gebhart/patrepeval huggingface dataset:
The Structure Of Liquid Water; Novel Insights From Materials Research; Potential Relevance To Homeopathy (2005)

This paper provides an interdisciplinary base of information on the structure of liquid water. It begins with a synthesis built on the information base on the structure 5 of noncrystalline, inorganic, covalently-bonded condensed liquid phases, such as SiO2, S, Se, P, and H2O, which exists in the materials science literature. The data for water are analyzed through the prism of well-established algorithms in materials research: the connection of properties to structure; the pressure-temperature (P-T) phase diagrams; the phenomenon of epitaxy; the phenomenon of liquid-liquid phase separation; the stability of two phase colloids; and, the recently discovered effects of weak magnetic and electric fields on the structure of simple inorganic oxides. A thorough combing of the literature of the condensed matter properties reflecting structural features of essentially pure water obtained via the normal processes of preparing homeopathic remedies, provides another rich data base. The examination of these data through the standard materials science paradigms leads to the following conclusion: Many different structures of liquid water must exist within the range of observations and processes encountered near ambient conditions. A typical sample of water in these experimental ranges no doubt consists of a statistical-mechanical-determined assemblage of monomers and oligomers (clusters) of various sizes up to at least several hundred H2O units. The importance of the structural similarity of SiO2 and OH2 is very relevant to the structure of the latter as well as to the probability of epitaxy in controlling at least the region contiguous to the silicate glass surfaces of many common containers. The most distinctive feature of bonding in liquid water is not only the “well-known hydrogen bonds, but the necessary presence of a wide range” of van der Waals bonds between and among the various oligomeric (cluster) structural units. It is this range of very weak bonds that could account for the remarkable ease of changing the structure of water, which in turn could help explain the half-dozen well-known anomalies in its properties. In its subtler form, such weak bonds would also allow for the changes of structure caused by electric and
Recombinant immunotoxin engineered for low immunogenicity and antigenicity by identifying and silencing human B-cell epitopes (2012)

Recombinant immunotoxins (RITs) are hybrid proteins used to treat cancer. These proteins are composed of an Fv that reacts with cancer cells joined to a portion of Pseudomonas exotoxin A, which kills the cell. Because the toxin is a foreign protein, it can induce neutralizing antibodies and thereby limit the number of doses a patient can receive. We previously identified seven major mouse B-cell epitopes in the toxin, and subsequently silenced them using point mutations that converted large hydrophilic amino acids to alanine, yet retained full antitumor activity. Here we present results in which we identify and silence human B-cell epitopes in the RIT HA22. We obtained B cells from patients with antibodies to RITs, isolated the corresponding variable fragments (Fvs), and constructed a phage-display library containing Fvs that bind to the RITs. We then used alanine scanning mutagenesis to locate the epitopes. We found that human and mouse epitopes frequently overlap but are not identical. Most mutations that remove mouse epitopes did not remove human epitopes. Using the epitope information, we constructed a variant immunotoxin, HA22-LR-LO10, which has low reactivity with human antisera, yet has high cytotoxic and antitumor activity and can be given to mice at high doses without excess toxicity. The toxin portion of this RIT (LR-LO10) can be used with Fvs targeting other cancer antigens and is suitable for clinical development.
The international collaborative study of maternal phenylketonuria: status report 1994 (1994)

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 mumol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 mumol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.
ADHD, comorbid disorders and psychosocial functioning: How representative is a child cohort study? Findings from a national patient registry (2017)

Self-selection was found to affect the proportions of ADHD, psychosocial adversity and child global functioning in the cohort. However, the differences from the general population were small. This indicates that studies on ADHD and multiaxial classifications in MoBa, as well as other cohort studies with similar self-selection biases, may have reasonable generalisability to the general child population.
The Challenge of Treating Biofilm-associated Bacterial Infections (2007)

