gebhart/patrepeval huggingface dataset:
Essential Role of Complement Mannose-Binding Lectin-Associated Serine Proteases-1/3 in the Murine Collagen Antibody-Induced Model of Inflammatory Arthritis (2010)

Gene-targeted mice deficient in the complement mannose-binding lectin-associated serine protease-1 and -3 (MASP1/3(-/-)) express only the zymogen of factor D (pro-factor D [pro-Df]), a necessary component of the alternative pathway (AP). We used the murine collagen Ab-induced arthritis (CAIA) model, in which the AP is unique among complement pathways in being both necessary and sufficient for disease induction, to determine whether MASP-1/3 are required in vivo for the development of tissue injury. Disease activity scores, complement C3 tissue deposition in the joint, and histopathologic injury scores were markedly decreased in MASP1/3(-/-) as compared with wild-type (WT) mice. MASP-1 protein was immunochemically localized to synovial cells of knees of WT mice with arthritis. Pro-Df was present in both synovial cells and chondrocytes of knees of WT and MASP1/3(-/-) mice without arthritis, with increased amounts present in synovial cells of WT mice with CAIA. No conversion of pro-Df to mature Df was detectable in the serum of MASP1/3(-/-) mice during the evolution of CAIA. C3 activation and deposition as well as C5a generation induced in vitro by adherent anti-type II collagen mAbs were absent using sera from MASP1/3(-/-) mice under conditions in which only the AP was active. The addition of human Df fully reconstituted in vitro C3 activation and C5a generation using sera from MASP1/3(-/-) mice. Our studies demonstrate for the first time, to our knowledge, the absolute requirement for the activity of MASP-1 protein in autoimmune-associated inflammatory tissue injury in vivo through activation of the AP of complement by cleavage of pro-Df to mature Df.
SiGe-based semiconductor-on-insulator substrate created by low-energy separation-by-implanted-oxygen (1998)

SiGe-based semiconductor-on-insulator (SOI) substrates have been successfully created by the separation-by-implanted-oxygen technique. Low-energy oxygen ion implantation was performed at 25 kV on a strain-relieved Si0.82Ge0.18 virtual substrate grown on Si(001). A good SOI geometry with a 25-nm top SiGe layer was obtained over a dose window of 2–2.5×1017 cm−2, and a flat SiGe surface and sharp SiGe/SiO2 interfaces were achieved at a low substrate temperature of 550°C. Compositional analysis shows that the top SiGe layer nearly conserves the same composition as the underlying alloy substrate.
Automatic recovery of the optic nervehead geometry in optical coherence tomography (2006)

Optical coherence tomography (OCT) uses retroreflected light to provide micrometer-resolution, cross-sectional scans of biological tissues. OCT's first application was in ophthalmic imaging where it has proven particularly useful in diagnosing, monitoring, and studying glaucoma. Diagnosing glaucoma is difficult and it often goes undetected until significant damage to the subject's visual field has occurred. As glaucoma progresses, neural tissue dies, the nerve fiber layer thins, and the cup-to-disk ratio increases. Unfortunately, most current measurement techniques are subjective and inherently unreliable, making it difficult to monitor small changes in the nervehead geometry. To our knowledge, this paper presents the first published results on optic nervehead segmentation and geometric characterization from OCT data. We develop complete, autonomous algorithms based on a parabolic model of cup geometry and an extension of the Markov model introduced by Koozekanani, et al. to segment the retinal-nervehead surface, identify the choroid-nervehead boundary, and identify the extent of the optic cup. We present thorough experimental results from both normal and pathological eyes, and compare our results against those of an experienced, expert ophthalmologist, reporting a correlation coefficient for cup diameter above 0.8 and above 0.9 for the disk diameter.
Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity. (1989)

alpha-Particles such as those emitted by 211At may be advantageous for radioimmunotherapy since they are radiation of high linear energy transfer, depositing high energy over a short distance. Here we describe a strategy for labeling monoclonal antibodies and F(ab')2 fragments with 211At by means of the bifunctional reagent N-succinimidyl 3-(trimethylstannyl)benzoate. An intact antibody, 81C6, and the F(ab')2 fragment of Me1-14 (both reactive with human gliomas) were labeled with 211At in high yield and with a specific activity of up to 4 mCi/mg in a time frame compatible with the 7.2-hr half-life of 211At. Quantitative in vivo binding assays demonstrated that radioastatination was accomplished with maintenance of high specific binding and affinity. Comparison of the biodistribution of 211At-labeled Me1-14 F(ab')2 to that of a nonspecific antibody fragment labeled with 211At and 131I in athymic mice bearing D-54 MG human glioma xenografts demonstrated selective and specific targeting of 211At-labeled antibody in this human tumor model.
The isocitrate dehydrogenase gene of oleaginous yeast Lipomyces starkeyi is linked to lipid accumulation (2009)

