gebhart/patrepeval huggingface dataset:
Production of Nanobodies against Prostate-Specific Membrane Antigen (PSMA) Recognizing LnCaP Cells (2014)

Prostate cancer is the most common type of cancer in men. The antibody-mediated therapy for cancer treatment depends on the identification of selected molecular targets. The prostate-specific membrane antigen (PSMA) is a potential molecular target in prostate cancer and is abundantly expressed in this type of cancer. This study is aimed at designing and producing a recombinant PSMA epitope and a monoclonal nanobody with a high affinity toward the PSMA protein. A DNA fragment encoding the dominant epitopes of PSMA was designed, synthesized, and expressed in E. coli BL21 (DE3). A camel was immunized with the purified recombinant PSMA (rPSMA). Following mRNA isolation and cDNA synthesis, the variable fragment of heavy-chain antibodies (VHH) fragments were cloned and displayed on the surface of an M13 phage and used in sequential panning rounds. After phage ELISA and selection of colonies with the highest affinity, soluble nanobodies were produced and evaluated. Affinity of the nanobodies to rPSMA was estimated to be 3.5 × 10-7. Adherence of the purified anti-PSMA VHH was tested in cell-ELISA in the LnCaP and PC3 cell lines. VHH efficiently bound to LnCaP cells. The high specificity and affinity of this nanobody suggests its possible application as an effective tool in the diagnosis and treatment of prostate cancer.
Use of Ethoxy-Homologs as Internal Standards for Determination of Urinary Vanillylmandelic Acid and Normetanephrine in Man by High Performance Liquid Chromatography (1986)

Abstract Synthesis of the ethoxy-homologs of vanillylmandelic acid (3-ethoxy-4-hydroxymandelic acid, EMA) and normetanephrine (3-ethoxy-4-hydroxyphenylethanolamine, EHPEA) and their use in minor modifications of existing assays on human urine are described. For analysis of vanillylmandelic acid, the homologous internal standard is added to an aliquot of urine, organic acids are then extracted into ethyl acetate and back extracted into 10% K2CO3, and finally extracted a second time into ethyl acetate. After evaporation of the ethyl acetate, the residue is redissolved in the mobile phase to be used in the chromatography, and injected onto a reverse phase column. Comparison of results with a gas chromatography-mass spectrometry (GCMS) assay gave almost identical results (96% ± 2%, mean ± SE, n=10). Analysis of normetanephrine is performed by addition of internal standard to an aliquot of urine before heat hydrolysis of amine conjugates. The amines are adsorbed onto columns of Bio Rex 70, and then eluted with a solution of 1 M NH4OH, which is then evaporated to dryness. After residue is redissolved in borate buffer, the amines are extracted into toluene:isoamyl alcohol and back extracted into 0.1 M acetic acid before injection onto a reverse phase column. Correlation with a GCMS assay gave similar results (102% ± 4%, mean ± SE, n=9).
Microrobotic tentacles with spiral bending capability based on shape-engineered elastomeric microtubes (2015)

Microscale soft-robots hold great promise as safe handlers of delicate micro-objects but their wider adoption requires micro-actuators with greater efficiency and ease-of-fabrication. Here we present an elastomeric microtube-based pneumatic actuator that can be extended into a microrobotic tentacle. We establish a new, direct peeling-based technique for building long and thin, highly deformable microtubes and a semi-analytical model for their shape-engineering. Using them in combination, we amplify the microtube's pneumatically-driven bending into multi-turn inward spiraling. The resulting micro-tentacle exhibit spiraling with the final radius as small as ~185 μm and grabbing force of ~0.78 mN, rendering itself ideal for non-damaging manipulation of soft, fragile micro-objects. This spiraling tentacle-based grabbing modality, the direct peeling-enabled elastomeric microtube fabrication technique, and the concept of microtube shape-engineering are all unprecedented and will enrich the field of soft-robotics.
Relationship between distance running mechanics, running economy, and performance (1987)

The relationships between biocmechanical aspects of distance running, running economy (VO2 submax), and performance were investigated. A variety of biomechanical measures for 31 subjects running at 3.6 m/s was obtained, including three-dimensional angular and translational kinematics, ground reaction forces and center of pressure patterns, mechanical power, and anthropometric measures. Physiological measures obtained included maximal and submaximal O2 consumption, muscle fiber composition, and measures of the ability to store and return elastic energy during knee bends. A subset of 16 runners was also evaluated in relation to performance in a 10-km run. Biomechanical variables were identified which showed significant differences or consistent trends between groups separated on the basis of VO2 submax, establishing the importance of biomechanical influences on running economy. It appears that no single variable or small subset of variables can explain differences in economy between individuals but rather that economy is related to a weighted sum of the influences of many variables.
Performance analysis of CDMA transmit diversity methods (2003)

