gebhart/patrepeval huggingface dataset:
Abstract IA14: Cell transfer immunotherapy targeting unique somatic mutations in cancer (2019)

Abstract Adoptive cell transfer (ACT) immunotherapy using T lymphocytes with antitumor activity is a living therapy that can be highly effective in patients with a variety of metastatic cancers. Naturally occurring tumor infiltrating lymphocytes (TIL) expanded in vitro and administered following a lymphodepleting preparative regimen mediated objective regression of metastatic melanoma in 55% of 194 patients including complete regressions in 24% of patients who remain ongoing disease-free 3 to 10 years later. To determine the antigens recognized by TIL we developed an approach based on deep exomic sequencing of the cancer and immunologic testing of TIL or peripheral lymphocytes to generate T-cells that recognized immunogenic mutations. TIL from 22 patients with metastatic melanoma recognized 54 random somatic mutations none of which were shared among different melanomas. We next extended these studies to patients with common epithelial cancers and showed that 81 of 99 (82%) patients with a variety human cancer types including esophageal, colorectal, bile duct, gastric, pancreatic, ovarian, cervical and lung cancer contained T-cells that recognized 197 neoantigens all of which were unique except for KRAS (2 patients). Targeting unique cancer mutations has extended the reach of ACT immunotherapy and was used to mediate objective regressions in selected patients with chemorefractory metastatic cancers of the bile duct, colon, cervix, and breast. In addition to the use of naturally occurring mutation-reactive cells, we have genetically engineered autologous lymphocytes to express shared antitumor T- cell receptors (TCR) or chimeric antigen receptors (CAR) for use in ACT immunotherapy that can mediate durable cancer regressions in heavily pretreated patients with refractory lymphomas, sarcomas and melanoma. Autologous T- cells can be used to provide a highly personalized immunotherapy for cancer patients refractory to conventional cancer treatments. Citation Format: Steven A. Rosenberg. Cell transfer immunotherapy targeting unique somatic mutations in cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA14.
Antiangiogenic agents can increase tumor oxygenation and response to radiation therapy (1994)

Abstract The Lewis lung carcinoma growing subcutaneously in the hind leg of male C57BL mice is very hypoxic, having 92% of the pO 2 measurements ≤ 5 mmHg as determined with a polarographic oxygen electrode. Administration of a perflubron emulsion (8 ml/kg) along with carbogen breathing increased the tumor oxygen level so that 82% of the pO 2 readings were ≤ 5 mmHg. Treating tumor‐bearing animals with TNP‐470 (30 mg/kg, s.c.) on alternate days and minocycline (10 mg/kg, i.p.) daily beginning on day 4 after tumor cell implantation resulted in decreased hypoxia in the tumors on day 9 when pO 2 measurements were made. The percent of pO 2 readings ≤ 5 mmHg in the tumors of the TNP‐470/ minocycline‐treated animals was 75%, which upon administration of the perflubron emulsion along with carbogen breathing was reduced to 45%. Therapeutically daily fractionated radiation (2, 3, or 4 Gy ≤ 5) was used as an oxygen‐dependent cytotoxic modality. The radiation response of the rumors in TNP‐470/minocycline‐treated animals was greater than that in the untreated tumors. The addition of carbogen breathing for 1 hr prior to and during radiation delivery further increased the radiation response so that overall there was a 2.2‐fold increase in the tumor growth delay produced by the fractionated radiation in the animals treated with TNP‐470/minocycline compared with untreated animals. Administration of the perflubron emulsion along with carbogen breathing prior to and during radiation delivery resulted in a 3.4‐fold increase in tumor growth delay by the fractionated radiation regimens in the TNP‐470/minocycline‐treated animals compared with the tumor growth delay obtained with radiation alone. There was a linear relationship between decrease in the percent of pO 2 readings ≤ 5 mmHg and tumor growth delay at each radiation dose indicating that the diminution in tumor hypoxia produced by these treatments may be directly responsible for the increase in the effectiveness of the radiation therapy. © 1995 Wiley‐Liss, Inc.
Cell-free expression of functional receptor tyrosine kinases (2015)

