gebhart/patrepeval huggingface dataset:
Human Carcinoma Cell Growth and Invasiveness Is Impaired by the Propeptide of the Ubiquitous Proprotein Convertase Furin (2005)

Furin, a potent proprotein convertase involved in activation of several cancer-related substrates, is synthesized as an inactive zymogen, thus minimizing the occurrence of premature enzymatic activity that would lead to inappropriate protein activation or degradation. This natural inhibitory mechanism is based on the presence of an inactivating prosegment at the NH2 terminal of the zymogen. After initial autocatalytic cleavage, the prosegment remains tightly associated with the convertase until it reaches the trans-Golgi network where the dissociation of the prosegment and activation of furin occurs. We hypothesized that the inhibitory properties of the preprosegment of furin (ppFur) could be beneficial if ectopically expressed in tumor cells. Transfection of four human head and neck squamous cell carcinoma cell lines with the complete ppFur cDNA sequence (pIRES-EGFP-ppFur) or with the empty expression vector (pIRES-EGFP) was done. The inhibitory effect was evaluated using in vivo tumorigenicity, invasion, anchorage-independent growth in soft agar, and proliferation assays, as well as by investigating impairment of furin substrates processing. Following transfection of ppFur, a significant reduction in cell proliferation, tumorigenicity, and invasiveness was observed in vitro and in vivo. These biological changes are directly related to the inhibition of furin-mediated activation of crucial cancer-related substrates, such as membrane type 1 matrix metalloproteinase, transforming growth factor-beta, insulin-like growth factor-1 receptor, and vascular endothelial growth factor-C. PpFur expression in head and neck squamous cell carcinoma cell lines showed a mechanistic link between furin inhibition, decreased substrate processing, cell proliferation, and invasive ability. These findings suggest that furin inhibition is a feasible approach to ameliorate and even abolish the malignant phenotype of various malignancies.
Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol (1997)

Fruits and vegetables have protective effects against many human cancers, including pancreatic cancer. Isoprenoids are one class of phytochemicals which have antitumor activity, but little is known about their effects on cancer of the pancreas. We tested the hypothesis that isoprenoids would inhibit the growth of pancreatic tumor cells. Significant (60-90%) inhibition of the anchorage-independent growth of human MIA PaCa2 pancreatic tumor cells was attained with 25 microM farnesol, 25 microM geranylgeraniol, 100 microM perillyl amine, 100 microM geraniol, or 300 microM perillyl alcohol. We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perillyl alcohol against transplanted PC-1 hamster pancreatic adenocarcinomas. Syrian Golden hamsters fed geraniol or farnesol at 20 g/kg diet exhibited complete inhibition of PC-1 pancreatic tumor growth. Both farnesol and geraniol were more potent than perillyl alcohol, which inhibited tumor growth by 50% at 40 g/kg diet. Neither body weights nor plasma cholesterol levels of animals consuming isoprenoid diets were significantly different from those of pair-fed controls. Thus, farnesol, geraniol, and perillyl alcohol suppress pancreatic tumor growth without significantly affecting blood cholesterol levels. These dietary isoprenoids warrant further investigation for pancreatic cancer prevention and treatment.
Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system (2018)

The unusually high demand for metals in the brain, along with insufficient understanding of how their dysregulation contributes to neurological diseases, motivates the study of how inorganic chemistry influences neural circuitry. We now report that the transition metal copper is essential for regulating rest-activity cycles and arousal. Copper imaging and gene expression analysis in zebrafish identifies the locus coeruleus-norepinephrine (LC-NE) system, a vertebrate-specific neuromodulatory circuit critical for regulating sleep, arousal, attention, memory and emotion, as a copper-enriched unit with high levels of copper transporters CTR1 and ATP7A and the copper enzyme dopamine β-hydroxylase (DBH) that produces NE. Copper deficiency induced by genetic disruption of ATP7A, which loads copper into DBH, lowers NE levels and hinders LC function as manifested by disruption in rest-activity modulation. Moreover, LC dysfunction caused by copper deficiency from ATP7A disruption can be rescued by restoring synaptic levels of NE, establishing a molecular CTR1-ATP7A-DBH-NE axis for copper-dependent LC function.
Protein Disulfide Isomerase Assists Protein Folding as Both an Isomerase and a Chaperonea (1998)

