gebhart/patrepeval huggingface dataset:
Hepatitis B virus integration in hepatitis B virus-related hepatocellular carcinoma in childhood (1991)

In Taiwan, hepatocellular carcinoma is one of the major malignancies in children between 5 and 14 yr of age. We studied the status of hepatitis B virus DNA in the hepatocellular carcinoma and nontumorous liver tissues of eight children with positive serum HBsAg and maternal HBsAg. The hepatocellular carcinoma tissues from five of the eight children showed integration of hepatitis B virus DNA into host cellular DNA sequences. A pattern of single-site integration in four children and a multiple-site integration pattern in one child were demonstrated. In the remaining three children, hepatitis B virus DNA could not be demonstrated in the tumor tissues. Using subgenomic fragments of the hepatitis B virus genome as probes, we found that the X gene fragment and the surface antigen gene fragment were the most conserved sequences. The single-site integration of hepatitis B virus DNA in childhood hepatocellular carcinoma may have hit the critical region, resulting in insertional mutagenesis and early development of hepatocellular carcinoma. With a short incubation period and less exposure to environmental carcinogens during early life, childhood hepatocellular carcinoma may provide a good model to study the carcinogenic potential of hepatitis B virus.
Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction (1992)

Systemic application of lidocaine in rats suppressed ectopic impulse discharge generated both at sites of experimental nerve injury and in axotomized dorsal root ganglion (DRG) cells. ED50 for DRGs was significantly lower than for the injury site. Lidocaine doses effective at blocking ectopic discharge failed to block the initiation or propagation of impulses by electrical stimulation, and only minimally affected normal sensory receptors. This selectivity may account for the effectiveness of systemic local anesthetics and other drugs that share the same mechanism of action (notably certain anticonvulsants and antiarrhythmics), in the management of neuropathic paresthesias and pain. In addition, it may account for the prolonged analgesia sometimes obtained using regional local anesthetic block.
Deletional mutant EGFR detected in circulating tumor-derived DNA from lung cancer patients treated with gefitinib. (2005)

479 NSCLC cells carrying the somatic mutation of epidermal growth factor receptor (EGFR) have been shown to be hyper-responsive to the EGFR-specific tyrosine kinase inhibitor gefitinib. The short, in-frame, 15-bp deletion of EGFR (E746_A750del) can be observed in serum DNA and may serve as a noninvasive source of information regarding the genotype of the original tumor cells that could influence treatment and the ability to predict a patient’s response to gefitinib. We identified the E746_A750del in tumor cells isolated from the serum of Japanese NSCLC patients treated with first-line gefitinib (Iressa ® ) monotherapy. Both the E746_A750del (10/27) and the wild-type EGFR (22/27) were detected in the pretreatment samples. No correlations were seen between the presence of the E746_A750del in the pretreatment samples and the response or the gender. When the presence of E746_A750del in pre-treatment and post-treatment samples was compared, E746_A750del was significantly more frequently observed in the post-treatment samples from patients with a partial response or stable disease than in those from patients with a progressive disease (p
Development of Emission Transfer Functions for Predicting the Deterioration of a Cu-Zeolite SCR Catalyst (2009)

