gebhart/patrepeval huggingface dataset:
Proteasome-Mediated Degradation and Functions of Hematopoietic Progenitor Kinase 1 in Pancreatic Cancer (2009)

Hematopoietic progenitor kinase 1 (HPK1) regulates stress responses, proliferation, and apoptosis in hematopoietic cells. In this study, we examined the expression, regulation, and functions of HPK1 in pancreatic ductal adenocarcinomas (PDA). We found that loss of HPK1 protein expression correlated significantly with the progression of pancreatic intraepithelial neoplasias (P = 0.001) and development of invasive PDA. Similarly, HPK1 protein was not expressed in any of eight PDA cell lines examined but was expressed in immortalized human pancreatic duct epithelial (HPDE) cells. There was no difference in HPK1 mRNA levels in PDA cell lines or primary PDA compared with those in HPDE cells or ductal epithelium in chronic pancreatitis and normal pancreas, respectively. Treatment of Panc-1 cells with a proteasome inhibitor, MG132, increased the HPK1 protein levels in a dose-dependent manner, suggesting that alteration in proteasome activity contributes to the loss of HPK1 protein expression in pancreatic cancer. Like the endogenous HPK1, both wild-type HPK1 and its kinase-dead mutant, HPK1-M46, overexpressed in Panc-1 cells, were also targeted by proteasome-mediated degradation. After MG132 withdrawal, wild-type HPK1 protein expression was markedly decreased within 24 hours, but kinase-dead HPK1 mutant protein expression was sustained for up to 96 hours. Therefore, HPK1 kinase activities were required for the loss of HPK1 protein in PDAs. Furthermore, restoring wild-type HPK1 protein in PDA cells led to the increase in p21 and p27 protein expression and cell cycle arrest. Thus, HPK1 may function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer.
Carbon-Fluorine Bond Cleavage (1966)

Studies on the mechanism of the reaction XCH&OO-+ OH----f X-+ HOCH&OO-(where X = F, Cl, and I) catalyzed by the enzyme haloacetate halidohydrolase indicate that the hydroxyl group of glycolate is derived from water.No evidence can be obtained for the reversibility of the dehalogenation.In addition, the exchanges between glycolate and H?*O and between chloroacetate and 3T1-are not catalyzed by the enzyme.
Extracting knowledge from evaluative text (2005)

Capturing knowledge from free-form evaluative texts about an entity is a challenging task. New techniques of feature extraction, polarity determination and strength evaluation have been proposed. Feature extraction is particularly important to the task as it provides the underpinnings of the extracted knowledge. The work in this paper introduces an improved method for feature extraction that draws on an existing unsupervised method. By including user-specific prior knowledge of the evaluated entity, we turn the task of feature extraction into one of term similarity by mapping crude (learned) features into a user-defined taxonomy of the entity's features. Results show promise both in terms of the accuracy of the mapping as well as the reduction in the semantic redundancy of crude features.
Molecular characterization of the Clostridium difficile toxin A gene (1990)

The gene encoding the toxin A protein of Clostridium difficile (strain VPI 10463) was cloned and sequenced. The coding region of 8,133 base pairs had a mol% G + C of 26.9 and encodes 2,710 amino acids. The deduced polypeptide has a molecular mass of ca. 308 kilodaltons. Nearly a third of the gene, at the 3' end, consists of 38 repeating sequences. The repeating units were grouped into two classes, I and II, on the basis of length and the low levels of DNA sequence similarities between them. There were seven class I repeating units, each containing 90 nucleotides, and 31 class II units, which, with two exceptions, were either 60 or 63 nucleotides in length. On the basis of DNA sequence similarities, the class II repeating units were further segregated into subclasses: 7 class IIA, 13 class IIB, 5 class IIC, and 6 class IID. The dipeptide tyrosine-phenylalanine was found in all 38 repeating units, and other amino acid sequences were unique to a specific class or subclass. This region of the protein has epitopes for the monoclonal antibody PCG-4 and includes the binding region for the Gal alpha 1-3Gal beta 1-4GlcNAc carbohydrate receptor. Located 1,350 base pairs upstream from the toxin A translation start site is the 3' end of the toxin B gene. Between the two toxin genes is a small open reading frame, which encodes a deduced polypeptide of ca. 16 or 19 kilodaltons. The role of this open reading frame is unknown.
Search Engines: Information Retrieval in Practice (2009)

