gebhart/patrepeval huggingface dataset:
Bone marrow-derived macrophages: development and regulation of differentiation markers by colony-stimulating factor and interferons. (1985)

To investigate the role of specific cytokines in the development of the fully mature macrophage, we have employed murine bone marrow cells that were grown in the presence of CSF-1, a colony-stimulating factor that has been shown to induce the proliferation and differentiation of macrophages from their precursor cells. The CSF-1 employed in these studies was partially purified to ensure removal of contaminating interferon (IFN) from the preparations. After 1 to 2 wk in the presence of the partially purified CSF-1, the adherent macrophages were removed from flasks enzymatically and were recultured at known densities in the absence of CSF-1. Cell surface antigens (Mac-1 and Ia) and Fc receptor capacity (as assessed by Fc-mediated phagocytosis) were examined as markers of macrophage differentiation. Basal levels of Fc receptor capacity and Mac-1 antigen were markedly influenced by exposure to CSF-1, and appear to be modulated by CSF-induced, macrophage-derived IFN. When the bone marrow-derived macrophages were exposed to exogenous IFN in the absence of CSF-1, they proved to be extremely inducible with respect to Fc-mediated phagocytosis (IFN-beta and rIFN-gamma) and Ia antigen expression (rIFN-gamma) when compared with thioglycollate-elicited macrophages. Thus, macrophage growth factors, such as CSF-1, promote macrophage maturation by inducing the production of autostimulatory signals, such as macrophage-derived IFN. In addition, exogenous cytokine stimuli, such as IFN-gamma, further amplify the differentiative potential of these cells. Bone marrow-derived macrophages, propagated under well-defined conditions and never exposed to eliciting agents, provide a powerful model for studying the role of cytokines, such as CSF-1 and IFN, in the differentiative pathway of macrophages.
ACE2 of the heart: From angiotensin I to angiotensin (1–7) (2006)

Angiotensin II (Ang II), a bioactive peptide of the renin-angiotensin system (RAAS), plays an important role in the development of cardiovascular diseases (CVD). Pharmacological inhibition of angiotensin-converting enzyme (ACE), the Ang II forming enzyme, or specific blockade of Ang II binding to angiotensin type 1 receptor (AT1R) through which it exerts its deleterious effects, were shown to provide some protection against progression of CVD. The ACE-Ang II-AT1R axis has been challenged over the last few years with RAAS components able to counterbalance the effects of the main axis. The ACE homologue ACE2 efficiently hydrolyses Ang II to form Ang (1-7), a peptide that exerts actions opposite to those of Ang II. In contrast to the Ang II axis, the role of the ACE2-Ang (1-7) axis in cardiac function is largely obscure. Ang (1-7) is present in the viable myocardium, and its formation depends on Ang II as a substrate. The expression of this peptide is associated with cardiac remodeling: it is lost in the infarcted area and significantly increased in the border area. Low doses of Ang (1-7) improve cardiac output and antagonize Ang II-induced vasoconstriction. The type of Ang (1-7) biological activity is tissue specific and dose dependent. These findings point to a possible protective role for Ang (1-7) in abating the Ang II-induced actions. The elevated expression of Ang (1-7) in failing heart tissue paralleled the expression of its forming enzyme, ACE2. Several observations and experimental evidence suggest a beneficial role for ACE2 in cardiovascular function. Elevated ACE2 expression at the initial stage of several pathologies which decline with progression of disease might indicate a protective role for ACE2. Genetic manipulation of ACE2 expression, either targeted disruption or overexpression, point to the possible significance of this enzyme in cardiac function. Based on the above, a therapeutic approach that will amplify the ACE2-Ang (1-7) axis could provide further protection against the development of CVD. It turns out that the merits of currently used drugs--ACE inhibitors, AT1R blockers and mineralocorticoid receptor blockers (MRB) - lay beyond their direct effects on suppression of the ACE-Ang II-AT1R axis as they also increase cardiac ACE2 and Ang (1-7) significantly.
Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions (2002)

