gebhart/patrepeval huggingface dataset:
Mitoenergetic failure in Alzheimer disease (2006)

Brain cells are highly energy dependent for maintaining ion homeostasis during high metabolic activity. During active periods, full mitochondrial function is essential to generate ATP from electrons that originate with the oxidation of NADH. Decreasing brain metabolism is a significant cause of cognitive abnormalities of Alzheimer disease (AD), but it remains uncertain whether this is the cause of further pathology or whether synaptic loss results in a lower energy demand. Synapses are the first to show pathological symptoms in AD before the onset of clinical symptoms. Because synaptic function has high energy demands, interruption in mitochondrial energy supply could be the major factor in synaptic failure in AD. A newly discovered age-related decline in neuronal NADH and redox ratio may jeopardize this function. Mitochondrial dehydrogenases and several mutations affecting energy transfer are frequently altered in aging and AD. Thus, with the accumulation of genetic defects in mitochondria at the level of energy transfer, the issue of neuronal susceptibility to damage as a function of age and age-related disease becomes important. In an aging rat neuron model, mitochondria are both chronically depolarized and produce more reactive oxygen species with age. These concepts suggest that multiple treatment targets may be needed to reverse this multifactorial disease. This review summarizes new insights based on the interaction of mitoenergetic failure, glutamate excitotoxicity, and amyloid toxicity in the exacerbation of AD.
Preparation of Gel-Core-Solid Lipid Nanoparticle: A Novel Way to Improve the Encapsulation of Protein and Peptide (2010)

Using thymopentin and insulin as the model protein-drugs, novel Gel-Core-solid lipid nanoparticle (SLN) with the hydrogel core and lipid shell were prepared by double emulsion and thermal sensitive gel technology, with the intention to improve the entrapment efficiency. Pluronic F127 and Glyceryl palmitostearate were selected as hydrogel material and lipid material, respectively. The particle sizes and zeta-potential were characterized by dynamic light scattering and electrophoretic light scattering. Transmission electron microscopy (TEM) was employed to investigate the structure of this Gel-Core-SLN. The Gel-Core-SLN was successfully prepared and the particle size was 305.2 nm with zeta potential of -17.15 mV. Observations by TEM confirmed that most solidified hydrogel particles were dispersed in the central of Gel-Core-SLN as a form of single core, which effectively prevented the diffusion of proteins to the external water phase during preparation process. The entrapment efficiency of thymopentin-loaded Gel-Core-SLN and insulin-loaded Gel-Core-SLN were 61.97% and 57.36%, respectively. Both the two drug-loaded Gel-Core-SLNs showed relatively low burst release. The pharmacological availability of insulin-loaded Gel-Core-SLN was 6.02%. It was suggested that the Gel-Core-SLN could be a promising drug delivery system with the outstanding encapsulation efficiency, low burst release and relatively high pharmacological availability.
Theory and Practice of Contemporary Pharmaceutics (2012)

Introduction: Methods of Data Representation, Interpretation, and Analysis Craig Svensson, Tapash K. Ghosh Thermodynamics and States of Matter Adam M. Persky, Laszlo Prokai, Jeffrey A. Hughes Solubility Jeffrey A. Hughes, Adam M. Persky , Xin Guo, Tapash K. Ghosh Physiochemical Factors Affecting Biological Activity Blisse Jain, Surajit Dey, Hemant Alur, Bhaskara R. Jasti, Thomas P. Johnston, Ashim K. Mitra Micromeritics and Rheology Sunil S. Jambhekar Principles and Applications of Surface Phenomena Laszlo Prokai, Vien Nguyen, Bhaskara R. Jasti, Tapash K. Ghosh Theory and Applications of Diffusion and Dissolution Xiaoling Li, Bhaskara R. Jasti Drug and Dosage Form Development: Regulatory Perspectives Edward Dennis Bashaw Chemical Kinetics and Stability Tapash K. Ghosh Oral Conventional Solid Dosage Forms: Powders and Granules, Tablets, Lozenges, and Capsules Melgardt M. de Villiers Oral Controlled Release Solid Dosage Forms Emmanuel O. Akala Oral Liquid Dosag Forms: Solutions, Elixirs, Syrups, Suspensions, and Emulsions William M. Kolling, Tapash K. Ghosh Parenteral Routes of Delivery Yon Rojanasakul, Carl J. Malanga Transdermal and Topical Drug Delivery Systems Bhaskara R. Jasti, William Abraham, Tapash K. Ghosh Rectal and Vaginal Routes of Drug Delivery Nikhil R. Shitut, Sumeet K. Rastogi, Somnath Singh, Feirong Kang, Jagdish Singh Ocular, Nasal, Pulmonary, and Otic Routes of Drug Delivery Harisha Atluri, Giridhar, S. Tirucherai, Clapton Dias, Jignesh Patel, Ashim K. Mitra Delivery of Peptide and Protein Drugs Emily Ha, Manjori Ganguly, Xiaoling Li, Bhaskara R. Jasti, Uday B. Kompella Index
Identification of a Hypoxia Response Element in the Transferrin Receptor Gene (1999)