KEY BENEFIT: Written by a leader in the field of information retrieval, this text provides the background and tools needed to evaluate, compare and modify search engines. KEY TOPICS: Coverage of the underlying IR and mathematical models reinforce key concepts. Numerous programming exercises make extensive use of Galago, a Java-based open source search engine. MARKET: A valuable tool for search engine and information retrieval professionals.
IMGN853, a Folate Receptor-α (FRα)–Targeting Antibody–Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors (2015)

A majority of ovarian and non-small cell lung adenocarcinoma cancers overexpress folate receptor α (FRα). Here, we report the development of an anti-FRα antibody-drug conjugate (ADC), consisting of a FRα-binding antibody attached to a highly potent maytansinoid that induces cell-cycle arrest and cell death by targeting microtubules. From screening a large panel of anti-FRα monoclonal antibodies, we selected the humanized antibody M9346A as the best antibody for targeted delivery of a maytansinoid payload into FRα-positive cells. We compared M9346A conjugates with various linker/maytansinoid combinations, and found that a conjugate, now denoted as IMGN853, with the N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB) linker and N(2')-deacetyl-N(2')-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4) exhibited the most potent antitumor activity in several FRα-expressing xenograft tumor models. The level of expression of FRα on the surface of cells was a major determinant in the sensitivity of tumor cells to the cytotoxic effect of the conjugate. Efficacy studies of IMGN853 in xenografts of ovarian cancer and non-small cell lung cancer cell lines and of a patient tumor-derived xenograft model demonstrated that the ADC was highly active against tumors that expressed FRα at levels similar to those found on a large fraction of ovarian and non-small cell lung cancer patient tumors, as assessed by immunohistochemistry. IMGN853 displayed cytotoxic activity against FRα-negative cells situated near FRα-positive cells (bystander cytotoxic activity), indicating its ability to eradicate tumors with heterogeneous expression of FRα. Together, these findings support the clinical development of IMGN853 as a novel targeted therapy for patients with FRα-expressing tumors.
Four-Dimensional Nonbinary LDPC-Coded Modulation Schemes for Ultra-High-Speed Optical Fiber Communication (2011)

In this letter, we propose a four-dimensional (4-D) nonbinary low-density parity-check-coded modulation (NB-LDPC-CM) scheme suitable for beyond 100-Gb/s optical fiber communication. Incorporating spectrally efficient modulation formats to achieve high aggregate bit rates and nonbinary LDPC codes for forward error correction (FEC), the proposed scheme offers a superior advanced FEC solution for optical fiber communication systems than the prior-art bit-interleaved LDPC-coded modulation (BI-LDPC-CM) scheme. Compared to the previously reported bit error rate (BER) performance results of BI-LDPC-CM, the proposed scheme offers additional net coding gains (NCGs) of 0.29 dB, 1.17 dB, and 2.17 dB at the BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-7</sup> when 16-, 32-, and 64-point 4-D constellations are used, respectively.
Regenerative medicine through mesenchymal stem cells for bone and cartilage repair. (2002)

Bone and cartilage defects are common features of bone fracture and joint diseases, such as rheumatoid arthritis or osteoarthritis, that have great social and economic impact on the aging occidental population. Despite progress in orthopedic surgery, bone and cartilage repair is a major challenge as large defects will not spontaneously heal. Recent investigations on the stromal mesenchymal stem cell (MSC) offer a new perspectivefor bone and cartilage tissue engineering. However, the standard offull healing is extremely demanding and may be achieved through the engineering of MSCs combined with scaffolds and growth factors as recombinant proteins, or using a gene therapy approach.
Production of Type VI Collagen by Human Macrophages: A New Dimension in Macrophage Functional Heterogeneity (2008)

