gebhart/patrepeval huggingface dataset:
Use of uridine rescue to enhance the antitumor selectivity of 5-fluorouracil. (1983)

We examined the ability of uridine to increase the therapeutic index of 5-fluorouracil (FUra) against C57BL/6 X DBA/2 F1 mice bearing a Day 1 B16 melanoma or L1210 leukemia. FUra (400, 600, or 800 mg/kg, i.p.) followed in 24 hr by a 5-day s.c. infusion with uridine (5 g/kg/day, s.c.) was compared with the maximum tolerated dose of FUra (200 mg/kg, i.p.) plus a 5-day infusion with 0.9% NaCl solution. High-dose FUra plus delayed infusion with uridine was more effective than FUra (200 mg/kg) in inhibiting the growth of the B16 melanoma. High-dose FUra plus uridine rescue was, however, no more effective than FUra (200 mg/kg) in increasing the survival times of mice bearing the L1210 leukemia. To see if uridine rescue from FUra toxicity correlated with effects against a sensitive normal tissue, bone marrow nucleated cellularity of normal, non-tumor-bearing mice was monitored after drug treatment. In mice treated with FUra (200 mg/kg) followed in 24 hr by a 5-day infusion with either uridine (5 g/kg/day) or 0.9% NaCl solution, there was not as great a decrease in cellularity at the nadir with uridine, and, in addition, uridine accelerated recovery as compared to 0.9% NaCl solution. Furthermore, uridine (5 g/kg/day), but not thymidine (dThd) (5 g/kg/day) or 2'-deoxyuridine (dUrd) (5 g/kg/day), had a sparing effect on the depression in bone marrow nucleated cellularity seen at the nadir on Day 4 after Fura (200 mg/kg). The specificity of uridine to rescue mice from the lethal toxicity of the related fluorinated pyrimidines, 5-fluorouridine and 5-fluoro-2'-deoxyuridine, was also examined. Mice were treated with 5-fluorouridine (250 mg/kg, i.p.) followed in 24 hr by a 5-day infusion with uridine (1, 5, or 10 g/kg/day), dThd (1, 5, or 10 g/kg/day), or dUrd (1 or 5 g/kg/day). Uridine (1, 5, or 10 g/kg/day) rescued mice from the lethal toxicity of 5-fluorouridine, whereas dThd or dUrd was ineffective. Similarly, a 5-day infusion with uridine, but not dThd or dUrd, rescued mice from the lethal toxicity of 5-fluoro-2'-deoxyuridine (1800 mg/kg, i.p.).
Diretrizes brasileiras para o tratamento da narcolepsia (2010)

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.
Settling Out of Court : How Effective is Alternative Dispute Resolution? (2011)

Alternative dispute resolution can help the justice system in a country function more efficiently. It often saves costs and time and increases user satisfaction. For cases that go back to court, however, the total cost and time may increase. Alternative dispute resolution can also have indirect benefits. It can increase the effectiveness of courts by reducing bottlenecks. And it can improve trust in the legal system, which may increase foreign investment.
Effect of rinsing hydrocolloid impressions using acidic electrolyzed water on surface roughness and surface hardness of stone models. (2002)

The present study investigated the effect on the surface quality of resultant stone models of rinsing hydrocolloid impressions using acidic electrolyzed water. Two brands of alginate impression materials (Aroma Fine DFIII, Jeltrate Plus), an agar impression material (Ajisai) designed for agar/alginate combined impression, and dental stone (New Plastone) were used to make the test specimens. For the rinsing of impressions, acidic electrolyzed water having a pH value of 2.3, an oxidation-reduction potential of 1, 230 mV, and a residual chlorine concentration of 45.0 ppm, was prepared. Alginate, agar and agar/alginate combined impressions were rinsed using acidic electrolyzed water or tap water for 30 sec and 3 min, and as a control, these impressions were not rinsed with any water. Disk-shaped stone specimens obtained from rinsed impressions were evaluated with respect to surface roughness (Ra) and surface hardness (scratch depth), and scanning electron microscope (SEM) observations were performed. The stone specimens obtained from rinsed impressions using acidic electrolyzed water showed a surface quality equivalent to that of the stone specimens obtained from the rinsed impression using tap water. This result suggests that the use of acidic electrolyzed water for rinsing is an acceptable treatment for hydrocolloid impressions, so long as the rinsing time is from 30 sec to 3 min (J. Oral Sci. 44, 141-146, 2002)
Blind Multiband Signal Reconstruction: Compressed Sensing for Analog Signals (2009)