We have simulated diffuse reflectance spectra of skin by assuming a wavelength-independent scattering coefficient for the different skin tissues and using the known wavelength dependence of the absorption coefficient of oxy- and deoxyhaemoglobin and water. A stochastic Monte Carlo method is used to convert the wavelength-dependent absorption coefficient and wavelength-independent scattering coefficient into reflected intensity. The absorption properties of skin tissues in the visible and near-infrared spectral regions are estimated by taking into account the spatial distribution of blood vessels, water and melanin content within distinct anatomical layers. The geometrical peculiarities of skin histological structure, degree of blood oxygenation and the haematocrit index are also taken into account. We demonstrate that when the model is supplied with reasonable physical and structural parameters of skin, the results of the simulation agree reasonably well with the results of in vivo measurements of skin spectra.
One-way image transmission and reconstruction through a thick aberrating medium by use of volume holography (1994)

We describe a method of transmitting two-dimensional images through a severe (thick) phase-aberrating medium. Critical components of the method are to determine and to store the spatial impulse responses (point-spread functions) of the aberrator that correspond to all the pixels of the input image plane. We accomplish this by a set of angularly multiplexed volume holograms that stores complete characteristics of the aberrator. The key advantage of our method is that it can correct for any random phase aberration, not just for exp(iΦ)-type (thin) aberrations as is the case for most of the previous efforts. In our experimental demonstration we successfully transmit and reconstruct an image through a multimode fiber, using LiNbO3 as the holographic medium.
Design of Novel β‐Carboline Derivatives with Pendant 5‐Bromothienyl and Their Evaluation as Phosphodiesterase‐5 Inhibitors (2013)

New derivatives with the tetrahydro-β-carboline-imidazolidinedione and tetrahydro-β-carboline-piperazinedione scaffolds and a pendant bromothienyl moiety at C-5/C-6 were synthesized and tested for their ability to inhibit PDE5 in vitro. The following SAR can be concluded: The tetracyclic scaffold is essential for PDE5 inhibition; the ethyl group is the most suitable among the adopted N-substituents on the terminal ring (hydantoin/piperazinedione); the appropriate stereochemistry of C-5/C-6 derived from the aldehyde rather than C-11a/C-12a derived from tryptophan appears crucial for inhibition of PDE5; surprisingly, derivatives with the hydantoin terminal ring are more active than their analogs with the piperazinedione ring; the selectivity versus PDE5 relative to PDE11 with cGMP as a substrate is mainly a function of the substitution and stereochemistry pattern of the external ring, in other words of the interaction with the H-loop residues of the isozymes. Thirteen derivatives showed PDE5 inhibitory activity with IC(50) values in the range of 0.16-5.4 µm. Compound 8 was the most potent PDE5 inhibitor and showed selectivity towards PDE5 versus other PDEs, with a selectivity index of 49 towards PDE5 rather than PDE11 with cGMP as the substrate.
Sequence specificity in the dimerization of transmembrane .alpha.-helixes (1992)

While several reports have suggested a role for helix-helix interactions in membrane protein oligomerization, there are few direct biochemical data bearing on this subject. Here, using mutational analysis, we show that dimerization of the transmembrane alpha-helix of glycophorin A in a detergent environment is spontaneous and highly specific. Very subtle changes in the side-chain structure at certain sensitive positions disrupt the helix-helix association. These sensitive positions occur at approximately every 3.9 residues along the helix, consistent with their comprising the interface of a closely fit transmembranous supercoil of alpha-helices. By contrast with other reported cases of interactions between transmembrane helices, the set of interfacial residues in this case contains no highly polar groups. Amino acids with aliphatic side chains define much of the interface, indicating that precise packing interactions between the helices may provide much of the energy for association. These data highlight the potential general importance of specific interactions between the hydrophobic anchors of integral membrane proteins.
Photochromic command surface induced switching of liquid crystal optical waveguide structures (1995)

