gebhart/patrepeval huggingface dataset:
Silk Fibroin Microparticles as Carriers for Delivery of Human Recombinant Bone Morphogenetic Protein-2: In Vitro and In Vivo Bioactivity (2009)

The in vitro and in vivo efficiency of fibroin microparticles as a delivery carrier for bone morphogenetic protein-2 (BMP-2) was evaluated. BMP-2 was encapsulated in silk fibroin particles that were produced by a simple and very mild processing method. The dose-response of BMP-2-loaded fibroin particles was examined in C2C12 cells, after 5 days of culture. The BMP-2 retained most of its activity as observed by the increase in alkaline phosphatase activity, which was much higher when BMP-2 was encapsulated into the particles rather than just surface-adsorbed. After 2 weeks of culture, increased mineralization was observed with BMP-2-loaded particles in comparison to soluble added growth factor. No significant cytotoxicity was detected. When implanted in a rat ectopic model, bone formation was observed by in vivo micro-computed tomography after 2 and 4 weeks postimplantation, with particles loaded with 5 or 12.5 microg BMP-2. An increase in bone density was observed over time. Histology revealed further evidence of ectopic bone formation, observed by strong alizarin red staining and osteocalcin immunostaining. Our findings show that fibroin microparticles may present an interesting option for future clinical applications in the bone tissue engineering field, and therefore, further studies have been planned.
Study of three laser systems for treatment of superficial varicosities of the lower extremity (1987)

Three separate laser modalities were investigated in the treatment of superficial varicosities/telangiectasias of the lower extremities. Sixteen patients were treated and followed for 12 months. The superpulse CO2, the pulsed focally specific CO2, and the Nd:YAG laser transmitted through a diffusing sapphire tip were able to produce cosmetically satisfactory permanent obliteration of vessels after a 12-month follow-up interval. These results were a significant improvement over six-month results indicating a long fading time for laser treatment of leg veins.
A Random Linear Network Coding Approach to Multicast (2006)

We present a distributed random linear network coding approach for transmission and compression of information in general multisource multicast networks. Network nodes independently and randomly select linear mappings from inputs onto output links over some field. We show that this achieves capacity with probability exponentially approaching 1 with the code length. We also demonstrate that random linear coding performs compression when necessary in a network, generalizing error exponents for linear Slepian-Wolf coding in a natural way. Benefits of this approach are decentralized operation and robustness to network changes or link failures. We show that this approach can take advantage of redundant network capacity for improved success probability and robustness. We illustrate some potential advantages of random linear network coding over routing in two examples of practical scenarios: distributed network operation and networks with dynamically varying connections. Our derivation of these results also yields a new bound on required field size for centralized network coding on general multicast networks
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer (2018)

Adoptive cell therapy has emerged as a powerful treatment for advanced cancers resistant to conventional agents. Most notable are the remarkable responses seen in patients receiving autologous CD19-redirected chimeric antigen receptor (CAR) T cells for the treatment of B lymphoid malignancies; however, the generation of autologous products for each patient is logistically cumbersome and has restricted widespread clinical use. A banked allogeneic product has the potential to overcome these limitations, yet allogeneic T-cells (even if human leukocyte antigen-matched) carry a major risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are bone marrow-derived innate lymphocytes that can eliminate tumors directly, with their activity governed by the integration of signals from activating and inhibitory receptors and from cytokines including IL-15, IL-12, and IL-18. NK cells do not cause GVHD or other alloimmune or autoimmune toxicities and thus, can provide a potential source of allogeneic "off-the-shelf" cellular therapy, mediating major anti-tumor effects without inducing potentially lethal alloreactivity such as GVHD. Given the multiple unique advantages of NK cells, researchers are now exploring the use of CAR-engineered NK cells for the treatment of various hematological and non-hematological malignancies. Herein, we review preclinical data on the development of CAR-NK cells, advantages, disadvantages, and current obstacles to their clinical use.
Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis (2006)

As indicators of responsiveness to a tumour necrosis factor (TNF)alpha blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination.
PKC-θ knockout mice are protected from fat-induced insulin resistance (2004)

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-theta KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. In contrast, PKC-theta inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes.
Quantitative proton MRS predicts outcome after traumatic brain injury (1999)

