gebhart/patrepeval huggingface dataset:
Topical Zinc in the Treatment of Mice Infected Intravaginally with Herpes Genitalis Virus (1980)

The course of the disease, HSV-2, inoculated intravaginally in immature mice was ascertained by studying the incidence of vaginitis, encephalitis, and mortality rate. The therapeutic efficacy of various zinc containing medications administered topically 4 hr after infection was studied. It was found that intravaginally applied zinc medicated collagen sponge containing 50 μg zinc sulfate (7H2O) in acetate buffer, pH 5.5, significantly improved the course of disease and was significantly more effective than zinc administered intravaginally in a cream base. A solution of zinc sulfate administered as a douche was as effective as the comparable concentration of zinc applied through resilient collagen sponge. We conclude that topical administration of zinc through resilient collagen sponge or as a douche used shortly after the infection significantly inhibits the course of the herpes genitalis infection in the mouse.
Modulation of annexin II tetramer by tyrosine phosphorylation (1995)

Annexin II tetramer (AIIt) is a Ca(2+)-dependent phospholipid-binding phosphoprotein. In cells either expressing transforming protein tyrosine kinases or treated with growth factors such as PDGF, AIIt has been shown to contain increased levels of phosphotyrosine. Therefore, we have examined the effects of the in vitro phosphorylation of AIIt by pp60c-src on several activities of the protein. AIIt was phosphorylated by pp60c-src to 0.91 +/- 0.07 mol of phosphate/mol of AIIt (mean +/- SD). The protein tyrosine phosphorylation of AIIt completely inhibited the ability of the protein to bind to and bundle F-actin. In contrast, the phosphoprotein and native protein bound to purified adrenal medulla chromaffin granules with similar affinity; however, the chromaffin granule bridging activity of the phosphoprotein was abolished. The inhibition of the chromaffin granule bridging activity of the phosphoprotein could be partially reversed by the addition of millimolar Ca2+. Furthermore, the phosphorylation of AIIt by pp60c-src inhibited the in vitro ability of this annexin to form a complex consisting of plasma membrane, chromaffin granules, and AIIt. In addition to binding to biological membranes, some annexin proteins have been shown to possess carbohydrate-binding activity. Although native AIIt bound to a heparin affinity column, tyrosine phosphorylation of AIIt blocked the ability of the protein to bind to the heparin affinity column. These results suggest that the tyrosine phosphorylation of AIIt is a negative modulator of AIIt and that the dephosphorylation of AIIt might be necessary for activation of the protein.
Total Synthesis of Sintokamide C (2010)

A convergent stereoselective synthesis of sintokamide C was accomplished in 14 steps with an overall yield of 3.8% starting from Garner's aldehyde, unambiguously confirming its structure.
Paclitaxel in combination with vinorelbine in pretreated advanced breast cancer patients. (1996)

This phase II study combined paclitaxel (Taxol; Bristol Myers Squibb Company, Princeton, NJ) 135 mg/m2 by 3-hour infusion on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 (in the first 14 patients) or on days 1 and 3 (in the subsequent 20 patients). The courses were repeated every 3 weeks. The second vinorelbine dose (on days 3 or 8) was reduced or omitted according to the toxicities encountered. Thirty-four patients have been treated to date; 21 had received one prior regimen of chemotherapy, 11 had two prior regimens, and two had three prior regimens. Only two patients (6%) had not been exposed to anthracyclines. One hundred twenty-six courses have been administered: 52 with vinorelbine given on days 1 and 8, and 74 with vinorelbine administered on days 1 and 3. The most frequent toxicity was grade 4 neutropenia, which occurred in 64% of the courses; 13 episodes of febrile neutropenia have been reported in eight patients. Filgrastim was administered in 43% of the courses because of febrile neutropenia or delayed recovery (> 72 hours) from grade 4 neutropenia. Mucositis was observed in 18% of the courses (12% grade 1, 3% grade 2, and 3% grade 3). The dose of vinorelbine was reduced or omitted in 86% of courses with the days 1 and 8 schedule, and in 48% of courses with the days 1 and 3 schedule. Among 28 evaluable patients, two complete and 10 partial responses have been observed (response rate, 43%, 95% confidence interval, 19% to 51%). Median duration of response is 5+ months (range, 1 to 15 months). In conclusion, this combination is active and has acceptable toxicities in anthracycline-pretreated breast cancer patients. The delivered dose intensity of vinorelbine is higher with the schedule adopted later in the study, with vinorelbine given on days 1 and 3.
Membranous nephropathy: from models to man (2014)