We report on optical waveguide structures containing a thin liquid crystal (LC) film held between two photochromic command surfaces. The command surfaces consist of three monomolecular layers of a polymer with azobenzene side chains deposited according to the Langmuir–Blodgett–Kuhn technique. When exposed to light of appropriate wavelength, the command surfaces undergo a trans↔cis photoisomerization process that induces a reversible change in the liquid crystalline orientation. Such an orientation change of the LC alters the optical properties of the optical waveguide. We present experiments on the dynamics of the LC orientation process. The transition is shown to be continuous, with the degree of orientation dependent on the ratio of the cis-trans chromophore concentration ratio in the command surface.
A serial-link transceiver based on 8-GSamples/s A/D and D/A converters in 0.25-μm CMOS (2001)

This paper presents a transceiver that uses a 4-bit flash analog-to-digital converter (ADC) for the receiver and an 8-bit current-steering digital-to-analog converter (DAC) for the transmitter. The 8-GSamples/s converters are 8-way time interleaved. Digital compensation reduces the input offset of the ADC comparators to less than 0.6 LSB, improves the accuracy of the interleaved sampling clocks to within 10 ps, and reduces systematic coupling noise to less than 18 mV on the 800-mV signal swing. 1.1-nH bondwire inductors distribute the parasitic capacitances at the transceiver input and output, reducing attenuation by 10 dB at 4 GHz. Equalization algorithms using the converters compensate for the 1.5-GHz transceiver bandwidth to allow 8-GSamples/s multilevel data transmission.
Blocking Cyclophilins in the Chronic Phase of Asthma Reduces the Persistence of Leukocytes and Disease Reactivation (2011)

Allergic asthma is characterized by acute influxes of proinflammatory leukocytes in response to allergen stimulation, followed by quiescent (chronic) periods between allergen challenges, during which sustained, low-level inflammation is evident. These chronic phases of disease are thought to be mediated by populations of leukocytes persisting within airways and tissues. The lack of any in situ proliferation by these cells, along with their limited lifespan, suggests that a continual recruitment of leukocytes from the circulation is needed to maintain disease chronicity. The mechanisms regulating this persistent recruitment of leukocytes are unknown. Although classic leukocyte-attracting chemokines are highly elevated after acute allergen challenge, they return to baseline levels within 24 hours, and remain close to undetectable during the chronic phase. In the present study, we investigated whether an alternative family of chemoattractants, namely, extracellular cyclophilins, might instead play a role in regulating the recruitment and persistence of leukocytes during chronic asthma, because their production is known to be more sustained during inflammatory responses. Using a new murine model of chronic allergic asthma, elevated concentrations of extracellular cyclophilin A, but not classic chemokines, were indeed detected during the chronic phase of asthma. Furthermore, blocking the activity of cyclophilins during this phase reduced the number of persisting leukocytes by up to 80%. This reduction was also associated with a significant inhibition of acute disease reactivation upon subsequent allergen challenge. These findings suggest that blocking the function of cyclophilins during the chronic phase of asthma may provide a novel therapeutic strategy for regulating disease chronicity and severity.
Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. (1994)

The trophism of brain-derived neurotrophic factor (BDNF) for dopaminergic cells in culture has led to significant interest in the role of BDNF in the etiology and potential treatment of Parkinson disease. Previous in vivo investigation of BDNF delivery to axotomized substantia nigra dopaminergic neurons in the adult rat has shown no protective effect. In this study, we produced nigral degeneration by infusing 1-methyl-4-phenylpyridinium (MPP+), a mitochondrial complex I inhibitor and the active metabolite of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), into the rat striatum. The subsequent loss of nigral neurons was presumably due to mitochondrial toxicity after MPP+ uptake and retrograde transport to the substantia nigra. We engineered immortalized rat fibroblasts to secrete human BDNF and implanted these cells near the substantia nigra 7 days before striatal MPP+ infusion. We found that BDNF-secreting fibroblasts markedly increased nigral dopaminergic neuronal survival when compared to control fibroblast implants. The observation that BDNF prevents MPTP-induced dopaminergic neuronal degeneration in the adult brain has significance for the treatment of neurodegenerative disorders, which may involve mitochondrial dysfunction, such as Parkinson disease.
Experimental Design for Sensitivity Analysis, Optimization and Validation of Simulation Models (1997)

