gebhart/patrepeval huggingface dataset:
Nanomedicine(s) under the Microscope (2011)

Depending on the context, nanotechnologies developed as nanomedicines (nanosized therapeutics and imaging agents) are presented as either a remarkable technological revolution already capable of delivering new diagnostics, treatments for unmanageable diseases, and opportunities for tissue repair or highly dangerous nanoparticles, nanorobots, or nanoelectronic devices that will wreak havoc in the body. The truth lies firmly between these two extremes. Rational design of "nanomedicines" began almost half a century ago, and >40 products have completed the complex journey from lab to routine clinical use. Here we critically review both nanomedicines in clinical use and emerging nanosized drugs, drug delivery systems, imaging agents, and theranostics with unique properties that promise much for the future. Key factors relevant to the design of practical nanomedicines and the regulatory mechanisms designed to ensure safe and timely realization of healthcare benefits are discussed.
Occult CD45 T cell developmental defect in type 1 diabetes. (1994)

Individuals with insulin-dependent diabetes mellitus, as well as high-risk prediabetic subjects who are identified prior to the onset of hyperglycaemia by abnormal autoantibodies to both insulin and islet cells have an autologous antigen presenting cell (APC) defect that results in sluggish T cell proliferation in the in vitro autologous mixed lymphocyte reaction (AMLR). In contrast, lower-risk relatives, who produce autoantibodies restricted to insulin and fail to develop overt hyperglycaemia, show apparently normal autologous antigen presenting cell function and paradoxically demonstrate excessive T cell proliferation in the AMLR. We have now characterized this lower-risk vigorous T cell response in the autologous mixed by lymphocyte reaction as a predominant and excessive proliferation of CD4+ T cells to self-antigens (n = 10, p < 0.001). In addition, the normal autologously driven transition of the expanding CD45RA+ subset of CD4+ cells into transient CD45RA+RO+ cells with subsequent progression to CD45RA-RO+ cells is partially blocked in the lower-risk autologous response compared to controls (n = 5, p = 0.01, respectively). Autologously driven T cell developmental transitions also appear to be blocked in these individuals in vitro; the peripheral blood of lower-risk relatives contains an increased number of CD4+ cells abnormally coexpressing CD45RA and CD45RO (p = 0.01). Interestingly, in two twin sets reconstitution of T cells from the diabetic twin of an identical twin-pair that is discordant for Type 1 diabetes with the APCs of the nondiabetic twin resulted in overly vigorous T cell proliferation dominated by CD4+ cells; phenotypically, these CD4+ cells at the end of the reaction were similar to those of lower-risk relatives in that the CD45RA+RO+ transition into CD45RA-RO+ cells was now observed to be defective. Therefore, T cells from lower-risk relatives and individuals with Type 1 diabetes appear to possess similar intrinsic T cell developmental defects in CD45 transitions that are apparent after normal autologous antigen stimulation.
Re-evaluating the Roles of Proposed Modulators of Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling (2008)

Signaling through mammalian target of rapamycin complex 1 (mTORC1) is stimulated by amino acids and insulin. Insulin inactivates TSC1/2, the GTPase-activator complex for Rheb, and Rheb.GTP activates mTORC1. It is not clear how amino acids regulate mTORC1. FKBP38 (immunophilin FK506-binding protein, 38 kDa), was recently reported to exert a negative effect on mTORC1 function that is relieved by its binding to Rheb.GTP. We confirm that Rheb binds wild type FKBP38, but inactive Rheb mutants showed contrasting abilities to bind FKBP38. We were unable to observe any regulation of FKBP38/mTOR binding by amino acids or insulin. Furthermore, FKBP38 did not inhibit mTORC1 signaling. The translationally controlled tumor protein (TCTP) in Drosophila was recently reported to act as the guanine nucleotide-exchange factor for Rheb. We have studied the role of TCTP in mammalian TORC1 signaling and its control by amino acids. Reducing TCTP levels did not reproducibly affect mTORC1 signaling in amino acid-replete/insulin-stimulated cells. Moreover, overexpressing TCTP did not rescue mTORC1 signaling in amino acid-starved cells. In addition, we were unable to see any stable interaction between TCTP and Rheb or mTORC1. Accumulation of uncharged tRNA has been previously proposed to be involved in the inhibition of mTORC1 signaling during amino acid starvation. To test this hypothesis, we used a Chinese hamster ovary cell line containing a temperature-sensitive mutation in leucyl-tRNA synthetase. Leucine deprivation markedly inhibited mTORC1 signaling in these cells, but shifting the cells to the nonpermissive temperature for the synthetase did not. These data indicate that uncharged tRNA(Leu) does not switch off mTORC1 signaling and suggest that mTORC1 is controlled by a distinct pathway that senses the availability of amino acids. Our data also indicate that, in the mammalian cell lines tested here, neither TCTP nor FKBP38 regulates mTORC1 signaling.
Fuzzy Neural Network Applied to Gene Expression Profiling for Predicting the Prognosis of Diffuse Large B‐cell Lymphoma (2002)

Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphomas. Less than 50% of patients can be cured by combination chemotherapy. Microarray technologies have recently shown that the response to chemotherapy reflects the molecular heterogeneity in DLBCL. On the basis of published microarray data, we attempted to develop a long-overdue method for the precise and simple prediction of survival of DLBCL patients. We developed a fuzzy neural network (FNN) model to analyze gene expression profiling data for DLBCL. From data on 5857 genes, this model identified four genes (CD10, AA807551, AA805611 and IRF-4) that could be used to predict prognosis with 93% accuracy. FNNs are powerful tools for extracting significant biological markers affecting prognosis, and are applicable to various kinds of expression profiling data for any malignancy.
A Novel Glycosulfopeptide Binds to P-selectin and Inhibits Leukocyte Adhesion to P-selectin (1999)

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric membrane mucin on leukocytes that binds selectins. The molecular features of PSGL-1 that determine this high affinity binding are unclear. Here we demonstrate the in vitro synthesis of a novel glycosulfopeptide (GSP-6) modeled after the extreme N terminus of PSGL-1, which has been predicted to be important for P-selectin binding. GSP-6 contains three tyrosine sulfate (TyrSO(3)) residues and a monosialylated, core 2-based O-glycan with a sialyl Lewis x (C2-O-sLe(x)) motif at a specific Thr residue. GSP-6 binds tightly to immobilized P-selectin, whereas glycopeptides lacking either TyrSO(3) or C2-O-sLe(x) do not detectably bind. Remarkably, an isomeric glycosulfopeptide to GSP-6, termed GSP-6', which contains sLe(x) on an extended core 1-based O-glycan, does not bind immobilized P-selectin. Equilibrium gel filtration analysis revealed that GSP-6 binds to soluble P-selectin with a K(d) of approximately 350 nM. GSP-6 (<5 microM) substantially inhibits neutrophil adhesion to P-selectin in vitro, whereas free sLe(x) (5 mM) only slightly inhibits adhesion. In contrast to the inherent heterogeneity of post-translational modifications of recombinant proteins, glycosulfopeptides permit the placement of sulfate groups and glycans of precise structure at defined positions on a polypeptide. This approach should expedite the probing of structure-function relationships in sulfated and glycosylated proteins, and may facilitate development of novel drugs to treat inflammatory diseases involving P-selectin-mediated leukocyte adhesion.
Identification and characterization of a gene cluster mediating enteroaggregative Escherichia coli aggregative adherence fimbria I biogenesis (1994)

The aggregative pattern of adherence (AA) exhibited by enteroaggregative Escherichia coli upon HEp-2 cells is a plasmid-associated property which correlates with aggregative adherence fimbria I (AAF/I) expression and human erythrocyte hemagglutination. By using cloning and mutagenesis strategies, two noncontiguous plasmid segments (designated regions 1 and 2) required for AA expression have previously been identified in enteroaggregative E. coli 17-2. TnphoA mutagenesis was performed on clones containing region 1, and 16 TnphoA mutants which were negative for the AA phenotype were analyzed. The TnphoA insertion site for each mutant was determined by junctional DNA sequencing. All 16 mutations occurred within a 4.6-kb span in region 1. Nucleotide sequence analysis of the region revealed four contiguous open reading frames, designated aggDCBA, in the same span. AA-negative TnphoA insertions into all open reading frames except aggB were obtained. On the basis of mutational analysis and protein homology data, it is inferred that aggA, aggC, and aggD are involved in biogenesis of AAF/I, encoding a major fimbrial subunit, outer membrane usher, and periplasmic fimbrial chaperone, respectively. By immunogold electron microscopy, polyclonal antiserum raised against the aggA gene product decorated AAF/I fimbriae, affirming that AggA encodes an AAF/I subunit.
A novel in vitro screening assay for trypanocidal activity using the fluorescent dye BCECF-AM. (1995)

