Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitoxantrone in combination with an inhibitor of DNA‐dependent protein kinase: a potential therapy for high risk B‐cell chronic lymphocytic leukaemia

Defects in the DNA damage response pathway [e.g. del(17p)] are associated with drug‐resistant B‐cell chronic lymphocytic leukaemia (CLL). We previously demonstrated that over‐expression of DNA‐dependent protein kinase (DNA‐PK) correlates with chemo‐resistance and that inhibition of DNA‐PK sensitizes CLL cells to chemotherapeutics. Here, we investigated expression of DNA‐PK and other proteins that impact on drug resistance, and evaluated the effects of a DNA‐PK inhibitor (NU7441) on mitoxantrone‐induced cytotoxicity in CLL cells. NU7441 sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization ranging from 2‐ to 200‐fold Co‐culture of CLL cells in conditioned stromal medium increased chemoresistance but did not reduce sensitization by NU7441. Mitoxantrone treatment induced γH2AX foci and NU7441 increased their longevity (24 h). NU7441 prevented mitoxantrone‐induced autophosphorylation of the DNA‐PK catalytic subunit (DNA‐PKcs) at Ser 2056, confirming that DNA‐PK participates in repair of mitoxantrone‐induced DNA damage. del(17p) cases were more resistant to mitoxantrone than del(13q) cases, but were resensitized (7–16 fold) by co‐incubation with NU7441. Expression of DNA‐PKcs, Ku80, P‐glycoprotein and topoisomerase IIβ were significantly higher in del(17p) cases. PRKDC mRNA levels correlated with DNA‐PKcs protein expression, which predicted shorter survival. These data confirm the potential of DNA‐PK as a therapeutic target in poor prognosis CLL.
Antibiotic‐induced SOS response promotes horizontal dissemination of pathogenicity island‐encoded virulence factors in staphylococci

Although mobile genetic elements have a crucial role in spreading pathogenicity‐determining genes among bacterial populations, environmental and genetic factors involved in the horizontal transfer of these genes are largely unknown. Here we show that SaPIbov1, a Staphylococcus aureus pathogenicity island that belongs to the growing family of these elements that are found in many strains, is induced to excise and replicate after SOS induction of at least three different temperate phages, 80α, φ11 and φ147, and is then packaged into phage‐like particles and transferred at high frequency. SOS induction by commonly used fluoroquinolone antibiotics, such as ciprofloxacin, also results in replication and high‐frequency transfer of this element, as well as of SaPI1, the prototypical island of S. aureus, suggesting that such antibiotics may have the unintended consequence of promoting the spread of bacterial virulence factors. Although the strains containing these prophages do not normally contain SaPIs, we have found that RF122‐1, the original SaPIbov1‐containing clinical isolate, contains a putative second pathogenicity island that is replicated after SOS induction, by antibiotic treatment, of the prophage(s) present in the strain. Although SaPIbov1 is not induced to replicate after SOS induction in this strain, it is transferred by the antibiotic‐activated phages. We conclude that SOS induction by therapeutic agents can promote the spread of staphylococcal virulence genes.
On the Tractable Counting of Theory Models and its Application to Truth Maintenance and Belief Revision

We address in this paper the problem of counting the models of a propositional theory under incremental changes to its literals. Specifcally, we show that if a propositional theory Δ is in a special form that we call smooth, deterministic, decomposable negation normal form (sd-DNNF), then for any consistent set of literals S, we can simultaneously count (in time linear in the size of Δ) the models of Δ ∪ S and the models of every theory Δ ∪ T where T results from adding, removing or flipping a literal in S. We present two results relating to the time and space complexity of compiling propositional theories into sd-DNNF. First, we show that if a conjunctive normal form (CNF) has a bounded treewidth, then it can be compiled into an sd-DNNF in time and space which are linear in its size. Second, we show that sd-DNNF is a strictly more space efficient representation than Free Binary Decision Diagrams (FBDDs). Finally, we discuss some applications of the counting results to truth maintenance systems, belief revision, and model-based diagnosis.
An Adjustable Gain-Clamped Semiconductor Optical Amplifier (AGC-SOA)

