Null Pairs Research Articles

Cluster effect for SNP–SNP interaction pairs for predicting complex traits

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Laboratory observation of electron energy distribution near three-dimensional magnetic nulls

The acceleration of electrons near three-dimensional (3D) magnetic nulls is crucial to the energy conversion mechanism in the 3D magnetic reconnection process. To explore electron acceleration in a 3D magnetic null topology, we constructed a pair of 3D magnetic nulls in the PKU Plasma Test (PPT) device and observed acceleration of electrons near magnetic nulls. This study measured the plasma floating potential and ion density profiles around the 3D magnetic null. The potential wells near nulls may be related to the energy variations of electrons, so we measured the electron distribution functions (EDFs) at different spatial positions. The axial variation of EDF shows that the electrons deviate from the Maxwell distribution near magnetic nulls. With scanning probes that can directionally measure and theoretically analyze based on curve fitting, the variations of EDFs are linked to the changes of plasma potential under 3D magnetic null topology. The kinetic energy of electrons accelerated by the electric field is 6 eV ( ) and the scale of the region where accelerating electrons exist is in the order of serval electron skin depths.

Three-dimensional magnetic reconnection in complex multiple X-point configurations in an ancient solar–lunar terrestrial system

Magnetic reconnection processes in three-dimensional (3D) complex field configurations have been investigated in different magneto-plasma systems in space, laboratory, and astrophysical systems. Two-dimensional (2D) features of magnetic reconnection have been well developed and applied successfully to systems with symmetrical property, such as toroidal fusion plasmas and laboratory experiments with an axial symmetry. But in asymmetric systems, the 3D features are inevitably different from those in the 2D case. Magnetic reconnection structures in multiple celestial body systems, particularly star–planet–Moon systems, bring fresh insights to the understanding of the 3D geometry of reconnection. Thus, we take magnetic reconnection in an ancient solar–lunar terrestrial magneto-plasma system as an example by using its crucial parameters approximately estimated already and also some specific applications in pathways for energy and matter transports among Earth, ancient Moon, and the interplanetary magnetic field (IMF). Then, magnetic reconnection of the ancient lunar–terrestrial magnetospheres with the IMF is investigated numerically in this work. In a 3D simulation for the Earth–Moon–IMF system, topological features of complex magnetic reconnection configurations and dynamical characteristics of magnetic reconnection processes are studied. It is found that a coupled lunar-terrestrial magnetosphere is formed, and under various IMF orientations, multiple X-points emerge at distinct locations, showing three typical magnetic reconnection structures in such a geometry, i.e., the X-line, the triple current sheets, and the A–B null pairs. The results can conduce to further understanding of reconnection physics in 3D for plasmas in complex magnetic configurations, and also a possible mechanism for energy and matters transport in evolutions of similar astrophysical systems.