The oleaginous yeast Lipomyces starkeyi can accumulate intracellular lipids to over 60% of its cell dry mass under a nitrogen-limited condition. We showed that extracellular and intracellular citrate concentrations of L. starkeyi AS 2.1560 increased and the nicotinamide adenine dinucleotide - isocitrate dehydrogenase (NAD+-IDH) activity decreased at the beginning of the lipid accumulation, suggesting that the attenuation of the NAD+-IDH activity might initiate lipid storage. We next cloned the IDH gene by the methods of degenerate PCR and rapid amplification of cDNA ends. Phylogenetic analyses of the evolutionary relationships among LsIDH1, LsIDH2, and other yeast NAD+-IDHs revealed that the L. starkeyi IDH had a closer relationship with the IDHs of Yarrowia lipolytica. Further real-time PCR analysis showed that the expression levels of both LsIDH1 and LsIDH2 decreased concurrently with the evolution of cellular lipids. Our data should be valuable for understanding the biology of oleaginous yeasts and for further strain engineering of L. starkeyi.
Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. (2000)

Many lines of evidence suggest that the retinoblastoma protein interacting zinc finger gene RIZ is a strong candidate for the tumor suppressor locus on 1p36, a region commonly deleted in many human cancers with chromosomal instability. In addition, a role for RIZ in tumors of the microsatellite instability pathway is suggested by frequent frameshift mutations in hereditary non-polyposis colorectal carcinomas. Here we studied RIZ mutations in sporadic cancers with microsatellite instability. Frameshift mutations in the two coding polyadenosine tracks of RIZ were found in 19 (48%) of 40 gastric carcinomas, 6 (33%) of 18 endometrial carcinomas, 14 (26%) of 51 of colorectal carcinomas, and 7 (54%) of 13 cell lines. Eleven tumor tissues showed biallelic inactivation of RIZ. In contrast, no frameshift mutations were found in 70 microsatellite stable tumors. These results suggest an important role for RIZ in sporadic cancers with microsatellite instability.
Contributions of the Complementarity Determining Regions to the Thermal Stability of a Single-Domain Antibody (2013)

Single domain antibodies (sdAbs) are the recombinantly-expressed variable domain from camelid (or shark) heavy chain only antibodies and provide rugged recognition elements. Many sdAbs possess excellent affinity and specificity; most refold and are able to bind antigen after thermal denaturation. The sdAb A3, specific for the toxin Staphylococcal enterotoxin B (SEB), shows both sub-nanomolar affinity for its cognate antigen (0.14 nM) and an unusually high melting point of 85°C. Understanding the source of sdAb A3's high melting temperature could provide a route for engineering improved melting temperatures into other sdAbs. The goal of this work was to determine how much of sdAb A3's stability is derived from its complementarity determining regions (CDRs) versus its framework. Towards answering this question we constructed a series of CDR swap mutants in which the CDRs from unrelated sdAbs were integrated into A3's framework and where A3's CDRs were integrated into the framework of the other sdAbs. All three CDRs from A3 were moved to the frameworks of sdAb D1 (a ricin binder that melts at 50°C) and the anti-ricin sdAb C8 (melting point of 60°C). Similarly, the CDRs from sdAb D1 and sdAb C8 were moved to the sdAb A3 framework. In addition individual CDRs of sdAb A3 and sdAb D1 were swapped. Melting temperature and binding ability were assessed for each of the CDR-exchange mutants. This work showed that CDR2 plays a critical role in sdAb A3's binding and stability. Overall, results from the CDR swaps indicate CDR interactions play a major role in the protein stability.
Computational Playability of Backward Induction Solutions (1997)

This paper considers the computational playability of backward induction solutions, $i.e$ .whether or not there is an algorithm to play them.We construct a two-person two-stage game with perfect information, in which both players have countably many feasible actions and their payoff functions are computable.We prove that the backward induction solutions of the game, which are proved to exist, are not computably playable because it is impossible to supply the players with algorithms regarding how they should play the solutions.Moreover, we show that if players' payoff functions are polynomial with rational coefficients, then the backward induction solutions are computably playable.
Optimal elimination of leukemic T cells from human bone marrow with T101-ricin A-chain immunotoxin (1985)