1H-MRS provides a rapid, noninvasive tool to assess the extent of diffuse injury after head trauma, a component of injury that may be the most critical factor in evaluating resultant neuropsychological dysfunction. 1H-MRS can be added to conventional MR examinations with minimal additional time, and may prove useful in assessing injury severity, guiding patient care, and predicting patient outcome.
Insulin Receptor Substrate 1 Binds Two Novel Splice Variants of the Regulatory Subunit of Phosphatidylinositol 3-Kinase in Muscle and Brain (1996)

We have identified two novel alternatively spliced forms of the p85alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase by expression screening of a human skeletal muscle library with phosphorylated baculovirus- produced human insulin receptor substrate 1. One form is identical to p85alpha throughout the region which encodes both Src homology 2 (SH2) domains and the inter-SH2 domain/p110 binding region but diverges in sequence from p85alpha on the 5' side of nucleotide 953, where the entire break point cluster gene and SH3 regions are replaced by a unique 34-amino-acid N terminus. This form has an estimated molecular mass of approximately 53 kDa and has been termed p85/AS53. The second form is identical to p85 and p85/AS53 except for a 24-nucleotide insert between the SH2 domains that results in a replacement of aspartic acid 605 with nine amino acids, adding two potential serine phosphorylation sites in the vicinity of the known serine autophosphorylation site (Ser-608). Northern (RNA) analyses reveal a wide tissue distribution of p85alpha, whereas p85/AS53 is dominant in skeletal muscle and brain, and the insert isoforms are restricted to cardiac muscle and skeletal muscle. Western blot (immunoblot) analyses using an anti-p85 polyclonal antibody and a specific anti-p85/AS53 antibody confirmed the tissue distribution of p85/AS53 protein and indicate a approximately 7-fold higher expression of p85/AS53 protein than of p85 in skeletal muscle. Both p85 and p85/AS53 bind to p110 in coprecipitation experiments, but p85alpha itself appears to have preferential binding to insulin receptor substrate 1 following insulin stimulation. These data indicate that the gene for the p85alpha regulatory subunit of PI 3-kinase can undergo tissue-specific alternative splicing. Two novel splice variants of the regulatory subunit of PI 3-kinase are present in skeletal muscle, cardiac muscle, and brain; these variants may have important functional differences in activity and may play a role in tissue-specific signals such as insulin-stimulated glucose transport or control of neurotransmitter secretion or action.
Differential tissue expression of the Lewis blood group antigens: enzymatic, immunohistologic, and immunochemical evidence for Lewis a and b antigen expression in Le(a-b-) individuals (1991)

The Lewis blood group system comprises two main carbohydrate antigens, Le(a) and Le(b). Lewis typing has traditionally been based on serologic determinations using erythrocytes and saliva. Several recent studies have demonstrated that erythrocyte Lewis phenotype may change during pregnancy or disease, and inappropriate Lewis antigens have been found in both normal and neoplastic tissue. To evaluate whether these observations are in conflict with the presently proposed genetic and biosynthetic basis of the Lewis blood group system, we performed a combined enzymatic, immunohistologic, and immunochemical study of Lewis antigen expression in normal and neoplastic tissues, as well as erythrocytes, plasma, and saliva of Le(a-b-)-typed individuals. Of six cancer-bearing patients typed Le(a-b-), three were identified as nongenuine owing to the presence of alpha 1----4fucosyltransferase activity (alpha 1----4FT) and Lewis antigens in saliva and three were identified as genuine (lacking alpha 1----4FT and Lewis antigens in saliva). These genuine Le(a-b-) individuals were shown to express significant alpha 1----4FT in tissues, and Lewis antigens were detected in tissues by immunohistology as well as immunochemistry. We conclude that the Lewis phenotype obtained by serologic determination of erythrocytes and saliva does not apply to all tissues. We discuss biosynthetic and genetic consequences of this finding.
Radiation signaling mediated by Jun activation following dissociation from a cell type-specific repressor. (1993)

