gebhart/patrepeval huggingface dataset:
CD38 as a Therapeutic Target (2006)

The CD38 molecule is well represented on cell surfaces in many cases of a variety of lymphoid tumors, notably multiple myeloma, AIDS-associated lymphomas, and post-transplant lymphoproliferations. As such, this molecule is a promising target for antibody therapy. After early disappointments, improved anti-CD38 antibodies of strong cytolytic potential have been described by 3 groups. First, a human IgG monoclonal anti-CD38 antibody raised in mice transgenic for human Ig has been found to induce potent complement and cellular cytotoxicities against both myeloma cell lines and fresh harvests from myeloma marrow and leukemic blood. This antibody also exhibits the singular property of inhibiting the CD38 cyclase activity. Second, a series of CD38-specific human antibodies, with high affinities and high ADCC activities against cell lines and primary cultures of myeloma, has been selected from a unique phage-display library. Finally, to enhance specificity for myeloma cells, bispecific domain antibodies targeting both CD38 and CD138 have been developed. As they lack any Fc module, these constructs rely on cytotoxicity for delivering a toxin to tumor cells. The list of candidate CD38-bearing neoplasms as targets for these antibody constructs can now be expanded to include acute promyelocytic leukemia, and possibly other myeloid leukemias, in which surface CD38 can be induced by retinoid treatment. One caveat here is that evidence has been produced to suggest that CD38 promotes pulmonary manifestations of the hazardous retinoic acid syndrome.
Toward measuring visualization insight (2006)

Recent visualization research literature has paid an increasing amount of attention to evaluating visualizations. It seems an appropriate time to reopen the question about what the ultimate purpose of visualization is and how it should be evaluated. One potential claim is: the purpose of visualization is insight. The purpose of visualization evaluation is to determine to what degree visualizations achieve this purpose. If this claim is true, then evaluating visualizations should seek to determine how well visualizations generate insight. Measuring insight would enable the direct comparison of visualization design alternatives, or the comparison against an insight goal. This article examines the capability of the controlled experiment method to measure insight
<title>Wavefront estimation in the human breast</title> (2001)

We acquired conventional and harmonic channel r.f. ultrasound echo data using a 3x80 element, 8.5 MHz multirow array from the breasts of eight volunteers. The data acquisition was interleaved to allow direct comparison normal and harmonic echo wavefronts. Harmonic imaging data was acquired using the pulse inversion technique. Data was acquired form extended regions of interest (25 mm deep, 10 mm wide). Time shift estimates from pairs of elements were combined using a weighted least squares algorithm to obtain a wavefront arrival time error estimate. Low spatial frequencies dominated most of the wavefront estimates, and many had a curvature suggesting a gross sound speed error. Wavefront estimates were often stable over lateral translations of a few millimeters, although they often changed significantly with range, particularly at tissue boundaries observed in the B-mode image. Averaging wavefront estimates over range yielded phase aberration estimates that generally improved image quality. We measured relatively small wavefront arrival errors with both conventional (22.9 +/- 7.6 ns r.m.s.) And harmonic (22.8 +/- 8.8 ns r.m.s.) echoes. For any particular measurement, the difference between conventional and harmonic wavefront estimates was small (0 +/- 4.5 ns r.m.s.). Our measurements suggest relatively mild phase aberrations in the breast, although they may be more significant for higher frequency transducers and deeper imaging depths.
Undecylenic acid in the treatment of psoriasis and neurodermatitis. (1951)

Undecylenic acid in a dosage tolerated by most patients is of doubtful value in the treatment of psoriasis and neurodermatitis.Thirty-one patients were given the drug. Exudative dermatitis developed in one case, generalized pruritus in another. One patient may have had a cardiac accident attributable to the drug.
OFDM Mobile Packet Transmission System with Multiuser Detection and Metric Combining ARQ (2005)

This paper proposes an OFDM mobile packet transmission scheme that increases throughput by using nonlinear multiuser detection (MUD) and automatic repeat request (ARQ) with metric-combining. The scheme identifies users by detecting user identification (ID) symbols located at the head of a packet, and can separate packets that have collided by using MUD. It also forces the respective transmitters to retransmit the same packets so as to reproduce the collision if the cyclic redundancy check (CRC) detects some errors, and it uses metric-combining to decrease the number of retransmissions. The results of computer simulations show that the proposed scheme can provide twice the throughput of the conventional schemes.
Efficient regression of general-activity human poses from depth images (2011)

