gebhart/patrepeval huggingface dataset:
Regulation of Gene Expression by a Metabolic Enzyme (2004)

Gene expression in eukaryotes is normally believed to be controlled by transcriptional regulators that activate genes encoding structural proteins and enzymes. To identify previously unrecognized DNA binding activities, a yeast proteome microarray was screened with DNA probes; Arg5,6, a well-characterized mitochondrial enzyme involved in arginine biosynthesis, was identified. Chromatin immunoprecipitation experiments revealed that Arg5,6 is associated with specific nuclear and mitochondrial loci in vivo, and Arg5,6 binds to specific fragments in vitro. Deletion of Arg5,6 causes altered transcript levels of both nuclear and mitochondrial target genes. These results indicate that metabolic enzymes can directly regulate eukaryotic gene expression.
Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate (1993)

Axial patterning in the nervous system of vertebrate embryos depends on inductive signals that derive from the organizer region (the dorsal lip in amphibians and the node in birds and mammals) and leter from the notochord and floor plate. Previous studies have shown that Pintallavis, a member of the HNF-3/fork head transcription factor family, is expressed selectively by these cell groups in frog embryos and may be involved in regulating neural development. We report here that in early rat and mouse embryos, the embryonic endoderm, the node, the notochord and the floor plate express two related transcription factors, HNF-3 alpha and HNF-3 beta, which also function in the control of liver cell differentiation. Early embryonic tissues express variant forms of HNF-3 beta which derive from the use of 5' alternative exons. Within the organizer region and notochord, HNF-3 beta and HNF-3 alpha have distinct temporal patterns of expression and appear in partially overlapping domains. The early expression pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate cells is similar to that of Pintallavis in frog embryos. There does not appear to be a Pintallavis homologue in mice. This prompted us to isolate and analyze the expression of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expressed in the dorsal lip, pharyngeal endoderm and floor plate. In contrast to mammalian HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after neural tube closure. Thus, the combined expression patterns of Pintallavis and HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within neural tissue, the onset of expression of these regulatory genes define successive stages in the differentiation of floor plate cells. The results reported here show that closely related members of the HNF-3/fork head gene family are expressed by axial midline cell groups involved in neural induction and patterning and suggest the involvement of these genes in the development of the vertebrate neuraxis.
Topical negative pressure (TNP): the evolution of a novel wound therapy (2003)

Topical negative pressure is a novel non-pharmacological therapy that is now being adopted as a standard of care in wound care management programmes. This review assesses where and how it can be best used.
Rethinking Atrous Convolution for Semantic Image Segmentation (2017)

In this work, we revisit atrous convolution, a powerful tool to explicitly adjust filter's field-of-view as well as control the resolution of feature responses computed by Deep Convolutional Neural Networks, in the application of semantic image segmentation. To handle the problem of segmenting objects at multiple scales, we design modules which employ atrous convolution in cascade or in parallel to capture multi-scale context by adopting multiple atrous rates. Furthermore, we propose to augment our previously proposed Atrous Spatial Pyramid Pooling module, which probes convolutional features at multiple scales, with image-level features encoding global context and further boost performance. We also elaborate on implementation details and share our experience on training our system. The proposed `DeepLabv3' system significantly improves over our previous DeepLab versions without DenseCRF post-processing and attains comparable performance with other state-of-art models on the PASCAL VOC 2012 semantic image segmentation benchmark.
Signals That Regulate Food Intake and Energy Homeostasis (1998)

Feeding behavior is critical for survival. In addition to providing all of the body's macronutrients (carbohydrates, lipids, and proteins) and most micronutrients (minerals and vitamins), feeding behavior is a fundamental aspect of energy homeostasis, the process by which body fuel stored in the form of adipose tissue is held constant over long intervals. For this process to occur, the amount of energy consumed must match precisely the amount of energy expended. This review focuses on the molecular signals that modulate food intake while integrating the body's immediate and long-term energy needs.
Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension (1997)

Chemokines are a group of small, homologous proteins that regulate leukocyte migration, hemopoiesis, and HIV-1 absorption. We report here the cloning and characterization of a novel murine and human C-C chemokine termed Exodus-2 for its similarity to Exodus-1/MIP-3alpha/LARC, and its chemotactic ability. This novel chemokine has a unique 36 or 37 (murine and human, respectively) amino acid carboxyl-terminal extension not seen in any other chemokine family member. Purified recombinant Exodus-2 was found to have two activities classically associated with chemokines: inhibiting hemopoiesis and stimulating chemotaxis. However, Exodus-2 also had unusual characteristics for C-C chemokines. It selectively stimulated the chemotaxis of T-lymphocytes and was preferentially expressed in lymph node tissue. The combination of these characteristics may be a functional correlate for the unique carboxyl-terminal structure of Exodus-2.
What goes around comes around (2006)

