gebhart/patrepeval huggingface dataset:
Abstract 2060: Combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin's lymphoma (2019)

Abstract MT-3724 is a novel recombinant fusion protein consisting of a CD20 binding variable fragment (scFv) fused to Shiga-like toxin-I A1 (SLTA) ribosome inactivating protein. Engineered Toxin Bodies (ETBs) are unique as they can induce internalization after binding to non- or poorly-internalizing receptors with subsequent enzymatic and permanent ribosome destruction through SLTA, representing a novel mechanism of direct cell-kill in oncology. MT-3724 has demonstrated single agent anti-tumor activity in heavily pre-treated relapsed/refractory (R/R) Non-Hodgkin’s lymphoma NHL patients in a Phase I clinical study. Specifically, in R/R diffuse large B cell lymphoma (DLBCL) patients who had low pre-existing serum levels of rituximab, an objective response rate (ORR) of 30% (3 of 10) and disease control rate of 70% (7 of 10) has been observed thus far (NCT02361346). Given the unique ribosomal inhibition mechanism of action for MT-3724, we hypothesized that combination of MT-3724 with agents possessing a differentiated mechanism of action could result in additive or synergistic cellular cytotoxicity in CD20 positive NHL cell lines. Preclinical studies were conducted to assess MT-3724 in combination with cytotoxic chemotherapeutic agents (doxorubicin, gemcitabine, bendamustine, and vincristine) or an immunomodulatory (IMiD) agent (lenalidomide) on selected NHL cell lines. The combination of MT-3724 with all agents demonstrated additive or synergistic cytotoxicity of NHL cell lines. The single agent clinical activity of MT-3724 in heavily pre-treated R/R NHL patients along with this preclinical combinatorial effect of MT-3724 with chemotherapy and IMiDs used in the treatment of R/R NHL have lead the opening of a Phase 2a study of MT-3724 in combination with Gemcitabine and oxaliplatin (GEMOX, NCT03488251) and another planned Phase 2a study of MT-3724 in combination with lenalidomide (NCT03645395). MT-3724 has demonstrated good tolerability and early signs of clinical activity as monotherapy in patients with R/R NHL along with additive and/or synergistic effects in combination with chemotherapy and IMiDs preclinically. Additional clinical studies to evaluate MT-3724 as single agent and in combination with GEMOX or lenalidomide are underway. Citation Format: Jack P. Higgins, Aimee Iberg, Caleigh Howard, Erin Willert. Combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin's lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2060.
The Behavior of Arsenic in a Rotary Kiln Incinerator (1992)

A research test program which focused on the partitioning of environmentally sensitive metals that resulted from controlled incineration of multi-contaminated soils (organics and metals) was carried out at the U.S. Environmental Protection Agency's (EPA) Incineration Research Facility (IRF). A synthetic matrix and an actual Superfund soil were the systems from which the partitioning of arsenic was measured. Incineration variables of kiln exit temperature, afterburner exit temperature, chlorine content and initial arsenic concentration were tested. The amount of arsenic partitioned to the ash was found to be dependent on kiln temperature, but independent of afterburner exit temperature and feed chlorine content. A distinct difference in arsenic volatility was observed between the different soil matrices, and the TCLP values for arsenic in the kiln ash of the Superfund soil was affected by the combustion conditions.
Effect of Processing on the Phytochemical Profiles and Antioxidant Activity of Corn for Production of Masa, Tortillas, and Tortilla Chips (2007)

The phytochemical profiles (total phenolics, anthocyanins, ferulic acid, carotenoids) and antioxidant activities of five types of corn (white, yellow, high carotenoid, blue, and red) processed into masa, tortillas, and tortilla chips were studied. The nixtamalization process significantly (p < 0.05) reduced total phenolics and antioxidant activities when compared to raw grains. Nixtamalized grains exhibited higher concentration of free phenolics and soluble conjugated ferulic acid and had lower concentrations of bound phenolics and ferulic acid than unprocessed grains. Among processed products, there was little difference in the phytochemical contents and antioxidant activities. Among types of corn, the highest concentrations of total phenolics, ferulic acid, and antioxidant activity were observed in the high-carotenoid genotype followed by the regular yellow counterpart. The white corn contained the lowest amount of total phenolics and antioxidant activity. The pigmented blue corn had the highest anthocyanin concentration followed by the red counterpart. These findings suggest that lime-cooking significantly reduced the phytochemical content of nixtamalized products but released phenolics and ferulic acid.
Evidence for involvement of ICAM-1 and VCAM-1 in lymphocyte interaction with endothelium in experimental autoimmune encephalomyelitis in the central nervous system in the SJL/J mouse. (1994)