Macrophages derived from human blood monocytes perform many tasks related to tissue injury and repair. The main effect of macrophages on the extracellular matrix is considered to be destructive in nature, because macrophages secrete metalloproteinases and ingest foreign material as part of the remodeling process that occurs in wound healing and other pathological conditions. However, macrophages also contribute to the extracellular matrix and hence to tissue stabilization both indirectly, by inducing other cells to proliferate and to release matrix components, and directly, by secreting components of the extracellular matrix such as fibronectin and type VIII collagen, as we have recently shown. We now report that monocytes and macrophages express virtually all known collagen and collagen-related mRNAs. Furthermore, macrophages secrete type VI collagen protein abundantly, depending upon their mode of activation, stage of differentiation, and cell density. The primary function of type VI collagen secreted by macrophages appears to be modulation of cell-cell and cell-matrix interactions. We suggest that the production of type VI collagen is a marker for a nondestructive, matrix-conserving macrophage phenotype that could profoundly influence physiological and pathophysiological conditions in vivo.
The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), induces IFN-β-mediated antiviral activity in vitro and in vivo (2010)

The 2009 outbreak of pandemic H1N1 influenza, increased drug resistance, and the significant delay in obtaining adequate numbers of vaccine doses have heightened awareness of the need to develop new antiviral drugs that can be used prophylactically or therapeutically. Previously, we showed that the experimental anti-tumor drug DMXAA potently induced IFN-β but relatively low TNF-α expression in vitro. This study confirms these findings in vivo and demonstrates further that DMXAA induces potent antiviral activity in vitro and in vivo. In vitro, DMXAA protected RAW 264.7 macrophage-like cells from VSV-induced cytotoxicity and moreover, inhibited replication of influenza, including the Tamiflu®-resistant H1N1 influenza A/Br strain, in MDCK cells. In vivo, DMXAA protected WT C57BL/6J but not IFN-β(-/-) mice from lethality induced by the mouse-adapted H1N1 PR8 influenza strain when administered before or after infection. Protection was accompanied by mitigation of weight loss, increased IFN-β mRNA and protein levels in the lung, and significant inhibition of viral replication in vivo early after DMXAA treatment. Collectively, this study provides data to support the use of DMXAA as a novel antiviral agent.
Spinal Cord Stimulation for Chronic Back and Leg Pain and Failed Back Surgery Syndrome: A Systematic Review and Analysis of Prognostic Factors (2005)

Despite an increase in the number of studies over the last 10 years, the level of evidence for the efficacy of spinal cord stimulation in chronic back and leg pain/failed back surgery syndrome remains "moderate." Prognostic factors found to be predictive of the level of pain relief following spinal cord stimulation were study quality, follow-up duration, study setting, and patient indication.
The beta amyloid protein precursor: mRNAs, membrane-associated forms, and soluble derivatives. (1989)

We used in situ hybridization to assess total beta amyloid protein precursor (beta APP) mRNA and the subset of beta APP mRNA containing the Kunitz protease inhibitor (KPI) insert in 11 Alzheimer's disease (AD) brains and 7 control brains well matched for age and postmortem interval. In AD, we observed a significant two-fold increase in total beta APP mRNA in nucleus basalis and locus ceruleus neurons but not in occipital cortical neurons, hippocampal subicular neurons, or neurons of the basis pontis. The increase in total beta APP mRNA in locus ceruleus and nucleus basalis neurons was due exclusively to an increase in KPI-free beta APP mRNA. We conclude that increased production of KPI-free beta APP in nucleus basalis and locus ceruleus neurons may contribute to the deposition of cerebral amyloid that occurs in AD. To identify the beta APP, we prepared antisera to synthetic peptides corresponding to the carboxyl-terminus (anti-C1), to a near amino-terminal domain (anti-beta APP45-62), and to the KPI domain (anti-KPI36-48). We established that these antisera detect the beta APP by showing that they specifically detect proteins that are markedly augmented in cells transfected with beta APP expression constructs. Anti-beta APP45-62 specifically labels (i) a set of approximately 110-135 kDa membrane-associated brain proteins previously detected by antisera to the carboxyl-terminus of the beta APP (anti-C1) and (ii) soluble approximately 105 and approximately 125 kDa proteins not detected by anti-C1. Anti-KPI36-48 specifically labels the two largest membrane-associated forms of the beta APP and the soluble approximately 125 kDa derivative, but does not label the two smallest membrane-associated forms or the approximately 105 kDa soluble derivative. Anti-beta APP45-62 and anti-C1 both specifically stain senile plaques. This finding suggests (i) that full-length beta APP is present in senile plaques and (ii) that proteolytic processing of the beta APP into insoluble amyloid fibrils occurs, at least in part, locally at the sites of amyloid deposition in AD brain. Analysis of cerebrospinal fluid (CSF) showed that the soluble KPI-containing (approximately 125 kDa) and KPI-free (approximately 105 kDa) derivatives present in brain are readily detected in CSF from both AD cases and controls.(ABSTRACT TRUNCATED AT 400 WORDS)
Determining the Cause of Hearing Loss: Differential Diagnosis Using a Comparison of Audiometric and Otoacoustic Emission Responses (2006)

