gebhart/patrepeval huggingface dataset:
Amelioration of Radiation-induced Fibrosis (2004)

Radiation-induced fibrosis is an untoward effect of high dose therapeutic and inadvertent exposure to ionizing radiation. Transforming growth factor-beta (TGF-beta) has been proposed to be critical in tissue repair mechanisms resulting from radiation injury. Previously, we showed that interruption of TGF-beta signaling by deletion of Smad3 results in resistance to radiation-induced injury. In the current study, a small molecular weight molecule, halofuginone (100 nm), is demonstrated by reporter assays to inhibit the TGF-beta signaling pathway, by Northern blotting to elevate inhibitory Smad7 expression within 15 min, and by Western blotting to inhibit formation of phospho-Smad2 and phospho-Smad3 and to decrease cytosolic and membrane TGF-beta type II receptor (TbetaRII). Attenuation of TbetaRII levels was noted as early as 1 h and down-regulation persisted for 24 h. Halofuginone blocked TGF-beta-induced delocalization of tight junction ZO-1, a marker of epidermal mesenchymal transition, in NMuMg mammary epithelial cells and suggest halofuginone may have in vivo anti-fibrogenesis characteristics. After documenting the in vitro cellular effects, halofuginone (intraperitoneum injection of 1, 2.5, or 5 microg/mouse/day) efficacy was assessed using ionizing radiation-induced (single dose, 35 or 45 Gy) hind leg contraction in C3H/Hen mice. Halofuginone treatment alone exerted no toxicity but significantly lessened radiation-induced fibrosis. The effectiveness of radiation treatment (2 gray/day for 5 days) of squamous cell carcinoma (SCC) tumors grown in C3H/Hen was not affected by halofuginone. The results detail the molecular effects of halofuginone on the TGF-beta signal pathway and show that halofuginone may lessen radiation-induced fibrosis in humans.
Activity and Regulation of the Centrosome-associated Proteasome (2000)

Regulated proteolysis is important for maintaining appropriate cellular levels of many proteins. The bulk of intracellular protein degradation is catalyzed by the proteasome. Recently, the centrosome was identified as a novel site for concentration of the proteasome and associated regulatory proteins (Wigley, W. C., Fabunmi, R. P., Lee, M. G., Marino, C. R., Muallem, S., DeMartino, G. N., and Thomas, P. J. (1999) J. Cell Biol. 145, 481-490). Here we provide evidence that centrosomes contain the active 26 S proteasome that degrades ubiquitinated-protein and proteasome-specific peptide substrates. Moreover, the centrosomes contain an ubiquitin isopeptidase activity. The proteolytic activity is ATP-dependent and is inhibited by proteasome inhibitors. Notably, treatment of cells with inhibitors of proteasome activity promotes redistribution of the proteasome and associated regulatory proteins to the centrosome independent of an intact microtubule system. These data provide biochemical evidence for active proteasomal complexes at the centrosome, highlighting a novel function for this organizing structure.
Synthesis of oligomeric mimics of lignin (1998)

The preparation of β-O-4 oligomeric compounds that mimic the lignin structure is pertinent to the study of the mechanism of action of lignin-degrading enzymes. A strategy for the synthesis of racemic oligomers β-O-4 phenolic models of lignin is reported here. The procedure is quite general with respect to the number of linked units. It starts from simple building blocks that are prepared in a few conventional steps from commercially available starting materials. The building blocks can be classified as three different units, an initiating 3, a repeating 4 and a terminating unit 5. The combination of these units by aldol-type reactions allows the synthesis of oligomeric materials containing the β-O-4 structure. The procedure allows the determination of the relative configurations of the stereocenters generated in the aldol-type reactions that provide the β-O-4 skeleton. The synthesis procedure reported here for the trimer 6 and tetramer 7 can be easily extended to higher oligomers and it is suitable also for automated synthesis.
Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease (2010)

Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid β(Aβ) immunization against Alzheimer's disease (AD), there has been concern that anti-Aβ immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβ immunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.
Advances in Therapy for Osteoporosis (2003)