Biofilm formation is a crucial step in the pathogenesis of many subacute and chronic bacterial infections, including foreign body-related infections. Biofilms are difficult to eradicate with conventional antimicrobial agents. Bacterial biofilms have several potential antimicrobial resistance mechanisms. Antimicrobial resistance mechanisms may act concurrently, and in some cases, synergistically. Persister cells play a major role in the tolerance of biofilm bacteria to antimicrobial agents. Understanding the mechanisms involved in biofilm-associated antimicrobial resistance is key to development of new therapeutic strategies.
Quantitative protein profiling using antibody arrays (2004)

Traditional approaches to microarrays rely on direct binding assays where the extent of hybridisation and the signal detected are a measure of the analyte concentration in the experimental sample. This approach, directly imported from the nucleic acid field, may fail if applied to antibody-antigen interactions due to the shortage of characterised antibodies, the significant heterogeneity of antibody affinities, their dependence on the extent of protein modification during labelling and the inherent antibody cross-reactivity. These problems can potentially limit the multiplexing capabilities of protein affinity assays and in many cases rule out quantitative protein profiling using antibody microarrays. A number of approaches aimed at achieving quantitative protein profiling in a multiplex format have been reported recently. Of those reported, the three most promising routes include signal amplification, multicolour detection and competitive displacement approaches to multiplex affinity assays. One in particular, competitive displacement, also overcomes the problems associated with quantitation of affinity interactions and provides the most generic approach to highly parallel affinity assays, including antibody arrays.
Treatment of Late Infantile Neuronal Ceroid Lipofuscinosis by CNS Administration of a Serotype 2 Adeno-Associated Virus Expressing CLN2 cDNA (2008)

Late infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive, neurodegenerative lysosomal storage disease affecting the CNS and is fatal by age 8 to 12 years. A total average dose of 2.5 10(12) particle units of an adeno-associated virus (AAV) serotype 2 vector expressing the human CLN2 cDNA (AAV2 CU h-CLN2) was administered to 12 locations in the CNS of 10 children with LINCL. In addition to safety parameters, a neurological rating scale (primary variable) and three quantitative magnetic resonance imaging (MRI) parameters (secondary variables) were used to compare the rate of neurological decline for 18 months in treated subjects compared with untreated subjects. Although there were no unexpected serious adverse events that were unequivocally attributable to the AAV2 CU hCLN2 vector, there were serious adverse effects, the etiology of which could not be determined under the conditions of the experiment. One subject died 49 days postsurgery after developing status epilepticus on day 14, but with no evidence of CNS inflammation. Four of the 10 subjects developed a mild, mostly transient, humoral response to the vector. Compared with control subjects, the measured rates of decline of all MRI parameters were slower, albeit the numbers were too small for statistical significance. Importantly, assessment of the neurologic rating scale, which was the primary outcome variable, demonstrated a significantly reduced rate of decline compared with control subjects. Although the trial is not matched, randomized, or blinded and lacked a contemporaneous placebo/sham control group, assessment of the primary outcome variable suggests a slowing of progression of LINCL in the treated children. On this basis, we propose that additional studies to assess the safety and efficacy of AAV-mediated gene therapy for LINCL are warranted.
Neural adaptation reveals state‐dependent effects of transcranial magnetic stimulation (2007)

Transcranial magnetic stimulation (TMS) is now widely used as a 'virtual' lesion paradigm to investigate behavioural functions, but the mechanisms through which it influences neural processing are unclear. To understand the differential effects of TMS on spatially overlapping populations of neurons we manipulated the relative activity levels of visual neurons by adapting subjects to a range of visual stimuli. By applying TMS to the visual cortex representing the central visual field we have shown in two experiments that the behavioural and perceptual effects of TMS depend on the state of adaptation of the neural population stimulated by TMS. Specifically, we have demonstrated that within the stimulated area TMS perceptually facilitates the attributes encoded by the less active neural population. We have demonstrated the generality of this principle for both suprathreshold and subthreshold TMS as well as for colour and orientation-contingent colour using both subjective reports and psychophsyical measures. These findings can explain how TMS disrupts cognitive functions and therefore have implications for all studies which use TMS to disrupt behaviour.
Intraband inversion due to ultrashort carrier lifetimes in proton-bombarded InP (1996)