The operation of a semiconductor optical amplifier (SOA)-ring laser-based subsystem, with the capability to provide adjustable gain-clamped operation, will be described, and preliminary characterization results will be presented. The device uses two SOAs in a ring-cavity topology: one to amplify the signal and the other to control the gain. This type of subsystem finds applications in packet-based dynamic systems where it may be used for power equalization and linear amplification.
Ecology and Catastrophic Mortality in Wild Horses: Implications for Interpreting Fossil Assemblages

The identities, sexes, and reproductive status of groups of wild horses (Equus caballus) living in the Great Basin Desert of North America were known prior to their deaths on ridgelines. Another group of very young horses died on a quagmire. Snow accumulation or drought was apparently responsible for the mass deaths. These data have implications for reconstructing some aspects of the social structure of fossil mammals on the basis of skewed sex or age ratios in bone assemblages.
Quantitative Evaluation of Changes in the Clock-Watching Behavior of a Patient With Semantic Dementia

Background: Clock-watching activity in patients with dementia has not been documented in detail. Methods: A male patient having semantic dementia was monitored at a dementia care unit in a general hospital in Japan. We used an integrated circuit monitoring system to record the distance and location of ambulation and the total number of movements that occurred outside the patient’s room. Results: The patient was reported to clock watch a couple of years prior to monitoring. In 2011, when monitoring started, he regularly came out of his room saying, “8 o’clock” about 40 minutes into every hour. It seemed as if he could only recognize the minute hand. The median number of sensor detections increased by 4-fold at this clock-watching phase. Behavior consistent with his clock-watching patterns was also detected during the night. In 2012, clock-watching activity disappeared. Conclusions: This study documented the progression of clock-watching and subsequent disappearance with worsening cognitive function.
Raman spectroscopy of graphite

We present a review of the Raman spectra of graphite from an experimental and theoretical point of view. The disorder–induced Raman bands in this material have been a puzzling Raman problem for almost 30 years. Double–resonant Raman scattering explains their origin as well as the excitation–energy dependence, the overtone spectrum and the difference between Stokes and anti–Stokes scattering. We develop the symmetry–imposed selection rules for double–resonant Raman scattering in graphite and point out misassignments in previously published works. An excellent agreement is found between the graphite phonon dispersion from double–resonant Raman scattering and other experimental methods.
Expression of Hyaluronan Synthases and CD44 Messenger RNAs in Porcine Cumulus-Oocyte Complexes During In Vitro Maturation1

Abstract The transient synthesis and accumulation of hyaluronan (HA), an extracellular matrix component of cumulus cells, brings about expansion of cumulus-oocyte complexes (COCs) in preovulatory mammalian follicles. In this study, we investigated the mRNA expressions of hyaluronan synthase 2 (has2), hyaluronan synthase 3 (has3), and CD44, as well as the responsiveness to eCG and porcine follicular fluid (pFF) of these genes, in porcine COCs, oocytectomized complexes (OXCs), and oocytes during in vitro maturation. Immunolocalization of CD44 was also analyzed in COCs. After 12 h of culture, the area of cumulus expansion in medium 199 supplemented with both 10 IU/ml eCG and 10% (v/v) pFF was significantly greater than that in the medium supplemented with eCG or pFF. Oocytectomy reduced the expansion area in the group supplemented with eCG. In reverse transcription-polymerase chain reaction analysis, all transcripts were identified in COCs, but has3 transcript was not found in OXCs. Only has3 mRNA was detectable in oocytes, indicating that cumulus cells express has2 and CD44 mRNAs, and oocytes express has3 mRNA. The expression levels of has2 and CD44 mRNAs in COCs and OXCs increased in the presence of eCG and pFF after 24 h of culture, suggesting that these genes have a positive dependency on eCG and pFF. In contrast, the high level of has3 mRNA was detected in COCs cultured in the medium alone. Oocytectomy slightly reduced the expression level of has2 mRNA. On immunostaining for CD44, CD44 was expressed apparently in COCs cultured with eCG and pFF for 24 h. The positive staining was distributed on cytoplasm along the perimembrane of cumulus cells and at the junctions between cumulus cells and oocytes. CD44 was also localized on cytoplasm of some oocytes. These results indicate that 1) porcine oocytes promote eCG-dependent cumulus expansion and the expression of has2 mRNA in cumulus cells, but these are not essential for expansion of cumulus cells and the expression of has2 mRNA; 2) HAS2 is involved in HA synthesis during cumulus expansion, and eCG and pFF up-regulate its expression; 3) the expression profile of the has3 mRNA that is transcribed in oocytes is different from those of has2 and CD44 mRNA; and 4) CD44 may participate in the interaction between cumulus cells and oocytes.
Pyrrolizidine alkaloid variation in Jacobaea hybrids : influence on resistance against generalist and specialist insect herbivores

