gebhart/patrepeval huggingface dataset:
Hybrid Antibodies (1993)

One of the major advantages of genetic engineering is the ability to produce novel, hybrid antibodies. Hybrid antibodies can be assembled using fragments from different antibodies with the objective of assembling novel combinations of antibody-related effector functions. To efficiently achieve this goal it is necessary to have a precise understanding of the structure-function relationships within the antibody molecule. Secondly, it is possible to produce hybrids of antibodies with non-immunoglobulin proteins thereby achieving unique combination of functional properties. In this case it is necessary to consider both the desired functional properties and the means of assembling the protein components so as to maintain these properties. In all cases it is necessary to have the cloned gene segments, appropriate vectors and expression systems.
Drug Delivery Systems: 3A. Role of Polymers in Drug Delivery (1990)

At present, polymers represent a class of ubiquitous materials. They are being used for a multitude of purposes and the almost inexhaustible varieties of molecular architecture that macromolecular materials can possess provides the possibility for a myriad of applications. Because of the increased interest being shown in the macromolecules by the pharmaceutical industry for the fabrication of drug delivery systems, numerous polymers have been synthesized and successfully used in drug delivery devices. The necessary conditions for developing the concept of pharmaceutically applicable polymers depend upon delineating a detailed knowledge of the relationship between the structure and properties of polymer networks. A number of polymers have been studied systematically from this point of view and there is every indication that the systems described have the potential to become clinically valuable and therefore marketable drug delivery systems. The potential of these promising polymers is still far from being exhausted and there is a strong possibility that many important developments will be forthcoming in this field in the future. In the current review article, polymers for controlled release have been divided into four major categories: diffusion-controlled systems; chemically controlled systems; solvent-activated systems; and magnetically controlled systems. Polymers as drug carriers also have been divided into various subgroups: soluble, biodegradable, mucoadhesive and other polymeric systems. The latter group includes polymers containing pendant bioactive substituents, matrix systems, heparin-releasing polymers, ionic polymers, oligomers and miscellaneous. At an introductory and fundamental level, an overview of these polymers and the materials science for the design of drug delivery systems will be discussed.
Epigallocatechin Gallate Suppresses Lung Cancer Cell Growth through Ras–GTPase-Activating Protein SH3 Domain-Binding Protein 1 (2010)

Green tea is a highly popular beverage globally. Green tea contains a number of polyphenol compounds referred to as catechins, and (-)-epigallocatechin gallate (EGCG) is believed to be the major biologically active compound found in green tea. EGCG has been reported to suppress lung cancer, but the molecular mechanisms of the inhibitory effects of EGCG are not clear. We found that EGCG interacted with the Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) with high binding affinity (K(d) = 0.4 micromol/L). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells, which express much lower levels of G3BP1. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1 H1299 cells were resistant to the inhibitory effects of EGCG on growth and colony formation compared with shMock-transfected H1299 cells. EGCG interfered with the interaction of G3BP1 and the Ras-GTPase-activating protein and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1 downstream signaling, including extracellular signal-regulated kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, in wild-type H1299 and shMock H1299 cells but had little effect on H460 or shG3BP1 H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1.
cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins (1990)

From neurohaemal lobes of corpora cardiaca of Locusta migratoria a 5-kDa peptide has been isolated and its sequence established [see the accompanying paper, by Hietter et al. (1990) Eur. J. Biochem. 187, 241-247]. We have designed oligonucleotide probes from the peptide sequence of this molecule and screened a library prepared from mRNA of the neurosecretory cell region of the brain of this insect. Several positive cDNAs were isolated, the combined nucleotide sequences of which predict a large precursor of 145 residues (15770 Da) containing the newly isolated 5-kDa peptide. The peptide is flanked by regions homologous to the A and B chains of the superfamily of insulins. The overall organization of the precursor is as follows: signal peptide/domain homologous to the B chain of insulins/C (connecting)-peptide (corresponding to the newly isolated 5-kDa peptide)/domain homologous to the A chain of insulins. The numbers and relative positions of the cysteines of the Locusta peptide are equivalent to those of the other members of the insulin superfamily and most of the hydrophobic core residues are conserved.
Strain Dependent Differences in a Histological Study of CD44 and Collagen Fibers with an Expression Analysis of Inflammatory Response-related Genes in Irradiated Murine Lung (2004)