The results clearly demonstrate the possibility of developing a clinical method of noninvasive differential diagnosis of hearing loss. The method demonstrated was to add to a standard audiometric evaluation the measurement of DPOAE growth functions over the range of frequencies where these emissions were relatively easy to measure and consistent. The DPOAE stimulus frequencies were chosen to match the audiometric frequencies, and the corresponding emission and audiometric thresholds were compared on a threshold-threshold plot for each individual at a number of stimulus frequencies. Responses in different regions in this plot were found to correspond to different types of sensorineural hearing loss.
DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus-infected cells (2003)

Expression of adenovirus E1A deregulates cell proliferation to facilitate viral DNA replication, prompting the initiation of apoptosis signaled primarily through proapoptotic BAK in productively infected cells. We demonstrate here that in uninfected cells, BAK is complexed with the anti-apoptotic BCL-2 family member Myeloid Cell Leukemia 1 (MCL-1). E1A expression during infection resulted in the specific down-regulation of MCL-1 through destabilization of the protein and loss of the mRNA. Upon loss of the MCL-1-BAK complex, BAK complexed with either BAX in proapoptotic E1B mutant adenovirus-infected cells, or with the adenovirus BCL-2 homolog E1B 19K in cells infected with the wild-type virus in which apoptosis is inhibited. Loss of MCL-1 was required to initiate the apoptotic pathway in infected cells as restoration of MCL-1 expression rescued infected cells from E1A-induced apoptosis. Analogous to E1A expression, DNA damage down-regulates MCL-1, and adenovirus infection resulted in the accumulation of phosphorylated H2AX and ataxia-telangiectasia mutant protein (ATM), hallmarks of DNA double-strand breaks. Thus, MCL-1 may function by maintaining BAK in an inactive state, and the loss of MCL-1 upon activation of the DNA damage response, perhaps through replication stress induced in virus infected cells, may be required to initiate the apoptotic response.
Genetic Evidence for Functional Redundancy of Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1): CD31-Deficient Mice Reveal PECAM-1-Dependent and PECAM-1-Independent Functions (1999)

Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31), a member of the Ig superfamily, is expressed strongly at endothelial cell-cell junctions, on platelets, and on most leukocytes. CD31 has been postulated to play a role in vasculogenesis and angiogenesis, and has been implicated as a key mediator of the transendothelial migration of leukocytes. To further define the physiologic role of CD31, we used targeted gene disruption of the CD31 gene in embryonic stem cells to generate CD31-deficient mice. CD31-deficient mice (CD31KO) are viable and born at the expected Mendelian frequency, remain healthy, and exhibit no obvious vascular developmental defects. In response to inflammatory challenge, polymorphonuclear leukocytes of CD31KO mice are arrested between the vascular endothelium and the basement membrane of inflammatory site mesenteric microvessels, confirming a role for CD31 in the migration of neutrophils through the subendothelial extracellular matrix. Normal numbers of leukocytes are recovered from inflammatory sites in CD31KO mice, however, suggesting that the defect in leukocyte migration across basal lamina observed in the absence of CD31 may be compensated for by the use of other adhesion molecules, or possibly an increased rate of migration. Homing of T lymphocytes in vivo is normal, and CD31KO mice are able to mount a cutaneous hypersensitivity response normally. In addition, CD31-mediated homophilic adhesion does not appear to play a role in platelet aggregation in vitro. This study provides genetic evidence that CD31 is involved in transbasement membrane migration, but does not play an obligatory role in either vascular development or leukocyte migration.
Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers (2000)

