gebhart/patrepeval huggingface dataset:
The Candida albicans CDR3 gene codes for an opaque-phase ABC transporter (1997)

We report the cloning and functional analysis of a third member of the CDR gene family in Candida albicans, named CDR3. This gene codes for an ABC (ATP-binding cassette) transporter of 1,501 amino acids highly homologous to Cdr1p and Cdr2p (56 and 55% amino acid sequence identity, respectively), two transporters involved in fluconazole resistance in C. albicans. The predicted structure of Cdr3p is typical of the PDR/CDR family, with two similar halves, each comprising an N-terminal hydrophilic domain with consensus sequences for ATP binding and a C-terminal hydrophobic domain with six predicted transmembrane segments. Northern analysis showed that CDR3 expression is regulated in a cell-type-specific manner, with low levels of CDR3 mRNA in CAI4 yeast and hyphal cells, high levels in WO-1 opaque cells, and undetectable levels in WO-1 white cells. Disruption of both alleles of CDR3 in CAI4 resulted in no obvious changes in cell morphology, growth rate, or susceptibility to fluconazole. Overexpression of Cdr3p in C. albicans did not result in increased cellular resistance to fluconazole, cycloheximide, and 4-nitroquinoline-N-oxide, which are known substrates for different transporters of the PDR/CDR family. These results indicate that despite a high degree of sequence conservation with C. albicans Cdr1p and Cdr2p, Cdr3p does not appear to be involved in drug resistance, at least to the compounds tested which include the clinically relevant antifungal agent fluconazole. Rather, the high level of Cdr3p expression in WO-1 opaque cells suggests an opaque-phase-associated biological function which remains to be identified.
Mitochondrial DNA (mtDNA) Biogenesis: Visualization and Duel Incorporation of BrdU and EdU Into Newly Synthesized mtDNA In Vitro (2009)

Mitochondria are key regulators of cellular energy and are the focus of a large number of studies examining the regulation of mitochondrial dynamics and biogenesis in healthy and diseased conditions. One approach to monitoring mitochondrial biogenesis is to measure the rate of mitochondrial DNA (mtDNA) replication. We developed a sensitive technique to visualize newly synthesized mtDNA in individual cells to study mtDNA replication within subcellular compartments of neurons. The technique combines the incorporation of 5-bromo-2-deoxyuridine (BrdU) and/or 5-ethynyl-2'-deoxyuridine (EdU) into mtDNA, together with a tyramide signal amplification protocol. Employing this technique, we visualized and measured mtDNA biogenesis in individual cells. The labeling procedure for EdU allows for more comprehensive results by allowing the comparison of its incorporation with other intracellular markers, because it does not require the harsh acid or enzyme digests necessary to recover the BrdU epitope. In addition, the utilization of both BrdU and EdU permits sequential pulse-chase experiments to follow the intracellular localization of mtDNA replication. The ability to quantify mitochondrial biogenesis provides an essential tool for investigating the alterations in mitochondrial dynamics involved in the pathogenesis of multiple cellular disorders, including neuropathies and neurodegenerative diseases.
Crime, Ethics and Occupational Choice: Endogenous Sorting in a Closed Model (2004)

We consider a simple model in which agents are endowed with heterogeneous abilities and differing degrees of honesty. Agents choose either to become criminals or invest in education and become workers instead. The model is closed in that all criminal proceeds are stolen from agents working in the formal sector and that expenditures on both deterrence and punishment of criminals are paid for through taxes levied on workers. Thus, although we assume that there no direct interactive effects among criminals, criminals crowd each other in two ways: positively in that enforcement and punishment resources become more widely diffused as more agents commit crimes, and negatively in that the presence of more criminals implies that there is less loot to be divided over a larger number of thieves. We establish the possibility of multiple equilibria and characterize the equilibrium properties. We then evaluate the effectiveness of deterrence policies under a balanced government budget.
All-optical label-free human breast tissue block histology using photoacoustic remote sensing (2020)