We report the evidence of occupation inversion in time average within the continuous band structure of the semiconductor InP. Ultrafast carrier trapping and recombination (\ensuremath{\tau}\ensuremath{\approxeq}1\ifmmode\times\else\texttimes\fi{}${10}^{\mathrm{\ensuremath{-}}13}$ s) as a consequence of proton bombardment prevents the thermalization of optically excited electron-hole pairs (n\ensuremath{\sim}3\ifmmode\times\else\texttimes\fi{}${10}^{16}$ ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}3}$). Beyond previous experimental observations of inverted time-averaged luminescence spectra, we present experimental data at lower carrier concentrations, which are in quantitative agreement with ensemble Monte Carlo simulations. Inverted electron and hole energy distributions are determined quantitatively. We propose the application for a solid-state free-electron laser. \textcopyright{} 1996 The American Physical Society.
Whole Genome Sequencing Reveals a Widely Expressed Mutation (MYD88 L265P) with Oncogenic Activity in Waldenstrom's Macroglobulinemia (2011)

Abstract Abstract 300 We performed whole genome sequencing (WGS) of lymphoplasmacytic cells from 30 Waldenstrom's Macroglobulinemia (WM) patients, with paired normal tissue sequencing for 10 patients. Tumor and normal genomes were both sequenced to an average of 66X coverage of mapped individual reads. A recurring sequence variant at position 38182641 in chromosome 3p22.2 was identified which resulted in a single nucleotide change from T®C in the myeloid differentiation primary response (MYD88) gene, and a predicted non-synonymous change at amino acid position 265 from leucine to proline (L265P). This variant was the most common of a median of 3,419 (range 2,540–4,011) somatic variants identified by WGS in paired patients, and was present in tumor cells from all 10 paired patients, and 16 of 20 unpaired patients. For 22 of 26 patients, the MYD88 L265P variant was heterozygous, whereas in 4 patients an acquired UPD event at 3p22.2 resulted in homozygous presence of the variant in at least a subset of tumor cells. Sanger sequencing confirmed the presence of the MYD88 L265P variant in all 26 patient tumor samples revealed by WGS, as well as in one additional patient's tumor sample that was not identified by the variant calling algorithms but for whom 12% of the WGS read level mappings showed the MYD88 L265P variant. In contrast, the MYD88 L265P variant was absent in normal paired tissues. Sanger sequencing therefore confirmed the somatic presence of the MYD88 L265P variant in tumor cells from 27 of 30 (90%) WM patients, and also identified this variant in BCWM.1 and MWCL-1 WM cells. In contrast, the MYD88 L265P variant was absent in CD138+ selected tumor cells from 8 of 8 multiple myeloma (MM) patients, and CD19+ cells from 12 of 12 healthy individuals, as well as in 7 of 8 patients with IgM monoclonal gammopathy of unknown significance (MGUS), in whom absence of the MYD88 L265P variant was further confirmed by TA cloning and sequencing of at least 100 clones. In the sole IgM MGUS patient in whom the MYD88 L265P mutation was detected, subsequent disease evolution occurred. Importantly, knock-down of MYD88 expression by lentiviral transduction led to loss of NF-κβ signaling and apoptosis of both BCWM.1 and MWCL-1 WM cells, with enhanced survival observed by complementary transduction with MYD88 L265P versus MYD88 wild type. The results of these studies therefore demonstrate a widely expressed somatic variant (MYD88 L265P) in malignant LPC of WM, whose presence confers oncogenic activity, and which may help distinguish WM disease from IgM MGUS or MM. Disclosures: No relevant conflicts of interest to declare.
Comparative mapping of the two wheat leaf rust resistance lociLr1andLr10in rice and barley (1998)

