gebhart/patrepeval huggingface dataset:
Ia+ murine epidermal Langerhans cells are deficient in surface expression of the class I major histocompatibility complex. (1986)

Murine epidermal Langerhans cells were analyzed with fluorescence microscopy and multicolor flow cytometry for the surface expression of major histocompatibility complex (MHC) class I and class II antigens. Langerhans cells of H-2k haplotype were identified in situ or in epidermal-cell suspensions by their surface expression of the MHC class II determinants I-Ak and I-Ek. More than 90% of class II-positive Langerhans cells in epidermal-cell suspensions expressed no or barely detectable amounts of MHC class I antigens. Quantitation by flow cytometry revealed that H-2k Langerhans cells expressed only 1.6-3.3% as much H-2Kk as did class II-negative keratinocytes in the same epidermal-cell suspensions. By fluorescence microscopy, class I MHC antigens were not detectable on Langerhans cells in situ when analyzed on sheets of intact epidermis. The deficient expression of class I MHC permitted highly purified Langerhans cell populations to be isolated from epidermal cell suspensions by treatment with anti-class I MHC monoclonal antibody and complement. It is likely that the uniquely low cell-surface expression of class I MHC antigen by Langerhans cells has relevance to both immune responses in the skin as well as to mechanisms of skin allograft rejection. In addition, it is conceivable that regulation of class I MHC expression on antigen-presenting cells in general is an important but hitherto unrecognized mechanism of immune regulation.
Phase transfer catalysis in the tert-butyloxycarbonylation of alcohols, phenols, enols, and thiols with di-tert-butyl dicarbonate (1985)

It is shown that the tert-butyloxycarbonylation of phenols, alcohols, enols, and thiols can be accomplished by reaction of these functionalities with di-tert-butyl dicarbonate under phase transfer conditions. The reactions proceed in high yield and can also be used for the introduction of t-BOC groups onto functionalized polymer backbones such as novolac or poly(p-hydroxystyrene). In addition, a study is made of the selectivity towards tert-butyloxycarbonylation of various polyfunctional compounds.
Uncovering Large Groups of Active Malicious Accounts in Online Social Networks (2014)

The success of online social networks has attracted a constant interest in attacking and exploiting them. Attackers usually control malicious accounts, including both fake and compromised real user accounts, to launch attack campaigns such as social spam, malware distribution, and online rating distortion. To defend against these attacks, we design and implement a malicious account detection system called SynchroTrap. We observe that malicious accounts usually perform loosely synchronized actions in a variety of social network context. Our system clusters user accounts according to the similarity of their actions and uncovers large groups of malicious accounts that act similarly at around the same time for a sustained period of time. We implement SynchroTrap as an incremental processing system on Hadoop and Giraph so that it can process the massive user activity data in a large online social network efficiently. We have deployed our system in five applications at Facebook and Instagram. SynchroTrap was able to unveil more than two million malicious accounts and 1156 large attack campaigns within one month.
The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint (2001)

The spindle checkpoint prevents cell cycle progression in cells that have mitotic spindle defects. Although several spindle defects activate the spindle checkpoint, the exact nature of the primary signal is unknown. We have found that the budding yeast member of the Aurora protein kinase family, Ipl1p, is required to maintain a subset of spindle checkpoint arrests. Ipl1p is required to maintain the spindle checkpoint that is induced by overexpression of the protein kinase Mps1. Inactivating Ipl1p allows cells overexpressing Mps1p to escape from mitosis and segregate their chromosomes normally. Therefore, the requirement for Ipl1p in the spindle checkpoint is not a consequence of kinetochore and/or spindle defects. The requirement for Ipl1p distinguishes two different activators of the spindle checkpoint: Ipl1p function is required for the delay triggered by chromosomes whose kinetochores are not under tension, but is not required for arrest induced by spindle depolymerization. Ipl1p localizes at or near kinetochores during mitosis, and we propose that Ipl1p is required to monitor tension at the kinetochore.
Failure semantics of mobile agent systems involved in network fault management (2002)

In this paper we examine what failure semantics are desirable for services provided by a mobile agent system (MAS) when assuming the MAS to be part of a network fault management system. We also present results from an evaluation project where the failure semantics of state of the art MAS were examined.
Laparoscopic treatment of perforated duodenal ulcer. (1993)