An emergent class of web applications blurs the boundary between single user application and online public space. Recently popular web applications like del.icio.us help manage information traditionally kept on personal machines, while allowing for sharing with the community at large. An analysis of del.icio.us, a web-based bookmarks manager, shows that users who perceive greater degrees of social presence are more likely to annotate their bookmarks with information that could facilitate the sharing and discovery of bookmarks for other del.icio.us users. The design principles of del.icio.us and similar systems along with the findings of the present analysis reveal useful implications for the design of information sharing systems and knowledge repositories.
Studies on oxytocinase activity in human pregnancy (1966)

Our knowledge of the endocrine functions of the pituitary gland is comparatively recent* Text-books of physiology published in the late 19th century (e.g* Michael Post Text-Book of Physiology, 1891 edition) gave a good histological description of the gland, emphasised its ductless nature, but could attribute no definite function to it. The first evidence suggesting any function for the ft pituitary body was presented by Oliver and 0chafer in 1895* They observed that extracts from the whole pit¬ uitary gland had a pressor activity when injected intra¬ venously into the anaesthetised dog. Howell (1898) showed that the substance responsible for this pressor action of pituitary extracts was obtainable only from one part of the organ, and rather surprisingly, only from its posterior, neural lobe. At the time this appeared to be quite an anomalous finding, as the main glandular structures were known to be localised to the anterior lobe of the pituitary.
Development of Polydimethylsiloxane Substrates with Tunable Elastic Modulus to Study Cell Mechanobiology in Muscle and Nerve (2012)

Mechanics is an important component in the regulation of cell shape, proliferation, migration and differentiation during normal homeostasis and disease states. Biomaterials that match the elastic modulus of soft tissues have been effective for studying this cell mechanobiology, but improvements are needed in order to investigate a wider range of physicochemical properties in a controlled manner. We hypothesized that polydimethylsiloxane (PDMS) blends could be used as the basis of a tunable system where the elastic modulus could be adjusted to match most types of soft tissue. To test this we formulated blends of two commercially available PDMS types, Sylgard 527 and Sylgard 184, which enabled us to fabricate substrates with an elastic modulus anywhere from 5 kPa up to 1.72 MPa. This is a three order-of-magnitude range of tunability, exceeding what is possible with other hydrogel and PDMS systems. Uniquely, the elastic modulus can be controlled independently of other materials properties including surface roughness, surface energy and the ability to functionalize the surface by protein adsorption and microcontact printing. For biological validation, PC12 (neuronal inducible-pheochromocytoma cell line) and C2C12 (muscle cell line) were used to demonstrate that these PDMS formulations support cell attachment and growth and that these substrates can be used to probe the mechanosensitivity of various cellular processes including neurite extension and muscle differentiation.
Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the γ2 subunit (1992)

The mammalian GABAA receptor is a multisubunit protein containing a variety of binding sites for psychotropic agents. One of the most widely used of these drugs, ethanol, enhances the function of GABAA receptors in certain circumstances but not others. Previous studies have demonstrated that alternative splicing of the gamma 2L GABA subunit results in an ethanol sensitive and an ethanol-insensitive form, when combined with alpha and beta subunits. We have used in vitro mutagenesis and expression in Xenopus oocytes to show that the consensus site for phosphorylation by protein kinase C contained in the gamma 2L insert is critical for modulation by ethanol but not benzodiazepines, and manipulation of the phosphorylating enzymes in oocytes containing alpha 1 beta 1 gamma 2L can prevent ethanol enhancement. It is likely that phosphorylation or dephosphorylation of a specific site on the GABAA receptor protein can act as a control mechanism for neuronal responses to alcohol exposure.
Engineering Escherichia coli for xylitol production from glucose‐xylose mixtures (2006)

The range of value-added chemicals produced by Escherichia coli from simple sugars has been expanded to include xylitol. This was accomplished by screening the in vivo activity of a number of heterologous xylitol-producing enzymes. Xylose reductases from Candida boidinii (CbXR), Candida tenuis (CtXR), Pichia stipitis (PsXR), and Saccharmoyces cerivisiae (ScXR), and xylitol dehydrogenases from Gluconobacter oxydans (GoXDH) and Pichia stipitis (PsXDH) were all functional in E. coli to varying extents. Replacement of E. coli's native cyclic AMP receptor protein (CRP) with a cyclic AMP-independent mutant (CRP*) facilitated xylose uptake and xylitol production from mixtures of glucose and xylose, with glucose serving as the growth substrate and source of reducing equivalents. Of the enzymes tested, overexpression of NADPH-dependent CbXR produced the highest concentrations of xylitol in shake-flask cultures (approximately 275 mM in LB cultures, approximately 180 mM using minimal medium). Expression of CbXR in strain PC09 (crp*, DeltaxylB) in a 10-L controlled fermentation containing minimal medium resulted in production of approximately 250 mM xylitol (38 g/L), with concomitant utilization of approximately 150 mM glucose. The ratio of moles xylitol produced (from xylose) per mole glucose consumed was improved to > 3.7:1 using metabolically active "resting" cells.
Targeting ανβ3 and ανβ5 inhibits photon-induced hypermigration of malignant glioma cells (2011)

