gebhart/patrepeval huggingface dataset:
V gene usage by seven hybrids derived from CD5+ B-cell chronic lymphocytic leukemia and displaying autoantibody activity (1993)

We report here the complete heavy and light chain variable region sequences of seven heterohybridomas derived from CD5+ chronic lymphocytic leukemia (CLL) B lymphocytes and displaying natural autoantibody activity. The three hybrids displaying a polyreactive pattern of binding used VH4 family members, ie, the VH4–18 gene in germinal configuration in two cases and a VH4 gene with 90% homology with VH4–21 for the third one. A hybrid expressing anti-Sm activity used a VH3 family member with 95.26% homology with the 30P1 gene. The three hybrids exclusively displaying rheumatoid factor activity expressed VH1 family genes: 51P1 gene for two (in germinal configuration in one, and with 93.2% homology in the other), whereas the third one used the V1–3b gene (98.8% homology). Definitive homology with known germline D segments was found for four of the seven hybrids (DN2 in 3 and DLR4 in 1) and JH use appeared to be random. The three hybrids displaying polyreactive activity expressed V kappa I, V lambda III, and V lambda II genes, all in germinal configuration. Among the three hybrids with rheumatoid factor activity, two used the same V kappa II gene with, respectively, 98% and 96% homology with a gene previously described; the third used a V lambda I gene in germinal configuration. Finally, the clone with anti-Sm activity used a V lambda III gene having 97% homology with a germinal gene. Overall, these results attempt to establish the relationship between frequent self- reactivity observed in CD5+ B-CLL and V gene usage. For VH genes, they confirm overexpression of the 51P1 gene in B-CLL and suggest nonstochastic use of two VH4 genes (4–21 and 4–18). For VL genes, available information is too scarce to lead to firm conclusions.
Neutralizing Anti-F Glycoprotein and Anti-Substance P Antibody Treatment Effectively Reduces Infection and Inflammation Associated with Respiratory Syncytial Virus Infection (2002)

Respiratory syncytial virus (RSV) is the most important virus mediating lower respiratory tract illness in infants and young children. RSV infection is associated with pulmonary inflammation and increased levels of substance P (SP), making the airways and leukocytes that express SP receptors susceptible to the proinflammatory effects of this peptide. This study examines combining neutralizing anti-F glycoprotein and anti-SP antibody treatment of RSV-infected BALB/c mice to inhibit RSV replication and inflammation associated with infection. BALB/c mice were prophylactically treated with antibody prior to RSV infection or were therapeutically treated at day 2 or 6 post-RSV infection. Prophylactic or therapeutic treatment with anti-SP antibodies promptly reduced pulmonary inflammatory cell infiltration and decreased the number of cells expressing proinflammatory cytokines, while anti-F antibody treatment reduced virus titers. The results suggest that combined anti-viral and anti-SP antibody treatment may be effective in treating RSV disease.
Assessment of the 18F-Labeled PET Tracer LMI1195 for Imaging Norepinephrine Handling in Rat Hearts (2013)

In rats, cardiac uptake of (18)F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting (18)F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.
Ultrastructural changes in Bruch's membrane of apolipoprotein E-deficient mice. (2000)

ApoE(-) mice exhibit accumulation of EL particles at an earlier age and have more membrane-bounded material in BM than control mice. This material has ultrastructural similarities to basal linear deposit, which accumulates in age-related maculopathy.
Sensitivity of Mammalian Cells Expressing Mutant Ubiquitin to Protein-damaging Agents (2001)

There is convincing evidence from studies in yeast that a functional ubiquitin/proteasome pathway is required to degrade misfolded or oxidatively damaged proteins but for technical reasons, it has been difficult to perform comparable studies in mammalian cells. To investigate the possibility that the ubiquitin/proteasome pathway is cytoprotective for mammalian cells, we have introduced epitope-tagged wild-type ubiquitin or dominant-negative mutant versions of ubiquitin into mouse HT4 neuroblastoma cells. Cells expressing mutant versions of ubiquitin were found to be sensitive to cadmium, an agent that causes oxidative damage to cellular components, and to canavanine, an amino acid analog that generates misfolded proteins. The greatest sensitivity to canavanine was observed in cells expressing a mutant version of ubiquitin unable to support the formation of Lys(48) linkages. Substrates of the proteasome were found to accumulate in these cells, suggesting a general deficit in proteolysis. Our data suggest that defects in the ubiquitin-mediated proteolytic system predispose mammalian cells to the toxic effects of abnormal protein.
Novel Series of Potent, Nonsteroidal, Selective Androgen Receptor Modulators Based on 7H-[1,4]Oxazino[3,2-g]quinolin-7-ones (2007)

Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.
Growth Analysis of Wronskians in terms of Slowly Changing Functions (2013)

