gebhart/patrepeval huggingface dataset:
Despeckling of medical ultrasound images using data and rate adaptive lossy compression (2005)

A novel technique for despeckling the medical ultrasound images using lossy compression is presented. The logarithm of the input image is first transformed to the multiscale wavelet domain. It is then shown that the subband coefficients of the log-transformed ultrasound image can be successfully modeled using the generalized Laplacian distribution. Based on this modeling, a simple adaptation of the zero-zone and reconstruction levels of the uniform threshold quantizer is proposed in order to achieve simultaneous despeckling and quantization. This adaptation is based on: (1) an estimate of the corrupting speckle noise level in the image; (2) the estimated statistics of the noise-free subband coefficients; and (3) the required compression rate. The Laplacian distribution is considered as a special case of the generalized Laplacian distribution and its efficacy is demonstrated for the problem under consideration. Context-based classification is also applied to the noisy coefficients to enhance the performance of the subband coder. Simulation results using a contrast detail phantom image and several real ultrasound images are presented. To validate the performance of the proposed scheme, comparison with two two-stage schemes, wherein the speckled image is first filtered and then compressed using the state-of-the-art JPEG2000 encoder, is presented. Experimental results show that the proposed scheme works better, both in terms of the signal to noise ratio and the visual quality.
Mouse models of inherited lipodystrophy (2009)

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and underpins the strong association between obesity and diabetes. Paradoxically, the metabolic consequences of having 'too much' fat (obesity) are remarkably similar to those of having 'too little' fat (lipodystrophy): a finding that has generated considerable interest in a rare disease. In both cases, excess energy accumulates as lipid in ectopic sites such as the liver (fatty liver) and skeletal muscle, where it plays a central role in the pathogenesis of insulin resistance, dyslipidemia and type 2 diabetes. Human lipodystrophies are characterised by a total or partial deficiency of body fat, and may be inherited or acquired in origin. Genetically engineered mice with generalised lipodystrophy manifest many of the features of the human disorder, including hyperphagia, fatty liver, hypertriglyceridaemia, insulin resistance and type 2 diabetes, providing a useful tractable model of the human disorder. Partial lipodystrophy, which causes similar, albeit milder, metabolic problems in humans has been more difficult to mimic in the mouse. This review discusses key translational studies in mice with generalised lipodystrophy, including fat transplantation and the use of recombinant leptin replacement therapy. These studies have been instrumental in advancing our understanding of the underlying molecular pathogenesis of ectopic lipid accumulation and insulin resistance, and have prompted the initiation and subsequent adoption of leptin replacement therapy in human lipodystrophies. This review also considers the possible reasons for the apparent difficulties in generating mouse models of partial lipodystrophy, such as interspecies differences in the distribution of fat depots and the apparent lack of sexual dimorphism in fat mass and distribution in mice compared with the dramatic differences present in adult humans.
CD28 costimulation inhibits TCR-induced apoptosis during a primary T cell response (1996)

Murine splenic T cells undergo apoptosis when the TCR complex is re-cross-linked in the absence of costimulation during a primary immune response. However, if the CD28 complex is also cross-linked, growth continues without induction of apoptosis. Prevention of apoptosis by CD28 costimulation was associated with increased expression of bcl-xL, while overexpression of bcl-2 in T cells from bcl-2 transgenic mice was not protective. In both situations, surviving cells can be recovered in a growth arrested state following the primary response, many more if CD28 was also religated. When these cells were restimulated in secondary response, those surviving TCR religation without CD28 costimulation could not be induced to proliferate further. In contrast, cells given CD28 costimulation during the primary response proliferated well after restimulation. Thus, the CD28 signaling pathway may function not only in the initial activation of naive T cells, but also in maintaining their viability and responsiveness during a primary immune response. In addition, the results further suggest that bcl-2 and bcl-xL regulate T cell survival under different conditions, with bcl-xL being perhaps more important in maintaining viability of activated T cells traversing the cell cycle.
Intraventricular Somatostatin-14, Arginine Vasopressin, and Oxytocin: Analgesic Effect in a Patient with Intractable Cancer Pain (1987)