Receptor tyrosine kinases (RTKs) play critical roles in physiological and pathological processes, and are important anticancer drug targets. In vitro mechanistic and drug discovery studies of full-length RTKs require protein that is both fully functional and free from contaminating proteins. Here we describe a rapid cell-free and detergent-free co-translation method for producing full-length and functional ERBB2 and EGFR receptor tyrosine kinases supported by water-soluble apolipoprotein A-I based nanolipoprotein particles.
A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration (2007)

Genetic variants at chromosomes 1q31-32 and 10q26 are strongly associated with susceptibility to age-related macular degeneration (AMD), a common blinding disease of the elderly. We demonstrate, by evaluating 45 tag SNPs spanning HTRA1, PLEKHA1, and predicted gene LOC387715/ARMS2, that rs10490924 SNP alone, or a variant in strong linkage disequilibrium, can explain the bulk of association between the 10q26 chromosomal region and AMD. A previously suggested causal SNP, rs11200638, and other examined SNPs in the region are only indirectly associated with the disease. Contrary to previous reports, we show that rs11200638 SNP has no significant impact on HTRA1 promoter activity in three different cell lines, and HTRA1 mRNA expression exhibits no significant change between control and AMD retinas. However, SNP rs10490924 shows the strongest association with AMD (P = 5.3 x 10(-30)), revealing an estimated relative risk of 2.66 for GT heterozygotes and 7.05 for TT homozygotes. The rs10490924 SNP results in nonsynonymous A69S alteration in the predicted protein LOC387715/ARMS2, which has a highly conserved ortholog in chimpanzee, but not in other vertebrate sequences. We demonstrate that LOC387715/ARMS2 mRNA is detected in the human retina and various cell lines and encodes a 12-kDa protein, which localizes to the mitochondrial outer membrane when expressed in mammalian cells. We propose that rs10490924 represents a major susceptibility variant for AMD at 10q26. A likely biological mechanism is that the A69S change in the LOC387715/ARMS2 protein affects its presumptive function in mitochondria.
Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer (1995)

A tumor-specific cytotoxic T lymphocyte (CTL) immune response has been well documented in melanoma, renal cell carcinoma, and ovarian cancer. Conflicting evidence exists regarding the existence of tumor-specific CTL populations in breast cancer. Tumor cells and tumor-associated lymphocytes (TAL) were isolated from the pleural effusions of six consecutive patients with metastatic breast cancer. After solid-phase anti-CD3 stimulation, TAL cultures were expanded with weekly autologous tumor stimulation and low-dose IL-2 for 3 wk. T cell populations were characterized using flow cytometric analysis and ranged from 49 to 91% CD8+, > 98% CD3+, and < 3% CD16+. Functionally, tumor-stimulated TAL showed tumor-specific recognition of autologous tumor cells (241 +/- 142 LU20/10(7)) and no detectable lysis of autologous fibroblasts, Daudi or K562. Cytotoxicity of TAL against HLA-A2+ allogeneic targets was significantly higher when compared with HLA-A2- tumor cell lines (127 +/- 76 vs 6 +/- 18 LU, p = 0.0001). This cytotoxicity against autologous and allogeneic tumor cells was blocked by anti-HLA-A2 mAb and cold HLA-A2+ targets in cold-target inhibition assays. TAL from all HLA-A2+ patients recognized GP2, a known, HER2/neu-derived tumor-associated peptide Ag that is HLA-A2 restricted. We have shown that TAL obtained from metastatic effusions of breast cancer patients contain lymphocytes that can recognize and lyse autologous and allogeneic tumor cells in a tumor-specific, HLA-A2-restricted fashion. In addition, tumor-specific TAL derived from breast cancer patients can selectively lyse HLA-A2+ pancreatic and ovarian tumor cell targets, suggesting a common HLA-A2-restricted tumor-associated Ag between these distinct epithelial cancers. Further elucidation of the cell-mediated immune response to breast cancer and the identification of shared TAA could result in the development of broadly applicable vaccine therapies for many cancers.
Link Prediction Approach for Opportunistic Networks Based on Recurrent Neural Network (2018)

