Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mitotic Spindle Checkpoint Is a Critical Determinant for Topoisomerase-based Chemotherapy*

A novel strategy in cancer therapy is the induction of mitotic cell death by the pharmacological abrogation of cell cycle checkpoints. UCN-01 is such a compound that overrides the G2 cell cycle arrest induced by DNA damage and forces cells into a deleterious mitosis. The molecular pathways leading to mitotic cell death are largely unknown although recent evidence indicates that mitotic cell death represents a special case of apoptosis. Here, we demonstrate that the mitotic spindle checkpoint is activated upon chemotherapeutic treatment with topoisomerase II poisons and UCN-01. Cells that are forced to enter mitosis in the presence of topoisomerase inhibition arrest transiently in a prometaphase like state. By using a novel pharmacological inhibitor of the spindle checkpoint and spindle checkpoint-deficient cells we show that the spindle checkpoint function is required for the mitotic arrest and, most importantly, for efficient induction of mitotic cell death. Thus, our results demonstrate that the mitotic spindle checkpoint is an important determinant for the outcome of a chemotherapy based on the induction of mitotic cell death. Its frequent inactivation in human cancer might contribute to the observed resistance of tumor cells to these chemotherapeutic drugs.
Intracellular Distribution of Human T-Cell Leukemia Virus Type 1 Gag Proteins Is Independent of Interaction with Intracellular Membranes

ABSTRACT Retrovirus Gag proteins are synthesized on free ribosomes, and are sufficient to govern the assembly and release of virus particles. Like type C retroviruses, human T-cell leukemia virus type 1 (HTLV-1) assembles and buds at the plasma membrane. After immunofluorescence staining, HTLV-1 Gag proteins appear as punctuated intracellular clusters, which suggests that they are associated either with intracellular membranes or with the plasma membrane. However, colocalization experiments using a panel of markers demonstrated that Gag proteins were not associated with the membranes involved in the secretory or endocytosis pathway. Small amounts of Gag proteins were detected at the plasma membrane and colocalized with the envelope glycoproteins. Moreover, Gag proteins were excluded from streptolysin-O permeabilized cells and in this respect behaved like cytoplasmic proteins. This suggests that the trafficking of HTLV-1 Gag proteins through the cytoplasm of the host cell is independent of any cell membrane system.
Overcoming obstacles to metastasis ‐ defenses against host defenses: Osteopontin (OPN) as a shield against attack by cytotoxic host cells

Osteopontin (OPN) serves both a cell attachment function and a cell signalling function via the αvβ3 integrin, in its cell attachment capacity it can promote attachment of both osteolasts to bone hydroxyapatite and various other cell types to basement membrane/extracellular matrix. In its cell signalling capacity it initiates a signal transduction cascade that includes changes in the intracellular calcium ion levels and the tyrosine phosophorylation status of several proteins including paxillin. Effects on gene expression include suppression of the induction of nitric oxide synthase by inflammatory mediators. OPN can also reduce cell oxidant and inhibit the killing of tumor cells by activated macrophages and endothelial cells. We hepothesize that those cancer cells that produce OPN at elevated levels can suppress the oxidative burst, inhibit NO production, and thus protect themselves from killing by specific host cell types.
In Brief

Biological roles for naturally occurring, extracellular physiological electric fields have been proposed over the past century. However, in the molecular era, many biologists presume that electric fields have little physiological relevance because there has been no unequivocal demonstration of their importance at the single-cell level in vivo. We have used an in vivo rat corneal model, which generates its own endogenous electric field and show that nerve sprouting, the direction of nerve growth and the rate of epithelial wound healing are controlled coordinately by the wound-induced electric field.
Head injury screening and intimate partner violence: A brief report

