gebhart/patrepeval huggingface dataset:
HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. (1995)

Growth of human breast cells is closely regulated by steroid hormone as well as peptide hormone receptors. Members of both receptor classes are important prognostic factors in human breast cancer. Clinical data indicate that overexpression of the HER-2 gene is associated with an estrogen receptor-negative phenotype. In this study, we demonstrate that introduction of a HER-2 cDNA, converting non-overexpressing breast cancer cells to those which overexpress this receptor, results in development of estrogen-independent growth which is insensitive to both estrogen and the antiestrogen, tamoxifen. Moreover, activation of the HER-2 receptor in breast cancer cells by the peptide growth factor, heregulin, leads to direct and rapid phosphorylation of ER on tyrosine residues. This is followed by interaction between ER and the estrogen-response elements in the nucleus and production of an estrogen-induced protein, progesterone receptor. In addition, overexpression of HER-2 receptor in estrogen-dependent tumor cells promotes ligand-independent down-regulation of ER and a delayed autoregulatory suppression of ER transcripts. These data demonstrate a direct link between these two receptor pathways and suggest one mechanism for development of endocrine resistance in human breast cancers.
Current status and future prospects of human gene therapy (1996)

Gene therapy is defined as the treatment of diseases by the transfer of genes into patients. Clinical trials of gene therapy became feasible as a result of the development of retroviral mediated gene transfer techniques. The first trial was begun in September 1990 at the National Institutes of Health when a four year old girl was treated for adenosine deaminase deficiency. Currently, more than 500 patients are being treated by this innovative therapeutic strategy. In the present review article, the basic concepts and present status of human gene therapy are summarized.
Chromosome mapping of cell membrane antigens expressed on activated B cells (1985)

Abstract Hybrids formed by fusion of either human acute lymphoblastic or chronic lymphocy‐tic leukemia cells and the mouse myeloma P3.X63.Ag81653 have been used to show that the expression of two cell surface antigens, Bp37 and p76, associated with B cell activation and detected by the monoclonal antibodies BB1 and BB2, respectively, segregate with human chromosomes 12 and 19, respectively. Another antigen expressed on activated B cells (p24) also maps to chromosome 12 (Katz et al., Eur. J. Immunol. 1984. 13 :1008) which is of interest in the light of the frequent involvement of this chromosome in certain B cell leukemias and lymphomas.
Tetrodotoxin inhibits neuropathic ectopic activity in neuromas, dorsal root ganglia and dorsal horn neurons (1997)

Neuropathic pain or persistent dysesthesias may be initiated by mechanical, chemical, or ischemic damage to peripheral sensory nerves. In animal models of neuropathic pain, transection or constrictive injury to peripheral nerves produces ectopic discharges originating at both injury sites and related dorsal root ganglia (DRG), and, consequently, hyperexcitability in associated dorsal horn (DH) neurons of the spinal cord. Since ectopic discharges are inhibited by agents that block voltage-sensitive Na+ channels, it has been postulated that accumulation of Na+ channels in the membrane at nerve injury sites may contribute to, or be responsible for, the development of ectopic neuronal activity (ENA). The present study therefore, tested the sensitivity of ENA to intravenously administered tetrodotoxin (TTX), an extremely potent and selective Na+ channel blocker. Comparative effects of TTX on cardiac parameters such as heart rate (HR) and diastolic blood pressure (DBP) were also studied. Experiments were performed on adult male Sprague-Dawley rats in which the common sciatic nerve had been transected 4-10 days earlier. Neuromal activity was measured in fine bundles of microfilaments teased from sciatic nerves, and extracellular microelectrode recordings were made from DRG and DH neurons. Cardiovascular parameters were recorded simultaneously. Intravenously administered TTX induced dose-dependent inhibition of ENA, with that originating from neuromas being the most sensitive; ED50 values (expressed as microg/kg, with 95% confidence limits) for neuromal, DRG and DH neuron activity were: 0.8 (0.6-1.2), 4.3 (2.2-8.4) and 36.2 (16.1-81.3), respectively. Inhibition of ENA in neuromas and DRG did not recover within 10 min after 100 or 300 microg/kg TTX. By comparison, the ED50 value for the initial decrease of HR was 17.9 (15.0-21.5) microg/kg, and partial recovery occurred within approximately 3 min. These data support the hypothesis that Na+ channel accumulation contributes to the generation of ectopic discharges in neuromas and DRG, and suggest that TTX-sensitive Na+ channels located at the nerve injury site and DRG play an important role in the genesis of neuropathic pain.
Shape and motion carving in 6D (2002)

