gebhart/patrepeval huggingface dataset:
Platelet-derived Growth Factor Stimulates Membrane Lipid Synthesis Through Activation of Phosphatidylinositol 3-Kinase and Sterol Regulatory Element-binding Proteins (2004)

We analyzed the transcriptional program elicited by stimulation of normal human fibroblasts with platelet-derived growth factor (PDGF) using cDNA microarrays. 103 significantly regulated transcripts that had not been previously linked to PDGF signaling were identified. Among them, a cluster of genes involved in fatty acid and cholesterol biosynthesis, including stearoyl-CoA desaturase (SCD), fatty acid synthase, and hydroxymethylglutaryl-CoA synthase (HMGCS), was up-regulated by PDGF after 24 h of treatment, and their expression correlated with increased membrane lipid production. These genes are known to be controlled by sterol regulatory element-binding proteins (SREBP). PDGF increased the amount of mature SREBP-1 and regulated the promoters of SCD and HMGCS in an SREBP-dependent manner. In line with these results, blocking SREBP processing by addition of 25-hydroxycholesterol blunted the effects of PDGF on lipogenic enzymes. SREBP activation was dependent on the phosphatidylinositol 3-kinase (PI3K) pathway, as judged from the effects of the inhibitor LY294002 and mutation of the PDGFbeta receptor tyrosines that bind the PI3K adaptor subunit p85. Fibroblast growth factors (FGF-2 and FGF-4) and other growth factors mimicked the effects of PDGF on NIH3T3 and human fibroblasts. In conclusion, our results suggest that growth factors induce membrane lipid synthesis via the activation SREBP and PI3K.
Reconstitution of CD3 zeta coupling to calcium mobilization via genetic complementation (1994)

The integrity of the T cell receptor complex (CD3-TCR) transduction machinery is central to T cell development and to T cell effector function. Molecular dissection of the multimeric CD3-TCR complex revealed that at least two associated polypeptides, CD3 zeta and CD3 epsilon, autonomously couple antigenic recognition event to early and late events of the intracytoplasmic activation cascade. A 18-amino acid motif based on a tandem YXXL stretch, the activation receptor homology sequence 1 (ARH-1) motif, is necessary and sufficient to the transducing properties of both CD3 zeta and CD3 epsilon. Stimulation of chimeric molecules made of ecto- and transmembrane domains of various cell surface proteins and intracytoplasmic domains of CD3 epsilon or CD3 zeta leads to an increase in the intracellular Ca2+ concentration ([Ca2+]i) in Jurkat cells. We describe here that a similar CD25/zeta chimeric molecule was unable to induce a detectable [Ca2+]i rise upon CD25 cross-linking once expressed in the murine thymoma BW-. A Ca2+ influx could, however, be triggered in BW- cells by thapsigargin, i.e. following depletion of Ca2+ stores. Somatic cell hybrids made from BW- and either thymocytes or mature lymph node T cells reconstituted the coupling of CD3 zeta to the Ca2+ signal via an ARH-1 motif-dependent pathway. However, pervanadate-induced Ca2+ mobilization, a phenomenon attributed to tyrosine phosphorylation, was impaired in BW-cells and reconstituted in hybridomas. In contrast to the Ca2+ response, IL-2 production was induced in both BW- and hybrids cells, which questions the functional relevance of [Ca2+]i augmentation in T cell activation. In conclusion, the properties of the BW- thymoma, which define a novel group of CD3 zeta transduction cell mutants, as well as its complementation by somatic cell fusion demonstrate that this cell line represents a useful model to dissect the signaling pathway that couples CD3 zeta to Ca2+ mobilization by genetic reconstitution.
Efficient CD4 binding and immunosuppressive properties of the 13B8.2 monoclonal antibody are displayed by its CDR-H1-derived peptide CB1 (2001)

73 ref.
Redox Behavior of an Organometallic Palladium(II)/Palladium(IV) System. A New Method for the Synthesis of Cationic Palladium(IV) Complexes (2005)

A new method for the synthesis of cationic Pd(IV) complexes, based on the chemical oxidation of an anionic Pd(II) metallacycle in the presence of an additional ligand, is presented. Electrochemical analysis of these compounds reveals that the stability of the +4 oxidation state is sensitive to the electron-donor capability of the added co-ligand and to the steric features of the Tp‘ ligand.
Adenovirus type 9 E4 open reading frame 1 encodes a transforming protein required for the production of mammary tumors in rats (1994)