Plants produce a vast array of secondary metabolites (SMs). Some hypotheses were put forward to explain the diversity of structurally related SMs within the framework of plant defense against herbivores:1) SMs could be Selectively Neutral; 2) SM diversity is a result of the “Arms Race” between plants and the herbivores; 3) Plants benefit from the SM diversity because of the Synergistic Effects among the SMs; 4) The SM diversity may be a response to the Selection from Multiple Herbivores. In this thesis, a hybrid family originated from an artificial cross between Jacobaea aquatica and Jacobaea vulgaris was used as a model system to study the selective forces from insect herbivores on pyrrolizidine alkaloids (PAs) evolution. The Jacobaea hybrid family showed great variation in PA variation and herbivore resistance. By means of three bioassays, one with a specialist (Tyria jacobaea) and two with generalist insect herbivores (Frankliniella occidentalis and Liriomyza trifolii), I could show that Jacobaea hybrid genotypes differed in the resistance to these herbivores and these differences were related to PA variation in the plants. Several PAs were involved in the resistance to insect herbivores. These results support the three hypotheses except Selectively Neutral Theory.
Bile Salt‐ and Lysophosphatidylcholine‐induced Membrane Damage in Human Erythrocytes

Abstract— The interaction of bile salts and lysophosphatidylcholine (LPC) with membranes has implications both in understanding the aetiology of a number of gastrointestinal disorders, including gastritis, gastric ulcers and colonic cancer, and in enhancing drug absorption by various epithelia. The membrane toxicity of nine bile salts (the sodium (S) salts of chenodeoxycholate (CDC), deoxycholate (DC) and cholate (C) and their glycine (G) and taurine (T) conjugates) and LPC was determined using erythrocyte haemolysis as a model parameter. Washed human erythrocytes were incubated for 15–60 min at 20°C with media buffered at pH 8, 7 and 6. Bile salt toxicity was shown to be a function of type, concentration, pH and contact time with the membrane. At pH 7 toxicity decreased in the order LPC > unconjugated dihydroxy salts (SDC and SCDC) > conjugated deoxycholates (SGDC and STDC) > conjugated chenodeoxycholates (SGCDC and STCDC) > unconjugated trihydroxy salt (SC) > conjugated trihydroxy salts (SGC and STC). Incubation with equimolar combinations of bile salts (SDC + SCDC; STCDC + SGDC; SDC + STDC) indicated that the resultant damage was an additive function of the damage induced by the individual bile salts.
Measurement of Harmonics in Power Systems Using Near Perfect Reconstruction Filter Banks

In this letter, the use of near perfect reconstruction filter banks on the harmonic analysis of power system waveforms is investigated. For this aim, wavelet packet transform for the rms measurement is implemented. Besides commonly used wavelet filters, the influence of several of Johnston's filters is examined. Experimental tests are performed under different conditions in case of stationary and nonstationary signals. The obtained results show that Johnston filters outperform the commonly used wavelet filters for harmonic analysis.
Transients in intracellular free calcium in subconfluent and confluent cultures of a rat smooth muscle cell line