The current status of detection and treatment of osteoporosis is reviewed. Despite substantial advances in the past ten years, most patients with osteoporotic fractures are still not being treated for the underlying bony cause of the fracture, and most people at risk for fracture are not being offered known protective regimens. The foundation of any therapeutic program is adequate nutrition--specifically protein, calcium, phosphorus and vitamin D. Current anti-resorptive agents reduce vertebral fracture risk by 30% to 50% and teriparatide, a newly approved anabolic agent, reduces risk by up to 80+%. Effective treatments for chronic bony pain that occurs in some patients with spine fractures is affored by two minimally invasive procedures, kyphoplasty and vertebroplasty. Some of these chronically painful fractures represent instances of previously unrecognized non-union, and in them low-pressure vertebroplasty produces prompt and lasting relief. Fracture risk reductions with current anti-resorptive agents are at least twice as great as can be explained by drug effects on bone mass. Moreover, risk is reduced within a few months of starting therapy. These observations focus attention on bone remodeling and point to the need for improvement of biomarker technology, since it seems likely that reduction in remodeling activity underlies much of the fracture risk reduction and can therefore be used to monitor therapy.
A mutation in the human ortholog of theSaccharomyces cerevisiae ALG6gene causes carbohydrate-deficient glycoprotein syndrome type-Ic (1999)

Carbohydrate-deficient glycoprotein syndrome (CDGS) represents a class of genetic diseases characterized by abnormal N-linked glycosylation. CDGS patients show a large number of glycoprotein abnormalities resulting in dysmorphy, encephalopathy, and other organ disorders. The majority of CDGSs described to date are related to an impaired biosynthesis of dolichyl pyrophosphate-linked Glc3Man9GlcNAc2 in the endoplasmic reticulum. Recently, we identified in four related patients a novel type of CDGS characterized by an accumulation of dolichyl pyrophosphate-linked Man9GlcNAc2. Elaborating on the analogy of this finding with the phenotype of alg5 and alg6 Saccharomyces cerevisiae strains, we have cloned and analyzed the human orthologs to the ALG5 dolichyl phosphate glucosyltransferase and ALG6 dolichyl pyrophosphate Man9GlcNAc2 alpha1,3-glucosyltransferase in four novel CDGS patients. Although ALG5 was not altered in the patients, a C-->T transition was detected in ALG6 cDNA of all four CDGS patients. The mutation cosegregated with the disease in a Mendelian recessive manner. Expression of the human ALG5 and ALG6 cDNA could partially complement the respective S. cerevisiae alg5 and alg6 deficiency. By contrast, the mutant ALG6 cDNA of CDGS patients failed to revert the hypoglycosylation observed in alg6 yeasts, thereby proving a functional relationship between the alanine to valine substitution introduced by the C-->T transition and the CDGS phenotype. The mutation in the ALG6 alpha1,3-glucosyltransferase gene defines an additional type of CDGS, which we propose to refer to as CDGS type-Ic.
Targeted therapy of mesothelin expressing mesotheliomas (MM), ovarian cancer (OC) and pancreatic cancer (PC): Results of phase I study of SS1(dsFv)PE38 (SS1P) (2004)