The analgesic effect of intraventricular somatostatin-14 (SOM-14), arginine vasopressin (AVP), and oxytocin (OT) were tested in one terminally ill cancer patient with a diffuse mesothelioma suffering intractable continuous and incapacitating thoracic pain. SOM-14 reduced pain by 90% for 48 min; AVP reduced pain by 95% for 75 min, and OT reduced pain by 88% for 77 min. The only notable side effects were seen after the administration of AVP, which induced anesthesia and flaccid paralysis of the lower limbs, from which the patient fully recovered after 20 h.
Discovery of Spiro-Piperidine Inhibitors and Their Modulation of the Dynamics of the M2 Proton Channel from Influenza A Virus (2009)

Amantadine has been used for decades as an inhibitor of the influenza A virus M2 protein (AM2) in the prophylaxis and treatment of influenza A infections, but its clinical use has been limited by its central nervous system (CNS) side effects as well as emerging drug-resistant strains of the virus. With the goal of searching for new classes of M2 inhibitors, a structure-activity relation study based on 2-[3-azaspiro(5,5)undecanol]-2-imidazoline (BL-1743) was initiated. The first generation BL-1743 series of compounds has been synthesized and tested by two-electrode voltage-clamp (TEV) assays. The most active compound from this library, 3-azaspiro[5,5]undecane hydrochloride (9), showed an IC(50) as low as 0.92 +/- 0.11 microM against AM2, more than an order of magnitude more potent than amantadine (IC(50) = 16 microM). (15)N and (13)C solid-state NMR was employed to determine the effect of compound 9 on the structure and dynamics of the transmembrane domain of AM2 (AM2-TM) in phospholipid bilayers. Compared to amantadine, spiro-piperidine 9 (1) induces a more homogeneous conformation of the peptide, (2) reduces the dynamic disorder of the G34-I35 backbone near the water-filled central cavity of the helical bundle, and (3) influences the dynamics and magnetic environment of more residues within the transmembrane helices. These data suggest that spiro-piperidine 9 binds more extensively with the AM2 channel, thus leading to stronger inhibitory potency.
Design approaches for digitally dominated active pixel sensors: leveraging Moore's Law scaling in focal plane readout design (2008)

Although CMOS technology scaling has provided tremendous power and circuit density benefits for innumerable applications, focal plane array (FPA) readouts have largely been left behind due to dynamic range and signal-to-noise considerations. However, if an appropriate pixel front end can be constructed to interface with a mostly digital pixel, it is possible to develop sensor architectures for which performance scales favorably with advancing technology nodes. Although the front-end design must be optimized to interface with a particular detector, the dominant back end architecture provides considerable potential for design reuse. In this work, digitally dominated long wave infrared (LWIR) active pixel sensors with cutoff wavelengths between 9 and 14.5 &mu;m are demonstrated. Two ROIC designs are discussed, each fabricated in a 90-nm digital CMOS process and implementing a 256 x 256 pixel array on a 30-&mu;m pitch. In one of the implemented designs, the feasibility of implementing a 15-&mu;m pixel pitch FPA with a 500 million electron effective well depth, less than 0.5% non-linearity in the target range and a measured NEdT of less than 50 mK at f/4 and 60 K is demonstrated. Simple on-FPA signal processing allows for a much reduced readout bandwidth requirement with these architectures. To demonstrate the potential for commonality that is offered by a digitally dominated architecture, this LWIR sensor design is compared and contrasted with other digital focal plane architectures. Opportunities and challenges for application of this approach to various detector technologies, optical wavelength ranges and systems are discussed.
Cl- secretagogues increase basolateral K+ conductance of frog corneal epithelium (1987)

The stromal-to-tear transport of Cl- by the corneal epithelium of the frog is increased by pharmacological effectors (secretagogues) that are known to raise the intracellular levels of cyclic AMP or Ca2+. It has been shown in the past that the Cl- secretagogues increase the apical membrane permeability to Cl- and thus facilitate the cell-to-tear flux of the anion. In this report, we combine transepithelial and microelectrode studies to show that three of these secretagogues, epinephrine, the Ca2+ ionophore A23187, and forskolin, also increase the K+ conductance of the basolateral membrane by two- to threefold. The increase in the K+ conductance is not dependent on membrane potential, since this increase occurred equally when the basolateral membrane potential either exceeded 60 mV, as measured with microelectrodes, or was depolarized by voltage clamping after apical permeabilization with amphotericin B. It is proposed that both Cl- and K+ conductances are under the control of intracellular mediators that act independently on each pathway. The increase in basolateral K+ conductance favors the Cl- secretory process.
Evaluation of two methods for monitoring surface cleanliness—ATP bioluminescence and traditional hygiene swabbing (1999)

