Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel mechanism for the control of clinical cancer : Inhibition of the production of adenosine triphosphate ( ATP ) with a standardized extract of paw paw ( Asimincz triloba , Annonaceae )

The North American paw paw tree [Asiniina triloba (L.) Dunal, Annonaceae] contains complex mixtures of over 50 Annonaceous acetogenins. These are derivatives of long chain (C-32 or C34) fatty acids which are powerful inhibitors of mitochondrial (the PSST protein of complex I) and cytoplasmic (the plasma membrane NADH oxidase) production of adenosine triphosphate (ATP). A standardized extract of paw paw reduced tumor markers, reduced tumor sizes, and increased longevities among 94 cancer patients while causing minimal side effects. Ten case studies are presented. Inhibition of cellular energy (ATP), using the paw paw supplement, thus offers a novel, safe, and effective mechanism for the control of various types of clinical cancer.
Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey.

AIMS Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. METHODS AND RESULTS Patients (n = 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a significant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients <55 years, the odds ratios of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age 65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or =85 years, with no major differences across different types of admission or discharge diagnoses. CONCLUSION Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.
Pulmonary clearance and release of norepinephrine and epinephrine in newborn lambs.

To examine the pulmonary kinetics of the catecholamines norepinephrine and epinephrine immediately after birth, eight fetal lambs were instrumented with vascular catheters under general anesthesia at 133-134 days gestation (term = 147 days) and were delivered by cesarean section 1 wk later. Pulmonary norepinephrine and epinephrine kinetics were then studied 1 and 4 h after birth using radiotracer dilution methodology. The pulmonary fractional extraction of norepinephrine was similar in 1-h (0.111 +/- 0.021) and 4-h (0.117 +/- 0.023) lambs and constituted 24 +/- 5 and 32 +/- 9% of total body norepinephrine clearance, respectively. Pulmonary removal of epinephrine was less pronounced with a fractional extraction of 0.035 +/- 0.017 in 1-h and 0.036 +/- 0.013 in 4-h lambs, which corresponded to 8 +/- 4 and 9 +/- 3% of total body epinephrine clearance, respectively. Pulmonary spillover of norepinephrine into the circulation was similar in 1-h (79 +/- 26 ng.min-1.kg-1) and 4-h (82 +/- 18 ng.min-1.kg-1) lambs, and this comprised 27 +/- 8 and 42 +/- 8% of total body norepinephrine spillover, respectively. Pulmonary epinephrine spillover was not detectable at 1 h, but it occurred in all 4-h lambs, averaging 4.7 +/- 0.8 ng.min-1.kg-1 or 20 +/- 6% of epinephrine total body spillover. These findings indicate that the lungs of newborn lambs 1) are a major site for removal of norepinephrine and epinephrine from the circulation; 2) release a substantial quantity of norepinephrine into the circulation, consistent with the presence of tonic pulmonary sympathetic nerve activity; and 3) constitute a significant extra-adrenal source of plasma epinephrine.
LOW SURVIVAL OF PARASITE CHICKS MAY RESULT FROM THEIR IMPERFECT ADAPTATION TO HOSTS RATHER THAN EXPRESSION OF DEFENSES AGAINST PARASITISM

Abstract Host parents exhibit a variety of behaviors toward avian brood parasites, but not all of their actions have necessarily evolved in response to costs imposed by parasites. To investigate whether common waxbills (Estrilda astrild) have evolved defenses specifically against parasitic pin-tailed whydahs (Vidua macroura), I studied the specificity and flexibility of host behaviors toward nestlings at two sites that differed significantly in parasitism rates and intensities. I focused on documenting nestling survival because V. macroura young match the elaborate gape morphology of E. astrild nestlings, a pattern that suggests hosts may possess unique defenses against parasite chicks. Parasite young survived significantly worse than host young in mixed broods. However, this apparent discrimination was not associated with parasitism risk as would be expected if defenses had evolved specifically to counter parasitism. Parasite young may have survived poorly compared to host young because individual chicks were less able to stimulate sufficient care from foster parents or because they were more susceptible to nestling competition, disease, or reduced provisioning by hosts. Mortality may have also been exacerbated by poor timing of parasite egg laying. In nonparasitized and parasitized nests, rates of nestling survival were similar, further suggesting that parenting behaviors that result in chick mortality did not evolve solely in response to parasite young. In addition, orange-breasted waxbills (Amandava subflava) and zebra finches (Taeniopygia guttata), rarely parasitized and nonparasitized relatives of E. astrild, experience similar levels of nestling mortality presumably as a result of phylogenetically widespread parenting strategies. Despite the similarity of parasitic V. macroura nestlings and E. astrild nestlings, I found no evidence that E. astrild parents possess defenses that allow for specific discrimination against parasite chicks during the nestling period. Rather than being subject to host defenses evolved in an arms race, Vidua chicks may simply be imperfectly adapted to life in the nests of their hosts.
Mu opioid receptor activation reduces inhibitory postsynaptic potentials in hippocampal CA3 pyramidal cells of rat and guinea pig.

