gebhart/patrepeval huggingface dataset:
Development of a dendritic cell-targeting lipopeptide as an immunoadjuvant that inhibits tumor growth without inducing local inflammation (2014)

Materials used for the past 30 years as immunoadjuvants induce suboptimal antitumor immune responses and often cause undesirable local inflammation. Some bacterial lipopeptides that act as Toll-like receptor (TLR) 2 ligands activate immune cells as immunoadjuvants and induce antitumor effects. Here, we developed a new dendritic cell (DC)-targeting lipopeptide, h11c (P2C-ATPEDNGRSFS), which uses the CD11c-binding sequence of intracellular adhesion molecule-1 to selectively and efficiently activate DCs but not other immune cells. Although the h11c lipopeptide activated DCs similarly to an artificial lipopeptide, P2C-SKKKK (P2CSK4), via TLR2 in vitro, h11c induced more effective tumor inhibition than P2CSK4 at low doses in vivo with tumor antigens. Even without tumor antigens, h11c lipopeptide significantly inhibited tumor growth and induced tumor-specific cytotoxic T cells. P2CSK4 was retained subcutaneously at the vaccination site and induced severe local inflammation in in vivo experiments. In contrast, h11c was not retained at the vaccination site and was transported into the tumor within 24 hr. The recruitment of DCs into the tumor was induced by h11c more effectively, while P2CSK4 induced the accumulation of neutrophils leading to severe inflammation at the vaccination site. Because CD11b+ cells, but not CD11c+ cells, produced neutrophil chemotactic factors such as macrophage inflammatory protein (MIP)-2 in response to stimulation with TLR2 ligands, the DC-targeting lipopeptide h11c induced less MIP-2 production by splenocytes than P2CSK4. In this study, we succeeded in developing a novel immunoadjuvant, h11c, which effectively induces antitumor activity without adverse effects such as local inflammation via the selective activation of DCs.
Nutritional regulation of glucagon‐like peptide‐1 secretion (2008)

Glucagon-like peptide-1 (GLP-1), released from L-cells in the intestinal epithelium, plays an important role in postprandial glucose homeostasis and appetite control. Following the recent therapeutic successes of antidiabetic drugs aimed at either mimicking GLP-1 or preventing its degradation, attention is now turning towards the L-cell, and addressing whether it would be both possible and beneficial to stimulate the endogenous release of GLP-1 in vivo. Understanding the mechanisms underlying GLP-1 release from L-cells is key to this type of approach, and the use of cell line models has led to the identification of a variety of pathways that may underlie the physiological responses of L-cells to food ingestion. This review focuses on our current understanding of the signalling mechanisms that underlie L-cell nutrient responsiveness.
Structure of Tctex-1 and Its Interaction with Cytoplasmic Dynein Intermediate Chain (2001)

The minus-ended microtubule motor cytoplasmic dynein contains a number of low molecular weight light chains including the 14-kDa Tctex-1. The assembly of Tctex-1 in the dynein complex and its function are largely unknown. Using partially deuterated, (15)N,(13)C-labeled protein samples and transverse relaxation-optimized NMR spectroscopic techniques, the secondary structure and overall topology of Tctex-1 were determined based on the backbone nuclear Overhauser effect pattern and the chemical shift values of the protein. The data showed that Tctex-1 adopts a structure remarkably similar to that of the 8-kDa light chain of the motor complex (DLC8), although the two light chains share no amino acid sequence homology. We further demonstrated that Tctex-1 binds directly to the intermediate chain (DIC) of dynein. The Tctex-1 binding site on DIC was mapped to a 19-residue fragment immediately following the second alternative splicing site of DIC. Titration of Tctex-1 with a peptide derived from DIC, which contains a consensus sequence R/KR/KXXR/K found in various Tctex-1 target proteins, indicated that Tctex-1 binds to its targets in a manner similar to that of DLC8. The experimental results presented in this study suggest that Tctex-1 is likely to be a specific cargo adaptor for the dynein motor complex.
Oils and Fats as Renewable Raw Materials in Chemistry (2011)

Oils and fats of vegetable and animal origin have been the most important renewable feedstock of the chemical industry in the past and in the present. A tremendous geographical and feedstock shift of oleochemical production has taken place from North America and Europe to southeast Asia and from tallow to palm oil. It will be important to introduce and to cultivate more and new oil plants containing fatty acids with interesting and desired properties for chemical utilization while simultaneously increasing the agricultural biodiversity. The problem of the industrial utilization of food plant oils has become more urgent with the development of the global biodiesel production. The remarkable advances made during the last decade in organic synthesis, catalysis, and biotechnology using plant oils and the basic oleochemicals derived from them will be reported, including, for example, ω-functionalization of fatty acids containing internal double bonds, application of the olefin metathesis reaction, and de novo synthesis of fatty acids from abundantly available renewable carbon sources.
Gene therapy for collateral vessel development (1997)

Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application.
Progress and prospects for engineered T cell therapies (2014)

Proof-of-concept studies have demonstrated the therapeutic potential of engineered T cells. Transfer of recombinant antigen-specific T cell receptors (TCR) and chimaeric antigen receptors (CARs) against tumour and viral antigens are under investigation by multiple approaches, including viral- and nonviral-mediated gene transfer into both autologous and allogeneic T cell populations. There have been notable successes recently using viral vector-mediated transfer of CARs specific for B cell antigens, but also reports of anticipated and unanticipated complications in these and other studies. We review progress in this promising area of cellular therapy, and consider developments in antigen receptor therapies including the application of emerging gene-editing technologies.
Complete androgen insensitivity due to deletion of exon C of the androgen receptor gene highlights the functional importance of the second zinc finger of the androgen receptor in vivo. (1992)

Androgen-dependent gene transcription is mediated by the androgen receptor (AR) through interaction of its central zinc finger region with specific DNA sequences on target genes. Failure of this receptor-mediated gene transcription results in end organ resistance to androgens-the androgen insensitivity syndromes. In a pair of siblings with complete androgen insensitivity who had supranormal levels of androgen binding in genital skin fibroblasts, polymerase chain reaction and Southern blot analysis of the androgen receptor gene confirmed by polymerase chain reaction and sequence analysis of AR cDNA, revealed an in-frame deletion of exon C encoding the second zinc finger of the receptor. The mutant receptor in cultured genital skin fibroblasts had normal androgen binding affinity and was localized in the nucleus but had markedly reduced DNA-binding affinity. When recreated in vitro and tested in a cotransfection assay system the mutant receptor failed to activate transcription of an androgen-responsive reporter gene. This naturally occurring mutation highlights the functional dependence of the AR upon its second zinc finger in vivo and explains the complete insensitivity to androgen manifest by the affected individuals despite increased androgen binding. The elevated AR levels in the subjects' genital skin fibroblasts further suggests a possible role for the second zinc finger in autoregulation of receptor levels in vivo.
BCL9 Promotes Tumor Progression by Conferring Enhanced Proliferative, Metastatic, and Angiogenic Properties to Cancer Cells (2009)

Several components of the Wnt signaling cascade have been shown to function either as tumor suppressor proteins or as oncogenes in multiple human cancers, underscoring the relevance of this pathway in oncogenesis and the need for further investigation of Wnt signaling components as potential targets for cancer therapy. Here, using expression profiling analysis as well as in vitro and in vivo functional studies, we show that the Wnt pathway component BCL9 is a novel oncogene that is aberrantly expressed in human multiple myeloma as well as colon carcinoma. We show that BCL9 enhances beta-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases cell proliferation, migration, invasion, and the metastatic potential of tumor cells by promoting loss of epithelial and gain of mesenchymal-like phenotype. Most importantly, BCL9 knockdown significantly increased the survival of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis through down-regulation of c-Myc, cyclin D1, CD44, and vascular endothelial growth factor expression by tumor cells. Together, these findings suggest that deregulation of BCL9 is an important contributing factor to tumor progression. The pleiotropic roles of BCL9 reported in this study underscore its value as a drug target for therapeutic intervention in several malignancies associated with aberrant Wnt signaling.
Transfection of Lactobacillus bulgaricus protoplasts by bacteriophage DNA (1988)

A protoplast transfection system has been developed for Lactobacillus bulgaricus. The procedure involves a polyethylene glycol-mediated fusion of bacteriophage DNA encapsulated in liposomes into mutanolysin-treated cells. With L. bulgaricus B004 and DNA isolated from the phage phi c5004, transfection reached a maximum when at least 95% of the cells were osmotically fragile. The incorporation of phage DNA into liposomes was essential; no transfectants were detected in the absence of liposomes. The largest number of transfectants was observed after longer periods (20 min) of fusion of mutanolysin-treated cells and liposomes with polyethylene glycol. The maximum efficiency of 5 x 10(7) PFU/microgram of DNA was reached after a 24-h incubation in growth media prior to plating transfected cells in an agar overlay to detect the appearance of plaques. A minimum of 4 h of incubation in growth medium after fusion was required to detect the production and release of virions. The possibility that the high frequencies observed were due to bursting of transfected cells and subsequent infection of additional cells was found not to be a factor. The number of transfectants observed was directly proportional to the quantity of DNA added. These results define conditions appropriate for the introduction of DNA into L. bulgaricus.
Patterns of Antibody Recognition of Selected Conserved Amino Acid Sequences from the HIV Envelope in Sera from Different Stages of HIV Infection (1989)