The target of link prediction is used to estimate the possibility of future links among nodes through known network structures and nodes information. According to the time-varying characteristics of the opportunistic network, the historical information of node pairs has a significant influence on the future connection state. We propose a novel link prediction approach which is based on the recurrent neural network link prediction (RNN-LP) framework. With the help of time series method, we define the vector that is made up of the node information and historical connection information of the node pairs, in which a sequence vector is constructed. Benefiting from RNN in sequence modeling, the time domain characteristics were extracted in the process of the dynamic evolution of the opportunistic network. Hence, the future link prediction becomes significantly better. By utilizing iMote traces Cambridge and MIT reality datasets, experimental results are obtained to reveal that RNN-LP method gives better accuracy and stability than the prediction techniques of the common neighbor, Adamic-Adar, resource allocation, local path, and Katz.
Resistance of Morpholino Phosphorodiamidate Oligomers to Enzymatic Degradation (1996)

Oligomers possessing the Morpholino phosphorodiamidate backbone were evaluated for resistance to a variety of enzymes and biologic fluids. A 25-mer was incubated with nucleases, proteases, esterases, and serum, and the reaction mixtures were directly analyzed by MALDI-TOF mass spectrometry. The 25-mer was completely resistant to 13 different hydrolases and serum and plasma. The excellent resistance of Morpholino phosphorodiamidates to enzymatic attack indicates their suitability for in vivo use.
Pellet: An OWL DL Reasoner (2004)

In order to gain experience with description logic reasoner, and to contribute to the OWL Candidate Recommendation process, a small team at MINDSWAP set out to implement a tableau reasoner for the Lite and DL dialects of OWL (corresponding roughly to the description logics SHIF(D) and SHION(D)). Our group found existing, available DL reasoners lacking for our purposes, because we needed an open-source tool that provides ABox reasoning, that does not make Unique Name assumption, supports entailment checks and works with XML Schema datatypes. Pellet has been developed to addresses these issues and has become both our test bed for experiments with DL and Semantic Web reasoning, as well as our standard reasoning component. While not (yet) in the performance range of Racer or Fact, it has many usability features that makes it a good choice for various lighter weight situations. Technically, Pellet is a sound and complete tableau reasoners for SHIN(D) and SHON(D) (with ABoxes), and a sound but incomplete tableau reasoner for SHION(D) (with ABoxes). Pellet has the usual suite of optimizations including lazy unfolding, absorption, dependency directed backjumping, and semantic branching. It incorporates datatype reasoning for the built-in primitive XML Schema datatypes. Pellet is implemented in pure Java and available as open source software.
Commerce on the Internet (1994)

The article discusses the World Wide Web (Internet), focusing on using the WWW to support commerce-electronic marketing and digital publishing. Businesses are increasingly using the Web for advertising and electronic catalog based retail sales. Immediate benefits from the use of the technology include the ability to monitor and track the behavior of one's customers, provided by access statistics the WWW server maintains. In addition, many aspects of managing customer interaction can be automated, for example, submission and collection of customer surveys, billing, and so forth. In the future, more organizations will use the net for innovative ways of providing online magazines and electronic commerce. Although the approximately 20 million Internet users represent only a small fraction of the world population, the dramatic growth of the market in recent years will continue to lure commerce online.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
CpG-A Oligonucleotides Induce a Monocyte-Derived Dendritic Cell-Like Phenotype That Preferentially Activates CD8 T Cells (2003)