The motion of a non-rigid scene over time imposes more constraints on its structure than those derived from images at a single time instant alone. An algorithm is presented for simultaneously recovering dense scene shape and scene flow (i.e. the instantaneous 3D motion at every point in the scene). The algorithm operates by carving away hexels, or points in the 6D space of all possible shapes and flows that are inconsistent with the images captures at either time instant, or across time. The recovered shape is demonstrated to be more accurate than that recovered using images at a single time instant. Applications of the combined scene shape and flow include motion capture for animation, retiming of videos, and non-rigid motion analysis.
Expression of CCL20 and Its Corresponding Receptor CCR6 Is Enhanced in Active Inflammatory Bowel Disease, and TLR3 Mediates CCL20 Expression in Colonic Epithelial Cells (2015)

The CCL20-CCR6 axis is involved during active inflammation in both ulcerative colitis and Crohn's disease. The epithelial cells seem particularly involved in the CCL20 response, and results from this study strongly suggest that the innate immune system is important for activation of the epithelium, especially through TLR3.
152 Adoptive T cell therapy targeting somatic p53 mutations (2020)

<h3>Background</h3> Adoptive cell therapies (ACT) directed against the products of somatic mutations in cancer cells can lead to long lasting clinical responses. We focused on ACT against shared p53 mutations to be used to potentially treat a broad range of patients with common cancers. We have built a library of anti-mutant p53 T cell receptors (TCRs) to be used for the treatment of patients with epithelial cancers in the autologous setting and as ‘off-the-shelf’ reagents for patients sharing the same p53 mutation and HLA. <h3>Methods</h3> Tumor infiltrating lymphocytes (TILs) were screened for recognition of p53 mutations and were expanded as previously described.<sup>1</sup> For treatment of patient 4349 with metastatic breast cancer, the patient‘s peripheral blood T cells were retrovirally engineered to express the allogeneic anti-p53 R175H TCR. <h3>Results</h3> We identified TILs recognizing ‘hotspot’ p53 mutations, such as R175H, Y220C, and R273C as well as less frequent but recurrent mutations, such as L111R, C135Y, and Q331H (table 1). First, we adoptively transferred TILs that included T cells reactive to a p53 mutation in an autologous manner for the treatment of patients with metastatic epithelial cancers (n=12). Except for the two patients who exhibited an objective response (RECIST), most of the patients did not respond to the therapy, possibly due to low frequencies of anti-mutant p53 cells in the infusion product, exhausted phenotype, and/or poor persistence (table 2). To overcome these barriers to TIL treatment, we retrovirally transduced autologous peripheral blood T cells to express an allogeneic anti-mutant p53 TCR. We engineered the HLA-A*02:01-restricted anti-p53 R175H TCR into patient 4349’s lymphocytes (transduction efficiency of 64%) and saw less expression of exhaustion markers relative to the TIL infusion products (table 2). This patient with metastatic breast cancer was refractory to the six prior chemotherapy regimens. After the transfer of 5.3e10 cells, the patient experienced an objective partial response, showing regression by 55% of skin and mediastinal lesions for 7 months. The persistence of the infused T cells was higher than the other patients who received the TIL treatment (table 2). <h3>Conclusions</h3> The library of anti-mutant p53 TCRs we have generated can potentially be used to treat ~6% of all cancer patients. We are pursuing the adoptive transfer of TILs against mutant p53 naturally occurring in the tumor or TCR-engineered cells using ‘off-the-shelf’ receptors against mutant p53. <h3>Ethics Approval</h3> This study was approved by the Institutional Review Board (IRB) of the NCI, and the approval numbers are as follows:Protocol 10-C-0166 (TIL treatment); Protocol 18-C-0049 (allogeneic TCR engineered T cell therapy) <h3>Reference</h3> Lo, W., et al., Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer. Cancer Immunol Res, 2019. 7(4): p. 534–543.
Phase II Trial of Weekly Vinorelbine and Trastuzumab as First-Line Therapy in Patients with HER2+ Metastatic Breast Cancer (2002)

Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2(+) metastatic breast cancer. Further investigation of this novel regimen is planned.
Benefits and risks due to animal serum used in cell culture production. (1999)

Infection with bovine viral diarrhoea virus (BVDV) and other viruses is frequent in the bovine population. In utero infection leads to virus and antibody contamination of foetal and other serum used in cell culture production. The use of contaminated cells for vaccine production may result in contaminated vaccines, which may lead to seroconversion or disease in the vaccinated animal. Contaminated serum or cell cultures may also interfere with the diagnosis of viral infections. Methods for the detection of BVDV and other viruses in serum, cell cultures, seed viruses and vaccines at the CVB-L, and the frequency of detection are described. Reasons for continued use of serum in cell culture production, and the risks of using serum, are discussed.
Implementing a secure rlogin environment: a case study of using a secure network layer protocol (1995)

This paper describes our experiences building a secure rlogin environment. With minimal changes to the rlogin server and the use of a secure network layer protocol, we remove the vulnerability of hostname-based authentication and IP source address spoofing. We investigate how applications such as rlogin interact with this new layer, and propose extensions to the rlogin server that can utilize these services. We believe rlogin presents a situation where the application layer seems the most appropriate location for enforcing security policy, instead of in a lower layer. Our layered approach to rlogin security achieves functionality similar to the Kerberos klogin client and the encrypted telnet packages, without their complexity or loss of generality. Implementing the application layer rlogin server extensions required fewer than ninety lines of code. Even if our rlogin application layer extensions are omitted, rlogin connections still benefit from secure network layer services.
Solution Structure and Functional Characterization of Jingzhaotoxin-XI:  A Novel Gating Modifier of both Potassium and Sodium Channels, (2006)

JZTX-XI is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao. It contains 34 residues including six cysteine residues with disulfide bridges linked in the pattern of I-IV, II-V, and III-VI. Using 3'- and 5'-RACE methods, the full-length cDNA was identified as encoding an 86-residue precursor of JZTX-XI. In the electrophysiological assay, JZTX-XI shows activity toward the Kv2.1 channel in a way similar to hanatoxin1 and SGTx1 that both the activation and the deactivation processes are affected, which is in accordance with the high sequence homology among them (over 60% identity). On the other hand, JZTX-XI also exhibits specific interaction against the Nav channels of rat cardiac myocytes with a significant reduction in the peak current and slowing of channel inactivation. The solution structure of native JZTX-XI was determined by 1H NMR methods to identify the structural basis of these specific activities. Structural comparison of JZTX-XI with other gating modifier toxins shows that they all adopt a similar surface profile, a hydrophobic patch surrounded by charged residues such as Arg or Lys, which might be a common structural factor responsible for toxin-channel interaction. JZTX-XI might be an ideal tool to further investigate how spider toxins recognize various ion channels as their targets.
Multiple genomic alterations on 21q22 predict various TMPRSS2/ERG fusion transcripts in human prostate cancers (2007)

