gebhart/patrepeval huggingface dataset:
Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice (2000)

Huntington's disease (HD) is caused by an expanded N-terminal glutamine tract that endows huntingtin with a striatal-selective structural property ultimately toxic to medium spiny neurons. In precise genetic models of juvenile HD, HdhQ92 and HdhQ111 knock-in mice, long polyglutamine segments change huntingtin's physical properties, producing HD-like in vivo correlates in the striatum, including nuclear localization of a version of the full-length protein predominant in medium spiny neurons, and subsequent formation of N-terminal inclusions and insoluble aggregate. These changes show glutamine length dependence and dominant inheritance with recruitment of wild-type protein, critical features of the altered HD property that strongly implicate them in the HD disease process and that suggest alternative pathogenic scenarios: the effect of the glutamine tract may act by altering interaction with a critical cellular constituent or by depleting a form of huntingtin essential to medium spiny striatal neurons.
Molecular cloning of cDNA coding for human PGP 9.5 protein (1987)

The co-ordinate sequencing of the human neuronal and neuroendocrine marker protein PGP 9.5 and its cDNA is described. The cDNA encodes the complete protein (212 amino acids), and the 340 nucleotide 3'-noncoding region including the polyadenylation signal, indicating an mRNA slightly larger than 1 kb in size. Protein sequencing of 50% of PGP 9.5 confirms the deduced protein sequence.
Somatic Mutations in Human Cancer: Insights from Resequencing the Protein Kinase Gene Family (2005)

All cancers arise due to the accumulation of mutations in critical target genes that, when altered, give rise to selective advantage in the cell and its progeny that harbor them. Knowledge of these mutations is key in understanding the biology of cancer initiation and progression, as well as the development of more targeted therapeutic strategies. We have undertaken a systematic screen of all annotated protein kinases in the human genome for mutations in a series of cancers including breast, non-small-cell lung, and testicular cancer. Our results show a wide diversity in mutation prevalence within and between tumor types. We have identified a mutator phenotype in human breast previously undescribed. The results presented from sequencing the same 1.3 million base pairs through several tumor types suggest that most of the observed mutations are likely to be passenger events rather than causally implicated in oncogenesis. However, this work does provide evidence for the likely existence of multiple, infrequently mutated kinases.
Automated Brain Region Extraction Method in Head MR Image Sets (2002)

A noel automated brain region extraction method in single channel MR images for visualization and analysis of a human brain is presented. The method generates a volume of brain masks by automatic thresholding using a dual curve fitting technique and by 3D morphological operations. The dual curve fitting can reduce an error in clue fitting to the histogram of MR images. The 3D morphological operations, including erosion, labeling of connected-components, max-feature operation, and dilation, are applied to the cubic volume of masks reconstructed from the thresholded Drain masks. This method can automatically extract a brain region in any displayed type of sequences, including extreme slices, of SPGR, T1-, T2-, and PD-weighted MR image data sets which are not required to contain the entire brain. In the experiments, the algorithm was applied to 20 sets of MR images and showed over 0.97 of similarity index in comparison with manual drawing.
Photoimprint Photoacoustic Microscopy for Three-Dimensional Label-Free Subdiffraction Imaging (2014)

Subdiffraction optical microscopy allows the imaging of cellular and subcellular structures with a resolution finer than the diffraction limit. Here, combining the absorption-based photoacoustic effect and intensity-dependent photobleaching effect, we demonstrate a simple method for subdiffraction photoacoustic imaging of both fluorescent and nonfluorescent samples. Our method is based on a double-excitation process, where the first excitation pulse partially and inhomogeneously bleaches the molecules in the diffraction-limited excitation volume, thus biasing the signal contributions from a second excitation pulse striking the same region. The differential signal between the two excitations preserves the signal contribution mostly from the center of the excitation volume, and dramatically sharpens the lateral resolution. Moreover, due to the nonlinear nature of the signal, our method offers an inherent optical sectioning capability, which is lacking in conventional photoacoustic microscopy. By scanning the excitation beam, we performed three-dimensional subdiffraction imaging of varied fluorescent and nonfluorescent species. As any molecules have absorption, this technique has the potential to enable label-free subdiffraction imaging, and can be transferred to other optical imaging modalities or combined with other subdiffraction methods.
Nonsteroidal Anti-Inflammatory Drugs Promote Axon Regeneration via RhoA Inhibition (2007)

