detailed and comprehensive categorisation scheme to describe risk factors for mental illness. Methods: We conducted a rapid review of MEDLINE and Google Scholar for meta-analytic studies that examined the characteristics and exposures that typify the population with mental illness in order to identify and categorise potential risk factors. Results: The search uncovered 1628 relevant studies, from which 10 primary and 23 secondary categories of risk factors were identified, ranging from genetic and biomedical to psychological and sociocultural. The review revealed interesting distortions in the focus of the literature, with the majority of studies focused on a few disorders (schizophrenia, depression and neurodegenerative disorders) and genetic, psychological and physiological risks. In contrast, environmental (e.g. media exposure) and occupational (e.g. employee health) were under-represented. Conclusion: The categorisation scheme developed in this paper is a step towards a more detailed taxonomy of risk factors for mental illness; this will be most useful in guiding clinicians, researchers and policy-makers in driving the prevention agenda forward.
Living matter—nexus of physics and biology in the 21st century

Cells are made up of complex assemblies of cytoskeletal proteins that facilitate force transmission from the molecular to cellular scale to regulate cell shape and force generation. The “living matter” formed by the cytoskeleton facilitates versatile and robust behaviors of cells, including their migration, adhesion, division, and morphology, that ultimately determine tissue architecture and mechanics. Elucidating the underlying physical principles of such living matter provides great opportunities in both biology and physics. For physicists, the cytoskeleton provides an exceptional toolbox to study materials far from equilibrium. For biologists, these studies will provide new understanding of how molecular-scale processes determine cell morphological changes.
Broad-Spectrum Biofilm Inhibition by Kingella kingae Exopolysaccharide

ABSTRACT Cell-free extracts prepared from Kingella kingae colony biofilms were found to inhibit biofilm formation by Aggregatibacter actinomycetemcomitans, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, and K. kingae. The extracts evidently inhibited biofilm formation by modifying the physicochemical properties of the cell surface, the biofilm matrix, and the substrate. Chemical and biochemical analyses indicated that the biofilm inhibition activity in the K. kingae extract was due to polysaccharide. Structural analyses showed that the extract contained two major polysaccharides. One was a linear polysaccharide with the structure →6)-α-d-GlcNAcp-(1→5)-β-d-OclAp-(2→, which was identical to a capsular polysaccharide produced by Actinobacillus pleuropneumoniae serotype 5. The second was a novel linear polysaccharide, designated PAM galactan, with the structure →3)-β-d-Galf-(1→6)-β-d-Galf-(1→. Purified PAM galactan exhibited broad-spectrum biofilm inhibition activity. A cluster of three K. kingae genes encoding UDP-galactopyranose mutase (ugm) and two putative galactofuranosyl transferases was sufficient for the synthesis of PAM galactan in Escherichia coli. PAM galactan is one of a growing number of bacterial polysaccharides that exhibit antibiofilm activity. The biological roles and potential technological applications of these molecules remain unknown.
Tumour secreted grp170 chaperones full-length protein substrates and induces an adaptive anti-tumour immune response in vivo

Purpose: We employed a grp170-secreting tumour cell system to determine whether tumour cells engineered to secrete grp170 generate an antitumour-specific immune response. Further, we examine the possibility that secreted grp170 can bind to and co-transport out of tumour cells full-length tumour antigens that may play a role in the anti-tumour immune response. Materials and methods: Wild type Colon-26 and Colon-26 engineered to secrete grp170 were subcutaneously inoculated into BALB/c mice. Tumour growth was monitored, and variations in immunoregulatory mechanisms were evaluated using immunohistochemistry, lymphocyte depletion, ELISpot assays, and Western blot analysis. Results: Immunisation of animals with grp170-secreting tumour cells results in rejection of the tumour by induction of antigen-specific, CD8-dependent immune responses. The secreted grp170 is able to deliver full-length tumour antigens to the tumour microenvironment, thus making them available for uptake by antigen presenting cells (APCs) to initiate tumour-specific immune responses. Conclusions: These data parallel our studies showing that hsp110 or grp170 are able to chaperone full-length proteins, and when complexed with protein antigens and used as vaccines, these complexes elicit immune responses in vivo against the protein antigens. This cell-based approach has the potential to be utilised as a tumour-specific vaccine in tumours of various histological origins.
Refinement of a brief anxiety sensitivity reduction intervention.