As recently as 2002, most cases of primary membranous nephropathy (MN), a relatively common cause of nephrotic syndrome in adults, were considered idiopathic. We now recognize that MN is an organ-specific autoimmune disease in which circulating autoantibodies bind to an intrinsic antigen on glomerular podocytes and form deposits of immune complexes in situ in the glomerular capillary walls. Here we define the clinical and pathological features of MN and describe the experimental models that enabled the discovery of the major target antigen, the M-type phospholipase A2 receptor 1 (PLA2R). We review the pathophysiology of experimental MN and compare and contrast it with the human disease. We discuss the diagnostic value of serological testing for anti-PLA2R and tissue staining for the redistributed antigen, and their utility for differentiating between primary and secondary MN, and between recurrent MN after kidney transplant and de novo MN. We end with consideration of how knowledge of the antigen might direct future therapeutic strategies.
Direct and multistep conversion of lignin to biofuels (2012)

Lignin is the second most abundant biopolymer on Earth, right after cellulose, with a highly complex chemical structure that hinders its possible utilizations. Applications that utilize lignin in different manners are of great interest, due to its inexpensive nature. Present work is based on the notion of converting lignin into different biofuels that have only a few, however important, advantages over lignin as a direct energy source. The first part of current work (pyrolysis) details the analysis of lignin from a relatively new lignin isolation process called LignoBoost. It is obtained from the pulp and paper industry via CO₂ precipitation of lignin from black liquor (BL). This method is environment friendly, results lignin with minimal oxidation, eliminates the main bottleneck of the Kraft cycle (recovery boiler capacity), and yet leaves enough lignin in the process stream to recover pulping chemicals and generate energy for the pulp mill. Pyrolysis had converted this lignin into bio-oil with high aliphatic content and low oxidation level, all advantageous for application as liquid fuel. The second part of this dissertation proved the theory that lignin degradation and lipid accumulation metabolic pathways can be interconnected. Gram-positive Rhodococcus opacus species, DSM 1069 and PD630 were used to evaluate lignin to lipid bioconversion, starting with ethanol organosolv and Kraft lignin. This conversion is a first step in a multistep process towards biodiesel production, which includes transesterification, after lipids are extracted from the cells. Results clearly indicated that the lignin to lipid bioconversion pathway is viable, by cells gaining up to 4 % of their weight in lipids, while growing solely on lignin as a carbon and energy source.
Lung cancer and DNA repair genes: multilevel association analysis from the International Lung Cancer Consortium (2012)

Lung cancer (LC) is the leading cause of cancer-related death worldwide and tobacco smoking is the major associated risk factor. DNA repair is an important process, maintaining genome integrity and polymorphisms in DNA repair genes may contribute to susceptibility to LC. To explore the role of DNA repair genes in LC, we conducted a multilevel association study with 1655 single nucleotide polymorphisms (SNPs) in 211 DNA repair genes using 6911 individuals pooled from four genome-wide case-control studies. Single SNP association corroborates previous reports of association with rs3131379, located on the gene MSH5 (P = 3.57 × 10-5) and returns a similar risk estimate. The effect of this SNP is modulated by histological subtype. On the log-additive scale, the odds ratio per allele is 1.04 (0.84-1.30) for adenocarcinomas, 1.52 (1.28-1.80) for squamous cell carcinomas and 1.31 (1.09-1.57) for other histologies (heterogeneity test: P = 9.1 × 10(-)(3)). Gene-based association analysis identifies three repair genes associated with LC (P < 0.01): UBE2N, structural maintenance of chromosomes 1L2 and POLB. Two additional genes (RAD52 and POLN) are borderline significant. Pathway-based association analysis identifies five repair pathways associated with LC (P < 0.01): chromatin structure, DNA polymerases, homologous recombination, genes involved in human diseases with sensitivity to DNA-damaging agents and Rad6 pathway and ubiquitination. This first international pooled analysis of a large dataset unravels the role of specific DNA repair pathways in LC and highlights the importance of accounting for gene and pathway effects when studying LC.
[Kinetic study of the action of pancreatic lipase on emulsified triglycerides. Enzymology assay in heterogeneous medium]. (1965)

