gebhart/patrepeval huggingface dataset:
Immunological Markers for PML Prediction in MS Patients Treated with Natalizumab (2015)

Natalizumab (NTZ), a monoclonal antibody recognizing the alpha4 integrin chain, has been approved for the treatment of active multiple sclerosis, but expose to the onset of a rare side effect, progressive multifocal leukoencephalopathy (PML). Estimating the individual risk of PML in NTZ-treated patients is a major challenge, and therapeutic strategies are mainly guided by the overall PML risk assessed by identified risk factors: JC virus (JCV) seropositivity, treatment duration (with peak incidence after 24 months), and the previous use of immunosuppressive therapies. Given that this stratification does not yet allow a precise individual prediction of PML, other predictive markers are needed, and several immunological biomarkers have been described. Quantification of anti-JCV antibody levels may improve individual predictive value, with higher baseline titers indicating increased risk. Other immunological biomarkers such as leukocyte cell membrane markers (CD49d, CD11a, and CD62L), detection of circulating JCV-specific activated T effector memory cells (TEM) or genetic screening have been proposed. In this review, we discuss how recent progress in immunology has paved the way for «new combined monitoring», which will include immunological screening, in NTZ-treated patients.
Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome (2010)

Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.
Comparison of techniques for the successful detection of BRCA1 mutations in fixed paraffin-embedded tissue. (2002)

Genomic DNA isolated from archived paraffin-embedded tissues (PETs) has important applicability in genetic epidemiological studies. To determine the accuracy of the sequence data, using DNA derived from PET among patients with known mutations characterized from blood, we conducted a blinded factorial experiment to simultaneously examine the influence of mutation type, age of the PET, PCR product type, and Taq DNA polymerase on BRCA1 gene mutation detection. The probability of detecting sequencing artifacts was also investigated. We found that: (a) gene detection was most accurate for newer PET; (b) high fidelity Taq with shorter PCR amplicon length yielded the highest mutation detection success rate and lowest artifact rate; and (c) base substitutions were more often correctly identified than frameshift mutations or wild-type sequences. We concluded that DNA derived from PET that archived for less than 18 years can be used successfully for detecting BRCA1 gene mutations if quality control is strictly maintained.
Development of Accurate Computational Models for Patient-Specific Deep Brain Stimulation (2012)

Equation 1.1 MRI signal attenuation Equation 1.2 Three-dimensional (3D) diffusion tensor matrix Equation 1.3 Fractional anisotropy Equation 1.4 Linear relationship between the diffusion and conductivity Equation 2.1 Threshold voltage-distance equation for regression fit Equation 4.1 Spatial second-difference in three-dimensions Equations 4.2 Definition of the activation-function based predictor Equation 4.3 Ellipse used to define an active region Equation 4.4 Relationship of weights and biases used to build the artificial neural network (ANN)-based predictor functions Equation 4.5 Error metric used to compare the AF-based predictor function to the ANN-based predictor function
Unilateral intraputamenal glial cell line–derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal (2007)

The unilateral administration of GDNF results in significant, sustained bilateral benefits in patients with PD. These improvements are lost within 9 months of drug withdrawal. Safety concerns with GDNF therapy can be closely monitored and managed.
Chemical modification of lignin assisted by microwave irradiation (2011)

Abstract Soda lignin was converted into sulfonated lignin by oxidation, hydroxymethylation, and sulfonation assisted by microwave irradiation. Oxidation and hydroxymethylation under these circumstances led to lignins with much higher reactivity toward subsequent sulfonation, and the sulfonation degree could be elevated up to 2.75 mmol g -1 . A suitable microwave irradiation time is beneficial to obtain oxidized lignin with small molecular size, but the irradiation time must be selected adequately. Under optimal conditions, the sulfonated lignin exhibits a good dispersive effect to TiO 2 suspension. Compared to conventional water bath heating, microwave irradiation not only increases the sulfonation degree of lignin, but also sharply shortens the reaction time.
Protection against malaria by immunization with plasmid DNA encoding circumsporozoite protein. (1994)

