Miracle-dz/UniFAR-FTUs huggingface dataset:
Formation of Category Representations in Superior Temporal Sulcus

The human brain contains cortical areas specialized in representing object categories. Visual experience is known to change the responses in these category-selective areas of the brain. However, little is known about how category training specifically affects cortical category selectivity. Here, we investigated the experience-dependent formation of object categories using an fMRI adaptation paradigm. Outside the scanner, subjects were trained to categorize artificial bird types into arbitrary categories (jungle birds and desert birds). After training, neuronal populations in the occipito-temporal cortex, such as the fusiform and the lateral occipital gyrus, were highly sensitive to perceptual stimulus differences. This sensitivity was not present for novel birds, indicating experience-related changes in neuronal representations. Neurons in STS showed category selectivity. A release from adaptation in STS was only observed when two birds in a pair crossed the category boundary. This dissociation could not be explained by perceptual similarities because the physical difference between birds from the same side of the category boundary and between birds from opposite sides of the category boundary was equal. Together, the occipito-temporal cortex and the STS have the properties suitable for a system that can both generalize across stimuli and discriminate between them.
The Flavonoid Biosynthetic Enzyme Chalcone Isomerase Modulates Terpenoid Production in Glandular Trichomes of Tomato1[C][W][OPEN]

An isoform of chalcone isomerase that catalyzes flavonoid synthesis modulates terpenoid production in glandular trichomes of tomato. Flavonoids and terpenoids are derived from distinct metabolic pathways but nevertheless serve complementary roles in mediating plant interactions with the environment. Here, we show that glandular trichomes of the anthocyanin free (af) mutant of cultivated tomato (Solanum lycopersicum) fail to accumulate both flavonoids and terpenoids. This pleiotropic metabolic deficiency was associated with loss of resistance to native populations of coleopteran herbivores under field conditions. We demonstrate that Af encodes an isoform (SlCHI1) of the flavonoid biosynthetic enzyme chalcone isomerase (CHI), which catalyzes the conversion of naringenin chalcone to naringenin and is strictly required for flavonoid production in multiple tissues of tomato. Expression of the wild-type SlCHI1 gene from its native promoter complemented the anthocyanin deficiency in af. Unexpectedly, the SlCHI1 transgene also complemented the defect in terpenoid production in glandular trichomes. Our results establish a key role for SlCHI1 in flavonoid production in tomato and reveal a link between CHI1 and terpenoid production. Metabolic coordination of the flavonoid and terpenoid pathways may serve to optimize the function of trichome glands in dynamic environments.
Phenotypes and tolerances in the design space of biochemical systems

One of the major unsolved problems of modern biology is deep understanding of the complex relationship between the information encoded in the genome of an organism and the phenotypic properties manifested by that organism. Fundamental advances must be made before we can begin to approach the goal of predicting the phenotypic consequences of a given mutation or an organism's response to a novel environmental challenge. Although this problem is often portrayed as if the task were to find a more or less direct link between genotypic and phenotypic levels, on closer examination the relationship is far more layered and complex. Although there are some intuitive notions of what is meant by phenotype at the level of the organism, it is far from clear what this term means at the biochemical level. We have described design principles that are readily revealed by representation of molecular systems in an appropriate design space. Here, we first describe a generic approach to the construction of such a design space in which qualitatively distinct phenotypes can be identified and counted. Second, we show how the boundaries between these phenotypic regions provide a method of characterizing a system's tolerance to large changes in the values of its parameters. Third, we illustrate the approach for one of the most basic modules of biochemical networks and describe an associated design principle. Finally, we discuss the scaling of this approach to large systems.
Molecular and Functional Imaging of Internet Addiction

Maladaptive use of the Internet results in Internet addiction (IA), which is associated with various negative consequences. Molecular and functional imaging techniques have been increasingly used for analysis of neurobiological changes and neurochemical correlates of IA. This review summarizes molecular and functional imaging findings on neurobiological mechanisms of IA, focusing on magnetic resonance imaging (MRI) and nuclear imaging modalities including positron emission tomography (PET) and single photon emission computed tomography (SPECT). MRI studies demonstrate that structural changes in frontal cortex are associated with functional abnormalities in Internet addicted subjects. Nuclear imaging findings indicate that IA is associated with dysfunction of the brain dopaminergic systems. Abnormal dopamine regulation of the prefrontal cortex (PFC) could underlie the enhanced motivational value and uncontrolled behavior over Internet overuse in addicted subjects. Further investigations are needed to determine specific changes in the Internet addictive brain, as well as their implications for behavior and cognition.
Study of bacteria isolated from urinary tract infections and determination of their susceptibility to antibiotics.