In the paper we establish some new results depending on the comparative growth properties of composite entire or meromorphic functions using generalised <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msup><mml:mi>L</mml:mi><mml:mo>∗</mml:mo></mml:msup></mml:mrow></mml:math>-order and generalised <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:msup><mml:mi>L</mml:mi><mml:mo>∗</mml:mo></mml:msup></mml:mrow></mml:math>-type and Wronskians generated by one of the factors.
Quantum Storage of Three-Dimensional Orbital-Angular-Momentum Entanglement in a Crystal (2015)

Here we present the quantum storage of three-dimensional orbital-angular-momentum photonic entanglement in a rare-earth-ion-doped crystal. The properties of the entanglement and the storage process are confirmed by the violation of the Bell-type inequality generalized to three dimensions after storage (S=2.152±0.033). The fidelity of the memory process is 0.993±0.002, as determined through complete quantum process tomography in three dimensions. An assessment of the visibility of the stored weak coherent pulses in higher-dimensional spaces demonstrates that the memory is highly reliable for 51 spatial modes. These results pave the way towards the construction of high-dimensional and multiplexed quantum repeaters based on solid-state devices. The multimode capacity of rare-earth-based optical processors goes beyond the temporal and the spectral degree of freedom, which might provide a useful tool for photonic information processing.
Hydrophobic Collapse of Foldamer Capsules Drives Picomolar-Level Chloride Binding in Aqueous Acetonitrile Solutions (2013)

Aqueous media are competitive environments in which to perform host-guest chemistry, particularly when the guest is highly charged. While hydrophobic binding is a recognized approach to this challenge in which apolar pockets can be designed to recognize apolar guests in water, complementary strategies are required for hydrophilic anions like chloride. Here, we present evidence of such an alternative mechanism, used everyday by proteins yet rare for artificial receptors, wherein hydrophobic interactions are shown to be responsible for organizing and stabilizing an aryl-triazole foldamer to help extract hydrophilic chloride ions from increasingly aqueous solutions. Therein, a double-helical complex gains stability upon burial of ∼80% of the π surfaces that simultaneously creates a potent, solvent-excluding microenvironment for hydrogen bonding. The chloride's overall affinity to the duplex is substantial in 25% water v/v in acetonitrile (log β2 = 12.6), and it remains strong (log β2 = 13.0) as the water content is increased to 50%. With the rise in predictable designs of abiological foldamers, this water-assisted strategy can, in principle, be utilized for binding other hydrophilic guests.
Diagnostic Value of Immunohistochemical IMP3 Expression in Core Needle Biopsies of Pancreatic Ductal Adenocarcinoma (2011)

The oncofetal protein, insulin-like growth factor II messenger ribonucleic acid-binding protein 3 (IMP3), has been analyzed in many different tumors. Various studies have found that IMP3 is a marker for malignancy and is correlated with increased tumor aggressiveness and reduced overall survival. The diagnosis of pancreatic ductal adenocarcinoma (PDAC) in core needle biopsies can be challenging, and immunohistochemical markers are needed. We studied IMP3 expression in 177 core needle biopsies of the pancreas, including 112 PDACs, 55 cases with chronic sclerosing pancreatitis, and 10 biopsies with tumor-free pancreatic tissue without inflammation. An additional 18 biopsies of PDAC metastases (16 liver biopsies and 2 lymph node biopsies) were analyzed. To study IMP3 expression in large tissue sections, 45 pancreatic resection specimens (26 with PDAC and 19 with chronic sclerosing pancreatitis) were investigated. In contrast to normal or inflamed pancreatic tissue, which was negative in 47 of 65 (72.3%) cases and weakly positive in 15 of 65 (23.1%) cases, strong IMP3 expression was found in 99 of 112 (88.4%) PDACs. Therefore, sensitivity and specificity of IMP3 expression in the differential diagnosis of PDAC and chronic sclerosing pancreatitis using core needle biopsies were found to be 88.4% and 94.6%, respectively. These results were confirmed in the pancreas resection specimens. Furthermore, strong IMP3 expression was found in 17 of 18 (94.4%) of the PDAC metastases that were analyzed. Our study shows that IMP3 is an easy to use and potentially new immunohistochemical marker for the diagnosis of PDAC in core needle biopsies.
Fabrication of one-dimensional GaAs wires by focused ion beam implantation (1988)

