gebhart/patrepeval huggingface dataset:
Proteomic analysis reveals novel ligands and substrates for LNX1 E3 ubiquitin ligase (2017)

Ligand of Numb protein X1 (LNX1) is an E3 ubiquitin ligase that contains a catalytic RING (Really Interesting New Gene) domain and four PDZ (PSD-95, DlgA, ZO-1) domains. LNX1 can ubiquitinate Numb, as well as a number of other ligands. However, the physiological relevance of these interactions in vivo remain unclear. To gain functional insights into the LNX family, we have characterised the LNX1 interactome using affinity purification and mass spectrometry. This approach identified a large number of novel LNX1-interacting proteins, as well as confirming known interactions with NUMB and ERC2. Many of the novel interactions mapped to the LNX PDZ domains, particularly PDZ2, and many showed specificity for LNX1 over the closely related LNX2. We show that PPFIA1 (liprin-α1), KLHL11, KIF7 and ERC2 are substrates for ubiquitination by LNX1. LNX1 ubiquitination of liprin-α1 is dependent on a PDZ binding motif containing a carboxyl terminal cysteine that binds LNX1 PDZ2. Surprisingly, the neuronally-expressed LNX1p70 isoform, that lacks the RING domain, was found to promote ubiquitination of PPFIA1 and KLHL11, albeit to a lesser extent than the longer RING-containing LNX1p80 isoform. Of several E3-ligases identified in the LNX1 interactome we confirm interactions of LNX1 with MID2/TRIM1 and TRIM27. On this basis we propose a model whereby LNX1p70, despite lacking a catalytic RING domain, may function as a scaffold to promote ubiquitination of its ligands through recruitment of other E3-ligases. These findings provide functional insights into the LNX protein family, particularly the neuronal LNX1p70 isoform.
Inhibition of the von Willebrand (VWF)–collagen interaction by an antihuman VWF monoclonal antibody results in abolition of in vivo arterial platelet thrombus formation in baboons (2002)

The interaction between collagen, von Willebrand factor (VWF), and glycoprotein Ib is the first step in hemostasis and thrombosis especially under high shear conditions. We studied the inhibition of the VWF-collagen interaction by using an antihuman VWF monoclonal antibody 82D6A3 to prevent arterial thrombosis in baboons to develop a new kind of antithrombotic strategy and determine for the first time experimental in vivo data concerning the importance of the collagen-VWF interaction. We used a modified Folts model to study the antithrombotic efficacy of 82D6A3, where cyclic flow reductions (CFRs) were measured in the femoral artery. Administering a dose of 100, 300, and 600 microg/kg resulted in a 58.3%, 100%, and 100% reduction in the CFRs, respectively. When 100 microg/kg 82D6A3 was infused into the baboons, 80% of VWF-A3 domain was occupied, corresponding to 30% to 36% ex vivo inhibition of VWF binding to collagen, with no prolongation of the bleeding time. The bleeding time was also not significantly prolonged when the CFRs were abolished at doses of 300 microg/kg and 600 microg/kg. At these doses 100% of VWF was occupied by the antibody and 100% ex vivo inhibition of the VWF-collagen binding was observed. 82D6A3 has a high affinity for VWF; after 48 hours still 68% VWF (300 microg/kg) was occupied with a pharmacologic effect up to 5 hours after administration (80%-100% occupancy). In conclusion, these results clearly indicate that the VWF-collagen interaction is important in vivo in thrombosis under high shear conditions and thus might be a new target for preventing arterial thrombosis.
Long‐term kinetics of adult human antibody repertoires (2002)

In healthy humans, antibody repertoires change during ontogeny and senescence. The dynamics of antibody repertoires among adults over a longer period of time in one and the same individual has, however, not been extensively studied. In this study we analysed peripheral blood samples from five healthy adults, taken over a period of 10 weeks and once 9 years later. A competitive, quantitative polymerase chain reaction (PCR) was developed to investigate short and long-term variations in VH gene family repertoires. Serum antibody levels to common self and non-self antigens were determined in samples taken at the same time-points as the cell samples to analyse possible correlations between molecular and serological expression profiles. We found a high degree of stability in the VH gene family repertoire over time as well as between individuals with a Caucasian background. A specific change in the usage of primarily the VH3 and VH5 gene families was observed in one individual at one time-point. The deviating pattern resembled the VH gene family utilization pattern observed in naturally activated B lymphocytes. The fluctuations in VH3 and VH5 gene family expression correlated with the presence of rheumatoid factor in serum. We discuss the possible influence of polyclonal, transient stimulation of B cells on VH gene repertoires, as measured in circulating B cells.
Study of fin-tunnel FETs with doped pocket as capacitor-less 1T DRAM (2014)