Using intracellular recording techniques, we characterized synaptic responses of CA3 pyramidal cells to mu and kappa agonists in hippocampal slices from rats and guinea pigs. In rat CA3 pyramidal cells, the mu selective agonist (N-MePhe3,D-Pro4)-morphiceptin (PLO17) inhibited both the early and the late inhibitory postsynaptic potentials (IPSPs) and increased excitatory postsynaptic potential (EPSP) amplitudes. Voltage clamp analysis of synaptic currents indicated that the excitatory postsynaptic current were not increased by PLO17, showing that the apparent increase in EPSPs was a result of a decrease in the underlying IPSP. The kappa agonists trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate and dynorphin A (1-17) had no effect on EPSPs or IPSP conductances measured in rat pyramidal cells. Maximal inhibition of IPSPs by PLO17 resulted in a bursting response to stimulation in rat but not guinea pig CA3 pyramidal cells. In guinea pig CA3 pyramidal cells, PLO17 also inhibited IPSP conductances but did not affect EPSP amplitudes. In contrast to the lack of effect in rat pyramidal cells, trans-(+)-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methanesulfonate (100 nM) inhibited the late IPSP conductance without influencing the EPSP or the early IPSP conductance of guinea pig pyramidal cells. Dynorphin A (1-17) (0.01-10 microM) did not affect resting membrane properties or evoked synaptic conductances in either preparation. Mu receptor activationin the CA3 of rats and guinea pigs results in the inhibition of inhibitory synaptic input to pyramidal cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas

Preoperative T1 anatomic MR images of 384 patients with glioblastomas were evaluated by an automated computational image-analysis pipeline to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good and poor survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared. Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification. The authors conclude that voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment. BACKGROUND AND PURPOSE: Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes. MATERIALS AND METHODS: Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions. RESULTS: Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies. CONCLUSIONS: Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.
Mitotic crisis: The unmasking of a novel role for RPA

Mitotic DNA damage is a constant threat to genomic integrity, yet understanding of the cellular responses to this stress remain incomplete. Recent work by Anantha et al. (PNAS 2008; 105:12903–8) has found surprising evidence that RPA, the primary eukaryotic single-stranded DNA-binding protein, can stimulate the ability of cells to exit mitosis into a 2N G1 phase. Along with providing additional discussion of this study, we review evidence suggesting that DNA replication and repair factors can modulate mitotic transit by acting through Polo-like kinase-1 (Plk1) and the centrosome. “A crisis unmasks everyone. ”—Mason Cooley, US aphorist.
Network-Assisted Distributed Fairness-Aware Interference Coordination for Device-to-Device Communication Underlaid Cellular Networks

Device-to-device (D2D) communication underlaid cellular network is considered a key integration feature in future cellular network. However, without properly designed interference management, the interference from D2D transmission tends to degrade the performance of cellular users and D2D pairs. In this work, we proposed a network-assisted distributed interference mitigation scheme to address this issue. Specifically, the base station (BS) acts as a control agent that coordinates the cross-tier interference from D2D transmission through a taxation scheme. The cotier interference is controlled by noncooperative game amongst D2D pairs. In general, the outcome of noncooperative game is inefficient due to the selfishness of each player. In our game formulation, reference user who is the victim of cotier interference is factored into the payoff function of each player to obtain fair and efficient outcome. The existence, uniqueness of the Nash Equilibrium (NE), and the convergence of the proposed algorithm are characterized using Variational Inequality theory. Finally, we provide simulation results to evaluate the efficiency of the proposed algorithm.
A collaborative evaluation of the cytotoxicity of two surfactants by using the human corneal epithelial cell line and the WST-1 test.