The E4 region of human adenovirus type 9 (Ad9) transforms established rat embryo fibroblasts and encodes an essential determinant for the production of estrogen-dependent mammary tumors in rats. Testing of the seven Ad9 E4 open reading frames (ORFs) individually for transformation of the established rat embryo fibroblast cell line CREF indicated that only Ad9 E4 ORF1 possessed a significant ability to generate transformed foci on these cells. In contrast, the E4 ORF1 sequences from human Ad5 and Ad12 lacked the transforming potential exhibited by Ad9 E4 ORF1. Cell lines derived from Ad9 E4 ORF1-transformed foci expressed the 14-kDa Ad9 E4 ORF1 protein and formed colonies in soft agar. In addition, the Ad9 E4 ORF1 protein was required for initiation of mammary oncogenesis in vivo, as E4 ORF1 mutant viruses failed while E4 ORF2 and ORF3 mutant viruses succeeded in eliciting mammary tumors in animals. A role for Ad9 E4 ORF1 in tumor maintenance was suggested by the fact that 100% of virus-induced mammary tumors expressed the E4 ORF1 protein. Taken together, the facts that the Ad9 E4 ORF1 protein exhibits transforming potential in culture and is required by Ad9 to produce mammary tumors in animals suggest that Ad9 E4 ORF1 is a new viral oncoprotein.
A high-performance long wavelength superlattice complementary barrier infrared detector (2009)

We describe a long wavelength infrared detector where an InAs/GaSb superlattice absorber is surrounded by a pair of electron-blocking and hole-blocking unipolar barriers. A 9.9 μm cutoff device without antireflection coating based on this complementary barrier infrared detector design exhibits a responsivity of 1.5 A/W and a dark current density of 0.99×10−5 A/cm2 at 77 K under 0.2 V bias. The detector reaches 300 K background limited infrared photodetection (BLIP) operation at 87 K, with a black-body BLIP D∗ value of 1.1×1011 cm Hz1/2/W for f/2 optics under 0.2 V bias.
Co-catalytic effect of nickel in Pt-Ru/C and Pt-Sn/C electrocatalysts for ethanol electrooxidation (2010)

-In the present study, we examined the effect of adding nickel to Pt-Ru and Pt-Sn catalysts for ethanol electrooxidation. The alcohol-reduction process with ethylene glycol was used to prepare ten electrocatalysts. These were microchemically and physically characterized by EDX and XRD analysis. The electrocatalysts were evaluated at minielectrodes with cyclic voltammetry at 25 and 50 °C in sulfuric acid and ethanol solutions, and as anodes in fuel cell tests. Nickel addition to Pt-Ru mixtures significantly increased the catalytic activity toward ethanol electrooxidation. For Pt-Ru-Ni catalysts, the current density was around five times greater than all other investigated mixtures. Nickel also duplicated the catalytic activity of the Pt-Sn catalyst. Furthermore ethanol electrooxidation increased with temperature for most catalytic mixtures, and the electrocatalytic activity of mixtures containing nickel, demonstrate a considerable increase with temperature. Pt-Ru-Ni catalytic activity was higher than that of all other investigated mixtures. The fuel cell test demonstrated that the addition of nickel to Pt-Ru and Pt-Sn catalysts enhances the performance of the DEFC. Keywords-Ethanol; Electrooxidation; PtRuNi; PtSnNi; Fuel cell.
G-OPEP: An On-Demand Group Key Agreement Protocol for MANETs (2006)

Securing a multicast architecture is a basic procedure in order to avoid attacks and guarantee the communication integrity and confidentiality. This becomes more vital when dealing with ad hoc network. The lack of physical and administrative infrastructure and the dynamic topology, make the ad-hoc network more arduous to be secured. In this paper, we propose a key management protocol to secure ad-hoc network. Our proposal relies on the routing mechanism.
Glass coating for PDMS microfluidic channels by sol–gel methods (2008)

Soft lithography using polydimethylsiloxane (PDMS) allows one to fabricate complex microfluidic devices easily and at low cost. However, PDMS swells in the presence of many organic solvents significantly degrading the performance of the device. We present a method to coat PDMS channels with a glass-like layer using sol-gel chemistry. This coating greatly increases chemical resistance of the channels; moreover, it can be functionalized with a wide range of chemicals to precisely control interfacial properties. This method combines the ease of fabrication afforded by soft-lithography with the precision control and chemical robustness afforded by glass.
Calcium Depletion Dissociates and Activates Heterodimeric Notch Receptors (2000)

