gebhart/patrepeval huggingface dataset:
Stem Cells in Epithelial Tissues (2000)

Most, if not all, epithelial tissues contain stem cells. They are responsible for normal tissue renewal or for regeneration following damage. Our present knowledge of their properties is limited and is mainly derived from studies of cell kinetics and from clonal analysis.
Report of a phase II study of sphingosomal vincristine (SV) in patients with relapsed or refractory Hodgkin’s disease (2005)

6624 Background: Combination therapy is often not an option for multiple relapsed/refractory Hodgkin’s disease patients particularly after salvage high-dose chemotherapy and transplant. Vincristine is a cell cycle-specific anticancer drug, with established activity in Hodgkin’s disease. Sphingosomal vincristine (SV) is a novel sphingosome encapsulated formulation of vincristine, which presents several advantages over regular vincristine. SV has a longer half-life (15 hours versus 15 minutes), can be given uncapped, and shows accumulation in tumor sites in experimental models, providing a rationale for this cell-cycle specific agent. Methods: : SV was evaluated as a single agent for the treatment of patients with relapsed or refractory Hodgkin’s disease including those who failed auto or allogeneic transplantation. SV was administered at 2 mg/m2 (no dose capping) IV over 1 hour every 14 days. Patients were restaged every two cycles, responders continued two cycles beyond their best response to a maximum of 12 cycles. Results: Data is reported on 29 patients, 16 males and 13 females; median age was 32 years (range 19–58). Patients had a median of 4 prior chemotherapy regimens (range 2–10), 20 patients had also received prior radiation therapy and 22/29 pts (76%) failed prior transplant. Patients received a median of 4 cycles of SV (range 1–12). Among 27 patients evaluable, 8 responded with 2 CR, 2 CRu, and 4 PR for an overall response rate (ORR) of 30%. Other patients had stable disease (10 pts) or progression (9 pts). Among the responders the median number of prior therapy was 3 (range 2–6), 6/8 responders failed prior auto transplant. Grade 3 toxicity included: sensory neuropathy (2 pts), constipation (2 pts), pain/myalgia (2 pts), fatigue (2 pts), fever (w/o neutropenia) (1 pt). There was no grade 4 toxicity. Conclusions: SV is a promising agent for the treatment of relapsed/refractory Hodgkin’s disease with a 30% ORR in a heavily pretreated population. This therapy was well tolerated with mostly mild to moderate toxicities reported and few grade 3 toxicities despite the number of prior therapies. The ORR and manageable toxicity observed in this study supports further investigation of SV in this disease. No significant financial relationships to disclose.
Simple and Reliable Method for Detection and Genotyping of Hepatitis C Virus RNA in Dried Blood Spots Stored at Room Temperature (2002)

We describe a simple, sensitive, and reproducible method for using whole blood collected onto filter paper (dried blood spots) for detection and genotyping of hepatitis C virus RNA that can be useful in large field studies, particularly in settings where collection, preparation, storage, and shipment of samples at controlled temperature can be difficult.
Fault Diagnosis of a Wind Turbine Benchmark via Identified Fuzzy Models (2014)

In order to improve the availability of wind turbines and to avoid catastrophic consequences, the detection of faults in their earlier occurrence is fundamental. This paper proposes the development of a fault diagnosis scheme relying on identified fuzzy models. The fuzzy theory is exploited since it allows approximating uncertain models and managing noisy data. These fuzzy models, in the form of Takagi-Sugeno prototypes, represent the residual generators used for fault detection and isolation (FDI). A wind turbine benchmark is used to validate the achieved performances of the designed FDI scheme. Finally, extensive comparisons with different fault diagnosis methods highlight the features of the suggested solution.
Roles of the Complex Formation of SHPS-1 with SHP-2 in Insulin-stimulated Mitogen-activated Protein Kinase Activation (1998)

