gebhart/patrepeval huggingface dataset:
Segmentation of Intra-Retinal Layers From Optical Coherence Tomography Images Using an Active Contour Approach (2010)

Optical coherence tomography (OCT) is a noninvasive, depth-resolved imaging modality that has become a prominent ophthalmic diagnostic technique. We present a semi-automated segmentation algorithm to detect intra-retinal layers in OCT images acquired from rodent models of retinal degeneration. We adapt Chan-Vese's energy-minimizing active contours without edges for the OCT images, which suffer from low contrast and are highly corrupted by noise. A multiphase framework with a circular shape prior is adopted in order to model the boundaries of retinal layers and estimate the shape parameters using least squares. We use a contextual scheme to balance the weight of different terms in the energy functional. The results from various synthetic experiments and segmentation results on OCT images of rats are presented, demonstrating the strength of our method to detect the desired retinal layers with sufficient accuracy even in the presence of intensity inhomogeneity resulting from blood vessels. Our algorithm achieved an average Dice similarity coefficient of 0.84 over all segmented retinal layers, and of 0.94 for the combined nerve fiber layer, ganglion cell layer, and inner plexiform layer which are the critical layers for glaucomatous degeneration.
L-leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway (2012)

Haploinsufficiency of ribosomal proteins (RPs) has been proposed to be the common basis for the anemia observed in Diamond-Blackfan anemia (DBA) and myelodysplastic syndrome with loss of chromosome 5q [del(5q) MDS]. We have modeled DBA and del(5q) MDS in zebrafish using antisense morpholinos to rps19 and rps14, respectively, and have demonstrated that, as in humans, haploinsufficient levels of these proteins lead to a profound anemia. To address the hypothesis that RP loss results in impaired mRNA translation, we treated Rps19 and Rps14-deficient embryos with the amino acid L-leucine, a known activator of mRNA translation. This resulted in a striking improvement of the anemia associated with RP loss. We confirmed our findings in primary human CD34⁺ cells, after shRNA knockdown of RPS19 and RPS14. Furthermore, we showed that loss of Rps19 or Rps14 activates the mTOR pathway, and this is accentuated by L-leucine in both Rps19 and Rps14 morphants. This effect could be abrogated by rapamycin suggesting that mTOR signaling may be responsible for the improvement in anemia associated with L-leucine. Our studies support the rationale for ongoing clinical trials of L-leucine as a therapeutic agent for DBA, and potentially for patients with del(5q) MDS.
Preliminary assessment of a shortcut in nitrogen removal from wastewater (1986)

The objective of this long-term research project was to demonstrate the feasibility of removing nitrogen from highly nitrogenous wastewater by (a) blocking the nitrification process at the intermediary nitrite level through the action of free ammonia and (b) subsequently reducing the nitrite to nitrogen gas. The success of such a process could lead to substantial reductions in nitrogen removal costs.Two identical bench-scale activated sludge systems were operated for 147 days, in the initial phase. Each system was composed of four equal-sized, completely mixed cells in series. The free ammonia concentration was highest in the first cell of each system. It averaged 2 mg NH 3 -N/L in the first system and 5 mg NH 3 -N/L in the second. Nitrite buildup, in excess of 80% of the oxidized nitrogen present, was induced and sustained for around 2 months in all cells of the second system, after which time a steady decline occurred. Nitrite buildup could not be sustained in the first system. Average chemical oxygen demand (COD) for nitrite reduction was 40% lower than that for nitrate reduction. The nitrification rate for the ammonia oxidizers was similar for both systems. The presence of up to 100 mg [Formula: see text] nitrite in system 2 caused no discernible inhibition. Subsequent runs proved that nitrite accumulation could not be sustained indefinitely, owing to acclimation to free ammonia levels as high as 22 mg NH 3 -N/L. Periodic resting and flushing may be required; further research is being pursued along these lines. Key words: biological treatment, denitrification, nitrification, nitrite, nitrogen removal, nitrogenous wastewater.
Resonant Energy Transfer in PbS Quantum Dots (2007)