This chapter gives a survey on the use of statistical designs for what-if analysis in simula- tion, including sensitivity analysis, optimization, and validation/verification. Sensitivity analysis is divided into two phases. The first phase is a pilot stage, which consists of screening or searching for the important factors among (say) hundreds of potentially important factors. A novel screening technique is presented, namely sequential bifurcation. The second phase uses regression analysis to approximate the input/output transformation that is implied by the simulation model; the resulting regression model is also known as a metamodel or a response surface. Regression analysis gives better results when the simu- lation experiment is well designed, using either classical statistical designs (such as frac- tional factorials) or optimal designs (such as pioneered by Fedorov, Kiefer, and Wolfo- witz). To optimize the simulated system, the analysts may apply Response Surface Metho- dology (RSM); RSM combines regression analysis, statistical designs, and steepest-ascent hill-climbing. To validate a simulation model, again regression analysis and statistical designs may be applied. Several numerical examples and case-studies illustrate how statisti- cal techniques can reduce the ad hoc character of simulation; that is, these statistical techniques can make simulation studies give more general results, in less time. Appendix 1 summarizes confidence intervals for expected values, proportions, and quantiles, in termi- nating and steady-state simulations. Appendix 2 gives details on four variance reduction techniques, namely common pseudorandom numbers, antithetic numbers, control variates or regression sampling, and importance sampling. Appendix 3 describes jackknifing, which may give robust confidence intervals.
Some Physicochemical Parameters of 11H-Indole[3,2-c]quinoline (1989)

The hydrophobicity (log P), pKa and limiting solubility of 3chloro-8-mcthoxy-11~-indo10[3,2-~]quinolinc (I) , a rcprcscntativc llaindalo[3,2-~lquinolinc, were determined.A significant diflerencc was observed between the basicity of I and its nan-cyclized nnaloguc, 7chlora-4-Y-(p-mcthoxyphenyl)aminoquinolic (11).I was iound to bc 3 wcnker base (pKa 3.99) than I1 (pKa 7.59), which sllggested that the indola N, unlike the &-amino group of 11, did not affcct the basicity oi the quinolyl N. I was also much less hydrophobic and morc water soluble than 1 1 , which could only bc attributed partly to 3 reduction or surl.lccarea on ring formation.Dased on the present detcrminotions, thc unique hydrophobicity of the llg-indola[3,2-clquinoline ring system was
Control of a switched-reluctance aircraft engine starter-generator over a very wide speed range (2003)

An electric direct-drive gearless starter-generator has been designed and built for an aircraft-engine application. The system is based on a switched reluctance motor, which was chosen for its simplicity, ruggedness, high-speed capability, and efficiency. A description is given of motor control system algorithms and hardware, which are used to control the motor over its operating speed range from standstill to 48000 RPM in both monitoring and generating modes. Novel features of the starter-generator control system are a closed-loop regulator which controls the amount of firing angle advance to maintain optimum torque production at high speed, and a hardware-based digital commutation controller which generates phase firing pulses for the inverter on the basis of machine rotor angle, pulse width, and pulse advance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Newly diagnosed iron deficiency anaemia in a premenopausal woman (2007)

A 40 year old woman with persistent fatigue has come back to you for the results of blood tests. The results show a hypochromic, microcytic anaemia with a haemoglobin concentration of 100 g/l and a ferritin concentration of 5 µg/l, the classic features of iron deficiency anaemia (IDA). 