The Ca2+ mobilizing mechanisms in the smooth muscle cell line A7r5 were found to undergo changes related to the degree of confluence of the cultures. In sparse cultures resting calcium was stable and exposure to arginine vasopressin (AVP) resulted in a single transient increase in intracellular free calcium (Ca2+i). In confluent cultures the cells could be divided into two general groups, those with a stable resting Ca2+i and those which demonstrated spontaneous brief elevations in Ca2+i of variable frequency. Application of AVP elevated Ca2+i, induced oscillations in quiescent confluent cells, increased the frequency of oscillatory activity in cells which were already active and, in cells which exhibited high frequency spontaneous fluctuations, inhibited this activity. Isotonic K+ depolarizing solution and normal solutions containing Co2+ inhibited Ca2+ spikes. These data suggest that the mechanism underlying the transients involves cyclical electrical phenomena at the cell membrane possibly utilizing calcium channels. There is no indication that the mechanism involves cytoplasmic oscillators.
Intramitochondrial free calcium in cardiac myocytes in relation to dehydrogenase activation.

OBJECTIVE The aim was to quantitate intramitochondrial free Ca2+ ([Ca2+]m) in cardiac myocytes under conditions of stimulation previously shown to cause activation of pyruvate dehydrogenase. METHODS [Ca2+]m was monitored in single, isolated rat cardiac myocytes using fluorescence microscopy following the loading of the cells with the fluorescent chelating agent indo-1, in its permeant acetoxymethylester form, and the selective quenching of cytosolic fluorescence with MnCl2. The extent of contraction upon electrical stimulation was also measured. RESULTS Electrical stimulation at 2 Hz and higher frequency raised [Ca2+]m significantly, and this was potentiated by exposure to isoprenaline. However, isoprenaline had no effect in quiescent cells, in which [Ca2+]m was raised above resting values by partial replacement of Na+ in the medium. The mitochondrial uncoupling agent carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) raised [Ca2+]m in unstimulated cells, but lowered it in cells subjected to electrical stimulation at 2 Hz or more, to partial Na+ replacement, or to the alkaloid veratridine. CONCLUSIONS The values of [Ca2+]m in quiescent myocytes (approximately 100 nmol.litre-1) would be associated with very little activation by Ca2+ of pyruvate dehydrogenase phosphatase, based on determination of K0.5 value of 650 nmol.litre-1 in work with mitochondrial suspensions. By contrast, the values of [Ca2+]m associated with electrical stimulation at 2 Hz or greater in the presence of beta adrenergic activation (> 500 nmol.litre-1) would be associated with significant dehydrogenase activation. The effect of beta adrenergic activation is only seen in the presence of electrical stimulation and probably involves enhancement of systolic transients in cytosol [Ca2+]. Effects of uncoupling agents validate the conclusions on the direction and magnitude of the mitochondrial Ca2+ gradient in situ in living myocytes.
Inequality in maternal health-care services and safe delivery in eastern India

Background: The target for Millennium Development Goal 5 (MDG-5) is to reduce the maternal mortality ratio by three quarters between 1990 and 2015. The United Nations 2014 report on MDG-5 concluded that little progress had been made in the South Asian countries, including India, which accounts for 17% of all maternal deaths globally. In resource-poor economies with widespread disparities even within the same country, it is very important to explore inequalities in safe delivery during childbirth by key socioeconomic factors in order to provide insights for future programming and policy actions. Methods: Data from the Indian District Level Household and Facility Survey 3 were analysed to examine inequalities in safe delivery in eastern India. Univariate and multivariate logistic regression models were used. Results: There were substantial inequalities in safe delivery by asset quintile, education of the woman and her husband, area of residence (rural or urban), religion and age at marriage (<18 years or ≥18 years); however, not all inequalities were the same. After adjusting for education levels of both parents, area of residence, religion and mother’s age at marriage, the odds of having a safe delivery were almost eightfold higher for those in the highest asset quintiles compared with those in the lowest quintiles. The odds for a safe pregnancy were three times higher for educated women compared with a base case of no education. The chances of having a safe delivery were twofold higher for women living in urban areas compared with those in rural areas (odds ratio 2.04, 95% confidence interval 1.91-2.17). Conclusion: Addressing inequalities in maternal health should be viewed as a central policy goal together with the achievement of MDG-5 targets. In addition to following the indirect route of improving maternal health via poverty alleviation, direct interventions are needed urgently. Women’s education has a strong potential to improve access for poor pregnant women to safe delivery services and to reduce disparities in maternal health outcomes in resource-poor economies.
Aberrant expression of p53 tumour‐suppressor protein in non‐melanoma skin cancer