Protein disulfide isomerase (PDI) is the physiological catalyst of native disulfide bond formation of nascent peptides in the cells. As a foldase, PDI has both isomerase and chaperone activities. The chaperone activity is intrinsic and independent of its isomerase activity. Both chaperone and isomerase activities are required for PDI to assist folding of denatured and reduced disulfide-containing proteins. PDI may have great applications in protein production by bioengineering for its function as a foldase.
Quantum Clustering Algorithm based on Exponent Measuring Distance (2008)

The principle advantage and shortcoming of quantum clustering algorithm (QC) is analyzed. Based on its shortcomings, an improved algorithm - exponent distance-based quantum clustering algorithm (EQDC) is produced. It improved the iterative procedure of QC algorithm and used exponent distance formula to measure the distance between data points and the cluster centers. Experimental results demonstrate that the cluster accuracy of EDQC outperforms that of QC, and the exponent distance formula used in the clustering process performs better than the Euclidean distance in data preprocessing. What's more, the IRIS dataset can come to a satisfied result without preprocessing.
Retroviral Transduction of CD34-Enriched Hematopoietic Progenitor Cells Under Serum-Free Conditions (1996)

The use of defined or serum-free culture conditions during retroviral transduction of hematopoietic cells would be desirable for standardization and safety reasons, as well as potentially allowing greater expansion of progenitor cells. Retroviral vector supernatants were concentrated and purified via tangential flow filtration polyethylene glycol (PEG)-precipitation, and ultracentrifugation, allowing serum-free transductions at standard multiplicities of infection (moi). Protein content of transductions using these concentrated vectors was 5-6 logs lower than in standard transductions. Transduction efficiencies of these concentrated vector preparations added back to serum-free or serum-containing media were equivalent to standard retroviral supernatant transductions of CD34-enriched progenitors. Absolute progenitor (CFU-C) numbers at the end of transduction were higher in serum-free + concentrated virus transductions, as opposed to transductions in standard vector supernatants containing fetal calf serum.
Harnessing ester bond chemistry for protein ligation (2017)

The hydrolysis potential of ester bonds in covalently cross-linking proteins is captured in our novel protein ligation technology. This new type of "molecular superglue" based on the spontaneously-formed Thr-Gln ester bonds found in cell-surface adhesins, affords a unique mechanism to both rationally assemble and disassemble complex protein nanomaterials.
PI3K Inhibition As a Potential Therapeutic Strategy in Peripheral T-Cell Lymphomas, (2011)

