gebhart/patrepeval huggingface dataset:
Characterization of Lipopolysaccharide of Haemophilus influenzae (1978)

Lipopolysaccharide from strains of Haemophilus influenzae was extracted and isolated by the hot phenol-water procedure. The preparations were relatively insoluble in water but could be solubilized with surface-active agents. The preparations contained carbohydrate (30%), fatty acid (29%), and phosphate (4.7%); protein content was less than 1%. Thin-layer chromatography, gas-liquid chromatography, and colorimetric assays detected glucose, galactose, glucosamine, heptose, and a 2-keto-3-deoxy-octonate-like molecule (less than 1%). Neither methylpentose nor dideoxyhexose was detected. The lipid portion was composed of fatty acids common to lipopolysaccharide of Salmonella. The preparations provoked positive dermal Shwartzman reactions and biphasic febrile responses in rabbits, responses typical of endotoxic activity. The 50% lethal dose for mice was decreased from 16.5 microgram/g to 0.015 microgram/g by concomitant administration of actinomycin D. The preparations were shown to be polyclonal activators of bone marrow-derived (B) cells. Limulus lysate gelation was seen with 8.0 ng of lipopolysaccharide. Preliminary hemagglutination data suggested at least three different antigenic factors associated with the lipopolysaccharide of H. influenzae type b. The H. influenzae lipopolysaccharide appeared biologically similar to that of enterobacteria but chemically different.
Group lassoing change-points in piecewise-stationary AR signals (2011)

Regularizing the least-squares criterion with the total number of coefficient changes, it is possible to estimate time-varying (TV) autoregressive (AR) models with piecewise-constant coefficients. Such models emerge in various applications including speech segmentation, biomedical signal processing, and geophysics. To cope with the inherent lack of continuity and the high computational burden when dealing with high-dimensional data sets, this paper introduces a convex regularization approach enabling efficient and continuous estimation of TV-AR models. To this end, the problem is cast as a sparse regression one with grouped variables, and is solved by resorting to the group least-absolute shrinkage and selection operator (Lasso). The fresh look advocated here permeates benefits from advances in variable selection and compressive sampling to signal segmentation. An efficient block-coordinate descent algorithm is developed to implement the novel segmentation method. Issues regarding regularization and uniqueness of the solution are also discussed. Finally, an alternative segmentation technique is introduced to improve the detection of change instants. Numerical tests using synthetic and real data corroborate the merits of the developed segmentation techniques in identifying piecewise-constant TV-AR models.
Sigma receptors regulate contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation elicited by both electrical stimulation and exogenous serotonin (1989)