The minimum bacterial detection limits and operator reproducibility of the Biotrace Clean-Tracetrade mark Rapid Cleanliness Test and traditional hygiene swabbing were determined. Areas (100 cm2) of food grade stainless steel were separately inoculated with known levels of Staphylococcus aureus (NCTC 6571) and Escherichia coli (ATCC 25922). Surfaces were sampled either immediately after inoculation while still wet, or after 60 min when completely dry. For both organisms the minimum detection limit of the ATP Clean-Tracetrade mark Rapid Cleanliness Test was 10(4) cfu/100 cm2 (p < 0.05) and was the same for wet and dry surfaces. Both organism type and surface status (i.e. wet or dry) influenced the minimum detection limits of hygiene swabbing, which ranged from 10(2) cfu/100 cm2 to >10(7) cfu/100 cm2. Hygiene swabbing percentage recovery rates for both organisms were less than 0.1% for dried surfaces but ranged from 0.33% to 8.8% for wet surfaces. When assessed by six technically qualified operators, the Biotrace Clean-Tracetrade mark Rapid Cleanliness Test gave superior reproducibility for both clean and inoculated surfaces, giving mean coefficients of variation of 24% and 32%, respectively. Hygiene swabbing of inoculated surfaces gave a mean CV of 130%. The results are discussed in the context of hygiene monitoring within the food industry.
Optical absorption of small metal particles with adsorbed dye coats (1981)

The optical transmission spectrum of a discontinuous metal-island film is strongly affected by extremely thin layers (<1 monolayer) of dye adsorbate. Experimentally observed splitting and broadening of the plasma resonance of silver films with adsorbed rhodamine B and nile blue dyes can be described by an effective-medium calculation for the optical response: These observations and interpretations have important implications for understanding of surface-enhanced electromagnetic processes.
Intersubband Absorption in In0.15Ga0.85As/Al0.35Ga0.65As Multiple Quantum Wells (1990)

Intersubband absorptions within pseudomorphic quantum wells of the conduction band in In 0.15 Ga 0.85 As/Al 0.35 Ga 0.65 As multiple layers have been studied with various well widths and doping concentrations. The band-offset ratio of the conduction band is estimated to be from 55% to 70% by the calculation of intersubband absorption energies, taking into account the strain effects, the doping effects, and the nonparabolic nature of the energy band.
Exploiting ILP, TLP, and DLP with the polymorphous trips architecture (2003)

The Tera-op reliable intelligently adaptive processing system (TRIPS) architecture seeks to deliver system-level configurability to applications and runtime systems. It does so by employing the concept of polymorphism, which permits the runtime system to configure the hardware execution resources to match the mode of execution and demands of the compiler and application.
The Tautomerism of Heterocycles: Substituent Tautomerism of Six‐Membered Ring Heterocycles (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
C-Reactive Protein in Viral and Bacterial Respiratory Infection in Children (1993)

C-reactive protein (CRP) was studied in 209 children treated in hospital due to middle or lower respiratory tract infection with serologically demonstrated viral or bacterial aetiology. Of the 110 patients with serological evidence of bacterial infection, either alone or in association with viral infection, 52% had CRP > 20 mg/l, 35% > 40 mg/l and 15% > 80 mg/l. Of the 99 patients with serological evidence of viral infection alone, 35% had CRP > 20 mg/l, but only 12% > 40 mg/l and 5% > 80 mg/l. Nearly all, 88%, of the 25 patients with CRP > 40 mg/l in association with viral infection had either an infectious focus, specific microbial or non-specific laboratory evidence suggestive of bacterial infection. By calculating diagnostic parameters at 3 cut-off levels of CRP, the level 40 mg/l seemed more useful than 20 mg/l or 80 mg/l for differentiation between viral and bacterial infections. By using a CRP value of 40 mg/l as a screening limit sensitivity was 0.55, specificity 0.88, positive predictive value 0.76, negative predictive value 0.55, and likelihood ratios of a positive and negative test result 2.9 and 0.74, respectively. It is concluded that low CRP values do not rule out bacterial aetiology of respiratory infection in children. On the other hand viral infection without bacterial involvement is very improbable if CRP is > 40 mg/l. Our results suggest that high CRP values rule out viral infection as a sole aetiology of infection; bacterial infection and antibiotic treatment should be considered in these cases.
PARP Inhibitor Upregulates PD-L1 Expression and Enhances Cancer-Associated Immunosuppression (2017)

