gebhart/patrepeval huggingface dataset:
Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors (2002)

The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the zeta chain of the T cell receptor. After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth.
NovoHMM:  A Hidden Markov Model for de Novo Peptide Sequencing (2005)

De novo sequencing of peptides poses one of the most challenging tasks in data analysis for proteome research. In this paper, a generative hidden Markov model (HMM) of mass spectra for de novo peptide sequencing which constitutes a novel view on how to solve this problem in a Bayesian framework is proposed. Further extensions of the model structure to a graphical model and a factorial HMM to substantially improve the peptide identification results are demonstrated. Inference with the graphical model for de novo peptide sequencing estimates posterior probabilities for amino acids rather than scores for single symbols in the sequence. Our model outperforms state-of-the-art methods for de novo peptide sequencing on a large test set of spectra.
Bone grafts prepared with selective cell retention technology heal canine segmental defects as effectively as autograft (2006)

Using a canine critical-size segmental defect model, a two-phased study was undertaken to evaluate the healing efficacy of demineralized bone and cancellous chips (DBM-CC) enriched with osteoprogenitor cells using a Selective Cell Retention (SCR) technology. The goals of this study were: 1) to determine the bone-healing efficacy of SCR-enriched grafts versus autograft, and 2) to assess the value of clotting SCR-enriched grafts with platelet-rich plasma (PRP). Thirty dogs were included in Phase I: 18 dogs were treated with an SCR-enriched DBM-CC graft clotted with autologous bone marrow, and were compared to 12 autograft controls. In Phase II, 24 animals were divided into 4 groups of 6 animals, each treated with a different bone graft material: 1) iliac crest autograft, 2) DBM-CC alone, 3) DBM-CC saturated with marrow, and 4) SCR-enriched DBM-CC clotted with PRP. All grafts were placed unilaterally in a 21-mm long osteoperiosteal femoral, instrumented, critical-size defect. Radiographs were obtained for all animals postoperatively and every 4-16 weeks; animals were then sacrificed. All femurs were prepared for histology. Femurs in the Phase II study were also analyzed by micro-CT. At 16 weeks, healing--defined by bridging bone across the defects--was observed in 50% of the DBM-CC alone group and 67% of the DBM-CC saturated with marrow group; 100% of the autograft and SCR-enriched DBM-CC groups were healed. Histologically, grafts clotted with PRP showed more mature bone than those implanted with autologous bone, which in turn were similar to those implanted with bone marrow clotted SCR-enriched grafts. These results demonstrated that: 1) SCR-enriched DBM-CC was equivalent to autograft to repair critical-size defects, and 2) while not statistically significant, PRP may have accelerated bone maturation when used to clot osteoprogenitor-enriched DBM-CC grafts--as compared to cell-enriched, DBM-CC grafts without PRP--in large animal models.
Leg intramuscular pressures during locomotion in humans (1998)

To assess the usefulness of intramuscular pressure (IMP) measurement for studying muscle function during gait, IMP was recorded in the soleus and tibialis anterior muscles of 10 volunteers during treadmill walking and running by using transducer-tipped catheters. Soleus IMP exhibited single peaks during late-stance phase of walking [181 +/- 69 (SE) mmHg] and running (269 +/- 95 mmHg). Tibialis anterior IMP showed a biphasic response, with the largest peak (90 +/- 15 mmHg during walking and 151 +/- 25 mmHg during running) occurring shortly after heel strike. IMP magnitude increased with gait speed in both muscles. Linear regression of soleus IMP against ankle joint torque obtained by a dynamometer produced linear relationships (n = 2, r = 0.97 for both). Application of these relationships to IMP data yielded estimated peak soleus moment contributions of 0.95-1.65 N . m/kg during walking, and 1.43-2.70 N . m/kg during running. Phasic elevations of IMP during exercise are probably generated by local muscle tissue deformations due to muscle force development. Thus profiles of IMP provide a direct, reproducible index of muscle function during locomotion in humans.
Antibodies to GM1 and GD1b in patients with motor neuron disease without plasma cell dyscrasia (1989)