Resonant nonradiative energy transfer between close-packed PbS quantum dots is observed in continuous-wave and time-resolved fluorescence experiments. Samples of nominally a single dot size, and two dot sizes, were investigated. In both cases, the time-integrated fluorescence exhibits a substantial redshift compared to the emission from dots in solution, and energy transfer can be observed directly in spectrally resolved fluorescence transients.
Effects of Surgically Implanted Transmitter Weights on Growth and Swimming Stamina of Small Adult Westslope Cutthroat Trout (2005)

Abstract The generally accepted 2% ratio of transmitter weight to body weight constrains or precludes telemetry studies examining the timing and location of spawning of small adult westslope cutthroat trout Oncorhynchus clarkii lewisi in headwater streams. We empirically determined effects of surgically implanted dummy transmitters ranging in weight from 1 to 5 g on the swimming stamina and growth of small (81.3–206.9 g) adult westslope cutthroat trout in the laboratory to establish acceptable transmitter weights for field studies on this species. Mean growth rates and swimming stamina were not significantly different among treatments, including controls. No precipitous decline or threshold beyond which performance deteriorated markedly was observed. Data collected using telemetered westslope cutthroat trout implanted with transmitters less than about 4% of body weight should therefore approximate information about untelemetered individuals without significant bias. However, we also detected subtle effects on growth within this transmitter weight range related to individual transmitter–body weight ratios (0.5–5.3% initially), and there were indications that swimming stamina was affected similarly. Each 1% increase in transmitter– body weight ratio elicited an 11.6% decrease in growth and a possible 5.6% decrease in swimming stamina at 6 weeks postimplantation. Therefore, transmitter selection should weigh the costs of increased transmitter weight on fish performance against the benefits of longer transmission durations. In the case in which transmitter weights approaching 4% of body weight are necessary to complete a study and slight decreases in performance are not expected to affect findings materially, such weights may be acceptable. In other cases, researchers should choose the lightest possible transmitters that allow study goals to be achieved and not automatically select transmitters weighing 4% of body weight.
Conductor-like Screening Model for Real Solvents: A New Approach to the Quantitative Calculation of Solvation Phenomena (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConductor-like Screening Model for Real Solvents: A New Approach to the Quantitative Calculation of Solvation PhenomenaAndreas KlamtCite this: J. Phys. Chem. 1995, 99, 7, 2224–2235Publication Date (Print):February 1, 1995Publication History Published online1 May 2002Published inissue 1 February 1995https://pubs.acs.org/doi/10.1021/j100007a062https://doi.org/10.1021/j100007a062research-articleACS PublicationsRequest reuse permissionsArticle Views7323Altmetric-Citations3285LEARN 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 options Get e-Alerts
The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis (2003)

The role of the cytokine network in mediating inflammation and joint destruction in rheumatoid arthritis (RA) has been investigated extensively in recent years. Interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha) are two pivotal proinflammatory cytokines that have been shown to contribute to the clinical manifestations of RA. The ability of IL-1 to drive inflammation and joint erosion and to inhibit tissue repair processes has been clearly established in in vitro systems and animal models. Under physiological conditions, the activity of IL-1 is balanced by IL-1 receptor antagonist (IL-1R alpha). Understanding of the respective roles of IL-1 and IL-1R alpha in conditions of health and disease has led to the development of a recombinant IL-1ra, anakinra (Kineret; Amgen Inc., Thousand Oaks, CA), which offers a new therapeutic modality for RA.
Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases (2007)