The link performance of transmit diversity (TD) schemes for third generation CDMA systems is analyzed. Orthogonal transmit diversity (OTD) and space-time transmit diversity (STTD) are compared. It is shown that the link performances of OTD and STTD are nearly the same. However, STTD requires additional receiver processing, and STTD is not directly extendable to more than 2 antennas, because rate one space-time block codes do not exist for greater than 2 antennas. Also, an interleaving approach is shown that works for various TD schemes as well as non-TD.
IL-22 Is Required for Imiquimod-Induced Psoriasiform Skin Inflammation in Mice (2011)

Psoriasis is a common chronic autoimmune skin disease of unknown cause that involves dysregulated interplay between immune cells and keratinocytes. IL-22 is a cytokine produced by the TH1, TH17, and TH22 subsets that are functionally implicated in the psoriatic pathology. We assessed the role of IL-22 in a mouse model where psoriasiform skin inflammation is triggered by topical application of the TLR7/8 agonist imiquimod. At the macroscopic level, scaly skin lesions induced by daily applications of imiquimod in wild-type mice were almost totally absent in IL-22-deficient mice or in mice treated with a blocking anti-IL-22 Ab. At the microscopic level, IL-22-deficient mice showed a dramatic decrease in the development of pustules and a partial decrease in acanthosis. At the molecular level, the absence or inhibition of IL-22 strongly decreased the expression of chemotactic factors such as CCL3 and CXCL3 and of biomarkers such as S100A8, S100A7, and keratin 14, which reflect the antimicrobial and hyperproliferative responses of keratinocytes. IL-22 also played a major role in neutrophil infiltration after imiquimod treatment. IL-23 was required for IL-22 production, and γδ TCR lymphocytes represented the major source of IL-22 in lymph nodes from imiquimod-treated mice. However, T cells were not absolutely required for IL-22 production because imiquimod-induced IL-22 expression in the skin is still preserved in Rag2(-/-) mice. Taken together, our data show that IL-22 is required for psoriasis-like lesions in the mouse imiquimod model and is produced by both T cells and innate immune cells.
Analysis of Human Peripheral Blood Samples from Fatal and Nonfatal Cases of Ebola (Sudan) Hemorrhagic Fever: Cellular Responses, Virus Load, and Nitric Oxide Levels (2004)

Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. Blood smears revealed thrombocytopenia, a left shift in neutrophils (in some cases degenerating), and atypical lymphocytes. Infected patients who died had reduced numbers of T cells, CD8(+) T cells, and activated (HLA-DR(+)) CD8(+) T cells, while the opposite was noted for patients who survived the disease. Expression levels of cytokines, Fas antigen, and Fas ligand (TaqMan quantitation) in PBMC from infected patients were not significantly different from those in uninfected patients (treated in the same isolation wards), nor was there a significant increase in expression compared to healthy volunteers (United States). This unresponsive state of PBMC from infected patients despite high levels of circulating antigen and virus replication suggests that some form of immunosuppression had developed. Ebola virus RNA levels (virus load) in PBMC specimens were found to be much higher in infected patients who died than patients who survived the disease. Similarly, blood levels of nitric oxide were much higher in fatal cases (increasing with disease severity), and extremely elevated levels (>/=150 microM) would have negatively affected vascular tone and contributed to virus-induced shock.
Directed Evolution of 2-Keto-3-deoxy-6-phosphogalactonate Aldolase To Replace 3-Deoxy-d-arabino-heptulosonic Acid 7-Phosphate Synthase (2007)

Directed evolution of 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolase for microbial synthesis of shikimate pathway products provides an alternate strategy to circumvent the competition for phosphoenolpyruvate between 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) synthase and the phosphoenolpyruvate:carbohydrate phosphotransferase system in Escherichia coli. E. coli KDPGal aldolase was evolved using a combination of error-prone polymerase chain reaction, DNA shuffling, and multiple-site-directed mutagenesis to afford KDPGal aldolase variant NR8.276-2, which exhibits a 60-fold improvement in the ratio kcat/KM relative to that of wild-type E. coli KDPGal aldolase in catalyzing the addition of pyruvate to d-erythrose 4-phosphate to form DAHP. On the basis of its nucleotide sequence, NR8.276-2 contains seven amino acid changes from the wild-type E. coli KDPGal aldolase. Amplified expression of NR8.276-2 in the DAHP synthase and shikimate dehydrogenase-deficient E. coli strain NR7 under fed-batch fermentor-controlled cultivation conditions resulted in synthesis of 13 g/L 3-dehydroshikimic acid in 6.5% molar yield from glucose. Increased coexpression of the irreversible downstream enzyme 3-dehydroquinate synthase increased production of 3-dehydroshikimic acid to 19 g/L in 9.7% molar yield from glucose. Coamplification with transketolase, which increases d-erythrose 4-phosphate availability, afforded 16 g/L 3-dehydroshikimic acid in 8.5% molar yield.
Analysis of MAP 4 function in living cells using green fluorescent protein (GFP) chimeras. (1995)