Fifty-nine percent of 49 patients with motor neuron disease and 25% of 91 control subjects had IgM antibodies to ganglioside GM1 but usually not to GD1b at titers less than 1:80. This suggests that antibodies to GM1 may be part of the normal human antibody repertoire. However, given the higher incidence of antibodies to GM1 in patients with motor neuron disease, there may be specific epitopes important in antiganglioside antibodies associated with motor neuron disease.
Signal Sequences Initiate the Pathway of Maturation in the Endoplasmic Reticulum Lumen (2003)

An interaction between an N-terminal signal sequence and the translocon leads to the initiation of protein translocation into the endoplasmic reticulum lumen. Subsequently, folding and modification of the substrate rapidly ensue. The close temporal coordination of these processes suggests that they may be structurally and functionally coordinated as well. Here we show that information encoded in the hydrophobic domain of a signal sequence influences the timing and efficiency of at least two steps in maturation, namely N-linked glycosylation and signal sequence cleavage. We demonstrate that these consequences correlate with and likely stem from the nature of the initial association made between the signal sequence and the translocon during the initiation of translocation. We propose a model by which these maturational events are controlled by the signal sequence-translocon interaction. Our work demonstrates that the pathway taken by a nascent chain through post-translational maturation depends on information encoded in its signal sequence.
Imiquimod 5% cream in the treatment of anogenital warts in female patients (2002)

In these studies, imiquimod 5% cream was an effective and well-tolerated treatment for anogenital warts in females and continued to be safe and effective in the small proportion of patients who needed to re-apply imiquimod after wart recurrence.
Effects of K-76 Monocarboxylic Acid, an AnticomplementaryAgent, on Various in vivo Immunological Reactions and onExperimental Glomerulonephritis (1984)

K-76 monocarboxylic acid (K-76 COOH) caused rapid reduction in hemolytic activities of complement and some of its components, especially C5, when injected into guinea pigs or rats. K-76 COOH suppressed Forssman shock in guinea pigs and mice and heterologous passive cutaneous anaphylaxis in guinea pigs. It also reduced the amount of protein excreted in the urine of rats with nephrotoxic nephritis and greatly prolonged the survival of (NZB X NZW) FI female mice with a spontaneous systemic lupus erythematosus-like disease. The glomeruli of mice treated with K-76 COOH retained almost the normal histological appearance even at 1 year of age. K-76 COOH-treated mice became less sensitive to the infection of Escherichia coli, Staphylococcus aureus, or Streptococcus pneumoniae, probably by enhancement of phagocytosis due to inhibition of factor I. K-76 COOH did not have any significant effect on a delayed-type contact skin reaction in mice, or on experimental allergic encephalitis in guinea pigs.
A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis (2001)

Infection with Helicobacter pylori causes chronic gastritis, which is characterized by a dense mucosal infiltration by inflammatory cells such as monocytes/macrophages. H. pylori-induced inflammation is a risk factor for the development of gastric adenocarcinoma, but the mechanisms involved in H. pylori-associated carcinogenesis are poorly understood. A cecropin-like H. pylori peptide, Hp(2-20), was found to be a monocyte chemoattractant and activated the monocyte NADPH-oxidase to produce oxygen radicals. The receptors mediating monocyte activation were identified as FPRL1 and the monocyte-specific orphan receptor FPRL2. Hp(2-20)-activated monocytes inhibited lymphocytes with antitumor properties, such as CD56+ natural killer (NK) cells and CD3epsilon+ T cells. The changes observed in NK cells and T cells--a reduced antitumor cytotoxicity, downregulation of CD3zeta expression, and apoptosis--were mediated by Hp(2-20)-induced oxygen radicals. Histamine, a gastric mucosal constituent, rescued NK cells and T cells from inhibition and apoptosis by suppressing Hp(2-20)-induced oxygen radical formation. We conclude that H. pylori expression of this monocyte-activating peptide contributes to its ability to attract and activate monocytes and reduces the function and viability of antineoplastic lymphocytes. These novel mechanisms may be subject to local, histaminergic regulation in the gastric mucosa.
On a new class of embedded hypersurfaces in with nonzero constant mean curvature (2007)

