gebhart/patrepeval huggingface dataset:
Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation (2002)

Imatinib mesylate (STI571) is a promising new treatment for chronic myelogenous leukemia (CML). The effect of imatinib mesylate on primitive malignant progenitors in CML has not been evaluated, and it is not clear whether suppression of progenitor growth represents inhibition of increased proliferation, induction of apoptosis, or both. We demonstrated here that in vitro exposure to concentrations of imatinib mesylate usually achieved in patients (1-2 microM) for 96 hours inhibited BCR/ABL-positive primitive progenitors (6-week long-term culture-initiating cells [LTCICs]) as well as committed progenitors (colony-forming cells [CFCs]). No suppression of normal LTCICs and significantly less suppression of normal CFCs were observed. A higher concentration of imatinib mesylate (5 microM) did not significantly increase suppression of CML or normal LTCICs but did increase suppression of CML CFCs, and to a lesser extent, normal CFCs. Analysis of cell division using the fluorescent dye carboxyfluorescein diacetate succinimidyl ester indicated that imatinib mesylate (1-2 microM) inhibits cycling of CML primitive (CD34(+)CD38(-)) and committed (CD34(+)CD38(+)) progenitors to a much greater extent than normal cells. Conversely, treatment with 1 to 2 microM imatinib mesylate did not significantly increase the percentage of cells undergoing apoptosis. Although a higher concentration of imatinib mesylate (5 microM) led to an increase in apoptosis of CML cells, apoptosis also increased in normal samples. In summary, at clinically relevant concentrations, imatinib mesylate selectively suppresses CML primitive progenitors by reversing abnormally increased proliferation but does not significantly increase apoptosis. These results suggest that inhibition of Bcr-Abl tyrosine kinase by imatinib mesylate restores normal hematopoiesis by removing the proliferative advantage of CML progenitors but that elimination of all CML progenitors may not occur.
Rhodium-Catalyzed Addition of Organoboronic Acids to Aldehydes (1998)

Highly inert to ionic additions to aldehydes, aryl- and 1-alkenylboronic acids succumb to a catalytic variant mediated by a [Rh(acac)(CO)<sub>2</sub> ]-diphosphane complex in aqueous phase at 80-95°C to yield secondary alcohols [Eq. (a)]. A key step in the catalytic cycle is the transmetalation between the boron reagent and the rhodium complex. L<sub>n</sub> =diphosphane (e.g. 1,1'-bis(diphenylphosphanyl)ferrocene); R=aryl, 1-alkenyl; R'=alkyl, aryl; acac=acetylacetonate.
Implanted functional electrical stimulation system for mobility in paraplegia: a follow-up case report (1999)

A 16-channel functional electrical stimulation (FES) system has been implanted in a person with T10 paraplegia for over a year. The system consists of two eight-channel radio frequency controlled receiver-stimulators delivering stimuli through a network of 14 epimysial and two intramuscular electrodes. Using this system and a walker for support, the subject was able to stand up for 8 min and walk regularly for 20 m. The standing duration was limited by arm fatigue since upper extremities supported an average of 25% of body weight. This was due to suboptimal hip extension and some undesired recruitment of rectus femoris and sartorius with stimulation of quadriceps electrodes. The left quadriceps exhibited rapid fatigue that limited walking distance and duration. The metabolic energy requirements were well within the aerobic limits of the sedentary paraplegic population. At one-year follow-up evaluation all electrodes are functional except one intramuscular electrode. The implant caused no adverse physiological effects and the individual reported health benefits such as increased energy and overall fitness as a result of the FES system use. With further improvements in muscle response through innovative surgical techniques, the 16-channel implanted FES system can be a viable addition to exercise and mobility function in persons with paraplegia.
A constitutive nuclear localization signal from the second zinc-finger of orphan nuclear receptor TR2 (1998)