Using a mouse model, we investigated the mechanisms of heterogeneity in response to ionizing radiation in this research. C57BL/6J and C3H/HeMs mice were irradiated with gamma rays at 10 and 20 Gy. The animals were sacrificed at times corresponding to the latent period, the pneumonic phase, and the start of the fibrotic phase for histological investigation. Small areas of fibrosis initially appeared in C57BL/6J mice at 4 weeks postirradiation with 20 Gy, whereas small inflammatory lesions appeared at 4 and 8 weeks after 20 and 10 Gy, respectively. The alveoli septa were thickened by an infiltration of inflammatory cells, and alveoli were obliterated in lungs from C57BL/6J mice after 20 Gy irradiation. At 24 hours and from 2 to 4 weeks postirradiation, fourfold more CD44 positive cells had accumulated in the lungs of C3H/HeMs than in C57BL/6J mice. Hyaluronan accumulated 12 hours after irradiation, and the rapid resolution was achieved within 2 weeks in the lungs in both strains of mice. C57BL/6J mice lungs accumulated dense collagen at 8 weeks. Quantitative RT-PCR assay was performed for several genes selected by cDNA microarray analysis. The expression of several genes, such as Cap1, Il18, Mmp12, Per3, Ltf, Ifi202a, and Rad51ap1 showed strain-dependent variances. In conclusion, a histological investigation suggested that C3H/HeMs mice were able to induce a more rapid clearance of matrix after irradiation than C57BL/6J mice. The expression analysis showed that the several genes are potentially involved in interstrain differences in inflammatory response causing radiation-induced lung fibrosis.
Antibody-Based HIV-1 Vaccines: Recent Developments and Future Directions (2007)

The Policy Forum allows health policy makers around
Olanzapine Treatment of Residual Positive and Negative Symptoms (2004)

Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.
Textural Features for Image Classification (1973)

Texture is one of the important characteristics used in identifying objects or regions of interest in an image, whether the image be a photomicrograph, an aerial photograph, or a satellite image. This paper describes some easily computable textural features based on gray-tone spatial dependancies, and illustrates their application in category-identification tasks of three different kinds of image data: photomicrographs of five kinds of sandstones, 1:20 000 panchromatic aerial photographs of eight land-use categories, and Earth Resources Technology Satellite (ERTS) multispecial imagery containing seven land-use categories. We use two kinds of decision rules: one for which the decision regions are convex polyhedra (a piecewise linear decision rule), and one for which the decision regions are rectangular parallelpipeds (a min-max decision rule). In each experiment the data set was divided into two parts, a training set and a test set. Test set identification accuracy is 89 percent for the photomicrographs, 82 percent for the aerial photographic imagery, and 83 percent for the satellite imagery. These results indicate that the easily computable textural features probably have a general applicability for a wide variety of image-classification applications.
Exchange coupling between ferromagnetic and antiferromagnetic layers via Ru and application for a linear magnetic field sensor (2006)

Exchange coupling is observed in a trilayer structure of ferromagnet-Ru-antiferromagnet and the coupling strength is found to be a function of the thickness of the Ru spacer layer. This is the first observation for such a trilayer structure and may help to shed light on the illusive mechanism of exchange coupling in these systems. This unique coupling is used to bias the sense layer in a magnetic tunnel junction structure so that the magnetization orientations of the sense layer and the pinned layer can be independently controlled. Sensor devices are fabricated with a bipolar output, a medium sensitivity, and a wide field range. The results show that this biasing scheme is well suited for magnetic tunnel junctions used in magnetic field sensors.
Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB‐1893 and MPEP (2003)

