gebhart/patrepeval huggingface dataset:
CD19 Antigen in Leukemia and Lymphoma Diagnosis and Immunotherapy (1995)

The CD19 antigen plays an important role in clinical oncology. In normal cells, it is the most ubiquitously expressed protein in the B lymphocyte lineage. CD19 expression is induced at the point of B lineage commitment during the differentiation of the hematopoietic stem cell, and its expression continues through preB and mature B cell differentiation until it is finally down-regulated during terminal differentiation into plasma cells. CD19 expression is maintained in B-lineage cells that have undergone neoplastic transformation, and therefore CD19 is useful in diagnosis of leukemias and lymphomas using monoclonal antibodies (mAbs) and flow cytometry. Interestingly, CD19 is also expressed in a subset of acute myelogenous leukemias (AMLs) indicating the close relationship between the lymphoid and myeloid lineages. Because B lineage leukemias and lymphomas rarely lose CD19 expression, and because it is not expressed in the pluripotent stem cell, it has become the target for a variety of immunotherapeutic agents, including immunotoxins. Treatment of non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL) with anti-CD19 mAbs coupled to biological toxins has proven to be effective in vitro and in animal models, and has shown some promising results in Phase I clinical trials. Recently, the analysis of anti-CD19 effects on lymphoma cell growth has highlighted a novel mechanism of immunotherapy. Engagement of cell surface receptors like CD19 by mAbs can have anti-tumor effects by the activation of signal transduction pathways which control cell cycle progression and programmed cell death (apoptosis).
Phase 1 pharmacokinetic and pharmacodynamic trial of docetaxel and 17AAG (17-allylamino-17-demethoxygeldanamycin) (2004)

3032 Background: 17AAG is an ansamycin antibiotic that binds to the Hsp90 chaperone protein and inhibits its function. Hsp90 is required for the refolding of proteins during cellular stress and the conformational maturation of a subset of signaling proteins. Treatment of cancer cells with 17AAG causes the proteasomal degradation of Hsp90 client proteins, which include HER2, steroid receptors, Raf, cdk4, and Akt. The combination of 17AAG and taxanes is synergistic in cell culture and animal model systems. Methods: We initiated a phase 1 study of docetaxel and 17AAG to define the maximally tolerated dose, toxicity profile, and pharmacodynamics of these agents when administered in combination to patients (pts) with advanced solid tumors. Pts were treated with docetaxel (55 and 70 mg/m2) and 17AAG (80 to 300 mg/m2) in 6 cohorts. Docetaxel and 17AAG were administered sequentially (each over 1 hour) without delay on day 1 of each 21 day cycle. Results: To date, we have enrolled 16 pts (median age 61, range: 32–78) with cancers of the prostate (5), H&N (4), renal (2), melanoma (1) and others (4 pts). Pts have received a median of 3 cycles (range: 2–6). No dose limiting toxicities have been observed to date. Three pts had Grade 4 neutropenia of less than 7 days duration. No objective responses have been seen. Three pts had stable disease of at least 3 cycles duration and one pt with prostate cancer had a decline in PSA. Plasma serum levels of docetaxel and 17AAG were not altered by co-administration at the dose levels studied. Peripheral blood lymphocytes (PBL) were collected to study changes in Hsp90-dependent client proteins following therapy as a function of dose. Post-treatment increases in Hsp70 in PBL have been observed in all pts treated with 17-AAG at or above 110 mg/m2. Declines in Raf and Akt in PBL have been seen in some but not all pts treated at doses of 17-AAG above 160 mg/m2. Conclusions: The combination of docetaxel and 17AAG is well tolerated at the dose levels studied to date. Accrual continues at the 17AAG 300 mg/m2 dose level and at the time of the meeting updated accrual, response and correlative data will be reported. Supported by NIH P50-CA92629 and CaPCURE. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Conforma Aventis
The detection of DNA using a silicon nanopore (2004)