Abstract Abstract 3493 Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of very aggressive malignancies lacking efficient therapy. Unfortunately, there are neither animal models nor representative cell lines for most PTCL types, making functional and pharmacodynamic studies even more difficult. PI3K signaling is essential for cell proliferation and survival, is frequently altered in human cancer and seems to play a critical role in T-cell development and activation. The aim of this work is to determine the efficiency of PI3K inhibition in PTCL, looking for pharmacodynamic biomarkers, and to identify markers that could distinguish responders from non-responders. Twenty two PTCL cases and seven reactive lymph nodes were studied using gene expression profiling. We performed an in silico analysis using the Connectivity Map program to identify drugs that could potentially reverse the PTCL gene expression signature. Among them, several PI3K/mTOR inhibitors were found. Moreover, genomic studies using Gene Set Enrichment Analysis identified PIK3CD gene (encoding for the delta isoform of PI3K) to be the only one significantly correlated to the activation of CD40, NF-kB and TCR pathways. Quantitative RT-PCR confirmed the strong overexpression of PIK3CD in 6 PTCL-derived cell lines compared to normal T cells from healthy donors. Sequence analyses for the coding region of the PIK3CD gene identified a point mutation in one of these cell lines, described as activating in solid tumors. A panel of 6 PTCL cell lines belonging to different PTCL subgroups was treated with 3 PI3K inhibitors (LY294002, ETP-45658, GDC-0941). Moreover, genetic inhibition was also carried out using small interference RNA to specifically abolish the expression of alpha and delta isoforms of PI3K (PIK3CA and PIK3CD genes, respectively). In vitro studies showed very similar results with the three pharmacological PI3K inhibitors we used: they induced G1 cell cycle arrest in all cell lines, and apoptosis in some of them, in a time/dose-dependent manner. We also observed a decrease in the levels of pAKT(S473) in all cell lines, while pGSK3B(S9) and p-p70S6K(T389) were reduced after treatment only in sensitive cell lines. Our results indicate that genetic inhibition of PI3K delta isoform could induce apoptosis in those PTCL cell lines that were sensitive to PI3K inhibitors, but not in the resistant cell lines; while genetic inhibition of PI3K alpha isoform did not display such effects. Taken together these results could highlight the relevance of PI3K delta isoform in at least a subset of PTCL, indicating that PI3K inhibition, especially delta isoform, could be an effective therapeutic approach for PTCL and identifying potential markers for patients' stratification and pharmacodynamic assessment. Disclosures: No relevant conflicts of interest to declare.
PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A (2012)

The programmed cell death-1 (PD)-1 receptor (CD279) is a potent T cell inhibitor with a critical role in peripheral tolerance, but it can also compromise anti-viral and antitumor T cell responses. The effects of PD-1 on the cell cycle leading to inhibition of T cell expansion are poorly understood. Recently, we examined the effects of PD-1 on the molecular control of the cell cycle machinery and on TCR-activated signaling pathways that regulate these downstream outcomes. Our studies showed that PD-1 blocks cell cycle progression in the G1 phase. PD-1 did not alter the expression of G1 phase cyclins or cyclin-dependent kinases (Cdks) but, instead, suppressed the transcription of SKP2, the substrate recognition component of the SCFSkp2 ubiquitin ligase that leads p27kip1 to degradation and resulted in accumulation of p27kip1. Subsequently, T cells receiving PD-1 signals displayed impaired Cdk2 activation and failed to phosphorylate two critical Cdk2 substrates, the retinoblastoma gene product (Rb) and the TGFβ-specific transcription factor Smad3, leading to suppression of E2F target genes but enhanced Smad3 transactivation. These events resulted in upregulation of the Cdk4/6 inhibitor p15INK4B and repression of the Cdk-activating phosphatase Cdc25A. The suppressive effect of PD-1 on Skp2 expression was mediated by inhibition of both PI3K/Akt and Ras/MEK/Erk pathways and was only partially reversed by IL-2, which restored activation of MEK/Erk but not Akt. Thus, PD-1 targets Ras and PI3K/Akt signaling to inhibit transcription of Skp2 and to activate Smad3 as an integral component of a pathway that regulates blockade of cell cycle progression in T lymphocytes. Here, we discuss the detailed sequence of these signaling events and their implications in mediating cell-intrinsic and -extrinsic mechanisms that inhibit proliferation of T effector cells in response to PD-1-mediated signaling.
Conformational studies on polypeptides. The effect of sodium perchlorate on the conformation of poly‐L‐lysine and of random copolymers of L‐lysine and L‐phenylalanine in aqueous solution (1972)

Abstract Circular Dichroism measurements have been carried out on poly‐ L ‐lysine (PLL) and on random copolymers of lysine and phenylalanine at various p H values and in the presence of different amounts of NaClO 4 . The results indicate that either the homopolymer or the copolymers at p H conditions at which the side‐chain amino groups are fully protonated, assume the right‐handed α‐helical conformation in the presence of NaClO 4 . The results are interpreted in terms of specific binding of ClO 4 − ions on charged side‐chain amino groups.
Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer (2005)

