Miracle-dz/UniFAR-FTUs huggingface dataset:
Defective Acidification in Human Breast Tumor Cells and Implications for Chemotherapy

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.
The Case of "Adam": Reflections and Future Directions

Three commentaries on "Targeting Sexual Stigma: The Hybrid Case Study of 'Adam' " (Mandel, 2014) present additional insights into providing psychotherapy for sexual minority clients who struggle with internalized homophobia, minority stress, and identity formation concerns. In his thoughtful response, Christopher Martell (2014) writes about heteronormativity, behavioral activation, multidimensional treatment, and the issue of “readiness” to address sexual orientation and identity in treatment. Rachel Proujansky and John Pachankis (2014) describe their exciting principle- and evidence-based LGB-affirmative psychotherapy, and explain the importance of addressing sexual behavior when working with sexual minority clients. Additionally, Daniel Chazin and Sam Klugman (2014) highlight key issues related to the coming-out process and systemic-level interventions. In the following response, I summarize the psychologists’ comments and provide feedback to further the dialogue regarding how to best serve the needs of sexual minority clients.
The Role of Cartilage Stress in Patellofemoral Pain.

PURPOSE Elevated cartilage stress has been identified as a potential mechanism for retropatellar pain; however, there are limited data in the literature to support this mechanism. Females are more likely to develop patellofemoral pain than males, yet the causes of this dimorphism are unclear. We used experimental data and computational modeling to determine whether patients with patellofemoral pain had elevated cartilage stress compared with pain-free controls and test the hypothesis that females exhibit greater cartilage stress than males. METHODS We created finite element models of 24 patients with patellofemoral pain (11 males and 13 females) and 16 pain-free controls (8 males and 8 females) to estimate peak patellar cartilage stress (strain energy density) during a stair climb activity. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and muscle forces from an EMG-driven model. RESULTS We found no difference in peak patellar strain energy density between those with patellofemoral pain (1.9 ± 1.23 J·m(-3)) and control subjects (1.66 ± 0.75 J·m(-3), P = 0.52). Females exhibited greater cartilage stress compared with males (2.2 vs 1.3 J·m(-3), respectively; P = 0.0075), with large quadriceps muscle forces (3.7 body weight in females vs 3.3 body weight in males) and 23% smaller joint contact area (females, 467 ± 59 mm2, vs males, 608 ± 95 mm2). CONCLUSIONS Patients with patellofemoral pain did not display significantly greater patellar cartilage stress compared with pain-free controls; however, there was a great deal of subject variation. Females exhibited greater peak cartilage stress compared with males, which might explain the greater prevalence of patellofemoral pain in females compared with that in males, but other mechanical and biological factors are clearly involved in this complex pathway to pain.
The Intrinsic Electrostatic Potential and the Intermediate Ring of Charge in the Acetylcholine Receptor Channel

A ring of aligned glutamate residues named the intermediate ring of charge surrounds the intracellular end of the acetylcholine receptor channel and dominates cation conduction (Imoto et al. 1988). Four of the five subunits in mouse-muscle acetylcholine receptor contribute a glutamate to the ring. These glutamates were mutated to glutamine or lysine, and combinations of mutant and native subunits, yielding net ring charges of −1 to −4, were expressed in Xenopus laevis oocytes. In all complexes, the α subunit contained a Cys substituted for αThr244, three residues away from the ring glutamate αGlu241. The rate constants for the reactions of αThr244Cys with the neutral 2-hydroxyethyl-methanethiosulfonate, the positively charged 2-ammonioethyl-methanethiosulfonate, and the doubly positively charged 2-ammonioethyl-2′-ammonioethanethiosulfonate were determined from the rates of irreversible inhibition of the responses to acetylcholine. The reagents were added in the presence and absence of acetylcholine and at various transmembrane potentials, and the rate constants were extrapolated to zero transmembrane potential. The intrinsic electrostatic potential in the channel in the vicinity of the ring of charge was estimated from the ratios of the rate constants of differently charged reagents. In the acetylcholine-induced open state, this potential was −230 mV with four glutamates in the ring and increased linearly towards 0 mV by +57 mV for each negative charge removed from the ring. Thus, the intrinsic electrostatic potential in the narrow, intracellular end of the open channel is almost entirely due to the intermediate ring of charge and is strongly correlated with alkali-metal-ion conductance through the channel. The intrinsic electrostatic potential in the closed state of the channel was more positive than in the open state at all values of the ring charge. These electrostatic properties were simulated by theoretical calculations based on a simplified model of the channel.
Recognizing well-parenthesized expressions in the streaming model