Peripheral glioma cells are at risk of attraction into the adjacent healthy brain by serum components leaking through the blood brain barrier (BBB). Radiation therapy is associated with upregulation of Vn receptor integrins and enhanced glioma cell migration at sublethal doses. This effect can be inhibited by specific integrin blockade. Future therapeutical benefit may be derived from pharmacological integrin inhibition in combination with photon irradiation.
Emotional and Behavioural Problems in Children and Adolescents with Congenital Heart Disease (2005)

Major physical illnesses usually have an impact on the psychological well-being of any individual. An illness of early onset, with necessity of frequent diagnostic and therapeutic interventions can adversely affect the emotional balance and behavioural adaptation of children and adolescents. This is applicable for congenital heart disease, especially if it is severe and life-threatening. Psychological implications are a significant part of chronic illnesses and they can affect prognosis and outcome. Congenital heart diseases which are diagnosed early can influence mother infant interactions from the beginning, in a crucial period of the infant’s psychological development and thus may adversely affect the mental health of children and adolescents. Children and adolescents with congenital heart diseases can have anxiety, depressive reactions, low self esteem or impulsiveness. The behavioural and emotional problems of children and adolescents, if not diagnosed and managed early, can lead on to significant psychological morbidity in later life.
Stability analysis of the spatiotemporal Lugiato-Lefever model for Kerr optical frequency combs in the anomalous and normal dispersion regimes (2014)

We propose a detailed stability analysis of the Lugiato-Lefever model for Kerr optical frequency combs in whispering-gallery-mode resonators when they are pumped in either the anomalous- or normal-dispersion regime. We analyze the spatial bifurcation structure of the stationary states depending on two parameters that are experimentally tunable; namely, the pump power and the cavity detuning. Our study demonstrates that, in both the anomalous- and normal-dispersion cases, nontrivial equilibria play an important role in this bifurcation map because their associated eigenvalues undergo critical bifurcations that are actually foreshadowing the existence of localized and extended spatial dissipative structures. The corresponding bifurcation maps are evidence of a considerable richness from a dynamical standpoint. The case of anomalous dispersion is indeed the most interesting from the theoretical point of view because of the considerable variety of dynamical behavior that can be observed. For this case we study the emergence of super- and subcritical Turing patterns (or primary combs) in the system via modulational instability. We determine the areas where bright isolated cavity solitons emerge, and we show that soliton molecules can emerge as well. Very complex temporal patterns can actually be observed in the system, where solitons (or soliton complexes) coexist with or without mutual interactions. Our investigations also unveil the mechanism leading to the phenomenon of breathing solitons. Two routes to chaos in the system are identified; namely, a route via the destabilization of a primary comb, and another via the destabilization of solitons. For the case of normal dispersion, we unveil the mechanism leading to the emergence of weakly stable Turing patterns. We demonstrate that this weak stability is justified by the distribution of stable and unstable fixed points in the parameter space (flat states). We show that dark cavity solitons can emerge in the system, and also show how these solitons can coexist in the resonator as long as they do not interact with each other. We find evidence of breather solitons in this normal dispersion regime as well. The Kerr frequency combs corresponding to all these spatial dissipative structures are analyzed in detail, along with their stability properties. A discussion is led about the possibility to gain unifying comprehension of the observed spectra from the dynamical complexity of the system.
Ultrafast dynamic computed tomography myelography for the precise identification of high-flow cerebrospinal fluid leaks caused by spiculated spinal osteophytes (2015)

Spinal osteophytes piercing the dura are a more frequent cause of high-flow CSF leaks than previously recognized. Ultrafast dynamic CT myelography adds value beyond standard dynamic myelography or digital subtraction myelography in the diagnosis and anatomical characterization of high-flow spinal CSF leaks caused by these osteophytes. This information allows for appropriate planning for percutaneous or surgical treatment.
A chimeric thyroid hormone receptor constitutively bound to DNA requires retinoid X receptor for hormone-dependent transcriptional activation in yeast. (1994)