ABSTRACT Objective: Although the importance of traumatic brain injury has gained public attention in recent years, relatively little attention has been paid to head injuries among women who have experienced intimate partner violence (IPV). The present study screened for lifetime exposure to mild traumatic brain injuries (mTBIs) among a sample of women who had experienced recent IPV (median days since target incident = 26). Method: Participants included ethnically diverse women whose IPV experiences were reported to law enforcement. Women (n = 225) were asked about injuries to the head sustained during the target IPV incident as well as over the lifetime, and related symptoms. Results: The vast majority of women (80%) reported a lifetime head injury. More than half (56%) screened positive for mTBI, defined as at least one instance in which they experienced a change in consciousness or a period of being dazed and confused as a result of a head injury. A minority of women (13%) reported injuries to the head during the target IPV incident. Most women who had experienced a lifetime head injury reported frequent and current cognitive difficulties. Conclusion: These findings highlight the importance of assessing head injuries and related symptoms among women who have experienced IPV, pointing to important implications for policy and practice.
Hospitalization for community-acquired, rotavirus-associated diarrhea: a prospective, longitudinal, population-based study during the seasonal outbreak. The Greater Toronto Area/Peel Region PRESI Study Group. Pediatric Rotavirus Epidemiology Study for Immunization.

OBJECTIVES To determine the age-specific hospitalization rate for rotavirus-associated diarrhea in Canadian children during the seasonal outbreak, and to characterize children and their households, for assessment of the need for a rotavirus vaccine. DESIGN Prospective multisite cohort study. SETTINGS AND PARTICIPANTS Children with an admission diagnosis of diarrhea admitted to 18 hospitals serving 132 study census tracts of a major urban region, from November 1, 1997, through June 30, 1998. Prospective centralized testing of stools was performed; research nurses administered a follow-up questionnaire to parents. MAIN OUTCOME MEASURE Age-specific diarrhea and rotavirus-associated hospitalization rates. RESULTS Of 224160 children younger than 5 years, the diarrhea hospitalization rate was 4.8 in 1000 (n = 1086) during the seasonal epidemic. Based on testing of 65% of the hospitalized children, the rotavirus-associated diarrhea hospitalization rate was 1.3 in 1000; the cumulative incidence to 5 years of age was 1 in 160. Rotavirus-associated diarrhea was reported in 37% of the 1001 hospitalized children undergoing testing inside and outside of the census tracts; in children aged 6 to 35 months, this rose to more than 70% during April and May. Ages of children with rotavirus-associated diarrhea were 0 to 2 months (2%), 3 to 5 months (5%), 6 to 23 months (60%), 24 to 35 months (15%), and 36 months or older (19%). Of children aged 0 to 5 and 6 to 11 months, 4 (19%) of 21 and 6 (10%) of 59, respectively, had been born prematurely; 20 (24%) of 83 younger than 1 year were breastfed at the time of illness. Of children younger than 36 months, 77% were cared for in their homes; 13%, in family day care homes; and 8%, in child care centers. The mean (+/- SD) duration of rotavirus hospitalization based on hospital records and parental questioning was 2.4 +/- 1.7 and 3.1 +/- 1.6 days, respectively; it was significantly longer (P < or = .001) in children with an underlying medical condition. One child required intensive care unit hospitalization. Diarrhea occurred concurrently in 74% of household contacts younger than 3 years; 38%, aged 3 to 18 years; and 29%, older than 18 years. Seventy-six percent of parents were married. Household incomes in Canadian dollars in the 81% reporting were less than $20000 in 20%, $20000 to $60000 in 44%, and greater than $60000 in 36%. Ethnicity was reported as 53% white, 15% black, 10% Asian, 12% East Indian, and 11% other. CONCLUSIONS Based on testing of 65% of children with diarrhea, rotavirus resulted in hospitalization in a minimum of 1 in 160 children by 5 years of age during the seasonal outbreak. Had 100% of young children with diarrhea undergone testing, the extrapolated cumulative incidence of rotavirus-associated diarrhea by 5 years of age may have been 1 in 106.
Human sleep and tissue restitution: some qualifications and doubts.