After a CNS injury in the adult mammals, axonal regeneration is very limited because of the reduced intrinsic growth capacity and nonpermissive environment for axonal elongation. The growth inhibitions from CNS myelin and astroglial chondroitin sulfate proteoglycans partially account for the lack of CNS repair. Here, we show that the nonsteroidal antiinflammatory drugs (NSAIDs) ibuprofen and indomethacin, the drugs widely used as pain relievers in the clinic, can surmount axon growth restrictions from myelin and proteoglycans by potently inhibiting their downstream pathway RhoA signal. Similar to Rho and Rock inhibitors C3 transferase or Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide], both NSAID drugs stimulate a significant neurite growth in the cultured dorsal root ganglion neurons exposed to the inhibitory substrates. Systemic administration of ibuprofen to spinal cord-lesioned rodents reverses the active RhoA signal around injury area measured via Rho-GTP binding assay. Subcutaneous injections of ibuprofen via minipumps to rats with a thoracic spinal cord transection or contusion injury result in substantial corticospinal and serotonergic axon sprouting in the caudal spinal cord and promote locomotor functional recovery, even delaying the treatment 1 week after trauma. In contrast, the non-RhoA-inhibiting NSAID naproxen does not have the axon growth-promoting effects on cultured or lesioned neurons. These studies demonstrate the therapeutic potential of RhoA-inhibiting NSAIDs in treating CNS injuries characterized by axonal disconnection including spinal cord injury.
Antibody Therapy with Rituximab for Patients with Low-Grade Non-Hodgkin’s Lymphoma (1999)

Rituximab (Mabthera<sup>®</sup> , Rituxan<sup>®</sup> ) is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes; it has recently been licensed in the United States and Europe as a novel antibody therapy for patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin’s lymphoma (NHL). Preclinical studies have shown that rituximab specifically recognizes the CD20 antigen, can induce human effector mechanisms in vitro, and effectively depletes B cells in cynomolgus monkeys with limited toxicity. Previous clinical studies have demonstrated that 4 infusions of 375 mg/m<sup>2</sup> rituximab given over a 22-day period in patients with low-grade NHL is effective, with an overall response rate of 50%. Adverse events associated with treatment are primarily mild and are most frequent with the first infusion, decreasing with subsequent infusions. B cells are effectively depleted during treatment: Levels return to normal ranges between 9 and 12 months post-treatment. Immunoglobulin levels of IgM, IgG, and IgA remain within the normal range. A human anti-chimeric antibody response has been detected in only less than 1% of patients treated and has not interfered with treatment. Rituximab offers a novel, effective, well-tolerated alternative treatment for NHL compared with existing therapies. The clinic al success of rituximab reinforces the promising potential of antibody therapy.
Collectins — soluble proteins containing collagenous regions and lectin domains — and their roles in innate immunity (1994)

The collectins are a group of mammalian lectins containing collagen-like regions. They include mannan binding protein, bovine conglutinin, lung surfactant protein A, lung surfactant protein D, and a newly discovered bovine protein named collectin-43. These proteins share a very similar modular domain composition and overall 3-dimensional structure. They also appear to play similar biological roles in the preimmune defense against micro-organisms in both serum and lung surfactant. The close evolutionary relationship between the collectins is further emphasized by a common pattern of exons in their genomic structures and the presence of a gene cluster on chromosome 10 in humans that contains the genes known for the human collectins. Studies on the structure/function relationships within the collectins could provide insight into the properties of a growing number of proteins also containing collagenous regions such as C1q, the hibernation protein, the alpha- and beta-ficolins, as well as the membrane acetylcholinesterase and the macrophage scavenger receptor.
Surface Registration in the Presence of Missing Patches and Topology Change. (2015)