3035 Background: Mesothelin, a cell surface glycoprotein is an attractive candidate for antibody-based therapies given its limited expression on normal mesothelial cells and overexpression in MM, OC and PC. To target mesothelin we developed the immunotoxin-SS1P, consisting of an anti-mesothelin Fv linked to a mutated Pseudomonas exotoxin that mediates cell killing. Based on the antitumor activity of SS1P in preclinical studies we initiated a multicenter phase I clinical trial of SS1P. Methods: Eligible patients (pts) had previously treated MM, OC and PC, ECOG PS 0–2, and tumor mesothelin expression as determined by immunohistochemistry. SS1P was administered intravenously over 30 minutes every other day (QOD) for 6 or 3 doses. Results: A total of 20 pts (7 peritoneal MM; 4 pleural MM; 8 OC; 1 PC) have been treated to date. On the QOD x 6 schedule 17 pts were treated at 4 dose levels (8, 12, 18 and 25 μg/kg/dose) and the maximum tolerated dose (MTD) of SS1P was 18 μg/kg/dose. Dose limiting toxicities (DLT's) included Grade 3 urticaria (1 pt) and vascular leak syndrome (VLS) (2 pts). Grade 2 toxicities included hypoalbuminemia, abdominal pain, pleuritic pain, asymptomatic pleural and pericardial effusion and VLS. Since the DLT's on the SS1P QOD x 6 schedule were seen in pts who had received more than 4 doses of SS1P, the protocol was amended to treat pts QOD x 3 doses to allow further dose escalation. Three pts have been treated on the QOD x 3 schedule at 25 μg/kg/dose with no DLT's and dose escalation is ongoing. Of the 17 evaluable pts treated, 10 had stable disease; 2 had minor response and 5 had progressive disease. One pt with OC had complete resolution of abdominal and pelvic ascites lasting 6 months; 1 pt with peritoneal MM has had complete resolution of abdominal ascites lasting >30 months and has required no further treatment. Conclusions: SS1P is well tolerated and shows promising clinical activity including resolution of ascites and stable disease in some pts. SS1P could be potentially useful in pts with small volume disease and ascites who have failed standard chemotherapy. Dose escalation on the QOD x 3 schedule is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm Inc.
Growth Hormone (GH) Retardation of Muscle Damage due to Immobilization in Old Rats (1996)

Four weeks immobilization of the right leg of aged rats (26 months old) caused a marked 31% and 27% reduction of muscle mass of the plantaris and soleus muscles, respectively. In animals treated with 0.6 mg/kg body weight of growth hormone (GH), the reduction of weight of the above muscles was only 14.7 and 16.1%, respectively. Biochemical studies of the level of acid phosphatase as a marker of muscle catabolism showed a significant increase of this enzyme in the immobilized muscles. GH treatment had a positive effect in curtailing the increase due to immobilization. Studies on muscle protein oxidation used as another measure of damage in immobilized animals, showed a 400% increase in protein carbonyls in plantaris muscles. GH administration reduced this value significantly. One major issue hampering the clinical use of human GH (hGH) is its short half-life in vivo (14 min). In a previous work it was possible to enhance the in vivo longevity of other hormones such as follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) by fusing carboxyl-terminal peptide (CTP) of the hCG gene to the above hormones. The CTP has four serine-linked oligosaccharides, which have been shown to be important in maintaining the longer half-lives of these hormones. With the above rationale of using the CTP as a general target to increase the potency of bioactive hormones, we have now fused the CTP with hGH. This has provided us with a new successfully constructed recombinant hGH, which is currently being tested for its biological potency and for possible use in aging animals.
Dynamic video bitrate adaptation for WebRTC-based remote teaching applications (2018)

Remote teaching applications are common nowa-days. Very often, these applications resemble video-on-demand streaming platforms rather than real virtual classrooms, where a group of students (the receivers) can remotely attend a live lecture held by a lecturer (the sender). To better support this live scenario, Real-Time Communication (RTC) solutions can be used. WebRTC is an open-source project for real-time browser- based conferencing, developed with a peer-to-peer architecture in mind. To use WebRTC, each receiver requires a dedicated encoder at sender-side. Using such approach is expensive in terms of encoders, and does not scale well for a large number of users. To overcome this issue, a WebRTC-compliant framework is proposed, where only a limited number of encoders are used. A centralized node, the conference controller, dynamically forwards the most suitable stream to the receivers, based on their bandwidth conditions. Moreover, the controller dynamically recomputes the encoding bitrates of the sender. This approach allows to closely follow the long-term bandwidth variations of the receivers, even with a limited number of encoders at sender-side. To evaluate the performance of the proposed framework in a realistic environment, a testbed has been implemented using the Chrome browser and the open-source Jitsi-Videobridge. In a scenario with 10 receivers and 3 encoders, and under realistic network conditions, the proposed framework improves the received video bitrate up to 11%, compared to a static solution where the encoding bitrates do not change over time.
Characterization of nanostructured hybrid and organic solar cells by impedance spectroscopy (2011)