Motivated by a concrete problem and with the goal of understanding the relationship between the complexity of streaming algorithms and the computational complexity of formal languages, we investigate the problem Dyck(s) of checking matching parentheses, with s different types of parenthesis. We present a one-pass randomized streaming algorithm for Dyck(2) with space O(√ n log(n)) bits, time per letter polylog(n), and one-sided error. We prove that this one-pass algorithm is optimal, up to a log(n) factor, even when two-sided error is allowed, and conjecture that a similar bound holds for any constant number of passes over the input. Surprisingly, the space requirement shrinks drastically if we have access to the input stream "in reverse". We present a two-pass randomized streaming algorithm for Dyck(2) with space O((log n)2), time polylog(n) and one-sided error, where the second pass is in the reverse direction. Both algorithms can be extended to Dyck(s) since this problem is reducible to Dyck(2) for a suitable notion of reduction in the streaming model. Except for an extra O(√ log(s)) multiplicative overhead in the space required in the one-pass algorithm, the resource requirements are of the same order. For the lower bound, we exhibit hard instances Ascension(m) of Dyck(2) with length Θ(mn). We embed these in what we call a "one-pass" communication problem with 2m-players, where m=~O(n). To establish the hardness of Ascension(m), we prove a direct sum result by following the "information cost" approach, but with a few twists. Indeed, we play a subtle game between public and private coins for Mountain, which corresponds to a primitive instance Ascension(1). This mixture between public and private coins for m results from a balancing act between the direct sum result and a combinatorial lower bound for m.
Paper-supported 3D cell culture for tissue-based bioassays

Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. Microfabrication can create architecturally complex scaffolds for 3D cell cultures that circumvent some of these limitations; unfortunately, these approaches require instrumentation not commonly available in biology laboratories. Here we report that stacking and destacking layers of paper impregnated with suspensions of cells in extracellular matrix hydrogel makes it possible to control oxygen and nutrient gradients in 3D and to analyze molecular and genetic responses. Stacking assembles the “tissue”, whereas destacking disassembles it, and allows its analysis. Breast cancer cells cultured within stacks of layered paper recapitulate behaviors observed both in 3D tumor spheroids in vitro and in tumors in vivo: Proliferating cells in the stacks localize in an outer layer a few hundreds of microns thick, and growth-arrested, apoptotic, and necrotic cells concentrate in the hypoxic core where hypoxia-sensitive genes are overexpressed. Altering gas permeability at the ends of stacks controlled the gradient in the concentration of the O2 and was sufficient by itself to determine the distribution of viable cells in 3D. Cell cultures in stacked, paper-supported gels offer a uniquely flexible approach to study cell responses to 3D molecular gradients and to mimic tissue- and organ-level functions.
Comparison of Prediction-Error-Modelling Criteria

Single and multi-step prediction-error-methods based on the maximum likelihood and least squares criteria are compared. The prediction-error methods studied are based on predictions using the Kalman filter and Kalman predictors for a linear discrete-time stochastic state space model, which is a realization of a continuous-discrete multivariate stochastic transfer function model. The proposed prediction error-methods are demonstrated for a SISO system parameterized by the transfer functions with time delays of a continuous-discrete-time linear stochastic system. The simulations for this case suggest to use the one-step-ahead prediction-error maximum-likelihood (or maximum a posteriori) estimator. It gives consistent estimates of all parameters and the parameter estimates are almost identical to the estimates obtained for long prediction horizons but with consumption of significantly less computational resources. The identification method is suitable for predictive control.
Aberrant Topological Patterns of Structural Cortical Networks in Psychogenic Erectile Dysfunction

Male sexual arousal (SA) has been known as a multidimensional experience involving closely interrelated and coordinated neurobehavioral components that rely on widespread brain regions. Recent functional neuroimaging studies have shown relation between abnormal/altered dynamics in these circuits and male sexual dysfunction. However, alterations in the topological1 organization of structural brain networks in male sexual dysfunction are still unclear. Here, we used graph theory2 to investigate the topological properties of large-scale structural brain networks, which were constructed using inter-regional correlations of cortical thickness between 78 cortical regions in 40 patients with psychogenic erectile dysfunction (pED) and 39 normal controls. Compared with normal controls, pED patients exhibited a less optimal global topological organization with reduced global and increased local efficiencies. Our results suggest disrupted neural integration among distant brain regions in pED patients, consistent with previous reports of impaired white matter structure and abnormal functional integrity in pED. Additionally, disrupted global network topology in pED was observed to be primarily relevant to altered subnetwork and nodal properties within the networks mediating the cognitive, motivational and inhibitory processes of male SA, possibly indicating disrupted integration of these networks in the whole brain networks and might account for pED patients' abnormal cognitive, motivational and inhibitory processes for male SA. In total, our findings provide evidence for disrupted integrity in large-scale brain networks underlying the neurobehavioral processes of male SA in pED and provide new insights into the understanding of the pathophysiological mechanisms of pED.
Young People, Social Media, Social Network Sites and Sexual Health Communication in Australia: "This is Funny, You Should Watch It"