The promoter regions of several radiation-inducible genes contain AP-1 cis-acting regulatory elements that are dependent upon protein kinase C signaling. We analyzed nuclear protein from irradiated human tumor cell lines for binding to the AP-1 consensus sequence. The increase in nuclear protein binding following irradiation was specific for the AP-1 sequence and was reduced by antibodies to c-Jun and c-Fos. The AP-1 DNA binding sequence was found to regulate transcription in irradiated cells and mutation of the AP-1 site within the c-jun promoter abolished transcriptional induction by radiation. The gene encoding the chimeric transcription factor Gal4-Jun5-253, which includes the DNA binding region of Gal4 and the transcriptional regulatory region of c-Jun, was cotransfected with the reporter plasmid with Gal4 binding sequences (G5B-CAT). Transfection of RIT-3 and HeLa cells revealed that the regulatory region of Jun was sufficient to activate transcription following irradiation. Conversely, Hep G2 cells, which do not contain the cell type-specific Jun repressor, were not responsive to radiation-induced Jun activation. The c-Jun repressor was found to regulate Jun activation by experiments using the expression vector CMV-jun, which competes for Jun inhibitor and eliminates radiation-induction of Jun. We propose transcription factor dissociation from inhibitor proteins may participate in the initiation of cellular responses to ionizing radiation.
Interactions Between the Microbiota and the Immune System (2012)

The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.
Validating and Restoring Defense in Depth Using Attack Graphs (2006)

Defense in depth is a common strategy that uses layers of firewalls to protect supervisory control and data acquisition (SCADA) subnets and other critical resources on enterprise networks. A tool named NetSPA is presented that analyzes firewall rules and vulnerabilities to construct attack graphs. These show how inside and outside attackers can progress by successively compromising exposed vulnerable hosts with the goal of reaching critical internal targets. NetSPA generates attack graphs and automatically analyzes them to produce a small set of prioritized recommendations to restore defense in depth. Field trials on networks with up to 3,400 hosts demonstrate that firewalls often do not provide defense in depth due to misconfigurations and critical unpatched vulnerabilities on hosts. In all cases, a small number of recommendations was provided to restore defense in depth. Simulations on networks with up to 50,000 hosts demonstrate that this approach scales well to enterprise-size networks
An Audience Flow Model of Television Viewing Choice (1984)

A model for the prediction and explanation of individual television viewing choice is presented, incorporating considerations of utility, audience flow, and audience segmentation. The proposed model provides a quantifiably explicit theoretical explanation of television viewing choice, and its validation on large-sample network viewing data provides a baseline degree of accuracy against which the performance of future television viewing models may be compared. Of direct relevance to advertising agencies and the television networks is the suitability of the model for estimating the comparative impact of alternative programs on the audience size and composition of competing programs in the immediate and subsequent time slots.
Post-transcriptional Regulation of the GLI1 Oncogene by the Expression of Alternative 5′ Untranslated Regions (2001)

The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway. In this study, we have identified alternative GLI1 transcripts that differ in their 5' untranslated regions (UTRs) and are generated by exon skipping. These are denoted alpha-UTR, beta-UTR, and gamma-UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The alpha- and beta-UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the gamma-UTR is present at relatively low levels but is markedly induced in mouse skin treated with 12-O-tetradecanoylphorbol 13-acetate. Transcripts corresponding to the murine beta and gamma forms were identified in human tissues, but significantly, only the gamma-UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the gamma-UTR variant expresses a heterologous reporter gene 14-23-fold higher than the alpha-UTR and 5-13-fold higher than the beta-UTR in a variety of cell types. Because expression of the gamma-UTR variant correlates with proliferation, consistent with a role for GLI1 in growth promotion, up-regulation of GLI1 expression through skipping of 5' noncoding exons may be an important tumorigenic mechanism.
AMG 531, a Thrombopoiesis-Stimulating Protein, for Chronic ITP (2006)

AMG 531 caused no major adverse events and increased platelet counts in patients with ITP. (ClinicalTrials.gov number, NCT00111475 [ClinicalTrials.gov].).
Electrochemical Reductions in Ethylenediamine (1966)

The effect of operating variables on the electrochemical reduction of tetralin used at a model compound for the hydrogenation of coal it described. The effect of adding a proton donor (tert-butyl alcohol) on the reduction of an olefin was also investigated.
THE EFFECT OF AGLYCOSYLATION ON THE IMMUNOGENICITY OF A HUMANIZED THERAPEUTIC CD3 MONOCLONAL ANTIBODY (1995)

