gebhart/patrepeval huggingface dataset:
Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation (2017)

RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here, we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs. In mouse urothelial organoids, PPAR agonism is sufficient to drive growth-factor-independent growth in the context of concurrent tumor suppressor loss. Similarly, mutant RXRA stimulates growth-factor-independent growth of <i>Trp53/Kdm6a</i> null bladder organoids. Mutant RXRA-driven growth of urothelium is reversible by PPAR inhibition, supporting PPARs as targetable drivers of bladder cancer.
Determination of Mitochondrial Respiration and Glycolysis in <em>Ex Vivo</em> Retinal Tissue Samples (2021)

Mitochondrial respiration is a critical energy-generating pathway in all cells, especially retinal photoreceptors that possess a highly active metabolism. In addition, photoreceptors also exhibit high aerobic glycolysis like cancer cells. Precise measurements of these metabolic activities can provide valuable insights into cellular homeostasis under physiological conditions and in disease states. High throughput microplate-based assays have been developed to measure mitochondrial respiration and various metabolic activities in live cells. However, a vast majority of these are developed for cultured cells and have not been optimized for intact tissue samples and for application ex vivo. Described here is a detailed step-by-step protocol, using microplate-based fluorescence technology, to directly measure oxygen consumption rate (OCR) as an indicator of mitochondrial respiration, as well as extracellular acidification rate (ECAR) as an indicator of glycolysis, in intact ex vivo retinal tissue. This method has been used to successfully assess metabolic activities in adult mouse retina and demonstrate its application in investigating cellular mechanisms of aging and disease.
Convenient Synthesis ofN-(2, 2-Dimethyl-1, 3-dioxan-5-yl)-1H-indazole-3-carboxamide, the Intermediate of 5-HT3Receptor Antagonist (1997)

Abstract The convenient large-scale synthesis of the title compound, which is the intermediate of potent 5-HT3 receptor antagonist, N-(1-benzyl-4-memylhexahydro-1H-1,4-diazepin-6-yl)-1H-indazole-3-carboxamide (1), is described.
Liposomes for Antibiotic Encapsulation and Delivery (2020)

When antibiotics are administered, orally or intravenously, they pass through different organs and layers of tissue on their way to the site of infection; this can cause dilution and/or intoxication. To overcome these problems, drug delivery vehicles have been used to encapsulate and deliver antibiotics, improving their therapeutic index while minimizing their adverse effects. Liposomes are self-assembled lipid vesicles made from at least one bilayer of phospholipids with an inner aqueous compartment. Liposomes are attractive vehicles to deliver antibiotics because they can encapsulate both hydrophobic and hydrophilic antibiotics, they have low toxicity, and they can change the biodistribution of the drug. Furthermore, liposomes have been approved by regulatory agencies. However, most developmental and mechanistic research in the field has been focused on encapsulation and delivery of anticancer drugs, a class of molecules that differ significantly in chemistry from antibiotics. In this critical Review, we discuss the state of knowledge regarding the design of liposomes for encapsulation and delivery of antibiotics and offer insight into the challenges and promises of using liposomes for antibiotic delivery.
Modal Estimation of Civil Structures Subject to Ambient and Harmonic Excitation (2008)

<p style="text-align: left">In this paper addresses the problems of separating structural modes and harmonics arising from sinusoidal excitation. Though the problem is mostly know in mechanical engineering applications such as rotating machinery, some civil engineering applications experiences the same challenges. A robust and fast harmonic detection procedure is presented and illustrated on a civil engineering case.
Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients. (1992)

Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.
Multiparameter Flow Cytometry Analysis of the Human Spleen Applied to Studies of Plasma-Derived EVs From Plasmodium vivax Patients (2021)