The direct imaging of tissue preserved in formalin-fixed paraffin-embedded (FFPE) blocks remains a challenge. There are presently millions of tissues preserved as FFPE blocks whose assessment via bright-field microscopes requires them to be sectioned and subsequently stained. These processes are laborious, resource-intensive, and time consuming. In this Letter, we utilize an ultraviolet laser with photoacoustic remote sensing to provide a novel method that enables direct label-free pathological assessment of FFPE blocks. We demonstrate the efficacy of this technique by imaging human breast tissue, highlighting salient features such as ducts, adipocytes, and ductal hyperplasia. This direct imaging of FFPE blocks facilitates pathological assessment much earlier in the histopathological workflow, saving valuable time in clinical and research settings. The presented non-contact label-free reflection-mode device enables augmentation of existing histopathological workflows and aims to expand the arsenal of imaging technologies available to clinicians.
Trait and state binge eating predispose towards cocaine craving (2015)

Binge eating (BE) and drug seeking share similar behavioral features, including loss of control over consumption and compulsive seeking of the craved substance. Previous studies in animal models have demonstrated a complex interaction between 'state' BE, produced by intermittent access to a palatable diet, and 'trait' BE, a phenotypical proneness towards overeating. In the present study, we examined the relationship between state and trait BE and cocaine seeking. We used Otsuka Long Evans Tokushima Fatty rats, a genetic model for obesity that demonstrates BE-like behavior, and Long Evans Tokushima Otsuka controls. They received a schedule of limited access to a palatable diet (3 days/week or 5 days/week access to Ensure for a month). Next, they underwent cocaine self-administration training (1 mg/kg, 1 hour/day for 10 days) followed by extinction sessions (7 days). We found that the degree of BE-like behavior and the state and trait BE combination predicted cocaine craving patterns. Lower levels of dopamine D2 receptors in the prefrontal cortex were correlated with increased drug craving. Moreover, restricted access to an attractive diet was found to be a risk factor for heightened cocaine craving, particularly in trait binge eaters, as rats on the 3 days/week access schedule persistently failed to cease cocaine seeking throughout extinction. Hence, we postulate a joint role of state and trait BE as risk factors for heightened cocaine craving.
Harnessing Complex Mixtures for Catalyst Discovery (2016)

To complement high-throughput experimental approaches to catalyst discovery and optimization, we have employed a simple algorithmic approach to screening and deconvoluting complex mixtures of catalyst components with the goal of rapidly identifying new catalysts and cooperative effects. This Synpacts article highlights how interplay between screening mixtures and mechanistic studies can allow users to rapidly move from initial discovery to rationally developed second-generation catalytic systems. 1 Introduction 2 Application to Lewis and Brønsted Acid Catalysis 3 Application to Transition-Metal Catalysis 4 Conclusion and Perspective
Antihypertensive effect of total flavonoid fraction of Astragalus complanatus in hypertensive rats. (2005)

The purpose of the present study was to quantify the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R. Brown, and to observe its effect on the renin-angiotensin system (RAS) in both renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). RHR were created by the two-kidney one clip (2K1C) method. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Plasma angiotensin II (AngII) and plasma renin activity (PRA) were measured with radioimmunoassay at 60 min after drug administration. The effects of TF on cardiac hemodynamics were also recorded in anesthetized RHR and SHR. TF was given by oral administration in low dose (100 mg/kg) and high dose (200 mg/kg) respectively. Compared to pre-administration control, TF induced an obvious decrease in systolic blood pressure in conscious normotensive Wistar rat, RHR and SHR. In the three groups the systolic blood pressure reached the lowest value at 60 min after TF. TF also induced a significant decrease in blood pressure in anesthetized RHR and SHR. At 60 min after treatment of TF, mean arterial pressure in high dose group (200 mg/kg) was decreased by 17% in RHR and by 17% in SHR respectively (P < 0.01). The depressor effect of TF lasted for at least 60 min. Cardiac output, heart rate and +/- dp/dtmax did not change. Conversely, total peripheral resistance was significantly decreased. The decrease in plasma AngII was found in both RHR and SHR. On the contrary, PRA increased at the same time. These findings suggested that TF is effective in reducing blood pressure in both RHR and SHR. The antihypertensive action of TF was attributed to a decrease in TPR secondary to a decrease in plasma concentration of AngII caused by TF.
Pex9p is a new yeast peroxisomal import receptor for PTS1-containing proteins (2016)