Human B cells and plasmacytoid dendritic cells recognize CpG motifs within microbial DNA via Toll-like receptor 9. Two functionally distinct types of CpG motif containing oligonucleotides (CpG ODN) have been described, CpG-A and CpG-B. In contrast to CpG-B, CpG-A induces high amounts of type I IFN (IFN-alpha and IFN-beta) in plasmacytoid dendritic cells. In the present study, we examined the effects of CpG-A on human primary monocytes. In PBMC stimulated with CpG-A and GM-CSF, monocytes showed excellent survival, increased in size and granularity, and within 3 days developed a dendritic cell-like phenotype that was characterized by down-regulation of CD14, partial up-regulation of CCR7, and an increased surface expression of costimulatory and Ag-presenting molecules. This effect could be inhibited by a combination of blocking Abs to type I IFN, and no such CpG-A-induced changes were observed in purified monocytes. Although IL-12 production by this dendritic cell-like phenotype required additional stimulation with CD40 ligand, this cell type spontaneously up-regulated IL-15 expression. Consistent with the known effect of IL-15 on effector and memory CD8 T cells, the frequency of CCR7(-)/CD45RA(-) CD8 T cells was selectively increased in allogeneic T cell assays. Furthermore, this dendritic cell type was more potent to support both the generation and the IFN-gamma production of autologous influenza matrix peptide-specific memory CD8 T cells as compared with dendritic cells generated in the presence of GM-CSF and IL-4. In conclusion, monocytes exposed to the cytokine milieu provided by CpG-A rapidly develop a dendritic cell-like phenotype that is well equipped to support CD8 T cell responses.
The deoxyribonucleic acid unwinding protein of Escherichia coli. Properties and functions in replication. (1975)

The DNA unwinding protein of Escherichia coli (Sigal, N., Delius, H., Kornberg, T., Gefter, M., and Alberts, B. (1972) Proc. Nat. Acad. Sci. U.S.A. 69, 3537-3541) has been purified to homogeneity by a simple procedure which utilizes its stability to heating. The protein is an asymmetric tetramer of 18,500 dalton subunits which binds preferentially to single-stranded DNA at a ratio of one protein molecule per 32 nucleotides. Binding to DNA is complete in less than 10 s at 0 degrees while release of the protein from single-stranded DNA is relatively slow even at 37 degrees. A simple functional assay for unwinding protein depends on its essential role in the conversion of phage G4 single-stranded DNA to the replicative form. Unwinding protein stimulates initiation of replication of all single-stranded phage DNAs. Approximately 300 copies of unwinding protein are present per cell, as estimated by antibody titration, an amount sufficient to cover substantial lengths of DNA in several replicating forks.
A Comparative Study of Water Clusters by Classical and Polarizable Water Models (2007)

Several classical water models (SPC,TIPnP (n=3-5)) and polarizable water models (POL3,DANG,AMOEBA,SPC-FQ,TIP4P-FQ),combining the results of ab initio methods were employed to study the properties of water clusters,such as structures,dipoles,induced dipoles,charge transfer,polarized energies,many-body energies and binding energies,and were evaluated against the related literature works. Whether the polarized effect could be neglected in the modelng of water clusters,it was judged by the total potential and the decomposed energy terms. All in all,the polarizable water models,especially the induced multiple model (AMOEBA),do better job than classical fixed charge models. Fluctuating charge and four sites model are more realistic to be applied to the biological sytems in consideration of the balance of efficiency and accuracy. The comparable studies of this paper provide a reference for developing the polarized models and applying them to other systems.
Design, Synthesis, and Evaluation of New Noncross-Linking Pyrrolobenzodiazepine Dimers with Efficient DNA Binding Ability and Potent Antitumor Activity (2002)