Introduction and objective: Approximately 1 in 3 women will require antimicrobial treatment for a Urinary Tract Infection (UTI) before age 24, and 40% to 50% of women will have a UTI during their lifetime. UTIs in male patients are considered complicated. Escherichia coli is the most common cause of UTIs. Materials and methods: In the present study 7056 patients with clinical symptoms and suspected to UTI were sampled. Clean-Catch midstream urine of the patients was collected. Urine specimens were cultured for isolation of the microbial agents of UTI. The isolated bacteria were identified using biochemical tests. Disk diffusion susceptibility test was used to determine susceptibility of bacterial agents to antibiotics. Results: In this study 553(8.7%) patients out of 7056 were shown to be urine culture positive (68% females and 32% males). The most isolated bacterium was E. coli with frequency rate of 59%. The other bacteria were Klebsiella spp. (11.6%), Enterobacter spp. (9.8%), Pseudomonas spp. (7.2 %), Proteus spp. (2.9%), Acinetobacter spp. (2.7%), Congolese positive Staphylococci (2.2%), Coagolase negative Staphylococci (2.3%), Citrobacter spp. (1.3%) and Streptococci α hemolytic (1.1%). All Gram-negative bacteria were more sensitive to amikacin (90.5-100%). The Gram-positive cocci isolated were more sensitive to tobramycin, kanamycin and ciprofloxacin (100%). Conclusion: It is concluded that Gram-negative bacilli were responsible for UTI infections in our patients. The most common isolated bacteria from urinary tract infections were E. coli and the most effective antimicrobial agents were amikacin, tobramicin and ciprofleoxacin against Gram-negative bacilli and also the most effective antibiotics against Gram-positive cocci were kanamicin, tobramicin and ciprofleoxacin.
ACHIEVEMENT: An Integrative Review

The purpose of this review is to document the directions and recent progress in our understanding of the motivational dynamics of school achievement. Based on the accumulating research it is concluded that the quality of student learning as well as the will to continue learning depends closely on an interaction between the kinds of social and academic goals students bring to the classroom, the motivating properties of these goals and prevailing classroom reward structures. Implications for school reform that follow uniquely from a motivational and goal-theory perspective are also explored.
A Dynamic Model for Stem Cell Homeostasis and Patterning in Arabidopsis Meristems

Plants maintain stem cells in their meristems as a source for new undifferentiated cells throughout their life. Meristems are small groups of cells that provide the microenvironment that allows stem cells to prosper. Homeostasis of a stem cell domain within a growing meristem is achieved by signalling between stem cells and surrounding cells. We have here simulated the origin and maintenance of a defined stem cell domain at the tip of Arabidopsis shoot meristems, based on the assumption that meristems are self-organizing systems. The model comprises two coupled feedback regulated genetic systems that control stem cell behaviour. Using a minimal set of spatial parameters, the mathematical model allows to predict the generation, shape and size of the stem cell domain, and the underlying organizing centre. We use the model to explore the parameter space that allows stem cell maintenance, and to simulate the consequences of mutations, gene misexpression and cell ablations.
Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space.

Experiments were made on the posterior parietal association cortical areas 5 and in 17 hemispheres of 11 monkeys, 6 M. mulatta and 5 M. arctoides. The electrical signs of the activity of single cortical cells were recorded with microelectrodes in waking animals as they carried out certain behavioral acts in response to a series of sensory cues. The behavioral paradigms were one for detection alone, and a second for detection plus projection of the arm to contact a stationary or moving target placed at arm's length. Of the 125 microelectrode penetrations made, 1,451 neurons were identified in terms of the correlation of their activity with the behavioral acts and their sensitivity or lack of it to sensory stimuli delivered passively; 180 were studied quantitatively. The locations of cortical neurons were identified in serial sections; 94 penetrations and 1,058 neurons were located with certainty. About two-thirds of the neurons of area 5 were activated by passive rotation of the limbs at their joints; of these, 82% were related to single, contralateral joints, 10% to two or more contralateral joints, 6% to ipsilateral, and 2% to joints on both sides of the body. A few of the latter were active during complex bodily postures. A large proportion of area 5 neurons were relatively insensitive to passive joint rotations, as compared with similar neurons of the postcentral gyrus, but were driven to high rates of discharge when the same joint was rotated during an active movement of the animal.
The USTC system for blizzard machine learning challenge 2017-ES2

