Miracle-dz/UniFAR-FTUs huggingface dataset:
Migratory defect of mesencephalic dopaminergic neurons in developing reeler mice

Reelin, an extracellular glycoprotein has an important role in the proper migration and positioning of neurons during brain development. Lack of reelin causes not only disorganized lamination of the cerebral and cerebellar cortex but also malpositioning of mesencephalic dopaminergic (mDA) neurons. However, the accurate role of reelin in the migration and positioning of mDA neurons is not fully elucidated. In this study, reelin-deficient reeler mice exhibited a significant loss of mDA neurons in the substantia nigra pars compacta (SNc) and a severe alteration of cell distribution in the retrorubal field (RRF). This abnormality was also found in Dab1-deficinet, yotari mice. Stereological analysis revealed that total number of mDA neurons was not changed compared to wild type, suggesting that the loss of mDA neurons in reeler may not be due to the neurogenesis of mDA neurons. We also found that formation of PSA-NCAM-positive tangential nerve fibers rather than radial glial fibers was greatly reduced in the early developmental stage (E14.5) of reeler. These findings provide direct evidence that the alteration in distribution pattern of mDA neurons in the reeler mesencephalon mainly results from the defect of the lateral migration using tangential fibers as a scaffold.
Excitotoxic Amino Acid Injections into the Medial Amygdala Facilitate Maternal Behavior in Virgin Female Rats

The inhibitory role of the medial amygdala (MA) in maternal behavior control was explored. Injections of N-methyl-D,L-aspartic acid (NMA), an excitotoxic amino acid, into the MA resulted in a dramatic facilitation of maternal behavior in virgin female rats when pups were presented to them 12 days following the injections. This effect was specific to MA in that NMA injections into the basolateral amygdala were ineffective. The facilitatory effect of NMA injections into MA was found to be hormone dependent in that ovariectomies abolished the effect. Subsequent experiments provided evidence that NMA injections into MA induced a pseudopregnant state lasting about 13 days, and that maternal behavior was greatly facilitated only when pups were presented to such females coincident with pseudopregnancy termination. When pups were presented 24 days following injections of NMA into MA, rather than 12 days, only a modest facilitation of maternal behavior was observed. It was concluded that NMA injections into MA influence maternal behavior in two ways: By inducing an hormonal state stimulatory for maternal behavior and by removing neural inhibition over maternal behavior.
Human-level concept learning through probabilistic program induction

Handwritten characters drawn by a model Not only do children learn effortlessly, they do so quickly and with a remarkable ability to use what they have learned as the raw material for creating new stuff. Lake et al. describe a computational model that learns in a similar fashion and does so better than current deep learning algorithms. The model classifies, parses, and recreates handwritten characters, and can generate new letters of the alphabet that look “right” as judged by Turing-like tests of the model's output in comparison to what real humans produce. Science, this issue p. 1332 Combining the capacity to handle noise with probabilistic learning yields humanlike performance in a computational model. People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms—for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world’s alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches. We also present several “visual Turing tests” probing the model’s creative generalization abilities, which in many cases are indistinguishable from human behavior.
Effect of lactation stage and concurrent pregnancy on milk composition in the bottlenose dolphin