&lt;div class="htmlview paragraph"&gt;Urea selective catalytic reduction (SCR) catalysts have the capability to deliver the high NOx conversion efficiencies required for future emission standards. However, the potential for the occasional over-temperature can lead to the irreversible deactivation of the SCR catalyst. On-board diagnostics (OBD) compliance requires monitoring of the SCR function to make sure it is operating properly. Initially, SCR catalyst performance metrics such as NOx conversion, NH&lt;sub&gt;3&lt;/sub&gt; oxidation, NH&lt;sub&gt;3&lt;/sub&gt; storage capacity, and BET surface area are within normal limits. However, these features degrade with high temperature aging. In this work, a laboratory flow reactor was utilized to determine the impact on these performance metrics as a function of aging condition. Upon the completion of a full time-at-temperature durability study, four performance criteria were established to help determine a likely SCR failure. The following four performance criteria were established: (1) &amp;lt; 80% NOx conversion (between 200°C–400°C), (2) &amp;lt; 100% NH&lt;sub&gt;3&lt;/sub&gt; oxidation (at T &amp;gt; 500°C), (3) &amp;lt; 600mg/L NH&lt;sub&gt;3&lt;/sub&gt; storage capacity, and (4) &amp;lt; 70% normalized BET surface area. Implementation of the performance criteria resulted in the identification of the following five “Borderline” failure aging conditions: (1) 1hr/1000°C, (2) 2hr/950°C, (3) 8hr/900°C, (4) 64hr/850°C, and (5) 256hr/800°C. Based on these SCR performance time and temperature limits, two simple mathematical equations were developed that related the threshold temperature to the threshold duration time. In addition, two transfer functions were developed that characterized the NH&lt;sub&gt;3&lt;/sub&gt; storage capacity and the BET surface area results (via N&lt;sub&gt;2&lt;/sub&gt; adsorption) as functions of both aging time and aging temperature. From these two functions, a NOx conversion transfer function was also developed that predicted the NOx conversion vs. the measured NOx conversion within 10% margin of error.&lt;/div&gt;
Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats (2006)

A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of 125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport.
[Leu27] INSULIN-LIKE GROWTH FACTOR II IS HIGHLY SELECTIVE FOR THE TYPE-II IGF RECEPTOR IN BINDING, CROSS-LINKING AND THYMIDINE INCORPORATION EXPERIMENTS (1991)

Insulin-like growth factor-II (IGF-II) is able to interact with three different receptors: the type-I and type-II IGF receptors, and the insulin receptor, although with a lower affinity. This cross reactivity obscures the mechanisms via which the biological activities of IGF-II are mediated. We have synthesized an IGF-II analog, [Leu27]IGF-II, that is highly selective for the type-II IGF receptor. Receptor binding experiments demonstrate a high affinity for the type-II IGF receptor, analogous to synthetic (syn) and recombinant (rec) IGF-II, but no affinity for the type-I IGF and the insulin receptor at concentrations up to 50 and 200 ng/ml, respectively. The lack of affinity for these two receptors is confirmed by biological studies which demonstrated that this analog, in contrast with synIGF-II, did not stimulate [3H]thymidine incorporation in Balb/c 3T3 cells. [Leu27]IGF-II opens new ways to identify which actions of IGF-II are mediated via the type-II receptor and which are due to cross reactivity with the type-I IGF or the insulin receptor.
Purification and partial characterization of an extracellular β‐glucosidase of Trichoderma reesei using cathodic run, polyacrylamide gel electrophoresis (1988)

P-Glucosidase (BG) is a hydrolytic enzyme which acts on various compounds with p-D-glucosidic linkages. It has been shown to play a key role in the cellulase complex of T. reesei by hydrolyzing cellobiose to glucose.' Numerous methods have been employed to purify P-glucosidase from
A previously unidentified host protein protects retroviral DNA from autointegration (1998)

Integration of a DNA copy of the viral genome into a host chromosome is an essential step in the retrovirus life cycle. The machinery that carries out the integration reaction is a nucleoprotein complex derived from the core of the infecting virion. To successfully integrate into host DNA, the viral DNA within this complex must avoid self-destructive integration into itself, a reaction termed autointegration. We have previously shown [Lee, M. S. and Craigie, R. (1994) Proc. Natl. Acad. Sci. USA 91, 9823-9827] that viral nucleoprotein complexes isolated from Moloney murine leukemia virus-infected cells exhibit a barrier to autointegration. This autointegration barrier could be destroyed by stripping factors from the complexes and subsequently restored by incubation with a host cell extract, but not by incubation with an extract of disrupted virions. We have now used this autointegration barrier reconstitution assay to purify the host factor from uninfected NIH 3T3 fibroblasts. It is a single polypeptide of 89 aa that does not match any previously identified protein. The identity of the protein was confirmed by expressing it in Escherichia coli and demonstrating the activity of the heterologously expressed protein in the reconstitution assay.
Increased production of 4 kDa amyloid beta peptide in serum deprived human primary neuron cultures: possible involvement of apoptosis (1995)