Sigma receptors are specific, highly localized binding sites in limbic and sensorimotor structures of the brain that interact with many psychotropic drugs. These agents include the psychotomimetic benzomorphan opiates, the psychotomimetic drug phencyclidine and its analogs, as well as numerous typical and atypical antipsychotics such as haloperidol, chlorpromazine, and the novel drugs BMY 14802 and rimcazole. So far, no physiological function has been assigned to these binding sites. We have synthesized a number of novel sigma receptor-active drugs derived from the selective sigma ligand N,N'-di(o-tolyl)guanidine (DTG). DTG and its congeners were found to inhibit contractions of the guinea pig ileal longitudinal muscle/myenteric plexus (LMMP) preparation evoked by electrical stimulation. In addition, the sigma ligands noncompetitively antagonized contractions of the LMMP preparation evoked by serotonin (5-HT). The 5-HT-evoked contractions were found to be largely due to 5-HT's activation of 5-HT3 receptors to release ACh. The activity of DTG congeners in inhibiting electrically or 5-HT-evoked contractions of the LMMP highly correlated with their potency to inhibit binding of both 3H-DTG and (+)3H-3-PPP [3(3-OH-phenyl)-N-(1-propyl)piperidine] to sigma receptors in guinea pig brain homogenates. Two DTG congeners that did not bind to sigma receptors also showed no activity in the bioassay. Many other (but not all) sigma receptor ligands showed a high correlation between their potency to inhibit electrically evoked contractions of the LMMP and their sigma receptor binding affinity. The benzomorphans (+)SKF 10,047 and (+)cyclazocine potentiated electrically evoked contractions of the LMMP. Sigma ligands also inhibited the contractions of the LMMP in the presence of the opiate antagonist naloxone and in preparations in which opioid receptors had been inactivated by treatment with the irreversible opiate antagonist beta-chlornaltrexamine. Control experiments suggested that the sigma ligands act via a neuronal mechanism to inhibit ACh release evoked by electrical stimulation or by stimulation with 5-HT. These results suggest that there are functional sigma receptors on cholinergic nerve terminals or within the myenteric plexus and that these receptors can inhibit stimulated ACh release through an opioid receptor-independent mechanism. However, sigma receptor activation in the ileum has the same effect on ACh release as activation of naloxone-sensitive opioid receptors. The LMMP may be an in vitro bioassay system for characterizing the mechanism of action of sigma receptors and for determining the biological efficacy of drugs known to bind to sigma receptors in radioligand binding assays.
8 Genetic Analysis of Retroviral Reverse Transcriptase Structure and Function (1993)

Central to their life cycle, the process of reverse transcription in retroviruses comprises (1) the copying of genetic information present in the viral RNA genome to produce a double-stranded DNA and (2) the rearrangement of viral transcriptional elements and genes into an order that produces a viral DNA poised for expression upon chromosomal integration (Weiss et al. 1984; Goff 1990). The reverse transcriptase (RT) enzyme is a complex and multifunctional machine that is responsible for single-handedly carrying out all of the steps in the process. Genetic approaches to understanding the structure and function of this enzyme have been exceedingly fruitful in yielding information about the organization of the active domains, the residues needed for its various activities, and the interdependencies displayed by its domains. This chapter discusses the results of these genetic studies, first for several RTs in general and then in considerable detail for the human immunodeficiency virus type-1 (HIV-1) RT. The crucial role played by RT in viral replication has made it an attractive target for antiviral therapy for human retroviruses such as HIV, the causative agent of AIDS (Chandra et al. 1985; Mitsuya and Broder 1987; Mitsuya et al. 1990), and human T-lymphotropic virus type I (HTLV-I), the agent of adult T-cell leukemia (ATL). To further our knowledge of molecular events during retroviral DNA synthesis, it is essential to understand the architecture and functional organization of the RT molecule. Studies aimed at unraveling the structural features of RT should therefore reveal fundamental aspects of this class of...
Leukocyte depletion for safe blood transfusion (2009)

Leukocytes have ability to distinguish between self cells (body own cells) and foreign (allogenic) cells on the basis of human leukocyte antigen (HLA) proteins that are present on the cell membrane and are effectively unique to a person. During allogenic blood transfusion a person receives large number of allogenic donor leukocytes and these are recognized as foreign cells by the recipient immune system which leads to several adverse reactions. To avoid such leukocyte-mediated adverse reactions leukodepleted blood transfusion is required. Leukocytes can be separated on the basis of size, dielectric properties, by affinity separation, freeze-thawing and centrifugation but all these methods are time consuming and costly. Filtration is another method for leukocyte depletion that is comparatively less expensive and more efficient as it gives more than 90% leukodepletion of blood along with minimal cell loss. However, present filtration procedures also have some limitations as they work efficiently with blood components but not with whole blood and show non-specific adhesion of large number of platelets and red blood cells along with leukocytes. All the currently available filters are costly, which has been a major reason for their limited application. Therefore, demand for a more efficient and cost-effective filter is high in medical community and scientists are attenpting to improve the efficiency of currently available filters. The present review gives an overview of the significance of leukodepleted blood transfusion and focuses on different methods for leukocyte depletion and challenges involved in all these technologies.
Optical coherence tomography image‐guided smart laser knife for surgery (2017)