A total of six amino acid sequences encoded in conserved regions of the HIV-env (three from gp120 and three from gp41) were selected as potential antigenic domains. These sequences (11-20 amino acids) were fused to the NH2 terminus of beta-galactosidase by recombinant DNA techniques, and the purified chimeric proteins were used to titer (by immunodots) 75 sera from HIV-infected individuals of various stages. All the HIV antigens were recognized by some or all the HIV-seropositive sera but by none of the control sera. Of the three conserved domains in gp41, two are highly immunodominant. All (100%) HIV-seropositive sera reacted with one of these immunodominant domains in titers (approximately 1:100,000) almost two orders of magnitude higher than any other tested domain. This emphasizes the diagnostic value of the epitopes (ERYLKDQLLGIWGCSGKLIC) previously (see Refs. 11 and 12) identified in this domain. A decrease in average antibody titers is observed in late stages of infection for all the antigens tested, yet distribution of antibody reactivity was independent of stage for only three of the six domains. A significantly higher proportion of reactivity of seropositive sera in early stage (62%) compared with late stage (11%) of infection was found for a domain (NVTENFNMWKN) mapped at the NH2 terminus of gp120; serum antibody reactivity with this domain also correlated with a lack of culturable HIV in blood mononuclear cells.
p53 protein accumulation detected by five different antibodies: relationship to prognosis and heat shock protein 70 in breast cancer. (1994)

Nuclear accumulation of p53 protein is associated with a poorer clinical outcome in breast cancer patients. Heat shock protein 70 (hsp70) is a chaperone that binds to mutant p53 and consequently could regulate its accumulation or localization. The aims of this study were to determine if the prognostic significance of p53 accumulation was dependent on the type of antibody used for detection and whether hsp70 was associated with this accumulation. Node-negative breast tumors (n = 169) were examined by immunohistochemistry for nuclear p53, cytoplasmic or nuclear hsp70, and for p53 gene alteration by single-strand conformation polymorphism analysis. Frozen sections of pulverized breast tumors were stained with five p53 antibodies (240, 1801, 421, BP53-12, and CM1), a cocktail of both 240 and 1801, and the hsp70 antibody C92. Protein level was expressed as the sum of a proportion and intensity score (total 0, 2-8) with > or = 2 defined as positive staining. The cocktail 240/1801 gave the highest rate of positive staining (45%), followed by BP53-12 (35%), 1801 (27%), 240 (25%), CM1 (24%), and 421 (18%), with a high correlation between antibodies. Positive staining with each individual antibody or the cocktail was significantly associated with estrogen receptor and progesterone receptor negativity, age < 50, and high S-phase fraction. Only staining detected by the 240/1801 cocktail was associated with significantly worse overall survival; 85 versus 70% at 5 years for p53-negative compared to p53-positive tumors, respectively (P = 0.02). There was no association between nuclear or cytoplasmic hsp70 staining and accumulation of p53. Patients that were p53-negative/cytoplasmic hsp70-positive had a better overall survival than those that were p53-negative/cytoplasmic hsp70-negative. No other combination of p53 and hsp70 status could further define subsets of patients with a significantly different prognosis compared to p53 status alone. Tumors without a detectable p53 gene alteration by single-strand conformation polymorphism but with accumulated p53 protein did not have relatively increased levels of hsp70. We conclude that in node-negative breast cancer, the cocktail of two antibodies, 240/1801, resulted in the highest rate of positive staining and was most strongly associated with overall survival compared with either antibody alone or with the other individual antibodies. By immunohistochemistry, nuclear accumulation of p53 was not associated with cytoplasmic or nuclear hsp70 levels.
Noncontact Speckle Contrast Diffuse Correlation Tomography of Blood Flow Distributions in Burn Wounds: A Preliminary Study (2019)

The unique noncontact 3D imaging capability makes the scDCT applicable for intraoperative assessment of burns/wounds, without risk of infection and without interfering with sterility of the surgical field. The portable scDCT device holds the potential to be used by surgeons in combat surgical hospitals to improve the acute management of battlefield burn injuries.
Comparison of the human versus murine cytomegalovirus immediate early gene promoters for transgene expression by adenoviral vectors. (1997)

We have developed a number of replication defective adenoviral (Ad) vectors which express transgenes under the control of the human cytomegalovirus (HCMV) immediate early (IE) gene promoter. The orientation of the expression cassette replacing E1 in the vector backbone had a significant effect on the level of transgene expression, with vectors containing expression cassettes directed towards the right end of the Ad genome expressing 7-fold higher levels of beta-galactosidase (beta-gal) than those with inserts in the opposite orientation. Murine cells infected with any of several different Ad vectors in which transgene expression was under the control of the HCMV IE promoter produced 10-100-fold less transgene product (such as beta-gal) than similarly infected human cells. Replacing the HCMV IE promoter with the murine CMV (MCMV) IE promoter resulted in an increase in the levels of beta-gal produced in murine and rat cells by approximately 5-30-fold compared to levels obtained with the HCMV IE promoter, and levels produced in human cells were the same or greater using the MCMV IE promoter compared to the HCMV IE promoter. Similar results were obtained using a luciferase reporter gene. The MCMV IE promoter, therefore, was able to drive high levels of expression without the pronounced species preferences observed for the HCMV IE promoter. The MCMV IE promoter also directed high levels of expression in vivo, suggesting that Ad vectors carrying the MCMV IE promoter may be more effective than those with the HCMV IE promoter for transgene expression in animal models.
Decentralized robust receding horizon control for multi-vehicle guidance (2006)