SDF-1 can increase the invasiveness and migration of breast cancer cells. Its levels correlated with node involvement and long-term survival in patients with breast cancer. SDF-1 may therefore have potential value in assessing clinical outcomes of patients with breast cancer.
Smart electric vehicle charging infrastructure overview (2014)

WINSmartEV™ is a smart electric vehicle charging system that has been built and is currently in operation. It is a software and network based EV charging system designed and built around the ideas of intelligent charge scheduling, multiplexing (connecting multiple vehicles to each circuit) and flexibility. This paper gives an overview of this smart charging system with an eye toward its unique features and capabilities.
Hierarchical splatting (1991)

This paper presents a progressive refinement algorithm for volume rendering which uses a pyramidal volume representation. Besides storing average values, the pyramid stores estimated error, so an octtree can be fit to the pyramid given a user-supplied precision. This octtree is then drawn using a set of splats, or footprints, each scaled to match the size of the projection of a cell. The splats themselves are approximated with RGBA Gouraud-shaded polygons, so that they can be drawn efficiently on modern graphics workstations. The result is a real-time rendering algorithm suitable for interactive applications.
Pronephric Tubulogenesis Requires Daam1-Mediated Planar Cell Polarity Signaling (2011)

Canonical β-catenin-mediated Wnt signaling is essential for the induction of nephron development. Noncanonical Wnt/planar cell polarity (PCP) pathways contribute to processes such as cell polarization and cytoskeletal modulation in several tissues. Although PCP components likely establish the plane of polarization in kidney tubulogenesis, whether PCP effectors directly modulate the actin cytoskeleton in tubulogenesis is unknown. Here, we investigated the roles of Wnt PCP components in cytoskeletal assembly during kidney tubule morphogenesis in Xenopus laevis and zebrafish. We found that during tubulogenesis, the developing pronephric anlagen expresses Daam1 and its interacting Rho-GEF (WGEF), which compose one PCP/noncanonical Wnt pathway branch. Knockdown of Daam1 resulted in reduced expression of late pronephric epithelial markers with no apparent effect upon early markers of patterning and determination. Inhibiting various points in the Daam1 signaling pathway significantly reduced pronephric tubulogenesis. These data indicate that pronephric tubulogenesis requires the Daam1/WGEF/Rho PCP pathway.
Automatic word sense discrimination (1998)

This paper presents context-group discrimination, a disambiguation algorithm based on clustering. Senses are interpreted as groups (or clusters) of similar contexts of the ambiguous word. Words, contexts and senses are represented in Word Space, a high-dimensional real-valued space in which closeness corresponds to semantic similarity. Similarity in Word Space is based on second-order co-occurrence: two tokens (or contexts) of the ambiguous word are assigned to the same sense cluster if the words they co-occur with in turn occur with similar words in a training corpus. The algorithm is automatic and unsupervised in both training and application: senses are induced from a corpus without labeled training instances or other external knowledge sources. The paper demonstrates good performance of context-group discrimination for a sample of natural and artificial ambiguous words.
Vaginal Immunization of Monkeys against Urinary Tract Infection with a Multi-Strain Vaccine (1994)

Cynomolgus monkeys were treated with a vaccine containing 10 heat-killed uropathogenic bacteria including 6 Escherichia coli strains. The multi-strain vaccine was administered either as a vaginal surface immunogen or intramuscularly. Following an induced E. coli cystitis, bladder infections were significantly reduced compared with controls at 1 and 2 weeks (intramuscular route) or 1 week (vaginal route) after UTI. This vaccine has been shown to be efficacious against cystitis in humans when given parenterally and has now proved efficacious in nonhuman primates by the vaginal mucosal route.
Nonmevalonate Terpene Biosynthesis Enzymes as Antiinfective Drug Targets:  Substrate Synthesis and High-Throughput Screening Methods (2006)