A number of TMPRSS2/ERG fusion transcripts have been reported since the discovery that recurrent genomic rearrangements result in the fusion of TMPRSS2 and ETS family member genes. In this article we present evidence demonstrating that multiple genomic alterations contribute to the formation of various TMPRSS2/ERG transcripts. Using allele-specific analysis of the data generated from the GeneChip 500K SNP array we observed both hemizygous and homozygous deletions occurring at different locations between and within TMPRSS2 and ERG in prostate cancers. The 500K SNP array enabled us to fine map the start and end of each deletion to specific introns of these two genes, and to predict a variety of fusion transcripts, including a new form which was confirmed by sequence analysis of the fusion transcripts in various tumors. We also inferred that translocation is an additional mechanism of fusion for these two genes in some tumors, based on largely diploid genomic DNA between TMPRSS and ERG, and different fusion transcripts produced in these tumors. Using a bioinformatics approach, we then uncovered the consensus sequences in the regions harboring the breakpoints of the deletions. These consensus sequences were homologous to the human Alu-Sq and Alu-Sp subfamily consensus sequences, with more than 80% homology. The presence/absence of Alu family consensus sequence in the introns of TMPRSS2 and ERG correlates with the presence/absence of fusion transcripts of theses two genes, indicating that these consensus sequences may contribute to genomic deletions and the fusion of TMPRSS2 and ERG in prostate cancer.
Stochastic Activation Pruning for Robust Adversarial Defense (2018)

Neural networks are known to be vulnerable to adversarial examples. Carefully chosen perturbations to real images, while imperceptible to humans, induce misclassification and threaten the reliability of deep learning systems in the wild. To guard against adversarial examples, we take inspiration from game theory and cast the problem as a minimax zero-sum game between the adversary and the model. In general, for such games, the optimal strategy for both players requires a stochastic policy, also known as a mixed strategy. In this light, we propose Stochastic Activation Pruning (SAP), a mixed strategy for adversarial defense. SAP prunes a random subset of activations (preferentially pruning those with smaller magnitude) and scales up the survivors to compensate. We can apply SAP to pretrained networks, including adversarially trained models, without fine-tuning, providing robustness against adversarial examples. Experiments demonstrate that SAP confers robustness against attacks, increasing accuracy and preserving calibration.
An Investigation of the Metabolism of Valine to Isobutyl Alcohol in Saccharomyces cerevisiae (1998)

The metabolism of valine to isobutyl alcohol in yeast was examined by 13C nuclear magnetic resonance spectroscopy and combined gas chromatography-mass spectrometry. The product of valine transamination, alpha-ketoisovalerate, had four potential routes to isobutyl alcohol. The first, via branched-chain alpha-ketoacid dehydrogenase to isobutyryl-CoA is not required for the synthesis of isobutyl alcohol because abolition of branched-chain alpha-ketoacid dehydrogenase activity in an lpd1 disruption mutant did not prevent the formation of isobutyl alcohol. The second route, via pyruvate decarboxylase, is the one that is used because elimination of pyruvate decarboxylase activity in a pdc1 pdc5 pdc6 triple mutant virtually abolished isobutyl alcohol production. A third potential route involved alpha-ketoisovalerate reductase, but this had no role in the formation of isobutyl alcohol from alpha-hydroxyisovalerate because cell homogenates could not convert alpha-hydroxyisovalerate to isobutyl alcohol. The final possibility, use of the pyruvate decarboxylase-like enzyme encoded by YDL080c, seemed to be irrelevant, because a strain with a disruption in this gene produced wild-type levels of isobutyl alcohol. Thus there are major differences in the catabolism of leucine and valine to their respective "fusel" alcohols. Whereas in the catabolism of leucine to isoamyl alcohol the major route is via the decarboxylase encoded by YDL080c, any single isozyme of pyruvate decarboxylase is sufficient for the formation of isobutyl alcohol from valine. Finally, analysis of the 13C-labeled products revealed that the pathways of valine catabolism and leucine biosynthesis share a common pool of alpha-ketoisovalerate.
The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic (2015)

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies.
Wide Area Neutral Atmosphere Models for GNSS Applications (2006)