### Symptoms of anaemia

Fatigue and mild dyspnoea after exertion may be the only symptoms in otherwise healthy people with slow onset anaemia. More serious symptoms such as angina, marked ankle oedema, or dyspnoea at rest don't generally occur unless the haemoglobin concentration is less than about 70 g/l. Presence of such symptoms in a case like this indicate additional cardiorespiratory pathology. 

### Causes of the anaemia

Blood loss —Seek any history of haemorrhage. In the 5-10% of premenopausal women who develop IDA the commonest cause is menorrhagia. For reliable assessment simple pictogram charts may be better than subjective reporting. 

Coeliac disease —In younger patients coeliac disease often …
Scaling EM (Expectation Maximization) Clustering to Large Databases (1998)

: Practical statistical data clustering algorithms require multiple data scans to converge. For large databases, these scans become prohibitively expensive. We present a scalable clustering framework requiring at most one scan of the database, and apply it to the Expectation-Maximization (EM) algorithm. Unlike distance-based or hard membership algorithms (such as k-Means) EM is known to be an appropriate optimization algorithm for constructing proper statistical models of the data. It also easily accommodates categorical and continuous data fields. It admits varying degrees of data membership in multiple clusters. Our scalable method is based on identifying regions of the data that are compressible and regions that must be maintained in memory. The approach operates within the confines of a limited memory buffer. Data resolution is preserved to the extent possible based upon the size of the memory buffer and the fit of the current clustering model to the data. We extend the framework ...
Some Thiazolines and Thiazolidinones with Antituberculous Activity (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome Thiazolines and Thiazolidinones with Antituberculous ActivityR. H. Mizzoni and P. C. EismanCite this: J. Am. Chem. Soc. 1958, 80, 13, 3471–3475Publication Date (Print):July 1, 1958Publication History Published online1 May 2002Published inissue 1 July 1958https://pubs.acs.org/doi/10.1021/ja01546a066https://doi.org/10.1021/ja01546a066research-articleACS PublicationsRequest reuse permissionsArticle Views214Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Discovery of a High Affinity and Selective Pyridine Analog as a Potential Positron Emission Tomography Imaging Agent for Cannabinoid Type 2 Receptor (2015)

As part of our efforts to develop CB2 PET imaging agents, we investigated 2,5,6-substituted pyridines as a novel class of potential CB2 PET ligands. A total of 21 novel compounds were designed, synthesized, and evaluated for their potency and binding properties toward human and rodent CB1 and CB2. The most promising ligand 6a was radiolabeled with carbon-11 to yield 16 ([(11)C]RSR-056). Specific binding of 16 to CB2-positive spleen tissue of rats and mice was demonstrated by in vitro autogadiography and verified in vivo in PET and biodistribution experiments. Furthermore, 16 was evaluated in a lipopolysaccharid (LPS) induced murine model of neuroinflammation. Brain radioactivity was strikingly higher in the LPS-treated mice than the control mice. Compound 16 is a promising radiotracer for imaging CB2 in rodents. It might serve as a tool for the investigation of CB2 receptor expression levels in healthy tissues and different neuroinflammatory disorders in humans.
Narcolepsy and Syndromes of Primary Excessive Daytime Somnolence (2004)

Excessive daytime sleepiness (EDS) or somnolence is common in our patients and in society in general. The most common cause of EDS is "voluntary" sleep restriction. Other common causes include sleep-fragmenting disorders such as the obstructive sleep apnea syndrome. Somewhat less familiar to the clinician are EDS conditions arising from central nervous system dysfunction. Of these so-called primary disorders of somnolence, narcolepsy is the most well known and extensively studied, yet often misunderstood and misdiagnosed. Idiopathic hypersomnia, the recurrent hypersomnias, and EDS associated with nervous system disorders also must be well-understood to provide appropriate evaluation and management of the patient with EDS. This review summarizes the distinguishing features of these clinical syndromes of primary EDS. A brief overview of the pharmacological management of primary EDS is included. Finally, in view of the tremendous advances that have occurred in the past few years in our understanding of the pathophysiology of canine and human narcolepsy, we also highlight these discoveries.