Peroxisomal proteins carrying a type 1 peroxisomal targeting signal (PTS1) are recognized by the well-conserved cycling import receptor Pex5p. The yeast YMR018W gene encodes a Pex5p paralog and newly identified peroxin that is involved in peroxisomal import of a subset of matrix proteins. The new peroxin was designated Pex9p, and it interacts with the docking protein Pex14p and a subclass of PTS1-containing peroxisomal matrix enzymes. Unlike Pex5p, Pex9p is not expressed in glucose- or ethanol-grown cells, but it is strongly induced by oleate. Under these conditions, Pex9p acts as a cytosolic and membrane-bound peroxisome import receptor for both malate synthase isoenzymes, Mls1p and Mls2p. The inducible Pex9p-dependent import pathway provides a mechanism for the oleate-inducible peroxisomal targeting of malate synthases. The existence of two distinct PTS1 receptors, in addition to two PTS2-dependent import routes, contributes to the adaptive metabolic capacity of peroxisomes in response to environmental changes and underlines the role of peroxisomes as multi-purpose organelles. The identification of different import routes into peroxisomes contributes to the molecular understanding of how regulated protein targeting can alter the function of organelles according to cellular needs.
The effects of acyl chain length on the micelle properties of poly(ethylene oxide)-block-poly(N-hexylL-aspartamide)-acyl conjugates (2002)

Derivatives of poly(ethylene oxide)-block-poly(beta-benzyl-aspartate), 12:25 have been prepared via aminolysis of the benzyl protecting group with 6-amino-1-hexanol, followed by subsequent acylation with acetic anhydride, hexanoic acid, lauric acid, or stearic acid. A series of amphiphilic diblock copolymers based on poly(ethylene oxide)-block-poly(N-hexyl-aspartamide)acyl conjugates with various acyl chain lengths have been prepared. The extent of esterification was determined by 1H-NMR. Aqueous micelle solutions were prepared by a dialysis method and the polymer series was characterized as a function of the acyl chain length. Transmission electron microscopy and dynamic light scattering revealed micelle-like structures of nanoscopic dimensions (< 100 nm). Environmentally sensitive fluorescent probes were loaded into the micelles in order to study the properties of the hydrophobic microdomain and to determine the critical micelle concentration (CMC). Steady-state fluorescence measurements indicated that the relative apparent core viscosity and polarity are modulated by the relative length of the attached acyl chains, as is the CMC. Increasing the acyl chain length results in a decreased CMC and a more viscous and less polar core region. Carefully chosen chemical moieties can be introduced in order to influence the properties of the poly(L-Asp) blocks of the micelles. As a result, the micellar properties can be altered via chemical modification in order to impact several key properties relevant to drug delivery.
ITERATE: a conceptual clustering algorithm for data mining (1998)

The data exploration task can be divided into three interrelated subtasks: 1) feature selection, 2) discovery, and 3) interpretation. This paper describes an unsupervised discovery method with biases geared toward partitioning objects into clusters that improve interpretability. The algorithm ITERATE employs: 1) a data ordering scheme and 2) an iterative redistribution operator to produce maximally cohesive and distinct clusters. Cohesion or intraclass similarity is measured in terms of the match between individual objects and their assigned cluster prototype. Distinctness or interclass dissimilarity is measured by an average of the variance of the distribution match between clusters. The authors demonstrate that interpretability, from a problem-solving viewpoint, is addressed by the intraclass and interclass measures. Empirical results demonstrate the properties of the discovery algorithm and its applications to problem solving.
P2‐065: IN VITRO PHARMACOLOGICAL CHARACTERIZATION OF S68890, AN ALLOSTERIC MODULATOR OF ALPHA7 NICOTINIC RECEPTORS (2019)