Expression of the transferrin receptor, which mediates iron uptake from transferrin, is negatively regulated post-transcriptionally by intracellular iron through iron-responsive elements in the 3'-untranslated region of the transferrin receptor mRNA. Transcriptional mechanisms are also involved in receptor expression, but these are poorly understood. In this study we have characterized the transferrin receptor promoter region and identified a functional hypoxia response element that contains a binding site for hypoxia-inducible factor-1 (HIF-1). Exposure of K562 and HeLa cells to hypoxia for 16 h resulted in a 2- to 3-fold increase in transferrin receptor mRNA expression. A motif with multipartite organization similar to the hypoxia response element of a number of hypoxia-inducible genes such as erythropoietin was identified within a 100-base pair sequence upstream of the transcriptional start site. Mutation of a site similar to the consensus HIF-binding site (HBS) in this motif attenuated the hypoxic response by 80%. Transient co-expression of the two HIF-1 subunits (HIF-1alpha and HIF-1beta) enhanced the wild type transferrin receptor promoter activity, but that which contained a mutated HBS yielded no such response. Electrophoretic mobility shift assays revealed that HIF-1 was stimulated and bound to the transferrin receptor HBS upon hypoxic challenge. Our results indicate that the transferrin receptor is a target gene for HIF-1.
Redesign of High-Affinity Nonspecific Nucleases with Altered Sequence Preference (2009)

It is of crucial importance to elucidate the underlying principles that govern the binding affinity and selectivity between proteins and DNA. Here we use the nuclease domain of Colicin E7 (nColE7) as a model system to generate redesigned nucleases with improved DNA-binding affinities. ColE7 is a bacterial toxin, bearing a nonspecific endonuclease domain with a preference for hydrolyzing DNA phosphodiester bonds at the 3'O-side after thymine and adenine; i.e., it prefers Thy and Ade at the -1 site. Using systematic computational screening, six nColE7 mutants were predicted to bind DNA with high affinity. Five of the redesigned single-point mutants were constructed and purified, and four mutants had a 3- to 5-fold higher DNA binding affinity than wild-type nColE7 as measured by fluorescence kinetic assays. Moreover, three of the designed mutants, D493N, D493Q, and D493R, digested DNA with an increased preference for guanine at +3 sites compared to the wild-type enzyme, as shown by DNA footprint assays. X-ray structure determination of the ColE7 mutant D493Q-DNA complex in conjunction with structural and free energy decomposition analyses provides a physical basis for the improved protein-DNA interactions: Replacing D493 at the protein-DNA interface with an amino acid residue that can maintain the native hydrogen bonds removes the unfavorable electrostatic repulsion between the negatively charged carboxylate and DNA phosphate groups. These results show that computational screening combined with biochemical, structural, and free energy analyses provide a useful means for generating redesigned nucleases with a higher DNA-binding affinity and altered sequence preferences in DNA cleavage.
Determining the Colloidal Behavior of Ionically Cross-Linked Polyelectrolytes with Isothermal Titration Calorimetry (2013)