Social media and social network sites (SNS) are an evolving area for sexual health communication with young people. They present opportunities and challenges for sexual health professionals and young people alike, such as learning through interactivity and addressing concerns about privacy. In this article, we present and discuss the findings from six rural and urban focus groups with young people in Australia about the use of social media and SNS for sexual health communication. We discuss a number of issues related to the use of social media and SNS for sexual health communication, such as concerns about bullying, privacy, and the stigma attached to sexual health.
A Comparison of Label-Induced Expectancy Bias in Two Preservice Teacher Education Programs

The purpose of this study was to determine whether a special education minor would reduce the likelihood of preservice elementary teachers developing negative expectancies regarding students labeled behaviorally disordered. Participating as subjects were 12 students from the Specialized Instruction program (SI) and 12 students from the Elementary and Early Childhood Education ElEd) Department at the University of Illinois Urbana-Champaign campus. The investigation was divided into two phases. In phase one, subjects filled out the Distributing Behavior Checklist (Algozzine, 1978), a measure of tolerance towards behavior problems. In phase two, subjects viewed two videotapes. Each tape focused on an average second grade boy in a reading group. Subjects were told that one of the videotaped boys was behaviorally disordered. After each videotape, subjects completed the Behavior Problem Checklist (Quay & Peterson, 1967) as a measure of bias. Results indicated that both groups had similar tolerances toward behavior problems and rated the student labeled behaviorally disordered more negatively. However, the bias effect was more pronounced in the ElEd group. Tolerance, teacher education program, and knowledge of the experimental intent accounted for 32% of the variance in expectancy bias.
Linking Neural Representation to Function in Stereoscopic Depth Perception: Roles of the Middle Temporal Area in Coarse versus Fine Disparity Discrimination

Neurons selective for binocular disparity form the neural substrate for stereoscopic depth perception and are found in several areas of primate visual cortex. Presumably, multiple representations of disparity exist to serve different functions, but the specific contributions of different visual areas to depth perception remain poorly understood. We examine this issue by comparing the contributions of the middle temporal (MT) area to performance of two depth discrimination tasks: a “coarse” task that involves discrimination between absolute disparities in the presence of noise, and a “fine” task that involves discrimination of very small differences in relative disparity between two stimuli in the absence of noise. In the fine task, we find that electrical microstimulation of MT does not affect perceptual decisions, although many individual MT neurons have sufficient sensitivity to account for behavioral performance. In contrast, microstimulation at the same recording sites does bias depth percepts in the coarse task. We hypothesized that these results may be explained by the fact that MT neurons do not represent relative disparity signals that are thought to be essential for the fine task. This hypothesis was supported by single-unit recordings that show that MT neurons signal absolute, but not relative, disparities in a stimulus configuration similar to that used in the fine task. This work establishes a link between the neural representation of disparity in MT and the functional contributions of this area to depth perception.
The Invisible Man: A Self-help Guide for Men With Eating Disorders, Compulsive Exercise and Bigorexia

Part I: Fat is More Than a Feminist Issue. Snakes and Ladders: Barriers to Recovery. Stories From the Past: The First Case of Anorexia Nervosa and Lord Byron's Eating Disorder. Part II: Do You Have a Body Image Disorder? Anorexia Nervosa. Bulimia Nervosa and Binge Eating. Muscle Dysmorphia (Bigorexia). Obesity. Part III: Science Fiction and Science Fact. What Causes Body Image Disorders in Men? Compulsive Exercise: When Does Exercise Become Unhealthy? The Poisoned Chalice: Anabolic Steroid Abuse. Physical Health and Body Image Disorders. Mental Health and Body Image Disorders. The Role of Culture: 'Fat is Not Just a Feminist Issue'. Part IV: 7 Stages to Recovery. Stage 1: Motivation - A Cost-benefit Analysis of Recovery. Stage 2: Sharing the Secret. Stage 3: Healthy Habits. Stage 4: Thinking Straight. Stage 5: Feeling Good. Stage 6: Seeking Professional Help - A Consumer's Guide. Stage 7: Remaining Well - Sadder and Wiser.
Dynamics of Responses in Compatible Potato - Potato virus Y Interaction Are Modulated by Salicylic Acid