We have developed a novel strategy for producing nanopores in inorganic, CMOS-compatible membranes using a tightly focused, high energy electron beam. We are able to characterize the nanopores physically (TEM, AFM) as well as electrically (ionic conductivity and "wetting" curves). Subsequently, we used the nanopore as a molecular Coulter counter to detect the size of a DNA molecule. This is the first report of the use of an inorganic nanopore for discriminating DNA molecules.
FAB: Flash-Aware Buffer Management Policy for Portable Media Players (2006)

This paper presents a novel buffer management scheme for portable media players equipped with flash memory. Though flash memory has various advantages over magnetic disks such as small and lightweight form factor, solid-state reliability, low power consumption, and shock resistance, its physical characteristics imposes several limitations. Most notably, it takes relatively long time to write data in flash memory and the data cannot be overwritten before being erased first. Since an erase operation is performed as a unit of larger block, the employed strategy for mapping logical blocks onto physical pages affects real performance of flash memory. This article suggests a flash-aware buffer management scheme that reduces the number of erase operations by selecting a victim based on its page utilization rather than based on the traditional LRU policy. Our scheme effectively minimizes the number of write and erase operations in flash memory, reducing the total execution time by 17% compared to the LRU policy.
Removal of metal ions from wood chips during acidic leaching 2: Modeling leaching of calcium ions from softwood chips (2006)

Article Removal of metal ions from wood chips during acidic leaching 2: Modeling leaching of calcium ions from softwood chips was published on November 1, 2006 in the journal Nordic Pulp & Paper Research Journal (volume 21, issue 4).
Reconstitution of apo‐porphobilinogen deaminase: Structural changes induced by cofactor binding (1989)

Expression of porphobilinogen deaminase in a hemB- strain of E. coli has permitted the isolation of the apoenzyme, i.e. deaminase lacking the porphobilinogen-derived dipyrromethane cofactor. Incubation of purified apoenzyme with porphobilinogen resulted in reconstitution of the covalently attached dipyrromethane cofactor, indicating no additional cofactors or enzymes are required for biosynthesis of holoenzyme. Electrophoretic and 13C-NMR spectroscopic analyses demonstrate that the apoenzyme exists in a conformationally unstable form which is converted to a highly stable tertiary structure on covalent attachment of the dipyrromethane cofactor.
Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells (2006)

The role of innate immune recognition by intestinal epithelial cells (IECs) in vivo is ill-defined. Here, we used highly enriched primary IECs to analyze Toll-like receptor (TLR) signaling and mechanisms that prevent inappropriate stimulation by the colonizing microflora. Although the lipopolysaccharide (LPS) receptor complex TLR4/MD-2 was present in fetal, neonatal, and adult IECs, LPS-induced nuclear factor kappaB (NF-kappaB) activation and chemokine (macrophage inflammatory protein 2 [MIP-2]) secretion was only detected in fetal IECs. Fetal intestinal macrophages, in contrast, were constitutively nonresponsive to LPS. Acquisition of LPS resistance was paralleled by a spontaneous activation of IECs shortly after birth as illustrated by phosphorylation of IkappaB-alpha and nuclear translocation of NF-kappaB p65 in situ as well as transcriptional activation of MIP-2. Importantly, the spontaneous IEC activation occurred in vaginally born mice but not in neonates delivered by Caesarean section or in TLR4-deficient mice, which together with local endotoxin measurements identified LPS as stimulatory agent. The postnatal loss of LPS responsiveness of IECs was associated with a posttranscriptional down-regulation of the interleukin 1 receptor-associated kinase 1, which was essential for epithelial TLR4 signaling in vitro. Thus, unlike intestinal macrophages, IECs acquire TLR tolerance immediately after birth by exposure to exogenous endotoxin to facilitate microbial colonization and the development of a stable intestinal host-microbe homeostasis.
Pupillary responses index cognitive resource limitations (1996)

