Miracle-dz/UniFAR-FTUs huggingface dataset:
Copper Control as an Antiangiogenic Anticancer Therapy: Lessons from Treating Wilson's Disease

The search for new anticopper drugs for Wilson's disease is culminating in two excellent new drugs: zinc for maintenance therapy and tetrathiomolybdate (TM) for initial therapy. Both are effective and nontoxic. TM is a very potent, fast-acting new anticopper drug and its properties may be useful well beyond Wilson's disease. Angiogenesis (new blood vessel growth) is required for tumor growth, and a sufficient level of copper appears to be required for angiogenesis. We hypothesize that there is a “window” to which the copper level can be reduced that inhibits angiogenesis in tumors, but does not interfere with vital cellular functions of copper. Using TM therapy, this approach has worked to slow or stabilize tumor growth in several animal tumor models, and preliminary results are also very encouraging in human patients with a variety of advanced and metastatic malignancies. A hypothesis is advanced that copper availability has played a fundamental role in growth regulation throughout evolution and that is the reason that so many angiogenic promoters appear to be dependent upon copper levels.
Surface plasmons modulate the spatial coherence of light in Young's interference experiment

A simplified analytic model is employed to demonstrate how surface plasmons propagating between the slits in Young's interference experiment can modulate the spatial coherence of the light field radiated by the two slits. The model is verified by comparison with results from rigorous numerical simulations. Our simulations reveal that the coherence can indeed be enhanced or suppressed, depending on the distance between the slits. Extending our analysis to a three-slit geometry, the effect on the degree of modulation when another slit is placed between the two slits is investigated. It is found that, compared to the two-slit case, the center slit serves not only as a barrier that can reduce the modulation, but can also act to enhance the amount of modulation. These results are promising for the development of novel "coherence converting" devices with suitable metallic arrays of subwavelength apertures.
Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study.

BACKGROUND Large international variations in rates of prostate cancer incidence and mortality suggest that environmental factors have a strong influence on the development of this disease. The purpose of this study was to identify predictive variables for prostate cancer mortality in data from 59 countries. METHODS Data on prostate cancer mortality, food consumption, tobacco use, socioeconomic factors, reproductive factors, and health indicators were obtained from United Nations sources. Linear regression models were fit to these data. The influence of each variable fit in the regression models was assessed by multiplying the regression coefficient b by the 75th (X75) and 25th (X25) percentile values of the variable. The difference, bX75 - bX25, is the estimated effect of the variable across its interquartile range on mortality rates measured as deaths per 100000 males aged 45-74 years. Reported P values are two-sided. RESULTS Prostate cancer mortality was inversely associated with estimated consumption of cereals (bX75 - bX25 = -7.31 deaths; P = .001), nuts and oilseeds (bX75 - bX25 = -1.72 deaths; P = .003), and fish (bX75 - bX25 = -1.47 deaths; P = .001). In the 42 countries for which we had appropriate data, soy products were found to be significantly protective (P = .0001), with an effect size per kilocalorie at least four times as large as that of any other dietary factor. Besides variables related to diet, we observed an association between prostate cancer mortality rates and a composite of other health-related, sanitation, and economic variables (P = .003). CONCLUSIONS The specific food-related results from this study are consistent with previous information and support the current dietary guidelines and hypothesis that grains, cereals, and nuts are protective against prostate cancer. The findings also provide a rationale for future study of soy products in prostate cancer prevention trials.
The structure and function of the helical heart and its buttress wrapping. III. The electric spiral of the heart: The hypothesis of the anisotropic conducting matrix.

The study of the dissemination of the electric impulse throughout the ventricular myocardium, which gave rise to the current theories, was performed without taking into consideration the complex architecture of the cardiac muscle elucidated by more recent researchers. We propose a novel hypothesis based on the special macroscopic structure of the heart, the anisotropic electric and mechanical behavior of the myocardium, the characteristics of the intercellular matrix and its very special collagen scaffolding, chemical composition, and biochemistry. The unique properties of the intercellular matrix would make it especially suited to function, in conjunction with the specialized conducting system (His-Purkinje system), as an efficient anisotropic conductor for the spread of electric activation in the heart, and to allow an optimal sequence of excitation-contraction coupling that results in the coordination of effective myocardial contraction in birds and mammals of the most varied known heart rates.
Expression of the UDP-glucuronosyltransferase 1A Locus in Human Colon