OBJECTIVE Anxiety disorders are the most prevalent psychiatric disorders in the United States and result in substantial burden to the individual and society. Although effective treatments for anxiety disorders have been developed, there has been substantially less focus on interventions aimed at the amelioration of anxiety-related risk and maintenance factors. Anxiety sensitivity (AS) is a well-established, malleable risk and maintenance factor for panic disorder and other psychopathology. The aim of the current investigation was to enhance the efficacy of AS treatment through the refinement of a previously validated intervention. METHOD This 1-session intervention utilized psychoeducation and interoceptive exposure to target AS and was compared with a health-focused control intervention among a nontreatment seeking sample (N = 104) of individuals with elevated AS. RESULTS Study findings indicate that the active treatment group demonstrated significantly greater reductions in AS than the control group at posttreatment and across the 1-month study period. These treatment gains were seen across the ASI subscales. A Month 6 follow-up assessment indicated that the treatment group retained the majority of their AS reduction, whereas the control group retained their elevated AS scores. The intervention responses of participants meeting Axis I diagnostic criteria did not differ from the responses of those without a current diagnosis. CONCLUSIONS Despite the brevity of the treatment intervention, findings demonstrate that it resulted in substantial reductions in AS that were largely maintained 6 months posttreatment. Anxiety treatment and prevention implications are discussed.
Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL.

To the editor: Reinduction therapy (also known as delayed intensification, DI) is an essential part of childhood acute lymphoblastic leukemia (ALL) treatment. [1][1],[2][2] In Berlin-Frankfurt-Munster (BFM) studies, it includes same/similar drugs as those employed in induction therapy. The Children
Ownership and the Price of Residential Electricity: Evidence from the United States, 1935-1940

In this paper, we quantify the difference between public and private prices of residential electricity immediately before and after major federal reforms in the 1930s and 1940s. Previous research found that public prices were lower in a sample of large, urban markets. Based on new data covering over 15,000 markets and nearly all electricity generated for residential consumption, we find the difference between public and private prices was small in 1935 and negligible in 1940 for typical levels of monthly consumption. These findings are consistent with a market for ownership that helped to discipline electricity prices during this period. That is, private rents were mitigated by the threat that municipalities would use public ownership to respond to constituent complaints and public rents were limited by electoral competition and the growth of private provision.
A comparison of the Assessment of Quality of Life (AQoL) with four other generic utility instruments

As part of the validation of the Assessment of Quality of Life (AQoL) instrument comparisons were made between five multiattribute utility (MAU) instruments, each purporting to measure health-related quality of life (HRQoL). These were the AQoL, the Canadian Health Utilities Index (HUI) 3, the Finnish 15D, the EQ-5D (formerly the EuroQoL) and the SF6D (derived from the SF-36). The paper compares absolute utility scores, instrument sensitivity, and incremental differences in measured utility between different instruments predicted by different individuals. The AQoL predicted utilities are similar to those from the HUI3 and EQ-5D. By contrast the 15D and SF6D predict systematically higher utilities, and the differences between individuals are significantly smaller. There is some evidence that the AQoL has greater sensitivity to health states than other instruments. It is concluded that at present no single MAU instrument can claim to be the ‘gold standard’, and that researchers should select an instrument sensitive to the health states they are investigating. Caution should be exercised in treating any of the instrument scores as representing a trade-off between length of life and HRQoL.
Role of TET enzymes in DNA methylation, development, and cancer

Ten eleven translocation (TET) genes, and especially TET2, are frequently mutated in various cancers, but how the TET proteins contribute to the onset and maintenance of these malignancies is largely unknown. In this review, Rasmussen and Helin highlight recent advances in understanding the physiological function of the TET proteins and their role in regulating DNA methylation and transcription.
Serum Lipoprotein and Apolipoprotein Changes During Treatment with a Contraceptive Vaginal Ring Containing Levonorgestrel and Estradiol