Cognitive task-evoked pupillary responses reliably index information-processing loads. However, previous studies have reported inconsistent findings regarding the nature of the pupillary response when processing demands approach or exceed available processing resources. This condition was examined in 22 normal undergraduates by using pupillometric recordings during a digit span recall task, with 5 (low load), 9 (moderate load), and 13 (excessive load) digits per string. Pupillary responses increased systematically with increased processing load (to-be-recalled digits) until the limit of available resources (memory capacity of 7 +/- 2 digits), when they reached asymptote and then declined with resource overload (> 9 digits). These findings suggest that pupillary responses increase systematically with increased processing demands that are below resource limits, change little during active processing at or near resource limits, and begin to decline when processing demands exceed available resources.
Digital tomosynthesis (DTS) for verification of target position in early stage lung cancer patients (2013)

Short-arc DTS verification of time averaged lung tumor position is feasible using free-breathing kV projection data and the AvIP of the 4DCT as a reference. Observed differences between DTS and online CBCT registration with AvIP were ≤3 mm (mean + 2 SD), however, the increased temporal resolution of DTS + triangulation also identified short period deviations from the average target position on the CBCT. Short-arc DTS appears promising for intrafraction tumor position monitoring during stereotactic lung radiotherapy delivered with a rotational technique.
Clinical results using biochemotherapy as a standard of care in advanced melanoma (2002)

Phase II studies of biochemotherapy in metastatic melanoma patients have reported response rates of 47-63%. Even though these were highly selected patients, we were intrigued by these promising response rates and began using this regimen as standard care in advanced melanoma patients. We report the results of the first 65 patients with AJCC stage IV melanoma (n = 57) or unresectable stage III (n = 8) melanoma treated with concurrent biochemotherapy at Memorial Hospital. Treatment was repeated every 3 weeks and patients were assessed for antitumour effects after every other cycle. The overall response rate among the 63 patients evaluable for response was 29% (three complete responses, 15 partial responses). The median duration of responses was 3.7 months. The response rate among previously treated and previously untreated patients was 6% and 38%, respectively. The estimated median survival for all patients was 8.5 months; the median survival for previously untreated patients was 9.2 months. Tumour response did not correlate with survival. Our experience, which is a retrospective evaluation, does not provide support for the routine use of biochemotherapy as standard treatment. The low response rate among previously treated patients indicates that biochemotherapy is not useful as second-line therapy.
Combinatorial Libraries: Studies in Molecular Recognition and the Quest for New Catalysts (1997)

Abstract Combinatorial libraries offer a new powerful tool for gathering empirical information about host/guest interactions and for developing catalysts for organic reactions. Combinatorial approaches to molecular recognition are discussed, i.e. screening of libraries of ligands with synthetic receptors and libraries of synthetic receptors with the ligands for which selective binding is desired. Recent achievements in the development of new catalysts for organic synthesis using combinatorial approaches are also reviewed.
Neurogenesis in the Diseased Adult Human Brain: New Therapeutic Strategies for Neurodegenerative Diseases (2003)

No abstract available.
Biochemical and Molecular Characterization of a Novel Choline-specific Glycerophosphodiester Phosphodiesterase Belonging to the Nucleotide Pyrophosphatase/Phosphodiesterase Family (2005)

Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that release nucleoside 5'-monophosphate from a variety of nucleotides and nucleotide derivatives. The mammalian NPP family comprises seven members, but only three of these (NPP1-3) have been studied in some detail. Previously we showed that lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid, is identical to NPP2. More recently an uncharacterized novel NPP member (NPP7) was shown to have alkaline sphingomyelinase activity. These findings raised the possibility that other members of the NPP family act on phospholipids. Here we show that the sixth member of the NPP family, NPP6, is a choline-specific glycerophosphodiester phosphodiesterase. The sequence of NPP6 encodes a transmembrane protein containing an NPP domain with significant homology to NPP4, NPP5, and NPP7/alkaline sphingomyelinase. When expressed in HeLa cells, NPP6 was detected in both the cells and the cell culture medium as judged by Western blotting and by enzymatic activity. Recombinant NPP6 efficiently hydrolyzed the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine, but not the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'-monophosphate. In addition, NPP6 hydrolyzed LPC to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. NPP6 showed a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. It also hydrolyzed glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. In mice, NPP6 mRNA was predominantly detected in kidney with a lesser expression in brain and heart, and in human it was detected in kidney and brain. The present results suggest that NPP6 has a specific role through the hydrolysis of polyunsaturated LPC, glycerophosphorylcholine, or sphingosylphosphorylcholine in these organs.
Expanding the design horizon of antisense oligonucleotides with alpha-L-LNA (2003)