UDP-glucuronosyltransferases (UGT) catalyze the conjugation of lipophilic exobiotic and endobiotic compounds, which leads to the excretion of hydrophilic glucuronides via bile or urine. By a mechanism of exon sharing, the transcripts of individual first exon cassettes located at the 5′ end of the human UGT1Alocus are spliced to exons 2–5, leading to the expression of at least nine individual UGT genes. Recently, the tissue-specific expression of the UGT1A locus has been demonstrated in extrahepatic tissue, leading to the identification of UGT1A7 and UGT1A10 mRNA (Strassburg, C. P., Oldhafer, K., Manns, M. P., and Tukey, R. H. (1997) Mol. Pharmacol. 52, 212). However,UGT1A expression has not been defined in human colon, which is a metabolically active, external surface organ and a common route of drug administration. UGT1A expression was analyzed in 5 colonic, 16 hepatic, 4 biliary, and 13 gastric human tissue specimens by quantitative duplex reverse transcription-polymerase chain reaction and Western blot analysis, demonstrating lower UGT1A mRNA in the extrahepatic tissues. The precise analysis of unique UGT1A transcripts by exon 1-specific duplex reverse transcription-polymerase chain reaction revealed the expression of UGT1A1, UGT1A3, UGT1A4, UGT1A6, and UGT1A9 in the colon, which are also present in human liver. In addition, the expression of extrahepatic UGT1A10 and UGT1A8 was demonstrated. UGT1A8 was found to be closely related to gastric UGT1A7 with a 93.8% identity of first exon sequences. Expressed UGT1A7 and UGT1A10 protein showed unique catalytic activity profiles, while UGT1A8 was not active with the substrates tested. The ability of UGT1A10 to glucuronidate estrone represents only the second example of a human estrone UGT. The highly related human UGT1A7–1A10 cluster is expressed in a tissue-specific fashion and underlines the role and diversity of physiological glucuronidation at the distal end of the digestive tract.
Phosphorylation-dependent Cellular Localization and Thermoprotective Role of Heat Shock Protein 25 in Hippocampal Progenitor Cells*

The present study examined phosphorylation-dependent cellular localization and the thermoprotective role of heat shock protein (HSP) 25 in hippocampal HiB5 cells. HSP25 was induced and phosphorylated by heat shock (at 43 °C for 3 h). HSP25, which was located in the cytoplasm in the normal condition, translocated into the nucleus after the heat shock. Transfection experiments with hsp27 mutants in which specific serine phosphorylation residues (Ser78and Ser82) were substituted with alanines or aspartic acids showed that phosphorylation of HSP27 is accompanied by its nuclear translocation. Phosphorylation of mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK was markedly increased by the heat shock, and SB203580 (a p38 MAPK kinase inhibitor) and/or PD098059 (a MEK inhibitor) inhibited the phosphorylation of HSP25, indicating that p38 MAPK and ERK are upstream regulators of HSP25 phosphorylation in the heat shock condition. In the absence of heat shock, actin filament stability was not affected by SB203580 and/or PD098059. Heat shock caused disruption of the actin filament and cell death when phosphorylation of HSP25 was inhibited by SB203580 and/or PD098059. In addition, actin filament was more stable in Asp78,82-hsp27 (mimics the phosphorylated form) transfected HiB5 cells than in the normal and Ala78,82-hsp27 (nonphosphorylative form) transfected cells. In accordance with actin filament stability, the survival rate against the heat shock increased markedly in Asp15,78,82-hsp27 expressing HiB5 cells but decreased in Ala15,78,82-hsp27 expressing cells. These results support the idea that phosphorylation of HSP25 is critical for the maintenance of actin filament and enhancement of thermoresistance. Interestingly, HSP25 was dephosphorylated and returned to cytoplasm in a recovery time-dependent manner. This phenomenon was accompanied by an increment of apoptotic cell death as determined by nuclear and DNA fragmentation and fluorescence-activated cell sorter analysis. These results suggest that nuclear-translocated HSP25 might function to protect nuclear structure, thereby preventing apoptotic cell death.
Quantitation of intrinsic magnetic susceptibility‐related effects in a tissue matrix. Phantom study

