Takshan/R1 huggingface dataset:
Feeling the future: A meta-analysis of 90 experiments on the anomalous anticipation of random future events.

In 2011, one of the authors (DJB) published a report of nine experiments in the Journal of Personality and Social Psychology purporting to demonstrate that an individual's cognitive and affective responses can be influenced by randomly selected stimulus events that do not occur until after his or her responses have already been made and recorded, a generalized variant of the phenomenon traditionally denoted by the term precognition. To encourage replications, all materials needed to conduct them were made available on request. We here report a meta-analysis of 90 experiments from 33 laboratories in 14 countries which yielded an overall effect greater than 6 sigma, z = 6.40, p = 1.2 × 10 (-10 ) with an effect size (Hedges' g) of 0.09. A Bayesian analysis yielded a Bayes Factor of 5.1 × 10 (9), greatly exceeding the criterion value of 100 for "decisive evidence" in support of the experimental hypothesis. When DJB's original experiments are excluded, the combined effect size for replications by independent investigators is 0.06, z = 4.16, p = 1.1 × 10 (-5), and the BF value is 3,853, again exceeding the criterion for "decisive evidence." The number of potentially unretrieved experiments required to reduce the overall effect size of the complete database to a trivial value of 0.01 is 544, and seven of eight additional statistical tests support the conclusion that the database is not significantly compromised by either selection bias or by intense " p-hacking"-the selective suppression of findings or analyses that failed to yield statistical significance. P-curve analysis, a recently introduced statistical technique, estimates the true effect size of the experiments to be 0.20 for the complete database and 0.24 for the independent replications, virtually identical to the effect size of DJB's original experiments (0.22) and the closely related "presentiment" experiments (0.21). We discuss the controversial status of precognition and other anomalous effects collectively known as psi.
Host preferences and feeding patterns of Anopheles sinensis Wiedemann in three sites of Shandong province, China.

Background & objectives: Anopheles sinensis Wiedemann is a major vector of malaria and is among the dominant species in Shandong province of China. Knowledge of the blood-feeding patterns of mosquitoes is crucial for elimination of malaria vectors. However, little information is available on the blood-feeding behaviour of An. sinensis mosquitoes in Shandong province. This study was carried out to compare the blood-feeding behaviour of An. sinensis in malaria-endemic areas of Shandong province China. Methods: Adult Anopheles mosquitoes were collected from three malaria-endemic areas (Jimo, Yinan and Shanxian), during the peak months of mosquito population (August and September) from 2014 to 2015. Indoor-resting mosquitoes and outdoor-resting blood-fed females were sampled in the morning hours (0600 to 0900 hrs) from 10 randomly selected houses using pyrethrum spray catch method, and sweeping with an insect net. ELISA was used for the identification of blood meal. The blood meal of each mosquito was tested against antisera specific to human, pig, dog, cow, goat, horse (mule) and fowl. Results: At all indoor study locations of Jimo, Yinan and Shanxian, 59.4, 68.1 and 98.8% blood-engorged female An. sinensis collected from cattle sheds fed almost exclusively on bovines, respectively. For outdoor locations, at Jimo site, 27.27 and 49.55% An. sinensis fed on cattle and pigs; at Yinan, 30.42% fed on cattle and 36.88% fed both on cattle and goats, while no pig antibodies were detected. At Shanxian, percent of An. sinensis that fed on cattle, pigs and cattle-goat was 20.72, 27.62 and 21.78%, respectively. Interpretation & conclusion: The analysis of An. sinensis blood meals in all the three studied areas from human houses, cattle sheds, pig sheds and mixed dwellings revealed that An. sinensis prefers cattle hosts, and can feed on other available animal hosts if the cattle hosts are absent, and the mosquitoes readily feed on humans when domestic animals (cattle and pigs) are not nearby for feeding. The analysis of blood meal revealed that An. sinensis follow opportunistic feeding in Shandong province, China.
A reassessment of the artificial infection of three predominant mosquito species with Plasmodium vivax in Shandong Province, China.