The Blizzard Machine Learning Challenge (BMLC) aims to liberate participants from speech-specific processing when building speech synthesis systems. This paper describes the USTC system for the ES2 sub-task in BMLC2017, which requires participants to train a model to directly predict waveforms from linguistic features. We investigate three aspects of waveform modeling when preparing our system for this task. First, two different model structures for waveform modeling, i.e., WaveNet and SampleRNN, are compared on this task. Second, a strategy of using features extracted from waveforms as intermediate representations for waveform modeling is studied. Experimental results show that using low-level features (STFT amplitude spectra) as intermediate representations can achieve similar performance as using high-level features (mel-cepstra and F0). Third, the feasibility of applying WaveNet to wideband speech signals with more than 256 quantization levels is verified by experiments. Finally, a system which adopts STFT amplitude spectra as intermediate representations to model 24kHz speech waveforms with 1024 mu-law quantization levels is submitted for evaluation. The evaluation results of BMLC2017 demonstrate the effectiveness of our proposed methods.
Sensitivity of the 2‐oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion

The mitochondrial pool of reduced glutathione (mGSH) is known to play a protective role against liver injury and cytokine‐mediated cell death. However, the identification of the mitochondrial carriers involved in its transport in hepatocellular mitochondria remains unestablished. In this study, we show that the functional expression of the 2‐oxoglutarate carrier from HepG2 cells in mitochondria from Xenopus laevis oocytes conferred a reduced glutathione (GSH) transport activity that was inhibited by phenylsuccinate, a specific inhibitor of the carrier. In addition, the mitochondrial transport of GSH and 2‐oxoglutarate in isolated mitochondria from rat liver exhibited mutual competition and sensitivity to glutamate and phenylsuccinate. Interestingly, the kinetics of 2‐oxoglutarate transport in rat liver mitochondria displayed a single Michaelis‐Menten component with a Michaelis constant of 3.1 ± 0.3 mmol/L and maximum velocity of 1.9 ± 0.1 nmol/mg protein/25 seconds. Furthermore, the initial rate of 2‐oxoglutarate was reduced in mitochondria from alcohol‐fed rat livers, an effect that was not accompanied by an alcohol‐induced decrease in the 2‐oxoglutarate messenger RNA levels but rather by changes in mitochondrial membrane dynamics induced by alcohol. The fluidization of mitochondria by the fluidizing agent 2‐(2‐methoxyethoxy)ethyl 8‐(cis‐2‐n‐octylcyclopropyl) (A2C) restored the initial transport rate of both GSH and 2‐oxoglutarate. Finally, these changes were reproduced in normal liver mitochondria enriched in cholesterol where the fluidization of cholesterol‐enriched mitochondria with A2C restored the order membrane parameter and the mitochondrial 2‐oxoglutarate uptake. In conclusion, these findings provide unequivocal evidence for 2‐oxoglutarate as a GSH carrier and its sensitivity to membrane dynamics perturbation contributes in part to the alcohol‐induced mGSH depletion.
Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease.
Status of B-Vitamins and Homocysteine in Diabetic Retinopathy: Association with Vitamin-B12 Deficiency and Hyperhomocysteinemia

Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case–control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.
Bayesian Clustering by Dynamics Contents 1 Introduction 1 2 Clustering Markov Chains 2

This paper introduces a Bayesian method for clustering dynamic processes. The method models dynamics as Markov c hains and then applies an agglomerative clustering procedure to discover the most probable set of clusters capturing diierent dynamics. To increase eeciency, the method uses an entropy-based heuristic search strategy. An experiment suggests that the method is very accurate when applied to artiicial time series in a broad range of conditions. When the method is applied to clustering simulated military engagements and sensor data from mobile robots, it produces clusters that are meaningful in the domains of application.
Serum HDL/total cholesterol ratio and blood pressure in asymptomatic atherosclerotic lesions of the cervical carotid arteries in men.