The etiology of the amyloid beta peptide in sporadic Alzheimer's disease (AD) is not known. Amyloid beta peptide (A beta), a proteolytic product of the amyloid precursor protein (APP), is deposited in the senile plaques and cerebrovascular tissues of individuals with either sporadic or familial AD (FAD). Increased A beta production from mutant APPs in FAD fosters the hypothesis that overexpression of A beta plays a primary role in the pathogenesis of AD. The absence of APP mutations in sporadic AD which displays identical pathological features than FAD such as synapse and neuronal loss, senile plaques and neurofibrillary tangles, suggests other causes for overexpression and/or deposition of A beta. To investigate the effect of neuronal death on APP metabolism and A beta secretion, human primary neuron cultures were induced to undergo apoptosis by serum deprivation. Serum deprived neurons display shrunken and rounded morphology, contain condensed chromatine and fragmented DNA, which are characteristic of apoptosis. In serum deprived neurons, metabolism of APP through the nonamyloidogenic secretory pathway is decreased to 20% from 40% in control cultures whereas 4kDa A beta is increased three- to fourfold. The results suggest that human neurons undergoing apoptosis generate excess A beta and indicates a possible mechanism for increased A beta in the absence of APP mutations.
Soybean Disease Loss Estimates for the Top 10 Soybean Producing Countries in 1994 (1997)

Soybean disease loss estimates were compiled for the 1994 harvested crop from the 10 countries with the greatest soybean production. The objective was to document the major soybean disease problems in these countries and any recent changes in the severity of individual soybean diseases. Total yield losses caused by Heterodera glycines in these 10 countries were greater than those caused by any other disease. Next in order of importance were stem canker, brown spot, and charcoal rot. The total yield loss due to disease during 1994 in these countries was 14.99 million metric tons, valued at $3.31 billion. Methods used to estimate soybean disease losses were field surveys, plant disease diagnostic clinic samples, variety trial data, information from field workers and university extension staff, research plots, grower demonstrations, and private crop consultant reports. Yield loss estimates due to a particular disease varied by country. For example, yield losses due to rust were reported from China and Indonesia, but no losses due to this disease were reported from any of the remaining eight countries. Soybean disease control research and extension efforts are needed to provide more effective preventive and therapeutic disease management strategies and systems to producers.
Jean Mallard's world map (ca.1538-39) (2016)

This article discusses a world map in two hemispheres (ca.1538-39) by Frenchman Jean Mallard, whose stated aim was to draw a world map showing the results of French voyages. The outcome may be the earliest to show an imagined southern continent with a promontory extending north of the Tropic of Capricorn, south of modern day Indonesia. The promontory is named 'La Gatigare.' The map has been described as a prototype of the Dieppe school charts, and La Gatigare as a typical outline of Java-la-Grande. The argument presented is that there are material differences between Mallard's map and the Dieppe charts leading to the conclusion La Gatigare is not an early example of Java-la-Grande. It is suggested that Mallard's map should be looked upon not as a part of, but as a forerunner to, the Dieppe school of cartographers. The article also discusses two maps from the 1590s, of Portuguese origin, with similar promontories of the assumed southern continent extending north towards the Indonesian islands.
Deep brain stimulation creates an informational lesion of the stimulated nucleus (2004)

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the mechanisms are unclear. DBS generates inhibition of neurons surrounding the electrode while simultaneously activating the output axons of local neurons. This dual effect does not explain two hallmarks of DBS effectiveness: symptom relief is dependent on using a sufficiently high-stimulation frequency, and clinical effects are analogous to those produced by lesion. The effect of DBS at different frequencies on the output of intrinsically active neurons was studied using computational models. DBS produced frequency-dependent modulation of the variability of neuronal output, and above a critical frequency stimulation resulted in regular output with zero variance. The resulting loss of information offers an explanation for the two hallmarks of DBS effectiveness.
Phase ib/2a study of PLX51107, a small molecule BET inhibitor, in subjects with advanced hematological malignancies and solid tumors. (2018)