We present a new approach to general-activity human pose estimation from depth images, building on Hough forests. We extend existing techniques in several ways: real time prediction of multiple 3D joints, explicit learning of voting weights, vote compression to allow larger training sets, and a comparison of several decision-tree training objectives. Key aspects of our work include: regression directly from the raw depth image, without the use of an arbitrary intermediate representation; applicability to general motions (not constrained to particular activities) and the ability to localize occluded as well as visible body joints. Experimental results demonstrate that our method produces state of the art results on several data sets including the challenging MSRC-5000 pose estimation test set, at a speed of about 200 frames per second. Results on silhouettes suggest broader applicability to other imaging modalities.
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis (2013)

In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6 expression thus suppresses proliferation by upregulating p16INK4a, providing an internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full tumor-promoting function by enhancing proliferation and stimulating angiogenesis. The finding that CDK6 connects cell-cycle progression to angiogenesis confirms CDK6's central role in hematopoietic malignancies and could underlie the selection pressure to upregulate CDK6 and silence p16INK4a.
Modeling, simulation, and control of flexible manufacturing systems a Petri net approach (1999)

One critical barrier leading to successful implementation of flexible manufacturing and related automated systems is the ever-increasing complexity of their modeling, analysis, simulation, and control. Research and development over the last three decades has provided new theory and graphical tools based on Petri nets and related concepts for the design of such systems. The purpose of this book is to introduce a set of Petri-net-based tools and methods to address a variety of problems associated with the design and implementation of flexible manufacturing systems (FMSs), with several implementation examples.There are three ways this book will directly benefit readers. First, the book will allow engineers and managers who are responsible for the design and implementation of modern manufacturing systems to evaluate Petri nets for applications in their work. Second, it will provide sufficient breadth and depth to allow development of Petri-net-based industrial applications. Third, it will allow the basic Petri net material to be taught to industrial practitioners, students, and academic researchers much more efficiently. This will foster further research and applications of Petri nets in aiding the successful implementation of advanced manufacturing systems
Induction of Apoptosis in BCR/ABL+ Cells By Histone Deacetylase Inhibitors Involves Reciprocal Effects on the RAF/MEK/ERK and JNK Pathways (2003)

Signal transduction events regulating induction of apoptosis by the histone deacetylase inhibitors (HDIs) sodium butyrate (SB) and SAHA have been examined in Bcr/Abl+ human leukemia cells (K562, LAMA 84). Exposure of K562 cells to greater or less than 3.0 mM SB or 3.0 mM SAHA for 24-48 hr resulted in a marked induction of mitchondrial damage (e.g., cytochrome c release) and apoptosis, events associated with downregulation of Bcr/Abl and Raf-1, induction of p21CIP1, inactivation of MEK1/2, ERK1/2, and p70S6K, and a dramatic increase in JNK activation. HDI-mediated apoptosis was attenuated by pharmacologic JNK inhibitors and enhanced by the MEK1/2 inhibitor U0126 as well as by the JNK activator anisomycin. Interestingly, HDI-induced JNK activation was potentiated by pharmacologic MEK inhibition. Furthermore, HDI lethality was significantly diminished in cells ectopically expressing constitutively active MEK1, confirming a functional role for MEK/ERK inactivation in HDI-mediated apoptosis. Similar events were observed in Bcr/Abl+ LAMA 84 cells. Lastly, the free radical scavenger L-N-acetylcysteine (LNAC) attenuated HDI-mediated ROS generation, JNK activation, and apoptosis. Together, these findings support a model in which induction of apoptosis in Bcr/Abl+ cells by HDIs involves coordinate inactivation of the cytoprotective Raf/MEK/ERK pathway in conjunction with the ROS-dependent activation of JNK.
DNA vaccines suppress tumor growth and metastases by the induction of anti‐angiogenesis (2004)

Four novel oral DNA vaccines provide long-lived protection against melanoma, colon, breast, and non-small cell lung carcinoma in mouse model systems. The vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and are directed against targets such as carcinoembryonic antigen, tyrosine-related protein, vascular endothelial growth factor receptor-2 [also called fetal liver kinase-1 (FLK-1)], and transcription factor Fos-related antigen-1 (Fra-1). The FLK-1 and Fra-1 vaccines are effective in suppressing angiogenesis in the tumor vasculature. All four vaccines are capable of inducing potent cell-mediated protective immunity, breaking peripheral T-cell tolerance against these self-antigens resulting in effective suppression of tumor growth and metastasis. It is anticipated that such research efforts will contribute toward the rational design of future DNA vaccines that will be effective for prevention and treatment of human cancer.
The molecular rotations of polycyclic compounds. Part III. Polycyclic alcohols and their derivatives (1954)