BACKGROUND & OBJECTIVES: Under certain ecological circumstances, pathogens are able to rapidly adapt to new vectors. The great capacity of Plasmodium spp. to adapt to new anopheline mosquito vectors on different continents and the continuous ecological changes attributed to humans might promote their adaptation to culicine vectors, which are known to infect humans. Based on our current knowledge, it is difficult to predict whether such adaptations will occur. This study was aimed to determine the infection susceptibility of Anopheles sinensis, Culex tritaeniorhynchus and Cx. pipiens pallens to Plasmodium vivax in Shandong Province of China. METHODS: The susceptibility of the three predominant species of mosquitoes -An. sinensis, Cx. tritaeniorhynchus and Cx. pipiens pallens in Shandong Province was compared with a direct membrane feeding assay with 15 batches of Shandong strain mono-infected gametocyte-containing blood collected from Plasmodium vivax-infected patients. Infectivity was measured by dissecting the midguts and salivary glands of the mosquitoes. The presence of oocysts and sporozoites was determined by microscopy at 6 and 22 days post-blood feeding. RESULTS: From the 15 batches of mosquitoes that were fed infected blood, oocysts and sporozoites were detected only in 7th, 13th and 15th batches of infection for An. sinensis, and no oocysts or sporozoites were detected in Cx. tritaeniorhynchus or Cx. pipiens pallens. The positive rate of An. sinensis infection was 21.2, 13 and 36.3% in the three batches of mosquitoes, with an average infection rate of 23.5%. INTERPRETATION & CONCLUSION: The susceptibility of An. sinensis to P. vivax was very high in Shandong Province. Cx. tritaeniorhynchus and Cx. pipiens pallens failed to exhibit susceptibility to P. vivax.
Evaluation of Isotope (32)P Method to Mark Culex pipiens (Diptera: Culicidae) in a Laboratory.

BACKGROUND: The aim of the current study was to develop a marking technique as an internal marker to mark post blood meal mosquitoes by using stable phosphate isotope (32)P and determine the optimal concentration of it. METHODS: An isotonic physiological saline solution, containing different concentration of radioactive isotope (32)P-labeled disodium phosphate (Na2H(32)PO4) was injected into rabbits via the jugular vein in the laboratory. Emerged Cx. pipiens were marked after feeding on rabbit. At the same time, the labeled conditions of emerged Cx. pipiens were also measured by placing feces of No. 6 rabbit into containers with mosquito larvae and pupae inside. RESULTS: According to the label condition of Cx. pipiens after taking blood and the effect of different dosage Na2H(32)PO4 on rabbit health, the optimal concentration of radioactive isotope was determined, that is, 0.1211 mCi/kg. By placing feces of No. 6 rabbit into containers with mosquito larvae and pupae inside, the emerged mosquitoes were also labeled. Therefore, feeding mosquitoes on the animal injected with radioactive Na2H(32)PO4 was more practical for detecting and tracing mosquitoes. CONCLUSION: The method was less time-consuming, more sensitive and safer. This marking method will facilitate post-bloodmeal studies of mosquitoes and other blood-sucking insects.
The onset of widespread marine red beds and the evolution of ferruginous oceans.

Banded iron formations were a prevalent feature of marine sedimentation ~3.8-1.8 billion years ago and they provide key evidence for ferruginous oceans. The disappearance of banded iron formations at ~1.8 billion years ago was traditionally taken as evidence for the demise of ferruginous oceans, but recent geochemical studies show that ferruginous conditions persisted throughout the later Precambrian, and were even a feature of Phanerozoic ocean anoxic events. Here, to reconcile these observations, we track the evolution of oceanic Fe-concentrations by considering the temporal record of banded iron formations and marine red beds. We find that marine red beds are a prominent feature of the sedimentary record since the middle Ediacaran (~580 million years ago). Geochemical analyses and thermodynamic modelling reveal that marine red beds formed when deep-ocean Fe-concentrations were > 4 nM. By contrast, banded iron formations formed when Fe-concentrations were much higher (> 50 μM). Thus, the first widespread development of marine red beds constrains the timing of deep-ocean oxygenation. The evolution of oceanic redox state in the past is poorly known. Here, the authors present a temporal record of banded iron formations and marine red beds, which indicate deep-ocean oxygenation occurred in the middle Ediacaran, coinciding with the onset of widespread marine red beds.
New insights into the nonconserved noncoding region of the subtype-determinant hemagglutinin and neuraminidase segments of influenza A viruses.

UNLABELLED: The noncoding regions (NCRs) of the eight-segmented viral RNAs (vRNAs) of influenza A virus consist of the highly conserved promoter region and the nonconserved segment-specific NCRs at both the 3' and 5' ends. The roles of the segment-specific NCRs of the eight segments have been extensively studied. However, the diversities in the same region of the two subtype-determinant hemagglutinin (HA) and neuraminidase (NA) segments have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs of influenza A viruses and found that nucleotides in the segment-specific NCRs of HA and NA vRNAs are subtype specific and vary significantly in sequence and length at both the 3' and 5' ends among different subtypes. We then systematically studied the biological significance of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes (H1 to H7 and H9) in the context of the WSN (H1N1) reverse genetics system. We found that the HA ssNCRs play a critical role in HA vRNA virion incorporation. Upon HA vRNA incorporation, the 3'-end HA ssNCR plays a more critical role than the 5'-end HA ssNCR, and no stringent compatibility between the two ends is required. Furthermore, our data imply that, in addition to a particular nucleotide(s), the length of the HA ssNCR is involved in regulating HA vRNA incorporation efficiency. These results provide new insights into the HA segment virion incorporation that is critical for the emergence of epidemic and pandemic influenza A virus strains. IMPORTANCE: The nonconserved noncoding regions (NCRs) of the vRNAs of influenza A virus have been extensively studied, whereas the diversities in the nonconserved NCRs of the two subtype-determinant segments hemagglutinin (HA) and neuraminidase (NA) have received little attention. In this study, we bioinformatically analyzed all available NCRs of HA and NA vRNAs and discovered that the HA and NA vRNAs contain key subtype signatures in the NCRs. Our functional studies of the HA subtype-specific NCRs (HA ssNCRs) of the common HA subtypes in the context of WSN virus (H1N1) demonstrated that the HA ssNCR modulates virus replication efficiency by influencing HA segment virion incorporation. Moreover, we revealed important features of the HA ssNCR in determining HA vRNA incorporation efficiency. These data not only show new genetic characteristics of influenza A viruses, but also provide further evidence for understanding the selective genome packaging of influenza virus required for the emergence of epidemic and pandemic influenza virus strains.
Facilitating access to health research through a participatory research register: a feasibility study in outpatient clinics.