A theoretical background and experimental method that allows a separation of intrinsic, tissue‐matrix‐specific magnetic‐field inhomogeneity effects from both macroscopic (large compared with voxel dimensions) and microscopic (on the order of molecular dimensions) inhomogeneities is proposed. Such separation allows one to take full advantage of these tissue‐matrix‐specific magnetic field inhomogeneity effects to extract information about tissue structure. A method to measure the volume fraction occupied by the susceptibility‐perturbing component in a tissue matrix, the R2′ relaxation rate constant, and the susceptibility difference between the bulk component and the susceptibility‐perturbing component in a tissue matrix has been developed and tested on phantoms. This method offers the potential to assess a variety of tissue parameters, including cerebral blood volume, blood volume and blood oxygenation‐level changes in functional MRI, the structure of trabecular bone, and other physiologically important issues.
p16INK4a Is a Useful Marker for the Diagnosis of Adenocarcinoma of the Cervix Uteri and Its Precursors: An Immunohistochemical Study With Immunocytochemical Correlations

p16INK4a is a tumor suppressor gene that plays a central role in the regulation of the cell cycle. In squamous cervical cancers, overexpression of p16INK4a is induced by HPV and associated with the carcinogenesis of cervical epithelia. The aim of this study was to determine whether immunostaining of p16INK4a is useful in detecting adenocarcinomas of the cervix uteri in histologic and cytologic routine specimens. A total of 45 surgical specimens, including 18 cases of invasive carcinoma, 8 cases of adenocarcinoma in situ, 4 cases of endocervical glandular atypia (cervical glandular intraepithelial neoplasia), and 15 reactive lesions of the endocervical glands were immunostained using a specific anti-human p16INK4a monoclonal antibody (clone E6H4, mtm laboratories AG, Heidelberg, Germany). Furthermore, immunocytochemical analysis was performed on 10 preoperative ThinPrep cytologic samples with abnormal glandular cells and compared with the human papillomavirus status as assessed with the Hybrid Capture II test. p16INK4a was detected immunohistochemically in all 26 cases of adenocarcinoma of the cervix uteri, including 18 invasive and 8 in situ carcinomas. Only a focal expression was evidenced in the four specimens with endocervical glandular atypia, and no reaction was found in reactive lesions. Also, the immunocytochemical analysis on the 10 ThinPrep specimens evidenced a strong expression of p16INK4a in neoplastic endocervical cells. In all cases this was associated with a high-risk HPV-positive typing. p16INK4a is a useful marker for the detection of the adenocarcinoma of the cervix uteri and its precursors. The immunocytochemical detection on ThinPrep specimens may contribute to an early detection of endocervical lesions.
Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors

p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. Protective p53-dependent cell-cycle checkpoints are activated in response to a wide variety of stresses, including not only DNA damage but also arrest of DNA synthesis and of mitosis. In addition to its role in activating the G1 and G2 checkpoints, p53 also helps to protect cells in S phase when they are starved for DNA precursors by treatment with the specific aspartate transcarbamylase inhibitor N-phosphonacetyl-l-aspartate (PALA), which blocks the synthesis of pyrimidine nucleotides. Even though p53 is activated, PALA-treated cells expressing low levels of p53 or lacking expression of p21 do not arrest in G1 or G2 but are blocked in S phase instead. In the complete absence of p53, PALA-treated cells continue to synthesize DNA slowly and eventually progress through S phase, suffering severe DNA damage that in turn triggers apoptosis. Expression of the secreted protein macrophage inhibitory cytokine 1 (MIC-1), a member of the TGF-β superfamily, increases substantially after PALA treatment, and application of exogenous MIC-1 or its constitutive expression from a cDNA provides remarkable protection of p53-null cells from PALA-mediated apoptosis, arguing that the p53-dependent secretion of MIC-1 provides a major part of such protection. Stimulation of MIC-1-dependent S phase arrest in normal gut epithelial cells might help to revitalize the clinical use of PALA, which has been limited by gut toxicity.
Intra- and inter-rater reliability of lower leg waterplethysmography, bioelectrical impedance and muscle twitch force for the use in standing work evaluation