In this work we propose and validate by experimentally calibrated simulations a silicon Tunnel FET(TFET) based capacitorless DRAM cell, implemented as a fully-depleted FinFET with CMOS compatible process. The devices have a conventional FinFET structure except for a p+ (for n-type TFET) doped pocket of length L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PKT</sub> and doping N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">PKT</sub> between the intrinsic channel and the (n++) drain. This doped pocket creates a necessary condition to store holes injected from the source-to-body junction. In [1], there was a need to induce a potential well in order to store the excess charges; whereas in the present case a potential well is permanently present due to the doped pocket. The drain voltage is used as a control voltage to either fill the potential well with carriers (WRITE “1”) by attracting holes from the p++ source or repel them to empty the well of carriers (WRITE “0”). In contrast with the SOI Z-RAM® there is no need of impact ionization to create/inject the hole charge in the device body, the holes being injected by the forward-bias p+i junction, which significantly improves the device reliability. Measurements on FDSOI TFET devices as reported in [1,2] were performed at elevated temperatures and used to calibrate the non-local band-to-band (B2B) tunnelling model in Sentaurus TCAD [3]. The retention characteristics of the proposed memory cell is simulated at an elevated temperature of 85°C and is shown to be not degrading at higher temperature as is the case in conventional capacitorless DRAMs [4].
Islet-1 marks the early heart rudiments and is asymmetrically expressed during early rotation of the foregut in the chick embryo (2000)

Islet-1 (Isl-1), the LIM domain homeobox gene, is a well-known early marker of neuronal specification. Here, we show its spatial and temporal patterns of expression during early heart and gut development in the chick embryo. Isl-1 transcripts are first detected in the early cardiac progenitors and underlying endoderm at late stage 4. By stages 5-6, it is also expressed in the prechordal plate. From stage 6 onward, transcripts are also detected in the endoderm forming the anterior intestinal portal and floor of the caudal foregut. With progressive rostrocaudal fusion of the paired cardiac rudiments, Isl-1 expression is maintained in the cardiac mesoderm and associated endoderm. By the onset of heart beating, transcripts become restricted to the dorsal mesocardium and more caudal medial splanchnic mesoderm flanking the open gut. Within the foregut, Isl-1 is expressed in the endoderm of the oral membrane, thyroid rudiment, and second pharyngeal pouches, as well as within the second branchial grooves adjacent to the secondary pouches. Interestingly, with the onset of gut rotation, Isl-1 expression is detected unilaterally in the splanchnic mesodermal wall of the future greater curvature of the caudal stomach/rostral duodenum. Thus, Isl-1 is a novel and useful marker of the early cardiac rudiments and of the original left side of the rotating foregut. During early organogenesis, Isl-1 is also expressed in several other discrete domains as reported previously. Additionally, it is expressed at the interface between the hind limbs and trunk.
Vascularized tissue‐engineered chambers promote survival and function of transplanted islets and improve glycemic control (2006)

We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."
Genes encoding melanoma antigens (1993)

Ludwig Institute for Cancer Research, Brussels Branch, Belgium and Université Catholique de Louvain, Brussels, Belgium
A Large Kindred With 17q-Linked Breast and Ovarian Cancer: Genetic, Phenotypic, and Genealogical Analysis (1994)

Women with the BRCA1 mutation are at increased risk of developing breast and ovarian cancer. In our study population, the mutation appears to confer a lower risk of cancer at younger ages than found in previous studies. Continued interaction with family K2082 will be useful in longitudinal follow-up studies and in studies of the psychosocial implications of providing DNA diagnosis of BRCA1.
Rapid ‘de novo’ peptide sequencing by a combination of nanoelectrospray, isotopic labeling and a quadrupole/time-of-flight mass spectrometer (1997)

Protein microanalysis usually involves the sequencing of gel-separated proteins available in very small amounts. While mass spectrometry has become the method of choice for identifying proteins in databases, in almost all laboratories 'de novo' protein sequencing is still performed by Edman degradation. Here we show that a combination of the nanoelectrospray ion source, isotopic end labeling of peptides and a quadrupole/ time-of-flight instrument allows facile read-out of the sequences of tryptic peptides. Isotopic labeling was performed by enzymatic digestion of proteins in 1:1 16O/18O water, eliminating the need for peptide derivatization. A quadrupole/time-of-flight mass spectrometer was constructed from a triple quadrupole and an electrospray time-of-flight instrument. Tandem mass spectra of peptides were obtained with better than 50 ppm mass accuracy and resolution routinely in excess of 5000. Unique and error tolerant identification of yeast proteins as well as the sequencing of a novel protein illustrate the potential of the approach. The high data quality in tandem mass spectra and the additional information provided by the isotopic end labeling of peptides enabled automated interpretation of the spectra via simple software algorithms. The technique demonstrated here removes one of the last obstacles to routine and high throughput protein sequencing by mass spectrometry.
Interleukin-13 Receptor Alpha 2-Targeted Glioblastoma Immunotherapy (2014)