Mixtures of polyelectrolytes and multivalent counterions can self-assemble into colloidal complexes. These complexes attract widespread interest in applications such as medicine, household product formulations, and separation processes. To facilitate the development of these colloidal dispersions, we examined isothermal titration calorimetry (ITC) as an automated screening tool for identifying the polymer and multivalent counterion compositions that (1) form ionically cross-linked colloidal complexes and (2) lead to their rapid coagulation (and macroscopic phase separation). By studying various polyelectrolyte/multivalent counterion mixtures, we have identified and generalized the features in the ITC data that indicate colloidal complex formation and coagulation. The limitations of this calorimetric screening method were also elucidated. These analyses suggest that ITC can be effective for screening the short-term colloidal behavior of polyelectrolyte/multivalent counterion mixtures but are unreliable in revealing their long-term (equilibrium) properties.
Clonal Origin of Epithelial Ovarian Carcinoma: Analysis by Loss of Heterozygosity, p53 Mutation, and X-Chromosome Inactivation (1992)

These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer.
Synthesis and analgesic activities of 2-substituted-1H-phenantro [9,10-d] imidazoles. (1999)

Some 2-substituted-1H-phenantro [9, 10-d] imidazole compounds were synthesized and their analgesic activities were determined on the Swiss albino mice (25-35 g) of either sex. In the synthesis, phenantre-nequinone molecule was reacted with different aldehyde derivatives in acetic acid presence of ammonium acetate and finally 16 compounds were gained. All spectral and elemental analyses of the original compounds were completed and their structures were elucidated. Analgesic activity of the compounds were examined by using the Tail-Clip method. 2-Phenyl-1H-phenantro [9, 10-d] imidazole (comp.1) and 2-(4-chlorophenyl)-1H-phenantro [9, 10-d] imidazole (comp. 6) were found to be more active than the others and their LD50 values were found to be greater than 100 mg/kg (i.p.).
Escherichia coli Biofilms Have an Organized and Complex Extracellular Matrix Structure (2013)

Bacteria can form biofilms in diverse niches, including abiotic surfaces, living cells, and at the air-liquid interface of liquid media. Encasing these cellular communities is a self-produced extracellular matrix (ECM) that can be composed of proteins, polysaccharides, and nucleic acids. The ECM protects biofilm bacteria from environmental insults and also makes the dissolution of biofilms very challenging. As a result, formation of biofilms within humans (during infection) or on industrial material (such as water pipes) has detrimental and costly effects. In order to combat bacterial biofilms, a better understanding of components required for biofilm formation and the ECM is required. This study defined the ECM composition and architecture of floating pellicle biofilms formed by Escherichia coli.
Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development (2013)

An increased rate of lipid synthesis in cancerous tissues has long been recognised as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids to cellular transformation, tumour development and tumour progression, as well as their potential role in facilitating the spread of cancerous cells to secondary sites, are not yet fully understood. In this article, we review the recent findings that support the importance of lipid synthesis and metabolism in tumorigenesis. Specifically, we explore the role of aberrant lipid biosynthesis in cancer cell migration and invasion, and in the induction of tumour angiogenesis. These processes are crucial for the dissemination of tumour cells and formation of metastases, which constitute the main cause of cancer mortality.
Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans (2010)

Oxytocin (OT) is becoming increasingly established as a prosocial neuropeptide in humans with therapeutic potential in treatment of social, cognitive, and mood disorders. However, the potential of OT as a general facilitator of human learning and empathy is unclear. The current double-blind experiments on healthy adult male volunteers investigated first whether treatment with intranasal OT enhanced learning performance on a feedback-guided item-category association task where either social (smiling and angry faces) or nonsocial (green and red lights) reinforcers were used, and second whether it increased either cognitive or emotional empathy measured by the Multifaceted Empathy Test. Further experiments investigated whether OT-sensitive behavioral components required a normal functional amygdala. Results in control groups showed that learning performance was improved when social rather than nonsocial reinforcement was used. Intranasal OT potentiated this social reinforcement advantage and greatly increased emotional, but not cognitive, empathy in response to both positive and negative valence stimuli. Interestingly, after OT treatment, emotional empathy responses in men were raised to levels similar to those found in untreated women. Two patients with selective bilateral damage to the amygdala (monozygotic twins with congenital Urbach-Wiethe disease) were impaired on both OT-sensitive aspects of these learning and empathy tasks, but performed normally on nonsocially reinforced learning and cognitive empathy. Overall these findings provide the first demonstration that OT can facilitate amygdala-dependent, socially reinforced learning and emotional empathy in men.
Continuous speech recognition by statistical methods (1976)