Objectives. Prolonged standing is associated with multiple risk factors for musculoskeletal and venous disorders. In Germany over 50% of the working population spend most of their working time in a standing position. Basic understanding of prolonged standing physiology is lacking. We therefore plan to investigate the influence of 5 h standing (including breaks) on lower limb oedema measured by waterplethysmography (WP) and bioelectrical impedance (BI) and fatigue in the triceps surae muscle using muscle twitch force (MTF). In order to interpret our results, test-retest and inter-rater reliability of these measurement methods was evaluated first. Approach. 20 subjects (9 female) were included to test each method three times (M1, M2, M3) in 30 min periods with two raters (R1, R2) on separate days. Intraclass correlation coefficient (ICC; 2,1), standard error of measurement (SEM) and smallest real difference (SRD) were calculated for both raters. Main results. The SEM and SRD calculated for WP were 27 and 75 ml, respectively, for R1 and 23 and 64 ml, respectively, for R2 with an ICC of 0.98 (p < 0.0001). Statistically significant mean differences between M1 and M2 (R1 = 23 ml, p = 0.004; R2 = 19 ml, p = 0.027) but not significant mean differences between M2 and M3 (R1 = −6 ml, p = 0.45; R2 = 4 ml, p = 0.27) were calculated for both raters. BI data revealed SEM and SRD values of 3.8 and 10.5 Ω, respectively, for R1 and 3.4 and 9.4 Ω, respectively, for R2 with an ICC of 0.24 (p = 0.001). The differences between M1 and M2 (R1 = 3.9 Ω, p = 0.0001; R2 = 2.4 Ω, p = 0.049) and between M2 and M3 (R1 = 2.3 Ω, p = 0.012; R2 = 2.0 Ω, p = 0.008) were found to be statistically significant for both raters. SEM and SRD for MTF were 0.19 and 0.53 N, respectively, for R1 and 0.23 and 0.64 N, respectively, for R2 with an ICC of 0.71 (p < 0.0001). Mean differences between M1 and M2 were statistically significant for rater 1 but not for rater 2 (R1 = 0.13 N, p = 0.022; R2 = 0.12 N, p = 0.082) and the same was found for the difference between M2 and M3 for both raters (R1 = 0.04 N, p = 0.37; R2 = 0.08 N, p = 0.12). Significance. All three measurement methods showed good reliability and should be suitable for detecting effects of standing work on oedema development and fatigue as seen in previous results of long term standing experiments. Inter-rater reliability is found to be satisfactory as well, demonstrated by the small differences in SEM values of R1 and R2. Statistically significant differences shown for all three measurement methods could be due to lacking standardisation of leg placement and thus an actual lower leg volume change between measurements, indicating possibilities for further improvement of SEM values.
The Directionality and Age Selectivity of the Health-Migration Relation: Evidence from Sequences of Disability and Mobility in the United States

Evidence regarding the effects of health status on migration are mixed, with some concluding that there is a positive relation while others conclude a negative relation. This study examines the analytical bases for conflicting findings and proposes a model of the health-migration relation which allows for age selectivity, nonlinearities, interactions, and dynamic effects.
Nystagmus during Attacks of Vestibular Migraine: An Aid in Diagnosis

Introduction: An estimated one-fourth to one-third of patients with migraine will experience vertigo associated with their migraine attacks. Vestibular migraine frequently presents as a diagnostic challenge as objective neurological findings consistent with this entity have not been well described. Objective: The aim of this study is to characterize eye movements of patients presenting with nystagmus during attacks of migrainous vertigo. Design: A retrospective study of 26 patients presenting with nystagmus during an acute vestibular migraine was performed. All patients were examined while symptomatic during a migraine spell, and also while asymptomatic. All patients underwent tests of vestibular function with either bithermal water caloric or rotary chair electronystagmography. Results: The most common patient was a female of perimenopausal age. Spontaneous nystagmus was seen in 19% of patients and nystagmus provoked by horizontal headshaking was seen in 35%. Nystagmus could be provoked with positional testing in 100% of symptomatic patients with fixation blocked. The positional nystagmus most commonly was sustained, of low velocity, and could be horizontal, vertical or torsional. Bithermal water caloric or rotary chair tests obtained during symptom-free intervals were normal in all patients. Conclusions: Although nystagmus characteristics are quite variable during vestibular migraine, the finding on examination of low-velocity, sustained nystagmus with positional testing in a young to middle-aged adult patient presenting with vertigo, nausea and headache is highly suggestive of vestibular migraine as long as the nystagmus dissipates when the patient is free of symptoms.
Changing seasonality of panarctic tundra vegetation in relationship to climatic variables

