gebhart/patrepeval huggingface dataset:
Mycobacterium tuberculosis Thymidine Monophosphate Kinase Inhibitors: Biological Evaluation and Conformational Analysis of 2′‐ and 3′‐Modified Thymidine Analogues (2003)

Abstract Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) has recently been introduced as a potential target for the structure‐based design of anti‐tuberculosis drugs. Based on the TMPKmt X‐ray structure and previous S.A.R. studies, we synthesised the nucleoside analogues 3a − b , 6a − b , 7a − b , and 8a − b , modified in 2′‐ and 3′‐position of the ribofuranose ring moiety. To our surprise, these analogues showed only moderate binding affinity (i.e. K i between 118 and 1260 μ M ). This prompted us to investigate the conformational features of these nucleosides. We concluded that compounds of this series, especially 8a − b , are strongly biased towards the “Northern” furanose ring conformation, whereas X‐ray crystallography reveals a preference of TMPKmt for the opposite “Southern” conformers. This paper covers the synthesis, biological evaluation and conformational features (i.e. preferred ring puckering) of the 2′‐ and 3′‐modified dT analogues. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
A guide to drug evaluation for chronic pain (2000)

In the past, management of pain was more empirical but with the understanding of mechanisms, biochemistry and molecular basis of pain, future drug development will be more rational. This article provides a brief overview of the pathomechanism of pain, the clinical situation, current treatments and methods of evaluation of pain therapies such as measurement of pain in clinical trials. A wide spectrum of agents are available, including non-steroid anti-inflammatory drugs (NSAIDs), opioids and adjuvant analgesics, such as antidepressants and certain anticonvulsants that are useful in neuropathic pain. Current management of pain is inadequate due to lack of understanding of pain mechanisms by healthcare providers and the lack of availability of adequate analgesic medications. Acute pain, if treated inadequately, changes into chronic pain with changes in the nervous system. Chronic pain, particularly neuropathic pain, is a neurological disorder, which is more difficult to treat. The total value of the pain management market, including drugs and devices, is estimated to be $5 billion in the year 2000, and will increase to $9 billion in the year 2005. A large number of drugs in development for pain include opioid receptor agonists and antagonists of glutamate receptors, adenosine triphosphate (ATP), serotonin (5-HT) and vanilloid receptors (VR1). Analgesics acting on ion channels and NSAIDs, which inhibit the cyclooxygenase (COX) pathways, are still in development. The ideal analgesic is defined and methods of pain drug delivery are also reviewed. A novel compound with an effective method of delivery has a better chance in the competitive marketplace of analgesic drug development.
Reversal of thalamic hand syndrome by long-term motor cortex stimulation (2000)

The authors describe a case of complete recovery from the so-called "thalamic hand" syndrome following chronic motor cortex stimulation in a 64-year-old man suffering from poststroke thalamic central pain. As of the 2-year follow-up examination, the patient's dystonia and pain are still controlled by electrical stimulation. It is speculated that a common mechanism in which the thalamocortical circuit loops are rendered out of balance may sustain hand dystonia and central pain in this case of thalamic syndrome. To the authors' knowledge this is the first reported case of its kind.
The I Domain of Integrin Leukocyte Function-associated Antigen-1 Is Involved in a Conformational Change Leading to High Affinity Binding to Ligand Intercellular Adhesion Molecule 1 (ICAM-1) (1998)

On T cells the leukocyte integrin leukocyte function-associated antigen-1 (LFA-1) (CD11a/CD18) can be induced to bind its ligand intercellular adhesion molecule 1 (ICAM-1) (CD54) either by increasing the affinity of the receptor with Mg2+ and EGTA or by receptor clustering following activation with phorbol ester. The existence of these two adhesion-inducing pathways implies that alternative mechanisms might exist by which LFA-1 engages ICAM-1. The LFA-1 alpha subunit I domain contains a major binding site for ICAM-1. In this study we show that soluble LFA-1 I domain blocks ICAM-1 binding of the high affinity Mg2+-induced form of LFA-1 but not the phorbol ester-induced form. Under conditions of Mg2+-activation, the soluble I domain also prevents expression of an activation dependent epitope on LFA-1, implying that it inhibits a conformational change necessary for conversion to the high affinity form of this integrin. In addition, the binding of Mg2+-activated LFA-1 to ICAM-1 is blocked by peptides covering the alpha4-beta3 loop, the beta3-alpha5 loop, and the alpha5 helix of the I domain, whereas none of the peptides tested blocks phorbol ester-mediated adhesion. The blocking peptides localize to the same face of the crystal structure of the LFA-1 I domain and define an area that, during activation, may be involved in association of the I domain with another region of LFA-1, potentially the beta-propeller domain. This is the first evidence linking a structural domain of an integrin, in this case the I domain, with a particular activation mechanism.
A novel cellular site-specific DNA-binding protein cooperates with the viral NS1 polypeptide to initiate parvovirus DNA replication (1997)