The spleen is a secondary lymphoid organ with multiple functions including the removal of senescent red blood cells and the coordination of immune responses against blood-borne pathogens, such as malaria parasites. Despite the major role of the spleen, the study of its function in humans is limited by ethical implications to access human tissues. Here, we employed multiparameter flow cytometry combined with cell purification techniques to determine human spleen cell populations from transplantation donors. Spleen immuno-phenotyping showed that CD45<sup>+</sup> cells included B (30%), CD4<sup>+</sup> T (16%), CD8<sup>+</sup> T (10%), NK (6%) and NKT (2%) lymphocytes. Myeloid cells comprised neutrophils (16%), monocytes (2%) and DCs (0.3%). Erythrocytes represented 70%, reticulocytes 0.7% and hematopoietic stem cells 0.02%. Extracellular vesicles (EVs) are membrane-bound nanoparticles involved in intercellular communication and secreted by almost all cell types. EVs play several roles in malaria that range from modulation of immune responses to vascular alterations. To investigate interactions of plasma-derived EVs from Plasmodium vivax infected patients (PvEVs) with human spleen cells, we used size-exclusion chromatography (SEC) to separate EVs from the bulk of soluble plasma proteins and stained isolated EVs with fluorescent lipophilic dyes. The integrated cellular analysis of the human spleen and the methodology employed here allowed in vitro interaction studies of human spleen cells and EVs that showed an increased proportion of T cells (CD4+ 3 fold and CD8+ 4 fold), monocytes (1.51 fold), B cells (2.3 fold) and erythrocytes (3 fold) interacting with PvEVs as compared to plasma-derived EVs from healthy volunteers (hEVs). Future functional studies of these interactions can contribute to unveil pathophysiological processes involving the spleen in vivax malaria.
Kinetics of Phase Transitions (2009)

We review developments in the field of phase ordering dynamics, viz., the evolution of a homogeneous multi-component mixture which has been rendered thermodynamically unstable by a rapid quench below the critical temperature. We discuss results for cases with both nonconserved and conserved order parameters. We also highlight recent research directions in this field, i.e., the incorporation of experimentally relevant effects in the studies of phase ordering systems.
Scalable Algorithms for Aggregating Disparate Forecasts of Probability (2006)

In this paper, computational aspects of the panel aggregation problem are addressed. Motivated primarily by applications of risk assessment, an algorithm is developed for fusing large corpora of internally incoherent probability assessments. The algorithm is characterized by a provable performance guarantee, and is demonstrated to be orders of magnitude faster than existing tools when tested on several real-world data-sets. In addition, unexpected connections between research in risk assessment and wireless sensor networks are exposed, as several key ideas are illustrated to be useful in both fields
Chapter 3. Purine Nucleoside Phosphorylase (2007)

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides and 2′-deoxypurine ribonucleosides to the free base, and ribose 1-phosphate or 2′-deoxyribose 1-phosphate, respectively.1–3 PNPs are found in most prokaryotic and eukaryotic organisms where the en...
Classical-Wigner Phase Space Approximation to Cumulative Matrix Elements in Coherent Control (2003)

The classical limit of the Wigner-Weyl representation is used to approximate products of bound-continuum matrix elements that are fundamental to many coherent control computations. The range of utility of the method is quantified through an examination of model problems, single-channel Na_2 dissociation and multi-arrangement channel photodissociation of CH_2IBr. Very good agreement with the exact quantum results is found for a wide range of system parameters.
Administração oral de peptídios e proteínas: III. Aplicação à insulina Oral delivery systems for peptides and proteins: III. Application to insulin (2003)

A insulina é um peptídeo biologicamente ativo, normalmente administrado por via subcutânea, pelos obstáculos que se colocam a sua administração oral. O desenvolvimento de uma forma farmacêutica passível de ser administrada oralmente tem sido razão de uma investigação persistente, acentuada na última década, conforme é descrito. As estratégias utilizadas têm sido muito variadas, a saber, a utilização de inibidores das enzimas proteolíticas, promotores da absorção, modificação química e fórmulas farmacêuticas específicas, como sistemas de partículas, emulsões, sistemas de liberação targeting e sistemas bioadesivos. Embora ainda nenhuma abordagem tenha sido suficientemente eficaz, os resultados são encorajadores. A microencapsulação e, em particular, os métodos que utilizam polímeros naturais, mostram-se promissores neste propósito, pelas características vantajosas que apresentam.&lt;br&gt;Insulin is an important therapeutic protein, generally administered subcutaneously due to the obstacles of oral delivery. A number of different methods have been explored to improve the low oral bioavailability of insulin, particularly in the last decade, namely protease inhibitors, absorption enhancers, chemical modification and the formulation approach which includes particulate systems, emulsions, targeting delivery systems and bioadhesive systems. Although an effective formulation for oral insulin delivery remains to be achieved, the results are encouraging. Microencapsulation has proven to be a promising method of choice, especially when using natural polymers.
Tissue Microarray Analysis of Cdh1 Scoring in Tumor Lymph Node Samples from PCBP1/HNRNP E1 Protects Chromosomal Integrity by Translational Regulation of CDC27 (2023)