SHPS-1 is a receptor-like protein that undergoes tyrosine phosphorylation and binds SHP-2, an SH2 domain-containing protein tyrosine phosphatase, in response to insulin and other mitogens. The overexpression of wild-type SHPS-1, but not of a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region were mutated to phenylalanine, markedly enhanced insulin-induced activation of mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress the human insulin receptor. Mutation of each tyrosine residue individually revealed that the major sites of tyrosine phosphorylation of SHPS-1 in response to insulin are Tyr449 and Tyr473. In addition, mutation of either Tyr449 or Tyr473 abolished the insulin-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2. Surface plasmon resonance analysis showed that glutathione S-transferase fusion proteins containing the NH2-terminal or COOH-terminal SH2 domains of SHP-2 bound preferentially to phosphotyrosyl peptides corresponding to the sequences surrounding Tyr449 or Tyr473, respectively, of SHPS-1. Furthermore, phosphotyrosyl peptides containing Tyr449 or Tyr473 were effective substrates for the phosphatase activity of recombinant SHP-2 in vitro. Together, these results suggest that insulin may induce phosphorylation of SHPS-1 at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH-terminal SH2 domains, respectively. SHPS-1 may play a crucial role both in the recruitment of SHP-2 from the cytosol to a site near the plasma membrane and in increasing its catalytic activity, thereby positively regulating the RAS-mitogen-activated protein kinase signaling cascade in response to insulin.
OpenState (2014)

Software Defined Networking envisions smart centralized controllers governing the forwarding behavior of dumb low-cost switches. But are "dumb" switches an actual strategic choice, or (at least to some extent) are they a consequence of the lack of viable alternatives to OpenFlow as programmatic data plane forwarding interface? Indeed, some level of (programmable) control logic in the switches might be beneficial to offload logically centralized controllers (de facto complex distributed systems) from decisions just based on local states (versus network-wide knowledge), which could be handled at wire speed inside the device itself. Also, it would reduce the amount of flow processing tasks currently delegated to specialized middleboxes. The underlying challenge is: can we devise a stateful data plane programming abstraction (versus the stateless OpenFlow match/action table) which still entails high performance and remains consistent with the vendors' preference for closed platforms? We posit that a promising answer revolves around the usage of extended finite state machines, as an extension (super-set) of the OpenFlow match/action abstraction. We concretely turn our proposed abstraction into an actual table-based API, and, perhaps surprisingly, we show how it can be supported by (mostly) reusing core primitives already implemented in OpenFlow devices.
A neural network systems component (2002)

A CMOS device designed to interface the CNAPS (connected network of adaptive processors)-1064 neural processor IC to traditional computing environments is presented. The encapsulation of flexible I/O models and sequencer control into a modular architecture enables the creation of systems across a wide spectrum of performance capabilities. The CNAPS sequencer chip (CSC) provides a simple co-processor interface that can be easily adapted to different target environments and, at the same time, utilize the CNAPS architecture at the maximum performance possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
B Cell Antigen Receptor Engagement Inhibits Stromal Cell–derived Factor (SDF)-1α Chemotaxis and Promotes Protein Kinase C (PKC)-induced Internalization of CXCR4 (1999)

The entry of B lymphocytes into secondary lymphoid organs is a critical step in the development of an immune response, providing a site for repertoire shaping, antigen-induced activation and selection. These events are controlled by signals generated through the B cell antigen receptor (BCR) and are associated with changes in the migration properties of B cells in response to chemokine gradients. The chemokine stromal cell-derived factor (SDF)-1alpha is thought to be one of the driving forces during those processes, as it is produced inside secondary lymphoid organs and induces B lymphocyte migration that arrests upon BCR engagement. The signaling pathway that mediates this arrest was genetically dissected using B cells deficient in specific BCR-coupled signaling components. BCR-induced inhibition of SDF-1alpha chemotaxis was dependent on Syk, BLNK, Btk, and phospholipase C (Plc)gamma2 but independent of Ca2+ mobilization, suggesting that the target of BCR stimulation was a protein kinase C (PKC)-dependent substrate. This target was identified as the SDF-1alpha receptor, CXCR4, which undergoes PKC- dependent internalization upon BCR stimulation. Mutation of the internalization motif SSXXIL in the COOH terminus of CXCR4 resulted in B cells that constitutively expressed this receptor upon BCR engagement. These studies suggest that one pathway by which BCR stimulation results in inhibition of SDF-1alpha migration is through PKC-dependent downregulation of CXCR4.
Xenografted Human Amniotic Membrane–Derived Mesenchymal Stem Cells Are Immunologically Tolerated and Transdifferentiated Into Cardiomyocytes (2010)