The orphan nuclear receptor TR2 and its truncated isoform deleted in the ligand binding domain (LBD) were localized exclusively in the nuclei as revealed by two methods of detection. An anti-hemagglutinin (HA) antibody detected specific nuclear localization of HA-tagged receptors and the green fluorescent protein (GFP)-tagged receptors were found to be distributed in the nuclei of living cells. By deletion analyses, the sequence responsible for targeting this receptor into the nucleus was defined. A stretch of 20 amino acid residues (KDCVINKHHRNRCQYCRLQR) within the second zinc-finger of this receptor is required for its nuclear localization and this signal is constitutively active. No nuclear localization signal was found in the N-terminus or the LBD. The GFP-tagged receptor remained biologically active, as evidenced by its repressive activity on the reporter that carried a binding site for this receptor, a direct repeat-5 (DR5). An electrophoretic mobility shift assay was performed to characterize the binding property of TR2 and its truncated isoform. TR2 bound to the DR5 as dimers whereas its truncated isoform bound as monomers.
Neural Correlates of Suicidal Ideation and Its Reduction in Depression (2014)

The infralimbic cortex may be implicated in suicidal ideation.
Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. (1994)

Mutational inactivation and allelic loss of the von Hippel-Lindau (VHL) gene appear to be causal events for the majority of spontaneous clear-cell renal carcinomas. We now show that hypermethylation of a normally unmethylated CpG island in the 5' region provides another potentially important mechanism for inactivation of the VHL gene in a significant portion of these cancers. This hypermethylation was found in 5 of 26 (19%) tumors examined. Four of these had lost one copy of VHL while one retained two heavily methylated alleles. Four of the tumors with VHL hypermethylation had no detectable mutations, whereas one had a missense mutation in addition to hypermethylation of the single retained allele. As would be predicted for the consequence of methylation in this 5' CpG island, none of the 5 tumors expressed the VHL gene. In contrast, normal kidney and all tumors examined with inactivating VHL gene mutations but no CpG island methylation had expression. In a renal cell culture line, treatment with 5-aza-2'-deoxycytidine resulted in reexpression of the VHL gene. These findings suggest that aberrant methylation of CpG islands may participate in the tumor-suppressor gene inactivations which initiate or cause progression of common human cancers.
Single-nucleotide polymorphisms and genome diversity in Plasmodium vivax (2003)

The study of genetic variation in malaria parasites has practical significance for developing strategies to control the disease. Vaccines based on highly polymorphic antigens may be confounded by allelic restriction of the host immune response. In response to drug pressure, a highly plastic genome may generate resistant mutants more easily than a monomorphic one. Additionally, the study of the distribution of genomic polymorphisms may provide information leading to the identification of genes associated with traits such as parasite development and drug resistance. Indeed, the age and diversity of the human malaria parasite Plasmodium falciparum has been the subject of recent debate, because an ancient parasite with a complex genome is expected to present greater challenges for drug and vaccine development. The genome diversity of the important human pathogen Plasmodium vivax, however, remains essentially unknown. Here we analyze an approximately 100-kb contiguous chromosome segment from five isolates, revealing 191 single-nucleotide polymorphisms (SNPs) and 44 size polymorphisms. The SNPs are not evenly distributed across the segment with blocks of high and low diversity. Whereas the majority (approximately 63%) of the SNPs are in intergenic regions, introns contain significantly less SNPs than intergenic sequences. Polymorphic tandem repeats are abundant and are more uniformly distributed at a frequency of about one polymorphic tandem repeat per 3 kb. These data show that P. vivax has a highly diverse genome, and provide useful information for further understanding the genome diversity of the parasite.
Identification of a new class of inducible receptors on platelets. Thrombospondin interacts with platelets via a GPIIb-IIIa-independent mechanism. (1986)

