Miracle-dz/UniFAR-FTUs huggingface dataset:
Ancient DNA analyses exclude humans as the driving force behind late Pleistocene musk ox (Ovibos moschatus) population dynamics

The causes of the late Pleistocene megafaunal extinctions are poorly understood. Different lines of evidence point to climate change, the arrival of humans, or a combination of these events as the trigger. Although many species went extinct, others, such as caribou and bison, survived to the present. The musk ox has an intermediate story: relatively abundant during the Pleistocene, it is now restricted to Greenland and the Arctic Archipelago. In this study, we use ancient DNA sequences, temporally unbiased summary statistics, and Bayesian analytical techniques to infer musk ox population dynamics throughout the late Pleistocene and Holocene. Our results reveal that musk ox genetic diversity was much higher during the Pleistocene than at present, and has undergone several expansions and contractions over the past 60,000 years. Northeast Siberia was of key importance, as it was the geographic origin of all samples studied and held a large diverse population until local extinction at ≈45,000 radiocarbon years before present (14C YBP). Subsequently, musk ox genetic diversity reincreased at ca. 30,000 14C YBP, recontracted at ca. 18,000 14C YBP, and finally recovered in the middle Holocene. The arrival of humans into relevant areas of the musk ox range did not affect their mitochondrial diversity, and both musk ox and humans expanded into Greenland concomitantly. Thus, their population dynamics are better explained by a nonanthropogenic cause (for example, environmental change), a hypothesis supported by historic observations on the sensitivity of the species to both climatic warming and fluctuations.
The panicolytic-like effect of fluoxetine in the elevated T-maze is mediated by serotonin-induced activation of endogenous opioids in the dorsal periaqueductal grey

Serotonin (5-HT), opioids and the dorsal periaqueductal grey (DPAG) have been implicated in the pathophysiology of panic disorder. In order to study 5-HT–opioid interaction, the opioid antagonist naloxone was injected either systemically (1 mg/kg, i.p.) or intra-DPAG (0.2 μg/0.5 μL) to assess its interference with the effect of chronic fluoxetine (10 mg/kg, i.p., daily for 21 days) or of intra-DPAG 5-HT (8 μg/0.5 μL). Drug effects were measured in the one-escape task of the rat elevated T-maze, an animal model of panic. Pretreatment with systemic naloxone antagonized the lengthening of escape latency caused by chronic fluoxetine, considered a panicolytic-like effect that parallels the drug’s therapeutic response in the clinics. Pretreatment with naloxone injected intra-DPAG antagonized both the panicolytic effect of chronic fluoxetine as well as that of 5-HT injected intra-DPAG. Neither the performance of the inhibitory avoidance task in the elevated T-maze, a model of generalized anxiety nor locomotion measured in a circular arena was affected by the above drug treatments. These results indicate that the panicolytic effect of fluoxetine is mediated by endogenous opioids that are activated by 5-HT in the DPAG. They also allow reconciliation between the serotonergic and opioidergic hypotheses of panic disorder pathophysiology.
A Unifying Framework for Learning Bag Labels from Generalized Multiple-Instance Data

We study the problem of bag-level classification from generalized multiple-instance (GMI) data. GMI learning is an extension of the popular multiple-instance setting. In GMI data, bags are labeled positive if they contain instances of certain types, and avoid instances of other types. For example, an image of a "sunny beach" should contain sand and sea, but not clouds. We formulate a novel generative process for the GMI setting in which bags are distributions over instances. In this model, we show that a broad class of distribution-distance kernels is sufficient to represent arbitrary GMI concepts. Further, we show that a variety of previously proposed kernel approaches to the standard MI and GMI settings can be unified under the distribution kernel framework. We perform an extensive empirical study which indicates that the family of distribution distance kernels is accurate for a wide variety of real-world MI and GMI tasks as well as efficient when compared to a large set of baselines. Our theoretical and empirical results indicate that distribution-distance kernels can serve as a unifying framework for learning bag labels from GMI (and therefore MI) problems.
Collaborative pricing model for bundling information goods