W. Klyne and W. M. Stokes, J. Chem. Soc., 1954, 1979 DOI: 10.1039/JR9540001979
Dra-nupC-pdp operon of Bacillus subtilis: nucleotide sequence, induction by deoxyribonucleosides, and transcriptional regulation by the deoR-encoded DeoR repressor protein (1996)

The genes encoding deoxyriboaldolase (dra), nucleoside uptake protein (nupC), and pyrimidine nucleoside sequences were determined. Sequence analysis showed that the genes were localized immediately downstream of the hut operon. Insertional gene disruption studies indicated that the three genes constitute an operon with the gene order dra-nupC-pdp. A promoter mapping immediately upstream of the dra gene was identified, and downstream of the pdp gene the nucleotide sequence indicated the existence of a factor-independent transcription terminator structure. In wild-type cells growing in succinate minimal medium, the pyrimidine nucleoside phosphorylase and deoxyriboaldolase levels were five- to eightfold higher in the presence of thymidine and fourfold higher in the presence of deoxyadenosine. By the use of lacZ fusions, the regulation was found to be at the level of transcription. The operon expression was subject to glucose repression. Upstream of the dra gene an open reading frame of 313 amino acids was identified. Inactivation of this gene led to an approximately 10-fold increase in the levels of deoxyriboaldolase and pyrimidine nucleoside phosphorylase, and no further induction was seen upon the addition of deoxyribonucleosides. The upstream gene most likely encodes the regulator for the dra-nupC-pdp operon and was designated deoR (stands for deoxyribonucleoside regulator).
Industrial‐scale proteomics: From liters of plasma to chemically synthesized proteins (2004)

Human blood plasma is a useful source of proteins associated with both health and disease. Analysis of human blood plasma is a challenge due to the large number of peptides and proteins present and the very wide range of concentrations. In order to identify as many proteins as possible for subsequent comparative studies, we developed an industrial-scale (2.5 liter) approach involving sample pooling for the analysis of smaller proteins (M(r) generally < ca. 40 000 and some fragments of very large proteins). Plasma from healthy males was depleted of abundant proteins (albumin and IgG), then smaller proteins and polypeptides were separated into 12 960 fractions by chromatographic techniques. Analysis of proteins and polypeptides was performed by mass spectrometry prior to and after enzymatic digestion. Thousands of peptide identifications were made, permitting the identification of 502 different proteins and polypeptides from a single pool, 405 of which are listed here. The numbers refer to chromatographically separable polypeptide entities present prior to digestion. Combining results from studies with other plasma pools we have identified over 700 different proteins and polypeptides in plasma. Relatively low abundance proteins such as leptin and ghrelin and peptides such as bradykinin, all invisible to two-dimensional gel technology, were clearly identified. Proteins of interest were synthesized by chemical methods for bioassays. We believe that this is the first time that the small proteins in human blood plasma have been separated and analyzed so extensively.
Factor VIII Fractionation on Aminohexyl Sepharose with Possible Reduction in Hepatitis B Antigen (1982)

The method of factor VIII purification by chromatography on aminohexyl Sepharose has been extended so that up to 100 ml of intermediate purity concentrate can be processed on an 8.6 ml column. The product has a specific activity of 1.8 International Units of factor VIII per mg of protein. Most of the fibrinogen is removed and antibodies to blood group substances A and B are not detectable by haemagglutination techniques. Hepatitis B antigen has been reduced to one sixteenth of that in the starting material, in preliminary experiments. The process has the added advantage that it concentrates the factor VIII relative to the starting material.
Regulation of transcriptional activation of mdm2 gene by p53 in response to UV radiation. (1998)

The mdm2 oncogene is expressed at elevated levels in a variety of human tumors, and its product inactivates the p53 tumor suppressor protein. MDM2 forms an autoregulatory loop with p53, because the mdm2 gene contains a promoter that is responsive to p53. Synthesis of MDM2 protein increases in a p53-dependent manner in response to DNA-damaging agents such as UV light. Although this increase likely results from enhanced transcription, the amount of MDM2 protein does not correspond to the amount of p53 protein in cells exposed to UV light. Here we show that the p53-specific internal promoter in the mdm2 gene is induced after exposure to UV light, whereas the upstream constitutive promoter is not induced. The amount of the mdm2 transcript does not parallel the ability of p53 to bind DNA, indicating that transcription is regulated at a step distinct from activation of the DNA-binding function of p53.
Controle de Constitucionalidade das Leis: uma visão geral (2005)