On etudie successivement les fonctions et la liberation en fonction du sommeil de la STH, le renouvellement des proteines, la charge d'energie cellulaire et la division cellulaire au cours du sommeil, les rapports entre effort et sommeil, les effets de la privation totale de sommeil sur le fonctionnement corporel et sur le systeme nerveux central
Strained bilayer graphene: Band structure topology and Landau level spectrum

We show that topology of the low-energy band structure in bilayer graphene critically depends on mechanical deformations of the crystal which may easily develop in suspended graphene flakes. We describe the Lifshitz transition that takes place in strained bilayers upon splitting the parabolic bands at intermediate energies into several Dirac cones at the energy scale of a few meV. Then, we show how this affects the electron Landau level spectra and the quantum Hall effect.
Inhibition of glycogen synthase kinase-3 protects cells from intrinsic but not extrinsic oxidative stress

Oxidative stress is linked to neuronal dysfunction and death in many diseases. Glycogen synthase kinase-3 often promotes apoptosis, so this investigation tested whether glycogen synthase kinase-3 is linked to oxidative stress-induced apoptosis. Both intrinsic oxidative stress induced by the mitochondrial inhibitor rotenone and extrinsic oxidative stress induced by exogenously added H2O2 activated Bax, caspase-2, and caspase-3 in human neuroblastoma SH-SY5Y cells. Inhibitors of glycogen synthase kinase-3 blocked rotenone-induced, but not H2O2-induced, activation of both caspases, but not Bax activation. Thus, glycogen synthase kinase-3 is an important component of intrinsic oxidative stress-induced apoptosis that acts downstream of mitochondrial Bax activation, and there are substantial differences in the role of glycogen synthase kinase-3, and lithium's effects, in apoptotic signaling induced by intrinsic and extrinsic oxidative stress.
Heredity of nasal polyps.

BACKGROUND Nasal polyps is a common disease but little is known about its` pathogenesis. Our hypothesis was that there are genetic factors involved in the development of this disease. The aim of this study was to examine close relatives of patients with nasal polyps and comparing them with a general population with regard to prevalence of polyps. METHODOLOGY Patients with nasal polyps who attended the clinic were recruited to the study and were asked whether they had any close adult relatives (siblings, parents or children). We intended to recruit two relatives per patient, one of each gender, for nasal endoscopy. The prevalence of nasal polyps in these relatives was compared with the prevalence of nasal polyps in a general population. RESULTS During a 4-year period, 368 patients and 410 relatives were recruited to the study. Although we were unable to recruit two close relatives for every patient, we were able to calculate nasal polyp prevalence within families as being 19.2%. Compared with the prevalence of nasal polyps among individuals in a general Swedish population from the same geographical area, the relative risk for polyps among relatives was almost five times higher. CONCLUSION This study strongly indicates that heredity is a factor of importance for development of nasal polyps.
A thermodynamic scale for leucine zipper stability and dimerization specificity: e and g interhelical interactions.

The leucine zipper is a dimeric coiled‐coil protein structure composed of two amphipathic alpha‐helices with the hydrophobic surfaces interacting to create the dimer interface. This structure has been found to mediate the dimerization of two abundant classes of DNA binding proteins: the bZIP and bHLH‐Zip proteins. Several workers have reported that amino acids in the e and g positions of the coiled coil can modulate dimerization stability and specificity. Using the bZIP protein VBP as a host molecule, we report a thermodynamic scale (delta delta G) for 27 interhelical interactions in 35 proteins between amino acids in the g and the following e positions (g<==>e’) of a leucine zipper coiled coil. We have examined the four commonly occurring amino acids in the e and g positions of bZIP proteins, lysine (K), arginine (R), glutamine (Q), glutamic acid (E), as well as the only other remaining charged amino acid aspartic acid (D), and finally alanine (A) as a reference amino acid. These results indicate that E<==>R is the most stable interhelical pair, being 0.35 kcal/mol more stable than E<==>K. A thermodynamic cycle analysis shows that the E<==>R pair is 1.33 kcal/mol more stable than A<==>A with ‐1.14 kcal/mol of coupling energy (delta delta Gint) coming from the interaction of E with R. The E<==>K coupling energy is only ‐0.14 kcal/mol. E interacts with more specificity than Q. The R<==>R pair is less stable than the K<==>K by 0.24 kcal/mol. R interacts with more specificity than K. Q forms more stable pairs with the basic amino acids K and R rather than with E. Changing amino acids in the e position to A creates bZIP proteins that form tetramers.
X-Ray Absorption Spectroscopy of Strontium(II) Coordination.