MAP 4 is a ubiquitous microtubule-associated protein thought to play a role in the polymerization and stability of microtubules in interphase and mitotic cells. We have analyzed the behavior of protein domains of MAP 4 in vivo using chimeras constructed from these polypeptides and the green fluorescent protein (GFP). GFP-MAP 4 localizes to microtubules; this is confirmed by colocalization of GFP-MAP 4 with microtubules that have incorporated microinjected rhodamine-tubulin, and by loss of localized fluorescence after treatment of cells with anti-microtubule agents. Different subdomains of MAP 4 have distinct effects on microtubule organization and dynamics. The entire basic domain of MAP 4 reorganizes microtubules into bundles and stabilizes these arrays against depolymerization with nocodazole. Within the basic domain, the PGGG repeats, which are conserved with MAP 2 and tau, have a weak affinity for microtubules and are dispensable for microtubule binding, whereas the MAP 4-unique PSP region can function independently in binding. The projection domain shows no microtubule localization, but does modulate the association of various binding subdomains with microtubules. The acidic carboxy terminus of MAP 4 strongly affects the microtubule binding characteristics of the other domains, despite constituting less than 6% of the protein. These data show that MAP 4 association with microtubules is modulated by sequences both within and outside the basic domain. Further, our work demonstrates that GFP chimeras will allow an in vivo analysis of the effects of MAPs and their variants on microtubule dynamics in real time.
NTera2: A Model System to Study Dopaminergic Differentiation of Human Embryonic Stem Cells (2005)

NTera2, a human embryonal carcinoma (EC) stem cell line, shares many characteristics with human embryonic stem cells (hESCs). To determine whether NTera2 can serve as a useful surrogate for hESCs, we compared global gene expression between undifferentiated NTera2, multiple undifferentiated hESC cell lines, and their differentiated derivatives, and we showed that NTera2 cells share multiple markers with hESCs. Similar to hESCs, NTera2 cells differentiated into TH-positive cells that express dopaminergic markers including AADC, DAT, Nurr1, TrkB, TrkC, and GFRA1 when co-cultured with PA6 cells. Flow cytometry analysis showed that tyrosine hydroxylase (TH) and neural cell adhesion molecule (NCAM) expression increased, whereas SSEA4 expression decreased as cells differentiated. Medium conditioned by PA6 cells stimulated differentiation of NTera2 cells to generate TH-positive cells that expressed dopaminergic markers. Flow cytometry selected polysialylated (PSA-NCAM) cells responded to medium conditioned by PA6 cells by differentiating into TH-positive cells and expressed dopaminergic markers. Sorted cells differentiated for 4 weeks in PA6 cell conditioned media included functional neurons that responded to neurotransmitters and exhibited electronic excitability. Therefore, NTera2 cell dopaminergic neuronal differentiation and PSA-NCAM enrichment provides a useful system for the future study of hESCs.
A Packet Loss Concealment Algorithm Robust to Burst Packet Loss for CELP-type Speech Coders (2008)

In this paper, a packet loss concealment (PLC) algorithm for CELP-type speech coders is proposed which improves the quality of decoded speech under burst packet loss conditions. The proposed PLC algorithm is based on the reconstruction of excitation by combining voiced excitation and random excitation, where the voice excitation is obtained from the adaptive codebook excitation scaled by a voicing probability and the random excitation is generated by permutating the previous decoded excitation. The voicing probability is estimated from the correlation using the decoded excitation and pitch of the previous frames. In addition, a linear regression-based gain amplitude is estimated and applied to the reconstructed excitation for the compensatation of the undesirable amplitude change under a burst packet loss condition. The proposed algorithm is implemented as a PLC algorithm for G.729 and its performance is compared with PLC employed in G.729 by means of perceptual evaluation of speech quality (PESQ), a waveform comparison, and an A-B preference test under random and burst packet loss rates of 3% and 5%. It is shown that the proposed algorithm provides significanlty better speech quality than the PLC of G.729, especially under burst packet losses.
Entanglement Partitioning of Quantum Particles for Data Clustering (2006)