<b>Purpose:</b> To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and determine whether blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression.<b>Experimental Design:</b> Breast cancer cell lines, xenograft tumors, and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation. The therapeutic efficacy of PARPi alone, PD-L1 blockade alone, or their combination was tested in a syngeneic tumor model. The tumor-infiltrating lymphocytes and tumor cells isolated from syngeneic tumors were analyzed by CyTOF and FACS to evaluate the activity of antitumor immunity in the tumor microenvironment.<b>Results:</b> PARPi upregulated PD-L1 expression in breast cancer cell lines and animal models. Mechanistically, PARPi inactivated GSK3β, which in turn enhanced PARPi-mediated PD-L1 upregulation. PARPi attenuated anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 resensitized PARPi-treated cancer cells to T-cell killing. The combination of PARPi and anti-PD-L1 therapy compared with each agent alone significantly increased the therapeutic efficacy <i>in vivo</i><b>Conclusions:</b> Our study demonstrates a cross-talk between PARPi and tumor-associated immunosuppression and provides evidence to support the combination of PARPi and PD-L1 or PD-1 immune checkpoint blockade as a potential therapeutic approach to treat breast cancer. <i>Clin Cancer Res; 23(14); 3711-20. ©2017 AACR</i>.
Enhancing Glioblastoma-Specific Penetration by Functionalization of Nanoparticles with an Iron-Mimic Peptide Targeting Transferrin/Transferrin Receptor Complex (2015)

Treatment of glioblastoma (GBM) remains to be the most formidable challenge because of the hindrance of the blood-brain barrier (BBB) along with the poor drug penetration into the glioma parenchyma. Nanoparticulate drug delivery systems (DDS) utilizing transferrin (Tf) as the targeting ligand to target the glioma-associated transferrin receptor (TfR) had met the problem of loss of specificity in biological environment due to the high level of endogenous Tf. Here we conjugated CRT peptide, an iron-mimicry moiety targeting the whole complex of Tf/TfR, to poly(ethylene glycol)-poly(l-lactic-co-glycolic acid) nanoparticles (CRT-NP), to open a new route to overcome such obstacle. High cellular associations, advanced transport ability through the BBB model, and penetration in 3-dimensional C6 glioma spheroids in vitro had preliminarily proved the advantages of CRT-NP over Tf-nanoparticle conjugates (Tf-NP). Compared with Tf-NP, NP, and Taxol, paclitaxel-loaded CRT-NP (CRT-NP-PTX) displayed a superior antiproliferation effect on C6 glioma cells and stronger inhibitory effect on glioma spheroids. Favored pharmacokinetics behavior and enhanced accumulation in glioma foci was observed, together with a much deeper distribution pattern in glioma parenchyma compared with unmodified nanoparticles and Tf-NP. Eventually, mice treated with CRT-NP-PTX showed a remarkably prolonged median survival compared to those treated with Taxol, NP, or Tf-NP. In conclusion, the modification of CRT to nanoparticles holds great promise for enhancement of antiglioma therapy.
Threonine 157 of Influenza Virus PA Polymerase Subunit Modulates RNA Replication in Infectious Viruses (2003)