A cell viability assay, using fluorescence measurements has been developed for the screening of new compounds against African trypanosomes. 2',7'-Bis-(carboxyethyl)-5(6)-carboxyfluorescein-pentaacetoxymethyles ter (BCECF-AM), an esterase substrate, was used in the assay as a marker for cell viability. Fluorescence was quantified using an automated fluorescence scanner for multi-well plates. Trypanosoma brucei rhodesiense, T. congolense, T. evansi and T. equiperdum from continuously growing cultures were exposed to various concentrations of trypanocidal drugs for an incubation period of 72 h at 37 degrees C. Then BCECF-AM was added to the cell suspensions and after 60 minutes the fluorescence of the trypanosome suspension was measured using the Millipore Cytofluor 2300 fluorescence scanner, at 485 nm excitation and 530 nm emission wavelengths. Results of kinetic studies of the hydrolysis of the non-fluorescent BCECF-AM in trypanosomes showed that BCECF-AM is readily cleaved by non-specific esterases to a highly fluorescent product. Drug concentrations causing 50% inhibition of fluorescence (IC50-values) were measured fluorimetrically. Minimum inhibitory concentration (MIC) was determined microscopically.
Production and properties of a raw‐starch‐degrading amylase from the thermophilic and alkaliphilic Bacillus sp. TS‐23 (1998)

The optimum temperature and initial medium pH for amylase production by Bacillus sp. TS-23 were 55 degrees C and 8.5 respectively. Maximum amylase activity was obtained in a medium containing peptone and soluble starch as nitrogen and carbon sources. Activity staining revealed that two amylases with molecular masses of 150 and 42 kDa were produced when maltose, soluble starch or amylose was used as carbon source for growth, whereas only the 150 kDa protein was detected in the medium containing water-insoluble carbon sources. A raw-starch-degrading amylase was purified from culture supernatant of Bacillus sp. TS-23. The molecular mass of the purified amylase was estimated at 42 kDa by electrophoresis. The enzyme had a pI of 4. 2. The optimal pH and temperature for activity were 9.0 and 70 degrees C respectively. The thermoactivity of the purified enzyme was enhanced in the presence of 5 mM Ca2+; under this condition, enzyme activity could be measured at a temperature of 90 degrees C. The enzyme was strongly inhibited by Hg2+, Pb2+, Zn2+, Cu2+ and EDTA, but less affected by Ni2+ and Cd2+. The enzyme preferentially hydrolysed high-molecular-mass substrates with an alpha-1, 4-glucosidic bond except glycogen. The raw starches were partly degraded by the purified amylase to yield predominantly oligosaccharides with degrees of polymerization 3, 4 and 5.
Flavor composition of wines: A review (1979)

The formation of flavor in fermented beverages is due to various biosynthetic mechanisms. In wine, flavors arise as the result of compounds: 1. Originating from the native fruit (grap) 2. Which are formed or altered during the various processes employed in production 3. Which are developed or transformed by yeast during fermentation 4. Arise during the aging process In this review the results of investigations on the development of flavors in grape and wine will be discussed. Special attention will be devoted to the effects of specific processes in winemaking on the development of flavor.
Stimulation of B-cell proliferation by membrane-associated molecules from activated T cells. (1988)