Although many toothed whales (Cetacea: Odontoceti) lactate for 2–3 years or more, it is not known whether milk composition is affected by lactation stage in any odontocete species. We collected 64 pooled milk samples spanning 1–30 months postpartum from three captive bottlenose dolphins Tursiops truncatus. Milks were assayed for water, fat, crude protein (TN × 6.38) and sugar; gross energy was calculated. Ovulation and pregnancy were determined via monitoring of milk progesterone. Based on analysis of changes in milk composition for each individual dolphin, there were significant increases (P<0.05) in fat (in all three dolphins) and crude protein (in two of three), and a decrease (P<0.05) in water (in two of three) over the course of lactation, but the sugar content did not change. In all three animals, the energy content was positively correlated with month of lactation, but the percentage of energy provided by crude protein declined slightly but significantly (P<0.05). At mid-lactation (7–12 months postpartum, n=17), milk averaged 73.0±1.0% water, 12.8±1.0% fat, 8.9±0.5% crude protein, 1.0±0.1% sugar, 1.76±0.09 kcal g−1 (=7.25 kJ g−1) and 30.3±1.3% protein:energy per cent. This protein:energy per cent was surprisingly high compared with other cetaceans and in relation to the growth rates of calves. Milk progesterone indicated that dolphins ovulated and conceived between 413 and 673 days postpartum, following an increase in milk energy density. The significance of these observed compositional changes to calf nutrition will depend on the amounts of milk produced at different stages of lactation, and how milk composition and yield are influenced by sampling procedure, maternal diet and maternal condition, none of which are known.
Antioxidant indices and amino acid composition of phenolic containing Lima beans (Phaseolus lunatus) after simulated human gastrointestinal digestion

The present investigation was designed to characterize the phenolic profile of Lima beans ( Phaseolus Lunatus) and also to evaluate the antioxidant indices: total phenolic content (TPC), total flavonoid content (TFC), ferric reducing antioxidant power (FRAP), 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and amino acid composition at different stages of simulated gastrointestinal digestion (oral, gastric, intestinal). High Performance Liquid Chromatography (HPLC-DAD) analysis revealed the presence of some phenolic compounds (gallic acid, catechin, caffeic acid, rutin, quercitrin, quercetin, kaempferol and apigenin), with a reduced amount (mg/g) after cooking; gallic acid (raw: 1.96 ± 0.02; cooked: 1.82 ± 0.01); catechin (raw: 0.83 ± 0.01; cooked: 0.73 ± 0.01); rutin (raw: 2.61 ± 0.03; cooked:1.74 ±0.03); quercitrin (raw: 5.73 ± 0.01; cooked: 5.68 ± 0.01); apigenin (raw: 2.09 ±0.01; cooked:1.79 ± 0.02), with exception of quercetin (raw: 2.11 ±0.02; cooked: 5.73 ± 0.02) and caffeic acid (raw: 2.08 ±0.04; cooked: 2.95 ± 0.04) . The results of antioxidant indices of in vitro enzyme digested lima beans revealed higher values for cooked Lima beans compared to the raw counterpart, with a stepwise increase at the differe nt stages of in vitro digestion, with the exception of ferric reducing antioxidant power; TPC (oral digestion: 65.44 ± 0.96; gastric digestion: 134.87 ± 0.46; intestinal digestion: 517.72 ± 4.70; mg/g tannic acid equivalent), TFC ( oral digestion: 199.30 ± 6.43 ; gastric digestion: 1065.97 ± 1.22; intestinal digestion: 3691.87 ± 4.2; mg/g quercetin equivalent), DPPH ( oral digestion: 85800.00 ± 305.50 ; gastric digestion: 99066.66 ± 115.47 ; intestinal digestion: 211354.20 ± 360.84 µmol TE/g sample ) . The results also revealed a progressive increase in the antioxidant indices and amino acid composition (mg/kg) for both raw and processed lima beans at various stages of the in vitro digestion, with the intestinal phase of simulated digestion ranking higher. This implied that the Lima beans contained some essential amino acids and antioxidant molecules that would be readily available after passing through the gastrointestinal tract and could therefore be explored as functional food in the management of free radical mediated diseases.
Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition

Background and aims: The effect of adiponectin on colorectal carcinogenesis has been proposed but not fully investigated. We investigated the effect of adiponectin deficiency on the development of colorectal cancer. Methods: We generated three types of gene-deficient mice (adiponectin-deficient, adiponectin receptor 1-deficient, and adiponectin receptor 2-deficient) and investigated chemical-induced colon polyp formation and cell proliferation in colon epithelium. Western blot analysis was performed to elucidate the mechanism which affected colorectal carcinogenesis by adiponectin deficiency. Results: The numbers of colon polyps were significantly increased in adiponectin-deficient mice compared with wild-type mice fed a high-fat diet. However, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. A significant increase in cell proliferative activity was also observed in the colonic epithelium of the adiponectin-deficient mice when compared with wild-type mice fed a high-fat diet; however, no difference was observed between wild-type and adiponectin-deficient mice fed a basal diet. Similarly, an increase in epithelial cell proliferation was observed in adiponectin receptor 1-deficient mice, but not in adiponectin receptor 2-deficient mice. Western blot analysis revealed activation of mammalian target of rapamycin, p70 S6 kinase, S6 protein and inactivation of AMP-activated protein kinase in the colon epithelium of adiponectin-deficient mice fed with high-fat diet. Conclusions: Adiponectin suppresses colonic epithelial proliferation via inhibition of the mammalian target of the rapamycin pathway under a high-fat diet, but not under a basal diet. These studies indicate a novel mechanism of suppression of colorectal carcinogenesis induced by a Western-style high-fat diet.
Rapid characterisation of hERG channel kinetics I: using an automated high-throughput system

Predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug-development, and requires a deep understanding of a compound’s action on ion channels. In vitro hERG-channel current recordings are an important step in evaluating the pro-arrhythmic potential of small molecules, and are now routinely performed using automated high-throughput patch clamp platforms. These machines can execute traditional voltage clamp protocols aimed at specific gating processes, but the array of protocols needed to fully characterise a current is typically too long to be applied in a single cell. Shorter high-information protocols have recently been introduced which have this capability, but they are not typically compatible with high-throughput platforms. We present a new high-information 15 s protocol to characterise hERG (Kv11.1) kinetics, suitable for both manual and high-throughput systems. We demonstrate its use on the Nanion SyncroPatch 384PE, a 384 well automated patch clamp platform, by applying it to CHO cells stably expressing hERG1a. From these recordings we construct 124 cell-specific variants/parameterisations of a hERG model at 25 °C. A further 8 independent protocols are run in each cell, and are used to validate the model predictions. We then combine the experimental recordings using a hierarchical Bayesian model, which we use to quantify the uncertainty in the model parameters, and their variability from cell to cell, which we use to suggest reasons for the variability. This study demonstrates a robust method to measure and quantify uncertainty, and shows that it is possible and practical to use high-throughput systems to capture full hERG channel kinetics quantitatively and rapidly. Statement of Significance We present a method for high-throughput characterisation of hERG potassium channel kinetics, via fitting a mathematical model to results of over one hundred single cell patch clamp measurements collected simultaneously on an automated voltage clamp platform. The automated patch clamp data are used to parameterise a mathematical ion channel model fully, opening a new era of automated and rapid development of mathematical models from quick and cheap experiments. The method also allows ample data for independent validation of the models and enables us to study experimental variability and propose its origins. In future the method can be applied to characterise changes to hERG currents in different conditions, for instance at different temperatures (see Part II of the study) or under mutations or the action of pharmaceuticals; and should be easily adapted to study many other currents.
Topology Change in ( 2 + 1 )-Dimensional Gravity

In (2+1)-dimensional general relativity, the path integral for a manifold M can be expressed in terms of a topological invariant, the Ray-Singer torsion of a flat bundle over M . For some manifolds, this makes an explicit computation of transition amplitudes possible. In this paper, we evaluate the amplitude for a simple topology-changing process. We show that certain amplitudes for spatial topology change are nonvanishing—in fact, they can be infrared divergent—but that they are infinitely suppressed relative to similar topology-preserving amplitudes. ∗email: carlip@dirac.ucdavis. edu †email: cosgrove@bethe.ucdavis. edu
Relevance of early stretching in overhead athletes