The lymphoid-specific tyrosine phosphatase (Lyp) has generated enormous interest because a single-nucleotide polymorphism in the gene (PTPN22) encoding Lyp produces a gain-of-function mutant phosphatase that is associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis, Graves disease, and systemic lupus erythematosus. Thus, Lyp represents a potential target for a broad spectrum of autoimmune disorders. Unfortunately, no Lyp inhibitor has been reported. In addition, little is known about the structure and biochemical mechanism that directly regulates Lyp function. Here, we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy. Structural and mutational analyses indicate that the inhibitor binds both the active site and a nearby peripheral site unique to Lyp, thereby furnishing a solid foundation upon which inhibitors with therapeutic potency and selectivity can be developed. Moreover, a comparison of the apo- and inhibitor-bound Lyp structures reveals that the Lyp-specific region S(35)TKYKADK(42), which harbors a PKC phosphorylation site, could adopt either a loop or helical conformation. We show that Lyp is phosphorylated exclusively at Ser-35 by PKC both in vitro and in vivo. We provide evidence that the status of Ser-35 phosphorylation may dictate the conformational state of the insert region and thus Lyp substrate recognition. We demonstrate that Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling. Our data establish a mechanism by which PKC could attenuate the cellular function of Lyp, thereby augmenting T cell activation.
The effects of post-ovulatory administration of onapristone on the development of a secretory endometrium (1996)

The purpose of this study was to assess the ability of the anti-progestin onapristone administered in the immediate post-ovulatory period to disrupt endometrial differentiation as a potential method of fertility control. In all, 10 healthy female volunteers were given 400 mg onapristone 2 days after the mid-cycle luteinizing hormone (LH) surge in urine (LH+2). An endometrial biopsy was taken 4 or 6 days after the LH surge (i.e. LH+4 or LH+6) in a control cycle and on the corresponding day of the treatment cycle. Biopsies were assessed for histological dating and immunolocalization of oestrogen receptors, progesterone receptors and 15-hydroxyprostaglandin dehydrogenase (PGDH). On day LH+12, blood was taken for the measurement of insulin-like growth factor binding protein-1 (IGFBP-1) and placental protein 14 (PP14). Hormonal measurements in blood and urine were used to monitor the effects on the menstrual cycle. In addition, the concentration of cortisol in plasma was measured to determine if this dose of onapristone exerted significant anti-glucocorticoid activity. Treatment with onapristone retarded the development of secretory changes within the endometrium without affecting the length of the luteal phase. Intense nuclear immunostaining of oestrogen and progesterone receptors was evident in glands and stroma after treatment, suggesting that the progesterone-dependent down-regulation of steroid receptors was inhibited by the anti-progestin. Onapristone also affected the production of luteal phase endometrial proteins, as judged by the pronounced reduction in immunostaining of PGDH within the glands and the significant reduction in plasma concentrations of PP14. However, plasma concentrations of IGFBP-1 did not differ between cycles. Onapristone did not appear to exert significant anti-glucocorticoid activity because concentrations of cortisol were unaffected. These findings suggest that onapristone could potentially be used as a method of postovulatory fertility control.
Encapsulating Bacteria in Agarose Microparticles Using Microfluidics for High-Throughput Cell Analysis and Isolation (2010)

The high-throughput analysis and isolation of bacterial cells encapsulated in agarose microparticles using fluorescence-activated cell sorting (FACS) is described. Flow-focusing microfluidic systems were used to create monodisperse microparticles that were ∼30 μm in diameter. The dimensions of these particles made them compatible with flow cytometry and FACS, and the sensitivity of these techniques reduced the incubation time for cell replication before analyses were carried out. The small volume of the microparticles (∼1-50 pL) minimized the quantity of reagents needed for bacterial studies. This platform made it possible to screen and isolate bacteria and apply a combination of techniques to rapidly determine the target of biologically active small molecules. As a pilot study, Escherichia coli cells were encapsulated in agarose microparticles, incubated in the presence of varying concentrations of rifampicin, and analyzed using FACS. The minimum inhibitory concentration of rifampicin was determined, and spontaneous mutants that had developed resistance to the antibiotic were isolated via FACS and characterized by DNA sequencing. The β-subunit of RNA polymerase, RpoB, was confirmed as the target of rifampicin, and Q513L was the mutation most frequently observed. Using this approach, the time and quantity of antibiotics required for the isolation of mutants was reduced by 8- and 150-fold, respectively, compared to conventional microbiological techniques using nutrient agar plates. We envision that this technique will have an important impact on research in chemical biology, natural products chemistry, and the discovery and characterization of biologically active secondary metabolites.
ATP-SENSITIVE POTASSIUM CHANNELS: A Model of Heteromultimeric Potassium Channel/Receptor Assemblies (1999)