The information economy engenders consideration of certain issues such as information goods cost/pricing, technology infrastructure, and information policy in the era of knowledge economy. Due to the unique cost structure and product characteristics of information goods, conventional pricing strategies are unfeasible, and a differential pricing strategy is crucial. Nevertheless, few models exist for pricing information goods in the e-service industry. This study proposes a novel collaborative pricing model in which customers are active participants in determining product prices and adopt prices and services that meet their changing needs. This study also shows that the collaborative pricing model generates an optimal bundle price at equilibrium with optimal profit and utility. Theoretical proofs and practical implications justify this pricing model, which is essential for future information goods pricing in the information economy.
A current controlled oscillator based readout front-end for neurochemical sensing in 65nm CMOS technology

This paper presents the design of an integrated current-controlled oscillator (CCO) based readout front-end for neurochemical sensing applications. The readout front-end chip is implemented in 65 nm CMOS technology and occupies an area of 0.059 mm2. The proposed design supports an input current range of 1.2 μA (±600 nA) and can also be configured to support wider current range. The CCO-based structure utilized in this design results in noise averaging of the detected neurochemical input signal due to its inherent ΔΣfirst-order noise shaping and anti-alias filtering characteristics. Thus, the prototype chip achieves a current resolution of 100 pA and can detect dopamine concentrations as small as 10 μMol based on measured data from novel diamond-like carbon electrodes. In addition, the digital codes obtained from the readout front-end attain a signal-to-noise (SNR) of 82 dB and linearity limited effective-number-of-bits (ENOB) of 8 at full current range input, without employing any calibration or linearization techniques. The proposed read-out front-end consumes 33.7 μW of power in continuous operation.
Optical types of inland and coastal waters

Inland and coastal waterbodies are critical components of the global biosphere. Timely monitoring is necessary to enhance our understanding of their functions, the drivers impacting on these functions and to deliver more effective management. The ability to observe waterbodies from space has led to Earth observation (EO) becoming established as an important source of information on water quality and ecosystem condition. However, progress toward a globally valid EO approach is still largely hampered by inconsistences over temporally and spatially variable in‐water optical conditions. In this study, a comprehensive dataset from more than 250 aquatic systems, representing a wide range of conditions, was analyzed in order to develop a typology of optical water types (OWTs) for inland and coastal waters. We introduce a novel approach for clustering in situ hyperspectral water reflectance measurements (n = 4045) from multiple sources based on a functional data analysis. The resulting classification algorithm identified 13 spectrally distinct clusters of measurements in inland waters, and a further nine clusters from the marine environment. The distinction and characterization of OWTs was supported by the availability of a wide range of coincident data on biogeochemical and inherent optical properties from inland waters. Phylogenetic trees based on the shapes of cluster means were constructed to identify similarities among the derived clusters with respect to spectral diversity. This typification provides a valuable framework for a globally applicable EO scheme and the design of future EO missions.
Impact of Nutritional Factors on the Proteome of Intestinal Escherichia coli: Induction of OxyR-Dependent Proteins AhpF and Dps by a Lactose-Rich Diet

ABSTRACT To study the impact of nutritional factors on protein expression of intestinal bacteria, gnotobiotic mice monoassociated with Escherichia coli K-12 were fed three different diets: a diet rich in starch, a diet rich in nondigestible lactose, and a diet rich in casein. Two-dimensional gel electrophoresis and electrospray-tandem mass spectrometry were used to identify differentially expressed proteins of bacteria recovered from small intestine and cecum. Oxidative stress response proteins such as AhpF, Dps, and Fur, all of which belong to the oxyR regulon, were upregulated in E. coli isolates from mice fed the lactose-rich diet. Luciferase reporter gene assays demonstrated that osmotic stress caused by carbohydrates led to the expression of ahpCF and dps, which was not observed in an E. coli ΔoxyR mutant. Growth of ahpCF and oxyR deletion mutants was strongly impaired when nondigestible sucrose was present in the medium. The wild-type phenotype could be restored by complementation of the deletions with plasmids containing the corresponding genes and promoters. The results indicate that some OxyR-dependent proteins play a major role in the adaptation of E. coli to osmotic stress. We conclude that there is an overlap of osmotic and oxidative stress responses. Mice fed the lactose-rich diet possibly had a higher intestinal osmolality, leading to the upregulation of OxyR-dependent proteins, which enable intestinal E. coli to better cope with diet-induced osmotic stress.
Tonically active neurons in the striatum differentiate between delivery and omission of expected reward in a probabilistic task context