Glioblastoma (GBM) is the most lethal primary brain tumor, and despite several refinements in its multimodal management, generally has very poor prognosis. Targeted immunotherapy is an emerging field of research that shows great promise in the treatment of GBM. One of the most extensively studied targets is the interleukin-13 receptor alpha chain variant 2 (IL13Rα2). Its selective expression on GBM, discovered almost two decades ago, has been a target for therapy ever since. Immunotherapeutic strategies have been developed targeting IL13Rα2, including monoclonal antibodies as well as cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-expressing T cells. Advanced therapeutic development has led to the completion of several clinical trials with promising outcomes. In this review, we will discuss the recent advances in the IL13Rα2-targeted immunotherapy and evaluate the most promising strategy for targeted GBM immunotherapy.
Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa (2004)

rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.
Long Thin Networks (2000)

In view of the unpredictable and problematic nature of long thin networks (for example, wireless WANs), arriving at an optimized transport is a daunting task. We have reviewed the existing proposals along with future research items. Based on this overview, we also recommend mechanisms for implementation in long thin networks.
Examining Our Assumptions – Have Oversimplifications Jeopardized Our Ability to Design Optimal Fracture Treatments? (2009)

Abstract In the design of hydraulic fractures, it is necessary to make simplifying assumptions. Fifty years ago, our industry was mathematically obliged to describe fractures as simple, planar structures when attempting to predict fracture geometry and optimize treatments. Although computing tools have improved, as an industry we remain incapable of fully describing the complexity of the fracture, reservoir, and fluid flow regimes. Generally, we make some or all of the following assumptions: –Simple, planar, bi-wing fractures–Completely vertical fractures with perfect connection to the wellbore–Flow capacity that is reasonably described by published conductivity data–Predictable fracture width providing dependable hydraulic continuity (lateral and vertical continuity) To forecast production from these fractures, we frequently make the additional assumptions: –Reservoir is laterally homogeneous–Modest/no barriers to vertical flow in formation (simplified description of layering compared to reality) However, we must recognize that all of these assumptions are imperfect. This paper will investigate the evidence suggesting that fractures are often subject to: –Complicated flow regimes–Complicated geometry–Irregular frac faces–Imperfect proppant distribution–Imperfect hydraulic continuity–Imperfect wellbore-to-fracture connection–Residual gel damage, possibly including complete plugging or fracture occlusion Additionally, reservoirs are known to contain flow barriers that amplify the need for fractures to provide hydraulic continuity in both vertical and lateral extent. The paper appendix tabulates the results from more than 200 published field studies in which fracture design was altered to improve production. Frequently the field results cannot be explained with our simplistic assumptions. This paper will list the design changes successfully implemented to accommodate real-world complexities that are not described in simplistic models or conventional rules of thumb. Field examples from a variety of reservoir and completion types [tight gas, modest perm oil, coalbed methane, low rate shallow gas, annular gravel packs] will be provided to demonstrate where the field results differ from expectations, and what adjustments are necessary to history-match the results.
Chemical Composition and Antimicrobial Activity of Essential Oils ofJasonia candicansandJ. montana (1993)

The essential oils of the aerial parts of Jasonia candicans and J. montana were analyzed by gas chromatography-mass spectrometry (GC/MS) technique. Of twenty-one components identified in the volatile oil of J. candicans, intermediol was the main constituent. Fifty-eight components were characterized in the essential oil of J. montana. Camphor, borneol, bornyl acetate, chrysanthemol, intermediol, and 1,8-cineole were the major constituents in this oil. The two oils showed antibacterial activity against Bacillus subtilis. They also showed a marked antifungal activity against Trichophyton mentagrophytes, Cryptococcus neoformans, and Candida albicans.
A phase I/II study of INCB018424, an oral, selective JAK inhibitor, in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF) (2008)