Novel, simple techniques were developed to fabricate very narrow GaAs conducting wires by utilizing direct focused ion beam (FIB) implantation. We employed two methods for fabrication of the wires. The first method makes use of high-resistivity (HR) regions formed by FIB implantation without successive annealing to define a very narrow conducting wire (HR method). In the second one, focused Si ions are line implanted into p-type GaAs, forming an n-type conducting wire in the p-type region. Then, reverse-bias is applied across the pn junction in order to make the wire narrower by expanding the depletion layer (PN method). This structure has an advantage that the thickness of the wire can be varied by bias voltage. Magnetoconductances measured in all the fabricated wires show evidences of weak electron localization and conductance fluctuations due to a quantum interference effect. The minimum widths of the wires are evaluated to be ∼20 nm (HR method) and ∼100 nm (PN method) by fitting the theory of one-dimensional weak localization to the experimental data. The phase coherent length of the electronic waves in the wires is also derived to be ∼120 nm at 1.3 K.
Residual disease after radical surgery or radiation therapy for prostate cancer. Clinical significance and therapeutic implications (1993)

Radical treatment for prostate cancer aims at complete eradication of tumor. This review of published data makes clear that the goal is less frequently achieved than commonly presumed. Following radical prostatectomy extracapsular disease, carrying a significant risk of local recurrence, is found from 12-68% of the time depending on the clinical tumor stage. Local regrowth is associated with a poorer prognosis. A substantial proportion of patients whose prostate glands are rebiopsied more than 18 months after radiation therapy also have residual tumor. This again predicts for clinical relapse. The likelihood of a positive rebiopsy is dependent on original tumor size and current prostate specific antigen (PSA) levels. Strategies for managing residual disease are critically discussed.
Risk for human immunodeficiency virus (HIV) infection among persons with severe mental illnesses (1997)

Individuals diagnosed with a severe mental illness are at significantly enhanced risk for infection with the human immunodeficiency virus (HIV). To better understand elevated seroprevalence in this population, we review the research literature that has investigated HIV-related risk behavior among adults who have a severe and persistent mental illness. This review indicates that 54%-74% of adults report that they have been sexually active in the last year with approximately one third reporting two or more partners. Among those who were sexually active, condom use was inconsistent. A significant minority (4%-35%) of adults also reported a history of injection drug use. Overall, the data indicate that the severely mentally ill engage regularly in practices known to involve increased risk for HIV transmission. We introduce and modify Fisher and Fisher's (1992) theoretical model to organize the possible determinants of HIV-related risk taking among severely mentally ill adults, and encourage use of this model in the design of behavioral epidemiological and risk reduction studies. We also identify several methodological challenges to HIV-related research, including problems associated with the use of self-report measures; diagnostic imprecision; and participant recruitment and retention.
Copy-Number Variations, Noncoding Sequences, and Human Phenotypes (2011)

Whereas single-nucleotide polymorphisms and their role in predisposition to disease have been studied extensively, the analysis of structural variants--genomic changes such as insertions, deletions, inversions, duplications, and translocations--is still in its infancy. Changes in copy number, also known as copy-number variations (CNVs), constitute one such group of these structural variants. CNVs are structural genomic variants that arise from deletions (loss) or duplications (gain), and as a consequence result in a copy-number change of the respective genomic region. CNVs may include entire genes or regions of transcribed sequence, or, indeed, comprise only nontranscribed sequences. Whereas the duplication or deletion of a gene can be expected to have an effect on gene dosage, the consequences of CNVs in nontranscribed sequences are less obvious. Here we review CNVs that involve regulatory nontranscribed regions of the genome, describe the associated human phenotypes, and discuss possible disease mechanisms.
Allogeneic Hematopoietic Cell Transplantation for Metastatic Renal Cell Carcinoma after Nonmyeloablative Conditioning (2004)

Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. CD8(+) CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft-versus-tumor effect. Such antigens may represent therapeutic targets for posttransplant vaccination or adoptive T-cell therapy to augment the antitumor effects of allogeneic hematopoietic cell transplantation.
Online pattern recognition in intensive care medicine. (2001)

In intensive care physiological variables of the critical-ly ill are measured and recorded in short time intervals. The existing alarm systems based on fixed thresholds produce a large number of false alarms. Usually the change of a variable over time is more informative than one pathological value at a particular time point. Intelligent alarm systems which detect important changes within a physiological time series are needed for suitable bedside decision support. There are various approaches to modeling time-dependent data and also several methodologies for pattern detection in time series. We compare several methodologies de-signed for online detection of measurement artifacts, level changes, and trends for a proper classification of the patient s state by means of a comparative case-study.
Matrix metalloproteinases and their inhibitors in gastric cancer (1998)

This study shows the presence of matrix metalloproteinases, particularly MMP-2, and TIMPs in stomach cancer. Antibodies which are effective in formalin fixed, paraffin wax embedded sections are useful for the identification of MMPs and TIMPs in diagnostic specimens.
OXIDATIVE STRESS REPRODUCES PLACENTAL ABNORMALITIES OF PREECLAMPSIA (2002)