We present a case of a perforated duodenal ulcer in an elderly malnourished, septic, diabetic patient with abnormal renal function. This patient was treated successfully with laparoscopic surgery. We suggest that similar cases can be treated by this method.
Rate of CRL4CRBN substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4 (2015)

Recent discoveries suggest that the critical events leading to the anti-proliferative activity of the IMiD immunomodulatory agents lenalidomide and pomalidomide in multiple myeloma (MM) cells are initiated by Cereblon-dependent ubiquitination and proteasomal degradation of substrate proteins Ikaros (IKZF1) and Aiolos (IKZF3). By performing kinetic analyses, we found that the downregulation or proteasomal degradation of Ikaros and Aiolos led to specific and sequential downregulation of c-Myc followed by IRF4 and subsequent growth inhibition and apoptosis. Notably, to ensure growth inhibition and cell death, sustained downregulation of Ikaros and Aiolos, c-Myc or IRF4 expression was required. In addition, we found that the half-maximal rate, rather than the final extent of Ikaros and Aiolos degradation, correlated to the relative efficacy of growth inhibition by lenalidomide or pomalidomide. Finally, we observed that all four transcription factors were elevated in primary MM samples compared with normal plasma cells. Taken together, our results suggest a functional link between Ikaros and Aiolos, and the pathological dysregulation of c-Myc and IRF4, and provide a new mechanistic understanding of the relative efficacy of lenalidomide and pomalidomide based on the kinetics of substrate degradation and downregulation of their downstream targets.
Estimation of absolute vehicle speed using fuzzy logic rule-based Kalman filter (2005)

Accurate knowledge on the absolute or true speed of a vehicle, if and when available, can be used to enhance advanced vehicle dynamics control systems such as anti-lock brake systems (ABS) and auto-traction systems (ATS) control schemes. Current conventional method uses wheel speed measurements to estimate the speed of the vehicle. As a result, indication of the vehicle speed becomes erroneous and, thus, unreliable when large slips occur between the wheels and terrain. This paper describes a fuzzy rule-based Kalman filtering technique which employs an additional accelerometer to complement the wheel-based speed sensor, and produce an accurate estimation of the true speed of a vehicle. We use the Kalman filters to deal with the noise and uncertainties in the speed and acceleration models, and fuzzy logic to tune the covariances and reset the initialization of the filter according to slip conditions detected and measurement-estimation condition. Experiments were conducted using an actual vehicle to verify the proposed strategy.
Iodide-Induced Thyrotoxicosis (1983)

Iodide-induced thyrotoxicosis (IIT) occurs in patients with: 1) endemic goiter; 2) nonendemic goiter; 3) no previous thyroid disease. Iodine prophylaxis for endemic goiter caused transient increase of 0.01-0.04% over the basal incidence of hyperthyroidism peaking at 1-3 years and normalizing in 3-10 years despite continued iodide exposure. Elderly subjects with large nodular goiters of long standing are at greater risk. In nonendemic areas, iodine-containing drugs such as amiodarone, radiographic contrast media or iodochlorhydroxyquinoline are implicated in IIT more often than iodides. With nonendemic goiter, IIT occurs more commonly in women whereas, in the absence of preexisting thyroid disease, men are more often affected. In both groups, exophthalmos and antithyroid antibodies are absent, radioiodine uptake is low, there is no thyroid tenderness or pain, and the hyperthyroidism is self-limited (1-6 months) and should thus be treated conservatively. IIT occurs more frequently in areas of marginal iodine intake (Europe) than in the U.S. In view of the extensive exposure to iodine, it is a rare complication in this country. It is postulated that defective autoregulation of hormone biosynthesis may contribute to IIT.
Ultratructure of Gastric Myxofibroma with Intracytoplasmic Collagen (1982)

Electron microscopy of a small mass removed from the stomach of a 65-year-old women demonstrated a myxofibroma composed of a pure population of fibroblasts, many of which contained intracytoplasmic, membrane-bound collagen fibers similar to those found in a few other human tumors and in certain experimental conditions. This ultrastructural documentation supports the hypothesis that pure fibrous neoplasms of the stomach do occur. Electron microscopy of gastric mesenchymal tumors almost always allows for confident differentiation among fibrous, neural, and smooth muscle neoplasms.
Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice (1999)