Overhead athletes often develop, over time, a tightness of the posterior structures of the shoulder, which may be associated with injuries. Ten symptomatic (with pain) and ten asymptomatic players with a tight shoulder were compared and the effect of a selfapplied stretching program was evaluated. Before and after the stretching program, pain and stiffness of the shoulder were evaluated. Our results demonstrate that risk factors for shoulder pain such as glenohumeral internal rotation deficit and total range of motion deficit may only be limited in symptomatic athletes. The mobility of the shoulder was significantly improved after the stretching program for both groups. Pain was reduced when present. Because of the limited differences between the symptomatic and asymptomatic athletes, clinicians may find it advantageous to initiate early prevention or rehabilitation programs.
High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy

Resistance to tamoxifen in breast cancer patients is a serious therapeutic problem and major efforts are underway to understand underlying mechanisms. Resistance can be either intrinsic or acquired. We derived a series of subcloned MCF7 cell lines that were either highly sensitive or naturally resistant to tamoxifen and studied the factors that lead to drug resistance. Gene-expression studies revealed a signature of 67 genes that differentially respond to tamoxifen in sensitive vs. resistant subclones, which also predicts disease-free survival in tamoxifen-treated patients. High-throughput cell-based screens, in which >500 human kinases were independently ectopically expressed, identified 31 kinases that conferred drug resistance on sensitive cells. One of these, HSPB8, was also in the expression signature and, by itself, predicted poor clinical outcome in one cohort of patients. Further studies revealed that HSPB8 protected MCF7 cells from tamoxifen and blocked autophagy. Moreover, silencing HSBP8 induced autophagy and caused cell death. Tamoxifen itself induced autophagy in sensitive cells but not in resistant ones, and tamoxifen-resistant cells were sensitive to the induction of autophagy by other drugs. These results may point to an important role for autophagy in the sensitivity to tamoxifen.
A game theoretic study of energy efficient cooperative wireless networks

In wireless networks, it is well-known that intermediate nodes can be used as cooperative relays to reduce the transmission energy required to reliably deliver a message to an intended destination. When the network is under a central authority, energy allocations and cooperative pairings can be assigned to optimize the overall energy efficiency of the network. In networks with autonomous selfish nodes, however, nodes may not be willing to expend energy to relay messages for others. This problem has been previously addressed through the development of extrinsic incentive mechanisms, e.g., virtual currency, or the insertion of altruistic nodes in the network to enforce cooperative behavior. This paper considers the problem of how selfish nodes can decide on an efficient energy allocation and endogenously form cooperative partnerships in wireless networks without extrinsic incentive mechanisms or altruistic nodes. Using tools from both cooperative and non-cooperative game theory, the three main contributions of this paper are (i) the development of Pareto-efficient cooperative energy allocations that can be agreed upon by selfish nodes, based on axiomatic bargaining techniques, (ii) the development of necessary and sufficient conditions under which "natural" cooperation is possible in systems with fading and non-fading channels with- out extrinsic incentive mechanisms or altruistic nodes, and (iii) the development of techniques to endogenously form cooperative partnerships without central control. Numerical results with orthogonal amplify-and-forward cooperation are also provided to quantify the energy efficiency of a wireless network with sources selfishly allocating transmission/relaying energy and endogenously forming cooperative partnerships with respect to a network with centrally optimized energy allocations and pairing assignments.
Constraining the cosmological parameters with the gas mass fraction in local and $\mathsf{{\vec z}>0.7}$ galaxy clusters