This research was done with the objective of showing the creation, the evolution and the basis of the constitutionality control in the world laws , mainly in Brazil, where it has tried to register many instruments created to control the constitu-tionality.In this context, the basic kinds of control systems of constitutionality were brought about civilized nations, among them Brazil, also outstanding the Brazilian constitu-tional pattern, its main aspects and instruments that provide the control of ordinary laws and rules regarding the Federal Constitution.
Regulation of mouse somatostatin receptor type 2 gene expression by glucocorticoids (1999)

Somatostatin is a regulatory peptide with important inhibitory functions. Its effects are mediated by five receptors, sst1-sst5. Previous studies revealed that sst2 contains three alternative, tissue specific promoters. Here, molecular mechanisms for the regulation of sst2 transcription by glucocorticoids were investigated. Reporter gene assays in NG 108-15 cells and electrophoretic mobility shift assays revealed that a glucocorticoid responsive element at position -1044 on the second promoter mediates dexamethasone induction. These findings, the existence of a cAMP response element and the tissue dependent activity (brain, pituitary and gastrointestinal tissues) indicate the importance of the second sst2 gene promoter.
PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus (2001)

The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage.
Bisphosphonates Are Potent Inhibitors of Trypanosoma cruzi Farnesyl Pyrophosphate Synthase (2001)

We report the cloning and sequencing of a gene encoding the farnesyl pyrophosphate synthase of Trypanosoma cruzi. The protein (T. cruzi farnesyl pyrophosphate synthase, TcFPPS) is an attractive target for drug development, since the growth of T. cruzi is inhibited by carbocation transition state/reactive intermediate analogs of its substrates, the nitrogen-containing bisphosphonates currently in use in bone resorption therapy. The protein predicted from the nucleotide sequence of the gene has 362 amino acids and a molecular mass of 41.2 kDa. Several sequence motifs found in other FPPSs are present in TcFPPS. Heterologous expression of TcFPPS in Escherichia coli produced a functional enzyme that was inhibited by the nitrogen-containing bisphosphonates alendronate, pamidronate, homorisedronate, and risedronate but was less sensitive to the non-nitrogen-containing bisphosphonate etidronate, which, unlike the nitrogen-containing bisphosphonates, does not affect parasite growth. The protein contains a unique 11-mer insertion located near the active site, together with other sequence differences that may facilitate the development of novel anti-Chagasic agents.
Accuracy and precision of compartmental model parameters obtained from directly estimated dynamic SPECT time-activity curves (2002)

No abstract prepared.
ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia (2007)

In 15% to 30% of patients with acute myeloid leukemia (AML), aberrant proliferation is a consequence of a juxtamembrane mutation in the FLT3 gene (FMS-like tyrosine kinase 3-internal tandem duplication [FLT3-ITD]), causing constitutive kinase activity. ABT-869 (a multitargeted receptor tyrosine kinase inhibitor) inhibited the phosphorylation of FLT3, STAT5, and ERK, as well as Pim-1 expression in MV-4-11 and MOLM-13 cells (IC(50) approximately 1-10 nM) harboring the FLT3-ITD. ABT-869 inhibited the proliferation of these cells (IC(50) = 4 and 6 nM, respectively) through the induction of apoptosis (increased sub-G(0)/G(1) phase, caspase activation, and PARP cleavage), whereas cells harboring wild-type (wt)-FLT3 were less sensitive. In normal human blood spiked with AML cells, ABT-869 inhibited phosphorylation of FLT3 (IC(50) approximately 100 nM), STAT5, and ERK, and decreased Pim-1 expression. In methylcellulose-based colony-forming assays, ABT-869 had no significant effect up to 1000 nM on normal hematopoietic progenitor cells, whereas in AML patient samples harboring both FLT3-ITD and wt-FLT3, ABT-869 inhibited colony formation (IC(50) = 100 and 1000 nM, respectively). ABT-869 dose-dependently inhibited MV-4-11 and MOLM-13 flank tumor growth, prevented tumor formation, regressed established MV-4-11 xenografts, and increased survival by 20 weeks in an MV-4-11 engraftment model. In tumors, ABT-869 inhibited FLT3 phosphorylation, induced apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]) and decreased proliferation (Ki67). ABT-869 is under clinical development for AML.