To elucidate the role of cardiac myosin-binding protein-C (MyBP-C) in myocardial structure and function, we have produced mice expressing altered forms of this sarcomere protein. The engineered mutations encode truncated forms of MyBP-C in which the cardiac myosin heavy chain-binding and titin-binding domain has been replaced with novel amino acid residues. Analogous heterozygous defects in humans cause hypertrophic cardiomyopathy. Mice that are homozygous for the mutated MyBP-C alleles express less than 10% of truncated protein in M-bands of otherwise normal sarcomeres. Homozygous mice bearing mutated MyBP-C alleles are viable but exhibit neonatal onset of a progressive dilated cardiomyopathy with prominent histopathology of myocyte hypertrophy, myofibrillar disarray, fibrosis, and dystrophic calcification. Echocardiography of homozygous mutant mice showed left ventricular dilation and reduced contractile function at birth; myocardial hypertrophy increased as the animals matured. Left-ventricular pressure-volume analyses in adult homozygous mutant mice demonstrated depressed systolic contractility with diastolic dysfunction. These data revise our understanding of the role that MyBP-C plays in myofibrillogenesis during cardiac development and indicate the importance of this protein for long-term sarcomere function and normal cardiac morphology. We also propose that mice bearing homozygous familial hypertrophic cardiomyopathy-causing mutations may provide useful tools for predicting the severity of disease that these mutations will cause in humans.
A High-Mobility Electron-Transport Polymer with Broad Absorption and Its Use in Field-Effect Transistors and All-Polymer Solar Cells (2007)

An electron-transport polymer with good solution processibility, excellent thermal stability, and high electron affinity based on alternating perylene diimide and dithienothiophene units has been synthesized. Electron mobilities as high as 1.3 × 10-2 cm2 V-1 s-1 have been measured in field-effect transistor geometry. The polymer shows broad absorptions throughout the visible and extending into the near-IR. A power conversion efficiency of over 1%, under simulated AM 1.5, 100 mW/cm2, was measured for a single-layer solar cell using this polymer as an acceptor and a polythiophene derivative as a donor.
Role of Phosphorylation in Agonist-promoted β2-Adrenergic Receptor Sequestration (1995)

The beta 2-adrenergic receptor (beta 2AR) belongs to the large family of G protein-coupled receptors. Mutation of tyrosine residue 326 to an alanine resulted in a beta 2AR mutant (beta 2AR-Y326A) that was defective in its ability to sequester and was less well coupled to adenylyl cyclase than the wild-type beta 2AR. However, this mutant receptor not only desensitized in response to agonist stimulation but down-regulated normally. In an attempt to understand the basis for the properties of this mutant, we have examined the ability of this regulation-defective mutant to undergo agonist-mediated phosphorylation. When expressed in 293 cells, the maximal response for phosphorylation of the beta 2AR-Y326A mutant was impaired by 75%. Further characterization of this phosphorylation, using either forskolin stimulation or phosphorylation site-deficient beta 2AR-Y326A mutants, demonstrated that the beta 2AR-Y326A mutant can be phosphorylated by cAMP-dependent protein kinase (PKA) but does not serve as a substrate for the beta-adrenergic receptor kinase 1 (beta ARK1). However, overexpression of beta ARK1 led to the agonist-dependent phosphorylation of the beta 2AR-Y326A mutant and rescue of its sequestration. beta ARK1-mediated rescue of beta 2AR-Y326A sequestration could be prevented by mutating putative beta ARK phosphorylation sites, but not PKA phosphorylation sites. In addition, both sequestration and phosphorylation of the wild-type beta 2AR could be attenuated by overexpressing a dominant-negative mutant of beta ARK1 (C20 beta ARK1-K220M). These findings implicate a role for beta ARK1-mediated phosphorylation in facilitating wild-type beta 2AR sequestration.
Borane O-Adduct Can Be an Intermediate in Chiral N-Sulfonyloxazaborolidine-Catalyzed Enantioselective Reduction of Ketones (1995)