7004 Background: Mutations in JAK2 and MPL have been recognized in Philadelphia chromosome-negative myeloproliferative disorders, including PV, ET and PMF, making Janus associated kinase (JAK) a therapeutic target for these diseases. INCB018424 is a potent, selective and orally bioavailable JAK inhibitor with an excellent safety profile supporting its clinical evaluation. Methods: A phase I/II trial of INCB018424 given orally BID is being conducted in patients with PMF and Post-PV/ET MF. Primary end points in this study are responses according to the International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia (IWG-MRT). Results: Overall characteristics of the 32 patients enrolled include median age of 65 yrs; 67% males; 47% PMF, 38% post-PV and 15% post ET; and 87% with JAK2V617F mutation. The starting dose of 25 mg PO BID was demonstrated to be the maximum tolerated dose (MTD) (N = 6 pts). Two patients had grade 4 thrombocytopenia in the 50 mg PO BID cohort (N = 5 pts) which defined the dose limiting toxicity. No other significant drug-related toxicities were noted. An expanded cohort of 21 additional patients has also been enrolled at the MTD, all of whom completed at least 1 month of therapy. A rapid and significant reduction in splenomegaly was observed in the patients with palpable spleens at baseline with reductions of 53% at 1 month (N = 24), and 76% at 3 months (N = 7). In addition, the majority of patients had improvement in their ECOG PS to 0 and their constitutional symptoms resolved or were significantly reduced. Additional drug- related improvements included transfusion independence in the initial patient enrolled on the study, significant reduction in JK2V617F allele burden, marked reduction in proinflammatory and angiogenic cytokines, significant increases in hematopoietic growth factors and normalization of phosphorylated Stat3. Conclusions: Treatment with INCB018424 results in unprecedented clinical activity in PMF and post-PV/ET MF without significant toxicity. Clinical improvements occurred regardless of mutation status or MPD diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Incyte Corporation Incyte Corporation Incyte Corporation Incyte Corporation
Characterization of Microstructure of Interfacial Transition Zone in Concrete (2005)

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Localization of thioredoxin from Escherichia coli in an osmotically sensitive compartment. (1982)

The low molecular weight dithiol protein thioredoxin was released from Escherichia coli strain W3110 grown to mid-log phase b y several nondisruptive treatments.Rapid freezing of cells in media or in a Tris buffer (pH 7.4) containing 3 mM EDTA released greater than 90% of the thioredoxin.Thioredoxin was also quantitatively released b y the osmotic shock procedures described by
Fibroblast transgelin and smooth muscle SM22α are the same protein, the expression of which is down-regulated in many cell lines (1997)

In this report we investigate the expression and relationship of transgelin (Tg), a transformation and shape-change sensitive actin gelling protein found in fibroblasts and smooth muscle [Shapland et al., 1988: J. Cell. Biol. 107:153-161; Shapland et al., 1993: J. Cell. Biol. 121:1065-1073], to SM22alpha, a smooth muscle protein of unknown function [Lees-Millar et al., 1987: J. Biol. Chem. 262:2988-2993; Solway et al., 1995: J. Biol. Chem. 270:13460-13469]. To clarify their relationship we have cloned and sequenced the cDNA encoding Tg from cultures of rat embryo fibroblasts. The sequences of fibroblast Tg and the smooth muscle isoform SM22 are identical [Prinjha et al., 1994: Cell Motil. Cytoskeleton 28:243-255; Shanahan et al., 1993: Circ. Res. 73:193-204; Solway et al., 1995]. These data, coupled with our immunoblot analysis and previous observations [Shapland et al., 1988; Shapland et al., 1993], demonstrate that Tg expression is not restricted to smooth muscle since this protein is also present in normal mesenchymal cells. However, we also show that Tg, although present in secondary cultures of mouse and rat embryo fibroblasts, is absent in many apparently normal fibroblast cell lines. Tg down-regulation may therefore be an early and sensitive marker for the onset of transformation. A functional role for Tg is unlikely to directly involve Ca2+ since it neither contains a functional EF hand nor binds 45Ca2+.
Human Protein MCM6 on HeLa Cell Chromatin (1998)

Minichromosome maintenance (Mcm) proteins perform essential functions regulating the replication of chromatin. Human cells, like other eukaryotic cells, express at least six Mcm proteins conserved in the central region. We have earlier described the primary structures of five human Mcm proteins, but the primary structure of the sixth human Mcm protein, MCM6, was identified only recently. We now use antibodies, specific for the MCM6 protein, to assess its intranuclear distribution. We find that a fraction of MCM6 protein occurs in the nucleosol, forming multiprotein complexes with other Mcm proteins. More importantly, we use for the first time micrococcal nuclease as a tool to investigate the association of MCM6 protein with chromatin. After short digestion times, a considerable fraction of the MCM6 protein is released from chromatin as a multiprotein complex that includes other Mcm proteins as well. In addition, fractions of MCM3 and MCM6 proteins are released by nuclease digestion as monomeric proteins indicating that at least these two Mcm proteins may also occur as single molecules on chromatin. The data also suggest that the chromatin regions with bound Mcm proteins are more vulnerable to nuclease attack than bulk chromatin and may therefore differ in the arrangement of nucleosomes.
Weekly Trastuzumab and Paclitaxel Therapy for Metastatic Breast Cancer With Analysis of Efficacy by HER2 Immunophenotype and Gene Amplification (2001)

Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.