Thymidylate Synthase Inhibition with Capped F10 Is Effective in TP53 Null Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is an aggressive cancer of the myeloid linage characterized by progressive marrow failure and death. Responses to therapy are between 50 and 80% but relapse is common and salvage rates once relapsed are low. The risk of relapse is greatly influenced by specific somatic mutations. One of the highest risk mutations in AML involves loss of the tumor suppressor TP53. Patients with AML harboring loss of TP53 function have a dismal prognosis and there is a clear need for new approaches. To identify novel agents with activity against TP53 null AML, a TP53 null and WT isogenic cell line pair was generated using CRISPR/CAS9 in a genetically defined murine AML cell line. Clonal isolates were generated by serial dilution and loss of detectable TP53 was confirmed by Western blotting. A high throughput screen of currently FDA approved agents was performed on these cell lines. When agents were ranked by equal cytotoxicity against TP53 null and WT AML cells 20% (6/30) of the top 30 agents either directly targeted thymidylate synthase or its substrates via inhibition of the folate cycle. This finding suggests that thymidylate synthase (TS) is a key enzyme in TP53 null AML cells. To confirm and extend these results, an additional murine AML TP53 null/WT cell line pair was generated. Chemotherapy resistance was confirmed in the TP53 null cell lines when treated with doxorubicin (Figure 1). Capped F10 (CF10) is a second generation fluoropyrimidine oligonucleotide that is a highly potent inhibitor of TS. In contrast to doxorubicin, CF10 treatment resulted in significant cell death when dosed in the low picomolar range with minimal differences between the null and WT cell lines (Figure 1). To extend this result TP53 null cells were injected into syngeneic recipients and upon engraftment mice were treated with CF10 at 300mg/kg twice weekly or doxorubicin 3mg/kg and cytarabine at 100 mg/kg daily for 5 days. CF10 provided a significant survival benefit in the TP53 null AML in this highly aggressive model where doxorubicin and cytarabine did not (p=0.0057, Figure 2). To confirm a TP53 independent mechanism, competition assays were performed with CAS9 expressing AML cells partially infected with a vector expressing an sgRNA targeting TP53 and containing a GFP reporter. When the mixed population was treated with a titration of doxorubicin there was a highly significant increase in GFP+ cells indicating the involvement of TP53 in doxorubicin mediated cell death. In contrast when cells were treated with a titration of CF10 there was a no significant increase in GFP+ population consistent with CF10 inducing a TP53 independent mechanism of cell death. For CF10 to of use clinically there must be an acceptable therapeutic window. Fluoropyrimidine based therapy can be myelosuppressive especially in patients with low dihydropyrimidine dehydrogenase (DPD) activity. To assess the tolerability of CF10, healthy WAG/RAJ rats were treated with the DPD inhibitor ethynyl uracil at 2mg/kg to mimic DPD deficiency. Animals were then treated with repeated doses of either 141 mg/kg CF10 or the molar equivalent of 50 mg/kg 5-flurouracil (5-FU) and weight determined. In contrast to 5-FU, CF10 treated animals maintained their weight compared to controls (data not shown). Taken together these data suggest that TS is a viable target in TP53 null AML and CF10 is well tolerated and provides a survival benefit in a highly aggressive, chemotherapy resistant model. Ongoing studies will explore the mechanisms involved in CF10 induced cell death.

High-Gain Third-Order Filtering Patch Antenna Array With Two Radiation Nulls Using Cross-Radiation

A compact third-order filtering antenna array with high gain and two controllable radiation nulls is proposed. The antenna consists of one narrow patch in the center fed by the coaxial port and four wide patches placed around it. Four shortend stub-loaded resonators are capacitively coupled between the center patch and the outer patches, which makes the radiated Efields of the center patch and the outer patches in-phase at the center frequency of the passband to realize the high gain and outof-phase at the low and high stopbands to introduce a pair of radiation nulls. The working principle of the filtering antenna array can be explained by the coupled-resonator network. Finally, a filtering antenna array centered at 3.5 GHz with a fractional bandwidth of 4.26%, a high maximum gain of 12.2 dBi, high out-of-band selectivity, and wide stopband is designed, fabricated, and measured.

Capped F10, a novel DNA directed fluoropyrimidine, in TP53 mutated acute myeloid leukemia (AML).