Chiral N-sulfonylamino alcohols were found to serve as an effective chiral source in the borane reduction of ketones, though stoichiometric. Contrary to the previous report, this result suggests that borane and N-sulfonyloxazaborolidine form a complex (borane O-adduct) and that the borane O-adduct reduces ketones enantioselectively.
Targeting Proliferating Cell Nuclear Antigen and Its Protein Interactions Induces Apoptosis in Multiple Myeloma Cells (2013)

Multiple myeloma is a hematological cancer that is considered incurable despite advances in treatment strategy during the last decade. Therapies targeting single pathways are unlikely to succeed due to the heterogeneous nature of the malignancy. Proliferating cell nuclear antigen (PCNA) is a multifunctional protein essential for DNA replication and repair that is often overexpressed in cancer cells. Many proteins involved in the cellular stress response interact with PCNA through the five amino acid sequence AlkB homologue 2 PCNA-interacting motif (APIM). Thus inhibiting PCNA's protein interactions may be a good strategy to target multiple pathways simultaneously. We initially found that overexpression of peptides containing the APIM sequence increases the sensitivity of cancer cells to contemporary therapeutics. Here we have designed a cell-penetrating APIM-containing peptide, ATX-101, that targets PCNA and show that it has anti-myeloma activity. We found that ATX-101 induced apoptosis in multiple myeloma cell lines and primary cancer cells, while bone marrow stromal cells and primary healthy lymphocytes were much less sensitive. ATX-101-induced apoptosis was caspase-dependent and cell cycle phase-independent. ATX-101 also increased multiple myeloma cells' sensitivity against melphalan, a DNA damaging agent commonly used for treatment of multiple myeloma. In a xenograft mouse model, ATX-101 was well tolerated and increased the anti-tumor activity of melphalan. Therefore, targeting PCNA by ATX-101 may be a novel strategy in multiple myeloma treatment.
Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease. (1987)

The availability of recombinant human interleukin 2 (rH IL 2) has resulted in its clinical utilization both as a single agent and in combination with lymphokine-activated killer cells. In this report, we discuss the effects of rH IL 2, administered by various routes, on effector cell function, pharmacokinetics and bioavailability, and therapeutic activity. Studies of the pharmacokinetics of in vitro natural killer (NK) cell augmentation by rH IL 2 revealed that a short exposure to high levels of rH IL 2 can augment NK cell activity; however, a prolonged exposure (greater than 12 h) was required to augment NK cell activity at lower doses of rH IL 2. These observations suggested that chronic administration of rH IL 2 might improve immunomodulatory and therapeutic activity. This hypothesis was supported by the results of studies in which we treated experimental and spontaneous metastasis, which revealed that the daily i.p. administration of rH IL 2 resulted in significantly greater therapeutic activity than administration three times/week. The therapeutic protocol for daily i.p. administration had a biphasic dosage optimum, such that low dose therapeutic activity was observed at approximately 100-1000 units/animal in the treatment of experimental metastases or 10 to 100 units/animal in the treatment of spontaneous metastases. There was a second dosage optimum at greater than or equal to 100,000 units/animal rH IL 2 delivered i.p. on a daily basis. Intermediate doses had no significant therapeutic activity. Additional studies revealed that low dose therapeutic activity was not observed in nude mice. In contrast, therapeutic activity was observed in nude mice at high doses of rH IL 2 suggesting that low dose activity was associated with a T-cell-mediated effect, whereas high dose activity may have been mediated by NK or lymphokine-activated killer-like cells. This observation was in agreement with the dose response for T-cell adjuvant activity supporting the hypothesis that low dose therapeutic activity was T-cell associated, because adjuvant activity was observed when rH IL 2 was given daily at approximately 100 units/animal for 3 days, and higher doses had no activity or had a suppressive effect. Because we were concerned about the pharmacological aspects of rH IL 2 treatment, we also examined its therapeutic properties after continuous administration i.p. by osmotic pumps. Under these conditions, therapeutic activity was observed after administration of 600 units/h, whereas lower or higher doses did not have significant therapeutic activity.
A Caveolar Complex between the Cationic Amino Acid Transporter 1 and Endothelial Nitric-oxide Synthase May Explain the “Arginine Paradox” (1997)