ATP-sensitive K+ channels (KATP channels) play important roles in many cellular functions by coupling cell metabolism to electrical activity. By cloning members of the novel inwardly rectifying K+ channel subfamily Kir6.0 (Kir6.1 and Kir6.2) and the receptors for sulfonylureas (SUR1 and SUR2), researchers have clarified the molecular structure of KATP channels. KATP channels comprise two subunits: a Kir6.0 subfamily subunit, which is a member of the inwardly rectifying K+ channel family; and a SUR subunit, which is a member of the ATP-binding cassette (ABC) protein superfamily. KATP channels are the first example of a heteromultimeric complex assembled with a K+ channel and a receptor that are structurally unrelated to each other. Since 1995, molecular biological and molecular genetic studies of KATP channels have provided insights into the structure-function relationships, molecular regulation, and pathophysiological roles of KATP channels.
TREATMENT OF ACUTE GRAFT-VERSUS-HOST DISEASE WITH MONOCLONAL ANTIBODY OKT3 (1984)

Eight recipients of a bone-marrow graft from HLA-identical, MLR-nonreactive sibling donors who had developed grade II-IV acute graft-versus-host disease (aGVHD), were given 14 consecutive daily injections of 5 mg of a murine anti-T-cell monoclonal antibody (MCA) called OKT3. Four patients with grade II aGVHD showed a complete response; two patients with grade II had a partial response, and two patients (one with grade II and one with grade IV) showed no improvement at all. The main side effect was a high spiking fever after the first injection. T cells were monitored with monoclonal antibodies, indirect immunofluorescence, and flow cytometry. Circulating T3+ T cells dropped to virtually zero within 1 hr following the first injection. Low numbers of E-rosetting cells were still demonstrable during OKT3 therapy. During the second week of treatment, T-cell markers (T3, T4, T8) started to increase again, in spite of excess antibody in the circulation. At that time, T cells showed weaker fluorescence with OKT3 than before OKT3 therapy, suggesting modulation of the T3 antigen. After cessation of OKT3 therapy, T cells reached pretreatment levels within one week. None of the six patients studied developed anti-mouse-Ig antibodies. These results suggest that OKT3 therapy is effective in limited aGVHD. The absence of anti-mouse-Ig antibody formation may allow repeated courses of MCA that may add to their therapeutical potential.
Cluster of diplopia cases after periocular anesthesia without hyaluronidase (1999)

Hyaluronidase may be more important than previously suspected in preventing anesthetic-related damage to the extraocular muscles. The inferior rectus muscle is particularly vulnerable, presumably because of the injection technique.
ChemInform Abstract: Imidazo[2,1‐b]benzothiazoles. Part 2. New Immunosuppressive Agents. (1986)

Abstract Ausgehend von den Phenacylbromiden (I) und den Benzothiazolen (II) werden die im Titel genannten Verbindungen (III) entweder auf direktem Wege oder über die Zwischenprodukte (IV) dargestellt.
Evidence That 2-Arachidonoylglycerol but Not N-Palmitoylethanolamine or Anandamide Is the Physiological Ligand for the Cannabinoid CB2 Receptor (2000)