Abstract We build a new class of embedded hypersurfaces in which have nonzero constant mean curvature and are O( m )×O( n )-invariant. For this we consider a 1-parameter family of planar vector fields associated to the differential equation of mean curvature.
Human plasma transport of vitamin D after its endogenous synthesis. (1993)

Transport of vitamin D3 from its sites of cutaneous synthesis into the circulation has been assumed to be via the plasma vitamin D binding protein (DBP). We studied vitamin D transport from the skin in seven healthy volunteers who received whole body irradiation with 27 mJ/cm2 dosage of ultraviolet B light (290-320 nm). Samples of venous blood were collected serially in EDTA and immediately chilled. In KBr, plasma samples were ultracentrifuged to provide a rapid separation of proteins of density < and > 1.3 g/ml. Upper and lower phases and serial fractions were analyzed for vitamin D3 (extraction, HPLC), cholesterol (enzyme assay), and human DBP (hDBP) (radial immunodiffusion). Total plasma vitamin D (basal level < 1 ng/ml) increased by 10 h and peaked at 24 h (9 +/- 1 ng/ml). 98% of the D3 remained at the density > 1.3 layers for up to 7 d, whereas cholesterol (> 85%) was detected at density < 1.3 and all of the hDBP was at density > 1.3. In three volunteers who each ingested 1.25 mg of vitamin D2, the total plasma D2 increased to 90 +/- 32 ng/ml by 4 h, and the D2 was evenly distributed between the upper and lower layers at 4, 8, and 24 h after the dose, indicating a continuing association of the vitamin with chylomicrons and lipoproteins, as well as with hDBP. Actin affinity chromatography removed D3 from plasma of irradiated subjects, indicating the association of the D3 with DBP. These findings indicate that endogenously synthesized vitamin D3 travels in plasma almost exclusively on DBP, providing for a slower hepatic delivery of the vitamin D and the more sustained increase in plasma 25-hydroxycholecalciferol observed after depot, parenteral administration of vitamin D. In contrast, the association of orally administered vitamin D with chylomicrons and lipoproteins allows for receptor-mediated, rapid hepatic delivery of vitamin D, and the reported rapid but less-sustained increases in plasma 25-hydroxycholecalciferol.
Recurrent neural network and LSTM models for lexical utterance classification (2015)

Utterance classification is a critical pre-processing step for many speech understanding and dialog systems. In multi-user settings, one needs to first identify if an utterance is even directed at the system, followed by another level of classification to determine the intent of the user’s input. In this work, we propose RNN and LSTM models for both these tasks. We show how both models outperform baselines based on ngram-based language models (LMs), feedforward neural network LMs, and boosting classifiers. To deal with the high rate of singleton and out-of-vocabulary words in the data, we also investigate a word input encoding based on character ngrams, and show how this representation beats the standard one-hot vector word encoding. Overall, these proposed approaches achieve over 30% relative reduction in equal error rate compared to boosting classifier baseline on an ATIS utterance intent classification task, and over 3.9% absolute reduction in equal error rate compared to a the maximum entropy LM baseline of 27.0% on an addressee detection task. We find that RNNs work best when utterances are short, while LSTMs are best when utterances are longer.
Carbon Nanotubes on Carbon Nanofibers: A Novel Structure Based on Electrospun Polymer Nanofibers (2004)

Electrospun nanofibers of polyacrylonitrile , containing an iron compound, have been converted to carbon nanofibers, with iron particles on their surfaces. The iron particles catalyze the growth of carbon nanotubes with iron tips (see Figure). A mechanically strong and electrically conducting path exists between each metal particle and the supporting nanofiber network, which extends to macroscopic dimensions.
Computation of the acoustic radiation force on a sphere based on the 3-D FDTD method (2010)