We have identified 2-methyl-6-(2-phenylethenyl)pyridine (SIB-1893) and 2-methyl-6-phenylethynyl pyridine hydrochloride (MPEP) as positive allosteric modulators for the hmGluR4. SIB-1893 and MPEP enhanced the potency and efficacy of L-2-amino-4-phophonobutyrate (L-AP4) in guanosine 5'-O-(3-[(35)S]thiotriphosphate ([(35)S]GTPgammaS) binding and efficacy in cAMP studies. These effects were fully blocked by the mGluR4 competitive antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG), indicating a dependency on receptor activation. Although SIB-1893 and MPEP had no effects alone in GTPgammaS binding, effects were observed in the cell-based cAMP assay due to media-derived activation as indicated by CPPG inhibition. Positive modulation of the mGluR4 was a receptor-specific effect since SIB-1893 and MPEP had neither effects on mGluR2-expressing cells nor on the parent BHK cell line. In [(3)H]L-AP4 binding, a two-fold decrease in K(D) but not in B(max) was observed with 100 micro M SIB-1893, whereas MPEP affected neither parameter. Finally, SIB-1893 and MPEP failed to displace [(3)H]L-AP4 binding. Taken together, these data identify positive allosteric modulators for the hmGluR4.
Graphene Based Electrochemical Sensors and Biosensors: A Review (2010)

Abstract Graphene, emerging as a true 2‐dimensional material, has received increasing attention due to its unique physicochemical properties (high surface area, excellent conductivity, high mechanical strength, and ease of functionalization and mass production). This article selectively reviews recent advances in graphene‐based electrochemical sensors and biosensors. In particular, graphene for direct electrochemistry of enzyme, its electrocatalytic activity toward small biomolecules (hydrogen peroxide, NADH, dopamine, etc.), and graphene‐based enzyme biosensors have been summarized in more detail; Graphene‐based DNA sensing and environmental analysis have been discussed. Future perspectives in this rapidly developing field are also discussed.
Unmanned Aerial Vehicles for High-Throughput Phenotyping and Agronomic Research (2016)

Advances in automation and data science have led agriculturists to seek real-time, high-quality, high-volume crop data to accelerate crop improvement through breeding and to optimize agronomic practices. Breeders have recently gained massive data-collection capability in genome sequencing of plants. Faster phenotypic trait data collection and analysis relative to genetic data leads to faster and better selections in crop improvement. Furthermore, faster and higher-resolution crop data collection leads to greater capability for scientists and growers to improve precision-agriculture practices on increasingly larger farms; e.g., site-specific application of water and nutrients. Unmanned aerial vehicles (UAVs) have recently gained traction as agricultural data collection systems. Using UAVs for agricultural remote sensing is an innovative technology that differs from traditional remote sensing in more ways than strictly higher-resolution images; it provides many new and unique possibilities, as well as new and unique challenges. Herein we report on processes and lessons learned from year 1-the summer 2015 and winter 2016 growing seasons-of a large multidisciplinary project evaluating UAV images across a range of breeding and agronomic research trials on a large research farm. Included are team and project planning, UAV and sensor selection and integration, and data collection and analysis workflow. The study involved many crops and both breeding plots and agronomic fields. The project's goal was to develop methods for UAVs to collect high-quality, high-volume crop data with fast turnaround time to field scientists. The project included five teams: Administration, Flight Operations, Sensors, Data Management, and Field Research. Four case studies involving multiple crops in breeding and agronomic applications add practical descriptive detail. Lessons learned include critical information on sensors, air vehicles, and configuration parameters for both. As the first and most comprehensive project of its kind to date, these lessons are particularly salient to researchers embarking on agricultural research with UAVs.
Improving the efficiency of genomic loci capture using oligonucleotide arrays for high throughput resequencing (2009)