We examined the effect of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, on the intracellular free Ca(2+) concentrations in HL-60 cells that express the cannabinoid CB2 receptor. We found that 2-arachidonoylglycerol induces a rapid transient increase in intracellular free Ca(2+) concentrations in HL-60 cells. The response was affected by neither cyclooxygenase inhibitors nor lipoxygenase inhibitors, suggesting that arachidonic acid metabolites are not involved. Consistent with this notion, free arachidonic acid was devoid of any agonistic activity. Importantly, the Ca(2+) transient induced by 2-arachidonoylglycerol was blocked by pretreatment of the cells with SR144528, a CB2 receptor-specific antagonist, but not with SR141716A, a CB1 receptor-specific antagonist, indicating the involvement of the CB2 receptor but not the CB1 receptor in this cellular response. G(i) or G(o) is also assumed to be involved, because pertussis toxin treatment of the cells abolished the response. We further examined the structure-activity relationship. We found that 2-arachidonoylglycerol is the most potent compound among a number of naturally occurring cannabimimetic molecules. Interestingly, anandamide and N-palmitoylethanolamine, other putative endogenous ligands, were found to be a weak partial agonist and an inactive ligand, respectively. These results strongly suggest that the CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic natural ligand for the CB2 receptor that is abundant in the immune system.
Atomic force microscopy reconstruction of G-wire DNAa) (1996)

A fundamental problem in atomic force microscopy (AFM) image interpretation is distinguishing features arising from tip geometry from true molecular detail. In this study, a novel 4-stranded form of DNA (the ‘‘G wire’’) was coadsorbed with 7.6-nm-diam colloidal gold probe calibration standards and examined by AFM. After the probe apices were reconstructed from AFM images of the standards, the artificial broadening of the coadsorbed G-wire DNA was removed, resulting in more reliable image interpretation. Using simple geometric models, a favorable comparison between observed and modeled G-wire cross sections suggests that reconstructions removed about 25% of the tip-broadened AFM image in these studies.
Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode (2007)

Atrial fibrillation (AF) is associated with impaired functional capacity and quality of life and significant morbidity and mortality. The current management approach fails to maintain stable sinus rhythm (SR) in the majority of patients. For many years, guidelines have recommended antiarrhythmic treatment of a first AF episode only if the AF is poorly tolerated, a position that has been reinforced by studies showing no mortality or morbidity advantage of rhythm control over rate control. During the last decade, research has shown mechanisms of self-perpetuation of AF based on electrophysiological and structural remodelling induced by AF itself. There is mounting evidence that 'lone' AF is because of a host of factors, some of which may be easily treatable, such as hypertension, sleep apnoea, and obesity, thus allowing secondary prevention at the time of the first episode of AF. According to these concepts, lack of early intervention could be one of the reasons for long-term failure of maintenance of SR. In this position paper, we propose testing the working hypothesis that if an SR maintenance strategy is selected, treatment of AF should commence at the first-detected episode and should be based on a double strategy of SR restoration and aggressive treatment of associated conditions that promote atrial remodelling.
Atomic force microscopy using a piezoresistive cantilever (2002)

An atomic force microscope (AFM) is an instrument which measures the topography of a surface by bringing a cantilever beam into contact with a sample and measuring the deflection of the cantilever as it is scanned across the surface. The complexity of an AFM is predominantly governed by the detector used for measuring the deflection of the cantilever probe. The authors describe the fabrication of a silicon cantilever beam with an integrated piezoresistor for sensing its deflection. A silicon-on-insulator material is used for the fabrication. A p-type resistor is fabricated at the surface of the cantilever along a <110> direction so that the piezoresistive effect of silicon causes its resistance to vary linearly with its deflection. The cantilevers considered typically have spring constants from 1 to 10 N/m and minimum detectable deflections from 1 to 10 AA over a 10-Hz-1-kHz frequency range. The cantilevers were successfully used in an AFM, and an image of a grating was obtained with this technique.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>