The acoustic radiation force on a steel sphere suspended freely in a plane progressive sound field is calculated by the three-dimensional (3-D) finite difference time domain (FDTD) method combined with the momentum-flux tensor. The radiation forces versus kr curve are in excellent agreement with those obtained by the scattering method.
Amino acid sequence and domain structure of entactin. Homology with epidermal growth factor precursor and low density lipoprotein receptor. (1988)

Entactin (nidogen), a 150-kD sulfated glycoprotein, is a major component of basement membranes and forms a highly stable noncovalent complex with laminin. The complete amino acid sequence of mouse entactin has been derived from sequencing of cDNA clones. The 5.9-kb cDNA contains a 3,735-bp open reading frame followed by a 3'-untranslated region of 2.2 kb. The open reading frame encodes a 1,245-residue polypeptide with an unglycosylated Mr of 136,500, a 28-residue signal peptide, two Asn-linked glycosylation sites, and two potential Ca2+-binding sites. Analysis of the deduced amino acid sequence predicts that the molecule consists of two globular domains of 70 and 36 kD separated by a cysteine-rich domain of 28 kD. The COOH-terminal globular domain shows homology to the EGF precursor and the low density lipoprotein receptor. Entactin contains six EGF-type cysteine-rich repeat units and one copy of a cysteine-repeat motif found in thyroglobulin. The Arg-Gly-Asp cell recognition sequence is present in one of the EGF-type repeats, and a synthetic peptide from the putative cell-binding site of entactin was found to promote the attachment of mouse mammary tumor cells.
Exploiting Vector Parallelism in Software Pipelined Loops (2006)

An emerging trend in processor design is the addition of short vector instructions to general-purpose and embedded ISAs. Frequently, these extensions are employed using traditional vectorization technology first developed for supercomputers. In contrast, scalar hardware is typically targeted using ILP techniques such as software pipelining. This paper presents a novel approach for exploiting vector parallelism in software pipelined loops. The proposed methodology (i) lowers the burden on the scalar resources by offloading computation to the vector functional units, (ii) explicitly manages communication of operands between scalar and vector instructions, (in) naturally handles misaligned vector memory operations, and (iv) partially (or fully) inhibits the optimization when vectorization will decrease performance. Our approach results in better resource utilization and allows for software pipelining with shorter initiation intervals. The proposed optimization is applied in the compiler backend, where vectorization decisions are more amenable to cost analysis. This is unique in that traditional vectorization optimizations are usually carried out at the statement level. Although our technique most naturally complements statically scheduled machines, we believe it is applicable to any architecture that tightly integrates support for instruction and data level parallelism. We evaluate our methodology using nine SPEC FP benchmarks. In comparison to software pipelining, our approach achieves a maximum speedup of 1.38times, with an average of 1.11times
Fertile Ground : Nutrient Trading's Potential to Cost-Effectively improve Water Quality (2000)

After nearly three decades of effort, the United States can take considerable pride in answering the mandates of the 1972 Clean Water Act. At great expense, much of the municipal and industrial pollution emanating from pipes, or "point" sources, has been reduced. But the largely voluntary effort to reduce "nonpoint" pollution from farms and elsewhere has been less successful. As we enter a new millennium, progress in improving water quality seems to have leveled off and our hopes of meeting the goals of the Clean Water Act seem to be receding.Some 3,600 waterways across the nation are listed as either impaired by nutrients or by algal blooms, which are typically caused by excess nutrients. The U.S. Environmental Protection Agency is locked in a contentious legal battle with many states over additional requirements to improve water quality. Part of the problem is the complex nature of water pollution and the difficult challenge of controlling nonpoint pollution. Clearly another part of the problem is the question of costs. States are heavily constrained by cost considerations and reluctant to embark on another costly round of stricter point source controls.In Fertile Ground: Nutrient Trading's Potential to Cost-Effectively Improve Water Quality, the Director of WRI's Economics Program, Paul Faeth, proposes a way out of this dilemma. Using case studies in three states, he develops a framework to assess the cost-effectiveness of various policies and combinations of policies to reduce phosphorus loads in specific watersheds. In all three cases, policy approaches incorporating nutrient trading programs are dramatically less expensive than conventional approaches and can achieve comparable benefits.
Therapy of Advanced B-Lymphoma Xenografts with a Combination of 90Y-anti-CD22 IgG (Epratuzumab) and Unlabeled Anti-CD20 IgG (Veltuzumab) (2008)