Detailed analyses of crystalline, hydrated, and precipitated strontium compounds and an aqueous strontium solution by synchrotron extended X-ray absorption fine structure (EXAFS) were used to quantify local thermal and static disorder and to characterize strontium coordination in a variety of oxygen-ligated bonding environments. Analysis of anharmonic vibrational disorder (i.e., significant contribution from a third cumulant term (C(3)) in the EXAFS phase-shift function) in compounds with low and high static disorder around strontium showed that first-shell anharmonic contributions were generally not significant above experimental error in the EXAFS fits (R+/-0.02 Å with and without C(3)). The only case in which a significant apparent decrease in Sr-O distance was observed with increasing temperature, and for which a third cumulant term was significant, was for dilute strontium in aqueous solution. Empirical parameterization of Debye-Waller factor (sigma(2)) for strontium compounds as a function of backscatterer atomic number (Z), interatomic Sr-Z distance, and temperature of spectral data collection showed systematic increases in sigma(2) as a function of increasing temperature and Sr-Z bond length. At values of sigma(2) greater than approximately 0.025 Å(2) (for N<12 and R(Sr)-Z>3 Å), backscattering was generally not significant above noise levels in spectra of compounds of known crystal structure. Comparison of the EXAFS spectra of freshly precipitated SrCO(3) (spectra collected wet) to that of dry, powdered strontianite (SrCO(3)(s)) indicated no significant differences in the local atomic structure around strontium. Analysis of partially hydrated strontium in natural Ca-zeolite (heulandite) showed that strontium is substituted only in the calcium (Ca2) site. Backscattering from aluminum and silicon atoms in the zeolite framework were apparent in the EXAFS spectra at low and room temperature at distances from central strontium of <4.2 Å. Comparison of strontium structural coordination determined in this and previous studies suggests that previous EXAFS determinations of hydrated strontium may have underestimated first-shell interatomic distances and coordination numbers because minor contributions to the EXAFS phase-shift and amplitude functions were not accounted for, either theoretically or empirically. Copyright 2000 Academic Press.
Shoulder muscle fatigue development in young and older female adults during a repetitive manual task

Age may modify the association between occupational physical demand and muscle loading, and ultimately increase the risk of musculoskeletal disorders. The goal of this study was to investigate age-related differences in shoulder muscle fatigue development during a repetitive manual task. Twenty participants in two age groups completed an 80-minute simulated low-intensity assembly task. Electromyographic (EMG) manifestation of muscle fatigue was observed in the upper trapezius, deltoid and infraspinatus muscles in both age groups, and coincided with an increase in the subjective ratings of perceived exertions. Compared with the younger group, older group showed a more monotonic decrease in EMG power frequency in the upper trapezius and deltoid muscles. However, the age-related difference in EMG amplitude was less consistent. Relative rest time of the upper trapezius muscle in the older group was less than the young group throughout the task. The observed patterns of EMG measures suggest that older participants may have disadvantages in fatigue resistance in the upper trapezius and posterior deltoid muscles during the simulated repetitive manual task. Practitioner Summary: A rapidly ageing workforce in the USA and other countries poses new challenges for preventing work-related injuries. This study showed that during an 80-minute repetitive light manual work, older adults exhibited more consistent patterns of electromyographic manifestation of shoulder muscle fatigue and less rest in the upper trapezius muscle than young adults.
A double-blind study of the efficacy and safety of the ICP10deltaPK vaccine against recurrent genital HSV-2 infections.