Expression of the cellular p53 tumour‐suppressor protein was examined in 78 epidermal tumours, including basal and squamous cell carcinomas, keratoacanthomas, solar keratoses, Bowen's disease and viral warts. An immunohistochemical study was employed using the antibody CM‐1, raised against recombinant human p55 protein. Positive staining for p53, not detectable in normal cells because wild‐type p53 is rapidly degraded, reflects abnormal stabilization of p53 protein, and in many cases suggests p53 gene mutation.
Cellular Retinoic Acid‐Binding Protein 1 Modulates Stem Cell Proliferation to Affect Learning and Memory in Male Mice

&NA; Retinoic acid (RA) is the active ingredient of vitamin A. It exerts its canonical activity by binding to nuclear RA receptors (RARs) to regulate gene expression. Increasingly, RA is also known to elicit nongenomic RAR‐independent activities, most widely detected in activating extracellular regulated kinase (ERK)1/2. This study validated the functional role of cellular retinoic acid‐binding protein 1 (Crabp1) in mediating nongenomic activity in RA, specifically activating ERK1/2 to rapidly augment the cell cycle by expanding the growth 1 phase and slowing down embryonic stem cell and neural stem cell (NSC) proliferation. The study further uncovered the physiological activity of Crabp1 in modulating NSC proliferation and animal behavior. In the Crabp1 knockout mouse hippocampus, where Crabp1 is otherwise detected in the subgranular zone, neurogenesis and NSC proliferation increased and hippocampus‐dependent brain functions such as learning and memory correspondingly improved. This study established the physiological role of Crabp1 in modulating stem cell proliferation and hippocampus‐dependent brain activities such as learning and memory.
Peripheral vascular and sweat-gland reflexes in diabetic neuropathy.

1. In two groups of diabetic patients, one with and one without signs of peripheral neuropathy, reflex short vasoconstrictor responses to such stimuli as a cough, a sharp inspiration or sudden noise were recorded from a finger and both big toes by volume plethysmography. Simultaneous electrodermal responses to the same stimuli were recorded from a hand and a foot. Vasodilator responses to body warming were also recorded. 2. Significant impairment of these vasomotor reflexes in diabetic patients with neuropathy indicates that the sympathetic vasomotor system can be involved in diabetic peripheral neuropathy. 3. Loss of the reflex electrodermal responses is also evidence of impairment of another sympathetic function in such patients. 4. Because stimuli vary in their effectiveness in causing responses in both groups of subjects, it is suggested that changes of central nervous conductivity also occur in diabetes.
Recognition memory for 2,578 monosyllabic words

In two studies, participants studied 30 lists of 50 words and were tested on 30 lists of 100 words. Item-level multiple regression analyses were conducted on hits, false alarms, hits minus false alarms, d′, and C. The predictor variables were objective frequency, subjective frequency, imageability, orthographic similarity, phonological similarity, phonological-to-orthographic N (PON), age of acquisition (AoA), and word length. The regression equations accounted for 45.9% of the variance in hit rates, 14.9% of the variance in false alarm rates, and 29.2% of the variance in hits minus false alarms. Other noteworthy results were that: (a) hit rates positively correlated with false alarms, (b) objective frequency negatively correlated with both hit rates and false alarm rates, (c) AoA positively correlated with hit rates and negatively correlated with false alarm rates, (d) length negatively correlated with hit rates and positively correlated with false alarm rates, (e) orthographic uniqueness was positively correlated with hit rates and negatively correlated with false alarms, (f) PON positively correlated with false alarm rates, (g) imageability produced the typical mirror pattern, and (h) imageability and length were the strongest predictors of performance. Results were largely compatible with predictions made by single- and dual-process theories of recognition memory.