The complete protocol introduced in this paper enables researchers to perform practical capture experiments, and includes two novel methods for increasing the targeting efficiency. Coupled with the new massively parallel sequencing technologies, this provides a powerful approach to identifying disease-causing genetic variants that can be localized within the genome by traditional methods.
Range of Motion in Total Knee Arthroplasty (1991)

A three-dimensional computer model of the knee was formulated based on sectional and coordinate data from knee specimens. The model was consistent with published data in terms of contact points and ligament length patterns. Prosthetic components were designed, and surgical placement was simulated. Maximum flexion was limited by tension in the posterior cruciate ligament. Increased dishing of the tibial surface reduced flexion, but some dishing was considered necessary for reduction of contact stresses. Anteroposterior translation of the tibial component had little effect on flexion. Femoral translation had some offset, and posterior positioning reduced flexion. The most important surgical variable was tibial component tilt in the sagittal plane. Posterior tilt increased motion, while anterior tilt decreased motion. The results apply to the choice of total knee system, instrument design, and surgical technique.
45세 이하의 유방암환자에서 조직미세배열법을 이용한 면역조직화학적 생체표지자의 역할 (2008)

목 적: 45세 이하의 유방암 환자의 종양조직의 파라핀 블록을 조직미세배열법(Tissue Microarray, TMA)으로 만들어
에스트로겐 수용체(ER), 프로게스테론 수용체(PR), HER-2, COX-2 및 Survivin 등 5가지의 생체표지자의 발현상태
와 상호관계, 환자의 치료 후 추적관찰 상태와 관련성을 분석하여 예후인자로서의 의의를...
Optimization study on periodic counter-current chromatography integrated in a monoclonal antibody downstream process (2020)

An optimization study of an integrated periodic counter-current chromatography (PCC) process in a monoclonal antibody (mAb) downstream process at lab scale, is presented in this paper. The optimization was based on a mechanistic model of the breakthrough curve in the protein-A capture step. Productivity and resin utilization were the objective functions, while yield during the loading of the capture column was set as a constraint. Different integration approaches were considered, and the effect of the feed concentration, yield and the protein-A resin was studied. The breakthrough curve and the length of the product recovery, which depended on the integration approach, determined the process scheduling. Several optimal Pareto solutions were obtained. At 0.5 mg mL−1 and 99% yield, a maximum productivity of 0.38 mg mL−1 min−1 with a resin utilization of 60% was obtained. On the other hand, the maximum resin utilization was 95% with a productivity of 0.10 mg mL−1 min−1. Due to the constraint of the process scheduling, a lower productivity could be achieved in the integration approaches with higher recovery time, which was more remarkable at higher concentrations. Therefore, it was shown that a holistic approach, where all the purification steps are considered in the process optimization, is needed to design a PCC in a downstream process.
Passive Local Immunotherapy of Experimental Staphylococcal Pneumonia with Human Intravenous Immunoglobulin (1993)

Staphylococcus aureus remains a life-threatening agent of nosocomial pneumonia in immunocompromised patients. The increasing incidence of strains exhibiting wide-spectrum resistance to antibiotics, such as methicillin-resistant S. aureus (MRSA), requires new therapeutic strategies. There is renewed interest in passive immunization with human plasma-derived immunoglobulins (IVIG) as antiinfective agents. The efficacy of IVIG was tested in an experimental model of staphylococcal pneumonia, using both an MRSA clinical isolate and reference strain Cowan III, in mice immunosuppressed with cyclophosphamide. Efficient antistaphylococcal activities were obtained with IVIG administered intravenously or intranasally. IVIG saturated with protein A or its F(ab')2 fragments were as efficient as intact IVIG, suggesting that protection did not require opsonization through IgG Fc-phagocyte Fc gamma-receptor interactions. Thus, topical administration of IVIG may replace a local antibody response to S. aureus in an immunocompromised host and may be useful in prophylaxis and treatment of nosocomial S. aureus pneumonia.
Enteric pathogens associated with gastrointestinal dysfunction in children with HIV infection (1996)