These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
Energetic Decomposition with the Generalized-Born and Poisson−Boltzmann Solvent Models: Lessons from Association of G-Protein Components (2010)

Continuum electrostatic models have been shown to be powerful tools in providing insight into the energetics of biomolecular processes. While the Poisson-Boltzmann (PB) equation provides a theoretically rigorous approach to computing electrostatic free energies of solution in such a model, computational cost makes its use for large ensembles of states impractical. The generalized-Born (GB) approximation provides a much faster alternative, although with a weaker theoretical framework. While much attention has been given to how GB recapitulates PB energetics for the overall stability of a biomolecule or the affinity of a complex, little attention has been given to how the contributions of individual functional groups are captured by the two methods. Accurately capturing these individual electrostatic components is essential both for the development of a mechanistic understanding of biomolecular processes and for the design of variant sequences and structures with desired properties. Here, we present a detailed comparison of the group-wise decomposition of both PB and GB electrostatic free energies of binding, using association of various components of the heterotrimeric-G-protein complex as a model. We find that, while net binding free energies are strongly correlated in the two models, the correlations of individual group contributions are highly variable; in some cases, strong correlation is seen, while in others, there is essentially none. Structurally, the GB model seems to capture the magnitude of direct, short-range electrostatic interactions quite well but performs more poorly with moderate-range "action-at-a-distance" interactions--GB has a tendency to overestimate solvent screening over moderate distances, and to underestimate the costs of desolvating charged groups somewhat removed from the binding interface. Despite this, however, GB does seem to be quite effective as a predictor of those groups that will be computed to be most significant in a PB-based model.
Combretastatin A-4 Analogues as Antimitotic Antitumor Agents (2003)

Tubulin protein is a major target for anticancer drug discovery. As a result, antimitotic agents constitute an important class of the current anticancer drugs. Hundreds of tubulin inhibitors, naturally occurring, semisynthetic or synthetic, have been reported. Among these, combretastatin A-4 (CA-4), isolated from a South African tree Combretum caffrum, is one of the most potent antimitotic agents. CA-4 shows strong cytotoxicity against a variety of cancer cells, including multi-drug resistant cancer cell lines. It has also been demonstrated to exert highly selective effects in proliferating endothelial cells. CA-4 disodium phosphate (CA4DP), a water-soluble prodrug of CA-4, shows potent antivascular and antitumor effects in a wide variety of preclinical tumor models. Consequently, a number of CA-4 analogues has been synthesized and evaluated. In this paper, the structure-activity relationships and pharmacological properties of the CA-4 derivatives as a class of potent antimitotic anticancer agents are reviewed and discussed.
Multifunctional Micellar Nanomedicine for Cancer Therapy (2008)

Polymeric micelles are supramolecular, core-shell nanoparticles that offer considerable advantages for cancer diagnosis and therapy. Their relatively small size (10-100 nm), ability to solubilize hydrophobic drugs as well as imaging agents, and improved pharmacokinetics provide a useful bioengineering platform for cancer applications. Several polymeric micelle formulations are currently undergoing phase I/II clinical trials, which have shown improved antitumor efficacy and reduced systemic toxicity. This minireview will focus on recent advancements in the multifunctional design of micellar nanomedicine with tumor targeting, stimulated drug release, and cancer imaging capabilities. Such functionalization strategies result in enhanced micellar accumulation at tumor sites, higher drug bioavailability, as well as improved tumor diagnosis and visualization of therapy. Ultimately, integrated nanotherapeutic systems (e.g., theranostic nanomedicine) may prove essential to address the challenges of tumor heterogeneity and adaptive resistance to achieve efficacious treatment of cancer.