T3 receptors (TRs) regulate transcription by binding to specific DNA response elements as heterodimers with the retinoid X receptors (RXRs). To study the consequences of this heterodimerization for transcriptional regulation in the absence of complications associated with its effects on DNA binding affinity, we expressed in the yeast Saccharomyces cerevisiae a chimeric protein consisting of the rat TR beta 1 ligand-binding domain fused to the DNA-binding domain of the bacterial repressor lexA (lexATR). LexATR is a weak, T3-responsive activator of a beta-galactosidase reporter gene controlled by upstream lexA-binding sites (lexA-beta-gal). In contrast, coexpression of human RXR alpha (hRXR alpha) strongly enhances both the basal and ligand-induced transcriptional activities. Both the N-terminal activation domain of RXR and sequences at the extreme C terminus of lexATR are required for this T3- and RXR-dependent transcriptional activation. The lexATR chimera was also used to characterize receptor-receptor interactions using the two-hybrid system. Coexpression of B42RXR, a fusion protein of the human RXR alpha ligand-binding domain and the B42 transcriptional activation domain, strongly increases the transcriptional activity of lexATR in the absence of T3 or 9-cis-retinoic acid. We conclude that RXR is essential for full, T3-dependent transcriptional activity of the TR in yeast, and that protein-protein interaction of TR and RXR in vivo is ligand-independent.
Influence of heat-stress induced dehydration on mental functions (1986)

The effect of primary dehydration of various levels (1, 2 and 3% body-weight deficits) on mental functions of different complexities were studied in eight heat-acclimatized subjects drawn from tropical regions of India. These subjects were also studied after a bout of exercise in heat under two conditions viz., Hot Dry (45°C DB, 30% rh), and Hot Humid (39DC DB, 60% rh) at 34°C WBGT. No significant change in routine mental work was seen either under dehydration per se of any level or after subsequent exercise under heat when compared with the normal state. On the other hand, at 2 and 3% levels of primary dehydration a further reduction was noted in all the functions though it was not significant. Inter-variations in Hot Humid and Hot Dry conditions were not significant except for more pronounced reductions in the concentration component in Hot Humid conditions.
Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity (2009)

The success of clinically relevant immunotherapies requires reversing tumor-induced immunosuppression. Here we demonstrated that linear polyethylenimine-based (PEI-based) nanoparticles encapsulating siRNA were preferentially and avidly engulfed by regulatory DCs expressing CD11c and programmed cell death 1-ligand 1 (PD-L1) at ovarian cancer locations in mice. PEI-siRNA uptake transformed these DCs from immunosuppressive cells to efficient antigen-presenting cells that activated tumor-reactive lymphocytes and exerted direct tumoricidal activity, both in vivo and in situ. PEI triggered robust and selective TLR5 activation in vitro and elicited the production of hallmark TLR5-inducible cytokines in WT mice, but not in Tlr5-/- littermates. Thus, PEI is a TLR5 agonist that, to our knowledge, was not previously recognized. In addition, PEI-complexed nontargeting siRNA oligonucleotides stimulated TLR3 and TLR7. The nonspecific activation of multiple TLRs (specifically, TLR5 and TLR7) reversed the tolerogenic phenotype of human and mouse ovarian tumor-associated DCs. In ovarian carcinoma-bearing mice, this induced T cell-mediated tumor regression and prolonged survival in a manner dependent upon myeloid differentiation primary response gene 88 (MyD88; i.e., independent of TLR3). Furthermore, gene-specific siRNA-PEI nanocomplexes that silenced immunosuppressive molecules on mouse tumor-associated DCs elicited discernibly superior antitumor immunity and enhanced therapeutic effects compared with nontargeting siRNA-PEI nanocomplexes. Our results demonstrate that the intrinsic TLR5 and TLR7 stimulation of siRNA-PEI nanoparticles synergizes with the gene-specific silencing activity of siRNA to transform tumor-infiltrating regulatory DCs into DCs capable of promoting therapeutic antitumor immunity.
Simulating price responsive distributed resources (2005)

Distributed energy resources (DER) include distributed generation, storage, and responsive demand. The integration of DER into the power system control framework is part of the evolutionary advances that allow these resources to actively participate in the energy balance equation. Price can provide a powerful signal for independent decision-making in distributed control strategies. To study the impact of price responsive DER on the electric power system requires generation and load models that can capture the dynamic coupling between the energy market and the physical operation of the power system in appropriate time frames. This paper presents modeling approaches for simulating electricity market price responsive DER, and introduces a statistical mechanics approach to modeling the aggregated response of a transformed electric system of pervasive, transacting DER.
MINE: Mutual Information Neural Estimation (2018)

We argue that the estimation of mutual information between high dimensional continuous random variables can be achieved by gradient descent over neural networks. We present a Mutual Information Neural Estimator (MINE) that is linearly scalable in dimensionality as well as in sample size, trainable through back-prop, and strongly consistent. We present a handful of applications on which MINE can be used to minimize or maximize mutual information. We apply MINE to improve adversarially trained generative models. We also use MINE to implement Information Bottleneck, applying it to supervised classification; our results demonstrate substantial improvement in flexibility and performance in these settings.