Replication of linear single-stranded parvovirus DNA proceeds by a rolling-hairpin mechanism which generates long, palindromic, duplex concatamers. Processing to monomer length requires initiation from origins of DNA replication located at the 3' and 5' ends of each embedded monomer, reactions which can be recapitulated in vitro for minute virus of mice (MVM). To determine which cellular proteins were essential for replication from these origins, S100 extracts from 293S cells were fractionated on phosphocellulose. When recombined, these fractions were able to support replication in vitro, dependent on the viral initiator protein NS1, using plasmid forms of the 5' origin or the minimal 3' origin as templates. Fraction P-cell 1 contains two factors, replication protein A (RPA) and proliferating-cell nuclear antigen (PCNA), known to be essential for simian virus 40 replication in vitro. When P-cell 1 was replaced with purified recombinant RPA and PCNA, NS1-mediated MVM replication initiated from the 5' origin but not from the 3' origin. The 3' origin is a 50-bp sequence containing three distinct recognition elements, an NS1 binding site, a site at which NS1 nicks the DNA to generate the priming 3' OH, and a region containing a consensus activated transcription factor (ATF) binding site. To identify the missing factor(s) for 3' origin replication, P-cell 1 was fractionated by further chromatography and active fractions were identified by their ability to complement RPA, PCNA, and P-cell 2 for NS1-mediated, origin-specific replication. Gel shift and UV cross-linking analysis of the replication-competent fractions revealed a novel 110-kDa sequence-specific DNA binding protein which recognized the consensus ATF binding site region of the origin and which we have termed parvovirus initiation factor, or PIF. Binding of PIF appears to activate the endonuclease function of NS1, allowing efficient and specific nicking of the 3' minimal origin under stringent conditions in vitro.
A novel porous collagen scaffold around an implantable biosensor for improving biocompatibility. I. In vitro/in vivo stability of the scaffold and in vitro sensitivity of the glucose sensor with scaffold (2007)

A new 3D porous and biostable collagen scaffold has been developed to improve the biocompatibility of implantable glucose sensors by minimizing tissue reactions while stimulating angiogenesis around the sensors. The novel collagen scaffold was crosslinked using nordihydroguaiaretic acid (NDGA) to enhance biostability. NDGA-treated collagen scaffolds were stable without physical deformation in the subcutaneous tissue of rats for 4 weeks. In contrast, glutaraldehyde (GA)-treated collagen scaffolds were extremely damaged following implantation. Both types of scaffolds (NDGA- and GA-crosslinked) were stable in vitro in the presence of collagenase with 70% retention of original weight after 4 weeks of incubation. The response current (i.e. sensitivity) of sensors with porous scaffolds was not significantly changed when compared with control sensors (no scaffold), while the response time (T(95%)) was slightly delayed after a glucose concentration increase from 5 to 15 mM. Above this range, the sensors coated with scaffolds had only a slightly lower sensitivity than the control sensors. These results indicate that we have developed a stable NDGA-crosslinked collagen scaffold for biosensors, and that the scaffold does not impair the function of our sensor. We plan to use this scaffold to enhance the function and lifetime of the implantable biosensors by providing a controlled local environment around the sensors with the help of various drugs and growth factors (dexamethasone, VEGF, PDGF).
In vivo full range complex Fourier domain optical coherence tomography (2007)

