gebhart/patrepeval huggingface dataset:
The hypochromic red cell: a new parameter for monitoring of iron supplementation during rhEPO therapy (1995)

Bone marrow iron supply may become rate limiting for hemoglobin synthesis during rhEPO-stimulated erythropoiesis. In the present study we followed the occurrence of hemoglobin-deficient red cells as a parameter of iron-deficient erythropoiesis in rhEPO-treated dialysis patients. rhEPO-treated patients with iron overload displayed very low numbers of hypochromic red cells (1%), while those with iron-deficiency had a hypochromic subpopulation of 22% (normal range < 2.5% of circulating red cells). Prior to rhEPO treatment, 10 dialysis patients showed normal numbers of hypochromic red cells (2.1%), despite mild iron deficiency (transferrin saturation: 17%). Once rhEPO (150 U/kg/week) was started, the percentage of hypochromic red cells rose significantly to 15.3% within 4 weeks of therapy. This was readily reversed when intravenous iron (750 mg/4 weeks) was added to the therapeutic regimen (5.5% after 4 weeks of i.v. iron). Taken together, quantitative red cell analysis seems to be a reliable tool to detect iron-deficient erythropoiesis in rhEPO-treated dialysis patients.
Exploitation of signal structure in array-based blind copy and copy-aided DF systems (2002)

A general approach to array-based blind copy and copy-aided DF of structured communication signals is presented that can substantially outperform conventional techniques, by exploiting additional information about the structure of the signals of interest to the reception system. The techniques are derived from optimal parameter estimation concepts that directly incorporate this additional information into the waveform or parameter estimation strategy. The resultant algorithms demonstrate strong theoretical, experimental, and implementation advantages over conventional techniques. Results are demonstrated for blind separation and copy-aided DF of co-channel FM, CPFSK, DSB-AM, and burst waveforms.
Polymer-Based Synthetic Dendritic Cells for Tailoring Robust and Multifunctional T Cell Responses (2014)

Dendritic cells (DCs) are antigen-presenting cells that play an essential role in T cell activation. Recent efforts in cancer immunotherapy have been directed at the development of artificial antigen presenting cells (aAPCs) loaded with tumor antigens. These aAPCs are designed to mimic DCs with the goal of triggering an efficient and specific T cell response directed against the tumor. We have designed a novel synthetic dendritic cell (sDC) that possesses the essential features of natural DCs. Our sDC is based on a semiflexible poly(isocyano peptide) polymer and carries anti-CD3 antibodies (αCD3) for triggering the T cell receptor/CD3 complex as well as anti-CD28 antibodies (αCD28) as a co-stimulatory signal. Multiple copies of both antibodies facilitate multivalent binding similar to natural DCs. The high mobility of these polymer-bound antibodies, reminiscent of protein motility in a natural plasma membrane, enables receptor rearrangements to occur during T cell activation. We show that our bifunctional αCD3/αCD28-sDC triggers T cell activation at significantly lower antibody concentrations than freely soluble antibodies. This superior performance is further demonstrated in comparison to a mixture of monofunctional αCD3-sDC and αCD28-sDC. The presence of both antibodies on the same polymer not only reduces the threshold for T cell activation but, more importantly, critically shapes the specificity of the T cell response. αCD3/αCD28-sDC is a far more efficient activator of multifunctional killer cells. These findings demonstrate the potential of multifunctional polymers for mimicking natural DCs, paving the way for their exploitation in immunotherapeutic strategies.
Prolonged Cell-free Protein Synthesis in a Batch System Using Wheat Germ Extract (1994)

Reaction conditions of cell-free protein synthesis using wheat germ extract were examined to prolong the period of protein synthesis in a batch reaction. By optimizing conditions for ATP regeneration system involved in the cell-free system, protein synthesis continued about 4 hours, so that about 17 micrograms dihydrofolate reductase protein was obtained in 1 ml of a reaction mixture. It suggests that maintaining ATP concentration is the primary requirement for long-life cell-free protein synthesis.
Click Chemistry and Bioorthogonal Reactions: Unprecedented Selectivity in the Labeling of Biological Molecules (2009)