7046 Background: Acute myeloid leukemia (AML) is an aggressive malignancy characterized by resistance to treatment and poor outcomes. One of the most devastating mutations in AML involves loss of the tumor suppressor TP53. AML harboring this loss carries a dismal prognosis and there is a clear need for new approaches. Methods: To identify new therapeutics, a TP53 null and WT isogenic cell line pair was generated using CRISPR/CAS9 using a murine AML cell line. Clonal isolates were obtained and loss of detectable TP53 was confirmed by Western Blotting. A high throughput screen of currently FDA approved anticancer agents was performed. Results: When agents were ranked by equal cytotoxicity against TP53 null and WT AML cells 20% (6/30) of the top 30 agents targeted the folate/thymidylate synthase axis. This suggests that thymidylate synthase (TS) is a vulnerability in TP53 null AML cells. To confirm TS as a target in TP53 null AML an additional murine AML TP53 null/WT cell line pair was generated using CRISPR/CAS9. When these cell lines were treated with doxorubicin the TP53 null cells were significantly more resistant (p≤0.001 at 10nM). Capped F10 (CF10) is a second generation fluoropyrimidine oligonucleotide that has been shown to be a highly potent inhibitor of TS. In contrast to doxorubicin, CF10 treatment resulted in significant cell death when dosed in the low picomolar range with minimal differences between the null and WT cell lines (p = 0.31 at 50pM). To extend this result TP53 WT or null cells were injected into syngeneic recipients and upon engraftment mice were treated with CF10 at 300mg/kg twice weekly. CF10 provided a significant survival benefit in the TP53 null but not WT injected mice consistent with CF10 having activity against TP53 null AML (p = 0.035 vs 0.13). To confirm a TP53 independent mechanism, competition assays were performed with CAS9 expressing AML cells partially infected with a vector expressing an sgRNA targeting TP53 and a GFP reporter. When the mixed population was treated with the IC90 concentration of 5-fluorouracil there was a highly significant increase in GFP+ cells indicating a TP53 mediated cell death (p = < 0.001). In contrast when cells were treated with the IC90 concentration of CF10 there was a non-significant increase in GFP+ population (p = 0.074) consistent with a mainly TP53 independent mechanism. Fluoropyrimidine based therapy can be myelosuppressive especially in patients with low dihydropyrimidine dehydrogenase (DPD) activity. To assess the tolerability of CF10, healthy WAG/RAJ rats were treated with the DPD inhibitor ethynyl uracil at 2mg/kg alone or in combination with either 141 mg/kg CF10 or the molar equivalent of 50 mg/kg 5-flurouracil (5-FU) and weight determined. In contrast to 5-FU, CF10 treated animals did not have a significant change in weight compared to controls. Conclusions: Taken together these data suggest that CF10 is a promising new agent for TP53 null AML.

Magnetic reconnections as the underlying cause of spontaneous generation and annihilation of three-dimensional magnetic nulls

Three-dimensional (3D) magnetic nulls are preferential sites for triggering solar coronal transients. Although these nulls are abundant in the solar atmosphere, their generation is yet to be thoroughly explored. This paper explores the mechanism of null generation as well as annihilation in detail by means of implicit large eddy simulations where magnetohydrodynamic equations are solved in the absence of an explicit magnetic diffusivity. The magnetofluid is idealized to be thermodynamically inactive, incompressible, and have perfect explicit electrical conductivity. The simulated dynamics is initiated by a prescribed flow in a magnetic configuration having an isolated current-free 3D null. The flow facilitates reconnections, which lead to the generation of primary null pairs in a way that preserves the topological degree. The formation process of these null pairs is novel and different from the standard pitchfork bifurcation. Contrarily, here we found creation of null pairs away from the central null, which we hypothesize is due to the interaction of the imposed flow and the reconnection outflow from the central current layer. Intriguingly, further evolution spontaneously generates new null pairs, which have a novelty by itself. As theorized, these spontaneously generated null pairs also preserve the net topological degree—adding credibility to the simulation. The simulation also shows null pair annihilation. Magnetic reconnections are identified to be responsible for the generation and annihilation of the nulls—opening up the possibility for the nulls to be self-organized structures. Furthermore, the reconnection being ubiquitous in the corona, it can explain the coronal abundance of magnetic nulls.

