gebhart/patrepeval huggingface dataset:
Construction and expression of a recombinant antibody-targeted plasminogen activator. (1987)

Covalent linkage of tissue-type plasminogen activator (t-PA) to a monoclonal antibody specific for the fibrin beta chain (anti-fibrin 59D8) results in a thrombolytic agent that is more specific and more potent than t-PA alone. To provide a ready source of this hybrid molecule and to allow tailoring of the active moieties for optimal activity, we have engineered a recombinant version of the 59D8-t-PA conjugate. The rearranged 59D8 heavy chain gene was cloned and combined in the expression vector pSV2gpt with sequence coding for a portion of the gamma 2b constant region and the catalytic beta chain of t-PA. This construct was transfected into heavy chain loss variant cells derived from the 59D8 hybridoma. Recombinant protein was purified by affinity chromatography and analyzed with electrophoretic transfer blots. These revealed a 65-kDa heavy chain-t-PA fusion protein that is secreted in association with the 59D8 light chain in the form of a 170-kDa disulfide-linked dimer. Chromogenic substrate assays showed the fusion protein to have 70% of the peptidolytic activity of native t-PA and to activate plasminogen as efficiently as t-PA. In a competitive binding assay, reconstituted antibody was shown to have a binding profile similar to that of native 59D8. Thus, by recombinant techniques, we have produced a hybrid protein capable of high-affinity fibrin binding and plasminogen activation.
Dominant resource fairness: fair allocation of multiple resource types (2011)

We consider the problem of fair resource allocation in a system containing different resource types, where each user may have different demands for each resource. To address this problem, we propose Dominant Resource Fairness (DRF), a generalization of max-min fairness to multiple resource types. We show that DRF, unlike other possible policies, satisfies several highly desirable properties. First, DRF incentivizes users to share resources, by ensuring that no user is better off if resources are equally partitioned among them. Second, DRF is strategy-proof, as a user cannot increase her allocation by lying about her requirements. Third, DRF is envy-free, as no user would want to trade her allocation with that of another user. Finally, DRF allocations are Pareto efficient, as it is not possible to improve the allocation of a user without decreasing the allocation of another user. We have implemented DRF in the Mesos cluster resource manager, and show that it leads to better throughput and fairness than the slot-based fair sharing schemes in current cluster schedulers.
Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice. (2005)

Our previous findings demonstrated that directly injecting embryonic stem cells (ESCs) into ischemic region of the heart improved cardiac function in animals with experimental myocardial infarction (MI). Tissue engineering with stem cells may provide tissue creation and repair. This study was designed to investigate the effectiveness of grafting of ESC-seeded biodegradable patch on infarcted heart. MI in mice was induced by ligation of the left coronary artery. Mouse ESCs were seeded on polyglycolic-acid (PGA) material patches. Three days after culture, an ESC-seeded patch was transplanted on the surface of ischemic and peri-ischemic myocardium. Eight weeks after MI operation and patch transplantation, hemodynamics and cardiac function were evaluated in four (sham-operated, MI, MI + cell-free patch, and MI + ESC-patch) groups of mice. The blood pressure and left ventricular function were significantly reduced in the MI animals. Compared with MI alone and MI + cell-free patch groups, the animals received MI + ESC-seeded patches significantly improved blood pressure and ventricular function. The survival rate of the MI mice grafted with MI + ESC-seeded patches was markedly higher than that in MI alone or MI + cell-free patch animals. GFP-positive tissue was detected in infarcted area with grafting of ESC-seeded patch, which suggests the survivors of ESCs and possible myocardial regeneration. Our data demonstrate that grafting of ESC-seeded bioabsorbable patch can repair infarcted myocardium and improve cardiac function in MI mice. This novel approach of combining stem cells and biodegradable materials may provide a therapeutic modality for repairing injured heart.
Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to acute myeloid leukemia blasts increases their costimulatory activity for autologous remission T cells (2001)

Transfection of tumor cells with the gene encoding the costimulatory molecule B7-1 (CD80), the ligand for CD28 and cytotoxic T lymphocye antigen-4 on T cells, has been shown to result in potent T-cell-mediated antitumor immunity. As an alternative approach, this study analyzed the costimulatory capacity of a human B7-1 immunoglobulin G (IgG) fusion protein targeted to the cell membrane of human acute myeloid leukemia (AML) blasts. Flow cytometric analysis revealed a low constitutive expression of B7-1 on human AML blasts (on average, 3.0 +/- 4.3%; n = 50). In contrast, the expression of B7-2 (CD86) was highly heterogeneous and higher in AML blasts of French-American-British classification types M4 and M5 (P <.0001). The B7-1 IgG fusion protein used in this study efficiently costimulated the proliferation of resting and preactivated T cells when immobilized on plastic. After preincubation with B7-1 IgG, specific binding of the fusion protein to the high-affinity Fcgammareceptor I (CD64) on leukemic cells was demonstrated and was found to increase the proliferation of both allogeneic and autologous T cells in costimulation experiments. Furthermore, targeting of B7-1 IgG to the tumor membrane resulted in increased proliferation of autologous remission T cells and had the potential to generate an enhanced redirected cytotoxic T-cell response against autologous AML blasts. In summary, the targeting of B7-1 IgG fusion protein described in this study represents a strategy alternative to gene therapy to restore the expression of the costimulatory molecule B7-1 on human AML blasts, thereby enhancing their immunogenicity for autologous T cells. This new approach may have implications for T-cell-mediated immunotherapy in AML.
Headspace solid‐phase microextraction analysis of artificial flavors (2005)

Abstract Using a non‐equilibrated solid‐phase microextraction/gas chromatography/mass spectrometry technique, differentiation between a wide variety of types and examples of artificial flavors has been demonstrated. Addition of an internal standard to the samples, as received, allowed for the calculation of yields on a µg g −1 basis for the majority of headspace volatiles. The relative standard deviation values expressed as percentages were between 3 and 5%. The precise nature of the approach coupled with the compound identification capacity of the mass spectrometer afforded the capability to easily differentiate between multiple sources of artificial flavors. With a total analysis time of approximately 30 min and the absence of solvent, this approach has the capability of detecting and quantifying the presence of the low‐molecular‐weight solvents often used in the preparation of artificial flavors. Such a capability represents a distinct advantage over more conventional methods of solvent dilution. Results from conventional gas chromatography/mass selective detector analyses are contrasted and compared with the results obtained from the headspace SPME approach. Copyright © 2005 Society of Chemical Industry
CpG Motifs as Proinflammatory Factors Render Autochthonous Tumors Permissive for Infiltration and Destruction (2004)

In a transgenic mouse model expressing SV40 T Ag (Tag) as a de novo tumor Ag, immune surveillance fails and islet cell carcinomas grow progressively. To develop an anticancer strategy that would be effective in eradicating solid, autochthonously growing tumors, we evaluated the effectiveness of immunostimulatory oligodeoxynucleotides (ODN) with cytosine-guanine-rich (CpG) motifs (CpG-ODN). In a classical vaccination protocol, Tag was administered with CpG-ODN as adjuvant. The antitumor vaccination, however, was only effective in a prophylactic setting, despite the successful activation of a Tag-specific CTL response in vivo. Histological examination demonstrated that even primed immune cells failed to infiltrate tumors once a malignant environment was established. To ensure that effector cells were not limiting, highly activated tumor Ag-specific T cells were transferred into tumor-bearing mice. However, this treatment also failed to result in tumor infiltration and rejection. Therefore, we further tested the efficacy of CpG-ODN as a proinflammatory agent in combination with the transfer of preactivated Tag-specific CD4(+) and CD8(+) T cells. Indeed, this combination therapy proved to be highly effective, because CpG-ODN rendered insulinomas permissive for massive infiltration and destruction. The opening of tumor tissue correlated with uptake of CpG-ODN by tissue-resident macrophages and a strong up-regulation of adhesion molecules such as ICAM and VCAM on blood vessel endothelia. These data demonstrate that systemic application of proinflammatory reagents drastically enhances extravasation of effector cells into tumor tissue, an observation that is of general importance for immunotherapy of solid tumors in a clinical setting.
Efficient implementation of PID control algorithm using FPGA technology (2004)

In this paper, an efficient design scheme for implementation of the proportional-integral-derivative (PID) controller using field programmable gate array (FPGA) technology is presented. The algorithm is implemented using a distributed arithmetic (DA)-based scheme where a look-up-table (LUT) mechanism inside the FPGA is utilized. Two novel DA-based PID controllers have been proposed for FPGA implementation. The implementation results show that, the two DA methods require 13% and 4% of logic devices, respectively, compared to the design using multipliers. Furthermore, the power consumption is reduced by about 40%. A design which is efficient in terms of power consumption and chip area while having adequate speed means that the FPGA chip can be used to accommodate more controllers with low power consumption, resulting in a cost reduction of the controller hardware.
PARA HACER CRITICA DE TEATRO HAY QUE APARTARSE DEL DISCURSO OPRESIVO (1996)

DURANTE SU PARTICIPACION EN COLOQUIO EL TEATRO Y SU CRITICA, MANUEL CAPETILLO, CATEDRATICO DE LA FACULTAD DE FILOSOFIA Y LETRAS (FFL), PRECISO QUE PARA REALIZAR CRITICA DE TEATRO HAY QUE APARTARSE DE LAS IDEAS RELATIVAS A LO ANALITICO Y DE LAS INDICACIONES QUE PLANTEAN UN DISCURSO OPRESIVO, LIMITADO Y LIMITANTE. EN EVENTO REALIZADO EN AULA MAGNA DE LA FFL, LECH HELLWING-GORZYNSKI, DIRECTOR DE TEATRO, ESTIMO QUE LA CRITICA PROFESIONAL DE TEATRO DEBIERA PERCIBIR LAS CARENCIAS DE LAS PUESTAS ESCENICAS.
NADP-Glutamate Dehydrogenase Isoenzymes of Saccharomyces cerevisiae (2001)

In the yeast Saccharomyces cerevisiae, two NADP(+)-dependent glutamate dehydrogenases (NADP-GDHs) encoded by GDH1 and GDH3 catalyze the synthesis of glutamate from ammonium and alpha-ketoglutarate. The GDH2-encoded NAD(+)-dependent glutamate dehydrogenase degrades glutamate producing ammonium and alpha-ketoglutarate. Until very recently, it was considered that only one biosynthetic NADP-GDH was present in S. cerevisiae. This fact hindered understanding the physiological role of each isoenzyme and the mechanisms involved in alpha-ketoglutarate channeling for glutamate biosynthesis. In this study, we purified and characterized the GDH1- and GDH3-encoded NADP-GDHs; they showed different allosteric properties and rates of alpha-ketoglutarate utilization. Analysis of the relative levels of these proteins revealed that the expression of GDH1 and GDH3 is differentially regulated and depends on the nature of the carbon source. Moreover, the physiological study of mutants lacking or overexpressing GDH1 or GDH3 suggested that these genes play nonredundant physiological roles. Our results indicate that the coordinated regulation of GDH1-, GDH3-, and GDH2-encoded enzymes results in glutamate biosynthesis and balanced utilization of alpha-ketoglutarate under fermentative and respiratory conditions. The possible relevance of the duplicated NADP-GDH pathway in the adaptation to facultative metabolism is discussed.
CD40-Specific Costimulation Blockade Enhances Neonatal Porcine Islet Survival in Nonhuman Primates (2011)

The widespread clinical implementation of alloislet transplantation as therapy for type 1 diabetes has been hindered by the lack of suitable islet donors. Pig-to-human islet xenotransplantation is one strategy with potential to alleviate this shortage. Long-term survival of porcine islets has been achieved using CD154-specific antibodies to interrupt the CD40/CD154 costimulation pathway; however, CD154-specific antibodies seem unlikely candidates for clinical translation. An alternative strategy for CD40/CD154 pathway interruption is use of CD40-specific antibodies. Herein, we evaluate the ability of a chimeric CD40-specific monoclonal antibody (Chi220) to protect islet xenografts. Neonatal porcine islets (~50,000 IEQ/kg) were transplanted intraportally into pancreatectomized diabetic macaques. Immunosuppression consisted of induction therapy with Chi220 and the IL-2 receptor-specific antibody basiliximab, and maintenance therapy with sirolimus and the B7-specific fusion protein belatacept. Chi220 effectively promoted xenoislet engraftment and survival, with five of six treated recipients achieving insulin-independent normoglycemia (median rejection-free survival 59 days; mean 90.8 days, maximum 203 days). No thromboembolic phenomena were observed. CD40 represents a promising alternative to CD154 as a therapeutic target, and the efficacy of CD40-specific antibodies in islet xenotransplantation warrants further investigation.
Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease. (1989)

The incidence of c-ERBB-2 amplification in breast cancers and its usefulness as a predictor of tumor recurrence after treatment have been subjects of controversy (Ali et al., 1988, Slamon et al., 1987). We re-examined this subject by analysing 157 primary and 14 metastatic breast cancers with c-ERBB-2 and 18 other molecular probes as controls. Five proto-oncogenes were found to be occasionally amplified in primary breast cancers: c-ERBB-2 (11%), c-MYB (3%), c-RAS-Ki (3%), INT-2 (4%) and c-MYC (6%). No statistically significant correlation between amplification of c-ERBB-2 and recurrence of tumors was observed. The only significant correlation observed was between early recurrence of advanced (stage III) tumors and amplification of one or another of the above five proto-oncogenes. We conclude that breast cancer utilize multiple genetic mechanisms in their progression and metastasis, and that analysis of c-ERBB-2 alone is not a useful guide.
Treatment of severe staphylococcal infections with cefotaxime and fosfomycin in combination (1984)

In a prospective study, 23 severe staphylococcal infections (9 meningitis, 10 bone and joint infections, 3 septicaemia, 1 superinfection of a congenital varicella) were treated with cefotaxime and fosfomycin in combination. There was a synergistic effect of the combination for 14 of the 17 strains tested. Three hours after the end of the infusion, mean CSF concentrations of cefotaxime and fosfomycin were respectively at day 2 3.2 mg/l and 31.4 mg/l, at day 4 2.9 mg/l and 33.9 mg/l. All the patients with meningitis or acute bone and joint infections recovered satisfactorily without relapses. Two superinfections were observed (one systemic candidosis and one septicaemia due to Pseudomonas aeruginosa). Clinical tolerance was good and treatment was discontinued for side effects in only three patients.
An effective video analysis method for detecting red light runners (2001)

This paper presents a novel method for automatic red light runner detection on a video, which is fundamentally different from the concept of conventional red light camera systems. In principle, it extracts the state of the traffic lights and vehicle motions without any physical or electronic interconnections to the traffic light control system or the buried loop detectors. Purely from the video, the new method first constructs a traffic light sequence and then it estimates vehicle motions beyond the stop line while the light is red. In the former, the spatial and temporal relationships of individual traffic lights are utilized. In the latter, the concept of virtual loop detector has been introduced to emulate the physical loop detectors. A prototype was implemented based on this method and was tested in a number of field trials. The results show that the new method is able to detect multiple red light runners in multiple lanes. It is also capable of tolerating a number of hostile but realistic situations such as: 1) minimum number of traffic light; 2) pseudomotions due to shadows; 3) poor contrast; 4) pedestrian motions; and 5) turning vehicles.
Formation of Adeno-Associated Virus Circular Genomes Is Differentially Regulated by Adenovirus E4 ORF6 and E2a Gene Expression (1999)

A central feature of the adeno-associated virus (AAV) latent life cycle is persistence in the form of both integrated and episomal genomes. However, the molecular processes associated with episomal long-term persistence of AAV genomes are only poorly understood. To investigate these mechanisms, we have utilized a recombinant AAV (rAAV) shuttle vector to identify circular AAV intermediates from transduced HeLa cells and primary fibroblasts. The unique structural features exhibited by these transduction intermediates included circularized monomer and dimer virus genomes in a head-to-tail array, with associated specific base pair alterations in the 5' viral D sequence. In HeLa cells, the abundance and stability of AAV circular intermediates were augmented by adenovirus expressing the E2a gene product. In the absence of E2a, adenovirus expressing the E4 open reading frame 6 gene product decreased the abundance of AAV circular intermediates, favoring instead the linear replication form monomer (Rfm) and dimer (Rfd) structures. In summary, the formation of AAV circular intermediates appears to represent a new pathway for AAV genome conversion, which is consistent with the head-to-tail concatemerization associated with latent-phase persistence of rAAV. A better understanding of this pathway may increase the utility of rAAV vectors for gene therapy.
HEPATOCELLULAR DYSFUNCTION OCCURS EARLIER THAN THE ONSET OF HYPERDYNAMIC CIRCULATION DURING SEPSIS (1995)

Studies indicate that hepatocellular dysfunction occurs at 2 h after cecal ligation and puncture (CLP, i.e., sepsis model) despite the increased cardiac output (CO) and hepatic perfusion. It, however, remains unknown whether hepatocellular function is depressed earlier than the onset of hyperdynamic circulation in sepsis. To determine this, rats were subjected to sepsis by CLP. At .5, 1, 1.5, or 2 h after CLP, CO was measured by dye dilution. Hepatocellular function (i.e., maximum velocity of indocyanine green clearance and the efficiency of the active transport) was determined using an in vivo indocyanine green clearance technique. Microvascular blood flow was measured by laser Doppler flowmetry. To determine whether there is any association between hemodynamics and prostaglandins (PGs), plasma levels of PGE2 and PGI2 were measured by radioimmunoassay. The results indicate that hepatocellular function decreased significantly as early as 1.5 h after CLP. Cardiac output and microvascular blood flow in the liver and small intestine, however, increased and vascular resistance decreased at 2 h after CLP. Thus, hepatocellular dysfunction occurs earlier than the occurrence of hyperdynamic circulation during sepsis. Although circulating PGE2 levels were not altered, plasma PGI2 increased significantly at 2 h after CLP. The elevated circulating PGI2 levels, therefore, may be partially responsible for the decreased vascular resistance and increased tissue perfusion at 2 h after CLP. Our findings also suggest that cellular dysfunction, observed in the very early stage of sepsis, is not due to any hyperdynamic circulation/hypermetabolism-related events, but may be associated with the release of proinflammatory cytokines.
Changes in brown-adipose-tissue mitochondrial processes in streptozotocin-diabetes (1988)

Diabetic rats were used as a source of brown-adipose-tissue mitochondria 2 days after a single subcutaneous injection of streptozotocin (100 mg/kg). Diabetes caused an 80% decrease in carnitine-dependent oxidation of palmitoyl-CoA and a 50-60% decrease in overt carnitine palmitoyltransferase activity. An additional lesion in brown-adipose-tissue mitochondrial oxidative capacity was also indicated, since diabetes increased by 30-50% the rate of oxidation under uncoupled conditions of several respiratory substrates (i.e. malate + palmitoylcarnitine, malate + pyruvate, succinate, NNN'N'-tetramethyl-p-phenylenediamine + ascorbate). This decrease in mitochondrial function was accompanied by an approx. 30% decrease in the abundance of cytochromes (a + a3) and total cytochromes b.
Internal standard tracked dilution to overcome challenges in dried blood spots and robotic sample preparation for liquid chromatography/tandem mass spectrometry assays (2011)

Dried blood spot (DBS) technology is an emerging alternative for sample collection in bioanalysis. Dilution for DBS samples is a challenge due to its solid sample format. Currently, DBS samples requiring dilution were first extracted as regular samples and then diluted with extracted blank samples containing internal standard (IS). Since the dilution step is a volume-critical step, extra care has to be taken to achieve accurate dilution when dealing with limited volume extracted samples. Here, we introduce an alternative sample dilution for liquid chromatography/tandem mass spectrometry (LC/MS/MS) assays using IS to track the dilution step. Dilution factor-adjusted IS working solution was first added to the sample requiring dilution before sample processing; subsequently, the processed sample was approximately diluted into the assay linear response range before LC/MS/MS analysis. We define this approach as "IS-tracked dilution". The advantage of this approach is that the diluting step is tracked by the IS and is no longer a volume-critical step. Another recognized challenge related to sample dilution is automatic sample dilution using a liquid handler. This "IS-tracked dilution" may also help address some of the challenges for automatic sample dilution of liquid samples. This new dilution approach was proven to be effective and convenient in both plasma assays and DBS assays using omeprazole as a probe compound.