We review the application of impedance spectroscopy in dye-sensitized solar cells, quantum dot-sensitized solar cells and organic bulk heterojunction solar cells. We emphasize the interpretation of the impedance parameters for determining the internal features of the device, concerning the carrier distribution, materials properties such as the density of states and/or doping of the semiconductors, and the match of energy levels for photoinduced charge generation and separation. Another central task is the determination of recombination mechanisms from the measured resistances, and the factors governing the device performance by combined analysis of resistances as a function of voltage and current-voltage curves.
The Use of Seawater-neutralised Bauxite Refinery Residues in the Management of Acid Sulphate Soils, Sulphidic Mine Tailings and Acid Mine Drainage (2000)

Seawater-neutralised bauxite refinery residues (red mud) have a soil reaction pH of about 8.4, but they retain an acid neutralising capacity of 3.65 moles per kg of dry red mud and they have the ability to bind up to about 1,000 meq of trace metals per kg of dry red mud; only a small proportion of the trace metals can later be removed by compulsive exchange reagents. These properties make the seawater-neutralised red mud suitable for treating acid mine drainage and tailings dam water, sulphidic mine tailings and waste rock, and acid sulphate soils; there are also other potential uses. In this paper we describe the properties of seawater-neutralised red mud, the results of small scale trials involving its use in environmental management and remediation applications, and the findings of large scale trials that are currently in progress.
Detection of Residual Tumor Cells in Patients with Malignant Melanoma Responding to Immunotherapy (1994)

Recently, a highly sensitive assay combining reverse transcription and polymerase chain reaction (PCR) to assess for melanoma cells in peripheral blood has been developed. Detection of tyrosinase mRNA, a tissue-specific enzyme in melanocytes and melanoma cells, indicates the presence of melanoma cells in peripheral blood. We examined blood samples and bone marrow aspirates from 28 patients with metastatic malignant melanoma for presence of melanoma cells prior to and after therapy with interferon (IFN)-alpha and interleukin (IL)-2. Ten patients showed antitumor response to immunotherapy, including three complete (CR) and seven partial remissions (PR). Four patients (three PR, one stable disease) underwent subsequent resection of residual tumor lesions and had no clinical evidence of disease after surgery. Tyrosinase mRNA was detected in blood and bone marrow samples from all patients with malignant melanoma prior to and after immunotherapy, including those with no clinical evidence of disease (median disease-free survival 21 months, range 19-28 months). Tyrosinase transcripts were also detected in all patients with amelanotic melanoma. In contrast, no tyrosinase mRNA was detectable in any of 30 healthy persons or in six patients with other malignancies. The presence of residual melanoma cells may be an important indicator of occurrence of delayed relapse.
Ruthenium Complexes of Quinone Related Ligands:  A Study of the Electrochemical Properties of 2-Aminothiophenolatobis(2,2‘-Bipyridine)Ruthenium(II) (1999)

Electrochemical properties of the newly synthesized 2-amino thiophenolatobis(2,2'-bipyridine)ruthenium(II) [Ru(bpy)(2)(NH(2).S)cat](+) (bpy = 2,2'-bipyridine, (NH(2).S) = 2-aminothiophenolate) are reported, using microelectrode, disk electrode, rotating disk electrode cyclic voltammetry, spectroelectrochemistry, and differential pulse voltammetry. The results are compared with the electrochemical properties of the previously studied [Ru(II)(bpy)(2)LL](n)()(+) compounds, where LL are 1,2-dihydroxybenzene (O.O), 2-aminophenol (NH(m)().O), and 1,2-diaminobenzene (NH(m)().NH(m)()). These ligands can exist in protonated (m = 2) or deprotonated (m = 1) forms. By means of cyclic voltammetry, the deprotonated [Ru(II)(bpy)(2)(NH.S)](0) displayed a series of one-electron reversible redox waves, consistent with the previously observed results for the [Ru(II)(bpy)(2)LL](n)()(+) complexes. However, the reversible waves observed for protonated [Ru(II)(bpy)(2)(NH(2).S) cat](+) are inconsistent with the irreversible waves observed for protonated [Ru(II)(bpy)(2)LL](n)()(+) complexes. An ECE mechanism is proposed to account for these differences and is used to interpret and simulate the cyclic voltammograms (CV)s of [Ru(II)(bpy)(2)(NH(2).S)cat](+) in organic solvents.
Web-based image processing using JavaScript and WebCL (2014)