Immunization with irradiated sporozoites protects animals and humans against malaria, and the circumsporozoite protein is a target of this protective immunity. We now report that adjuvant-free intramuscular injection of mice with plasmid DNA encoding the Plasmodium yoelii circumsporozoite protein induced higher levels of antibodies and cytotoxic T lymphocytes against the P. yoelii circumsporozoite protein than did immunization with irradiated sporozoites. Mice immunized with this vaccine had an 86% reduction in liver-stage parasite burden after challenge with 5 x 10(5) sporozoites (> 10(5) median infectious doses). Eighteen (68%) of 28 mice that received two or three doses of vaccine were protected against challenge with 10(2) sporozoites, and the protection was dependent on CD8+ T cells. These studies demonstrate the utility of plasmid DNA immunization against a nonviral infection. By obviating the requirement for peptide synthesis, expression and purification of recombinant proteins, and adjuvants, this method of immunization provides an important alternative for rapid identification of protective B- and T-cell epitopes and for construction of vaccines to prevent malaria and other infectious diseases.
Nonpeptidal P2 Ligands for HIV Protease Inhibitors:  Structure-Based Design, Synthesis, and Biological Evaluation (1996)

Design and synthesis of nonpeptidal bis-tetrahydrofuran ligands based upon the X-ray crystal structure of the HIV-1 protease-inhibitor complex 1 led to replacement of two amide bonds and a 10 pi-aromatic system of Ro 31-8959 class of HIV protease inhibitors. Detailed structure-activity studies have now established that the position of ring oxygens, ring size, and stereochemistry are all crucial to potency. Of particular interest, compound 49 with (3S,3aS,6aS)-bis-Thf is the most potent inhibitor (IC50 value 1.8 +/- 0.2 nM; CIC95 value 46 +/- 4 nM) in this series. The X-ray structure of protein-inhibitor complex 49 has provided insight into the ligand-binding site interactions. As it turned out, both oxygens in the bis-Thf ligands are involved in hydrogen-bonding interactions with Asp 29 and Asp 30 NH present in the S2 subsite of HIV-1 protease. Stereoselective routes have been developed to obtain these novel ligands in optically pure form.
Independent Predictors of Cognitive Decline in Healthy Elderly Persons (2002)

Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.
Polyreactions in Miniemulsions (2001)

The process of miniemulsification allows the generation of small, homogeneous, and stable droplets of monomer or polymer precursors, which are then transformed by (as many as possible) polymer reactions to the final polymer latexes, keeping their particular identity without serious exchange kinetics being involved. The main focus of this Review is laid on a detailed description of the working principles of miniemulsions, the examination of the kinetics during the polymerization process, and the generation of different particle structures by appropriate thermodynamic handling. It will be shown that the strength of miniemulsions is the formation of polymeric nanoparticles consisting of polymers or polymer structures, which are not accessible by other types of heterophase polymerization. Non-radical polymerizations and the formation of hybrid materials by the encapsulation of resins, inorganic materials, or liquids are some examples showing the wide applicability of miniemulsions also for technologically relevant questions. With the miniemulsification of molten inorganic materials followed by a reaction, miniemulsions cross the border of polymers and open new possibilities in the fabrication of solid particles for material science.
Phase Current Reconstruction for AC Motor Drives Using a DC Link Single Current Sensor and Measurement Voltage Vectors (2006)

Three-phase current measurement using only a single current sensor in the inverter dc link is appealing for ac motor drives because it minimizes the number of current sensors, thereby reducing sensor cost, weight, and volume. However, the basic dc link single current sensor technique poses special challenges because the duration of the active voltage vectors must be long enough to measure the dc link current reliably during every pulsewidth modulation switching interval. A new single current sensor algorithm for reconstructing the phase currents called the measurement vector insertion method (MVIM) is presented that overcomes this problem using active voltage vectors that are applied for brief measurement intervals only when needed during each fundamental frequency cycle. The insertion of measurement vectors makes it possible to reconstruct the output phase currents with minimum impact on the machine's performance and operating envelope. A combination of analytical and experimental results is provided to confirm that the MVIM algorithm offers attractive phase current reconstruction performance in comparison to alternative dc link single current sensor algorithms
Influence of diglycerides on crystallisation of palm oil (1999)