2550 Background: PLX51107 is an orally active small molecule inhibitor that exhibits low nanomolar potency in blocking interactions mediated by the four BET family proteins and a unique pharmacokinetic (PK) profile. Methods: We conducted a first-in-man 3+3 dose escalation study of PLX51107 in adult patients with relapsed or refractory solid tumors (lymphomas included) and AML to determine the recommended phase II dose (RP2D) (NCT02683395). Secondary endpoints included safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD). Enrollment through Cohort 7 (160 mg QD) is ongoing as of January 2018. Results: 36 subjects with advanced solid tumors (median age 60.5 years) received PLX51107 in escalating doses from 20mg to 160mg QD and 60mg BID. Uveal Melanoma (n = 11) was the most common tumor type followed by sarcoma (n = 6), and NSCLC, Breast and CRPC (n = 2 each). Most common toxicities in ≥ 15% of pts: fatigue (33%), vomiting (25%), diarrhea (25%), nausea (19%), bilirubin increase (17%), and INR increase (17%). Most were grade (G) 1-2. There were 3 treatment-related serious AEs (1 each of G3 nausea, G2 vomiting, and G2 kidney injury). Subjects with extensive hepatic metastases ( > approx. 50% of the liver) demonstrated higher exposure and more AEs. Dose limiting toxicity (DLT) was observed at 20mg (1 G3 thrombocytopenia), 120mg QD (1 G3 nausea) and 160mg QD (1 G2 kidney injury). PK was dose proportional with t1/2 < 2.5hr. Sixty mg BID dosing yielded same AUC as 120mg QD. RNA-seq analyses of peripheral blood mononuclear cells showed a dose-dependent induction of HEXIM1/WDR47 and reduction of CCR1/CCR2 gene expression within 3 hours of dosing. Eight pts achieved stable disease by RECIST (2 uveal melanoma, 3 sarcoma, 1 CRPC, 1 NSCLC), ranging from 4-14 months, and one subject with uveal melanoma demonstrated stable disease for 14 months. Conclusions: PLX51107 continues to enroll in dose escalation; patients with extensive hepatic metastasis are excluded going forward. Based on preclinical toxicology data, the expected Maximum Tolerated Dose will be in the 200-300 mg range. The BID dosing schedule will not move forward due to no increase in exposure observed. Clinical trial information: NCT02683395.
Delayed hematopoietic development in osteopetrotic (op/op) mice. (1993)

Changes in structure, cellularity, hematopoietic progenitor cell and macrophage content, and osteoclast activity were investigated in the hematopoietic organs of the colony-stimulating factor 1(CSF-1)-less osteopetrotic (op/op) mouse. The data indicated that op/op mice undergo an age-related hematopoietic recovery and resolution of osteopetrosis, suggesting that the hematopoietic system has the capacity to use alternative mechanisms to compensate for the absence of an important multifunctional growth factor, CSF-1. In young animals, op/op femurs were heavily infiltrated with bone, and marrow cellularity was significantly reduced. After 6 wk of age, there was an increase in the marrow space available for hematopoiesis. The femoral cavity of op/op mice progressively enlarged, and by 22 wk of age its appearance and marrow cellularity was comparable to that of controls. The percentage of op/op mononuclear phagocytes, defined by F4/80 antigen expression, progressively increased to normal levels by 35 wk of age. There was no difference in the incidence of both primitive and mononuclear phagocyte-committed, CSF-1-responsive progenitor cells in op/op marrow, but their femoral content was significantly reduced in young mice. During the period of reduced hematopoiesis in the marrow of young op/op mice, splenic hematopoietic activity was elevated. This mutant mouse represents a system for the study of the CSF-1-independent regulatory mechanisms involved in hematopoietic regulation.
c-Jun N-Terminal Kinase (JNK)-Interacting Protein-1b/Islet-Brain-1 Scaffolds Alzheimer's Amyloid Precursor Protein with JNK (2001)