We address the problem of reconstructing a multiband signal from its sub-Nyquist pointwise samples, when the band locations are unknown. Our approach assumes an existing multi-coset sampling. To date, recovery methods for this sampling strategy ensure perfect reconstruction either when the band locations are known, or under strict restrictions on the possible spectral supports. In this paper, only the number of bands and their widths are assumed without any other limitations on the support. We describe how to choose the parameters of the multi-coset sampling so that a unique multiband signal matches the given samples. To recover the signal, the continuous reconstruction is replaced by a single finite-dimensional problem without the need for discretization. The resulting problem is studied within the framework of compressed sensing, and thus can be solved efficiently using known tractable algorithms from this emerging area. We also develop a theoretical lower bound on the average sampling rate required for blind signal reconstruction, which is twice the minimal rate of known-spectrum recovery. Our method ensures perfect reconstruction for a wide class of signals sampled at the minimal rate, and provides a first systematic study of compressed sensing in a truly analog setting. Numerical experiments are presented demonstrating blind sampling and reconstruction with minimal sampling rate.
Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments (2001)

There have been important advances in basic science investigation of mechanisms underlying spontaneous miscarriages which lend support to empirical treatments such as intravenous immunoglobulin G and allogeneic leukocyte immunotherapy. The results from clinical trials of these and other proposed treatments have been problematic. There is only one published meta-analysis of sufficient power and appropriate stratification to qualify as Level 1 evidence, and that deals only with leukocyte immunotherapy. Here we critically review current trials and their flaws, update the meta-analysis, and comment on potential new approaches. Inadequate sample size, better definition of heterogeneity, and proper stratification to minimize the effects of heterogeneity remain as problems. Verification that the experimental or test treatment was active in producing the expected alteration in immunophysiology in the recipient is lacking in most trials; use of stored rather than fresh allogeneic leukocytes appears problematic. Hidden biases that affect trial significance emerge with critical analysis, and the focus on apparent 'high quality' of design in published reports may be misleading. We conclude that there seem to be enough patients to conduct clinical trials of sufficient size to achieve adequate power to test therapies showing promise in pilot studies, but at present, the only Level 1 evidence concerns leukocyte immunotherapy which appears to increase the chance of a live birth if given to appropriate patients.
An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction (2020)

Abstract SARS-CoV-2 is the etiologic agent of COVID-19, currently causing a devastating pandemic for which pharmacological interventions are urgently needed. The virus enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. The nanobody binds with high affinity in the low nM range to the RBD, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations and that Ty1 sterically hinders RBD-ACE2 binding. This 12.8 kDa nanobody does not need an Fc domain to neutralize SARS-CoV-2, and can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.
Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma (1994)

A prospective comparative trial of allogeneic versus autologous bone marrow transplant (BMT) was conducted. Sixty-six consecutive patients (median age, 41; range, 15 to 60; female:male ratio = 21:45) entered this clinical trial. Priority for allogeneic BMT was given to patients who were 55 or younger and had a major histocompatibility complex-matched or 1-antigen-disparate sibling donor. Autologous BMT was offered to all other patients whose age was 60 or younger. Patients who had no sibling donor and who had BM involvement at the time of evaluation were not eligible. Thirty-one patients received an allograft, and 35 patients received an autograft. Thirteen patients received a BM graft purged with 4-hydroperoxycyclophosphamide because of previous BM involvement. Patients who had previous radiation to the thoracic and/or abdominal areas of more than 20 Gy received a preparative regimen consisting of cyclophosphamide (1,800 mg/m2/d for 4 days), VP-16 (200 mg/m2 every 12 hours for 8 doses), and 1,3-bis(2-chloroethyl)-1-nitrosourea (600 mg/m2 as 1 dose). Other patients received cyclophosphamide 1,800 mg/m2/d for 4 days followed by total body irradiation of 12 Gy administered as a single daily fraction over 4 days. With a median follow-up of 14 months, the progression-free survival (PFS) for autograft and allograft recipients was 24% +/- 8% (+/- SE) and 47% +/- 9%, respectively, (P = .21). However, the probability of disease progression was significantly higher in the autologous group (69% +/- 9%) than in the allogeneic group (20% +/- 10%; P = .001). When other confounding prognostic factors were adjusted in the multivariate analysis, chemosensitive disease and allograft were found to have a significant favorable influence on probability of disease progression (P = .03 and .003), but only chemosensitive disease had a significant influence on the PFS (P < .002). Our results suggest the existence of graft-versus-lymphoma effect and also support the rationale of using immunotherapy after autologous BMT. Allogeneic BMT should be preferable to autologous BMT in younger patients with lymphoma.
Effects of a K <sup>+</sup> Channel Opener to Reduce Transmural Dispersion of Repolarization and Prevent Torsade de Pointes in LQT1, LQT2, and LQT3 Models of the Long-QT Syndrome (2000)