We describe a system that combines OCT and laser tissue modification with a Tm laser. Simulation results of the tissue removal rate using a simple model, as a function of average power, are in good agreement with experimental results using tissue phantoms. Lasers Surg. Med. 50:202-212, 2018. © 2017 Wiley Periodicals, Inc.
Geminiviruses: Genome structure and gene function (1992)

Abstract The plant pathogenic single‐strand DNA‐containing geminiviruses have been the recent focus of intense investigation, owing both to their agronomic importance and to their potential as vectors for the expression of foreign genes in plants. Molecular genetic studies have provided detailed information on the genomic organization of many of these viruses. A greater genetic complexity has been demonstrated among the members of this viral family than had previously been suspected, as well as an apparently rapid rate of evolution of genetic diversity. We now recognize fundamental differences in the genome structure and organization of the whitefly‐ and leafhopper‐transmitted viruses, as well as among those geminiviruses infecting dicotyledonous or monocotyledonous hosts. This knowledge has provided new insights into the evolution of these viruses. The viral genes involved in replication and in systemic movement in the plant have been defined, and viral origins for single‐strand (ss) and double‐strand (ds) DNA replication have been mapped to small nucleotide regions. With the structural features of the viral genomes now well defined, current efforts are focused on elucidating the molecular aspects of viral gene regulation and interactions with host‐cell components that lead to the production of disease. Recent progress in determining the mechanism of replication and systemic movement and the contributions of these to symptom and disease development are discussed in the context of the potential for genetically engineering disease‐resistant plants. Key words: geminivirusesDNA replicationgenome structuregene expressionpathogenesishost range determinants
Synthesis and Properties of O‐Glycosyl Calix[4]Arenes (Calixsugars) (1997)

Abstract Model O ‐glycosylation reactions at either rim of calix[4]arenes are described with the aim of providing access to a new family of carbohydrate‐containing calixarene derivatives named calixsugars. One or two sugar moieties (D‐mannofuranose and D‐glucopyranose) were introduced at the lower rim of the parent calix[4]arene by glycosylation of the phenolic hydroxyl groups by means of a Mitsunobu reaction. Tetrapropoxy calix[4]arenes bearing two or four hydroxymethyl groups at the upper rim were coupled with perbenzoylated thioethyl D‐galactoside and D‐lactoside in the presence of the thiophilic promoter copper(III) triflate. In this way β‐linked bis‐ and tetrakis‐ O ‐galactosyl calix[4]arenes were obtained in good yield, the latter showing some solubility in water. For the O ‐lactosyl derivatives only the bis‐substituted compound could be obtained because of the competing formation of an intramolecular ether linkage between 1,3‐hydroxymethyl groups. Preliminary binding studies showed some affinity of the galactose‐containing calixsugars toward charged carbohydrates and dihydrogen phosphate anion.
Tyrosine kinase signalling in breast cancer: Insulin-like growth factors and their receptors in breast cancer (2000)

The insulin-like growth factor (IGF) system exerts pleiotropic effects on mammalian cells. This review focuses on type I IGF receptor (IGF1R)-mediated signal transduction and its relevance in breast cancer. Upon activation by the IGFs, IGF1R, a transmembrane tyrosine kinase receptor, undergoes autophosphorylation, and then binds and phosphorylates additional signaling molecules. These intermediates initiate a series of downstream signaling events that are involved in multiple physiologic processes for cells. Recent data demonstrate that the IGF receptor system actively interacts with the estrogen receptor and integrin receptor systems. Cross-talk among these pathways regulates breast cancer proliferation, protection from cell death, and metastasis. Better understanding of IGF biochemical signaling pathways is of utmost importance for developing therapies for breast cancer.
Seven-Color, Homogeneous Detection of Six PCR Products (1999)