Oligonucleotides containing Locked Nucleic Acids (LNA) to various extents and at various positions were evaluated for antisense activity, RNase H recruitment, nuclease stability and thermal affinity. In this work, two different diastereoisomers of LNA were studied: the beta-D-LNA and the alpha-L-LNA (abbreviated as beta-D-LNA and alpha-L-LNA). Our findings show that the best antisense activity with 16mer gapmers containing beta-D-LNA (oligonucleotides containing consecutive segments of LNA and DNA with a central DNA stretch flanked by two LNA segments, LNA-DNA-LNA) is found with gap sizes between 7 and 10 nt. The optimal gap size is motif-dependent, and requires the right balance between gap size and affinity. Compared to beta-D-LNA, alpha-L-LNA shows superior stability against a 3'-exonuclease. The design possibilities of alpha-L-LNA were explored for different gapmers and other designs, collectively called chimeras. The placement of alpha-L-LNA in the junctions or in the flanks resulted in potent antisense oligonucleotides. Moreover, different chimeras with an alternate composition of DNA, alpha-L-LNA and beta-D-LNA were evaluated in terms of antisense activity and RNase H recruitment. Chimeras with an interrupted DNA stretch with alpha-L-LNA still recruit RNase H and show good levels of antisense activity, while the same design with beta-D-LNA results in a drop in antisense potency. Our findings indicate that alpha-L-LNA is a powerful and versatile nucleotide analogue for designing potent antisense oligonucleotides.
Abstract P4-15-17: A novel targeted engineered toxin body for treatment of HER2 positive breast cancer (2015)

Abstract The HER2 receptor is overexpressed in 20-30% of breast cancers. HER2 overexpression in breast cancer has been successfully targeted by both antibody and antibody-drug conjugate (ADC) approaches. The recently approved trastuzumab-emtansine (T-DM1, Kadcyla) ADC has shown promising clinical results in patients refractory to trastuzumab (Herceptin). Because DM1 is a chemotherapeutic and refractory breast cancer patients have typically progressed through several rounds of chemotherapy, we are developing a new targeted therapy approach utilizing a novel mechanism of action. MT-2H74 is an engineered toxin body comprised of the trastuzumab single chain variable fragment (scFv) and a modified ribosome-inactivating protein derived from Shiga-like toxin 1 A (SLT-1A). We have proprietarily modified SLT-1A for reduced immunogenic potential and increased stability. MT-2H74 selectively binds HER2-expressing breast cancer cells, and exerts a potent HER2-specific cytotoxic effect on several tested cell lines. MT-2H74 demonstrates effective cell kill at picomolar concentrations on cell lines expressing high levels of HER2 and is not cytotoxic to HER2 negative control cell lines. Multi-drug resistance transporter 1 (MDR1) has been reported to confer resistance to chemotherapeutic and ADC treatments, such as direct T-DM1 cell kill; however, MT-2H74 displays cytotoxic activity against HER2 transfected NCI/ADR-RES cells known to express MDR1. Murine models are under investigation to determine therapeutic efficacy in vivo. MT-2H74 is a promising HER2-targeted therapeutic agent against breast carcinomas with a unique mechanism of action and is currently under further development. Citation Format: Erin K Willert, Sangeetha Rajagopalan, Garrett L Robinson, Brigitte Brieschke, Jennifer Erdman, William Null, Jack P Higgins. A novel targeted engineered toxin body for treatment of HER2 positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-17.
Combinational profiles of sequential benchmark circuits (2003)