Summary The purpose of this paper was to study the action of pancreatic lipase (glycerol ester hydrolase, EC 3.1.1.3) on emulsified triglycerides. This type of action is an interesting example of an enzymatic process taking place in an heterogeneous medium. It is shown that: 1. Lipase is adsorbed by its emulsified substrate and the initial rate ( v ) of the reaction is a function of the number of enzyme molecules adsorbed at the interface. 2. By varying the dilution of a triglyceride emulsion in bile salts in the presence of 0.1 M NaCl, linear Lineweaver-Burk representations are obtained from which the reaction paramaters V m arid K m can easily be derived. However, the abscissae of the representation, and consequently the K m values, remain undefined as long as a right substitute for the substrate concentration concept is not found. Obviously, this concept cannot be used when the substrate is in an insoluble state. 3. By using two emulsions containing particles of different size, it can be shown that v does not depend directly on the weight of the insoluble substrate. For the same weight, the same amount of lipase and the same experimental conditions. v becomes higher when the average size of the particles decreases, v depends on the area ( I ) of the interface. I can be experimentally determined with a good accuracy by two techniques : centrifugation of the emulsions in a sucrose gradient and counting of the particles according to their size in an electronic Coulter counter. 4. On the other hand, v is inversely proportional to the total volume ( A 0 ) of the emulsion. Thus, lipase adsorption may be considered as fully reversible in our experimental conditions and to take place according to Langmuir's isotherms. The “interface concentration” I / A 0 , i.e. the interfacial area in a volume unit of emulsion, is playing, in the case of lipase, the role normally devoted to the concentration of the substrate. The K m (emulsion) of lipase corresponds to a certain value of this interface concentration. This does not mean that I / A 0 is the only significant variable in the process. Other variables such as electrical charge of emulsified particles and molecular organization at the interface may also play a role. 5. It may be supposed that the well-known influence of bile salts during the intraluminar phase of triglyceride digestion is at least partly related to the ability of these substances to favour the reversibility of lipase adsorption at the interface.
Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer’s disease (2009)

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Abeta1-40, Abeta1-42, total tau, phosphorylated tau, alpha-1 acid glycoprotein (A1GP), haptoglobin, zinc alpha-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of Abeta1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that Abeta1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using Abeta1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of Abeta1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Abeta1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Abeta1-42 alone. For the discrimination of AD from NADD subjects, measurement of Abeta1-42 alone was superior.
Loss-bounded analysis for differentiated services (2001)

We consider a network providing Differentiated Services (Diffserv) which allow network service providers to offer different levels of Quality of Service (QoS) to different traffic streams. We focus on loss and first show that only trivial bounds could be obtained by means of traditional competitive analysis. Then we introduce a new approach for estimating loss of an online policy called loss-bounded analysis. In loss-bounded analysis the loss of an online policy are bounded by the loss of an optimal offline policy plus a constant fraction of the benefit of an optimal offline policy. We derive tight upper and lower bounds for various settings of Diffserv parameters using the new loss-bounded model. We believe that loss-bounded analysis is an important technique that may complement traditional competitive analysis and provide new insight and interesting results.
Phase I trial of a human-mouse chimeric anti-disialoganglioside monoclonal antibody ch14.18 in patients with refractory neuroblastoma and osteosarcoma. (1998)

In summary, with the dose schedule used, ch 14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxicities. Further clinical trials of mAb ch 14.18 in patients with neuroblastoma are warranted.
Delay discounting of reward in ADHD: application in young children (2010)

ADHD is associated with a steeper delay gradient when contemplating hypothetical later rewards, but not independently of IQ. The interplay of cognitive processing and IQ with reward evaluation in ADHD requires further exploration.
Diquafosol tetrasodium: a novel dry eye therapy (2004)

The ophthalmic formulation of diquafosol tetrasodium (INS365), a P2Y2 receptor agonist, is targeted to treat dry eye disease through rehydration of the ocular surface. Existing pharmacological therapies for dry eye disease are limited, therefore, approval of this medication is anticipated. This review summarises key findings during development and in clinical trials including clinical effectiveness and safety. The relevance of P2Y2 receptor technology to dry eye disease and the disease process is discussed.
Role of p190RhoGAP in β2 Integrin Regulation of RhoA in Human Neutrophils (2001)