One hundred neurologically asymptomatic male subjects (aged 50-69 years), randomly selected through population registers, were screened for atherosclerotic lesions of the cervical carotid arteries, using a high resolution multi-gate pulsed Doppler system. In 93 subjects serum was assayed for total and HDL cholesterol. Besides, cuff arterial blood pressure measurements were made. Twenty-three of these subjects (Group III) were classified as abnormal according to the Doppler investigation (degree of narrowing less than 50% in 78% of the cases). Seven of these 23 subjects also had a history of ischemic heart disease or intermittent claudication. Of the 70 subjects with a normal Doppler examination 16 had a history of ischemic heart disease and/or intermittent claudication (Group II). The remaining 54 subjects served as controls (Group I). The frequency of asymptomatic atherosclerotic lesions of the cervical carotid arteries in the population under investigation was 23%. The HDL/total cholesterol ratio was lower and the frequency of high blood pressure higher in the Groups II and III than in Group I. The findings in this study support the idea that a low serum HDL/total cholesterol ratio and high blood pressure have a high degree of association with atherosclerotic lesions of the cervical carotid arteries. This association is already apparent at an early stage of the disease, i.e. in asymptomatic subjects with a slight to moderate degree of carotid artery narrowing.
Discrete Levels of Twist Activity Are Required to Direct Distinct Cell Functions during Gastrulation and Somatic Myogenesis

Twist (Twi), a conserved basic helix-loop-helix transcriptional regulator, directs the epithelial-to-mesenchymal transition (EMT), and regulates changes in cell fate, cell polarity, cell division and cell migration in organisms from flies to humans. Analogous to its role in EMT, Twist has been implicated in metastasis in numerous cancer types, including breast, pancreatic and prostate. In the Drosophila embryo, Twist is essential for discrete events in gastrulation and mesodermal patterning. In this study, we derive a twi allelic series by examining the various cellular events required for gastrulation in Drosophila. By genetically manipulating the levels of Twi activity during gastrulation, we find that coordination of cell division is the most sensitive cellular event, whereas changes in cell shape are the least sensitive. Strikingly, we show that by increasing levels of Snail expression in a severe twi hypomorphic allelic background, but not a twi null background, we can reconstitute gastrulation and produce viable adult flies. Our results demonstrate that the level of Twi activity determines whether the cellular events of ventral furrow formation, EMT, cell division and mesodermal migration occur.
Aspergillus SteA (Sterile12‐like) is a homeodomain‐C2/H2‐Zn+2 finger transcription factor required for sexual reproduction

Saccharomyces cerevisiae Ste12p plays a key role in coupling signal transduction through MAP kinase modules to cell‐specific or morphogenesis‐specific gene expression required for mating and pseudohyphal (PH)/filamentous growth (FG). Ste12p homologues in the pathogenic yeasts Candida albicans and Filobasidiela neoformans apparently play similar roles during dimorphic transitions. Here we report the isolation and characterization of the first Ste12 protein from a true filamentous fungus. Aspergillus nidulans steA encodes a protein with a homeodomain 63–75% identical to those of other Ste12 proteins, with greatest similarity to FnSte12αp. SteAp and Ste12αp lack the pheromone induction domain found in budding yeast Ste12p, but have C‐terminal C2/H2‐Zn+2 finger domains not present in the other Ste12 proteins. A ΔsteA strain is sterile and differentiates neither ascogenous tissue nor fruiting bodies (cleistothecia). However, the development of sexual cycle‐specific Hülle cells is unaffected. Filamentous growth, conidiation and the differentiation of PH‐like asexual reproductive cells (metulae and phialides) are normal in the deletion strain. Northern analysis of key regulators of the asexual and sexual reproductive cycles support the observation that although SteAp function is restricted to the sexual cycle, cross regulation between the two developmental pathways exists. Our results further suggest that while several classes of related proteins control similar morphogenetic events in A. nidulans and the dimorphic yeasts, significant differences must exist in the regulatory circuitry.