The author presents a system and algorithm to achieve full range complex Fourier domain optical coherence tomography (OCT) capable of imaging biological tissues in vivo. The method utilizes the Hilbert transformation to obtain the analytic functions for spatial interference signals obtained from each single wavelength covered in the broadband OCT light source before performing the Fourier transformation to localize the scatters within a sample. A constant carrier frequency is introduced in the spatial OCT interference signal so that its Hilbert transformation is strictly equal to its quadrature representation. The method is experimentally validated for in vivo imaging.
Small Intestinal Bacterial Overgrowth in Patients Suffering From Scleroderma: Clinical Effectiveness of Its Eradication (2008)

These data suggest that SIBO occurs more frequently in SSc patients than in controls. Intestinal symptoms in these patients may be related to this syndrome and its eradication seems useful to improve clinical features. OCTT is significantly delayed in SSc patients, suggesting an impairment of intestinal motility, a further risk factor for the development of SIBO.
Direct and Indirect Involvement of MicroRNA-499 in Clinical and Experimental Cardiomyopathy (2012)

miR-499 is increased in human and murine cardiac hypertrophy and cardiomyopathy, is sufficient to cause murine heart failure, and accelerates maladaptation to pressure overloading. The deleterious effects of miR-499 reflect the cumulative consequences of direct and indirect mRNA regulation, modulation of cardiac kinase and phosphatase pathways, and higher-order effects on posttranslational modification of myocardial proteins.
Blockade of tolerance to morphine but not to kappa opioids by a nitric oxide synthase inhibitor. (1993)

The nitric oxide synthase inhibitor NG-nitro-L-arginine (NO2Arg) blocks morphine tolerance in mice. After implantation of morphine pellets the analgesic response decreases from 100% on the first day to 0% on the third. Coadministration of NO2Arg along with the pellets markedly retards the development of tolerance; 60% of mice are analgesic after 3 days, and 50% of mice are analgesic after 5 days. In a daily injection paradigm the analgesic response to morphine is reduced from 60% to 0% by 5 days. Concomitant administration of morphine along with NO2Arg at doses of 2 mg/kg per day prevents tolerance for 4 weeks. A single NO2Arg dose retards morphine tolerance for several days, and dosing every 4 days is almost as effective as daily NO2Arg. NO2Arg slowly reverses preexisting tolerance over 5 days despite the continued administration of morphine along with NO2Arg. NO2Arg also reduces dependence and reverses previously established dependence. NO2Arg does not prevent tolerance to analgesia mediated by the kappa 1 agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolindinyl)cyclohexyl]- benzene-acetamide (U50,488H) or the kappa 3 agent naloxone benzoylhydrazone, indicating a selective action of NO in the mechanisms of mu tolerance and dependence.
Analysis of glucocorticoid receptors in human hepatocellular carcinoma and HepG2 cells (1993)

Hepatocellular carcinoma is the leading cause of male cancer death in Taiwan. We have found that the level of glucocorticoid receptor in hepatocellular carcinoma is significantly higher than that in the peritumoral tissue. In this study, we used a rat liver glucocorticoid receptor complementary DNA probe to examine the expression of glucocorticoid receptor gene in 15 paired samples of hepatocellular carcinoma and their peritumoral tissues. No differences in genomic DNA patterns of the glucocorticoid receptor gene were found between the tumor and peritumoral tissues. The amount of glucocorticoid receptor was found to be significantly higher in hepatoma samples than in peritumoral liver samples. The levels of glucocorticoid receptor messenger RNAs were increased in most tumors compared with their peritumoral samples. To examine the function of glucocorticoid receptors in hepatoma, we examined the expression of glucocorticoid receptor and its relation to cell-cycle progression in human HepG2 cells. Using specific monoclonal antibodies and flow cytometric study, we found glucocorticoid receptor to be expressed constitutively in all cell-cycle phases. In addition, hydrocortisone treatment of HepG2 cells resulted in increased expression of glucocorticoid receptors and increased secretion of alpha-fetoprotein. RU-486, a glucocorticoid antagonist, blocked the hydrocortisone effect, indicating that glucocorticoid receptors are functional in HepG2 cells. Taken together, our data suggest that glucocorticoids and their receptors play an important role in the growth of hepatoma.
Characterization of Distinct Immunophenotypes across Pediatric Brain Tumor Types (2013)

Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors' microenvironment has not been defined. To address this, the current study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common pediatric brain tumor types. The initial study cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5 glioblastoma (GBM), 6 medulloblastoma (MED), and 5 nontumor brain (NT) control samples obtained from epilepsy surgery. Immune cell types analyzed included both myeloid and T cell lineages and respective markers of activated or suppressed functional phenotypes. Immune parameters that distinguished each of the tumor types were identified. PA and EPN demonstrated significantly higher infiltrating myeloid and lymphoid cells compared with GBM, MED, or NT. Additionally, PA and EPN conveyed a comparatively activated/classically activated myeloid cell-skewed functional phenotype denoted in particular by HLA-DR and CD64 expression. In contrast, GBM and MED contained progressively fewer infiltrating leukocytes and more muted functional phenotypes similar to that of NT. These findings were recapitulated using whole tumor expression of corresponding immune marker genes in a large gene expression microarray cohort of pediatric brain tumors. The results of this cross-tumor comparative analysis demonstrate that different pediatric brain tumor types exhibit distinct immunophenotypes, implying that specific immunotherapeutic approaches may be most effective for each tumor type.
Sensor systems for interactive surfaces (2000)

This paper describes four different systems that we have developed for capturing various manners of gesture near interactive surfaces. The first is a low-cost scanning laser rangefinder adapted to accurately track the position of bare hands in a plane just above a large projection display. The second is an acoustic system that detects the position of taps on a large, continuous surface (such as a table, wall, or window) by measuring the differential time-of-arrival of the acoustic shock impulse at several discrete locations. The third is a sensate carpet that uses a grid of piezoelectric wire to measure the dynamic location and pressure of footfalls. The fourth is a swept radio frequency (RF) tag reader that measures the height, approximate location, and other properties (orientation or a control variable like pressure) of objects containing passive, magnetically coupled resonant tags, and updates the continuous parameters of all tagged objects at 30 Hz. In addition to discussing the technologies and sur veying different approaches, sample applications are given for each system.
Genome sequence of the hyperthermophilic crenarchaeon Pyrobaculum aerophilum (2002)

We determined and annotated the complete 2.2-megabase genome sequence of Pyrobaculum aerophilum, a facultatively aerobic nitrate-reducing hyperthermophilic (T(opt) = 100 degrees C) crenarchaeon. Clues were found suggesting explanations of the organism's surprising intolerance to sulfur, which may aid in the development of methods for genetic studies of the organism. Many interesting features worthy of further genetic studies were revealed. Whole genome computational analysis confirmed experiments showing that P. aerophilum (and perhaps all crenarchaea) lack 5' untranslated regions in their mRNAs and thus appear not to use a ribosome-binding site (Shine-Dalgarno)-based mechanism for translation initiation at the 5' end of transcripts. Inspection of the lengths and distribution of mononucleotide repeat-tracts revealed some interesting features. For instance, it was seen that mononucleotide repeat-tracts of Gs (or Cs) are highly unstable, a pattern expected for an organism deficient in mismatch repair. This result, together with an independent study on mutation rates, suggests a "mutator" phenotype.
A case-control study on the risk factors of lung cancer in Xi'an (2005)

Objective To study the risk factors of lu ng cancer patients in Xi'an. Methods The analysis was based on the data of a case-control study conducted during 1999~2002 in Xi'an, China, and evaluated by the odd ratio (OR). Results Single fact or analysis showed that tobacco smoking(OR=1.66), cooking smoke(OR=1.68), hi story of previous lung diseases(OR=1.46), family history of tumor(OR=2.08), and psychic trauma(OR=1.80)were the main risk factors of lung cancer, however, physical practice and fresh vegetables were the protective factors. Patients wi th COPD had an increased risk of lung cancer (OR=2.25). And the impairment of lu ng function was observed to increase the risk of lung cancer (OR=2.28). Conclusion Smoking, cooking smoke, history of previous lung dise ases, family history of tumor, and psychic trauma are related with lung cancer s ignificantly (P0.05).The risk of lung cancer increased in the pat ients with a history of COPD, and the impariment of lung function increases the risk of lung cancer.
Ellagic acid protects rat embryos in culture from the embryotoxic effects of N‐methyl‐N‐nitrosourea (1992)