In view of bone marrow purging before autologous transplantation in T cell malignancies, an anti-human T cell immunotoxin (IT) has been prepared by coupling ricin A-chain to the monoclonal antibody T101 that binds the T1 differentiation antigen expressed by T lymphocytes as well as by T cell-derived hematologic malignancies. Using a sensitive and reliable clonogenic assay, optimal conditions were defined for the elimination of clonogenic human T leukemic cells among bone marrow cells. Maximal cytoreduction was obtained with IT at a dose of 2 micrograms/mL in the presence of 10 mmol/L NH4Cl. This treatment led to the reduction of more than six orders of magnitude of T101-positive clonogenic leukemic cells, with no harm to T101-negative cells. Moreover, we observed no toxicity of IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow of healthy volunteers. Thus, pretreatment of bone marrow samples with IT plus NH4Cl offers a safe, simple, reliable, and highly efficient means to eliminate undesirable leukemic T cells from the graft.
ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy (2020)

ALKS 4230 exhibited enhanced pharmacokinetic and selective pharmacodynamic properties resulting in both improved antitumor efficacy and lower indices of toxicity relative to rhIL-2 in mice. These data highlight the potential of ALKS 4230 as a novel cancer immunotherapy, and as such, the molecule is being evaluated clinically.
A thiol protease inhibitor released from cultured human malignant melanoma cells. (1984)

A thiol protease inhibitor (TPI) was found in culture media of human malignant melanoma cells (Bowes) at 1.5 to 2.3 units/day/flask (full sheet, 75 sq cm). This amount well exceeded that for cultured nonmalignant cells (human fetal lung fibroblasts). In the intracellular region of the melanoma cells, TPI activity was localized mainly in the cytosol fraction. The difference in specific activities between the intracellular and extracellular TPI and the TPI accumulation in the culture media indicated that cultured melanoma cells release TPI. Partial purification and characterization of the TPI by column chromatography using Sephadex G-150, papain-Sepharose, and Sephadex G-50, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed two distinct TPIs with molecular weights of 56,000 and 9,800 to 10,800. The latter (main) TPI had a high specificity for thiol proteases and was heat stable (60 degrees for 60 min), like previously reported normal human TPIs. The inhibitor, however, differed from normal human TPIs in that it had a lower molecular weight than any normal TPI, was unable to inhibit bromelain, and exhibited a mosaic pattern; namely, the low-molecular-weight TPI resembled liver-type TPI but the pH stability curve resembled serum-type TPI. The thiol protease, cathepsin B, was not detected in culture media of this human melanoma cell line.
CD14+CD34+ Peripheral Blood Mononuclear Cells Migrate Across Endothelium and Give Rise to Immunostimulatory Dendritic Cells (1998)

We describe a subset of peripheral CD14+ cells, coexpressing the CD34 progenitor marker and able to migrate across endothelial cell monolayers. On culture with granulocyte-macrophage-CSF, this population differentiated into dendritic cells expressing CD83, CD80, HLA-DR(bright), CD86, and CD54. These dendritic cells were immunostimulatory, in that they induced proliferation of allogenic and tetanus toxoid-specific T lymphocytes. The CD14+ CD34+ population expressed higher levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and alpha4beta1 integrin than the CD14+ CD34- counterpart, being dull positive for other integrins. Using stably transfected PECAM-1+, VCAM-1+, or ICAM-1+ cells, we found that PECAM-1 and, to a lesser extent, VCAM-1, could support transmigration of CD14+ CD34+ cells, whereas the alphaL-ICAM-1 interaction was involved in cell adhesion. PECAM-1-driven transmigration was conceivably dependent on a haptotactic gradient, as it was reduced by 80% across NIH3T3 cells transfected with the PECAM-1-delta cyto deletion mutant. This mutant lacks the cytoplasmic tail and displays a reduced tendency to localize at the intercellular junctions, thus failing to form a molecular junctional gradient. Once differentiated, dendritic cells derived from CD14+ CD34+ precursors retained their transendothelial migratory capability, using both PECAM-1 and ICAM-1 for transmigration. We suggest that a subset of CD14+ CD34+ circulating leukocytes can localize to peripheral tissues and differentiate into functional dendritic cells, thus representing a functional reservoir of potential APC. PECAM-1, constitutively expressed on vascular endothelium, is likely to play a relevant role in the egress of this population from the bloodstream.
MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis (2017)

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.
Noncovalent Engineering of Carbon Nanotube Surfaces by Rigid, Functional Conjugated Polymers (2002)