The wheat genome is large, hexaploid, and contains a high amount of repetitive sequences. In order to isolate agronomically important genes from wheat by map-based cloning, a simpler model of the genome must be used for identifying candidate genes. The objective of this study was to comparatively map the genomic regions of two wheat leaf rust disease resistance loci, Lr1 and Lr10, in the putative model genomes of rice and barley. Two probes cosegregating with the Lr1 gene on chromosome 5DL of wheat were studied. The rice sequences corresponding to the two probes were isolated and mapped. The two probes mapped to two different rice chromosomes, indicating that the organization of the region orthologous to Lr1 is different in rice and wheat. In contrast, synteny was conserved between wheat and barley in this chromosomal region. The Lrk10 gene cosegregated with Lr10 on chromosome 1AS in wheat. The rice gene corresponding to Lrk10 was mapped on rice chromosome 1, where it occurred in many copies. This region on rice chromosome 1 corresponds to the distal part of the group 3S chromosomes in Triticeae. The synteny is conserved between rice chromosome 1 and the Triticeae group 3S chromosomes up to the telomere of the chromosomes. On group 3S chromosomes, we found a gene that is partially homologous to Lrk10. We conclude that in the genomic regions studied, there is limited and only partially useful synteny between wheat and rice. Therefore, barley should also be considered as a model genome for isolating the Lr1 and Lr10 genes from wheat.
c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis (2010)

These results suggest that c-Fms plays a central role in the pathogenesis of RA by mediating the differentiation and priming of monocyte lineage cells. Therapeutic targeting of c-Fms could provide benefit in RA.
The Aseptic Femoral and Tibial Shaft Non-Union in Healthy Patients – An Analysis of the Health-Related Quality of Life and the Socioeconomic Outcome (2011)

There is a profound influence on the quality of life following femoral or tibial non-unions after trauma. Compared to patients with uneventful fracture healing, patients with tibial and even more so femoral non-union show worse scores of the SF-12. Medical aids are frequently used following both, femoral and tibial non-unions. Not tibial, but femoral non-unions frequently lead to severe restrictions in professional life such as early retirement and unemployment.
Boosting Vaccinations with Peptide-Pulsed CD34+ Progenitor-Derived Dendritic Cells Can Expand Long-Lived Melanoma Peptide-Specific CD8+ T Cells in Patients with Metastatic Melanoma (2005)

The immunogenicity of dendritic cell (DC)-based vaccines has been shown in patients with advanced cancer, but it has not yet been established whether the elicited cancer-specific immunity is durable and whether it can be maintained by boosting vaccinations. The authors showed earlier, in 18 HLA-A*0201 metastatic melanoma patients, that four vaccinations over 6 weeks with peptide-loaded CD34-DCs (the induction phase) expand in the blood melanoma-specific CD8+ T cells, as documented by melanoma peptide-specific IFN-gamma ELISPOT and cytotoxic T-lymphocyte (CTL) activity against melanoma cell lines. The authors show here that the melanoma peptide-specific CD8+ T-cell immunity is short-lived, but it could be reactivated in 7 of 11 patients who received four boosting vaccinations with peptide-loaded CD34-DCs. Expansion of recall memory CD8+ T cells was confirmed by tetramer binding and CTL activity against melanoma peptide-pulsed T2 cells. In two patients boosted over 15 months, induced melanoma peptide-specific recall memory CD8+ T cells lasted at least 6 months. Thus, boosting vaccination with peptide-loaded CD34-DCs can expand long-lived tumor peptide-specific immunity.
A compact sensor array for blind separation of sources (2002)