Activation of B cells to proliferation and antibody secretion is dependent on soluble lymphokines secreted by activated T cells. Activation of T cells results from physical contact between B cells and T cells through binding of the T-cell antigen receptor to a complex of antigen and class II major histocompatibility complex (MHC) molecules. To determine whether this interaction also contributes to B-cell activation by mechanisms other than those mediated by soluble T cell-derived lymphokines, I examined the ability of isolated T-cell plasma membranes to stimulate proliferation in cultures of unfractionated B cells. Membranes prepared from a cloned antigen-specific helper T-cell line induced substantial proliferation provided that the T cells had been mitogen-activated before isolation of membranes. Membranes from splenic Con A-treated blasts also stimulated B-cell proliferation, suggesting that this activity may be a common property of some subsets of activated T cells. Induction of B-cell proliferation was not found to be antigen-dependent or MHC-restricted, indicating no significant contribution by the T-cell receptor for antigen. The presence of interleukins 4 and 5 in membrane fractions was indicated by proliferation of lymphokine-sensitive cell lines, although culture supernatants from mitogen-activated T cells proved to be far more potent sources of these activities. The combined effect of membranes and lymphokine-containing culture supernatants in B-cell cultures was greater than their added effects in separate cultures. This observation suggests that lymphokines or molecules with mitogenic activity for B cells other than those found in abundance in culture supernatants may be present on activated T-cell membranes.
Technology Challenges in Responding to Biological or Chemical Attacks in the Civilian Sector (2003)

Increasingly sophisticated technologies are needed for counterterrorism responses to biological and chemical warfare agents. Recently developed detection and identification systems are characterized by increased sensitivity, greater automation, and fewer false alarms. Attempts are also under way to reduce the cost and complexity of field-deployable systems. A broad range of decontamination reagents for equipment and personnel is emerging, but decontamination of large buildings, inaccessible spaces, and sensitive equipment remains problematic.
A space-partitioning-based indexing method for multidimensional non-ordered discrete data spaces (2006)

There is an increasing demand for similarity searches in a multidimensional non-ordered discrete data space (NDDS) from application areas such as bioinformatics and data mining. The non-ordered and discrete nature of an NDDS raises new challenges for developing efficient indexing methods for similarity searches. In this article, we propose a new indexing technique, called the NSP-tree , to support efficient similarity searches in an NDDS. As we know, overlap causes a performance degradation for indexing methods (e.g., the R-tree) for a continuous data space. In an NDDS, this problem is even worse due to the limited number of elements available on each dimension of an NDDS. The key idea of the NSP-tree is to use a novel discrete space-partitioning (SP) scheme to ensure no overlap at each level in the tree. A number of heuristics and strategies are incorporated into the tree construction algorithms to deal with the challenges for developing an SP-based index tree for an NDDS. Our experiments demonstrate that the NSP-tree is quite promising in supporting efficient similarity searches in NDDSs. We have compared the NSP-tree with the ND-tree, a data-partitioning-based indexing technique for NDDSs that was proposed recently, and the linear scan using different NDDSs. It was found that the search performance of the NSP-tree was better than those of both methods.
An Efficient Mixed Integer Programming Model Based on Timed Petri Nets for Diverse Complex Cluster Tool Scheduling Problems (2011)

Cluster tools are automated production cells which are largely used for semiconductor manufacturing. They consist of several processing modules (PMs) and a transportation robot. Since cluster tools have limited buffers and diverse scheduling requirements such as complex wafer flow patterns, parallel PMs, wafer residency time constraints, and dual-arm robot, and so on, their scheduling problems are difficult. Due to the diversity of scheduling problems, dealing with those problems one by one may be impractical. Computational complexity is another difficulty. In this paper, we propose an efficient scheduling method to deal with diverse complex cluster tool scheduling problems by using timed Petri nets (TPN). We propose TPN models of cluster tools with various scheduling requirements. Then, based on the TPN models and their state equations, we develop a new mixed integer programming (MIP) model that can efficiently determine the optimal cyclic schedules. We show that many kinds of scheduling requirements such as parallel, reentrant and multiple material flows, a dual-armed robot, and time constrained PMs can be dealt with by the MIP model. Through experiments, we also show that the MIP model can efficiently solve most practical cluster tool scheduling problems.
Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. (1989)

Cells of the murine hemopoietic cell line FDC-P1 were multiply infected with a retroviral construct containing cDNA encoding the leukemia inhibitory factor (LIF) to produce cells secreting high levels of LIF. Injection of these cells to unirradiated or irradiated syngeneic DBA/2 mice resulted in animals engrafted with LIF-producing cells in the marrow, spleen, and lymph nodes and with elevated serum LIF levels. These mice developed within 12-70 days a fatal syndrome characterized by cachexia, excess new bone formation, calcification in heart and skeletal muscle, pancreatitis, thymus atrophy, and abnormalities in the adrenal cortex and ovarian corpora lutea. Injection of mice with control FDC-P1 cells led to comparable organ engraftment, but the mice developed none of these lesions. The observations suggest that LIF may be a potent cachexia-inducing agent and may have marked effects on osteoblasts and calcium metabolism.
Combining static analysis and runtime monitoring to counter SQL-injection attacks (2005)