Infants and young children with HIV infection commonly suffer from gastrointestinal manifestations of their disease. Many HIV infected children have evidence of persistent diarrhoea, malabsorption, malnutrition or growth failure. The aetiology and pathogenesis of gastrointestinal dysfunction in HIV infected children have not been well defined. We performed immunocytochemical analyses on intestinal tissue from 19 HIV-infected children with gastrointestinal dysfunction or growth failure. None of these 19 children had microbial pathogens identified in faecal samples using standard microbiological methods. Intestinal tissues were obtained from the children by biopsy and were examined for antigens from Pneumocystis carinii, cytomegalovirus (CMV) and herpes simplex virus (HSV) using the avidin-biotin-complex immunohistochemical technique and monoclonal or monospecific antibodies. We detected at least one of these pathogens in samples from eight (42%) of 19 HIV infected children. P. carinii was the most prevalent pathogen, found in five of the eight HIV infected children. All of the children with intestinal pneumocystis infection were receiving prophylaxis directed at the prevention of pulmonary disease with this organism and none of them were undergoing active pulmonary infection. We also identified CMV antigens in intestinal tissues from four children and HSV antigens in intestinal tissues from one child. Two children were infected with more than one pathogen. On the other hand, none of these pathogens were found in the tissues obtained from 10 HIV-uninfected patients who had intestinal tissues obtained for chronic non-infectious diarrheal and inflammatory diseases (P < 0.01, Fisher's exact test). Our findings indicate that some children with HIV infection and gastrointestinal dysfunction may be infected with opportunistic pathogens despite negative analyses employing standard microbiological methods. Our study also indicates that HIV infected children can undergo intestinal infection with P. carinii despite the administration of standard immunoprophylactic regimens directed at the prevention of infection with this organism.
Lipid nanoparticle siRNA systems for silencing the androgen receptor in human prostate cancer in vivo (2011)

The androgen receptor (AR) plays a critical role in the progression of prostate cancer. Silencing this protein using short-hairpin RNA (shRNA) has been correlated with tumor growth inhibition and decreases in serum prostate specific antigen (PSA). In our study, we have investigated the ability of lipid nanoparticle (LNP) formulations of small-interfering RNA (siRNA) to silence AR in human prostate tumor cell lines in vitro and in LNCaP xenograft tumors following intravenous (i.v.) injection. In vitro screening studies using a panel of cationic lipids showed that LNPs containing the ionizable cationic lipid 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA) exhibited the most potent AR silencing effects in LNCaP cells. This is attributed to an optimized ability of DLin-KC2-DMA-containing LNP to be taken up into cells and to release the siRNA into the cell cytoplasm following endocytotic uptake. DLin-KC2-DMA LNPs were also effective in silencing the AR in a wild-type AR expressing cell line, LAPC-4, and a variant AR expressing cell line, CWR22Rv1. Importantly, it is demonstrated that LNP AR-siRNA systems containing DLin-KC2-DMA can silence AR gene expression in distal LNCaP xenograft tumors and decrease serum PSA levels following i.v. injection. To our knowledge, this is the first report demonstrating the feasibility of LNP delivery of siRNA for silencing AR gene expression in vivo.
Optical Recognition of Converted DNA Nucleotides for Single-Molecule DNA Sequencing Using Nanopore Arrays (2010)

We demonstrate the feasibility of a nanopore based single-molecule DNA sequencing method, which employs multicolor readout. Target DNA is converted according to a binary code, which is recognized by molecular beacons with two types of fluorophores. Solid-state nanopores are then used to sequentially strip off the beacons, leading to a series of detectable photon bursts, at high speed. We show that signals from multiple nanopores can be detected simultaneously, allowing straightforward parallelization to large nanopore arrays.