Statistical methods useful in automatic recognition of continuous speech are described. They concern modeling of a speaker and of an acoustic processor, extraction of the models' statistical parameters and hypothesis search procedures and likelihood computations of linguistic decoding. Experimental results are presented that indicate the power of the methods.
A MEMS differential affinity sensor for continuous glucose detection (2011)

This paper presents a differential affinity sensor for continuous glucose monitoring. The sensor, based on microelectromechanical systems (MEMS) technology, consists of two magnetically driven vibrating diaphragms each situated inside a microchamber. The chambers respectively contain solutions of poly(N-hydroxyethyl acrylamide-ran-3-acrylamidophenylboronic acid) (PHEAA-ran-PAAPBA), a glucose-binding polymer, and poly(acrylamide) (PAM), a glucose-insensitive polymer. As glucose permeates through a semi-permeable membrane into each chamber, the viscosity of the PHEAA-ran-PAAPBA solution increases due to glucose binding, while the viscosity of the PAM solution is unchanged due to a lack of glucose binding. Measurement of the viscosity difference between the two chambers, via differential capacitive detection of the vibration damping, thus allows determination of the glucose concentration while rejecting viscosity changes caused by environmental fluctuations. In-vitro and in-vivo testing demonstrates the potential of the device to be used as a subcutaneously implanted sensor for continuous glucose monitoring.
The DREAM: An Integrated Photonic Thresholder (2013)

We propose a novel all-optical integrated thresholder called the dual resonator enhanced asymmetric Mach-Zehnder interferometer (DREAM). Unlike prior integrated photonic devices, the DREAM exhibits properties of stable binary decision making, outputting a constant “one” power value for signals above a certain power level and “zero” for signals of lower powers. This thresholding shape arises from the interference of complementary nonlinear effects of two microring resonators (MRR), one in each arm of a Mach-Zehnder interferometer (MZI). The proposed device performs several orders of magnitude better in size, decision latency, energy efficiency, and stability compared to fiber-based methods of optical thresholding. It is best suited for application in densely integrated systems where rapid conversion between analog and digital signal domains is ubiquitous, such as hybrid analog-digital and neuromorphic processing architectures. We derive analytical steady-state solutions to the nonlinear MRR, which enable design simulation, optimization, and automation of a continuous signal thresholder about three orders of magnitude faster than with numerical simulation. Additional numerical simulations indicate the possibility of a 50 GHz pulse thresholder with a 380 pJ switching threshold in a silicon-on-insulator (SOI) platform. The proposed circuit design techniques are potentially applicable to a wide range of materials, waveguide platforms, and resonator types, but for concreteness, we limit the focus of this paper to MRRs in SOI.
Universal rateless coding with finite message set (2012)

Universal rateless coding over unknown discrete memoryless channels (DMC) is considered. In rateless codes each codeword is infinitely long, and the decoding time depends on the confidence level of the decoder. This work considers the finite message set case where a finite number of bits are transmitted over an unknown discrete memoryless channel, with a fix allowed error probability. Using rateless codes along with sequential universal decoding that utilizes a mixture probability law instead of the unknown channel law, an optimal universal scheme is obtained. The analysis specifies explicitly the attainable rate, at each message set size and allowed error probability, which reflects the cost of universality.
Assessment of thoracoabdominal bands to detect respiratory effort-related arousal (2003)