Modulation of the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) has become a prime target for improving cognition in Alzheimer's disease and schizophrenia. S68890 presents a unique mechanism of action, as it both increases the acetylcholine-evoked response at very low concentrations and negatively modulates the receptor at high concentrations. Competition binding studies were performed on human alpha7-nAChRs and on 120 other receptors, channels, enzymes and reuptake systems. Pharmacological properties were investigated with electrophysiological recordings from human alpha7-nAChRs and mutants expressed in Xenopus oocytes receptors. Similar approaches were used to determine its functionality at 5HT3A receptors. S68890 did not act as an agonist at alpha7-nAChRs but was able to inhibit, in a voltage-dependent manner, acetylcholine-mediated responses with an IC50 of about 10 μM. Moreover, S68890 did not activate the L9’T mutant alpha7 nAChRs, a mutation that yielded profound modifications of the receptor properties with an increase of sensitivity to ACh and a loss of desensitization, with competitive antagonists becoming agonists. Exposure at a low concentration of 3 nM of S68890, far below the IC50, caused an increase of the ACh-evoked current at alpha7-nAChRs (priming effect) that is in agreement with the procognitive effects seen in rodents at low doses. Binding studies revealed that S68890 did not markedly interact with any other targets tested. Experiments conducted at 5HT3A receptors revealed that S68890 exhibited a greater selectivity for nAChRs. Taken together, these results demonstrated that S68890 modulates alpha7-nAChRs receptors positively at very low concentrations and negatively at higher concentrations. Further in vivo evaluations confirm that S68890 possesses potent cognitive-enhancing properties at very low doses, likely associated to the receptor priming effects. This property together with a high safety profile gives evidence that S68890 represents an attractive drug candidate for the treatment of cognitive impairments associated to CNS diseases.
SUPPRESSION OF RING ARTEFACTS IN CT FAN-BEAM SCANNERS (1979)

Philips GmbH Forschungslaboratorium Hamburg, Postbox 54 08 40, 2000 Hamburg 54, Federal Republic of Germany).
TESTING URBAN DESIGN AND AIR QUALITY RELATIONSHIPS IN THE ATLANTA REGION. (2000)

This study presents evidence that households, located in areas of the Atlanta Region with moderately high levels of street connectivity and compactness, drive and pollute less on a daily basis. This analysis employs a rigorous methodology to assess the emissions per household on a per trip basis accounting for cold start cycles, speed, hot stabilized operation, distance, and regional fleet characteristics. Emissions per household are cross-sectionally correlated with the land use patterns at the place of residence. These findings support the argument that a nexus exists between land use policies implemented through local government development regulations and household travel behavior (i.e. mode choice, travel distance, travel time, and vehicle emissions). This research provides an initial and very critical step that is required to lend credibility to the argument that major metropolitan regions should consider alternatives to current land and travel intensive development patterns to meet future air quality objectives.
Separating different contributions to the shear force in near‐field microscopy (2001)

The shear force between a gold and a graphite sample and an approaching near-field optical probe using tuning fork detection is studied in detail. The adiabatic and dissipative contributions are clearly distinguished by monitoring the amplitude as well as the phase of the tip vibration when approaching the surfaces. Their relative strengths vary differently but characteristically with the distance. The interaction starts in case of graphite at a much larger distance. The adiabatic contribution is larger in the case of gold, whereas graphite shows mostly dissipative interaction. Measurements at various temperatures are performed using a gold sample, showing a dependence of the shear force on the temperature.
Inhaltsstoffe von Muira puama (1968)

Abstract Die Droge Muira puama enthält 0,4 bis 0,5% eines Estergemisches, das zu 2/3 aus dem Behensäureester eines α‐Sterols besteht. Für das α‐Sterol wird eine Konstitutionsformel vorgeschlagen. 1/3 der Säurekomponente besteht aus den nächsten Homologen der Behensäure. — In geringer Menge findet man frei und gebunden als Steroid auch β‐Sitosterin.
Fluorescence relaxation in the near–field of a mesoscopic metallic particle: distance dependence and role of plasmon modes (2008)

We analytically and numerically analyze the fluorescence decay rate of a quantum emitter placed in the vicinity of a spherical metallic particle of mesoscopic size (i.e with dimensions comparable to the emission wavelength). We discuss the efficiency of the radiative decay rate and non-radiative coupling to the particle as well as their distance dependence. The electromagnetic coupling mechanisms between the emitter and the particle are investigated by analyzing the role of the plasmon modes and their nature (dipole, multipole or interface mode). We demonstrate that near-field coupling can be expressed in a simple form verifying the optical theorem for each particle modes.
EFFICACY AND SAFETY OF INTRAVITREAL BEVACIZUMAB COMPARED WITH INTRAVITREAL AND POSTERIOR SUB-TENON TRIAMCINOLONE ACETONIDE FOR TREATMENT OF UVEITIC CYSTOID MACULAR EDEMA (2010)