In recent years, a number of bioorthogonal reactions have been developed, exemplified by click chemistry, that enable the efficient formation of a specific product, even within a highly complex chemical environment. While the exquisite selectivity and reliability of these transformations have led to their broad application in diverse research areas, they have proven to be particularly beneficial to biological studies. In this regard, the ability to rationally incorporate reactive tags onto a biomolecular target and subsequently achieve high selectivity in tag derivatization within a complex biological sample has revolutionized the toolbox that is available for addressing fundamental issues. Herein, an introduction to the impact of click chemistry and other bioorthogonal reactions on the study of biological systems is presented. This includes discussion of the philosophy behind click chemistry, the details and benefits of bioorthogonal reactions that have been developed, and examples of recent innovative approaches that have effectively exploited these transformations to study cellular processes. For the latter, the impacts of bioorthogonal reactions on drug design (i.e., in situ combinatorial drug design), biomolecule labeling and detection (site-specific derivatization of proteins, viruses, sugars, DNA, RNA, and lipids), and the recent strategy of activity-based protein profiling are highlighted.
Propagation of human blastic myeloid leukemias in the SCID mouse (1992)

Existing in vitro culture technology does not permit the routine propagation of most human myeloid leukemias. Previous work has shown the usefulness of mice with severe combined immunodeficiency (SCID) for the growth of human lymphoblastic leukemia. We show here that human myeloid cell lines and bone marrow samples from patients with acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow in SCID mice. Human AML or CML cell lines (three of three lines tested) grew in the bone marrow and peripheral blood of the mice after intravenous (IV) inoculation in a pattern closely resembling human AML. To define the best conditions for the growth of primary human myeloid leukemia cells, samples were transplanted into mice at several alternative sites. Using flow cytometry and Southern analysis, mice were analyzed at defined intervals up to 36 weeks after transplantation for the presence of human cells in various tissues. For four of four patients with AML and two of two patients with blast crisis of CML, myeloblasts grew locally at the site of implantation and were detected in the murine hematopoietic tissues. In contrast, marrow implants from patients in the chronic phase of CML (six patients) showed infrequent and limited myeloid growth in the mice. These findings demonstrate that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias. The differential growth of early- versus late-phase CML suggests that the SCID mouse may be a useful assay for identifying biologically aggressive leukemias early in their clinical presentation.
The CRISPR Craze (2013)

A bacterial immune system yields a potentially revolutionary genome-editing technique.
A Framework for Automatic Generation of Configuration Files for a Custom Hardware/Software RTOS (2002)

In this paper, we propose a framework for userdirected automatic generation of configuration files for a custom hardware/software real-time operating system (RTOS) for System-on-a-Chip. The main goal of this research is to help the user explore which configuration is most suitable for his or her specific application or set of applications. This work leverages three previous innovations in hardware/software RTOS design: Systemon -a-Chip Lock Cache (SoCLC) [i], System-on-a-Chip Deadlock Detection Unit (SoCDDU) [2] and System-ona -Chip Dynamic Memory Management Unit (SoCDMMU) [3]. However, in spite of the excellent performance of these innovations, the user may not need or have the chip space for all three of them. In this case, our framework enables automatic generation of different mixes of hardware and software versions of the SoCLC, SoCDDU and SoCDMMU. We show how to generate configuration files for custom RTOSes for two examples published previously [i, 2]. The average-case simulation result of a database application model with client-server pair of tasks on a four-processor system with SoCLC showed a 27% overall speedup in total execution time than that of the same system but with software synchronization. In the other example, the application execution time to end up in a deadlock state and then detect the deadlock showed a 38% speedup with the SoCDDU as compared to the same system but with a software deadlock detection implementation.
Mutational Profile of the PTEN Gene in Primary Human Astrocytic Tumors and Cultivated Xenografts (1999)