3D Reconnection Geometries With Magnetic Nulls: Multispacecraft Observations and Reconstructions

AbstractMagnetic reconnection is universal in various plasma environments like the solar atmosphere, planetary magnetosphere, and laboratory to trigger explosive phenomena. Its nature and magnetic structure in two dimensions (2D) have been abundantly analyzed. The three‐dimensional (3D) characteristics of reconnection are different from 2D, and the mysteries of its 3D geometry are under exploration. A critical character in 3D is the presence of magnetic nulls, which is essential when the magnetic field topology is changing. The four identical spacecraft from the Cluster mission enable several methods for analyzing and visualizing the 3D nature of the magnetic structure. In this paper, we focus on reviewing the magnetic topology of the reconnection geometry containing 3D magnetic null points. Applying the fitting‐reconstruction method to Cluster data, magnetic null pairs or multiple magnetic nulls linked by separators or helically wrapped spines are found in the reconnection diffusion region and turbulent outflow region. The reconstructed magnetic structures show that the 2D features are parts of local approximations of the 3D geometries. The 2D regimes of antiparallel and component reconnection can simultaneously occur in 3D separator reconnection. The flux ropes are formed along the spine line or in a region enclosed by wrapped fan surfaces in the presence of spiral null points.

Set-Theoretic Formalism for Treating Ligand-Target Datasets.

Data on ligand–target (LT) interactions has played a growing role in drug research for several decades. Even though the amount of data has grown significantly in size and coverage during this period, most datasets remain difficult to analyze because of their extreme sparsity, as there is no activity data whatsoever for many LT pairs. Even within clusters of data there tends to be a lack of data completeness, making the analysis of LT datasets problematic. The current effort extends earlier works on the development of set-theoretic formalisms for treating thresholded LT datasets. Unlike many approaches that do not address pairs of unknown interaction, the current work specifically takes account of their presence in addition to that of active and inactive pairs. Because a given LT pair can be in any one of three states, the binary logic of classical set-theoretic methods does not strictly apply. The current work develops a formalism, based on ternary set-theoretic relations, for treating thresholded LT datasets. It also describes an extension of the concept of data completeness, which is typically applied to sets of ligands and targets, to the local data completeness of individual ligands and targets. The set-theoretic formalism is applied to the analysis of simple and joint polypharmacologies based on LT activity profiles, and it is shown that null pairs provide a means for determining bounds to these values. The methodology is applied to a dataset of protein kinase inhibitors as an illustration of the method. Although not dealt with here, work is currently underway on a more refined treatment of activity values that is based on increasing the number of activity classes.

Null Darboux Curve Pairs in Minkowski 3-Space

Based on the fundamental theories of null curves in Minkowski 3-space, the null Darboux mate curves of a null curve are defined which can be regarded as a kind of extension for Bertrand curves and Mannheim curves in Minkowski 3-space. The relationships of null Darboux curve pairs are explored and their expression forms are presented explicitly.

Compact dual‐mode wideband MIMO filtering antenna array with high selectivity and improved isolation

A novel compact MIMO dual-mode filtering antenna array with wide bandwidth, high selectivity and good isolation is proposed. The filtering antenna unit consists of a patch radiator at the top layer coupled with a high-order dual-mode filter at the bottom layer through a rectangular slot in the middle ground layer. The fourth-order filter adopts two E-shape dual-mode resonators to achieve wide bandwidth and high selectivity. A pair of filtering antenna units form a MIMO array with a distance of 0.2λg by using three interdigital lines in the middle to enhance the port isolation. Finally, a 1 × 2 MIMO filtering antenna array operating at 2.45 GHz is designed and fabricated, which shows wide fractional bandwidth of 24.5%, sharp skirt slope with a pair of radiation nulls, smooth realized gain of 4.5 dBi as well as high isolation more than 20 dB.

Mannheim B-curve couples in Minkowski 3-space

In this paper, we define null Cartan and pseudo null Mannheim curves in Minkowski 3-space according to their Bishop frames. We obtain the necessary and the sufficient conditions for pseudo null curves to be Mannheim B-curves in terms of their Bishop curvatures. We prove that there are no null Cartan curves in Minkowski 3-space which are Mannheim B-curves, by considering the cases when their Mannheim B-mate curves are spacelike, timelike, null Cartan and pseudo null curves. Finally, we give some examples of pseudo null Mannheim B-curve pairs.