These data mimic the changes in placental SOD, GSH-Px, catalase, TX and lipid peroxidation that occur in preeclampsia suggesting that maternal hyperlipidemia and increased iron levels may be responsible for placental oxidative stress and abnormalities in antioxidants and thromboxane.
ERβ Ligands. 3. Exploiting Two Binding Orientations of the 2-Phenylnaphthalene Scaffold To Achieve ERβ Selectivity (2005)

The 2-phenylnaphthalene scaffold was explored as a simplified version of genistein in order to identify ER selective ligands. With the aid of docking studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted to be the most potentially influential positions to enhance ER selectivity using two different binding orientations. Both orientations have the phenol moiety mimicking the A-ring of genistein. Several compounds predicted to adopt orientations similar to that of genistein when bound to ERbeta were observed to have slightly higher ER affinity and selectivity than genistein. The second orientation we exploited, which was different from that of genistein when bound to ERbeta, resulted in the discovery of several compounds that had superior ER selectivity and affinity versus genistein. X-ray structures of two ER selective compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested that substituents at positions 1 and 8 were responsible for inducing selectivity. One compound (i.e., 47, WAY-202196) was further examined and found to be effective in two models of inflammation, suggesting that targeting ER may be therapeutically useful in treating certain chronic inflammatory diseases.
Viable Molecular Hybrids of Bacteriophage Lambda and Eukaryotic DNA (1974)

A bacteriophage lambda strain has been constructed and a method developed by which DNA from potentially any source can be covalently inserted through EcoRI cohesive ends into the middle of the lambda DNA. These hybrid DNAs can infect nonrestricting Escherichia coli cells and can then propagate as plaque-forming phage. A unique feature of this lambda strain is that extra DNA in the middle of its genome is required for plaque formation. A large number of such phages have been produced with E. coli DNA and Drosophila melanogaster DNA.
Application of the MultiScreen system to cytokine radioreceptor assays. (1990)

Radioreceptor assays are becoming increasingly valuable in the biotechnology community for a variety of basic and applied research applications. It is clear, for example, that assessing the potential spectrum of biological activities of a novel polypeptide regulatory factor can be greatly simplified by the development of a rapid radioreceptor assay, since a wide variety of cell types can be screened using a single type of assay. By contrast, searching for potentially diverse biological effects can be an extremely time-consuming process. In addition, screening for agonists/antagonists for hormones using radioreceptor assays has a marked advantage compared with biological assays, in that compounds or natural products that are toxic to cells will not read out as false positives in a binding assay. Our laboratory has developed a major program centered on the molecular characterization of receptors for polypeptide hormones involved in immune regulation, including a number of cytokines/interleukins and also several colony stimulating factors. We have developed a variety of radioreceptor- and fluorescence-based assay systems for ligand-receptor interactions, with applications in basic characterization, purification, cDNA cloning, and drug development screens for cytokine receptors. In this report we compare two assay formats, a standard phthalate oil centrifugation method and a novel plate filtration system, using the interaction between interleukin-1 alpha and its receptor as a test system.
Biodegradable microspheres of curcumin for treatment of inflammation. (2002)

Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7) was formulated as prolonged release biodegradable microspheres for treatment of inflammation. Natural biodegradable polymers, namely, bovine serum albumin and chitosan were used to encapsulate curcumin to form a depot forming drug delivery system. Microspheres were prepared by emulsion-solvent evaporation method coupled with chemical cross-linking of the natural polymers. Curcumin could be encapsulated into the biodegradable carriers upto an extent of 79.49 and 39.66% respectively with albumin and chitosan. Different drug:polymer ratios did not affect the mean particle size or particle size distribution significantly. However, the concentration of the crosslinking agent had remarkable influence on the drug release. In-vitro release studies indicated a biphasic drug release pattern, characterized by a typical burst-effect followed by a slow release which continued for several days. Evaluation of antinflammatory activity using Freund's adjuvant induced arthritic model in Wistar rats revealed significant difference between both the formulations, albumin microspheres and chitosan micropheres as well as against control. It was evident from the present study that the curcumin biodegradable microspheres could be successfully employed as prolonged release drug delivery system for better therapeutic management of inflammation as compared to oral or subcutaneous route.
Context Information-based Application Access Control Model (2016)

Access control has long been a central topic in software security. Having proposed a number of different control mechanisms, including MAC, DAC, and RBAC, researchers are now introducing control models that make use of new context information, such as time, and location. Unfortunately, because these have been based on existing security paradigms, their use of context is often unintuitive, and insufficiently separated from business and processing logic. This paper proposes a new model for access control called CIAAC (Context Information-based Application Access Control). CIAAC is specifically designed to separate context awareness and access control policies from business and processing logic, allowing operators of business applications to change access control policies more freely in response to the external security environment.