To investigate the dynamics of the potato – Potato virus Y (PVY) compatible interaction in relation to salicylic acid - controlled pathways we performed experiments using non-transgenic potato cv. Désirée, transgenic NahG-Désirée, cv. Igor and PVYNTN, the most aggressive strain of PVY. The importance of salicylic acid in viral multiplication and symptom development was confirmed by pronounced symptom development in NahG-Désirée, depleted in salicylic acid, and reversion of the effect after spraying with 2,6-dichloroisonicotinic acid (a salicylic acid - analogue). We have employed quantitative PCR for monitoring virus multiplication, as well as plant responses through expression of selected marker genes of photosynthetic activity, carbohydrate metabolism and the defence response. Viral multiplication was the slowest in inoculated potato of cv. Désirée, the only asymptomatic genotype in the study. The intensity of defence-related gene expression was much stronger in both sensitive genotypes (NahG-Désirée and cv. Igor) at the site of inoculation than in asymptomatic plants (cv. Désirée). Photosynthesis and carbohydrate metabolism gene expression differed between the symptomatic and asymptomatic phenotypes. The differential gene expression pattern of the two sensitive genotypes indicates that the outcome of the interaction does not rely simply on one regulatory component, but similar phenotypical features can result from distinct responses at the molecular level.
Joint Image-Text Clustering using Deep Neural Networks

Nowadays there is a large amount of image and text data available in several large databases, however, properly aligned image and sentence data, a crucial requirement of any joint learning model, is quite hard to come by. To address this problem, we present a system that can jointly cluster images and text descriptions, and provide aligned data from unaligned uni-modal databases. The contribution of this work is twofold: we first present a system that learns a common embedding space in which image and text description form valid and sensible clusters. Second, we use our system for image captioning and retrieval tasks, and compare to the state of the art approaches. We use Caltech Birds Dataset [29] as reference data set for training and testing.
Arbitrary viewpoint image synthesis for real-time processing system using multiple image sensors

We have studied arbitrary viewpoint image synthesis using multiple sensors based on image-based rendering, in which the depth estimation is required for generating precise virtual images. Major problems in this estimation process include the increase of computational efforts and the decrease in performance for occluded regions. To solve these difficulties, we improve our depth estimation process by using the multi-resolution method and by weighting similar pixels to the target pixel in the block matching. Furthermore, we incorporate the proposed method to our prototype hardware system using the CMOS image sensors we have originally developed. Experimental results show that our proposed method and prototype system are efficient and effective compared to the previous work and that arbitrary viewpoint images are synthesized favorably.
An advanced Diffie-Hellman approach to image steganography

Diffie-Hellman key exchange is one of the most popular key exchange algorithms used in cryptography. Steganography is the approach of hiding information in a medium. When that medium is an image it is called as image steganography. The most popular image steganography algorithm in use presently is the Least Significant bit Algorithm (LSB). However this algorithm has proved to be easy to crack and hence rather insecure. The proposed algorithm uses a variation of the Diffie-Hellman algorithm to determine the pixel positions of the image to embed the information in. Both the sender and receiver maintain private keys. Along with this a public key is shared between them. The sender sends a public key to the receiver and vice versa. This public key is nothing but the product of the private key with the public key. The shared secret key is then the public key received multiplied with the private key of each. Now this value obtained is considered to be the pixel to embed data in. So all pixels with multiples of this value are embedded first using LSB. If still some data persists, then the shared key is substracted by 1 and all multiples of this new value are then filled. The process is repeated till the entire information is hidden.
Using Distributional Similarity for Lexical Expansion in Knowledge-based Word Sense Disambiguation

We explore the contribution of distributional information for purely knowledge-based word sense disambiguation. Specifically, we use a distributional thesaurus, computed from a large parsed corpus, for lexical expansion of context and sense information. This bridges the lexical gap that is seen as the major obstacle for word overlap‐based approaches. We apply this mechanism to two traditional knowledge-based methods and show that distributional information significantly improves disambiguation results across several data sets. This improvement exceeds the state of the art for disambiguation without sense frequency information—a situation which is especially encountered with new domains or languages for which no sense-annotated corpus is available.