Palm oil diglycerides and pure synthetic diglycerides of 1,2-(2,3-) and 1,3-dipalmitoylglycerol, dioleoylglycerol and palmitoyloleoyl glycerol were added to purified triglycerides of palm oil. The crystallisation kinetics of the samples were studied by spectrophotometry, NMR analysis of the solid fat content and by X-ray diffraction of the crystals obtained at 20°C. Palm oil diglycerides inhibited the nucleation process and retarded the crystal growth rate of palm triglycerides. The effect was less pronounced at a higher degree of supercooling. The extent of inhibition depended on the nature of the diglycerides and the concentration. © 1999 Society of Chemical Industry
The Human Obesity Gene Map: The 2002 Update (2003)

This is the ninth update of the human obesity gene map, incorporating published results through October 2002 and continuing the previous format. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome-wide scans and various animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. For the first time, transgenic and knockout murine models exhibiting obesity as a phenotype are incorporated (N = 38). As of October 2002, 33 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and the causal genes or strong candidates have been identified for 23 of these syndromes. QTLs reported from animal models currently number 168; there are 68 human QTLs for obesity phenotypes from genome-wide scans. Additionally, significant linkage peaks with candidate genes have been identified in targeted studies. Seven genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 222 studies reporting positive associations with 71 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http://obesitygene.pbrc.edu.
Rescue, propagation, and partial purification of a helper virus-dependent adenovirus vector. (1995)

Adenoviral vectors are widely used as highly efficient gene transfer vehicles in a variety of biological research strategies including human gene therapy. One of the limitations of the currently available adenoviral vector system is the presence of the majority of the viral genome in the vector, resulting in leaky expression of viral genes particularly at high multiplicity of infection and limited cloning capacity of exogenous sequences. As a first step to overcome this problem, we attempted to rescue a defective human adenovirus serotype 5 DNA, which had an essential region of the viral genome (L1, L2, VAI + II, pTP) deleted and replaced with an indicator gene. In the presence of wild-type adenovirus as a helper, this DNA was packaged and propagated as transducing viral particles. After several rounds of amplification, the titer of the recombinant virus reached at least 4 x 10(6) transducing particles per ml. The recombinant virus could be partially purified from the helper virus by CsCl equilibrium density-gradient centrifugation. The structure of the recombinant virus around the marker gene remained intact after serial propagation, while the pBR sequence inserted in the E1 region was deleted from the recombinant virus. Our results suggest that it should be possible to develop a helper-dependent adenoviral vector, which does not encode any viral proteins, as an alternative to the currently available adenoviral vector systems.
Miliary pulmonary neuroblastoma: A risk of autologous bone marrow transplantation? (1988)

A case of miliary pulmonary neuroblastoma is described which occurred 8 months after autologous bone marrow transplantation for Stage IV neuroblastoma. The patient, a 4-year-old boy had pulmonary symptoms at this time. Disseminated metastatic disease was found, but there was no tumor at the primary site. This unusual pattern of relapse suggests that the patient's disseminated disease was related to infusion of malignant cells at the time of transplantation.
Abdominal aortic endografting: (2002)

The treatment goals for elective endovascular and open surgical repair of abdominal aortic aneurysms are identical. Anyone attempting to remedy this condition desires longterm freedom from aneurysm rupture in association with minimal morbidity and mortality for the intervention required. The methods by which these objectives are achieved differ significantly between open and endovascular procedures. This article will address the means by which endografts achieve proximal fixation and sealing, two concepts that are paramount in durable endovascular aneurysm repair. The surgical anastomosis, when properly constructed, is the most secure way to fixate graft material to a section of normal arterial wall. This serves to prevent flow outside of the designated conduit and to secure the graft material in place. Although this is conceptually straightforward, individuals who treat this condition maintain a healthy respect for the potentially complex anatomy of the proximal neck. The ability to make adjustments while sewing the proximal anastomosis is extremely advantageous. Similar situations can be encountered during endovascular aortic repairs, but we are frequently unable to modify the device or technique once the procedure has been initiated. Consequently, the preoperative imaging and planning is critical to successful endovascular grafting. Appropriate patient selection, the conceptual design of an endovascular graft, and detailed planning of the operation must be completed before arrival in the operating room. Most assessments of acute technical and clinical success of endovascular grafting have been quite favorable, but complex analyses of longterm durability raise concerns that dwarf the early favorable results. The inevitable deterioration of the arterial system associated with age and accelerated by aneurysmal disease, in conjunction with morphologic changes associated with sac shrinkage, requires endovascular prostheses to adapt to altering anatomy. Endograft design must be tailored to specific anatomic factors that must be determined preoperatively, and acute success, with respect to proximal fixation and sealing methods, must be coupled with materials that will accommodate anatomic changes.
Weight‐related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal insufficiency (2004)