This study was undertaken to investigate the use of the in vitro test WST-1, an assay of cell proliferation and viability, for a preliminary safety evaluation of topical ophthalmic preparations. The cytotoxicity of two surfactants, benzalkonium chloride (BAC) and polyoxyethylene-20-stearyl ether (Brij78, PSE) was independently investigated in four laboratories in the EU by using an immortalized human corneal epithelial (HCE) cell line. The HCE cells were exposed to BAC and PSE for 5 min, 15 min, and 1 hour, and the results of the HCE-WST-1 tests were collected and compared. After one-hour exposure, the EC(50) values in BAC-treated cells in the presence of serum ranged between 0.0650 +/- 0.0284 (mean +/- SD) mM, and those in the absence of serum 0.0296 +/- 0.0081 mM. The corresponding values for PSE were 0.0581 +/-. 0300 mM and 0.0228 +/-. 0063 mM. There were variations in the results between different laboratories, with coefficients of variation ranging from 31 to 121%, mean 58%. The use of one-hour exposure time is to be preferred, and the elimination of serum in the culture medium is recommended to avoid both underestimation of toxic effects and variability of the test results.
Fossil Foot Bones

ankle, accompanied by some muscular adaptation. The low robusticity index shows that relative elongation of the leg had accompanied these changes. On the slender evidence available it appears possible that the knee joint was less well adapted to bipedalism than it is in Homo sapiens. Thus while the fossil form was clearly a habitually bipedal plantigrade primate, its gait may well have differed considerably from that of modern man. I thank Dr. L. S. B. Leakey, Prof. R. E. M. Bowden, Dr. J. R. Napier, Dr. J. D. G. Troup and Mrs. A. Besterman for their help in this work.
Instability and the Incentives for Corruption

We investigate the relationship between corruption and political stability, from both theoretical and empirical perspectives. We propose a model of incumbent behavior that features the interplay of two effects: a horizon effect, whereby greater instability leads the incumbent to embezzle more during his short window of opportunity, and a demand effect, by which the private sector is more willing to bribe stable incumbents. The horizon effect dominates at low levels of stability, because firms are unwilling to pay high bribes and unstable incumbents have strong incentives to embezzle, whereas the demand effect gains salience in more stable regimes. Together, these two effects generate a non-monotonic, U-shaped relationship between total corruption and stability. On the empirical side, we find a robust U-shaped pattern between country indices of corruption perception and various measures of incumbent stability, including historically observed average tenures of chief executives and governing parties: regimes that are very stable or very unstable display higher levels of corruption when compared with those in an intermediate range of stability. These results suggest that minimizing corruption may require an electoral system that features some re-election incentives, but with an eventual term limit.
A Sparse Representation Method for DOA Estimation With Unknown Mutual Coupling

Sparse representation methods for direction-of-arrival (DOA) estimation have been applied to many situations, which include limited number of collected snapshots and highly correlated sources. However, they suffer from a lack of provision for mutual coupling effect. This letter describes a modified sparse representation method in the presence of unknown mutual coupling. The new method takes advantage of the special structure of the mutual coupling matrix (MCM) for uniform linear arrays (ULAs) so as to eliminate the mutual coupling effect completely. Simulation results verify the efficiency of the proposed method.
Hyperspherical Variational Auto-Encoders

Samples from this distribution are drawn using an acceptance/rejection algorithm when m 6= 3. The complete procedure is described in Algorithm 2. The Householder reflection (see Algorithm 3 for details) simply finds an orthonormal transformation that maps the modal vector e1 = (1, 0, · · · , 0) to μ. Since an orthonormal transformation preserves the distances all the points in the hypersphere will stay in the surface after mapping. Notice that even the transform Uz′ = (I− 2uu>)z′, can be executed in O(m) by rearranging the terms.
Antigenic Polypeptides of Israeli Spotted Fever Isolates Compared with Other Spotted Fever Group Rickettsiae a , b

Spotted fever group (SFG) rickettsial agents are found worldwide in disparate and dispersed geographical locations and ecological milieus. ’ In some cases, a given strain has been documented to appear outside its expected range, either in a locale associated with another species of Rickettsia or in a place where the ambiguous disease symptoms are not normally associated with rickettsial disease^. ^,^ In the latter case, a resulting delay in efficacious intervention might have serious consequences. Definitive rickettsial strain verification, while of minimal clinical value, is vital for surveillance and retrospective epidemiological and ecological studies. Over the past decade, several approaches have been used to differentiate between numerous isolates derived from arthropod vectors, and human and non-human host^. ^-^ Parallel antigenic comparison of many strains has been achieved by reciprocal titrations of pooled acute phase antisera, using indirect microimmunof l u o r e ~ c e n c e . ~ ~ ~ For comparing smaller numbers of strains, preadsorbtion of antisera with heterologous antigens has been useful for distinguishing locally collected Israeli patient isolates from standard strains of Rickettsia conorL4 Although such methodology has largely been superceded by the use of monoclonal a n t i b o d i e ~ , ~ ~ , ~ the use of polyclonal antibodies could be expected to be a more valid method of determining overall similarities between strains with respect to immunodominant determinants.
Coexistence of Ovarian Neoplasms and Endocervical Adenocarcinoma