Probabilistic hazard maps for operational use: the case of SO2 air pollution during the Holuhraun eruption (Bárðarbunga, Iceland) in 2014–2015

The Holuhraun fissure eruption (Iceland) in 2014–2015, which originated from the Barðarbunga volcanic system, was exceptional in several respects. It lasted 6 months and, throughout its duration, it released up to 9.6 Mt of SO2 in the atmosphere. The main recorded hazard affecting the entire country over the 6 months was the constant presence of a low-level gas cloud that led to recurrent air pollution episodes. The Icelandic Meteorological Office responded to this human health hazard by (1) setting up a forecasting system to anticipate the distribution of SO2 over Iceland and (2) preparing probabilistic hazard maps to support the decisions taken by the Icelandic Civil Protection in demarcating the accessible area around the eruption site. This paper introduces some technical aspects of the application of the CALPUFF numerical model to this eruption like the SO2 dispersal forecasting setup, the volcanic source numerical description, and the Monte Carlo procedure adopted for the creation of the probabilistic hazard maps. CALPUFF-based maps were created in January 2015, when the eruption was still ongoing, with the assumption that the eruption would be continuing with the same intensity. Maps for the entire country and for a smaller domain were produced, the latter showing the likelihood to exceeding an hourly concentration of 2600 μg/m3 (1 ppm) of SO2 for the spring season, a level chosen by the Icelandic Civil Protection for the delineation of the area of restricted access around the eruption site. As during the eruption there was no time for a rigorous evaluation of the model accuracy, we then undertook a retrospective analysis of CALPUFF model performance comparing the forecasted hourly SO2 concentration with real-time measurements at key-sites. The model did reproduce the hourly observations (the maximum within a 24-running window) with a level of agreement of 50.6% in Mývatn (85 km from the eruption site) and 50.4% in Reykjavik (258 km), when instances of null pairs have been removed. In Mývatn, the model overestimated the concentration more than 22% of the time. In Hofn (104 km), the model accuracy is 81.7% and occurrences of underestimation are higher than 11% of the time. In Reyðarfjorður (at 124 km), the model accuracy is assessed to be 82.7% and the model overestimates occurring 15.1% of the time. Possible explanations for the observed mismatch between model results and measurements include the spatial resolution of meteorological data field, the capability into reproducing chemical reactions of SO2 in atmosphere, and the reduced extension of the numerical domain. In addition, the model performance is strongly dependent on the source descriptors (e.g., strength of the SO2 flux and injection height) that, in this contribution, have been kept constant over long periods—neglecting, in this way, the natural variability of a dynamic emission of SO2. This consideration points toward the need of frequent and high-quality observation data for the initialization of dispersal numerical model. In light of this retrospective analysis, the probabilistic hazard maps possibly over-estimated the area exposed to high level of SO2 concentration. All the same, this paper reports on how quantitative probabilistic hazard mapping can be used for mitigating the health risk of volcanic SO2 emissions during a volcanic crisis to the benefit of operational hazard monitoring in support an effective crisis response.

Filtering dual‐patch antenna with flat gain response using F‐shaped feeding structure

AbstractA novel wideband filtering dual‐patch antenna with a flat gain response is presented in this letter. This filtering antenna mainly consists of two parts: two patches and an F‐shaped feeding structure. The upper and lower patches are fed by two different horizontally placed narrow strips from the F‐shaped structure. Two patch modes are simultaneously excited within the passband, yielding a 29.3% bandwidth with a very flat gain response and a stable radiation pattern. Furthermore, a pair of radiation nulls are generated symmetrically at the two sides of the passband owing to the mutual coupling between two patches. As a result, a filtering antenna without any extra filtering circuit is obtained which achieves a realized gain of 10 dBi within the passband and an out‐of‐band suppression level of 15 dB in the lower stopband and 20 dB in the upper stopband. Compared to the traditional patch antennas, this proposed filtering antenna demonstrates a very flat gain response, a sharp passband skirt, and a good selectivity, which is well designed and very suitable for high band cellular communication (2.0‐2.7 GHz).