We describe an extension of the fluorogenic PCR 5'-nuclease assay, or "Taq-Man" assay. Sequence-specific probes consisted of a novel nonfluorescent quencher, nitrothiazole blue (NTB), at the 3' terminus and six different reporter dyes at the 5' terminus. The six reporters were 6-FAM, dR110, dR6G, dTMR, dROX and JAZ dyes. The seventh color was from aluminum phthalocyanine tetrasulfonate and was utilized as a "passive reference" to calibrate concentration variations. Our test system was a set of three single-nucleotide polymorphisms (SNPs). Each SNP system consisted of two primers and two sequence-specific probes, each labeled with a different reporter dye and NTB. Following PCR, the reactions were diluted with water and measured in a microcuvette on a luminescence spectrometer in synchronous scanning mode. In this method, both the excitation and emission wavelengths were scanned, with a fixed wavelength difference (delta gamma) between excitation and emission wavelengths. The spectral overlap in the set was evaluated by calculation of the condition number of the 7 x 7 matrix (dye fluorescence vs. wavelength). The small value of the condition number (1.5) proved that the cross-talk between the dyes was minimal. SNP analyses of known, synthetic target sequences and genomic DNA were plotted both as normalized, subtracted spectra and as data points in three separate dot plots.
[New anti-arrhythmics--hope or disappointment?]. (2004)

The new anti-arrhythmic agents studied in the last decade have mostly come from research orientated towards determining the compounds which block the electrical currents implicated in the process of repolarisation (class III action). To this must be added dronedarone, which is related to amiodarone and as such displays the 4 classes of anti-arrhythmic properties. Pure class III agents prolong the cardiac action potential and therefore the refractory period and QT interval. The conduction velocity is unaltered. These agents act best on re-entry arrhythmias. Dofetilide is a prototype. The class III action is linked to blockade of the Ikr current and can paradoxically lower it at increased heart rates. Dofelitide has not shown a harmful effect on the survival of high risk ischaemic patients. The conversion of atrial tachyarrhythmias into sinus rhythm can be obtained in one to two thirds of cases. As for the prevention of these arrhythmias, its success rate can exceed 60%. On the other hand, the occurrence of torsades de pointe is in the order of 3%, justifying the initiation of treatment under hospital conditions. Ibutilide acts by blocking the Ikr and INa-s currents. Used only intravenously, this agent is capable of converting back to sinus rhythm a third of atrial fibrillation episodes and two thirds of flutter. The risk of torsades de pointe is 3.5% so this treatment must also be commenced in the hospital setting. Azimilide blocks multiple Iks channels as well as Ikr, Ica and Ina. The electrophysiological effect is sustained at rapid heart rates. When evaluated in patients with paroxysmal atrial fibrillation, azimide prolonged the interval until recurrence, associated with an excellent tolerance (torsades de pointe in 0.55% of cases). In a survival study, azimide demonstrated a neutral effect in high risk subjects with diminished ejection fraction and sinusal variability. Unlike the previous agents, dronedarone is a benzofurane with a similar structure to amiodarone but without iodine. The 800 mg dose is associated with the best risk-benefit ratio. In patients with left ventricular dysfunction, the administration of this agent has been associated with excess mortality. Two recent studies on the prevention of atrial fibrillation have demonstrated that dronedarone is moderately effective with an excellent general tolerance.
Cromolyn Reduces Levels of the Alzheimer’s Disease-Associated Amyloid β-Protein by Promoting Microglial Phagocytosis (2018)