Our data suggest that K(+) channel openers may be capable of abbreviating the long QT interval, reducing TDR, and preventing spontaneous and stimulation-induced TdP when congenital or acquired LQTS is secondary to reduced I(Kr) or I(Ks) but less so when it is due to augmented late I(Na).
Physical and Psychological Morbidity After Axillary Lymph Node Dissection for Breast Cancer (1999)

Surgery-related symptoms after ALND persist for a majority of women with breast cancer and are not significantly related to time since surgery or receipt of radiation therapy. These symptoms and associated disability are significantly predictive of cancer-specific quality of life and mental health.
Synaptic-membrane proteins (1980)

Conference Article| October 01 1980 Synaptic-membrane proteins ELISABETH BOCK ELISABETH BOCK 1The Protein Laboratory, University of Copenhagen, 34 Sigurdsgade, DK-2200 Copenhagen, Denmark Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1980) 8 (5): 483–484. https://doi.org/10.1042/bst0080483 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation ELISABETH BOCK; Synaptic-membrane proteins. Biochem Soc Trans 1 October 1980; 8 (5): 483–484. doi: https://doi.org/10.1042/bst0080483 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1980 Biochemical Society1980 Article PDF first page preview Close Modal You do not currently have access to this content.
The chicken lysozyme 5' matrix attachment region increases transcription from a heterologous promoter in heterologous cells and dampens position effects on the expression of transfected genes. (1990)

Matrix attachment regions (MARs) are DNA elements that dissect the genome into topologically separated domains by binding to a chromosomal skeleton. This study explored the putative influence of the MAR located 5' of the chicken lysozyme gene on expression of heterologous genes in heterologous cell systems. Expression of a construct with the chloramphenicol acetyltransferase (CAT) indicator gene controlled by the herpes simplex virus thymidine kinase promoter (TC) and a construct in which the same transcriptional unit is flanked by chicken lysozyme 5' MARs (MTCM) was assayed after stable transfection into rat fibroblasts. Median CAT activity per copy number in MTCM transfectants was elevated approximately 10-fold relative to that in TC transfectants. Total variation in normalized CAT activity decreased from more than 100-fold among TC transfectants to nearly 6-fold among MTCM transfectants. The steady-state level of transcripts and the relative rate of transcription were increased in MTCM transfectants, as shown by S1 nuclease and run-on transcription assays, respectively. The chicken lysozyme 5' MAR thus can confer elevated, less position-dependent expression on a heterologous promoter in cells of a different species by increasing the density of transcribing RNA polymerase molecules. MAR-mediated transcriptional enhancement suggests that MARs are important for gene expression and not just for DNA packaging.
Hypomethylation of β-hydroxy-β-methyl-glutaryl coenzyme A reductase gene and its expression during hepatocarcinogenesis in the rat (1992)

Our earlier studies had demonstrated that inhibition of DNA methylation following carcinogen treatment potentiated initiation of the carcinogenic process in the rat liver system. The hepatic nodules developed by initiation-promotion protocols showed a characteristic hypomethylation in the cell-cycle-related genes c-fos, c-myc and c-Ha-ras. In the present study we have found that the gene for beta-hydroxy-beta-methyl glutaryl coenzyme A reductase, a major rate-limiting enzyme in the biogenesis of mevalonate, is also hypomethylated at both CCGG and GCGC sites and expressed in hepatic nodules. This gene, however, did not exhibit hypomethylation in CCGG sequences in non-nodular surrounding liver, livers from rats subjected to two-thirds partial hepatectomy, or exposed to initiator alone (1,2-dimethylhydrazine given 18 h after partial hepatectomy) or to diets containing 1% orotic acid alone (promoting regimen). The activity of the enzyme and mevalonate formation are positively correlated with DNA synthesis and cell proliferation--two key components of the carcinogenic process. Taken together, the results suggest that hypomethylation of specific genes occurs in the carcinogenic process and this altered pattern of DNA methylation may play a role in the growth of the nodules.
Onartuzumab (MetMAb): Using Nonclinical Pharmacokinetic and Concentration–Effect Data to Support Clinical Development (2013)

Onartuzumab pharmacokinetics differed from typical bivalent glycosylated monoclonal antibodies with approximately 2-times faster CL in the linear dose range. Despite this higher CL, xenograft efficacy data supported dose flexibility with Q1W to Q3W dose regimens in the clinical setting with a TSC of 15 μg/mL as the Ctrough ss target. The projected human efficacious dose of 10 to 30 mg/kg Q3W should achieve the target TSC of 15 μg/mL. These data show effective pharmacokinetic/pharmacodynamic modeling to project doses to be tested in the clinic.
A potentially artifact‐free oral contrast agent for gastrointestinal MRI (1993)