The nonmevalonate isoprenoid pathway is an established target for antiinfective drug development. This paper describes high-throughput methods for the screening of 2C-methyl-D-erythritol synthase (IspC protein), 4-diphosphocytidyl-2C-methyl-D-erythritol synthase (IspD protein), 4-diphosphocytidyl-2C-methyl-D-erythritol kinase (IspE protein), and 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF protein) against large compound libraries. The assays use up to three auxiliary enzymes. They are all monitored photometrically at 340 nm and are robust as documented by Z-factors of >or=0.86. 13C NMR assays designed for hit verification via direct detection of the primary reaction product are also described. Enzyme-assisted methods for the preparation, on a multigram scale, of isoprenoid biosynthesis intermediates required as substrates for these assays are reported. Notably, these methods enable the introduction of single or multiple 13C labels as required for NMR-monitored assays. The preparation of 4-diphosphosphocytidyl-2C-methyl-D-erythritol 2-phosphate in multigram quantities is described for the first time.
Techniques to achieve optimal seed placement in salvage and primary brachytherapy for prostate cancer. (2000)

Prostate brachytherapy has attracted renewed interest, largely due to advancements in technique. The presented techniques allow brachytherapy to be performed optimally in a broad range of patients.
Delegation Signer (DS) Resource Record (RR) (2003)

The delegation signer (DS) resource record (RR) is inserted at a zone cut (i.e., a delegation point) to indicate that the delegated zone is digitally signed and that the delegated zone recognizes the indicated key as a valid zone key for the delegated zone. The DS RR is a modification to the DNS Security Extensions definition, motivated by operational considerations. The intent is to use this resource record as an explicit statement about the delegation, rather than relying on inference. This document defines the DS RR, gives examples of how it is used and describes the implications on resolvers.
Heat-Related Illnesses (1988)

This chapter in the 2nd edition of the Management of Wilderness and Environmental Emergencies provides background material in the following areas: Physics of heat transfer, physiology of human body temperature regulation, the CNS interface between thermosensors and thermoregulatory effectors, skin blood flow and vasodilation, and acclimatization. The heat illnesses coverage includes information on predisposing factors, thermometry, and fever versus hyperthermia. The review of heat illnesses includes heat cramps, heat edema, heat syncope, heat exhaustion and heat stroke. Treatment coverage includes the differential diagnosis, classical versus exertional forms of heatstroke, the systematic and cellular approach to pathophysiology which includes an organ by organ analysis. The specifies of treatment provides insight to electrolyte abnormalities, acid- base abnormalities and the ABC's of therapy including cooling, modalities, adjunctive measures and prevention. Keywords: Heat stress physiology.
Obesity and lipid profiles in middle aged men and women in Tanzania (2002)

Subjects from the urban area had greater lipid abnormalities related to obesity than those from the rural area and that, central adiposity had a greater effect on total cholesterol and LDL cholesterol among women than was BMI.
Shorthand writing on stylus keyboard (2003)

We propose a method for computer-based speed writing, SHARK (shorthand aided rapid keyboarding), which augments stylus keyboarding with shorthand gesturing. SHARK defines a shorthand symbol for each word according to its movement pattern on an optimized stylus keyboard. The key principles for the SHARK design include high efficiency stemmed from layout optimization, duality of gesturing and stylus tapping, scale and location independent writing, Zipf's law, and skill transfer from tapping to shorthand writing due to pattern consistency. We developed a SHARK system based on a classic handwriting recognition algorithm. A user study demonstrated the feasibility of the SHARK method.
Adaptive listening room equalization using a scalable filtering structure in thewave domain (2012)

Massive multichannel reproduction systems like wave field synthesis (WFS) are potentially well suited to be complemented by listening room equalization (LRE). However, their typically large number of reproduction channels makes this task challenging for both computational and algorithmic reasons. Wave-domain adaptive filtering (WDAF) was proposed earlier and is especially well-suited to adaptive filtering tasks in the context of WFS. In this paper, we propose to generalize the model originally used for WDAF to allow an adaptive LRE for a broader range of reproduction scenarios, while maintaining the advantages of the original approach. The proposed approach is evaluated for filtering structures of varying complexity along with considering the robustness to varying listener positions.