Thrombospondin with fibrinogen, fibronectin, and von Willebrand factor binds to platelets stimulated with agonists and support platelet adhesive functions. The receptors for the latter three proteins are associated with membrane glycoprotein GPIIb-IIIa. Thrombasthenic platelets deficient in GPIIb-IIIa have been utilized to examine the role of this membrane protein in the interactions of thrombospondin with platelets. Radioiodinated thrombospondin bound to thrombin-stimulated platelets from normal and thrombasthenic donors with a similar affinity and capacity. As monitored with a monoclonal antibody to thrombospondin, the divalent ion-dependent and -independent pathways for the expression of the endogenous pool of thrombospondin on the surface of thrombin-stimulated platelets from normal and thrombasthenic donors were also qualitatively and quantitatively similar. GPIIb-IIIa or ligands associated with GPIIb-IIIa thus are not essential for the binding of thrombospondin to platelets. Therefore, thrombospondin interacts with unique receptors on platelets.
Network intrusion detection (1994)

Intrusion detection is a new, retrofit approach for providing a sense of security in existing computers and data networks, while allowing them to operate in their current "open" mode. The goal of intrusion detection is to identify unauthorized use, misuse, and abuse of computer systems by both system insiders and external penetrators. The intrusion detection problem is becoming a challenging task due to the proliferation of heterogeneous computer networks since the increased connectivity of computer systems gives greater access to outsiders and makes it easier for intruders to avoid identification. Intrusion detection systems (IDSs) are based on the beliefs that an intruder's behavior will be noticeably different from that of a legitimate user and that many unauthorized actions are detectable. Typically, IDSs employ statistical anomaly and rulebased misuse models in order to detect intrusions. A number of prototype IDSs have been developed at several institutions, and some of them have also been deployed on an experimental basis in operational systems. In the present paper, several host-based and network-based IDSs are surveyed, and the characteristics of the corresponding systems are identified. The host-based systems employ the host operating system's audit trails as the main source of input to detect intrusive activity, while most of the network-based IDSs build their detection mechanism on monitored network traffic, and some employ host audit trails as well. An outline of a statistical anomaly detection algorithm employed in a typical IDS is also included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ChemInform Abstract: Synthesis and Structure‐Activity Relationships of Naftifine‐Related Allylamine Antimycotics. (1986)

Abstract β,γ‐Ungesättigte Amine wie (VII)‐(X) werden synthetisiert und auf antimykotische Wirkung geprüft, wobei das bereits bekannte Naftifin (Xb) als Vergleich dient.
Analysis of the inflammatory cytokine network among TNF alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8 in LPS-induced rabbit arthritis. (1997)

We investigated the cytokine network in rabbit lipopolysaccharide (LPS)-induced arthritis, using inhibitors against homologous TNF alpha, IL-1 beta, and IL-8. Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors (10 micrograms each), and the concentrations of each cytokine in the synovial fluids were measured. Maximum levels of TNF alpha and IL-8 were detected at 2 hours after LPS-injection, whereas IL-1 beta and IL-1 receptor antagonist (IL-1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry, synovial lining cells were positive for TNF alpha and IL-8, and infiltrating leukocytes were positive for IL-1 beta and IL-1 Ra. The effects of cytokine inhibitors on the release of each cytokine were then investigated. The maximum levels of TNF alpha and IL-8 were not affected by blocking the activities of other cytokines. In contrast, the peak concentration of IL-1 beta was reduced by anti-TNF alpha monoclonal Ab (mAb), IL-1 Ra or anti-IL-8 IgG. Peak concentrations of IL-1Ra were reduced by anti-TNF alpha mAb or anti-IL-8 IgG. Anti-TNF alpha mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the joint cavity, and the effect of anti-IL-8 IgG was less than that of anti-TNF alpha mAb plus IL-1Ra. The initial phase of the leukocyte influx was not inhibited. These results provide new evidence that IL-8 as well as TNF alpha are the most proximal cytokines and induce subsequent production of IL-1 beta and IL-1Ra. The data also raise the possibility that factor(s) other than IL-8 may be involved in the leukocyte influx in LPS-induced arthritis.
Host-guest complexation. 28. Hemispherands with four self-organizing units (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHost-guest complexation. 28. Hemispherands with four self-organizing unitsSteven P. Artz and Donald J. CramCite this: J. Am. Chem. Soc. 1984, 106, 7, 2160–2171Publication Date (Print):April 1, 1984Publication History Published online1 May 2002Published inissue 1 April 1984https://pubs.acs.org/doi/10.1021/ja00319a042https://doi.org/10.1021/ja00319a042research-articleACS PublicationsRequest reuse permissionsArticle Views482Altmetric-Citations61LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases (2006)