Amyloid-beta protein (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). Aβ deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Aβ levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APP<sup>Swedish</sup>-expressing Tg2576 mice. Mice were treated for 3 months starting at 5 months of age, when the earliest stages of β-amyloid deposition begin. Cromolyn, alone, or in combination with ibuprofen, almost completely abolished longer insoluble Aβ species, i.e. Aβ40 and Aβ42, but increased insoluble Aβ38 levels. In addition to its anti-aggregation effects on Aβ, cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial recruitment to, and phagocytosis of β-amyloid deposits in AD mice. Cromolyn also promoted Aβ42 uptake in microglial cell-based assays. Collectively, our data reveal robust effects of cromolyn, alone, or in combination with ibuprofen, in reducing aggregation-prone Aβ levels and inducing a neuroprotective microglial activation state favoring Aβ phagocytosis versus a pro-neuroinflammatory state. These findings support the use of cromolyn, alone, or with ibuprofen, as a potential AD therapeutic.
Mucosal inherent activity patterns in the rat: evidence from voltage-sensitive dyes (1995)

1. Fluorescence changes in the dye di-4-ANEPPS were monitored on the rat's nasal septum and medial surface of the turbinates in response to odorant stimuli. For each mucosal surface a 6.0 x 6.0-mm area was sampled at 100 contiguous sites with a 10 x 10 photodiode array. The odorants were propyl acetate, 2-propanol, citral, L-carvone and ethylacetoacetate, each presented at a low and high concentration. 2. Like previous work using optical recording techniques and potential-sensitive dyes on the amphibian epithelium, the fluorescence signals elicited by odorant stimuli in the rat preparation were nearly identical in shape, time course, and response characteristics as the electroolfactogram (EOG). As with the EOG, a response could only be recorded in the presence of odorant stimuli (that is, no response was detected when nonodorized, humidified air was presented as the stimulus); the amplitude depended on odorant concentration, and the response was abolished both by ether and Triton X-100. 3. Although the entire expanse of each sampled tissue (i.e., septum and medial surface of the turbinates) responded to stimulation with each odorant, each stimulus induced a distinct spatial pattern of activity that was independent of odorant concentration and consistent from animal to animal. Furthermore, the spatial activity patterns recorded for the septum were mirror images of those recorded from the medial surface of the turbinates. 4. Formal statistical analysis of the loci of maximal activity or "hot spot" indicated highly significant effects of the odorants for both the septum and medial surface of the turbinates. 5. The results of these studies give further support to the hypothesis that odorant quality is encoded by differential spatial activity patterns in the olfactory epithelium that are characteristic of different odorants.
Ptychography – a label free, high-contrast imaging technique for live cells using quantitative phase information (2013)

Cell imaging often relies on synthetic or genetic fluorescent labels, to provide contrast which can be far from ideal for imaging cells in their in vivo state. We report on the biological application of a, label-free, high contrast microscopy technique known as ptychography, in which the image producing step is transferred from the microscope lens to a high-speed phase retrieval algorithm. We demonstrate that this technology is appropriate for label-free imaging of adherent cells and is particularly suitable for reporting cellular changes such as mitosis, apoptosis and cell differentiation. The high contrast, artefact-free, focus-free information rich images allow dividing cells to be distinguished from non-dividing cells by a greater than two-fold increase in cell contrast, and we demonstrate this technique is suitable for downstream automated cell segmentation and analysis.
On channel estimation and detection for multicarrier signals in fast and selective Rayleigh fading channels (2001)

Time-domain channel estimation and detection techniques are presented for multicarrier signals in a fast and frequency-selective Rayleigh fading channel. As a consequence of the time-varying channel, the orthogonality between subcarriers is destroyed in conventional frequency-domain approaches, resulting in interchannel interference, which increases an irreducible error floor in proportion to the normalized Doppler frequency. An important feature of the proposed technique is the ability to exploit the time-selective channel as a provider of time diversity. This enables us to achieve performance superior to any other structure without increasing bandwidth or incorporating redundancy, in order to reduce the complexity of the estimator, we apply the theory of optimal low rank approximation to a minimum mean squared error channel estimator and present a theoretical calculation of mean squared error and simulations to confirm that the estimator is robust to changes in channel characteristics.