Immunohistochemistry of porcine pulmonary artery endothelial cells (PAEC) with antibodies specific for caveolin, endothelial nitric-oxide synthase (eNOS), and the arginine transporter (CAT1) demonstrates that all of these proteins co-localize in plasma membrane caveolae. When incubated with solubilized PAEC plasma membrane proteins, eNOS-specific antibody immunoprecipitates CAT1-mediated arginine transport. These results document the existence of a caveolar complex between CAT1 and eNOS in PAEC that provides a mechanism for the directed delivery of substrate arginine to eNOS. Direct transfer of extracellular arginine to membrane-bound eNOS accounts for the "arginine paradox" and explains why caveolar localization of eNOS is required for optimal nitric oxide production by endothelial cells.
Improving Workflovf In Home Healthcare Industry: A Case Study (2004)

Home healthcare industry is facing increasing pressure to change business processes and manage information flow electronically. With the help of a case example, this paper describes how a webbased system could improve the workflow communication problems in home healthcare companies. Every department of the case company has its own software to assist in everyday operations but is unable to communicate with one another electronically. All documents necessary in the coordination of care have to move physically between departments. The proposed solution is a web-based electronic form management system that would improve regulatory compliance and operating efficiency.
Immunogenicity and Safety of Recombinant Rabies Viruses Used for Oral Vaccination of Stray Dogs and Wildlife (2009)

Rabies is a zoonotic disease and stray dogs, wild carnivores and bats are the natural reservoirs of rabies. Oral immunization with live vaccines is the only practical approach to eradicate rabies in free ranging terrestrial animals. We have developed the double glycoprotein (G) rabies virus (RV) variant SPBNGAS-GAS that has great promise to be used as a live-attenuated vaccine. Oral immunization of rodents and several target animal species with this double G RV variant resulted in the induction of protective immunity, superior to that induced by a single RV G variant (SPBNGAS). The high oral efficacy of SPBNGAS-GAS is likely because of its increased ability to infect monocytes or immature dendritic cells (DCs), thereby inducing their conversion into mature DCs. Furthermore, infection of DCs with the double G variant resulted in a strong up-regulation of the expression of genes related to the NFjB signalling pathway including IFN-α and IFN-β, which might underlie the protection conferred by this live RV vaccine. A potential problem associated with the use of live RVs for oral vaccination could rest in the possibility of reversion to the pathogenic phenotype because of the high mutation rate characteristic for all RNA viruses. In this respect, the presence of a second non-pathogenic G gene decreases considerably the risk of reversion to the pathogenic phenotype because a nonpathogenic G is dominant over a pathogenic G in determining the pathogenicity of the double G RV variant. Because of its excellent efficacy and safety, the SPBNGAS-GAS vaccine may provide a distinct advantage over other live RV vaccine in its ability to vaccinate a broad range of mammalian species.
Gene Replacement Therapies for Duchenne Muscular Dystrophy Using Adeno-Associated Viral Vectors (2012)

The muscular dystrophies collectively represent a major health challenge, as few significant treatment options currently exist for any of these disorders. Recent years have witnessed a proliferation of novel approaches to therapy, spanning increased testing of existing and new pharmaceuticals, DNA delivery (both anti-sense oligonucleotides and plasmid DNA), gene therapies and stem cell technologies. While none of these has reached the point of being used in clinical practice, all show promise for being able to impact different types of muscular dystrophies. Our group has focused on developing direct gene replacement strategies to treat recessively inherited forms of muscular dystrophy, particularly Duchenne and Becker muscular dystrophy (DMD/BMD). Both forms of dystrophy are caused by mutations in the dystrophin gene and all cases can in theory be treated by gene replacement using synthetic forms of the dystrophin gene. The major challenges for success of this approach are the development of a suitable gene delivery shuttle, generating a suitable gene expression cassette able to be carried by such a shuttle, and achieving safe and effective delivery without elicitation of a destructive immune response. This review summarizes the current state of the art in terms of using adeno-associated viral vectors to deliver synthetic dystrophin genes for the purpose of developing gene therapy for DMD.