We have investigated the expression of vascular adhesion molecules during the first stage of chronic inflammation in experimental autoimmune encephalomyelitis in the SJL/J mouse. Immunocytochemical analysis of frozen sections of inflamed versus noninflamed brains and spinal cords showed that the vascular endothelium in brains and spinal cords from diseased animals expressed high levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) but no detectable mucosal addressin or peripheral lymph node addressin. In frozen section assays, anti-alpha 4 integrin and anti-VCAM-1 monoclonal antibodies inhibited binding of mouse peripheral lymphocytes to inflamed brains at both 4 C and 20 C. Antilymphocyte function-associated antigen-1 and anti-ICAM-1 monoclonal antibodies inhibited binding of mouse peripheral lymphocytes to inflamed brains at 20 C. These results are consistent with an important role for the vascular adhesion molecules VCAM-1 and ICAM-1 and for their lymphocytes receptors in lymphocyte recruitment to the central nervous system.
Clinical Studies with Anticoagulants to Improve Survival in Cancer Patients (2007)

Cancer is linked with hypercoagulability and risk of thrombosis and this close association was recognized by Armand Trousseau in 1865. The relation between cancer and blood coagulation is reciprocal: cancer induces a hypercoagulable state and predisposes to thrombosis and activation of platelets, blood coagulation and fibrinolysis interfere with tumor cell biology, tumor growth, angiogenesis and metastatic process. In the present article, we analyze the clinical trials which assessed the influence of anticoagulant treatment on the survival of patients with cancer. The available data show that low-molecular-weight heparins (LMWHs) tend to be more effective and safer than vitamin K antagonists (VKA) in improving survival in patients with cancer. The beneficial effect of anticoagulation with either LMWHs or VKA is not universal for all patients with cancer. There are some histological types of cancers which, at early stages, appear to be more sensitive than others to the effect of anticoagulant treatment. The available clinical trials, although limited, are encouraging for the beneficial effect of anticoagulant treatment on the survival of cancer patients. More clinical trials are needed, targeting groups of patients homogenous regarding the type of cancer, the stage of the disease and life expectancy. The forthcoming clinical trials have to address some issues regarding the optimal dose, the timing and the duration of treatment with LMWH in relation to chemotherapy or other anticancer therapies.
Tumor-specific peptide vaccination in newly-diagnosed patients with GBM (2006)

2529 Background: Despite multimodality approaches, survival with GBM is dismal. Induction of immune responses to suppress the infiltrative, residual component with an easily manufactured and administered immunotherapy has been a theoretical ideal. The epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific cell surface protein expressed on approximately 40% of GBMs. Methods: Newly-diagnosed GBM patients with a gross-total resection, a KPS ≥70, and EGFRvIII+, after undergoing radiation with concurrent temozolomide without tumor progression, were eligible to receive EGFRvIII peptide vaccination i.d. with GM-CSF. Primary endpoint was safety. Results: Accrual began in 06/14/2004 and is now complete. 19 patients were enrolled. Median follow-up is 18 months. Toxicity was minimal and without evidence of autoimmunity. Humoral and cellular immune responses were generated. Median TTP from surgery in vaccine-treated patients is 12 months (n = 12), comparing favorably with a historical matched unvaccinated cohort (gross total resection without progression during radiation, KPS≥70, EGFRvIII+) that had a median TTP of 7.1 months (n = 39) (p = 0.0058). These results also compared favorably with those reported for concurrent temozolomide and radiation followed by adjuvant temozolomide, with a median TTP of 6.9 months. Median survival in this trial has exceeded 18 months which compares favorably to all published analyses accounting for all known prognostic indicators. Among recurrent tumors evaluated by immunohistochemistry, 100% no longer expressed the EGFRvIII, suggesting immunological activation that eliminated EGFRvIII-expressing cells, as well as one potential mechanism of treatment failure. Conclusions: EGFRvIII peptide vaccination warrants further investigation in a larger randomized clinical trial in patients with EGFRvIII-expressing tumors. No significant financial relationships to disclose.
Millimeter-wave beamforming as an enabling technology for 5G cellular communications: theoretical feasibility and prototype results (2014)