Intravitreal bevacizumab was a well-tolerated and effective supplementary therapy for persistent uveitic cystoid macular edema, especially in Behcet uveitis and for patients with the risk of an increase in intraocular pressure. However, reinjection may be required because of the limited potency and duration of the positive effects of IVB.
Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary (2020)

Cancer of unknown primary (CUP) denotes a malignancy with histologically confirmed metastatic spread while the primary tumor remains elusive. Here, we address prognostic and therapeutic implications of mutations and copy number variations (CNVs) detected in tumor tissue in the context of a comprehensive clinical risk assessment. Targeted panel sequencing was performed in 252 CUP patients. 71.8% of patients had unfavorable CUP according to ESMO guidelines. 74.7% were adeno- and 13.7% squamous cell carcinomas. DNA was extracted from microdissected formalin-fixed, paraffin-embedded tissues. For library preparation, mostly multiplex PCR-based Ion Torrent AmpliSeq™ technology with Oncomine comprehensive assays was used. Most frequent genetic alterations were mutations/deletions of TP53 (49.6%), CDKN2A (19.0%) and NOTCH1 (14.1%) as well as oncogenic activation of KRAS (23.4%), FGFR4 (14.9%) and PIK3CA (10.7%). KRAS activation was predominantly found in adenocarcinomas (p = 0.01), PIK3CA activation in squamous cell carcinomas (p = 0.03). Male sex, high ECOG score, unfavorable CUP, higher number of involved organs and RAS activation predicted decreased event-free and overall survival in multivariate analysis. Deletions of CDKN2A were prognostically adverse regarding overall survival. TP53 mutations did not significantly influence prognosis in the overall cohort, but worsened prognosis in otherwise favorable CUP subtypes. Although not standard in CUP, for 17/198 (8.6%) patients molecularly targeted treatment was recommended and 10 patients (5.1%) were treated accordingly. In conclusion, besides the identification of drug targets, panel sequencing in CUP is prognostically relevant, with RAS activation and CDKN2A deletion emerging as novel independent risk factors in a comprehensive assessment with clinicopathological data.
Oral vaccine delivery: can it protect against non-mucosal pathogens? (2008)

Vaccination is an efficient and cost-effective form of preventing infectious diseases. However, most currently available vaccines are delivered by injection, which makes mass immunization more costly and less safe, particularly in resource-poor developing countries. Oral vaccines have several attractive features compared with parenteral vaccines, but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. Their potential for controlling non-mucosally transmitted diseases has not yet been appreciated in general. In this article, we provide evidence that oral immunization is a feasible alternative for preventing infections transmitted through non-mucosal routes, including infections such as malaria, Japanese encephalitis and hepatitis B. Although there are still hurdles to overcome before such approaches can be deployed widely, recent progress in the oral vaccination field and the availability of a range of delivery systems offers hope for the development of a larger number of oral vaccines.
Properties of a new calcium ion antagonist on cellular uptake and mitochondrial efflux of calcium ions (1984)

Compound YS 035 [NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine] is a new synthetic compound capable of inhibiting Ca2+ uptake by different cells. The inhibition of Ca2+ uptake by muscle cells isolated from chicken embryo is dose-dependent in the compound YS 035 concentration range 10-30 microM. The new compound also inhibits Ca2+ entry into rat brain synaptosomes and less effectively into baby-hamster kidney cells. Compound YS 035 partially inhibits the slow Ca2+ release induced by Ruthenium Red and the rapid Na+-dependent efflux from heart mitochondria. The inhibition of the Na+/Ca2+ exchange appears to be of a non-competitive type with an apparent Ki of 28 microM. The new Ca2+ antagonist totally inhibits the Ca2+ efflux from liver mitochondria induced by Ruthenium Red, but it does not affect the release induced by uncoupler, respiratory inhibitor or chelator, nor the mitochondrial ATP synthesis and membrane potential. The properties shown by the new compound indicate it to be a Ca2+ antagonist and a useful tool for studies on the mitochondrial Ca2+ transport.