The factors affecting the immunogenicity of a humanized gamma 1 CD3 monoclonal antibody (mAb) were investigated in transgenic mice that express the human CD3 antigen epsilon polypeptide (the mAb target antigen). Two derivatives of the mAb were employed, one with a normal, glycosylated Fc region (gamma 1 CD3 mAb), and the other with an aglycosylated Fc region (aglycosyl gamma 1 CD3 mAb). Comparisons of the antiglobulin responses elicited by the two derivatives in transgenic and nontransgenic mice demonstrated that Fab-mediated cell binding activity, dependent on target antigen expression, was a major positive determinant of CD3 mAb immunogenicity. A second positive factor was mAb Fc region glycosylation. At low dose levels the gamma 1 CD3 mAb consistently produced a higher antiglobulin response than the aglycosyl gamma 1 CD3 mAb. This was probably a result of the nonspecific, in vivo T cell activating property of the gamma 1 CD3 mAb, a consequence of its ability to cross-link T cells to Fc gamma receptor-bearing cells. (The aglycosyl gamma 1 CD3 mAb has a reduced Fc binding affinity for Fc gamma receptors and so does not activate T cells in vivo.) In support of this hypothesis, the gamma 1 CD3 mAb was able to nonspecifically enhance humoral immunity to an unrelated, coadministered antigen, whereas the aglycosyl gamma 1 CD3 mAb was not. The lower immunogenicity of the aglycosyl gamma 1 CD3 mAb correlated with a longer in vivo half-life and an improved capacity to block the target CD3 antigen. These results suggest that, as well as reducing the cytokine-induced side effects normally associated with CD3 mAb therapy, the nonactivating aglycosyl gamma 1 CD3 mAb will be less likely than the activating gamma 1 CD3 mAb to stimulate a neutralizing antiglobulin response.
Highly Enantioselective Reformatsky Reaction of Ketones:  Chelation-Assisted Enantioface Discrimination (2002)

[reaction: see text] Highly enantioselective Reformatsky reaction of ketones was accomplished using cinchona alkaloids as chiral ligands. Chelation with the sp(2)-nitrogen adjacent to the reactive carbonyl center contributed the enantioface discrimination for the high enantioselectivities.
Torsional properties of healed canine diaphyseal defects grafted with a fibrillar collagen and hydroxyapatite/tricalcium phosphate composite (1994)

The need for alternatives to autogenous bone grafts is widely recognized. This study compared the torsional strength of canine femora 1 year after grafting with one of three forms of a collagen/hydroxyapatite/tricalcium phosphate bone grafting material (COLLAGRAFTTM), autogenous bone, or no graft. The groups were compared to each other and to the unoperated contralateral femora. Results of torsional testing were evaluated for torsional strength, torsional displacement, total energy to fracture and White fracture mode. Data analysis showed lower torsional strength of the operated vs. unoperated femora with the exception of morsellized COLLAGRAFTTM material, which had higher strength. However, the only difference in the operated groups was that the morsellized COLLAGRAFTTM had greater strength than several groups including the autogenous bone group. There was no difference found in angular displacement between any of the groups. However, there was a difference in the energy to fracture in both strip forms of the COLLAGRAFTTM. The final conclusion is that in this model, grafting with COLLAGRAFTTM provided torsional properties at one year postoperatively at least equivalent to autogenous bone.
Control of Large-Scale Plasma Thawing for Recovery ofCryoprecipitate Factor VIII (1982)

Cryoprecipitation is commonly used as the primary step in the preparation of clinical factor VIII concentrates; yet recovery is usually very low. Much of this loss is due to poor temperature control and a process of continuous plasma thawing has been designed to overcome this. A substantial improvement has resulted, with an increase in both yield and purity of factor VIII :C of over 50% in comparison to a conventional batch thaw process.
A Cas9–guide RNA complex preorganized for target DNA recognition (2015)

Bacterial adaptive immunity uses CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) proteins together with CRISPR transcripts for foreign DNA degradation. In type II CRISPR-Cas systems, activation of Cas9 endonuclease for DNA recognition upon guide RNA binding occurs by an unknown mechanism. Crystal structures of Cas9 bound to single-guide RNA reveal a conformation distinct from both the apo and DNA-bound states, in which the 10-nucleotide RNA "seed" sequence required for initial DNA interrogation is preordered in an A-form conformation. This segment of the guide RNA is essential for Cas9 to form a DNA recognition-competent structure that is poised to engage double-stranded DNA target sequences. We construe this as convergent evolution of a "seed" mechanism reminiscent of that used by Argonaute proteins during RNA interference in eukaryotes.