It would be helpful to be able to identify respiratory effort-related arousal (RERA) without needing to measure oesophageal pressure. Thoracoabdominal movements yield an indirect flow measurement from which reduction of amplitude and alteration of the inspiratory flow curve can be detected. The aim of this study was to evaluate the accuracy of using the shape and amplitude of signals from thoracoabdominal bands (inductance plethysmography) to detect RERAs. Altogether, 94 subjects suspected of having sleep apnoea but with an apnoea/hypopnoea index < or = 10 in full polysomnography with oesophageal pressure were studied. A routine polysomnographical analysis was carried out. The polysomnographies were then reanalysed at random to determine which of the identified arousals were due to RERA, as determined either by oesophageal pressure or by induction bands without an oesophageal pressure signal. Altogether, 14,617 arousals were analysed. The sensitivity and specificity to find RERA (arousal by arousal) from bands versus oesophageal pressure were both 94%. The average difference of RERA index between oesophageal pressure and bands was -0.6. The correlation between RERA index determined by oesophageal pressure and bands was 0.98. To evaluate the intra and interobserver agreement, 1183 arousals were additionally analysed. The intraobserver agreement was 91% for RERAs by oesophageal pressure and 80% by bands. The interobserver agreement was 89% by oesophageal pressure and 85% by bands. The thoracoabdominal bands can be used to identify respiratory effort-related arousal (obstructive events not detected by thermistor) with similar efficacy to oesophageal pressure measurement. Since bands are routinely used in most polysomnographies, they can be used as the usual method to detect respiratory effort-related arousal, using a thermistor to evaluate apnoeas and hypopnoeas or as a complement to other methods, such as nasal cannula, which can detect apnoeas, hypopnoeas and respiratory effort-related arousal.
EGF Receptor-Targeted Synthetic Double-Stranded RNA Eliminates Glioblastoma, Breast Cancer, and Adenocarcinoma Tumors in Mice (2005)

The strategy described has yielded an effective treatment of EGFR over-expressing GBM in an animal model. If this strategy is translated successfully to the clinical setting, it may actually offer help to GBM patients. Moreover the elimination of two additional EGFR over-expressing cancers in vivo suggests that in principle this strategy can be applied to treat other tumors that over-express EGFR.
Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. (1994)

Nonreceptor tyrosine kinases such as the newly described 70-kDa (ZAP-70/Syk) and Src-related tyrosine kinases are coupled to a variety of receptors, including the antigen receptors on B- and T-cells and the Fc receptors for IgE (Fc epsilon RI) and IgG (Fc gamma RI, Fc gamma RIII/CD16). Various subunits of these receptors contain homologous activation motifs which appear capable of autonomously triggering cell activation. Two forms of this motif are present in the Fc epsilon RI multimeric complex: one in the beta chain and one in the gamma chain. Here we show that each of the two tyrosine kinases known to be involved in Fc epsilon RI signaling is controlled by a distinct motif-containing chain. Lyn associates with the nonactivated beta chain, whereas gamma promotes the activation of Syk. We also show that neither the beta nor the gamma motif alone can account for the full signaling capacity of the entire receptor. We propose that, upon triggering of the tetrameric receptor, Lyn already bound to beta becomes activated and phosphorylates beta and gamma; the phosphorylation of gamma induces the association of Syk with gamma and also the activation of Syk, resulting in the phosphorylation and activation of phospholipase C gamma 1. Cooperative recruitment of specific kinases by the various signaling chains found in this family of antigen receptors could represent a way to achieve the full signaling capacity of the multimeric complexes.
Hedgehog signaling in normal urothelial cells and in urothelial carcinoma cell lines (2004)

Constitutive activation of hedgehog signaling, often caused by PTCH1 inactivation and leading to inappropriate activation of GLI target genes, is crucial for the development of several human tumors including basal cell carcinoma of the skin and medulloblastoma. The PTCH1 gene at 9q22 is also considered as a candidate tumor suppressor in transitional cell carcinoma (TCC), of which >50% show LOH in this region. However, only rare mutations have been found in PTCH1. We have therefore investigated GLI-dependent promoter activity and expression of hedgehog pathway components in TCC cell lines and proliferating normal urothelial cells. Normal urothelial cells cultured in serum-free medium, but not TCC lines exhibited low, but significant promoter activity under standard growth conditions. Accordingly, GLI1-3 and PTCH1 mRNAs were expressed at moderate levels, and sonic hedgehog (SHH) mRNA expression was low to undetectable. In co-transfection experiments GLI1 increased promoter activity significantly in one TCC line and further in normal urothelial cells, but less strongly in other TCC lines. Expression patterns of GLI factor mRNAs did not correlate with inducibility. No significant effects of SHH or cyclopamine on proliferation were observed, ruling out autocrine effects. However, SHH induced GLI-dependent promoter activity in normal urothelial cells. Taken together, our data suggest that the hedgehog pathway is weakly active in normal adult urothelial cells and of limited importance in TCC.