&lt;p&gt;S4. Scoring of tissue microarray tumor lymph node samples for Cdh1 staining and patient recurrence status.&lt;/p&gt;
Direct Peptide Lipidation through Thiol–Ene Coupling Enables Rapid Synthesis and Evaluation of Self‐Adjuvanting Vaccine Candidates (2013)

A radical lipidation: Application of a novel thiol-ene lipidation enables the one-step synthesis of self-adjuvanting antigenic peptides as vaccine candidates. The resultant monoacyl lipopeptides are shown to activate monocytes in a robust manner.
Crack Tip Plasticity: A Different Approach to Modelling Fracture Propagation in Soft Formations (2000)

Abstract Over the last 15 years or so, the numerical simulation of hydraulic fracturing has improved beyond recognition. Considerable time and effort has been spent on the production of these models and on their verification with field trials. In spite of their differences, these models still employ, to a lesser or greater extent, the same basic theory of fracture propagation - first put forward in the 1920’s and used in the original 2-D fracture models – known as Linear Elastic Fracture Mechanics, or LEFM. Although the various organisations producing fracture propagation models have extensively modified the original LEFM theory, mainly to allow for the effects of non-linearity at the crack tip, the original assumptions of LEFM still hold true. Failure is by brittle fracture, with no significant plastic deformation of the rock – even at the fracture tip. This assumption is probably valid for most of the formations fractured by the industry today. However, an increasingly important sector of the industry is now stimulating very soft, ductile formations, where the assumptions of linear strain and no significant plastic deformation are not reliable. Fortunately, LEFM is not the only way to model fracture propagation. The Crack Tip Plasticity (CTP) method assumes a fracture tip of finite radius, with a zone of plastically deformed material around it. This plastic zone acts to absorb extra energy from the fracturing fluid, making it harder to propagate fractures through formations with significant plastic deformation. This in turn means that, for a given ductile material, fractures will be smaller and less conductive than those predicted by LEFM. An understanding of CTP could help predict how much smaller the fracture really is, and could also help explain why LEFM-based fracture simulators cannot adequately model very soft formations.
Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice (2001)

The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2-4 weeks apart. A standard psychiatric interview (Present State Examination - PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as 'cases'. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 > or = 11 then use HADS; then, if HADS > or = 9 = 'case' (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving 'case' detection in routine oncology practice while reducing the burden of questions put to 'non-cases'. Further work is needed to develop optimal choice of screening questions for this purpose.
Terahertz detectors for long wavelength multi-spectral imaging. (2007)

The purpose of this work was to develop a wavelength tunable detector for Terahertz spectroscopy and imaging. Our approach was to utilize plasmons in the channel of a specially designed field-effect transistor called the grating-gate detector. Grating-gate detectors exhibit narrow-linewidth, broad spectral tunability through application of a gate bias, and no angular dependence in their photoresponse. As such, if suitable sensitivity can be attained, they are viable candidates for Terahertz multi-spectral focal plane arrays. When this work began, grating-gate gate detectors, while having many promising characteristics, had a noise-equivalent power (NEP) of only 10{sup -5} W/{radical}Hz. Over the duration of this project, we have obtained a true NEP of 10{sup -8} W/{radical}Hz and a scaled NEP of 10{sup -9}W/{radical}Hz. The ultimate goal for these detectors is to reach a NEP in the 10{sup -9{yields}-10}W/{radical}Hz range; we have not yet seen a roadblock to continued improvement.
Design of piecewise maps for chaotic spread-spectrum communications using genetic programming (2002)

In this paper, we propose the use of genetic programming (GP) to design piecewise maps to generate chaotic spreading codes for direct sequence spread-spectrum communications. Using appropriate functional operators, we use GP to construct exploitable maps on the interval [0, 1]. The correlation performance of the maps is the objective function that is optimized using GP. Thus, the auto-correlation and cross-correlation performance of the maps are used as fitness measures to differentiate between potential solutions and a multi-objective GP is used to evolve maps. We are thus able to design specific maps under different number of users and show that it is better to design maps assuming large number of users as such maps work well for lower number of users. Further, in order to be able to design maps for use under different conditions of channel signal-to-noise ratio (SNR), we propose the use of the theoretical bit error rate performance of the maps as the objective function to be optimized by GP. Using this objective function, we can design maps for different conditions including channel SNR levels and number of users. We show that GP can design maps at degraded system conditions, which also work well at better system conditions. We compare the performance of the GP generated maps with other chaotic maps, as well as the traditionally used gold code through simulations. Finally, we apply GP to design maps in scenarios where mathematical design procedures cannot be applied. Using simulated channels under different channel conditions such as colored noise and multipath fading scenarios, we use GP to design maps whose performance is better than the other approaches. Thus, we show that GP can be used to design maps for different channel conditions and is therefore a promising means of solving the system design problem in communication systems.
Incompatibility of Trellis-Based NonCoherent SOQPSK Demodulators for Use in FEC Applications (2012)