Impact of Interpersonal Relationship on Risks Associated with Substance Abuse Among Senior Secondary School Students in Borno State, Nigeria

This study examined the impact of inter-personal relationship risks associated with substance abuse among senior secondary school students in Borno State. The population of the study comprised 25,580 senior secondary school students in Borno State. The schools were stratified into urban and rural. Borno State has a total of 73 schools comprising urban with 48 and rural schools with 25. 40% of the samples were drawn from the population. Thus, 29 schools were selected using simple random sampling technique of fish bowl method to draw 19 urban and 10 rural schools. 10% of the respondents were drawn from the entire population of 25,580 which comprised 15,572 males from single schools, 603 females also from single schools and 398 from mixed schools. A total of 2,558 copies of questionnaire were administered while 2,542 were retrieved. A researcher developed questionnaire was used as instrument for data collection and a reliability index of 0.76 was obtained after pilot tested. Frequency counts and percentages were used to analyse responses. A two-way Factorial Analysis of Variance was used to test the null hypotheses and pair wise comparison test was used to determine where differences existed at 0.05 level of significance. The findings revealed that significant differences existed between school location (urban/rural) and gender (male/female) students in their interpersonal relationship risk associated with substance abuse. It was recommended among others that, the school authority should advice the students to imitate good behaviour from parents, relatives and friends; and Students should be guided to make friends who are of good character and behaviour. Keywords: Impact, Interpersonal Relationship, Risk Associated, Substance Abuse DOI: 10.7176/JEP/11-8-09 Publication date: March 31 st 2020

A three-dimensional model of spiral null pair to form ion-scale flux ropes in magnetic reconnection region observed by Cluster

The magnetic structure and topology of the three-dimensional magnetic reconnection region are significantly dynamic and complex. Small-scale flux ropes and magnetic null points are frequently detected in the reconnection outflow region and diffusion region due to the increased in situ measurements at high temporal cadences. Previous studies have demonstrated that X-line and small-scale flux ropes are both related to null points. In this study, by applying a fitting-reconstruction method with the input of the Cluster dataset, we reveal three types of spiral null pairs that serve as the skeleton of the flux ropes. Two spiral nulls can be connected by a spine, or by a separator, or by both a spine and a separator. A theoretical model is proposed to explain these spiral null pairs. The observational results and the model indicate that the number of magnetic loops of the flux rope is restricted by the linkage pattern of two nulls, while the flux rope is confined by the two nulls and their fan surfaces. The model predicts that the magnetic perturbations in the reconnection region can transform the linkage types of the nulls and eventually lead to the evolution of flux ropes.

Harmonic evolutes of B-scrolls with constant mean curvature in Lorentz–Minkowski space

In this paper, we study harmonic evolutes of [Formula: see text]-scrolls, that is, of ruled surfaces in Lorentz–Minkowski space having no Euclidean counterparts. Contrary to Euclidean space where harmonic evolutes of surfaces are surfaces again, harmonic evolutes of [Formula: see text]-scrolls turn out to be curves. In particular, we show that the harmonic evolute of a [Formula: see text]-scroll of constant mean curvature together with its base curve forms a null Bertrand pair. This allows us to characterize [Formula: see text]-scrolls of constant mean curvature and reconstruct them from a given null curve which is their harmonic evolute.

Absence of Calcitriol Causes Increased Lactational Bone Loss and Lower Milk Calcium but Does Not Impair Post-lactation Bone Recovery in Cyp27b1 Null Mice.