Abstract. Contraceptive vaginal rings containing estradiol and levonorgestrel were used by 22 women during 219 cycles. The estrogenicity was low and the daily dose of levonorgestrel was about 290 μg. The triglyceride and cholesterol concentrations decreased in whole serum and, to varying degrees, in the different lipoprotein classes. The most consistent change was a 25% (p <0.001) reduction in the cholesterol content of the high‐density lipoprotein (HDL) fraction. The cholesterol concentration in low‐density lipoprotein decreased by 11% after the first 3 months, but increased during the ensuing 9 months of treatment to regain pretreat‐ment level. Percentagewise, the apolipoprotein B and A‐I concentrations, determined by rocket immunoelectro‐phoresis, were less affected than the LDL‐ and HDL‐cholesterol concentrations. The composition of the LDL and HDL particles seemed thus to alter during the treatment. The pronounced effect on the HDL levels seen is consistent with earlier findings of a dose‐dependent, androgenic effect of gestagens derived from 19‐nortestosterone. However, the low basal level of LDL and its further decrement during treatment alleviate the supposedly unfavorable effect of HDL reduction from the atherogenic point of view.
Modeling and simulation of photovoltaic system with soft switching SEPIC converter

Solar energy is the most promising source of renewable energy. Intensive research is carried out in all the areas associated with solar energy. In this paper a soft switching SEPIC converter is proposed for the inverter section of the PV system, this is aimed at reducing the switching losses in the converter section and hence the efficiency of the system increases. SEPIC converters used by the researchers have noninverted output but medium efficiency. A Soft Switching SEPIC converter has a non inverted output and a efficiency of about 94%. The converter uses two switches, and ZVS of both the switches are achieved by using a coupled inductor and a auxiliary inductor, and ZCS of the output diode is achieved by resonance in the voltage multiplier circuit. An Incremental conductance MPPT algorithm is used to control the converter. Simulation study has been done in MATLAB V3.2. Analysis proves that Soft Switching SEPIC converter has an efficiency of a 94%, an increase of 40% has been found out with respect to existing system. This increase is likely to contribute to overall system efficiency.
A Unity-Power-Factor IPT Pickup for High-Power Applications

This paper describes the design of a new unity-power-factor inductive-power-transfer (IPT) pickup using an LCL tuned network for application in high-power systems. This new topology has the potential to increase the efficiency and reduce the cost of high-power pickups by minimizing the reactive currents in the pickup coil and the reflected VAR loading on the power supply. In a practical system, the rectifier and associated processing circuitry distorts the current waveforms, adding an effective inductive loading to the pickup circuit. A series compensation capacitor is added to correct this loading. A design strategy is developed for the new topology, and two example circuits are constructed and compared experimentally with a traditional parallel-tuned (LC) pickup operating on a monorail-based IPT system.
Dynamics of accommodative facility in myopes.

PURPOSE To evaluate the dynamic changes in refraction during the accommodative facility test in myopes and emmetropes. METHODS Ten myopes and 10 emmetropes participated in the study. All were young adults, and refractive error in the myopes was corrected with soft contact lenses. Monocular accommodative facility measurements were taken for a 40-cm and a 6-m working distance with +2.00/-2.00-D and Plano/-2.00-D flippers, respectively. Subjective facility was recorded with automated flippers and objective measurements of dynamic accommodation response were simultaneously taken with a photorefractor. RESULTS Subjective and objective facility measurements showed a significantly lower facility rate in myopes when compared with emmetropes at distance (P < 0.05) but not at near (P > 0.05). The response amplitude of accommodation during facility tasks was found to be similar in the two refractive groups. However, the velocity of accommodation was found to be lower in myopes than in emmetropes for distance facility (P < 0.05) but not for near facility (P > 0.05). Velocity of disaccommodation was lower in myopes than in emmetropes at both distance and near (P < 0.05). CONCLUSIONS During distance accommodative facility testing, myopes exhibited a lower velocity of accommodation and disaccommodation, which led to a lower distance accommodative facility rate. For near facility measurements, however, although velocity of disaccommodation was lower in myopes, velocity of accommodation was found to be similar in the two refractive groups. A variety of factors that contribute to these differences are discussed.
Semen parameters in fertile US men: the Study for Future Families