Because hAMCs have a high ability to transdifferentiate into cardiomyocytes and to acquire immunologic tolerance in vivo, they can be a promising cellular source for allograftable stem cells for cardiac regenerative medicine.
Expanded bed adsorption of human serum albumin from very dense saccharomyces cerevesiae suspensions on fluoride‐modified zirconia (1999)

The adsorption of proteins from high cell density yeast suspensions on mixed-mode fluoride-modified zirconia (FmZr) particles (38 to 75 μm, surface area of 29 m2/g and density of 2.8 g/cm3) was investigated using human serum albumin (HSA) added to Saccharomyces cerevesiae as the model expression host. Because of the high density of the porous zirconia particles, HSA (4 mg/mL) can be adsorbed from a 100 g dry cell weight (DCW)/L yeast suspension in a threefold-expanded bed of FmZr. The expanded bed adsorption of any protein from a suspension containing >50 g DCW/L cells has not been previously reported. The FmZr bed expansion characteristics were well represented by the Richardson–Zaki correlation with a particle terminal velocity of 3.1 mm/s and a bed expansion index of 5.4. Expanded bed hydrodynamics were investigated as a function of bed expansion using residence time distribution studies with sodium nitrite as the tracer. The adsorption of HSA on FmZr exhibited features of multicomponent adsorption due to the presence of dimers. The protein binding capacity at 5% breakthrough decreased from 22 mg HSA/mL settled bed void volume for 20 g DCW/L yeast to 15 mg HSA/mL settled bed void volume for 40 g DCW/L yeast and remained unchanged for the higher yeast concentrations (60 to 100 g DCW/L). However, the batch (or equilibrium) binding capacity decreased monotonically as a function of yeast concentration (20 to 100 g DCW/L) and the binding capacity at 100 g DCW/L yeast was fivefold lower compared with that at 20 g DCW/L yeast. The lower batch binding capacity at high cell concentrations resulted from the adsorption of cells at the surface of the particles restricting access of HSA to the intraparticle surface area. Batch (or equilibrium) and column HSA adsorption results indicated that the adsorption of HSA on FmZr occurred at a time scale that may be much faster than that of yeast cells. The zirconia particles were cleaned of adsorbed HSA and yeast with a total of 1500 to 2000 column volumes (over many cycles) of 0.25 M NaOH, without any significant effect on the chromtographic performance. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 65: 282–290, 1999.
The murine platelet and plasma factor V pools are biosynthetically distinct and sufficient for minimal hemostasis (2003)

Coagulation factor V (FV) is a central regulator of the coagulation cascade. Circulating FV is found in plasma and within platelet alpha granules. The specific functions of these distinct FV pools are uncertain. We now report the generation of transgenic mice with FV gene expression restricted to either the liver or megakaryocyte/platelet lineage using bacterial artificial chromosome (BAC) constructs. Six of 6 independent albumin BAC transgenes rescue the neonatal lethal hemorrhage of FV deficiency. Rescued mice all exhibit liver-specific Fv expression at levels ranging from 6% to 46% of the endogenous Fv gene, with no detectable FV activity within the platelet pool. One of the 3 Pf4 BAC transgenes available for analysis also rescues the lethal FV null phenotype, with FV activity restricted to only the platelet pool (approximately 3% of the wild-type FV level). FV-null mice rescued by either the albumin or Pf4 BAC exhibit nearly normal tail bleeding times. These results demonstrate that Fv expression in either the platelet or plasma FV pool is sufficient for basal hemostasis. In addition, these findings indicate that the murine platelet and plasma FV pools are biosynthetically distinct, in contrast to a previous report demonstrating a plasma origin for platelet FV in humans.
Aerobic Exercise Attenuates Airway Inflammatory Responses in a Mouse Model of Atopic Asthma (2004)