Notch receptors participate in a highly conserved signaling pathway that regulates morphogenesis in multicellular animals. Maturation of Notch receptors requires the proteolytic cleavage of a single precursor polypeptide to produce a heterodimer composed of a ligand-binding extracellular domain (N(EC)) and a single-pass transmembrane signaling domain (N(TM)). Notch signaling has been correlated with additional ligand-induced proteolytic cleavages, as well as with nuclear translocation of the intracellular portion of N(TM) (N(ICD)). In the current work, we show that the N(EC) and N(TM) subunits of Drosophila Notch and human Notch1 (hN1) interact noncovalently. N(EC)-N(TM) interaction was disrupted by 0.1% sodium dodecyl sulfate or divalent cation chelators such as EDTA, and stabilized by millimolar Ca(2+). Deletion of the Ca(2+)-binding Lin12-Notch (LN) repeats from the N(EC) subunit resulted in spontaneous shedding of N(EC) into conditioned medium, implying that the LN repeats are important in maintaining the interaction of N(EC) and N(TM). The functional consequences of EDTA-induced N(EC) dissociation were studied by using hN1-expressing NIH 3T3 cells. Treatment of these cells for 10 to 15 min with 0.5 to 10 mM EDTA resulted in the rapid shedding of N(EC), the transient appearance of a polypeptide of the expected size of N(ICD), increased intranuclear anti-Notch1 staining, and the transient activation of an Notch-sensitive reporter gene. EDTA treatment of HeLa cells expressing endogenous Notch1 also stimulated reporter gene activity to a degree equivalent to that resulting from exposure of the cells to the ligand Delta1. These findings indicate that receptor activation can occur as a consequence of N(EC) dissociation, which relieves inhibition of the intrinsically active N(TM) subunit.
Peptide‐Based Methods for the Preparation of Nanostructured Inorganic Materials (2010)

With their unique sequence-specific self-assembly and their substrate recognition properties, peptides play critical roles in controlling the biomineralization of inorganic nanostructures in natural systems and in directing the assembly of important soft matter. These attributes render them particularly useful molecules for the fabrication of new materials. Researchers from many scientific disciplines now use peptides to direct the synthesis of new inorganic nanostructures and the assembly of soft biomaterials. In this Review we describe the developments in this field and focus on the versatility of peptides and their ability to direct the composition and structure of new inorganic materials.
Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy (2015)

The β-catenin signaling pathway has been demonstrated to promote the development of a tolerogenic dendritic cell (DC) population capable of driving regulatory T-cell (Treg) differentiation. Further studies have implicated tolerogenic DCs in promoting carcinogenesis in preclinical models. The molecular mechanisms underlying the establishment of immune tolerance by this DC population are poorly understood, and the methods by which developing cancers can co-opt this pathway to subvert immune surveillance are currently unknown. This work demonstrates that melanoma-derived Wnt5a ligand upregulates the durable expression and activity of the indoleamine 2,3-dioxygenase-1 (IDO) enzyme by local DCs in a manner that depends upon the β-catenin signaling pathway. These data indicate that Wnt5a-conditioned DCs promote the differentiation of Tregs in an IDO-dependent manner, and that this process serves to suppress melanoma immune surveillance. We further show that the genetic silencing of the PORCN membrane-bound O-acyl transferase, which is necessary for melanoma Wnt ligand secretion, enhances antitumor T-cell immunity, and that the pharmacologic inhibition of this enzyme synergistically suppresses melanoma progression when combined with anti-CTLA-4 antibody therapy. Finally, our data suggest that β-catenin signaling activity, based on a target gene expression profile that includes IDO in human sentinel lymph node-derived DCs, is associated with melanoma disease burden and diminished progression-free survival. This work implicates the Wnt-β-catenin signaling pathway as a novel therapeutic target in the melanoma immune microenvironment and demonstrates the potential impact of manipulating DC function as a strategy for optimizing tumor immunotherapy.
Neuron‐specific enolase: Complete structure of rat mRNA, multiple transcriptional start sites, and evidence suggesting post‐transcriptional control (1986)