The combination of diamagnetic barium sulfate and superparamagnetic iron oxide (SPIO) in one suspension produces a macroscopic cancellation of positive and negative magnetic susceptibility components that can potentially eliminate susceptibility artifacts even with gradient echo pulse sequences. The relaxation properties that make the SPIO suspension a useful negative contrast agent are retained.
Elucidation of the role of Grr1p in glucose sensing by through genome-wide transcription analysis (2004)

The role of Grr1p in glucose sensing in Saccharomyces cerevisiae was elucidated through genome-wide transcription analysis. From triplicate analysis of a strain with deletion of the GRR1-gene from the genome and an isogenic reference strain, 68 genes were identified to have significantly altered expression using a Student's t-test with Bonferroni correction. These 68 genes were widely distributed across different parts of the cellular metabolism and GRR1-deletion is therefore concluded to result in polytrophic effects, indicating multiple roles for Grr1p. Using a less conservative statistical test, namely the SAM test, 232 genes were identified as having significantly altered expression, and also these genes were widely distributed across different parts of the cellular metabolism. Promoter analyses on a genome-wide scale and on the genes with significant changes revealed an over-representation of DNA-binding motifs for the transcriptional regulators Mig1p and Rgt1p in the promoter region of the significantly altered genes, indicating that Grr1p plays an important role in the regulatory pathways that ultimately lead to transcriptional regulation by each of the components Mig1p and Rgt1p.
A fast probabilistic ego-motion estimation framework for radar (2015)

This paper presents a fast, joint spatial- and Doppler velocity-based, probabilistic approach for ego-motion estimation for single and multiple radar-equipped robots. The normal distribution transform is used for the fast and accurate position matching of consecutive radar detections. This registration technique is successfully applied to laser-based scan matching. To overcome discontinuities of the original normal distribution approach, an appropriate clustering technique provides a globally smooth mixed-Gaussian representation. It is shown how this matching approach can be significantly improved by taking the Doppler information into account. The Doppler information is used in a density-based approach to extend the position matching to a joint likelihood optimization function. Then, the estimated ego-motion maximizes this function. Large-scale real world experiments in an urban environment using a 77 GHz radar show the robust and accurate ego-motion estimation of the proposed algorithm. In the experiments, comparisons are made to state-of-the-art algorithms, the vehicle odometry, and a high-precision inertial measurement unit.
Isolation and characterization of a fructosyltransferase gene from Streptococcus mutans GS-5 (1986)

A fructosyltransferase (FTF) gene from Streptococcus mutans GS-5 has been isolated from a lambda L47.1 clone bank. The gene was contained on an 11.7-kilobase GS-5 DNA fragment and was initially subcloned into plasmid pACYC184 as a 5.4-kilobase HindIII fragment. However, further analysis revealed that transcription of the FTF gene was initiated at the P1 promoter contained on the vector. It was possible to subclone the FTF gene with its presumed promoter as a 3.4-kilobase EcoRI fragment to produce the chimeric plasmid pSS22 expressing FTF activity. The cloned enzyme was purified to apparent homogeneity after ammonium sulfate precipitation, gel filtration, and DEAE-Bio-Gel-A chromatography followed by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme displayed a lower molecular weight (63,000) compared with the multiple activities detected in the culture fluids of strain GS-5. In addition, storage of the purified enzyme resulted in the formation of even lower-molecular-weight enzymatically active species. These results suggested that proteolytic degradation of the FTF occurs both in S. mutans and in Escherichia coli. In addition, a comparison of the properties of the cloned enzyme with those previously characterized from another serotype c S. mutans strain suggests that multiple FTF genes may be present in these organisms.
Wide-field common-path incoherent correlation microscopy with a perfect overlapping of interfering beams (2013)

Incoherent correlation microscopy is recently discovered technique for digital imaging of three-dimensional objects in a quasi-monochromatic spatially incoherent light. Its operation is based on wavefront division carried out by a spatial light modulator and capturing correlation recordings of the observed scene. To achieve image reconstruction, at least a partial overlapping of the signal and reference waves created by the spatial light modulator is necessary. In the known experimental configurations, the overlapping of interfering beams is strongly reduced in off-axis areas of the object and the image can be reconstructed only in a very small portion of the field of view provided by the used microscope objective lens. Here, we propose and successfully demonstrate modified experimental system working with two-component relay optics inserted between the microscope objective and the spatial light modulator and providing full overlapping of correlated beams in all areas of the field of view of the objective lens. The benefits and applicability of the proposed system design are clearly demonstrated on the imaging of the USAF resolution targets.