Establishing reference norms for semen parameters in fertile men is important for accurate assessment, counselling and treatment of men with male factor infertility. Identifying temporal or geographic variability in semen quality also requires accurate measurement of semen parameters in well‐characterized, defined populations of men. The Study for Future Families (SFF) recruited men who were partners of pregnant women attending prenatal clinics in Los Angeles CA, Minneapolis MN, Columbia MO, New York City NY and Iowa City IA. Semen samples were collected on site from 763 men (73% White, 15% Hispanic/Latino, 7% Black and 5% Asian or other ethnic group) using strict quality control and well‐defined protocols. Semen volume (by weight), sperm concentration (hemacytometer) and sperm motility were measured at each centre. Sperm morphology (both WHO, 1999 strict and WHO, 1987) was determined at a central laboratory. Mean abstinence was 3.2 days. Mean (median; 5th–95th percentile) values were: semen volume, 3.9 (3.7; 1.5–6.8) mL; sperm concentration, 60 (67; 12–192) × 106/mL; total sperm count 209 (240; 32–763) × 106; % motile, 51 (52; 28–67) %; and total motile sperm count, 104 (128; 14–395) × 106 respectively. Values for sperm morphology were 11 (10; 3–20) % and 57 (59; 38–72) % normal forms for WHO (1999) (strict) and WHO (1987) criteria respectively. Black men had significantly lower semen volume, sperm concentration and total motile sperm counts than White and Hispanic/Latino men. Semen parameters were marginally higher in men who achieved pregnancy more quickly but differences were small and not statistically significant. The SFF provides robust estimates of semen parameters in fertile men living in five different geographic locations in the US. Fertile men display wide variation in all of the semen parameters traditionally used to assess fertility potential.
Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post- heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day- 14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN- gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man.
Atypical Wernicke’s Encephalopathy with Remarkable Cerebellar Lesions on Diffusion-Weighted MRI

sphere and posterior vermis, simulating acute bilateral cerebellar infarctions ( fig. 1 A). An initial diagnosis was made based on a history of chronic alcohol abuse, with typical symptoms that included altered mental state and ophthalmoplegia, and combined lesions on bilateral thalamus and periaqueductal gray matter on DWI ( fig. 1 B). Immediate administration of 300 mg thiamine commenced. On the second hospital day, he became drowsy and did respond to simple commands. Mild horizontal gaze palsy, gaze-evoked nystagmus, and limb dysmetria were evident. A follow-up DWI performed 8 days after onset showed that the previously high signal intensities in the cerebellum ( fig. 1 A), medial thalamus, and periaqueductal gray matter ( fig. 1 B) had mostly resolved. Follow-up T 2 -weighted images showed no high signal intensity, but severe atrophy of the cerebellar vermis and anterior hemisphere were evident ( fig. 1 A). MR angiography showed no definite stenosis or occlusion in the vertebrobasilar circulation. Over several days of hospitalization, he regained alertness, but showed considerable memory impairment and gait ataxia.
Loss of the Homotypic Fusion and Vacuole Protein Sorting or Golgi-Associated Retrograde Protein Vesicle Tethering Complexes Results in Gentamicin Sensitivity in the Yeast Saccharomyces cerevisiae

ABSTRACT Gentamicin continues to be a primary antibiotic against gram-negative infections. Unfortunately, associated nephro- and ototoxicity limit its use. Our previous mammalian studies showed that gentamicin is trafficked to the endoplasmic reticulum in a retrograde manner and subsequently released into the cytosol. To better dissect the mechanism through which gentamicin induces toxicity, we have chosen to study its toxicity using the simple eukaryote Saccharomyces cerevisiae. A recent screen of the yeast deletion library identified multiple gentamicin-sensitive strains, many of which participate in intracellular trafficking. Our approach was to evaluate gentamicin sensitivity under logarithmic growth conditions. By quantifying growth inhibition in the presence of gentamicin, we determined that several of the sensitive strains were part of the Golgi-associated retrograde protein (GARP) and homotypic fusion and vacuole protein sorting (HOPS) complexes. Further evaluation of their other components showed that the deletion of any GARP member resulted in gentamicin-hypersensitive strains, while the deletion of other HOPS members resulted in less gentamicin sensitivity. Other genes whose deletion resulted in gentamicin hypersensitivity included ZUO1, SAC1, and NHX1. Finally, we utilized a Texas Red gentamicin conjugate to characterize gentamicin uptake and localization in both gentamicin-sensitive and -insensitive strains. These studies were consistent with our mammalian studies, suggesting that gentamicin toxicity in yeast results from alterations to intracellular trafficking pathways. The identification of genes whose absence results in gentamicin toxicity will help target specific pathways and mechanisms that contribute to gentamicin toxicity.