The coexistence of ovarian neoplasms and adenocarcinoma of the cervix occurs more often than generally realized. Of 390 women with adenocarcinoma of the cervix, the ovaries were available for histologic review in 161. Neoplasms were present in the ovaries of 25 of the 161 women (16%). Eleven carcinomas were metastatic to the ovary, and 14 (9%) were independent primary tumors. These included four benign cystic teratomas, four benign epithelial tumors, and six primary carcinomas. The 54 women with endometrioid adenocarcinomas of the cervix were especially prone to ovarian carcinoma because four (7%) had coexistent or subsequent endometrioid carcinoma in the ovary.
Les fouilles du gisement paléolithique final de Saleux (Somme)

Decouvert sur le trace de l'autoroute Al 6, au niveau du franchissement de la vallee de la Selle, le gisement paleolithique et mesolithique de Saleux a fait l'objet d'une dizaine de campagnes de fouilles depuis 1993. Une douzaine de locus attribuables a la tradition des groupes a Federmesser et au Mesolithique moyen ont ete mis au jour. Les occupations archeologiques se situent en bordure de la plaine alluviale actuelle en marge d'un paleo-chenal. Les recherches menees apportent de nouvelles informations sur l'identite technique et culturelle des groupes qui ont occupe la region au cours de l'oscillation d'Allerod et de la chronozone du Boreal, mais egalement sur la structuration des habitats et les modalites d'occupation du territoire. La decouverte de restes humains attribuables au Paleolithique final apporte un interet supplementaire au gisement de Saleux qui constitue un site de reference pour l'etude du Tardiglaciaire et du debut de l'Holocene du Nord de la France.
Autophagy, Bafilomycin and Cell Death: The “A-B-Cs” of Plecomacrolide-Induced Neuroprotection

Bafilomycin A1 (BafA1), which is a member of the plecomacrolide sub-class of macrolide antibiotics, has differential, concentration-dependent effects on neuronal cell viability. When used at high concentrations, BafA1 inhibits vacuolar ATPase (V-ATPase), promotes the accumulation of autophagic vacuoles and triggers Bax-dependent apoptosis. These effects are similar to those induced by the lysosomotropic agent chloroquine. Conversely, at concentrations below its reported ability to completely inhibit V-ATPase, BafA1 dramatically attenuates chloroquine-induced apoptosis. The protective effects of BafA1 appear to be independent of the chloroquine-induced accumulation of autophagosomes. Rather, BafA1 appears to inhibit events downstream of chloroquine-induced autophagosome accumulation, such as the loss mitochondrial or lysosomal integrity. Our finding that BafA1 inhibits the death of neurons induced by autophagic stress suggests a potentially novel mechanism of action apart from its ability to inhibit V-ATPase. Here we provide further evidence of neuroprotection against chloroquine-induced death by plecomacrolide antibiotics that are structurally similar to BafA1, including bafilomycin B1 and concanamycin A, and discuss potential mechanism(s) of neuroprotection against autophagic stress. Addendum to: Bafilomycin A1 Inhibits Chloroquine-Induced Death of Cerebellar Granule Neurons John J. Shacka, Barbara J. Klocke, Masahiro Shibata, Yasuo Uchiyama, Geeta Datta, Robert E. Schmidt and Kevin A. Roth Mol Pharmacol 2006; 69:1125-36
pH‐Independent Endocytic Cycling of the Chemokine Receptor CCR5

Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin‐coated pits and delivered to recycling endosomes. Subsequently, ligand‐ free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G‐protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well‐characterised G protein coupled receptor, the β2‐adrenergic receptor, following agonist‐induced internalisation. CCR5‐bound RANTES (CCL5) and MIP‐1β (CCL4) only exhibit pH‐dependent dissociation at pH < 4.0, below the values normally found in endocytic organelles. Although receptor‐agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP‐1β dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.
DNA synthesis, cell proliferation index in normal and abnormal gallbladder epithelium

The observation of mitotic figures in the epithelium of the normal gallbladder is exceptional because cell renewal is occurring at a very slow rate. It is only after using 3H‐thymidine and autoradiography to observe the cells in DNA synthesis that evidence of a significant epithelial cell replication has been provided.