The protein encoded by a randomly selected rat brain cDNA clone was identified as neuron-specific enolase (NSE; 4.2.1.11; gamma subunit), based on homology to yeast enolase sequences and the presence of the corresponding 2.5-kb mRNA in rat brain but not in liver, kidney, or muscle tissue. The 2,222-nucleotide NSE and mRNA sequence presented identifies a 68-nucleotide 5' noncoding region, a 1,302-nucleotide open reading frame (corresponding to a primary translation product of 434 amino acids), and 852 noncoding 3' bases. Evolutionary implications based on sequence comparisons to yeast enolase and non-neuronal enolase are discussed. Primer extension analysis indicated the presence of several alternative initiation sites for transcription within 60 nucleotides on the NSE gene. The developmental onset of NSE mRNA expression correlates with the appearance of NSE protein; however, the mRNA reaches adult levels by postnatal week 3, whereas the protein continues to accumulate over the next few months, suggesting regulatory mechanisms in addition to transcriptional control.
Performance Evaluation of Trilateral Wells: Field Examples (1995)

Summary Recent advances in horizontal drilling and completion technology have led to the successful completion of multilateral horizontal wells (wells with two or more laterals penetrating separate zones that produce through a single wellbore to the surface). Evaluating performance of these commingled horizontal wells poses unique problems that have led to development of a practical procedure for that puφose. This paper demonstrates a practical procedure used in evaluating the performance of three lateral (trilateral) horizontal wells. The procedure, coupling the analysis of pressure-buildup and rate/time data, involves use of a consistent mathematical model to generate pressure and rate responses for pressure-test interpretation and performance prediction. The procedure is demonstrated for several new trilateral wells drilled in the Dos Cuadras field, offshore California. Results from field tests indicate that the procedure is efficient in evaluating the performance of these wells. Reservoir and well parameters are obtained and the contribution of all laterals is confirmed from pressure-test interpretation. The computed model parameters are then used in a rate history match and accurate long-term performance predictions are made. Deconvolution is shown to improve the history-match process. In addition, the performance evaluation of these trilateral wells is compared with previously drilled single-lateral horizontal wells in the same field. The comparison confirms that the new trilateral horizontal well technology is economically viable, allowing reserves to be developed for approximately two-thirds the cost of three single-lateral horizontal wells.
A phase 2, multicenter study to assess the efficacy and safety of autologous tumor-infiltrating lymphocytes (LN-144) for the treatment of patients with metastatic melanoma. (2018)

TPS9595 Background: Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) is recognized as an effective treatment in metastatic melanoma and other solid tumors elliciting durable and complete responses, even in heavily pretreated patients. Despite recent approvals of multiple checkpoint-directed therapies there remains an unmet need to improve therapeutic outcomes in patients with metastatic melanoma post checkpoint therapy. The C-144-01 study is evaluating TIL therapy with LN-144 in metastatic melanoma patients who have progressed on prior checkpoint-targeted therapy. C-144-01 is a phase 2 multicenter, open-label study enrolling patients in the US and Europe. LN-144 is manufactured at centralized GMP facilities providing either a non-cryopreserved (Gen 1), or a second generation cryopreserved (Gen 2) TIL infusion product. The Gen 2 process reduces manufacturing time for LN-144 to 22 days, allowing for dramatic efficiencies in scheduling, distribution and delivery needed for commercial use. Methods: Three treatment cohorts are being evaluated: Cohort 1 (N = 30) patients receive a single dose of Gen 1 LN-144; Cohort 2 (N = 30) patients receive a single dose of Gen 2 LN-144; and up to 10 eligible patients from either Cohort 1 or Cohort 2 may enroll in Cohort 3 for re-treatment with a second dose of LN-144. For patients in all cohorts, TIL for LN-144 manufacturing are extracted from surgically-resected tumors. LN-144 infusion is preceded by a non-myeloablative lymphodepletion regimen of Cy/Flu, and followed by up to 6 infusions of IV IL-2. Patients ≥ 18 years of age must have confirmed stage IIIc/IV met. melanoma and have progressed following ≥1 line of prior systemic therapy including an immune checkpoint inhibitor and BRAF-targeted therapy (if BRAF mutation-positive). Other major eligibility criteria include: minimum of 2 tumor lesions; adequate organ function; ECOG PS of 0 or 1. The primary endpoint is the evaluation of efficacy of LN-144 using ORR per RECIST 1.1; secondary endpoints are CR rate, DOR, DCR, PFS, OS, and safety. Key exploratory objectives include tumor response per irRECIST, immune correlates of response, and HRQoL. Clinical trial information: NCT02360579.
Measurements of Dynamic Properties of Materials. Volume 3. 6061-T6 Aluminum (1971)