Ellagic acid is a naturally occurring plant phenol that has demonstrated anticarcinogenic and antimutagenic activity in several test systems. Given the common proposed etiopathogenic processes of mutagenesis, carcinogenesis, and teratogenesis induced by genotoxic chemicals, the present study was initiated to determine whether ellagic acid would protect rat embryos in culture from the teratogenic effects of N-methyl-N-nitrosourea (MNU). Ellagic acid alone (as used in these experiments; 50 microM in DMSO) was not embryotoxic. Ellagic acid (50 microM) significantly (P less than 0.01) prevented MNU (75 microM)-induced effects including mortality (absence of heart beat), abnormal formation of the cephalic neural tube derivatives, and delayed differentiation as assessed by a morphological scoring system. These embryoprotective effects were dose responsive. Sequential treatment of embryos with ellagic acid followed by MNU in fresh media also was embryoprotective with no diminution of effect. The site at which ellagic acid interrupts the critical teratogenic events induced by MNU is apparently within the embryo and/or placenta. This model of chemical embryoprotection may be useful in determining the role of cell death and/or mutation in the teratogenic mechanism of action of methylating agents.
Temporal growth factor release from platelet‐rich plasma, trehalose lyophilized platelets, and bone marrow aspirate and their effect on tendon and ligament gene expression (2009)

Platelet-rich plasma (PRP) has generated substantial interest for tendon and ligament regeneration because of the high concentrations of growth factors in platelet alpha-granules. This study compared the temporal release of growth factors from bone marrow aspirate (BMA), PRP, and lyophilized platelet product (PP), and measured their effects on tendon and ligament gene expression. Blood and BMA were collected and processed to yield PRP and plasma. Flexor digitorum superficialis tendon (FDS) and suspensory ligament (SL) explants were cultured in 10% plasma in DMEM (control), BMA, PRP, or PP. TGF-beta1 and PDGF-BB concentrations were determined at 0, 24, and 96 h of culture using ELISA. Quantitative RT-PCR for collagen types I and III (COL1A1, COL3A1), cartilage oligomeric matrix protein (COMP), decorin, and matrix metalloproteinases-3 and 13 (MMP-3, MMP-13) was performed. TGF-beta1 and PDGF-BB concentrations were highest in PRP and PP. Growth factor quantity was unchanged in BMA, increased in PRP, and decreased in PP over 4 days. TGF-beta1 and platelet concentrations were positively correlated. Lyophilized PP and PRP resulted in increased COL1A1:COL3A1 ratio, increased COMP, and decreased MMP-13 expression. BMA resulted in decreased COMP and increased MMP-3 and MMP-13 gene expression. Platelet concentration was positively correlated with COL1A1, ratio of COL1A1:COL3A1, and COMP, and negatively correlated with COL3A1, MMP-13, and MMP-3. White blood cell concentration was positively correlated with COL3A1, MMP3, and MMP13, and negatively correlated with a ratio of COL1A1:COL3A1, COMP, and decorin. These findings support further in vivo investigation of PRP and PP for treatment of tendonitis and desmitis.
Characterization and correction of pulse pile‐up in simultaneous emission–transmission computed tomography (1996)

We have developed an emission-transmission CT (ETCT) system capable of both single-photon emission computed tomography (SPECT) imaging and x-ray transmission CT imaging using a common photon counting detector. In principle, SPECT and x-ray CT projection data can be acquired simultaneously with the ETCT system; however, doing so results in contamination of the SPECT projection data due to pulse pile-up caused by the relatively high x-ray fluence rate. In this study, we characterize the effects of pulse pile-up for simultaneous ETCT imaging through computer simulation and experimental studies. We demonstrate that pulse pile-up in the SPECT energy window can be well approximated by a simple quadratic relationship between the pile-up rate and the x-ray fluence rate for sufficiently small x-ray fluence rates. Using this quadratic relationship, we developed a simple pile-up correction scheme that subtracts the pile-up counts from the emission data and also truncates the exterior regions of the emission projection data. Analysis of difference images and profiles indicate that this method permits us to reconstruct SPECT images with no apparent noise or resolution degradation in comparison to those obtained via sequential emission and transmission scans.