Abstract : This paper examines the compatibility/incompatibility of trellis-based noncoherent shaped offset quadrature phase shift keying (SOQPSK) demodulators for use in forward error correction (FEC) applications. The noncoherent demodulators are of the type given in [1, 2]. These demodulators do not explicitly estimate and track the phase offset in the received signal, as is done by a coherent demodulator. Instead, they have implicit phase estimators associated with each state (survivor) in the trellis. We show, however, that these implicit phase estimators still lock onto the carrier phase, in a manner similar to that of a coherent demodulator. Furthermore, because of the extremely low signal-to-noise ratio (SNR) in FEC applications, the phase lock sometimes slips by 180 degrees, which causes the demodulator output symbols to be inverted. We show that this is a relatively minor problem for a serially concatenated convolutional code (SCCC), mainly because the SCCC system uses differential encoding and this encoding is immune to 180 degree phase shifts. On the other hand, a low density parity check (LDPC) coded system does not use differential encoding. Thus, in LDPC systems the 180 degree phase shift proves to be quite catastrophic. The solution to this problem is to adjust the forgetting factor parameter of the noncoherent detector to a value that yields a tighter phase lock. However, this diminishes the noncoherent nature of the demodulator. Therefore, another way of stating our conclusion is that coherent demodulators should be used in FEC applications, especially those using LDPC codes. In the end, while disappointing, this conclusion does not come as a major surprise, because one would not expect noncoherent demodulation to be applicable when differential encoding is not used.
Ring-Opening Polymerization (ROP) of Phenylalanine Derived O-Carboxyanhydride (OCA) Using Different Mono- and Bimolecular Conjugated Catalysts and Amino or Alcohol Initiators (2022)

In the present study, we investigated the activity of four groups of organocatalysts, initiators, and combined catalysts-initiators, through bimolecular reactions with linked catalysts-initiators operating during the polymerization, through a monomolecular pathway in ring-opening polymerization of O-carboxyanhydrides (OCAs) derived from phenylalanine, in the presence or absence of the cocatalyst 4-dimethyl aminopyridine (4-DMAP). The polymerization of the Phe-OCA process was measured by gel permeation chromatography and combined molecular weight determinations in different solvents and temperatures, at various concentrations of initiators and with/without the cooperative effect of cocatalysts. NMR estimated the rate constants of polymerization. Dimethylaminoethyl amine and dimethylaminopropyl amine, without 4-DMAP, were found as highly active catalysts for a more controlled polymerization reaction. 4-(Hydroxymethyl)-1H-imidazole, in the presence of 4-DMAP, was the most effective catalyst for the uncontrolled polymerization reaction of Phe-OCA. Phe-OCA polymers were found biocompatible in vitro proposing applicability for biomedical materials. The present study highlights different catalysts and has important implications for the synthesis of polymeric polyesters in translational medicine.
KPC and NDM-1 Genes in RelatedEnterobacteriaceaeStrains and Plasmids from Pakistan and the United States (2015)

To characterize the genomic context of New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae isolates from Pakistan and the United States encoding KPC, NDM-1, or no carbapenemase. High similarities of the results indicate rapid spread of carbapenem resistance between strains, including globally disseminated pathogens.
A direct sensitivity matrix approach for fast reconstruction in electrical impedance tomography (1994)

In electrical impedance imaging, several proposed reconstruction algorithms have employed the concept of a sensitivity matrix, which can be used to relate the magnitude of a boundary voltage change of a 2D object to the change in conductivity inside the object that has given rise to it. The search for an appropriate inversion of the sensitivity matrix is the key to these algorithms. In this work, a method called the direct sensitivity matrix (DSM) approach for fast image reconstruction is proposed. Both theoretical and experimental results showing the efficiency of this proposed method are also presented.