Tonically active neurons (TANs) in the primate striatum are responsive to rewarding stimuli and they are thought to be involved in the storage of stimulus–reward associations or habits. However, it is unclear whether these neurons may signal the difference between the prediction of reward and its actual outcome as a possible neuronal correlate of reward prediction errors at the striatal level. To address this question, we studied the activity of TANs from three monkeys trained in a classical conditioning task in which a liquid reward was preceded by a visual stimulus and reward probability was systematically varied between blocks of trials. The monkeys’ ability to discriminate the conditions according to probability was assessed by monitoring their mouth movements during the stimulus–reward interval. We found that the typical TAN pause responses to the delivery of reward were markedly enhanced as the probability of reward decreased, whereas responses to the predictive stimulus were somewhat stronger for high reward probability. In addition, TAN responses to the omission of reward consisted of either decreases or increases in activity that became stronger with increasing reward probability. It therefore appears that one group of neurons differentially responded to reward delivery and reward omission with changes in activity into opposite directions, while another group responded in the same direction. These data indicate that only a subset of TANs could detect the extent to which reward occurs differently than predicted, thus contributing to the encoding of positive and negative reward prediction errors that is relevant to reinforcement learning.
Idiopathic congenital true leukonychia totalis

A 16-year-old male presented with white-colored fingernails since birth [Figure 1]. Toenails were normal. None of the family members were affected. Hematological investigations were normal. On cutaneous examination all finger nails were milky, porcelain white in color and smooth surfaced. No knuckle pads, palmoplantar keratoderma, or hearing loss was observed. General and systemic examination was normal. On clinical correlation, a diagnosis of idiopathic congenital true leukonychia totalis was made. Figure 1 Milky, porcelain, white-colored smooth-surfaced finger nails Leukonychia is the white discoloration of nail that loses its normal pink color, with disappearance of the lunula. It is the commonest chromatic abnormality of the nail apparatus. It is also referred to as white nail, milk spots, and fortune or gift spots. It is derived from the Greek word “leukos” means white and “onyx” means nail. [1,2] Leukonychia is classified as: [Table 1]. Table 1 Classification of leukonychia The proposed white discoloration of the nail is attributable to reflection of light from large keratohyaline granules present in the parakeratotic cells of the ventral portion of nail plate thus preventing the visualisation of normal vascular tissue underlying the nail plate. [2,3] Total congenital leukonychia is very rare hereditary condition in which all nails are milky white with an autosomal dominant inheritance but it can be autosomal recessive in few cases. Hereditary leukonychia involves whole nail plate as against acquired one which shows transverse or punctate leukonychia. Mutations in PLCD1 gene on chromosome 3p21.3-p22 was identified as cause of hereditary leukonychia. This PLCD1 gene is localized to nail matrix and encodes phosphoinositide specific phospholipase C delta 1 subunit which is important enzyme in phosphoinositide metabolism required for molecular control of color and growth of nail. [4] Leukonychia totalis is associated with multiple systemic diseases such as diabetes, liver cirrhosis, renal failure, cardiac failure, gall stones, renal calculi, duodenal ulcers, pili torti, trichilemmal cyst, sebaceous cyst, congenital hyperparathyroidism, Hodgkin's lymphoma, Leopard syndrome, epiphyseal dysplasia syndrome, Bart Pumphrey syndrome, mental retardation, etc., However, there are very few reports in the literature on sporadic congenital leukonychia totalis without any systemic abnormalities. [1,3] Treatment is usually supportive with detailed investigation to check for association of any systemic or genetic disorders.
Rigidity-Preserving Team Partitions in Multiagent Networks