ABSTRACT Previous results have shown a correlation between the decrease in protease activity of several influenza A virus PA protein mutants and the capacity to replicate of the corresponding mutant ribonucleoproteins (RNPs) reconstituted in vivo . In this work we studied the phenotype of mutant viruses containing these mutations. Viruses with a T162A mutation, which showed a very moderate decrease both in protease and replication activities of reconstituted RNPs, showed a wild-type phenotype. Viruses with a T157A mutation, which presented a severe decrease in protease activity and replication of RNPs, showed a complex phenotype: (i) transport to the nucleus of PAT157A protein was delayed, (ii) virus multiplication was reduced at both low and high multiplicities, (iii) transcriptive synthesis was unaltered while replicative synthesis, especially cRNA, was diminished, and (iv) viral pathogenesis in mice was reduced, as measured by loss of body weight and virus titers in lungs. Finally, recombinant viruses with a T157E mutation in PA protein, which resulted in a drastic reduction of protease and replication activities of RNPs, were not viable. These results indicate that residue T157 in PA protein is important for the capacity of viral polymerase to synthesize cRNA.
S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. (1987)

The development of a radioimmunoassay for S-100 protein is described. This method was used in combination with a recently developed radioimmunoassay for neuron-specific enolase in cerebrospinal fluid and serum from 47 patients with cerebral infarction, transient ischemic attack, intracerebral hemorrhage, subarachnoid hemorrhage, and head injury. In cerebrospinal fluid, increased concentrations of both S-100 and neuron-specific enolase were found after large infarcts, whereas after small infarcts and transient ischemic attacks, only neuron-specific enolase increased. The increased concentrations of S-100 and/or neuron-specific enolase were noted 18 hours to 4 days after cerebral infarction and transient ischemic attacks. Cerebrospinal fluid concentrations of these proteins also reflected the severity of the disease in patients with intracerebral hematoma, subarachnoid hemorrhage, or head injury. Temporal changes in serum S-100 and neuron-specific enolase concentrations reflected the clinical course in 4 patients. In stroke patients, the S-100 and neuron-specific enolase concentrations may reflect the extent of brain damage and could be useful in selecting patients with major stroke for more aggressive treatment during the acute phase.
Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear. (1993)

The effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on contextual fear conditioning in rats were examined. Freezing behavior served as the measure of conditioning. Unlesioned control animals showed reliable conditional freezing in the testing chamber when observed both immediately and 24 hr after footshocks. In contrast, rats with amygdala or ventral PAG lesions exhibited a significant attenuation in freezing both immediately and 24 hr after the shocks. Dorsal PAG lesions had no effect on freezing at either time. Animals with hippocampal lesions displayed robust freezing behavior immediately following the shock, even though they showed a marked deficit in freezing 24 hr after the shock. These results indicate that there are anatomically dissociable short- and long-term conditional fear states.
Heterogeneous expression of four MAP kinase isoforms in human tissues (1992)

Mitogen-activated protein kinases (MAP kinases) are a group of closely related enzymes implicated in signal transduction pathways. We report the molecular cloning of four human proteins (p40mapk, p41mapk, p44mapk and p63mapk) with high homology to members of the MAP kinase family. Sequence analysis demonstrated that p44mapk and p63mapk were the products of distinct genes. However, the p40mapk and p41mapk were found to be related, and are likely to result from alternative processing of transcripts from a single gene. The heterogeneous expression of these human MAP kinase isoforms in different tissues may reflect the diversity of signal transduction pathways in differentiated cells.
Secretion of interleukin 1 (IL-1) by peritoneal macrophages upon contact with syngeneic T cells is Ia-restricted and antigen-independent process. (1988)

We deliver an evidence that secretion of interleukin 1 by macrophages upon contact with T cells is an Ia-restricted and antigen-independent event. Antigen-specific T cell lines or quiescent thymocytes induce comparable quantities of IL-1 from Ia-compatible macrophages. Addition of antigen together with antigen-specific T cells does not increase production of IL-1. Con A-activated thymocyte-derived blasts induce less IL-1 than unstimulated thymocytes. Peritoneal B cells do not secrete IL-1 although they present GAT effeciently to GAT-specific T cell clones. Lastly, the production of IL-1 can be inhibited by a treatment of macrophages with monoclonal antibodies against Ia but not H-2D antigens. The results indicate that the release of IL-1 is solely a result of an interaction between Ia molecules on macrophages and the receptor for Ia on interacting T cells. This process does not require antigen/lectin bridge between the interacting cells.