Alzheimer's disease (AD) and sporadic Parkinson's disease (PD) are the most frequently occurring degenerative illnesses of the human nervous system. Both involve multiple neuronal systems, but only a few types of nerve cells are prone to develop the disease-associated intraneuronal alterations. In AD affected neurons produce neurofibrillary tangles and neuropil threads, while in PD they develop Lewy bodies and Lewy neurites. In both illnesses select types of projection cells that generate long, unmyelinated or sparsely myelinated axons are particularly susceptible. This kind of selective vulnerability induces a distinctive lesional pattern which evolves slowly over time and remains remarkably consistent across cases. In the present review, lesions developing in the cerebral cortex are described against the backdrop of the internal organisation and interconnectivities linking involved cortical areas and subcortical nuclei. In AD, six and in PD, three stages can be distinguished, reflecting the predictable manner in which the proteinaceous intraneuronal inclusions spread through the cerebral cortex. In AD stages I-II and in PD stage 4, the pathological process makes inroads into the anteromedial temporal mesocortex, entorhinal allocortex, and Ammon's horn; thereafter, in AD stages III-IV and in PD stage 5, it proceeds into the adjoining high order association areas of the basal temporal neocortex. In AD stages V-VI and in PD stage 6, the damage affects additional neocortical association areas including first order association areas and eventually extends into the primary areas of the neocortex. The gradually evolving lesional pattern in AD and PD mirrors the ground plan of the cerebral cortex. The highest densities of lesions occur in the anterior mesocortical transitional zone between allo- and neocortex. From there, the involvement diminishes by degrees and extends into both the hippocampal formation and the neocortex. The severity of the neocortical lesions decreases in inverse proportion to the trajectories of increasing cortical differentiation and hierarchical refinement.
A nitric oxide (NO)‐releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain‐like behavior after spinal cord and peripheral nerve injury (2004)

1. Nitric oxide (NO) participates, at least in part, to the establishment and maintenance of pain after nerve injury. Therefore, drugs that target the NO/cGMP signaling pathway are of interest for the treatment of human neuropathic pain. Various compounds endowed with NO-releasing properties modulate the expression and function of inducible nitric oxide synthase (iNOS), the key enzyme responsible for sustained NO production under pathological conditions including neuropathic pain. 2. With this background, we synthesized a new chemical entity, [1-(aminomethyl)cyclohexane acetic acid 3-(nitroxymethyl)phenyl ester] NCX8001, which has a NO-releasing moiety bound to gabapentin, a drug currently used for the clinical management of neuropathic pain. We examined the pharmacological profile of this drug with respect to its NO-releasing properties in vitro as well as to its efficacy in treating neuropathic pain conditions (allodynia) consequent to experimental sciatic nerve or spinal cord injuries. 3. NCX8001 (1-30 microm) released physiologically relevant concentrations of NO as it induced a concentration-dependent activation of soluble guanylyl cyclase (EC(50)=5.6 microm) and produced consistent vasorelaxant effects in noradrenaline-precontracted rabbit aortic rings (IC(50)=1.4 microm). 4. NCX8001, but not gabapentin, counteracted in a concentration-dependent fashion lipopolysaccharide-induced overexpression and function of iNOS in RAW264.7 macrophages cell line. Furthermore, NCX8001 also inhibited the release of tumor necrosis factor alpha (TNFalpha) from stimulated RAW264.7 cells. 5. NCX8001 (28-280 micromol x kg(-1), i.p.) reduced the allodynic responses of spinal cord injured rats in a dose-dependent fashion while lacking sedative or motor effects. In contrast, gabapentin (170-580 micromol x kg(-1), i.p.) resulted less effective and elicited marked side effects. 6. NCX8001 alleviated the allodynia-like responses of rats to innocuous mechanical or cold stimulation following lesion of the sciatic nerve. This effect was not shared by equimolar doses of gabapentin. 7. Potentially due to the slow releasing kinetics of NO, NCX8001 alleviated pain-like behaviors in two rat models of neuropathic pain in a fashion that is superior to its parent counterpart gabapentin. This new gabapentin derivative, whose mechanism deserves to be explored further, offers new hopes to the treatment of human neuropathic pain.
Daily work experiences and police performance (2011)