Motivated by the strong influence network rigidity has on collaborative systems, in this paper, we consider the problem of partitioning a multiagent network into two sub-teams, a bipartition, such that the resulting sub-teams are topologically rigid. In this direction, we determine the existence conditions for rigidity-preserving bipartitions, and provide an iterative algorithm that identifies such partitions in polynomial time. In particular, the relationship between rigid graph partitions and the previously identified Z-link edge structure is given, yielding a feasible direction for graph search. Adapting a supergraph search mechanism, we then detail a methodology for discerning graphs cuts that represent valid rigid bipartitions. Next, we extend our methods to a decentralized context by exploiting leader election and an improved graph search to evaluate feasible cuts using only local agent-to-agent communication. Finally, full algorithm details and pseudocode are provided, together with simulation results that verify correctness and demonstrate complexity.
Synergy against drug-resistant HIV-1 with the microbicide antiretrovirals, dapivirine and tenofovir, in combination

Objective:To evaluate the candidate antiretroviral microbicide compounds, dapivirine (DAP) and tenofovir (TFV), alone and in combination against the transmission of wild-type and nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 from different subtypes. Design and methods:We determined single-drug efficacy of the RTIs, DAP and TFV, against subtype B and non-B wild-type and NNRTI-resistant HIV-1 in vitro. To assess breadth of activity, compounds were tested alone and in combination against wild-type and NNRTI-resistant subtype C primary HIV-1 isolates and complimentary clonal HIV-1 from subtypes B, C and CRF02_AG to control for viral variation. Early infection was quantified by counting light units emitted from TZM-bl cells less than 48-h postinfection. Combination ratios were based on drug inhibitory concentrations (IC50s) and combined effects were determined by calculating combination indices. Results:Both candidate microbicide antiretrovirals demonstrated potent anti-NNRTI-resistant HIV-1 activity in vitro, albeit the combination protected better than the single-drug treatments. Of particular interest, the DAP with TFV combination exhibited synergy (50% combination index, CI50 = 0.567) against subtype C NNRTI-resistant HIV-1, whereas additivity (CI50 = 0.987) was observed against the wild-type counterpart from the same patient. The effect was not compounded by the presence of subdominant viral fractions, as experiments using complimentary clonal subtype C wild-type (CI50 = 0.968) and NNRTI-resistant (CI50 = 0.672) HIV-1, in lieu of the patient quasispecies, gave similar results. Conclusion:This study supports the notion that antiretroviral drug combinations may retain antiviral activity against some drug-resistant HIV-1 despite subtype classification and quasispecies diversity.
An Energy Transport Model Describing Electro-Thermal Transport in Silicon Carbide Semiconductors

ABSTRACT By taking the moments of the coupled Boltzmann transport equations for electrons and phonons, an extended hydrodynamic model describing the electron transport in silicon carbide semiconductors has been obtained. This model is coupled with the heating of the crystal lattice. All the transport coefficients and the constitutive equations are determined by using the maximum entropy principle of extended thermodynamics. By using this model with a suitable limit, thermoelectric effects in silicon carbide devices are investigated.
G Protein-Coupled Receptors at the Crossroad between Physiologic and Pathologic Angiogenesis: Old Paradigms and Emerging Concepts

G protein-coupled receptors (GPCRs) have been implicated in transmitting signals across the extra- and intra-cellular compartments, thus allowing environmental stimuli to elicit critical biological responses. As GPCRs can be activated by an extensive range of factors including hormones, neurotransmitters, phospholipids and other stimuli, their involvement in a plethora of physiological functions is not surprising. Aberrant GPCR signaling has been regarded as a major contributor to diverse pathologic conditions, such as inflammatory, cardiovascular and neoplastic diseases. In this regard, solid tumors have been demonstrated to activate an angiogenic program that relies on GPCR action to support cancer growth and metastatic dissemination. Therefore, the manipulation of aberrant GPCR signaling could represent a promising target in anticancer therapy. Here, we highlight the GPCR-mediated angiogenic function focusing on the molecular mechanisms and transduction effectors driving the patho-physiological vasculogenesis. Specifically, we describe evidence for the role of heptahelic receptors and associated G proteins in promoting angiogenic responses in pathologic conditions, especially tumor angiogenesis and progression. Likewise, we discuss opportunities to manipulate aberrant GPCR-mediated angiogenic signaling for therapeutic benefit using innovative GPCR-targeted and patient-tailored pharmacological strategies.
Big Omicron and big Omega and big Theta