We recommend weight-adjusted HC dosing, thrice daily before food, monitored with a single serum cortisol measurement using a nomogram. This regimen was prospectively examined in 40 cortisol-insufficient patients, 85% of whom opted to remain on the new thrice-daily treatment regimen.
Identification of Regions of the Wiskott-Aldrich Syndrome Protein Responsible for Association with Selected Src Homology 3 Domains (1996)

Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.
Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. (1993)

Amphoterin is a heparin-binding protein that is developmentally regulated in brain and functionally involved in neurite outgrowth. Unexpectedly, amphoterin has a high mobility group 1 (HMG1)-type sequence. In the present study we have expressed amphoterin cDNA in a baculovirus vector and produced antibodies against the recombinant protein and several synthetic peptides. It was found that the amphoterin cDNA encodes the 30-kDa form of the protein isolated from tissues, whereas the co-purifying 28- and 29-kDa proteins (p28 and p29) have closely related but distinct primary structures. Partial amino acid sequencing shows several local changes in the sequences of p28 and p29 compared with amphoterin, suggesting the occurrence of a multigene family that encodes at least three different HMG1-type sequences in the rat. Studies using the probes that discern amphoterin from the other HMG1-type proteins indicate a high level expression in various transformed cell lines. Immunostaining of cells with the amphoterin-specific antibodies indicates a cytoplasmic localization that becomes remarkably enriched at the leading edges in spreading and motile cells. An extracellular localization is suggested by immunostaining of nonpermeabilized cells and by a plasminogen-dependent degradation of amphoterin in the substratum-attached material of cells. Tissue-derived and recombinant amphoterins strongly enhance the rate of plasminogen activation and promote the generation of surface-bound plasmin both by tissue-type and urokinase-type plasminogen activators. The results suggest an extracellular function for amphoterin in the leading edge of various invasive cells.
Analysis of Benzylisoquinoline-Type Alkaloids by Electrospray Tandem Mass Spectrometry and Atmospheric Pressure Photoionization (2005)

Benzylisoquinoline alkaloids found in the Papaveraceae family play a major role in pharmaceutical biology. This is the first systematic study dealing with electrospray tandem mass spectrometry (ESI-MS/MS) of all benzylisoquinolines found as biogenetic precursors of morphinan alkaloids. Tandem mass spectral data are presented for norlaudanosoline, laudanosoline, 4'-O-methyl-norlaudanosoline, 6-O-methyl-norlaudanosoline, norcoclaurine, coclaurine, N-methylcoclaurine, N-methyl-3'-hydroxycoclaurine, N-methyl-3'-O-methylcoclaurine, norreticuline and reticuline. This study compares results obtained using an ion trap mass spectrometer with those obtained using a triple quadrupole one. The results highlight the differences of the tandem-in-time versus the tandem-in-space principle, often hampering the development of ESI-MS/MS libraries. Additionally, the use of the atmospheric pressure photoionisation technique for the analysis of such substances is discussed.
Time Series Analysis (1996)

When you have finished working through this chapter you should be able to Appreciate the need for forecasting Be aware of the requirements of a forecasting system Know that there are various quantitative forecasting methods Distinguish between the requirements for short-term and LONG-TERM FORECASTING Be aware of the different forecasting techniques appropriate for new and for established outlets Understand what is meant by TIME SERIES ANALYSIS Be able to draw a hktorigram Identify the components of a time series: TREND, CYCLICAL VARIATION, SEASONAL VARIATION and RESIDUAL VARIATION Estimate the trend by the method of MOVING AVERAGES Estimate seasonal variations and calculate seasonal ADJUSTMENT FACTORS Estimate residual variations Be able to produce a forecast Be aware of the limitations of the forecasting process