A randomized double-blind trial to evaluate the safety of a novel recombinant virus, ICP10deltaPK, for reduction or prevention of recurrent herpes simplex virus type 2 (HSV-2) infection was carried out in public hospitals in Mexico City. Persons having a minimum of 5 documented herpetic recurrences in the previous year were randomized for vaccination. Patients were examined within 72 hours of lesion occurrence. If accepted into the study, the patient was inoculated subcutaneously in the upper deltoid muscle area at days 7, 17, and 28 after initiation of lesion occurrence. Recurrences were recorded by patient diary and physician examination. During the observation period (extending from 10 to 180 days after the last booster dose), recurrences in the vaccine (V) group were prevented completely in 37.5% of the patients, whereas in the placebo (P) group, 100% of the patients had at least one recurrence (P = .068). Vaccinated patients had fewer recurrences (V, 1.58; P, 3.13 [P = .028]). The mean number of illness days was 10 for the vaccine group and 18 for the placebo group (P = .028). Further studies to evaluate this vaccine and its dosimetry for the treatment of genital herpes infections appear warranted.
What's in a game?: A theory of game models

Game semantics is a rich and successful class of denotational models for programming languages. Most game models feature a rather intuitive setup, yet surprisingly difficult proofs of such basic results as associativity of composition of strategies. We seek to unify these models into a basic abstract framework for game semantics, game settings. Our main contribution is the generic construction, for any game setting, of a category of games and strategies. Furthermore, we extend the framework to deal with innocence, and prove that innocent strategies form a subcategory. We finally show that our constructions cover many concrete cases, mainly among the early models [5, 23] and the recent, sheaf-based ones [40].
Relations of Distinct Psychopathic Personality Traits with Anxiety and Fear: Findings from Offenders and Non-Offenders

Early descriptions of psychopathy emphasise fearlessness and a lack of nervousness or anxiety as key characteristics of the disorder. However, conflicting evidence suggests that anxiety may be positively correlated with some aspects of the psychopathy construct. This position may seem somewhat paradoxical when considered alongside impaired processing of fear related stimuli in psychopathic personality. The aim of the current paper was to examine the distinct relations of callous, egocentric, and antisocial psychopathic traits with measures of anxiety and social anxiety in samples of non-offenders (Study 1) and violent offenders (Study 2). In Study 2 we also used an emotion recognition task to examine fearful face recognition. In Studies 1 and 2 we showed distinct and opposite significant relationships of egocentric and antisocial psychopathic traits with trait anxiety. Thus, while trait anxiety was negatively predicted by egocentric traits, it was predicted in a positive direction by antisocial traits in both samples. In Study 2 we found that callous traits were predictive of greater impairments in fearful face recognition. These findings suggest that anxiety and fear are distinguishable constructs in relation to psychopathic personality traits, and are discussed in terms of potentially separable mechanisms for these two constructs.
A methodology for the pull-in voltage of clamped diaphragms

Due to the electrostatic excitation principle, MEMS based capacitive microphones exhibit a nonlinear behaviour and this communication investigates these nonlinearities with the aim to optimize the input voltage signal. The nonlinear electrostatic force due to the bias voltage is combined with the 2D load-deflection model of a square or circular diaphragm to evaluate the pull-in voltage. An analytical solution is derived to calculate the electrostatic pressure, the pull-in voltage and the deflection profile of the diaphragm. Numerical results with clamped square and circular diaphragms are presented showing the effectiveness of the method.
Appropriateness of surgical antimicrobial prophylaxis in the Latium region of Italy, 2008: a multicenter study.

BACKGROUND There is still wide variability in surgical antimicrobial prophylaxis (SAP) practice by different surgical teams and specialties, with potential impact on adverse events and the emergence of antibiotic resistance. METHODS We assessed SAP appropriateness in a regional prospective multicenter study on the basis of the agreement of the Surgical Care Improvement Project indicators (SCIP-Inf) with Italian guidelines (GL). RESULTS Prophylaxis was administered in 2,664 of 2,835 procedures (94%): In 2,346 of 2,468 (95%) as indicated and in 318 of 367 (86.6%) in which they were not indicated. The SCIP-Inf1 (timing), SCIP-Inf2 (antibiotic choice), and SCIP-Inf3 (duration) were in agreement with GL in 1,172 (50%), 1,983 (84.5%), and 1,121 (48%) of 2,346 procedures, respectively. CONCLUSIONS These results suggest the need for implementation of an antimicrobial stewardship program in this surgical setting.