Most of us have gotten accustomed to the idea of using the notation O(f(n)) to stand for any function whose magnitude is upper-bounded by a constant times f(n) , for all large n. Sometimes we also need a corresponding notation for lower-bounded functions, i.e., those functions which are at least as large as a constant times f(n) for all large n. Unfortunately~ people have occasionally been using the O-notation for lower bounds, for example when they reject a particular sorting method "because its running time is O(n 2) " I have seen instances of this in print quite of tent and finally it has prompted me to sit down and write a Letter to the Editor about the situation. The classical literature does have a notation for functions that are bounded below, namely ~(f(n)). The most prominent appearance of this notation is in Titchmarsh's magnum opus on Riemann's zeta function [8], where he defines ~(f(n)) on p. 152 and devotes his entire Chapter 8 to "~-theorems". See also Karl Prachar's Primzahlverteilung [7], P. 245. The ~ notation has not become very common, although I have noticed its use in a few places, most recently in some Russian publications I consulted about the theory of equidistributed sequences. Once I had suggested to someone in a letter that he use ~-notation "since it had been used by number theorists for years"; but later, when challenged to show explicit references, I spent a surprisingly fruitless hour searching in the library without being able to turn up a single reference. I have recently asked several prominent mathematicians if they knew what ~(n 2) meant, and more than half of them had never seen the notation before. Before writing this letter, I decided to search more carefully, and to study the history of O-notation and o-notation as well. Cajori's two-volume work on history of mathematical notations does not mention any of these. While looking for definitions of ~ I came across dozens of books from the early part of this century which defined O and o but not ~ .
Investigation of the Influence of Cracks on Vibration Processes in a Reinforced Concrete Structure

The validity of the mathematical model describing the propagation of vibrations in a reinforced concrete (RC) structure was verified by comparing the experimental and numerical data. The proposed model allowed one to perform numerical experiments aimed at comparing vibrorecords obtained from the structure without defects and the structure with cracks. A numerical experiment was performed aimed to explore the changes in vibrorecords when cracks appear in the structure. Based on the results these experiments, an informative diagnostic parameter controlling crack nucleation and propagation in the reinforced concrete structure was derived.
Testing the technology: playing games with video conferencing

Video connections can establish a media space in which games may be played, just as people play games while collocated. Experiments with participants playing the game 'Mafia' indicate that people in a video condition have similar levels of satisfaction, fun, and frustration, to those that play while collocated. This finding holds for both those with prior experience using video systems and those without, suggesting it is not merely a "novelty effect. " Results differ about whether there exist differences in focus of attention, suspicion/trust, and pointing for people playing the game while using a video system. Implications for both fun and work uses of video are suggested.
Use of Human Pluripotent Stem Cell Derived‐Cardiomyocytes to Study Drug‐Induced Cardiotoxicity

Drug‐induced cardiotoxicity is the one of the most common causes of drug withdrawal from market. A major barrier in managing the risk of drug‐induced cardiotoxicity has been the lack of relevant models to study cardiac safety. Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) have great potential in drug discovery and cardiotoxcity screens as they display many characteristics of the human myocardium and offer unlimited supply. This unit describes how to use pluripotent stem cells derived cardiomyocytes to study drug‐induced cardiotoxicty using doxorubicin as an example. We present a workflow that explains procedure for editing hPSC using the CRISPR/Cas9 system and for differentiation of hPSC into cardiomyocytes. We also report protocols to study drug effect on ROS production, intracellular calcium concentration, formation of DNA double strand breaks, gene expression and electrophysiological properties of hPSC‐CMs. © 2017 by John Wiley & Sons, Inc.