Recent reports indicate that aerobic exercise improves the overall physical fitness and health of asthmatic patients. The specific exercise-induced improvements in the pathology of asthma and the mechanisms by which these improvements occur, however, are ill-defined; thus, the therapeutic potential of exercise in the treatment of asthma remains unappreciated. Using an OVA-driven mouse model, we examined the role of aerobic exercise in modulating inflammatory responses associated with atopic asthma. Data demonstrate that moderate intensity aerobic exercise training decreased leukocyte infiltration, cytokine production, adhesion molecule expression, and structural remodeling within the lungs of OVA-sensitized mice (n = 6-10; p < 0.05). Because the transcription factor NF-kappaB regulates the expression of a variety of genes that encode inflammatory mediators, we monitored changes in NF-kappaB activation in the lungs of exercised/sensitized mice. Results show that exercise decreased NF-kappaB nuclear translocation and IkappaBalpha phosphorylation, indicating that exercise decreased NF-kappaB activation in the lungs of sensitized mice (n = 6). Taken together, these results suggest that aerobic exercise attenuates airway inflammation in a mouse model of atopic asthma via modulation of NF-kappaB activation. Potential exists, therefore, for the amelioration of asthma-associated chronic airway inflammation through the use of aerobic exercise training as a non-drug therapeutic modality.
Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression (2019)

The expression profiles and spatial distributions of RNAs regulate many cellular functions. Image-based transcriptomic approaches provide powerful means to measure both expression and spatial information of RNAs in individual cells within their native environment. Among these approaches, multiplexed error-robust fluorescence in situ hybridization (MERFISH) has achieved spatially resolved RNA quantification at transcriptome scale by massively multiplexing single-molecule FISH measurements. Here, we increased the gene throughput of MERFISH and demonstrated simultaneous measurements of RNA transcripts from ∼10,000 genes in individual cells with ∼80% detection efficiency and ∼4% misidentification rate. We combined MERFISH with cellular structure imaging to determine subcellular compartmentalization of RNAs. We validated this approach by showing enrichment of secretome transcripts at the endoplasmic reticulum, and further revealed enrichment of long noncoding RNAs, RNAs with retained introns, and a subgroup of protein-coding mRNAs in the cell nucleus. Leveraging spatially resolved RNA profiling, we developed an approach to determine RNA velocity in situ using the balance of nuclear versus cytoplasmic RNA counts. We applied this approach to infer pseudotime ordering of cells and identified cells at different cell-cycle states, revealing ∼1,600 genes with putative cell cycle-dependent expression and a gradual transcription profile change as cells progress through cell-cycle stages. Our analysis further revealed cell cycle-dependent and cell cycle-independent spatial heterogeneity of transcriptionally distinct cells. We envision that the ability to perform spatially resolved, genome-wide RNA profiling with high detection efficiency and accuracy by MERFISH could help address a wide array of questions ranging from the regulation of gene expression in cells to the development of cell fate and organization in tissues.
Method for determining oxygen consumption rates of static cultures from microplate measurements of pericellular dissolved oxygen concentration (2004)

We describe a simple protocol for determining the oxygen consumption of cells in static culture. The protocol is based on a noninvasive oxygen-sensing microplate and a simple mathematical model derived from Fick's Law. The applicability of the model is confirmed by showing the correlation of computed oxygen consumption rate (OCR) values to actual cell densities ascertained by direct cell counting and/or MTT for HL60 and U937 cells cultured in suspension. Correlation between computed OCR and these other indications of cell number was quite good, as long as the cultures were not diffusion-limited for oxygen. The impact of the geometric factors of media depth and well size were confirmed to be consistent with the model. Based on this demonstrated correlation, we also developed a simple, completely noninvasive algorithm for ascertaining the per-cell oxygen utilization rate (OUR), which is the ratio of OCR to cell number, and a fundamental cell characteristic. This is accomplished by correlating the known seed densities to extrapolated determinations of OCR at time zero. Such determinations were performed for numerous cell types, in varying well sizes. Resulting OUR values are consistent with literature values acquired by far more painstaking methods, and ranged from <0.01 fmol.min(-1).cell(-1) for bacteria to 0.1-10 fmol.min(-1).cell(-1) for immortalized mammalian and insect cell lines to >10 fmol.min(-1).cell(-1) for primary hepatocytes. This protocol for determining OCR and OUR is extremely simple and broadly applicable and can afford rapid, informative, and noninvasive insight into the state of the culture.
A Disaccharide Hapten from Streptococcal Group C Carbohydrate that Cross-Reacts with the Forssman Glycolipid (1977)