Discusses the separation of N source signals recorded simultaneously by M (M/spl ges/N) receivers. To solve this cocktail party problem, the authors propose to collect a set of microphones making up an array with a few centimeters in diameter. On each sensor, signals are received with different time delays. The linear memoryless conventional model for source separation is then not suitable. However, when time delays are small in comparison to the coherence time of each source, the authors show that this problem can be simplified building up a particular set of instantaneous mixtures involving derivatives of sources with respect to time. Sources can then be extracted using an adapted second-order method. When more microphones than sources are available, it is shown how to deal with noisy mixtures. The validity of the proposed approach is confirmed by computer simulations. Finally, the method is applied to an experiment where two-source signals are extracted from their mixtures observed with two omnidirectional microphones in a normal room.
N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (2007)

NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.
Wireless ad hoc networking—The art of networking without a network (2000)

Today, many people carry numerous portable devices, such as laptops,mobile phones, PDAs and mp3 players, for use in their professional andprivate lives. For the most part, these devices are used separatelyNthatis, their applications do not interact. Imagine, however, if they could inter-act directly: participants at a meeting could share documents or presenta-tions; business cards would automatically find their way into the addressregister on a laptop and the number register on a mobile phone; as com-muters exit a train, their laptops could remain online; likewise, incoming e-mail could now be diverted to their PDAs; finally, as they enter the office,all communication could automatically be routed through the wirelesscorporate campus network.These examples of spontaneous, ad hoc wireless communicationbetween devices might be loosely defined as a scheme, often referred toas ad hoc networking, which allows devices to establish communication,anytime and anywhere without the aid of a central infrastructure. Actually,ad hoc networking as such is not new, but the setting, usage and playersare. In the past, the notion of ad hoc networks was often associated withcommunication on combat fields and at the site of a disaster area; now,as novel technologies such as Bluetooth materialize, the scenario of adhoc networking is likely to change, as is its importance.In this article, the authors describe the concept of ad hoc networkingby giving its background and presenting some of the technical challengesit poses. The authors also point out some of the applications that can beenvisioned for ad hoc networking
Local anesthetics as effectors of allosteric gating. Lidocaine effects on inactivation-deficient rat skeletal muscle Na channels. (1996)

Time- and voltage-dependent local anesthetic effects on sodium (Na) currents are generally interpreted using modulated receptor models that require formation of drug-associated nonconducting states with high affinity for the inactivated channel. The availability of inactivation-deficient Na channels has enabled us to test this traditional view of the drug-channel interaction. Rat skeletal muscle Na channels were mutated in the III-IV linker to disable fast inactivation (F1304Q: FQ). Lidocaine accelerated the decay of whole-cell FQ currents in Xenopus oocytes, reestablishing the wild-type phenotype; peak inward current at -20 mV was blocked with an IC50 of 513 microM, while plateau current was blocked with an IC50 of only 74 microM (P < 0.005 vs. peak). In single-channel experiments, mean open time was unaltered and unitary current was only reduced at higher drug concentrations, suggesting that open-channel block does not explain the effect of lidocaine on FQ plateau current. We considered a simple model in which lidocaine reduced the free energy for inactivation, causing altered coupling between activation and inactivation. This model readily simulated macroscopic Na current kinetics over a range of lidocaine concentrations. Traditional modulated receptor models which did not modify coupling between gating processes could not reproduce the effects of lidocaine with rate constants constrained by single-channel data. Our results support a reinterpretation of local anesthetic action whereby lidocaine functions as an allosteric effector to enhance Na channel inactivation.
Synthesis of Stereodefined Polysubstituted Olefins. 1. Sequential Intermolecular Reactions Involving Selective, Stepwise Insertion of Pd(0) into Allylic and Vinylic Halide Bonds. The Stereoselective Synthesis of Disubstituted Olefins1 (2000)

Palladium-catalyzed allylic substitution and cross-coupling reactions have been combined into a sequential procedure to provide a range of disubstituted olefin products starting from two-, three-, and four-carbon common olefin templates. Diverse application of this template strategy is demonstrated in a variety of model studies and in a parallel synthesis (combinatorial) approach to prepare an allylic amine molecular library. An approach toward the preparation of astaxanthin beta-D-diglucoside, an interesting antioxidant whose total synthesis has yet to be reported, using the olefin-template approach is also discussed.