Using a yeast two-hybrid method, we searched for amyloid precursor protein (APP)-interacting molecules by screening mouse and human brain libraries. In addition to known interacting proteins containing a phosphotyrosine-interaction-domain (PID)-Fe65, Fe65L, Fe65L2, X11, and mDab1, we identified, as a novel APP-interacting molecule, a PID-containing isoform of mouse JNK-interacting protein-1 (JIP-1b) and its human homolog IB1, the established scaffold proteins for JNK. The APP amino acids Tyr(682), Asn(684), and Tyr(687) in the G(681)YENPTY(687) region were all essential for APP/JIP-1b interaction, but neither Tyr(653) nor Thr(668) was necessary. APP-interacting ability was specific for this additional isoform containing PID and was shared by both human and mouse homologs. JIP-1b expressed by mammalian cells was efficiently precipitated by the cytoplasmic domain of APP in the extreme Gly(681)-Asn(695) domain-dependent manner. Reciprocally, both full-length wild-type and familial Alzheimer's disease mutant APPs were precipitated by PID-containing JIP constructs. Antibodies raised against the N and C termini of JIP-1b coprecipitated JIP-1b and wild-type or mutant APP in non-neuronal and neuronal cells. Moreover, human JNK1beta1 formed a complex with APP in a JIP-1b-dependent manner. Confocal microscopic examination demonstrated that APP and JIP-1b share similar subcellular localization in transfected cells. These data indicate that JIP-1b/IB1 scaffolds APP with JNK, providing a novel insight into the role of the JNK scaffold protein as an interface of APP with intracellular functional molecules.
Thermal conductivity of amorphous ices (2002)

The thermal conductivities \ensuremath{\kappa} of high-density amorphous (HDA) ice and low-density amorphous (LDA) ice were measured under pressure. The results for HDA show typical glasslike behavior, i.e., positive $d\ensuremath{\kappa}/dT,$ whereas LDA exhibits crystal-like behavior, indicating that phonon-phonon scattering is dominant. LDA appears to be unique among apparently topologically disordered glasses to exhibit such behavior. Moreover, the results imply that LDA and glassy water formed by rapid cooling are different states.
The GPA machine: a generally partitionable MSIMD architecture (2002)

The GPA machine, a massively parallel, multiple single-instruction-stream-multiple-data-stream (MSIMD) system is described. Its distinguishing characteristics is the generality of its partitioning capabilities. Like the PASM system it can be dynamically reconfigured to operate as one or more independent SIMD machines. However, unlike PASM, the only constraint placed on partitioning is that an individual processing element is a member of at most one partition. This capability allows for reconfiguration based on the run-time status of dynamic data structures and for partitioning of disconnected and overlapping data structures. Significant speedups are expected from operating on data structures in place; copying of data to a newly configured partition is unnecessary. The GPA system consists of N processing-element/RAM pairs and an interconnection network providing access to and from P control processors or microcontrollers. With current technologies, values for N and P of 64K and 16, respectively, are feasible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Self-Assembled Nanostructured Materials (1996)

The “wet” colloid chemical construction of nanosized or nanostructured materials (i.e., those in the 1−100 nm range) has been inspired by biomineralization (the in vivo formation of inorganic crystals and/or amorphous particles in biological systems) and hierarchically organized self-assembly (spontaneous stepwise assembly of functional units). Subsequent to a summary of the molecular level organization of surfactant monolayers, Langmuir−Blodgett and self-assembled films emphasis is placed on the colloid chemistry underlying the self-assembly of nanostructured materials. Specifically, details are provided on (i) the preparation and stabilization of nanoparticle dispersions, (ii) the adsorption and desorption of nanoparticles onto solid surfaces, and (iii) the nanoreactors provided by polar liquids selectively adsorbed onto solid surfaces from binary polar−apolar liquid mixtures. The “wet” colloid chemical preparation of nanostructured materials in our laboratories is illustrated by the layer-by-layer self-assembly of (i) polyelectrolyte−semiconductor nanoparticle, (ii) polyelectrolyte−clay platelets−semiconductor nanoparticle, and (iii) polyelectrolyte−graphite oxide (and reduced graphite oxide) ultrathin films.