Results of an experimental study on the dynamic properties of 6061-T6 aluminum are presented. Areas studied included stress-strain-strain rate and reverse loading behavior, elastic constants, equation of state, compressive and release wave characteristics, and spall fracture. The shock wave equation of state (EOS) calculated from the elastic constants and comparisons made with the shock wave EOS. Compressive wave tests showed a well-defined elastic precursor with a steady-state value of approximately 5 kbar. The yield level from shock wave profile measurements was approximately the same as that determined from uniaxial stress and EOS tests. The impact velocity required for spall fracture was found to increase with decreasing pulse width, and to decrease with increasing temperature.
IP Fast Reroute Using Not-via Addresses (2006)

This draft describes a mechanism that provides fast reroute in an IP
network through encapsulation to not-via addresses. A single level
of encapsulation is used. The mechanism protects unicast, multicast
and LDP traffic against link, router and shared risk group failure,
regardless of network topology and metrics.
Involvement of 5-HT3receptors in pudendal inhibition of bladder overactivity in cats (2013)

In the present study, the role of 5-HT3 receptors in pudendal neuromodulation of bladder activity and its interaction with opioid receptors were investigated in anesthetized cats. The bladder was distended with either saline to induce normal bladder activity or with 0.25% acetic acid (AA) to induce bladder overactivity. Pudendal afferent nerves were activated by 5-Hz stimulation at multiples of the threshold (T) intensity for the induction of anal twitching. AA irritation significantly reduced bladder capacity to 16.5 ± 3.3% of saline control capacity, whereas pudendal nerve stimulation (PNS) at 1.5-2 and 3-4 T restored the capacity to 82.0 ± 12% (P = 0.0001) and 98.6 ± 15% (P < 0.0001), respectively. Cumulative doses (1-3 mg/kg iv) of ondansetron, a 5-HT3 receptor antagonist, eliminated low-intensity (1.5-2 T) PNS inhibition and reduced high-intensity (3-4 T) PNS inhibition of bladder overactivity. During saline distention, PNS at 1.5-2 and 3-4 T significantly increased bladder capacity to 173.2 ± 26.4% (P = 0.036) and 193.2 ± 22.5% (P = 0.008), respectively, of saline control capacity, but ondansetron (0.003-3 mg/kg iv) did not alter PNS inhibition. Ondansetron (0.1-3 mg/kg) also significantly (P < 0.05) increased control bladder capacity (50-200%) during either AA irritation or saline distention. In both conditions, the effects of low- and high-intensity PNS were not significantly different. After ondansetron (3 mg/kg) treatment, naloxone (1 mg/kg iv) significantly (P < 0.05) decreased control bladder capacity (40-70%) during either AA irritation or saline distention but failed to affect PNS inhibition. This study revealed that activation of 5-HT3 receptors has a role in PNS inhibition of bladder overactivity. It also indicated that 5-HT3 receptor antagonists might be useful for the treatment of overactive bladder symptoms.
Human GM-CSF: Molecular Cloning of the Complementary DNA and Purification of the Natural and Recombinant Proteins (1985)

Clones of complementary DNA encoding the human lymphokine known as granulocyte-macrophage colony-stimulating factor (GM-CSF) were isolated by means of a mammalian cell (monkey COS cell) expression screening system. One of these clones was used to produce recombinant GM-CSF in mammalian cells. The recombinant hematopoietin was similar to the natural product that was purified to apparent homogeneity from medium conditioned by a human T-cell line. The human T-cell GM-CSF was found to be 60 percent homologous with the GM-CSF recently cloned from murine lung messenger RNA.
Quality of life in psoriasis patients (2014)

Patient-reported outcomes are major components of decision making in clinical research, reimbursement, health policy and health care for psoriasis. The most important construct in patient-reported outcomes is health-related quality of life (HRQoL) which encompasses the individual's well-being with respect to health. HRQoL cannot directly be measured but is assessed in single dimensions, especially physical, emotional, social and functional aspects. For this, disease- and condition-specific instruments are used. Psoriasis is a chronic inflammatory disease affecting the skin as well as other tissues and organ systems. Patients suffer from a large scale of impairments, for example, physical symptoms, stigmatization and embarrassment, psychological strain and disabilities in profession. Improvement of HRQoL is a major objective of disease management. Current knowledge on determinants of HRQoL and the treatments available increase QoL in clinical care.