The genetic abnormality most frequently identified in glioblastomas is loss of alleles on chromosome 10. We have performed a comprehensive study of the PTEN tumor suppressor gene on 10q23, including loss of heterozygosity (LOH) analysis, multiplex PCR, mutation analysis, and reverse transcription PCR (RT-PCR). In total, 151 glioblastomas, 41 anaplastic astrocytomas, 15 astrocytomas, and 13 glioma cell lines were analyzed as well as 23 xenografts derived from primary glioblastomas, which allows a comparison of the PTEN gene status in primary tumors versus xenografts. Homozygous deletions were found in 7% of the glioblastomas and 40% showed mutation of a single retained allele. This mutation frequency is higher than reported previously. The large number of mutations identified allows the presentation of a mutational profile along the coding sequence. The majority of mutations appear to affect conserved residues or structurally conserved regions. PTEN alterations were selected for in xenografts, and there is evidence that they may even facilitate establishment of xenografts. No alterations were found in astrocytomas and only 5% of anaplastic astrocytomas had mutations. Thus, loss of wild type PTEN represents one of the major abnormalities associated with astrocytic tumor progression to glioblastoma and provides a strong selective growth advantage when cultivating glioblastoma tissue in xenografts. No correlation with EGFR amplification was evident.
Tape Cast Solid-Oxide Fuel Cells for the Direct Oxidation of Hydrocarbons (2001)

A tape casting method for fabricating solid-oxide fuel cells (SOFCs) that are active for the direct oxidation of dry hydrocarbons is presented. The method relies on the inclusion of pyrolyzable pore formers in the anode green tape in order to produce a porous yttria-stabilized zirconia anode matrix. Wet impregnation was used to add both a metal current collector and an oxidation catalyst to the anode. The performance characteristics for cells produced using this method while operating on and are presented. © 2001 The Electrochemical Society. All rights reserved.
A novel combined conjugate vaccine: Enhanced immunogenicity of bFGF with CRM197 as a carrier protein (2011)

Tumor growth is partly dependent on tumor-associated angiogenesis, which is regulated by angiogenic growth factors. As the first angiogenic growth factor to be identified, basic fibroblast growth factor (bFGF) plays a major role in angiogensis and tumor growth and has been an effective target for anti-tumor therapy. However, due to its low immunogenicity, injection with bFGF alone cannot stimulate the body to produce a strong immune response. In this study, we investigated the role of CF (containing bFGF and CRM197) assisted by CpG and alum in enhancing antigen-specific immune response and suppressing the growth of murine colon carcinoma. The results revealed that compared to bFGF, CF could not stimulate NIH-3T3 fibroblast proliferation even at a concentration of 10 µg/ml in vitro. In vivo, the CF-CpG-alum produced a stronger antigen-specific immune response and inhibited tumor growth. The anti-tumor activity was associated with generating antigen-specific antibody, suppressing angiogenesis, promoting the apoptosis of tumor cells and inducing the mixed Th1 and Th2 responses. This indicates that CRM197 may be an innovative intramolecular adjuvant and provides a rational preservation for mouse CT26 colon carcinoma.
Permanent Human Canines : Configuration And Deviations Of Root Canals : An In-Vitro Study (2003)

Two hundred permanent human canines (100 maxillary canines and 100 mandibular canines) were studied radiologically (50 maxillary canines: Group A-1 and 50 mandibular canines: Group A-2) and by decalcification and clearing method (50 maxillary canines: Group B-1 and 50 mandibular canines: Group B-2) as regards teh configuration and deviations of the root canals. Inradiological method the teeth were radiographed from two directions viz. mesiodistal and buccolingual. Group A-1: Type I canal configuration was observed in 98% and Type II in 2%. Root canals were straight in 46% and curved in 54% cases. Apical foramen was centrally located in 38% and laterally located in 62% cases. Accessory canals and apical deltas was observed in 18% each respectively. Group A-2: Type I canal configuration was observed in 18% and Type II, III and IV in 4% each. Root canals were straight in 53.84% and curved in 46.15% cases. Apical foramen was centrally located in 34.61% and laterally located in 65.38%. Accessory canals and apical deltas were observed in 15.28% each respectively. Group B-1: Type I canal configuration was observed in 98% and Type II in 2%. Root canals were straight in 44% and curved in 56% cases. Apical foramen was centrally located in 50% and laterally located in 50% cases. Accessory canals and apical deltas was observed in 10% each respectively. Group B-2: Type I canal configuration was observed in 70%, Type II in 12%. Type III in 6%, Type IV in 10% each and Type V in 2%. Root canals were straight in 60.71% and curved in 39.28% cases. Apical foramen was centrally located in 57.14% and laterally located in 42.85%. Accessory canals and apical deltas were observed in 16.07% each respectively. Since there can be wide variations in root canal configuration of permanent human canines. So more time should be devoted to study the radiographs so as to anticipate the canal configuration and deviations.
A seafloor electric field instrument. (1985)

A seafloor instrument has been constructed to measure a horizontal component of the electric field, using a long antenna (up to 1000m) to increase sensitivity. The instrument has a depth capability of 5200m and may be deployed for several months at a time, collecting over 14 Mbytes of data under the control of a microprocessor. Instrumental noise is mainly caused by the Ag-AgCl electrodes used to make contact with the sea water, and is about 10-24V2/m2Hz at frequencies above 1Hz, following an f-2 power law at frequencies (f) below 1Hz. For controlled source signals averaging techniques such as synchronous stacking and block averaging have been used to detect narrow band (5.6×10-4Hz) signals as small as 10-12V/m. The instrument is designed to include the pressure transducer described by COX et al. (1984) and has already been used for the study of ocean bottom seismic signals, magnetotelluric experiments and controlled source electromagnetic soundings.
Mechanism by which metformin reduces glucose production in type 2 diabetes. (2000)

To examine the mechanism by which metformin lowers endogenous glucose production in type 2 diabetic patients, we studied seven type 2 diabetic subjects, with fasting hyperglycemia (15.5 +/- 1.3 mmol/l), before and after 3 months of metformin treatment. Seven healthy subjects, matched for sex, age, and BMI, served as control subjects. Rates of net hepatic glycogenolysis, estimated by 13C nuclear magnetic resonance spectroscopy, were combined with estimates of contributions to glucose production of gluconeogenesis and glycogenolysis, measured by labeling of blood glucose by 2H from ingested 2H2O. Glucose production was measured using [6,6-2H2]glucose. The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 +/- 0.05 vs. 0.36 +/- 0.03 mmol x m(-2) min(-1), P < 0.0001). Metformin reduced that rate by 24% (to 0.53 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 +/- 0.9 mmol/l, P = 0.0002). The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 +/- 0.03 vs. 0.18 +/- 0.03 mmol x m(-2) min(-1) and metformin reduced that rate by 36% (to 0.38 +/- 0.03 mmol x m(-2) x min(-1), P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 +/- 0.04 mmol m(-2) x min(-1), which decreased by 33% after metformin treatment (0.28 +/- 0.03 mmol x m(-2) x min(-1), P = 0.0002). There was no glycogen cycling in the control subjects, but in the diabetic subjects, glycogen cycling contributed to 25% of glucose production and explains the differences between the two methods used. In conclusion, patients with poorly controlled type 2 diabetes have increased rates of endogenous glucose production, which can be attributed to increased rates of gluconeogenesis. Metformin lowered the rate of glucose production in these patients through a reduction in gluconeogenesis.
Differentiating Incretin Therapies Based on Structure Activity, and Metabolism: Focus on Liraglutide (2009)

The incretin effect, mediated by glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), plays an important role in the regulation of insulin secretion in response to oral glucose. The discovery of deficiencies in incretin pathways associated with development of type 2 diabetes mellitus has propelled the growth of incretin-based therapies in patients with this disease. The basic rationale for incretin-based therapies, including both GLP-1-receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors is reviewed, focusing on their roles in glucose regulation and potential therapeutic benefits. Increased awareness of the differences among incretin mimetics, GLP-1 analogs, and DPP-4 inhibitors, including their structures, half-lives, dosages, hemoglobin A(1c)-lowering capacities, effects on weight, and adverse events will help shape the future of these therapeutic agents. Improved understanding of the mechanism of action and clinical effects of incretin-based therapies will help advance their appropriate use within clinical practice.
New causal relationship between PLA2g6, store‐operated Ca 2+ entry, refilling of Ca 2+ stores and ER stress in mouse embryonic fibroblasts. (2013)

Store‐operated Ca 2+ entry (SOCE) is essential for maintenance and timely refilling of Ca 2+ stores in the endoplasmic reticulum (ER). Here we used molecular, imaging and genetic approaches to unmask new determinants of this process and their role in ER stress and the unfolded protein response (UPR). Analysis of endogenous SOCE in primary embryonic fibroblasts (MEF) from a new knockout mouse model revealed that constitutive genetic impairment of interaction of specific plasma membrane‐associated phospholipase A2 (PLA2g6) with STIM1 (ER‐resident Ca 2+ sensor) leads to impairment of endogenous SOCE. Such deficiency resulted in sustained depletion of intracellular Ca 2+ stores, and more than 50% reduction in ionomycin‐induced Ca 2+ release from the stores. We found that PLA2g6 and SOCE‐deficient MEF cells experience significant ER stress: qRT‐PCR analysis of ER stress markers showed a 2–4 fold increase in mRNA expression levels of BiP, CHOP, and TXNIP. Discovery of a new causal relationship between PLA2g6, SOCE, filling state of ER Ca 2+ stores and the UPR unveiled a novel mechanism of ER stress, and identified new molecular targets that can be used for prevention of ER stress‐related pathologies.
Model predictive control of automotive powertrains - first experimental results (2008)

This paper illustrates the capabilities of model predictive control for the control of automotive powertrains. We consider the minimization of the fuel consumption of a gasoline engine through dynamic optimization. The minimization uses a mean value model of the powertrain and vehicle. This model has two state variables: the pressure in the engine manifold and the engine speed. The control input is the throttle valve angle. The model is identified on a universal dynamometer. Optimal state and control trajectories are calculated using Bock¿s direct multiple shooting method implemented in the software MUSCOD-II. The developed approach is illustrated both in simulation and experimentally for a test case where a vehicle accelerates from 1100 rpm to 3700 rpm in 30 s. The optimized trajectories yield minimal fuel consumption. The experiments show that the optimal engine speed trajectory yields a reduction of the fuel consumption of 12% when compared to a linear trajectory. Thus, it is shown that, even with a simple model, a significant amount of fuel can be saved without loss of the fun-to-drive.
Cloning and analysis of the promoter region of the rat SM22α gene (1995)

We have cloned and sequenced a 1.9 kb fragment of the 5'-upstream sequence of the smooth-muscle-specific gene SM22 alpha. The region cloned consisted of the SM22 alpha promoter, a 65 bp exon containing most of the 5'-untranslated region and 307 bp of the first intron. A 1.5 kb fragment at the 5' end of this sequence was able to drive the expression of a reporter chloramphenicol acetyltransferase (CAT) gene in both vascular smooth-muscle cells and Rat-1 fibroblasts. This promoter region did not contain a consensus TATAA box but contained the sequence TTTAAA 25 bp from the major start site identified by primer extension. Deletion analysis showed that a fragment of the promoter from +65 to -303 was more active in both cell types than the 1.5 kb fragment suggesting that there are silencer sequences in the region 5' to the core promoter. CAT activity was also observed with fragments containing bases +65 to -193 and +65 to -117 in smooth-muscle cells. In contrast with the smooth-muscle cells, no CAT activity was detected in Rat-1 fibroblasts with the smallest two fragments. The residual promoter activity in the smallest fragment of the SM22 alpha promoter tested suggested that, unlike the smooth-muscle alpha-actin promoter, transcription from the SM22 alpha promoter can occur in smooth-muscle cells in the absence of factors binding to CC(A/Trich)6GG (CArG box) or CANNTG (E box) motifs.