This paper presents a generalized quantum particle model to greatly quicken and improve data clustering. The proposed model uses the random dynamics and quantum entanglement of quantum particles on a particle array. In comparison with classical nonquantum methods, the quantum particle model not only clusters much faster, but also has better clustering quality for multi-shape multi-distribution high-dimensional large-scale data sets with noise. The simulations and comparisons show the effectiveness of the quantum particle model
Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice (2016)

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjögren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjögren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjögren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjögren's syndrome.
Decomposition Kinetics of Ozone in Aqueous Solution (1996)

The influence of pH value, UV intensity, and anion species on the decomposition of ozone in aqueous solution was studied for the batch and semibatch systems. The results indicate that the decomposition efficiency of ozone increased with increasing pH value and UV intensity. The two-film theory was adopted to describe the different self-decomposition behaviors of ozone for the batch and semibatch systems. The extent of the chain reaction between ozone molecule and hydroxyl radical in the semibatch systems was found to be much higher than that in the batch systems on the basis of the mass balance calculation. The decomposition of ozone for the semibatch systems was postulated to occur mainly in the film region by the free radical chain reaction. With ultraviolet irradiation, the decomposition rate of dissolved ozone was found to be not significantly affected by solution pH. The overall decomposition rate equation of ozone with UV light irradiation in the range of solution pH 2−10 was established.
Transformation of Arabidopsis thaliana with Agrobacterium tumefaciens (1986)

Transformed Arabidopsis thaliana plants have been produced by a modified leaf disk transformation-regeneration method. Leaf pieces from sterilely grown plants were precultured for 2 days and inoculated with an Agrobacterium tumefaciens strain containing an avirulent Ti (tumor-inducing) plasmid with a chimeric gene encoding hygromycin resistance. After cocultivation for 2 days, the leaf pieces were placed on a medium that selects for hygromycin resistance. Shoots regenerated within 3 months and were excised, rooted, and transferred to soil. Transformation was confirmed by opine production, hygromycin resistance, and DNA blot hybridization of both primary transformants and progeny. This process for producing transgenic Arabidopsis plants should enhance the usefulness of the species for experimental biology.
The Electroencephalogram in Sepsis-Associated Encephalopathy (1992)

To define the EEG and associated clinical features of septic encephalopathy, we studied 62 patients with positive blood cultures. Patients were divided into three clinical groups: nonencephalopathic (NE), mildly encephalopathic (ME), and severely encephalopathic (SE); the latter two groups had diffuse cerebral dysfunction. EEGs were classified into five groups: normal, excessive theta, predominant delta, triphasic waves, and suppression or burst suppression, in ascending order of severity. The EEG (1) was more sensitive than our clinical criteria for encephalopathy, (2) showed features that were, when considered with clinical and laboratory characteristics, compatible with a potentially reversible encephalopathy, and (3) had well-defined categories that correlated with percent mortality, even within a single clinical group. We conclude that the EEG is a sensitive index of brain function in septic encephalopathy and that it is especially useful in the intensive care monitoring of patients with sepsis.
Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor. (1989)

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was investigated in 30 patients with advanced malignancy in a phase Ib trial. Patients were treated at four different dose levels (120 to 1,000 micrograms/m2/d) by either daily intravenous (IV) bolus injection or 24-hour continuous infusion. Administration of rh GM-CSF resulted in a broad spectrum of dose- and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total WBC count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets, and reticulocytes was not induced. Within five days after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always rapidly reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnea, and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules used and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase number and function of leukocytes in vivo may prevent neutropenia and infections when GM-CSF is added to cytotoxic cancer therapy.
Failure of a human immunodeficiency virus type 1 (HIV-1) subtype B-derived vaccine to prevent infection of chimpanzees by an HIV-1 subtype E strain (1996)

Generation of an effective vaccine against human immunodeficiency virus type 1 (HIV-1) must overcome problems associated with extensive genetic diversity. Although we previously reported vaccine-induced protection of chimpanzees against infection with an HIV-1 strain different from the one used to make the immunogens, both the HIV-1 vaccine and challenge strains were classified within subtype B. To determine whether the HIV-1-specific immunity elicited might also prevent infection by a strain of HIV-1 from a different clade, the same chimpanzees were given booster inoculations with the rgp160-MN/LAI (recombinant hybrid gp160 molecule) and V3-MN immunogens and then were challenged by intravenous inoculation of a comparable dose of a subtype E HIV-1 from the Central African Republic. Both animals became infected with the subtype E virus, indicating that intraclade vaccine-mediated protection does not predict interclade protection, at least in the context of intravenous challenge and the HIV-1 strains used. This study has important implications for planned phase III efficacy trials of similar vaccine preparations in Thailand where HIV-1 subtype B and E strains cocirculate.