Abstract This study examined police officers' perceptions of daily operational and organizational work experiences and their relationship with performance in two large urban police departments in the Midwest and the Middle Atlantic regions (USA). The findings were mixed: (1) organizational work experiences showed a higher mean score than operational work experiences; (2) there was no significant difference between cities on organizational and operational work experiences; and (3) multiple regression models for both organizational and operational work experiences predicted performance. Future research should examine work experiences in smaller and mid-size police agencies, suburban and rural agencies and widen the participant pool to include superior officers and civilian personnel. Keywords: organizational work experiencesoperational work experiencesdaily hassles scalepolice performance Notes 1. To respect both cities' confidentiality they are referred to as City 'A' and City 'B'. 2. Prior to multivariate analysis, tests for the presence of multicollinearity were performed using tolerance and variance inflation factor (VIF) statistics (Meyers, Gamst & Guarino, Citation2006). Multicollinearity was not detected.
Free Radical Scavenging Activity of the Medicinal Malaysian Leech Saliva Extract, Hirudinaria manillensis (2012)

Antioxidants from natural sources have been arisen as prophylactic and therapeutical agents in many lifethreatening disorders such as cancer and cardiovascular diseases. Leech therapy has been used since the extreme old ages in a variety of abnormalities. The current study was executed to examine the antioxidant activity of the salivary gland secretion of the medicinal Malaysian leech using DPPH free radical scavenging activity method. Leech saliva extract (LSE) was collected from starved leeches after feeding them on the phagostimulatory solution of 0.001M arginine in 0.15 M sodium chloride. Total protein concentration was 78.753 2.406 g/ml. A series of different dilutions of LSE were mixed with DPPH in a methanolic medium and the changes in absorbance were measured at 516nm. Results showed that LSE expressed a free radical scavenging activity with IC 50 of 7.282 g/ml compared with 5.803 g/ml of L-ascorbic acid as a positive control. Therefore, this study revealed that the proteomic contents of LSE are promising natural antioxidants.
Alphavirus-based expression vectors: strategies and applications. (1996)

Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in insect and vertebrate cells. Through recombinant DNA technology, the alphavirus RNA replication machinery has been engineered for high-level expression of heterologous RNAs and proteins. Amplification of replication-competent alpha-virus RNAs (replicons) can be initiated by RNA or DNA transfection and a variety of packaging systems have been developed for producing high titers of infectious viral particles. Although normally cytocidal for vertebrate cells, variants with adaptive mutations allowing noncytopathic replication have been isolated from persistently infected cultures or selected using a dominant selectable marker. Such mutations have been mapped and used to create new alphavirus vectors for noncytopathic gene expression in mammalian cells. These vectors allow long-term expression at moderate levels and complement previous vectors designed for short-term high-level expression. Besides their use for a growing number of basic research applications, recombinant alphavirus RNA replicons may also facilitate genetic vaccination and transient gene therapy.