New sequence selective mixed imine-amide pyrrolobenzodiazepine (PBD) dimers have been developed that are comprised of DC-81 and dilactam of DC-81 subunits tethered to their C8 positions through alkanedioxy linkers (comprised of three to five and eight carbons). Thermal denaturation studies show that after 18 h of incubation with calf thymus DNA at a 5:1 DNA/ligand ratio, one of them (5c) increases the DeltaT(m) value by 17.0 degrees C. Therefore, these unsymmetrical molecules exhibit significant DNA minor groove binding affinity and 5c linked through the pentanedioxy chain exhibits efficient DNA binding ability that compares with the cross-linking DSB-120 PBD dimer (DeltaT(m) = 15.4 degrees C). Interestingly, this imine-amide PBD dimer has been linked with a five carbon chain linker unlike DSB-120, which has two DC-81 subunits with a three carbon chain linker, illustrating the effect of the noncross-linking aspect by introducing the noncovalent subunit. The binding affinity of the compounds has been measured by restriction endonuclease digestion assay based on inhibition of the restriction endonuclease BamHI. This study reveals the significance of noncovalent interactions in combination with covalent bonding aspects when two moieties of structural similarities are joined together. This allows the mixed imine-amide PBD dimer with a five carbon chain linker to achieve an isohelical fit within the DNA minor groove taking in to account both the covalent bonding and the noncovalent binding components. This has been supported by molecular modeling studies, which indicate that the PBD dimer with a five carbon chain linker gives rise to maximum stabilization of the complex with DNA at the minor groove as compared to the other PBD dimers with three, four, and eight carbon chain linkers. The energy of interaction in all of the complexes studied is correlated to the DeltaT(m) values. Furthermore, this dimer 5c has significant cytotoxicity in a number of human cancer cell lines.
Three-dimensional motion estimation in elastography (2002)

In elastography we are capable of estimating the two in-plane principal strain components following an applied compression, namely the axial and lateral components, along and perpendicular to the compressor/transducer axis, respectively. However, the motion resulting from the compression is three-dimensional. Therefore, in order fully describe the resulting three-dimensional motion we need to also estimate the third strain, or elevational (out-of-plane) component. In this paper, we describe a method that estimates motion, i.e., displacement and strain, in the elevational direction. In a similar way as in the lateral motion estimation, and by assuming that ultrasonic frames are available in more than one parallel elevational planes, we used methods of interpolation and cross-correlation between elevationally displaced RF echo segments. We were thus able to obtain high resolution elevational displacement and strain estimates. An iterative method corrected for motion in the axial and lateral directions. As a result, together with the corrected axial and lateral strain estimates, we obtained the full 3D normal strain tensor resulting from a uniform compression. Results of this method from three-dimensional finite-element simulations are shown.
Downstream intensification effects associated with CO 2 laser mitigation of fused silica (2007)

Mitigation of 351nm laser-induced damage sites on fused silica exit surfaces by selective CO<sub>2</sub> treatment has been shown to effectively arrest the exponential growth responsible for limiting the lifetime of optics in high-fluence laser systems. However, the perturbation to the optical surface profile following the mitigation process introduces phase contrast to the beam, causing some amount of downstream intensification with the potential to damage downstream optics. Control of the laser treatment process and measurement of the associated phase modulation is essential to preventing downstream 'fratricide' in damage-mitigated optical systems. In this work we present measurements of the surface morphology, intensification patterns and damage associated with various CO<sub>2</sub> mitigation treatments on fused silica surfaces. Specifically, two components of intensification pattern, one on-axis and another off-axis can lead to damage of downstream optics and are related to rims around the ablation pit left from the mitigation process. It is shown that control of the rim structure around the edge of typical mitigation sites is crucial in preventing damage to downstream optics.
Transmission loss of phase-shifted fiber Bragg gratings in lossy materials: a theoretical and experimental investigation (2007)

Narrow linewidth transmission filters in lossy materials based phase-shifted fiber Bragg gratings have been investigated experimentally and analytically. A novel matrix technique has been developed in calculation of the transmission loss and linewidth. The elements of the matrix simply consist of the coefficients of the coupled mode equations. Simulation shows a small fiber loss could result in a significant transmission loss, which has not been explained properly yet to our knowledge. For phase-shifted gratings in erbium-doped fibers, the absorption could result in over 20 dB loss at transmission wavelengths. Such an approach can also be used to analyze cladding modes, radiation mode, and complex structure gratings.