BACKGROUND: A research register (Reach West) has been established to facilitate recruitment of people and patients to health-related research. We conducted a prospective feasibility study to investigate the practicality of recruiting through outpatient clinics. METHODS: Patients over 18 years of age attending dental, eye or oncology outpatient clinics in an acute hospital in the West of England were provided with the opportunity to participate in Reach West. In Phase I, recruitment packs were handed to clinic attendees who could place completed consent forms in secure drop-box or return them later on-line or by post. In Phase II, recruitment packs were posted directly to patients with consent forms to be returned by post or on-line. Response rates by age, sex, postcode (for level of deprivation), and clinic type were recorded for those agreeing to participate on paper or on-line. RESULTS: In Phase I, 2,314 of 4,500 (51.4%) of recruitment packs were handed out to clinic attendees, and 114 (5%) consented to join Reach West. In Phase II, 7,173 of 9000 packs were posted (79.7%), and 387 (5.4%) consented to participate. The overall consent rate was 6% (580), with the majority doing so on paper (87%) rather than on-line. The sample was balanced by sex, but mostly comprised people over 50 years located in less deprived postcodes. Non-staff costs for postal recruitment were lower than hand-outs in clinic (£6.84 compared with £8.05 per participant). CONCLUSIONS: Recruiting participants to the Reach West register was feasible among those with oncology, dental or eye outpatient appointments by post or with packs given out in the clinic. Response rates were similar to those achieved for other registers. Recruitment of participants can be achieved through outpatient clinics but other strategies will also be required to attract large numbers of participants and more diverse populations.
Crystal structure of the lytic CHAP(K) domain of the endolysin LysK from Staphylococcus aureus bacteriophage K.

BACKGROUND: Bacteriophages encode endolysins to lyse their host cell and allow escape of their progeny. Endolysins are also active against Gram-positive bacteria when applied from the outside and are thus attractive anti-bacterial agents. LysK, an endolysin from staphylococcal phage K, contains an N-terminal cysteine-histidine dependent amido-hydrolase/peptidase domain (CHAP(K)), a central amidase domain and a C-terminal SH3b cell wall-binding domain. CHAP(K) cleaves bacterial peptidoglycan between the tetra-peptide stem and the penta-glycine bridge. METHODS: The CHAP(K) domain of LysK was crystallized and high-resolution diffraction data was collected both from a native protein crystal and a methylmercury chloride derivatized crystal. The anomalous signal contained in the derivative data allowed the location of heavy atom sites and phase determination. The resulting structures were completed, refined and analyzed. The presence of calcium and zinc ions in the structure was confirmed by X-ray fluorescence emission spectroscopy. Zymogram analysis was performed on the enzyme and selected site-directed mutants. RESULTS: The structure of CHAP(K) revealed a papain-like topology with a hydrophobic cleft, where the catalytic triad is located. Ordered buffer molecules present in this groove may mimic the peptidoglycan substrate. When compared to previously solved CHAP domains, CHAP(K) contains an additional lobe in its N-terminal domain, with a structural calcium ion, coordinated by residues Asp45, Asp47, Tyr49, His51 and Asp56. The presence of a zinc ion in the active site was also apparent, coordinated by the catalytic residue Cys54 and a possible substrate analogue. Site-directed mutagenesis was used to demonstrate that residues involved in calcium binding and of the proposed active site were important for enzyme activity. CONCLUSIONS: The high-resolution structure of the CHAP(K) domain of LysK was determined, suggesting the location of the active site, the substrate-binding groove and revealing the presence of a structurally important calcium ion. A zinc ion was found more loosely bound. Based on the structure, we propose a possible reaction mechanism. Future studies will be aimed at co-crystallizing CHAP(K) with substrate analogues and elucidating its role in the complete LysK protein. This, in turn, may lead to the design of site-directed mutants with altered activity or substrate specificity.
C-terminal domain of mammalian complexin-1 localizes to highly curved membranes.