Potential climate drivers of Arctic tundra vegetation productivity are investigated to understand recent greening and browning trends documented by maximum normalized difference vegetation index (NDVI) (MaxNDVI) and time-integrated NDVI (TI-NDVI) for 1982–2015. Over this period, summer sea ice has continued to decline while oceanic heat content has increased. The increases in summer warmth index (SWI) and NDVI have not been uniform over the satellite record. SWI increased from 1982 to the mid-1990s and remained relatively flat from 1998 onwards until a recent upturn. While MaxNDVI displays positive trends from 1982–2015, TI-NDVI increased from 1982 until 2001 and has declined since. The data for the first and second halves of the record were analyzed and compared spatially for changing trends with a focus on the growing season. Negative trends for MaxNDVI and TI-NDVI were more common during 1999–2015 compared to 1982–1998. Trend analysis within the growing season reveals that sea ice decline was larger in spring for the 1982–1998 period compared to 1999–2015, while fall sea ice decline was larger in the later period. Land surface temperature trends for the 1982–1998 growing season are positive and for 1999–2015 are positive in May–June but weakly negative in July–August. Spring biweekly NDVI trends are positive and significant for 1982–1998, consistent with increasing open water and increased available warmth in spring. MaxNDVI trends for 1999–2015 display significant negative trends in May and the first half of June. Numerous possible drivers of early growing season NDVI decline coincident with warming temperatures are discussed, including increased standing water, delayed spring snow-melt, winter thaw events, and early snow melt followed by freezing temperatures. Further research is needed to robustly identify drivers of the spring NDVI decline.
Design of a waveguide dual-mode three-way power divider for dual-polarization beam forming networks at Ka-band

This paper presents the design and performance of a dual-mode 3-way power divider optimized for dual-polarization operation at Ka-band. Similar performance are obtained for the TE10 and TE01 modes with a well-balanced power division over the three output ports and input matching better than -23 dB over the frequency range 27.5-30.0 GHz. In combination with dual-mode directional couplers, this three-way power divider is of great interest for the design of dual-polarization beam forming networks.
Spatial spread of adaptation within the cone network of turtle retina.

1. The spatial characteristics of adaptation were studied in the red‐sensitive cones of the snapping turtle retina using intracellular microelectrodes. Light responses elicited with slit‐shaped test and adapting stimuli revealed that test response amplitudes and adaptation decline similarly with distance from the impaled cone. The spatial spread of adaptation and the light response cannot be accounted for by scattered light and must therefore result from electrical coupling between cones. 2. The reduction in the amplitude of the test response correlated strongly with the magnitude of the sustained hyperpolarization induced by the adapting fields. This dependence of adaptation on membrane potential was independent of the spatial configuration of the adapting field. 3. The time courses of flash responses were monotonically related to the membrane potential induced by adapting stimuli and were also independent of adapting field configuration. 4. Adapting slits imaged on the cone receptive field centres uniformly depressed sensitivity without altering the shape of the field or its exponential fall‐off. Since the membrane potential evoked by the adapting slit falls off exponentially, the invariance of receptive field shape implies that the spread of adaptation cannot be attributed solely to voltage‐dependent desensitization of the transduction apparatus in the cones. Therefore a substantial part of the membrane potential dependency of adaptation probably results from a shunting of signals across the plasma membrane of the cone. 5. Full field backgrounds depressed sensitivity but did not alter the receptive field profiles. On the model of electrical coupling proposed by Lamb & Simon (1976), this suggests that to the extent that the voltage‐dependent desensitization results from an increased conductance and hence an increased shunt of the signals at the plasma membrane, there must be a concomitant increase in the conductance of the electrical pathways linking cones to one another.