This paper presents a decentralized robust model predictive control algorithm for multi-vehicle trajectory optimization. The algorithm is an extension of a previous robust safe but knowledgeable (RSBK) algorithm that uses the constraint tightening technique to achieve robustness, an invariant set to ensure safety, and a cost-to-go function to generate an intelligent trajectory around obstacles in the environment. Although the RSBK algorithm was shown to solve faster than the previous robust MPC algorithms, the approach was based on a centralized calculation that is impractical for a large group of vehicles. This paper decentralizes the algorithm by ensuring that each vehicle always has a feasible solution under the action of disturbances. The key advantage of this algorithm is that it only requires local knowledge of the environment and the other vehicles while guaranteeing robust feasibility of the entire fleet. The new approach also facilitates a significantly more general implementation architecture for the decentralized trajectory optimization, which further decreases the delay due to computation time
Latency, activation, and binding proteins of TGF-? (2001)

The TGF-beta superfamily of growth factors consists of an increasing number of different polypeptide modulators of cell growth, differentiation, and morphogenesis. Three mammalian isoforms have been molecularly cloned. Numerous ways to regulate the expression of the TGF-beta genes have been identified. TGF-betas are, for example, subject to regulation by retinoids, steroid hormones, and vitamin D. A characteristic feature in the biology of TGF-betas is that they are usually secreted from cells in latent forms. The large latent complex consists of the small latent complex (TGF-beta and its propeptide) and a high molecular weight protease resistant binding protein, latent TGF-beta binding protein (LTBP). LTBPs are required for the proper folding and secretion of TGF-beta. TGF-beta is not just secreted from cultured cells but is deposited via LTBPs to the pericellular space, namely to the extracellular matrix. Release of these complexes and activation by proteases is under tight regulation and provides a means to rapidly increase local concentrations of TGF-beta. Biological events, where enhanced or focal proteolysis and activation of latent TGF-beta takes place, include cell invasion, tissue remodeling, and wound healing.
Effect of introducing the Modified Early Warning score on clinical outcomes, cardio‐pulmonary arrests and intensive care utilisation in acute medical admissions* (2003)

The effects of introducing Modified Early Warning scores to identify medical patients at risk of catastrophic deterioration have not been examined. We prospectively studied 1695 acute medical admissions. All patients were scored in the admissions unit. Patients with a Modified Early Warning score > 4 were referred for urgent medical and critical care outreach team review. Data was compared with an observational study performed in the same unit during the proceeding year. There was no change in mortality of patients with low, intermediate or high Modified Early Warning scores. Rates of cardio-pulmonary arrest, intensive care unit or high dependency unit admission were similar. Data analysis confirmed respiratory rate as the best discriminator in identifying high-risk patient groups. The therapeutic interventions performed in response to abnormal scores were not assessed. We are convinced that the Modified Early Warning score is a suitable scoring tool to identify patients at risk. However, outcomes in medical emergency admissions are influenced by a multitude of factors and so it may be difficult to demonstrate the score's benefit without further standardizing the response to abnormal values.
Indoor tracking in WLAN location with TOA measurements (2006)

Authors presented recently an indoor location technique based on Time Of Arrival (TOA) obtained from Round-Trip-Time (RTT) measurements at data link level and trilateration. This new approach uses the existing IEEE 802.11 WLAN infrastructure with minor changes to provide an accurate estimation of the position of static wireless terminals. This paper presents advances on how to incorporate tracking capabilities to this approach in order to achieve a noticeable enhancement in the positioning accuracy while maintaining the computational cost low, both essential requirements in some critical applications of indoor pedestrian navigation in which people carrying light mobile devices has to be tracked with precision. Taking as a basis the Discrete Kalman Filter, customizations and optimizations have been designed and presented. Results obtained after conducting extensive simulations fed with actual ranging observables demonstrate the validity and suitability of the researched algorithms and its ability to provide very high performance level in terms of accuracy and robustness.
Tanzania (1989)

The ethnic classification of Tanzania is adapted from Murdock (1959) and draws heavily on Moffett (1958). Because of the relative homogeneity in language and culture, despite the considerable number of identity groups, we have used geographical criteria more than usual in combining identity groups into clusters and types at a high level of abstraction.