We found that engagement of beta(2) integrins on human neutrophils induced activation of RhoA, as indicated by the increased ratio of GTP:GTP + GDP recovered on RhoA and translocation of RhoA to a membrane fraction. The clustering of beta(2) integrins also induced a time-dependent increase in GDP bound to RhoA, which correlated with beta(2) integrin-induced activation of p190RHOGAP: The activation of p190RhoGAP was completely blocked by [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), a selective inhibitor of Src family tyrosine kinases. However, clustering of beta(2) integrins did not increase the basal tyrosine phosphorylation of p190RhoGAP, nor did it affect the amount of p120RasGAP bound to p190RHOGAP: Instead, the beta(2) integrin-induced activation of p190RhoGAP was accompanied by increased tyrosine phosphorylation of a p190RhoGAP-associated protein, p120RasGAP, and accumulation of both p120RasGAP and p190RhoGAP in a membrane fraction. PP1 blocked the beta(2) integrin-induced phosphorylation of p120RasGAP, as well as the translocation of p190RhoGAP and p120RasGAP, but it did not affect the accumulation of RhoA in the membrane fraction. In agreement with the mentioned findings, PP1 also increased the GTP:GTP + GDP ratio recovered on RhoA immunoprecipitated from beta(2) integrin-stimulated cells. Thus, in neutrophils, beta(2) integrin-induced activation of p190RhoGAP requires a signal from a Src family tyrosine kinase, but it does not occur via the signaling pathway responsible for activation of RHOA:
Spectral Properties and Relaxation Dynamics of Surface Plasmon Electronic Oscillations in Gold and Silver Nanodots and Nanorods (1999)

The field of nanoparticle research has drawn much attention in the past decade as a result of the search for new materials. Size confinement results in new electronic and optical properties, possibly suitable for many electronic and optoelectronic applications. A characteristic feature of noble metal nanoparticles is the strong color of their colloidal solutions, which is caused by the surface plasmon absorption. This article describes our studies of the properties of the surface plasmon absorption in metal nanoparticles that range in size between 10 and 100 nm. The effects of size, shape, and composition on the plasmon absorption maximum and its bandwidth are discussed. Furthermore, the optical response of the surface plasmon absorption due to excitation with femtosecond laser pulses allowed us to follow the electron dynamics (electron−electron and electron−phonon scattering) in these metal nanoparticles. It is found that the electron−phonon relaxation processes in nanoparticles, which are smaller than the electron mean free path, are independent of their size or shape. Intense laser heating of the electrons in these particles is also found to cause a shape transformation (photoisomerization of the rods into spheres or fragmentation), which depends on the laser pulse energy and pulse width.
Iterative detection for pretransformed OFDM by subcarrier reconstruction (2005)

In this paper, an iterative detection method for an uncoded pretransformed (PT) orthogonal frequency division multiplexing (OFDM) system where the channel is not known at the transmitter is proposed. The iterative detection starts with linear detection. The noiseless received signal at the weakest subcarrier (corresponding to the smallest channel amplitude) is estimated based on all the detected data symbols using a hard or soft decision. Then, the actual received signal at the weakest subcarrier is replaced by the estimated one. This process is referred to as reconstruction here. After reconstruction, linear detection is carried out again to generate the next set of symbol estimates. The whole process proceeds iteratively to reconstruct the received signal at the next-weakest subcarrier. The transform coefficients and the iterative process are designed to maximize the minimum signal-to-noise power ratio. Under the assumption that the previous detection is error free, it is shown analytically that the iterative method achieves a diversity advantage of i+1 in the ith iteration, thus providing an explanation of its superior performance. Due to the flexibility of the transform design, the analysis conducted is applicable for other common systems as well. Simulations in realistic channels are carried out, and the bit-error rate performance of the iterative detection is superior as compared to that of the conventional detectors for the PT-OFDM or OFDM system.
Targeting Mcl-1 for the therapy of cancer (2011)

We discuss the potential issues that arise in targeting Mcl-1 and other Bcl-2 anti-apoptotic proteins, as well problems with acquired resistance. The application of combinatorial approaches that involve inhibiting Mcl-1 and manipulation of additional signaling pathways to enhance therapeutic outcomes is also highlighted. The ability to specifically inhibit key genetic/epigenetic elements and biochemical pathways that maintain the tumor state represent a viable approach for developing rationally based, effective cancer therapies.