Our dependence on web applications has steadily increased, and we continue to integrate them into our everyday routine activities. When we are making reservations, paying bills, and shopping on-line, we expect these web applications to be secure and reliable. However, as the availability of these services has increased, there has been a corresponding increase in the number and sophistication of attacks that target them. One of the most serious types of attack against web applications is SQL injection. SQL injection is a class of code-injection attacks in which user input is included in a SQL query in such a way that part of the input is treated as code. Using SQL injection. attackers can leak confidential information, such as credit card numbers, from web applications' databases and even corrupt the database. In this paper, we propose a novel technique to counter SQL-injection. The technique combines conservative static analysis and runtime monitoring to detect and stop illegal queries before they are executed on the database. In its static part, the technique builds a conservative model of the legitimate queries that could be generated by the application. In its dynamic part, the technique inspects the dynamically generated queries for compliance with the statically-built model. We also present a preliminary evaluation of the technique performed on two small web applications. The results of the evaluation are promising---our technique was able to prevent all of the attacks that we performed on the two applications.
Brain imaging correlates of cognitive impairment in depression (2009)

This review briefly summarises recent research on the neural basis of cognition in depression. Two broad areas are covered: emotional and non-emotional processing. We consider how research findings support models of depression based on disrupted cortico-limbic circuitry, and how modern connectivity analysis techniques can be used to test such models explicitly. Finally we discuss clinical implications of cognitive imaging in depression, and specifically the possible role for these techniques in diagnosis and treatment planning.
Hydrogels for Biomedical and Pharmaceutical Applications (2001)

Hydrogels are classiﬁed in several ways (Table 1). The most simple classiﬁcation is hydrogels obtained from natural products and hydrogels made of synthetic materials. Peppas classiﬁed hydrogels in three ways: method of preparation, ionic charge, and physical structure features (5). Based on the method of preparation, hydrogels are classiﬁed further into four groups: homopolymer hydrogels, copolymer hydrogels, multipolymer hydrogels, and interpenetrating polymeric hydrogels. Based on ionic charges, hydrogels are classiﬁed as neutral, cationic, anionic, or ampholytic hydrogels. Based on physical structural features, they are classiﬁed as amorphous hydrogels, semicrystalline hydrogels, or hydrogen-bonded structures.
Safety and efficacy of a new device combining radiofrequency and low-frequency pulsed electromagnetic fields for the treatment of facial rhytides. (2012)

The results of this study show that the combination of multipolar RF with PEMF is a safe, effective, and painless approach to treat facial rhytides and is suitable to answer the demands of patients for safe treatments without pain or downtime.
Routine susceptibility testing of four antibiotic combinations for improvement of laboratory guide to therapy of cystic fibrosis infections caused by Pseudomonas aeruginosa (1995)

Previous studies have demonstrated synergy between an aminoglycoside and a beta-lactam for treating Pseudomonas aeruginosa infections. Cystic fibrosis patients are prone to infection by this bacterium, which becomes very resistant with recurrent antibiotic treatments. The purpose of this study was to evaluate the susceptibility patterns of 122 isolates of P. aeruginosa isolated from cystic fibrosis patients to five individual antibiotics (tobramycin, ceftazidime, piperacillin, ticarcillin, and imipenem) and to four antibiotic combinations (tobramycin associated with one of the other antibiotics). Strains were selected because of their resistance to individual antimicrobial agents, which ranged from 21.3% for imipenem to 56.5% for tobramycin. By using an automated broth microdilution method, we were able to demonstrate synergy against 39 strains (32%) with tobramycin-ticarcillin, against 38 strains (31%) with tobramycin-piperacillin, against 47 strains (39%) with tobramycin-ceftazidime, and against 23 strains (19%) with tobramycin-imipenem. Of the 122 isolates, 77 (63%) were rendered significantly susceptible to at least one of the four antibiotic combinations by synergy. These results suggest that when appropriate technology is available, susceptibility to antibiotic combinations greatly improves the guide to antibiotic therapy for infections due to P. aeruginosa in cystic fibrosis patients.