We present a study of the baryonic fraction in galaxy clusters aimed at constraining the cosmological parameters $\Omega_{\rm m}$, $\Omega_{\Lambda}$ and the ratio between the pressure and density of the “dark” energy, w . We use results on the gravitating mass profiles of a sample of nearby galaxy clusters observed with the BeppoSAX X-ray satellite (Ettori et al. 2002) to set constraints on the dynamical estimate of $\Omega_{\rm m}$. We then analyze Chandra observations of a sample of eight distant clusters with redshift in the range 0.72 and 1.27 and evaluate the geometrical limits on the cosmological parameters $\Omega_{\rm m}$, $\Omega_{\Lambda}$ and w by requiring that the gas fraction remains constant with respect to the look-back time. By combining these two independent probability distributions and using a priori distributions on both $\Omega_{\rm b}$ and H 0 peaked around primordial nucleosynthesis and HST-Key Project results respectively, we obtain that, at 95.4 per cent level of confidence, (i) $w < -0.49$, (ii) $\Omega_{\rm m} = 0.34^{+0.11}_{-0.05}$, $\Omega_{\Lambda} = 1.30^{+0.44}_{-1.09}$ for $w=-1$ (corresponding to the case for a cosmological constant), and (iii) $\Omega_{\rm m} = 1-\Omega_{\Lambda} = 0.33^{+0.07}_{-0.05}$ for a flat Universe. These results are in excellent agreement with the cosmic concordance scenario which combines constraints from the power spectrum of the Cosmic Microwave Background, the galaxy and cluster distribution, the evolution of the X-ray properties of galaxy clusters and the magnitude-redshift relation for distant type Ia supernovae. By combining our results with the latter method we further constrain $\Omega_{\Lambda} =0.94^{+0.30}_{-0.30}$ and $w < -0.89$ at the $2 \sigma$ level.
Does intermittent sun exposure cause basal cell carcinoma? a case‐control study in Western Australia

Our report deals with the relationship of pattern and timing of sun exposure to basal cell carcinoma (BCC) in a population‐based case‐control study conducted in Western Australia in 1988. The main measure of intermittent exposure was based on the amount of exposure on non‐working days relative to that over the whole week. Outdoor recreational activities, holidays and sunburn were also considered to be markers of intermittent exposure. We observed a statistically significant increase in risk of BCC with increasing proportion of weekly sun exposure obtained at the weekend, especially in late teenage (OR = 3.9, 95% CI 1.9‐7.8 for maximum intermittency of exposure), exposure of the site of skin cancer during holidays (OR = 1.9, 95% CI 1.1‐3.1 for the highest exposure quarter) and sunburn to the site (ORs of 1.8 for 3‐10 and 1.5 for 11+ sunburns in a lifetime). Risk of BCC increased substantially with increasing intermittency in poor tanners but not at all in good tanners. Our data suggest that a particular amount of sun exposure delivered in infrequent, probably intense increments will increase risk of BCC more than a similar dose delivered more continuously over the same total period of time.
Oral Glucose Tolerance Test in Healthy Pregnant Nigerian Women

Oral glucose tolerance tests (OGTTs) with 75 g glucose were performed in 20 healthy pregnant Nigerian women in each trimester of pregnancy and the puerperium; 34 nonpregnant control subjects matched for age and parity were also studied. The blood glucose levels from fasting to 60 min were lower in pregnant subjects, but the 90- and 120-min values were higher. The highest blood glucose values were observed in the first trimester with an apparent improvement in glucose tolerance in the second and third trimesters. This observation is strikingly different from the established pattern of OCTT in pregnant Caucasian women. With pooled data from OGTT results in the three trimesters for the 20 pregnant women (60 OGTTs), a statistically derived criterion (based on mean + 2SD approximated to the nearest 5) for the interpretation of OGTT in pregnant Nigerian women was devised. This criterion defines the upper limits of normal for venous wholeblood glucose in pregnant Nigerian women during an OGTT with a 75-g glucose load as follows: fasting, 90; 30 min, 135; 60 min, 150; 90 min, 145; and 120 min, 125 mg/dl. These values are lower than those recommended for pregnant women by the National Diabetes Data Group (O'Sullivan and Mahan criteria) and the World Health Organization. The results from this study underscore the need for caution regarding uncritical application of data from one racial or ethnic group to others.