In this work we discuss developments related to neutral atmosphere delay prediction models at UNB. We are introducing a new model, which was designed to provide better predictions for different regions inside a delimited wide area. The goal of this new development is to have a more reliable model for wide area augmentation system users, with some homogeneity in terms of performance over the area of interest. The approach to create the new wide area neutral atmosphere model for North America (UNBw.na) is comprehensively described and discussed. All result analyses took into consideration the most recent version of UNB models, until now, UNB3m. Results for meteorological parameters prediction showed that the new grid-based model could perform better than a latitude (only) based model (such as UNB3m). The general results do not show a spectacular improvement for the new model, however it is consistently better than its predecessor, and, the improvement for certain regions is more significant than others. Regions where the performance of the old model was not satisfactory had results significantly improved with the new model. A validation of UNBw.na predicted zenith delays was realized using radiosonde-derived delays as reference. This analysis showed that different regions of the continent manifested improvement for the estimations with the new model. Investigation of the performance of both models (UNBw.na and UNB3m) with radiosonde ray-raced delays at a few sample stations showed that UNBw.na generally has a better fit to the yearly behavior of the zenith delays. It was also possible to notice that results from UNBw.na are more consistent between stations at different locations than when using UNB3m. UNBw.na was shown to be consistently better than UNB3m in several aspects, and the adopted procedure for the grid calibration works in an adequate way, resulting in a reliable model. INTRODUCTION Mitigating the neutral atmosphere refraction is a crucial step in GNSS positioning. Also often called tropospheric delays, the neutral atmosphere delays are one of the main sources of measurement errors in GNSS. One usual way to account for these effects is using prediction models. There are also other alternatives for neutral atmosphere delay mitigation, such as the parameterization of the zenith delay in the positioning model, when dual frequency carrier-phase measurements are available. However, even in this case, the parameter is commonly a
Depletion of Whey Proteins and Calcium by Microfiltration of Acidified Skim Milk Prior to Cheese Making (1999)

Pasteurized skim milk was microfiltered (0.2-m membrane) on a system equipped to provide uniform transmembrane pressure of 262 kPa (inlet:outlet pressure differential of 138 kPa, and crossflow velocity of 7.5 m/s). Retentates were gradually acidified to pH 6.6, 6.3, and 6.0 with glucono-delta-lactone during processing to promote solubilization of micelle-bound colloidal minerals into the serum phase of milk for subsequent transfer into permeate. Compositional characteristics of highly concentrated skim milk retentates (concentration factor 8 to 9) and composited permeates were determined to quantify retention and permeation of whey protein and Ca at specified pH conditions and to evaluate the suitability of retentate for cheese making. Final retentates contained an average 27.7% total solids, 20.2% total protein, 17.9% casein, 2.2% whey protein, 4.9% lactose, 2.3% ash, 0.62% Ca, and 0.4% fat. Dry basis retentate Ca and whey protein content significantly differed with pH level and contained 2.8, 2.4, and 1.9 weight percentage of Ca; and 7.2, 7.7, and 8.1 weight percentage of whey protein at pH levels of 6.6, 6.3, and 6.0, respectively. Microfiltration at pH 6.0, as compared with pH 6.6, reduced retentate Ca content by 20.1% but whey protein content was 12.6% higher. Retentate and butter oil were used to produce Mozzarella cheese with a normal Ca content and partial whey protein incorporation. Skim milk microfiltration, combined with in-process pH adjustment, is a useful method to produce highly concentrated retentate reduced in Ca and whey protein content with good potential for cheese manufacture.
Integrated Elastomer Fluidic Lab-on-a-chip Surface Patterning and DNA Diagnostics (2000)

We recently developed a method of multilayer fabrication for elastomeric devices, which we used to fabricate monolithic active valves and pumps. Here we describe efforts to use these pumps and valves in an integrated DNA diagnostic chip and show results of a key component, surface patterning, with two different kind of surface chemistries by using similar elastomeric channel devices. Flow control, reagent metering, in-line mixing and loop circulations are also demonstrated.