A disaccharide hapten was isolated in approximately 20% yield from an acid hydrolysate of the streptococcal Group C carbohydrate. This disaccharide was assigned the structure 3-0-alpha-N-acetylgalactosaminosyl-N-acetylgalactosamine on the basis of chemical and immunochemical data. The ability of the hapten to inhibit completely the binding between Group C carbohydrate and most Group C antibodies indicated that this disaccharide is the immunodominant feature of the Group C carbohydrate. Fractionation of antisera on an alpha-N-acetylgalactosamine immunoadsorbent column yielded several populations of anti-Group C antibodies. The reaction between labeled Group C carbohydrate and antibodies which strongly bound the immunoadsorbent column was 50% inhibitable by the disaccharide hapten when the hapten was added in approximately 15-fold excess (w/w) of the labeled antigen. On the other hand, the binding of those antibodies which did not bind to the immunoadsorbent column was poorly inhibited under these conditions. The Forssman glycosphingolipid, which has a common terminal digalactosamine unit, was shown to likewise inhibit Group C carbohydrate binding reactions.
Differential activation of mitogen-activated protein kinase in response to basic fibroblast growth factor in skeletal muscle cells. (1995)

In the MM14 mouse myoblast cell line, fibroblast growth factor (FGF) stimulates proliferation and represses differentiation. However, the intracellular signaling pathways used by FGF to affect these cellular processes are unknown. The predominant FGF receptor present on MM14 cells, FGFR1, is a receptor tyrosine kinase capable of activating the mitogen-activated protein kinase (MAPK) cascade in fibroblast and neuronal cell lines. To determine whether the FGF signal is mediated via the MAPK cascade in myoblasts, MM14 cells were stimulated with basic FGF (bFGF) and activities of the various kinases were measured. After withdrawal from serum and bFGF for 3 hr, bFGF stimulated MAPK kinase (MAPKK) activity, but MAPK and S6 peptide kinase activities were not detected. In contrast, when serum and bFGF were withdrawn for 10 hr, the activities of MAPKK, MAPK, and S6 peptide kinase were all stimulated by bFGF treatment. The inability of bFGF to stimulate MAPK after 3 hr of withdrawal may be due, in part, to the presence of a MAPK phosphatase activity that was detected in MM14 cell extracts. This dephosphorylating activity diminishes during commitment to terminal differentiation and is inhibited by sodium orthovanadate. Thus, the ability of bFGF to stimulate MAPK in MM14 cells is correlated with the loss of a MAPK phosphatase activity. These results show that although bFGF activates MAPKK in proliferating myoblasts, the mitogenic signal does not progress to the downstream kinases, providing a physiological example of an uncoupling of the MAPK cascade.
Structural Requirements for the Interaction of Human IgA with the Human Polymeric Ig Receptor (2005)

Transport of polymeric IgA onto mucosal surfaces to become secretory IgA is mediated by the polymeric Ig receptor (pIgR). To study the interaction of human dimeric IgA (dIgA) (the predominant form of IgA polymer) with the human pIgR (hpIgR), we generated recombinant wild-type dIgA1 and dIgA2m(1) and various mutant dIgA1 and analyzed their interaction with a recombinant human secretory component and membrane-expressed hpIgR. We found that wild-type dIgA1 and dIgA2m(1) bound to recombinant human secretory component with similar affinity and were transcytosed by the hpIgR to the same extent. Mutation of the IgA Calpha2 domain residue Cys311 to Ser reduced binding to hpIgR, possibly through disruption of noncovalent interactions between the Calpha2 domain and domain 5 of the receptor. Within the Calpha3 domain of IgA1, we found that combined mutation of residues Phe411, Val413, and Thr414, which lie close to residues previously implicated in hpIgR binding, abolished interaction with the receptor. Mutation of residue Lys377, located very close to this same region, perturbed receptor interaction. In addition, 4 aa (Pro440-Phe443), which lie on a loop at the domain interface and form part of the binding site for human FcalphaRI, appear to contribute to hpIgR binding. Lastly, use of a monomeric IgA1 mutant lacking the tailpiece revealed that the tailpiece does not occlude hpIgR-binding residues in IgA1 monomers. This directed mutagenesis approach has thus identified motifs lying principally across the upper surface of the Calpha3 domain (i.e., that closest to Calpha2) critical for human pIgR binding and transcytosis.