The ever growing traffic explosion in mobile communications has recently drawn increased attention to the large amount of underutilized spectrum in the millimeter-wave frequency bands as a potentially viable solution for achieving tens to hundreds of times more capacity compared to current 4G cellular networks. Historically, mmWave bands were ruled out for cellular usage mainly due to concerns regarding short-range and non-line-of-sight coverage issues. In this article, we present recent results from channel measurement campaigns and the development of advanced algorithms and a prototype, which clearly demonstrate that the mmWave band may indeed be a worthy candidate for next generation (5G) cellular systems. The results of channel measurements carried out in both the United States and Korea are summarized along with the actual free space propagation measurements in an anechoic chamber. Then a novel hybrid beamforming scheme and its link- and system-level simulation results are presented. Finally, recent results from our mmWave prototyping efforts along with indoor and outdoor test results are described to assert the feasibility of mmWave bands for cellular usage.
Genetically modified T cells in cancer therapy: opportunities and challenges (2015)

Tumours use many strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated in particular by the successful use of genetically modified T cells to treat B cell haematological malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cell immunotherapy to many patients with different tumour types remain. These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies.
Coagulopathy as a predictor of outcome in meningococcal sepsis and the systemic inflammatory response syndrome with purpura (1993)

We conclude that: a) outcome of pediatric patients with meningococcal sepsis or the systemic inflammatory response syndrome with purpura can be predicted rapidly, more easily, and with overall accuracy superior to classical prognostication strategies by the simple presence or absence of coagulopathy; b) when applied to a contemporary population, classical prognostication strategies lack value for prediction of mortality, yet remain valid for prediction of "poor outcome" (significant morbidity + mortality); c) when evaluating treatment strategies for such patients, the presence of serious coagulopathy may potentially be useful as an index of illness severity.
Splicing graphs and EST assembly problem (2002)

We introduce the notion of the splicing graph that is a natural and convenient representation of all splicing variants. The key difference with the existing approaches is that we abandon the linear (sequence) representation of each transcript and replace it with a graph representation where each transcript corresponds to a path in the graph. We further design an algorithm to assemble EST reads into the splicing graph rather than assembling them into each splicing variant in a case-by-case fashion.
Über Pterinchemie. 60. vorläufige Mitteilung [1]. Eine neue, regiospezifische Synthese von L‐Biopterin (1977)

A new, regiospecific synthesis of L ‐biopterine Pure L ‐biopterine (I) is obtained in 35–40% yield by condensation of 5‐desoxy‐ L ‐arabinose‐hydrazone acetate with 2,4,5‐triamino‐6‐hydroxy‐pyrimidine, followed by oxidation of the formed tetrahydro‐derivative and deacetylation of the L ‐bioterine diacetate. Catalytic reduction of the L ‐biopterine gives the expected mixture of two diastereomeric tetrahydro‐ L ‐biopterines.
Activation of cultured vascular endothelial cells by antiphospholipid antibodies. (1995)

Circulating antiphospholipid antibodies (aPL) are associated with a syndrome of thrombosis, recurrent fetal loss, and thrombocytopenia. We have demonstrated the activation of cultured human umbilical vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation of HUVEC for 4 h with purified IgG (100 micrograms/ml) from patients with high-titer aCL induced a 2.3-fold increase in monocyte adhesion over that seen in HUVEC incubated with IgG's from normal subjects. The effect of aCL was not attributable to LPS contamination, Fc receptors, or immune complexes. Monocyte adhesion was not induced when the aCL were added in serum-free media but was restored by the addition of purified beta 2GP1, previously described as a necessary cofactor for aCL reactivity. Purified rabbit polyclonal IgG raised against beta 2GP1 also induced monocyte adhesion when incubated with HUVEC. Preadsorption of patient serum with cardiolipin reduced monocyte adhesion by 60%. Immunofluorescent microscopy demonstrated that endothelial cells incubated with patient IgG expressed cell adhesion molecules, including E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1. These data support the hypothesis that aPL activate vascular endothelial cells, thereby leading to a pro-thrombotic state.
Targeting ion channels for drug discovery. (2010)

Ion channels are important therapeutic targets which are modulated by a range of currently prescribed drugs. Most of these were developed empirically by traditional pharmacology without knowing their precise target, and the discovery of novel ion channel drugs by high-throughput molecular approaches has proven challenging. A key stumbling-block has been the development of biologically relevant assays with the capacity for randomly screening sizeable compound libraries. While various screening formats exist, e.g., using ion- or voltage-sensitive fluorescent dyes, these lack the precision, temporal resolution, and voltage control normally required for monitoring channel modulation. On the other hand, traditional electrophysiology is too slow, technically demanding, and labor intensive for primary screening. Recently, these limitations have been addressed by the development of automated electrophysiology instruments. While retaining much of the fidelity and precision of electrophysiology, these systems also address the main disadvantages by using automation to increase throughput and "de-skill" the process. Though the capacities currently attainable are not yet compatible with primary screening, these instruments are nevertheless having a significant impact on drug discovery. By providing high quality, information-rich assays for medium-throughput secondary screening, these instruments bridge significant gaps that, historically, have hampered the early ion channel drug discovery pipeline.
Inflammatory bowel disease and airway diseases (2016)