We report a new nonwrapping approach to noncovalent engineering of carbon nanotube surfaces by short, rigid functional conjugated polymers, poly(aryleneethynylene)s. Our technique not only enables the dissolution of various types of carbon nanotubes in organic solvents, which represents the first example of solubilization of carbon nanotubes via pi-stacking without polymer wrapping, but could also introduce numerous neutral and ionic functional groups onto the carbon nanotube surfaces.
Hepcidin—A Potential Novel Biomarker for Iron Status in Chronic Kidney Disease (2009)

These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance.
Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen (2016)

TIL-ACT with a reduced IL2 decrescendo regimen results in long-lasting complete responses in patients with treatment-refractory melanoma. Larger randomized trials are needed to elucidate whether clinical efficacy is comparable with TIL-ACT followed by HD bolus IL2. Clin Cancer Res; 22(15); 3734-45. ©2016 AACR.
Physically violent behaviour in dementia care: Characteristics of residents and management of violent situations (2011)

This study shows that PVB is frequently displayed among residents in group homes for persons with dementia and the caregivers mainly manage PVB in a symptom-oriented way. To enhance the quality of care for patients with dementia, there is a need for interventions that aim to understand and manage the residents' physical violent behaviour.
HMG-1 as a Late Mediator of Endotoxin Lethality in Mice (1999)

Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
Identification of an Acute Ethanol Response Quantitative Trait Locus on Mouse Chromosome 2 (1999)

A two-stage strategy was used to identify and confirm quantitative trait loci (QTLs) associated with the changes in locomotor activity induced by a 1.5 gm/kg ethanol challenge. For stage 1, putative QTLs were identified by analysis of the strain means for 25 strains of the BXD recombinant inbred (RI) series (males only). QTLs were identified on chromosomes 1, 2, 4, and 6. The activity response to chlordiazepoxide generated similar QTLs on chromosomes 2 and 6. None of the QTLs were similar to those generated from analysis of the saline response data. For stage 2, 900 male C57BL/6J (B6) x DBA/2J (D2) F2 intercross animals were phenotyped for ethanol response, and the phenotypic extremes (those animals > and <1 SD from the mean) were identified. These extremes differed by >10,000 cm/15 min in their response to ethanol. The extreme progeny were used for a genome-wide scan both to confirm the putative RI-generated QTLs and to detect new QTLs. The F2 analysis generated no new QTLs with logarithm of the likelihood for linkage (LOD) scores >3. For RI-generated QTLs, only the QTL on chromosome 2 was confirmed (LOD = 5.3). The position of the peak LOD was estimated to be 47 cM with a 20 cM 1 LOD support interval; this QTL accounted for 6% of the phenotypic variance. The 1 LOD support interval overlaps with QTLs previously identified for alcohol preference and acute ethanol withdrawal (;; ).
Intracellular effect of ultrashort electrical pulses (2001)

A simple electrical model for biological cells predicts an increasing probability for electric field interactions with cell substructures of prokaryotic and eukaryotic cells when the electric pulse duration is reduced into the sub-microsecond range. The validity of this hypothesis was verified experimentally by applying electrical pulses with electric field intensities of up to 5.3 MV/m to human eosinophils in vitro. When 3-5 pulses of 60 ns duration were applied to human eosinophils, intracellular granules were modified without permanent disruption of the plasma membrane. In spite of the extreme electrical power levels applied to the cells thermal effects could be neglected because of the ultrashort pulse duration. The intracellular effect extends conventional electroporation to cellular substructures and opens the potential for new applications in apoptosis induction, gene delivery to the nucleus, or altered cell functions, depending on the electrical pulse conditions.
Neural Networks for Control: An Overview (1990)

The subject of neural networks for control (neurocontrol) is too broad and too complex to thoroughly review in the allowed 2 pages. However, such reviews have already been published in the past. This paper will simply give a few highlights and then cite some more detailed reviews. It will first talk about the subject in general terms, and then summarize the five generic designs or tools which have proven successful so far in control applications.
Thermal denaturation of the DNA-ethidium complex. Redistribution of the intercalated dye during melting (1975)

The temperature dependence of the circular dichroism of the DNA-ethidium bromide complex at elevated temperatures provides evidence that the optical activity of the complex near 307 nm originates from interactions between intercalated dye molecules while the optical activity near 515 nm results from singly intercalated ethidium bromide molecules. The behavior of the circular dichroism of the complex at elevated temperatures also explains the higher ellipticities near 307 nm which characterize complexes formed between ethidium bromide and denaturated DNA. Finally the circular dichroism data indicate that the melting of the complex takes place in a stepwise manner with some DNA regions, probably AT-rich regions, dissociating first. The implications of these findings regarding the inhibiting effect of ethidium bromide on the function of DNA polymerase are examined.