This paper presents a web-based image processing using JavaScript and WebCL. We modified the Pixastic library using the WebCL for GPU acceleration and evaluated its performance. As a result, we could achieve 2.4 times and 3.3 times on average for Webkit and FireFox, respectively. Also, we developed a platform and device selection algorithm for the best performance of the web-based execution on heterogeneous multicore environment.
Repression of β-catenin function in malignant cells by nonsteroidal antiinflammatory drugs (2005)

Activation of the Wnt/beta-catenin pathway promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents. Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to antagonize beta-catenin function, but their mechanism of action is not known. We demonstrate here that interference with beta-catenin function by NSAIDs does not correlate with cyclooxygenase (COX) inhibition. Instead, NSAID inhibition of beta-catenin requires the high level expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and its co-receptor retinoid-X-receptor alpha (RXR-alpha). Immunoprecipitation experiments show that beta-catenin interacts with RXR-alpha and PPAR-gamma in some malignant cells. Repression of beta-catenin-dependent transcription by NSAIDs is thus indirect and depends on the coexpression of other nuclear receptors.
Pharmacological Profiles of Acute Myeloid Leukemia Treatments in Patient Samples by Automated Flow Cytometry: A Bridge to Individualized Medicine (2013)

We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.
Identification and Three-dimensional Structural Analysis of Nine Novel Mutations in Patients with Prothrombin Deficiency (2000)

Prothrombin deficiency is an autosomal recessive disorder associated with a moderately severe bleeding tendency. In this study, 13 patients with prothrombin deficiency were screened for the presence of alterations in the prothrombin gene, and nine novel candidate mutations were identified. Of 11 patients with hypoprothrombinemia, ten are homozygous for five mutations and one patient is a compound heterozygote. The two patients with dysprothrombinemia are homozygous for two mutations. Eight of nine mutations are missense ones associated with single amino acid substitutions in the propeptide (Arg-1Gln, Arg-2Trp), the kringle-1 (Asp118Try) and kringle-2 (Arg220Cys) domains and the catalytic serine protease domain (Gly330Ser, Ser354Arg. Arg382His and Arg538Cys). The ninth mutation is an in-frame deletion of 3 bp that results in the omission of one amino acid (del Lys 301/302). The combination of these missense mutations with crystal structures for alpha-thrombin and the prothrombin fragments 1 and 2 resulted in new insight into the function of alpha-thrombin. The hypoprothrombinemia mutations were inferred to affect either the cleavage of the propeptide from the Gla domain, the stability of the kringle-1 and -2 domains, or the close association of the A and B chains of the serine protease domain. The dysprothrombinemia mutations were inferred to directly affect catalytic function through their location at the active site crevice or exosite 1 within the serine protease domain.
Increased Soluble C5b‐9 in CSF of Neuromyelitis Optica (2013)

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are two of the autoimmune inflammatory demyelinating diseases in the central nervous system. Complement is thought to have an important role in pathogenesis of these diseases, especially in NMO. However, the change of terminal complement complex (TCC, C5b-9) in patients with NMO is still unclear. Cerebrospinal fluid (CSF) C3a, C5a, sC5b-9 were measured by enzyme-linked immunosorbent assay in patients with NMO (n = 26), MS (n = 25) and other neurological disease (OND, n = 19). CSF levels of C5a in patients with NMO were higher than patients with OND (P = 0.006). Increased CSF sC5b-9 were found in the patients with NMO compared with patients with MS (P = 0.029) and OND (P = 0.0001). CSF sC5b-9 in patients with MS were also higher than patients with OND (P = 0.030). Patients with NMO revealed a trend to an increased disease disability with increased CSF sC5b-9 during relapse but not in MS (NMO: P = 0.006, MS: P = 0.097). CSF levels of sC5b-9 are increased in patients with NMO and reflect the activation of complement in NMO.