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.
Cryptic plasmids of Mycobacterium avium: Tn552 to the rescue (2002)

Plasmids have been described in almost all bacterial species analysed and have proven to be essential genetic tools. In many bacteria these extrachromosomal DNAs are cryptic with no known markers or function, which makes their characterization and genetic exploitation extremely difficult. Here we describe a system that will allow the rescue of any circular DNA (plasmid or phage) using an in vitro transposition system to deliver both a selectable marker (kanamycin) and an Escherichia coli plasmid origin of replication. In this study, we demonstrate the rescue of four cryptic plasmids from the opportunistic pathogen Mycobacterium avium. To evaluate the host range of the rescued plasmids, we have examined their ability to be propagated in Mycobacterium smegmatis and Mycobacterium bovis BCG, and their compatibility with other mycobacterial plasmids. In addition, we use a library of transposon insertions to sequence one plasmid, pVT2, and to begin a genetic analysis of plasmid genes. Using this approach, we identified a putative conjugative relaxase, suggesting this myco-bacterial plasmid is transferable, and three genes required for plasmid establishment and replication.
Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. (1994)

We tested the hypothesis that pulmonary surfactant-associated lectins--surfactant proteins A and D (SP-A, and -D)--contribute to initial protective mechanisms against influenza A viruses (IAVs). SP-D potently inhibited hemagglutination activity of several strains of IAV as well as causing viral aggregation. SP-D enhanced neutrophil binding of IAV and neutrophil respiratory burst responses to the virus. Neutrophil dysfunction resulting from IAV exposure was diminished when the virus was pre-incubated with SP-D. Each of these effects was mediated by the calcium-dependent carbohydrate-binding property of SP-D. Native SP-D preparations of both human and rat origin, as well as recombinant rat SP-D, had similar activity. SP-A also inhibited IAV hemagglutination activity. We have previously reported that related mammalian serum lectins (mannose-binding lectin [MBL] and conglutinin) have similar effects. SP-D was at least 10-fold more potent at causing hemagglutination inhibition than were SP-A or MBL. SP-D was shown to contribute to potent anti-IAV activity of human bronchoalveolar lavage fluid. These results suggest that SP-D--alone, and in conjunction with SP-A and phagocytic cells--constitutes an important component of the natural immune response to IAV infection within the respiratory tract.
LED-Based Projection Systems (2007)

A novel design methodology for LED-array-based projection displays has been developed. By combining etendue limitation, system intensity, and efficiency requirements, a novel parameter space is proposed. Using this parameter space, LED lens-array and compound parabolic concentrator (CPC)-array illumination systems have been designed. A 1000-lm LED light source is built. Based on these lens-array and CPC-array illuminators, several LED-based liquid crystal on silicon (LCOS) projection systems are suggested. Among them, a one-panel LCOS projection system is proposed and tested. The method discussed here should be useful in the design of LED-array illumination systems for projectors in general.
A Novel Schlemm's Canal Scaffold Increases Outflow Facility in a Human Anterior Segment Perfusion Model (2012)

The Hydrus Microstent provided an effective way to increase outflow facility in human eyes ex vivo.
Molecular Inversion Probe Assay for Allelic Quantitation (2009)

Molecular inversion probe (MIP) technology has been demonstrated to be a robust platform for large-scale dual genotyping and copy number analysis. Applications in human genomic and genetic studies include the possibility of running dual germline genotyping and combined copy number variation ascertainment. MIPs analyze large numbers of specific genetic target sequences in parallel, relying on interrogation of a barcode tag, rather than direct hybridization of genomic DNA to an array. The MIP approach does not replace, but is complementary to many of the copy number technologies being performed today. Some specific advantages of MIP technology include: less DNA required (37 ng vs. 250 ng), DNA quality less important, more dynamic range (amplifications detected up to copy number 60), allele-specific information "cleaner" (less SNP cross-talk/contamination), and quality of markers better (fewer individual MIPs versus SNPs needed to identify copy number changes). MIPs can be considered a candidate gene (targeted whole genome) approach and can find specific areas of interest that otherwise may be missed with other methods.