We hypothesized that adaptation to calcium supply demands of pregnancy and lactation do not require calcitriol. Adult Cyp27b1 null mice lack calcitriol and have hypocalcemia, hypophosphatemia, and rickets. We studied wild-type (WT) and null sister pairs raised on a calcium-, phosphorus-, and lactose-enriched "rescue" diet that prevents hypocalcemia and rickets. Bone mineral content (BMC) increased >30% in pregnant nulls, declined 30% during lactation, and increased 30% by 4 weeks post-weaning. WT showed less marked changes. Micro-CT revealed loss of trabecular bone and recovery in both genotypes. In lactating nulls, femoral cortical thickness declined >30%, whereas endocortical perimeter increased; both recovered to baseline after weaning; there were no such changes in WT. Histomorphometry revealed a profound increase in osteoid surface and thickness in lactating nulls, which recovered after weaning. By three-point bend test, nulls had a >50% decline in ultimate load to failure that recovered after weaning. Although nulls showed bone loss during lactation, their milk calcium content was 30% lower compared with WT. Serum parathyroid hormone (PTH) was markedly elevated in nulls at baseline, reduced substantially in pregnancy, but increased again during lactation and remained high post-weaning. In summary, pregnant Cyp27b1 nulls gained BMC with reduced secondary hyperparathyroidism, implying increased intestinal calcium delivery. Lactating nulls lost more bone mass and strength than WT, accompanied by increased osteoid, reduced milk calcium, and worsened secondary hyperparathyroidism. This implies suboptimal intestinal calcium absorption. Post-weaning, bone mass and strength recovered to baseline, whereas BMC exceeded baseline by 40%. In conclusion, calcitriol-independent mechanisms regulate intestinal calcium absorption and trabecular bone metabolism during pregnancy and post-weaning but not during lactation; calcitriol may protect cortical bone during lactation. © 2017 American Society for Bone and Mineral Research.

In-situ observations of flux ropes formed in association with a pair of spiral nulls in magnetotail plasmas

Signatures of secondary islands are frequently observed in the magnetic reconnection regions of magnetotail plasmas. In this paper, magnetic structures with the secondary-island signatures observed by Cluster are reassembled by a fitting-reconstruction method. The results show three-dimensionally that a secondary island event can manifest the flux rope formed with an As-type null and a Bs-type null paired via their spines. We call this As-spine-Bs-like configuration the helically wrapped spine model. The reconstructed field lines wrap around the spine to form the flux rope, and an O-type topology is therefore seen on the plane perpendicular to the spine. Magnetized electrons are found to rotate on and cross the fan surface, suggesting that both the torsional-spine and the spine-fan reconnection take place in the configuration. Furthermore, detailed analysis implies that the spiral nulls and flux ropes were locally generated nearby the spacecraft in the reconnection outflow region, indicating that secondary reconnection may occur in the exhaust away from the primary reconnection site.

The effects of weak versus strong relational judgments on response bias in Two-Alternative-Forced-Choice recognition: Is the test criterion-free?

It is widely believed that a Two-Alternative-Forced-Choice (2AFC) in an old/new recognition memory test is made by comparing the two items and choosing the item with the higher strength. For this reason, it is considered to be criterion-free by some researchers. We found evidence that subjects probabilistically compromised the comparison by choosing the left item when they recognized it as old. Using both normal test pairs (comprised of one new and one old item) and two types of null pairs (comprised of both-new or both-old items), we found that a left-biased choice was coupled with higher hit and false alarm rates and a shorter left than right-choice RT for the normal pairs, consistent with the hypothesis of a bias for making a choice on the basis of a left individual-item recognition. For the null pairs, RT was much longer for the both-new than for the both-old pairs, providing additional evidence for basing decision on an individual-item's absolute, rather than a relative, familiarity. Additionally, subjects gave higher confidence ratings to choices for the both-old than the normal and both-new pairs, again suggesting that their decision was based on absolute familiarity of the items. The results were found to be not due to a fast-response instruction. A comparative judgment experiment in which subjects chose the item higher or lower in an attribute magnitude did not show the response side bias and RT asymmetry. The presence of bias in the former, and the absence of it in the latter can be explained by a weak versus strong relational judgment in the former and the latter type of 2AFC, respectively. We discuss the implications these findings have for the use of the 2AFC as a method for testing recognition memory.