In presynaptic nerve terminals, complexin regulates spontaneous "mini" neurotransmitter release and activates Ca(2+)-triggered synchronized neurotransmitter release. We studied the role of the C-terminal domain of mammalian complexin in these processes using single-particle optical imaging and electrophysiology. The C-terminal domain is important for regulating spontaneous release in neuronal cultures and suppressing Ca(2+)-independent fusion in vitro, but it is not essential for evoked release in neuronal cultures and in vitro. This domain interacts with membranes in a curvature-dependent fashion similar to a previous study with worm complexin [Snead D, Wragg RT, Dittman JS, Eliezer D (2014) Membrane curvature sensing by the C-terminal domain of complexin. Nat Commun 5:4955]. The curvature-sensing value of the C-terminal domain is comparable to that of α-synuclein. Upon replacement of the C-terminal domain with membrane-localizing elements, preferential localization to the synaptic vesicle membrane, but not to the plasma membrane, results in suppression of spontaneous release in neurons. Membrane localization had no measurable effect on evoked postsynaptic currents of AMPA-type glutamate receptors, but mislocalization to the plasma membrane increases both the variability and the mean of the synchronous decay time constant of NMDA-type glutamate receptor evoked postsynaptic currents.
Preferential Formulation of Second Generation Antipsychotic Asenapine as Inclusion Complex with Sulphobutylether-βCD (Captisol): In vitro and In vivo Evaluation.

BACKGROUND: Asenapine is an anti-psychotic agent approved by the US-FDA for treatment of acute schizophrenia and manic or bipolar I disorder in adults. It is poorly absorbed when administered orally, hence exhibits poor oral bioavailability, which limits its use in clinical practice. OBJECTIVE: Enhancement in solubility of asenapine through complexation with three different cyclodextrins, viz. βCD, HPβCD and sulphobutylether-βCD (Captisol®) was attempted and compared due to its poor bioavailability. METHOD: Kneading method was used for preparation of inclusion complexes which were characterized by FTIR, DSC, and XRD methods. Extent of binding and stability of the 1:1 inclusion complexes were evaluated by molecular modelling and phase solubility studies. Pharmacokinetic studies were also carried out of these inclusion complexes. RESULTS: Captisol® complex was the most stable amongst all complexes showing 4.9 times solubility enhancement of asenapine and 96% drug release at the end of 60 min, whereas asenapine maleate (uncomplexed drug) was released completely at the end of 120min. The Cmax and AUC values of Captisol® asenapine complex (AS-Captisol complex) were 2.8 and 2.3 times higher than the uncomplexed drug. CONCLUSION: This study thus demonstrated that Captisol® inclusion complex is an effective strategy for solubility and bioavailability enhancement of asenapine.
A Computational Model for Docking of Noncompetitive Neuraminidase Inhibitors and Probing their Binding Interactions with Neuraminidase of Influenza Virus H5N1.

BACKGROUND: With cases of emergence of drug resistance to the current competitive inhibitors of neuraminidase (NA) such as oseltamivir and zanamavir, there is a present need for an alternative approach in the treatment of avian influenza. With this in view, some flavones and chalcones were designed based on quercetin, the most active naturally occurring noncompetitive inhibitor. OBJECTIVE: We attempt to understand the binding of quercetin to H5N1-NA, and synthetic analogs of quercetin namely flavones and its precursors the chalcones using computational tools. METHODS: Molecular docking was done using Libdock. Molecular dynamics (MD) simulations were performed using Amber14. We synthesized the two compounds; their structures were confirmed by infrared spectroscopy, 1H-NMR, and mass spectrometry. These molecules were then tested for H5N1-NA inhibition and kinetics of inhibition. RESULTS: Molecular docking studies yielded two compounds i.e., 4'-methoxyflavone and 2'-hydroxy-4-methoxychalcone, as promising leads which identified them as binders of the 150-cavity of NA. Furthermore, MD simulation studies revealed that quercetin and the two compounds bind and hold the 150 loop in its open conformation, which ultimately perturbs the binding of sialic acid in the catalytic site. Estimation of the free energy of binding by MM-PBSA portrays quercetin as more potent than chalcone and flavone. These molecules were then determined as non-competitive inhibitors from the Lineweaver-Burk plots rendered from the enzyme kinetic studies. CONCLUSION: We conclude that non-competitive type of inhibition, as shown in this study, can serve as an effective method to block NA and evade the currently seen drug resistance.
Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior.

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system. Molecular Psychiatry advance online publication, 14 February 2017; doi:10.1038/mp.2017.7.
Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.

In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10(-3)M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer.