gebhart/patrepeval huggingface dataset:
Triggering of interferon γ-primed macrophages by various known complement activators for nonspecific tumor cytotoxicity (1987)

Five known complement activators were evaluated for their capacity to directly activate murine macrophages and to trigger activation of lymphokine primed macrophages for nonspecific tumor cytotoxicity. Bacterial lipopolysaccharide (LPS), Lipid A, polyinosinic-polycytidylic acid, cobra venom factor (CVF), and zymosan directly activated macrophages in a dose-dependent fashion at high concentrations. Subactivating concentrations of each of these agents were found to effectively trigger macrophages which were preprimed either by macrophage-activating factor or by murine recombinant interferon gamma for enhanced tumoricidal activity. An Fc receptor blockade with opsonized sheep erythrocytes abrogated LPS-mediated direct activation and triggering of interferon gamma-primed macrophages, but had no inhibitory effect on direct activation or triggering by CVF for nonspecific tumor cytotoxicity. This study characterizes the capacity of a diverse group of known complement activators to serve as second signal triggers for culmination of the activation process of interferon-primed macrophages for nonspecific tumoricidal activity. These findings suggest that complement activators may directly activate macrophages by stimulation of interferon beta production by macrophages for self-priming and, as we have shown, act as self-triggers. The putative role of macrophage-associated complement components in the activation process is discussed.
A Constrained Optimization Method for Community Detection (2009)

Community detection is one of the most important problems in complex network research. In recent years, great efforts have been devoted to this problem in term of evaluating the resulting community structure. Our previous work has shown that in addition to the resolution limit of Q, both Q and D suffer from a more serious limitation, termed as extra weak community phenomenon, i.e. some derived communities do not satisfy even the weak community definition. In this paper, we provide a constrained optimization model to overcome extra weak community phenomenon. With an improved simulated annealing algorithm, we solve the constrained optimization model for both Q and D, and then use our new method in several practical community detection problems. The experimental results show that the new method can not only partition large networks into communities properly but also ensure that all resulting communities at least satisfy the weak community definition. In addition, we find that constrained optimization of Q finds fewer but large communities, while constrained optimization of D takes the network apart more detailed.
A Mucoadhesive Polymer Extracted from Tamarind Seed Improves the Intraocular Penetration and Efficacy of Rufloxacin in Topical Treatment of Experimental Bacterial Keratitis (2004)

Bacterial keratitis is a serious infectious ocular disease requiring prompt treatment to prevent frequent and severe visual disabilities. Standard treatment of bacterial keratitis includes topical administration of concentrated antibiotic solutions repeated at frequent intervals in order to reach sufficiently high drug levels in the corneal tissue to inhibit bacterial growth. However, this regimen has been associated with toxicity to the corneal epithelium and requires patient hospitalization. In the present study, a mucoadhesive polymer extracted from tamarind seeds was used for ocular delivery of 0.3% rufloxacin in the treatment of experimental Pseudomonas aeruginosa and Staphylococcus aureus keratitis in rabbits. The polysaccharide significantly increased the intra-aqueous penetration of rufloxacin in both infected and uninfected eyes. Rufloxacin delivered by the polysaccharide reduced P. aeruginosa and S. aureus in the cornea at a higher rate than that obtained by rufloxacin alone. In particular, use of the polysaccharide allowed a substantial reduction of S. aureus in the cornea to be achieved even when the time interval between drug administrations was extended. These results suggest that the tamarind seed polysaccharide prolongs the precorneal residence times of antibiotics and enhances drug accumulation in the cornea, probably by reducing the washout of topically administered drugs. The tamarind seed polysaccharide appears to be a promising candidate as a vehicle for the topical treatment of bacterial keratitis.
Shah Convolution Fourier Transform Detection (1999)

A new convolution-detection method was developed which converts multiple-point (Shah function) detection, time-domain electropherograms into frequency-domain plots by means of a Fourier transformation, allowing the analytes' speeds to be viewed in terms of their "blinking" frequency; we have named this method Shah convolution Fourier transform detection, or SCOFT. This paper represents proof of principle of the detection concept. A micromachined glass stucture with a patterned layer of Cr on its top surface to form regularly spaced detection slits was used to perform capillary electrophoresis separations with 55-point, laser-induced fluorescence detection over 3.78 cm of the 6.6 cm separation channel. While this method can be easily integrated into a miniaturized total analysis system (μ-TAS), the principle is equally applicable to detection in full-sized analytical instrumentation. Single-component samples (fluorescein) migrating through the separation channel yielded a single peak in the frequency domain, and two-component samples (fluorescein and fluorescein isothiocyanate) yielded two resolved peaks, each at the expected frequency; harmonics were also observed. Advantages were seen in terms of isolation of the analyte peaks from interference such as baseline drift and line noise. Resolution is somewhat inferior to that seen in single-point detection, but it is thought that improved chip design and mathematical and instrument optimization will lead to performance superior to that of single-point detection.
Scope and Mechanism of Enantioselective Michael Additions of 1,3-Dicarbonyl Compounds to Nitroalkenes Catalyzed by Nickel(II)−Diamine Complexes (2007)

Readily prepared Ni(II)-bis[(R,R)-N,N‘-dibenzylcyclohexane-1,2-diamine]Br2 was shown to catalyze the Michael addition of 1,3-dicarbonyl compounds to nitroalkenes at room temperature in good yields with high enantioselectivities. The two diamine ligands in this system each play a distinct role: one serves as a chiral ligand to provide stereoinduction in the addition step while the other functions as a base for substrate enolization. Ligand modification within the catalyst was also investigated to facilitate the reaction of aliphatic nitroalkenes, 1,3-diketones, and β-ketoacids. Ni(II)-bis[(R,R)-N,N‘-di-p-bromo-benzylcyclohexane-1,2-diamine]Br2 was found to be an effective catalyst in these instances. Furthermore, monodiamine complex, Ni(II)-[(R,R)-N,N‘-dibenzylcyclohexane-1,2-diamine]Br2, catalyzed the addition reaction in the presence of water. The proposed model for stereochemical induction is shown to be consistent with X-ray structure analysis.
Identification through bioinformatics of two new macrophage proinflammatory human chemokines: MIP-3α and MIP-3beta (1997)

An increasing number of proinflammatory peptides, known as chemokines, are constantly being described and characterized. Because of their proven biologic functions in allergy, AIDS and, in general, inflammatory processes, these proteins have recently gained more attention. In this study we report the identification through bioinformatics of two new human chemokines: MIP-3alpha and MIP-3beta. Both of them belong to the beta- or CC chemokine family. Expression studies indicate that MIP-3alpha is predominantly expressed in lymph nodes, appendix, PBL, fetal liver, fetal lung and several cell lines. However, MIP-3beta expression is restricted to lymph nodes, thymus and appendix. Interestingly enough, both chemokines manifested a pattern of expression strongly regulated by IL-10. In contrast with other CC chemokines, MIP-3beta maps to chromosome 9. Here we show the importance of bioinformatics to discover new molecules with possible therapeutic effects and regulatory functions.
A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus (2004)

Altered methylation patterns have been found to play a role in developmental disorders, cancer and aging. Increasingly, changes in DNA methylation are used as molecular markers of disease. Therefore, there is a need for reliable and easy to use techniques to detect and measure DNA methylation in research and routine diagnostics. We have established a novel quantitative analysis of methylated alleles (QAMA) which is essentially a major improvement over a previous method based on real-time PCR (MethyLight). This method is based on real-time PCR on bisulfite-treated DNA. A significant advantage over conventional MethyLight is gained by the use of TaqMan probes based on minor groove binder (MGB) technology. Their improved sequence specificity facilitates relative quantification of methylated and unmethylated alleles that are simultaneously amplified in single tube. This improvement allows precise measurement of the ratio of methylated versus unmethylated alleles and cuts down potential sources of inter-assay variation. Therefore, fewer control assays are required. We have used this novel technical approach to identify hypermethylation of the CpG island located in the promoter region of the retinoblastoma (RB1) gene and found that QAMA facilitates reliable and fast measurement of the relative quantity of methylated alleles and improves handling of diagnostic methylation analysis. Moreover, the simplified reaction setup and robustness inherent to the single tube assay facilitates high-throughput methylation analysis. Because the high sequence specificity inherent to the MGB technology is widely used to discriminate single nucleotide polymorphisms, QAMA potentially can be used to discriminate the methylation status of single CpG dinucleotides.
[Role of hyperammonemia in stuporous states induced by sodium valproate]. (1983)

Stuporous states induced by sodium valproate (VPA) are accompanied by an isolated marked hyperammonemia. In reality, hyperammonemia occurs after administration of VPA even in the absence of neurological complications. The hyperammonemia is of purely renal origin and results from modifications in glutamine metabolism, this compound being the main precursor of amino acid neurotransmitters. Combined administration of VPA and phenobarbitone increases the level of hyperammonemia due to lack of detoxification by the liver of the excess of ammonia produced by the kidneys. The anatomical site of origin of the ammoniogenesis, and its intensity, were studied in two patients with a history of stuporous states during combined VPA-phenobarbitone treatment. A single injection of VPA at a later date when they were being treated by combined phenobarbitone-carbamazepine therapy, induced disturbances in ammonia metabolism which did not differ qualitatively from those observed when intolerance to VPA is lacking. It is therefore not possible to rely on simple biological tests to detect patients at risk. Correlation is also lacking between the degree of hyperammonemia and disorders of vigilance. Ammonia does not therefore appear to be the only factor responsible for neurological complications and the role of other factors must be investigated. These include: disturbances of metabolism of inhibitory and excitatory aminoacid neurotransmitters, the condition of the cerebral parenchyma, and the excitatory effect of sodium valproate which could act to varying degrees in synergy with the hyperammonemia to provoke a stuporous state.
Linear Cryoablation of the Left Atrium Versus Pulmonary Vein Cryoisolation in Patients With Permanent Atrial Fibrillation and Valvular Heart Disease (2004)

In patients with permanent AF, left atrial dilatation and valvular heart disease linear lesions in the posterior region of the left atrium are more effective than PVI alone. With cryoablation, the surgical intent is fulfilled in only approximately 65% of the cases. Knowing the real anatomic and electrophysiological effects of surgical ablation is necessary to correctly interpret the clinical outcome.
Resistance to bismuth among Gram-negative bacteria is dependent upon iron and its uptake (1996)

Bismuth antimicrobial action is poorly understood. Many trivalent metals possess antibacterial activity, especially under low iron conditions. Protection of bacteria from the deleterious effects of bismuth and other trivalent metals was demonstrated in iron-fortified media. Near-equimolar quantities of Fe3+ neutralized the growth-inhibitory effects of 250 microM Bi3+. Resistance to bismuth action also depended on the production of virulence-related siderophores. Escherichia coli, Aeromonas hydrophila or Pseudomonas aeruginosa producing aerobactin, amonabactin or pyoverdin respectively, were most resistant to Bi3+. Enterochelin or pyochelin producers were less resistant to Bi3+, but more resistant than strains lacking siderophores. Purified pyoverdin restored Bi3+ resistance in a mutant lacking this siderophore, but not in one lacking the pyoverdin receptor. Bismuth-treated bacteria exhibited unique outer membrane proteins, similar in size to iron-repressible proteins. Thus, resistance to the inhibitory action of Bi3+ among Gram-negative bacteria is inversely related to iron concentration and strongly dependent on iron transport mechanisms. The data suggest that bismuth action is largely a nonspecific, competitive interference with iron-transport, related primarily to atomic valence Furthermore, resistance to Bi3+ among bacteria is predictive of virulence.
Joint Scheduling of URLLC and eMBB Traffic in 5G Wireless Networks (2018)

Emerging 5G systems will need to efficiently support both broadband traffic (eMBB) and ultra-low-latency (URLLC) traffic. In these systems, time is divided into slots which are further sub-divided into minislots. From a scheduling perspective, eMBB resource allocations occur at slot boundaries, whereas to reduce latency URLLC traffic is pre-emptively overlapped at the minislot timescale, resulting in selective superposition/puncturing of eMBB allocations. This approach enables minimal URLLC latency at a potential rate loss to eMBB traffic. We study joint eMBB and URLLC schedulers for such systems, with the dual objectives of maximizing utility for eMBB traffic while satisfying instantaneous URLLC demands. For a linear rate loss model (loss to eMBB is linear in the amount of superposition/puncturing), we derive an optimal joint scheduler. Somewhat counter-intuitively, our results show that our dual objectives can be met by an iterative gradient scheduler for eMBB traffic that anticipates the expected loss from URLLC traffic, along with an URLLC demand scheduler that is oblivious to eMBB channel states, utility functions and allocations decisions of the eMBB scheduler. Next we consider a more general class of (convex) loss models and study optimal online joint eMBB/URLLC schedulers within the broad class of channel state dependent but time-homogeneous policies. We validate the characteristics and benefits of our schedulers via simulation.
Testosterone, body composition and aging. (1999)

In addition to growth hormone (GH), sex hormones are important determinants of body composition. Aging is accompanied by a decrease in free testosterone levels and, as BMI as well as fat mass increase with age (with a redistribution of body fat), whereas muscle mass decreases, it is tempting to attribute a causal role to the decrease in androgen levels. In our study involving 372 males aged >20-85, age was found to be positively correlated with BMI and fat mass as measured by impedance, and negatively correlated with levels of free testosterone and free insulin-like growth factor-I. Multiple regression analysis revealed that BMI and age were independent determinants of testosterone levels. The latter decreased from 598+/-188 (SD) ng/dl in the young controls to 453+/-161 ng/dl in the elderly group, free testosterone decreasing from 15.35+/-4.10 to 8.38+/-2.51 ng/dl. Fat-free mass decreased by 18.9%. In a subgroup of 57 men aged 70-80 years, testosterone levels correlated negatively with percentage body fat (r=-0.57), abdominal fat (r=-0.56) and plasma insulin levels (r=-0.40). As GH levels and pulsatility also decrease with age and as, moreover, androgens amplify endogenous secretion of GH, it is not easy to determine the relative role of androgen deficiency in the age-associated changes in body composition. Moreover, increase in fat mass (obesity), as occurs in aging males, is in itself associated with low levels of free testosterone and GH which both normalize after weight reduction. The role of testosterone in the age-associated changes in body composition is, however, further suggested by the increase in lean body mass and in mid-arm circumference and the decrease in waist-to-hip ratio observed after testosterone treatment of elderly men with decreased testosterone levels. Also in healthy eugonadal men, testosterone treatment, at least in supraphysiological doses, causes an important increase in fat-free mass (+/-10%) and in muscle size. The changes in muscle volume are associated with an increase in muscle fibre diameter, suggesting that testosterone induces muscle cell hypertrophy. In conclusion, aging in males is accompanied by an important increase in fat mass and a decrease in lean body mass. Several indices of body composition are significantly correlated with plasma testosterone levels before and after correction for BMI and age. It is evident, however, that in addition to testosterone levels, the age-associated somatopause is also a determinant of the changes in body composition.
Characterization of toxins A and B of Clostridium difficile with monoclonal antibodies (1986)

Two monoclonal antibodies (MAbs) were used to learn more about the structures of Clostridium difficile toxins A and B. One of the antibodies, the PCG-4 MAb, reacted specifically with toxin A. This MAb precipitated toxin A and neutralized the enterotoxic but not the cytotoxic activity of the toxin. The site to which the antibody bound was resistant to denaturation with sodium dodecyl sulfate; however, it was destroyed by N-bromosuccinimide. Immunoblot analysis with the PCG-4 MAb revealed the presence of a large number of bands in preparations of denatured toxin A, suggesting that toxin A exists as an aggregate of smaller components. The antibody was covalently coupled to Affi-Gel 10, and the gel was used to purify toxin A from the culture filtrate of a highly toxigenic strain of C. difficile by immunoaffinity chromatography. The second antibody, the G-2 MAb, cross-reacted with toxins A and B. The cross-reaction was confirmed by immunoblot analysis. These results show that toxins A and B share an epitope and suggest that they have a common subunit. The G-2 MAb did not neutralize or precipitate either toxin. The site to which the G-2 MAb bound was partially destroyed by sodium dodecyl sulfate and was resistant to oxidation with N-bromosuccinimide.
Recent developments on JAK2 inhibitors: a patent review (2010)

The significant number of JAK2 inhibitors published and numerous clinical trials involving these compounds suggest that some of them might be approved in the next few years and can serve as novel drugs for the treatment of JAK2-dependent pathologies.
Molluscicidal saponins fromallium vineale (1987)

Several molluscicidal saponins have been isolated from the bulbs ofAllium vineale and their structures assigned using spectroscopic techniques. Particularly important were the use of 2D-NMR spectroscopy for resolved the structure of the saccharide unit.
Dexamethasone‐associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin (2003)

The addition of daunomycin led to a much larger increase in dexamethasone-related toxicity compared with the increase in prednisone-related toxicity. Although the use of daunomycin enhanced dexamethasone-related toxicity, this enhancement did not result in a higher mortality rate or the alteration of planned ALL therapy.
Phase II study of FOLFIRINOX for chemotherapy‐naïve Japanese patients with metastatic pancreatic cancer (2014)

The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for Japanese pancreatic cancer patients. Therefore, we carried out a phase II study to examine the efficacy and safety of FOLFIRINOX in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85 mg/m(2) oxaliplatin, 180 mg/m(2) irinotecan, and 200 mg/m(2) l-leucovorin, followed by a bolus of 400 mg/m(2) fluorouracil and a 46-h continuous infusion of 2400 mg/m(2) fluorouracil) was given every 2 weeks. The primary endpoint was the response rate. The 36 enrolled patients received a median of eight (range, 1-25) treatment cycles. The response rate was 38.9% (95% confidence interval [CI], 23.1-56.5); median overall survival, 10.7 months (95% CI, 6.9-13.2); and median progression-free survival, 5.6 months (95% CI, 3.0-7.8). Major grade 3 or 4 toxicities included neutropenia (77.8%), febrile neutropenia (22.2%), thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%), nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first cycle. There were no treatment-related deaths. FOLFIRINOX can be a standard regimen showing favorable efficacy and acceptable toxicity profile in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer.
Cytokine and chemokine mRNA produced in synovial tissue chronically infected with Chlamydia trachomatis and C. pneumoniae. (2002)

Our data suggest that while both C. trachomatis and C. pneumoniae have been associated with inflammatory joint disease, each elicits a somewhat different steady-state profile of mRNA encoding relevant cytokines and chemokines during chronic infection of synovial tissue. Precisely how these differing profiles relate to clinical aspects of synovial inflammation will require further study, but the observations confirm and extend data indicating potentially important differences in the pathobiology of these 2 bacterial species.