A set of 31 digital sequential circuits described at the gate level is presented. These circuits extend the size and complexity of the ISCAS'85 set of combinational circuits and can serve as benchmarks for researchers interested in sequential test generation, scan-based test generation, and mixed sequential/scan-based test generation using partial scan techniques. Although all the benchmark circuits are sequential, synchronous, and use only D-type flip-flops, additional interior faults and asynchronous behavior can be introduced by substituting for some or all of the flip-flops their appropriate functional models. The standard functional model of the D flip-flop provides a reference point that is independent of the faults particular to the flip-flop implementation. A testability profile of the benchmarks in the full-scan-mode configuration is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Loss of expression of transforming growth factor beta in skin and skin tumors is associated with hyperproliferation and a high risk for malignant conversion. (1993)

Mouse skin carcinomas arise from a small subpopulation of benign papillomas with an increased risk of malignant conversion. These papillomas arise with limited stimulation by tumor promoters, appear rapidly, and do not regress, suggesting that they differ in growth properties from the majority of benign tumors. The transforming growth factor beta (TGF-beta) proteins are expressed in the epidermis and are growth inhibitors for mouse keratinocytes in vitro; altered TGF-beta expression could influence the growth properties of high-risk papillomas. Normal epidermis, tumor promoter-treated epidermis, and skin papillomas at low risk for malignant conversion express TGF-beta 1 in the basal cell compartment and TGF-beta 2 in the suprabasal strata. In low-risk tumors, 90% of the proliferating cells are confined to the basal compartment. In contrast, the majority of high-risk papillomas are devoid of both TGF-beta 1 and TGF-beta 2 as soon as they arise; these tumors have up to 40% of the proliferating cells in the suprabasal layers. Squamous cell carcinomas are also devoid of TGF-beta, suggesting that they arise from the TGF-beta-deficient high-risk papillomas. In some high-risk papillomas, TGF-beta 1 loss can occur first and correlates with basal cell hyperproliferation, while TGF-beta 2 loss correlates with suprabasal hyperproliferation. Similarly, TGF-beta 1-null transgenic mice, which express wild-type levels of TGF-beta 2 in epidermis but no TGF-beta 1 in the basal layer, have a hyperproliferative basal cell layer without suprabasal proliferation. In tumors, loss of TGF-beta is controlled at the posttranscriptional level and is associated with expression of keratin 13, a documented marker of malignant progression. These results show that TGF-beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression.
Monoclonal Antibodies Inducing Conformational Changes on the Antigen Molecule (2003)

Monoclonal antibodies (MoAbs) are extensively used as biological tools because of their invariable specificity. However, the interpretation of results can be misled by the behaviour of MoAb displaying allosteric effects, i.e. long-range conformational changes on the antigen (Ag). It has been shown that some MoAbs are able to modify the spatial structure of the corresponding protein Ag, affecting in this way its biological activity as well as its binding to a second MoAb. Thus, a researcher using a MoAb as a tool to investigate some features of an antigenic molecule must be aware of the possible positive or negative allosteric properties of the antibody.
Practical Application of Real-Time Expert System for Automatic Well Control (1990)

ABSTRACT Expert systems are receiving widespread interest in many fields. One critical application in the drilling industry that is ideally suited to use this technology is automated well control. In some drilling situations, particularly slim hole drilling, the reaction time between detection of a kick and the need to take corrective action may be only a fraction of a minute. In this application, a significant amount of data must, be continuously collected, processed, and analyzed in a short period of time. Expert systems can automate these functions. This paper describes the design, development, and testing of an expert system for well control (XWC) on a slim hole drilling rig. The use of an expert system operating in real time to perform complex analysis of the drilling data from rig sensors can significantly reduce false alarm rates as well as the probability of a small kick developing into an uncontrolled situation. The system is unique in several ways. First, it operates in real time. It samples flow in, flow out, and other parameters, processes the data, and transfers the information to the expert system. Second, the system can be classified as a true hybrid system in that extensive algorithmic calculations and models are incorporated where necessary. Finally, the entire system has been validated in a test well.