These studies illustrate how combinations of unconjugated and radioconjugated antibodies against different B-cell markers can improve therapeutic outcome, and offer a new therapeutic paradigm for the treatment of B-cell lymphomas.
Purification of carbon nanotubes through an electric field near the arranged microelectrodes (2007)

In this work, we attempt to purify multi-walled carbon nanotubes (MWNTs) using electrophoresis induced by the application of an AC electric field to a set of microelectrodes in a microliquid channel. This purifying method is different from conventional methods based on chemical processes. It was observed that most of the MWNTs could pass along the microliquid channel without attaching to the electrode under specific conditions of 1 kHz, at 0.2 V-rms mu m(-1). On the other hand, the majority of the carbon impurities attached to the electrodes under identical conditions. Field emission scanning electron microscopy (FESEM) images and Raman spectra confirm that this condition is beneficial for removing carbon impurities. The proposed approach has potential applicability in the development of microdevices that can simultaneously perform the purification and fabrication of MWNTs.
Structure of the p53 Tumor Suppressor Bound to the Ankyrin and SH3 Domains of 53BP2 (1996)

Mutations in the p53 tumor suppressor are among the most frequently observed genetic alterations in human cancer and map to the 200-amino acid core domain of the protein. The core domain contains the sequence-specific DNA binding activity and the in vitro 53BP2 protein binding activity of p53. The crystal structure of the p53 core domain bound to the 53BP2 protein, which contains an SH3 (Src homology 3) domain and four ankyrin repeats, revealed that (i) the SH3 domain binds the L3 loop of p53 in a manner distinct from that of previously characterized SH3-polyproline peptide complexes, and (ii) an ankyrin repeat, which forms an L-shaped structure consisting of a beta hairpin and two alpha helices, binds the L2 loop of p53. The structure of the complex shows that the 53BP2 binding site on the p53 core domain consists of evolutionarily conserved regions that are frequently mutated in cancer and that it overlaps the site of DNA binding. The six most frequently observed p53 mutations disrupt 53BP2 binding in vitro. The structure provides evidence that the 53BP2-p53 complex forms in vivo and may have a critical role in the p53 pathway of tumor suppression.
AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia (2013)

Upregulation of Pim kinases is observed in several types of leukemias and lymphomas. Pim-1, -2, and -3 promote cell proliferation and survival downstream of cytokine and growth factor signaling pathways. AZD1208 is a potent, highly selective, and orally available Pim kinase inhibitor that effectively inhibits all three isoforms at <5 nM or <150 nM in enzyme and cell assays, respectively. AZD1208 inhibited the growth of 5 of 14 acute myeloid leukemia (AML) cell lines tested, and sensitivity correlates with Pim-1 expression and STAT5 activation. AZD1208 causes cell cycle arrest and apoptosis in MOLM-16 cells, accompanied by a dose-dependent reduction in phosphorylation of Bcl-2 antagonist of cell death, 4EBP1, p70S6K, and S6, as well as increases in cleaved caspase 3 and p27. Inhibition of p4EBP1 and p-p70S6K and suppression of translation are the most representative effects of Pim inhibition in sensitive AML cell lines. AZD1208 inhibits the growth of MOLM-16 and KG-1a xenograft tumors in vivo with a clear pharmacodynamic-pharmacokinetic relationship. AZD1208 also potently inhibits colony growth and Pim signaling substrates in primary AML cells from bone marrow that are Flt3 wild-type or Flt3 internal tandem duplication mutant. These results underscore the therapeutic potential of Pim kinase inhibition for the treatment of AML.