The fusion between an endoscopic movie and a CT poses a special surface registration problem. The surface extracted from CT is complete and accurate, whereas the surface extracted from endoscopy suffers from serious missing patches and topology change. We propose a surface registration method, Thin Shell Demons, that is robust under these two situations. Motivated by Thirion’s Demons idea, the partial surface can provide virtual forces to attract the complete surface, which is equipped with a novel physics-based deformation energy. This energy can help preserve the correct surface topology while producing realistic deformation for the regions that don’t have any attracting counterpart regions. The attraction direction assures the deformation is not affected by the surface completeness. Moreover, we propose to use geometric feature matching for computing virtual forces to handle inaccurate 3D point positions and large deformations. We test our method for CT/endoscope fusion and show its potential to achieve successful registration.
New antibiotics for bad bugs: where are we? (2013)

Bacterial resistance to antibiotics is growing up day by day in both community and hospital setting, with a significant impact on the mortality and morbidity rates and the financial burden that is associated. In the last two decades multi drug resistant microorganisms (both hospital- and community-acquired) challenged the scientific groups into developing new antimicrobial compounds that can provide safety in use according to the new regulation, good efficacy patterns, and low resistance profile. In this review we made an evaluation of present data regarding the new classes and the new molecules from already existing classes of antibiotics and the ongoing trends in antimicrobial development. Infectious Diseases Society of America (IDSA) supported a proGram, called "the '10 × ´20' initiative", to develop ten new systemic antibacterial drugs within 2020. The microorganisms mainly involved in the resistance process, so called the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae) were the main targets. In the era of antimicrobial resistance the new antimicrobial agents like fifth generation cephalosporins, carbapenems, monobactams, β-lactamases inhibitors, aminoglycosides, quinolones, oxazolidones, glycopeptides, and tetracyclines active against Gram-positive pathogens, like vancomycin-resistant S. aureus (VRSA) and MRSA, penicillin-resistant streptococci, and vancomycin resistant Enterococcus (VRE) but also against highly resistant Gram-negative organisms are more than welcome. Of these compounds some are already approved by official agencies, some are still in study, but the need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections. Therefore the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance.
Identification of Tumor-Specific Paclitaxel (Taxol)-Responsive Regulatory Elements in the Interleukin-8 Promoter (1997)

Paclitaxel (Taxol) is a novel chemotherapeutic drug that is effective against breast and ovarian cancers. Although the primary target of paclitaxel is microtubules, its efficacy exceeds that of conventional microtubule-disrupting agents, suggesting that it may have additional cellular effects. Previously, we demonstrated that paclitaxel can induce interleukin-8 (IL-8) gene expression at the transcriptional level in subsets of human ovarian cancer lines. In this as well as the previous report, we present evidence that this ability is not linked to the lipopolysaccharide pathway of IL-8 gene induction. The present study identifies the cis-acting elements and trans-acting factors involved in this induction by transfecting DNA constructs containing the 5'-flanking region of the IL-8 gene linked to the chloramphenicol acetyltransferase reporter gene into paclitaxel-responsive and nonresponsive ovarian cancer cells (responsiveness refers to the IL-8 response). Paclitaxel only activated the IL-8 promoter in responsive cells. The AP-1 and NF-kappaB binding sites in the IL-8 promoter are required for activation by paclitaxel; in contrast, a C/EBP site required for IL-8 promoter activation in other cell types is not involved. Gel shift assays demonstrate that paclitaxel causes a marked increase in protein binding to the NF-kappaB and AP-1 consensus binding sequences in the paclitaxel-responsive ovarian cells, but not the nonresponsive cells. The induction of NF-kappaB and AP-1 binding is reduced by the addition of protein kinase C inhibitors and cyclic AMP effector, respectively. These results demonstrate a molecular mechanism for cell-specific paclitaxel-induced IL-8 gene expression which may have clinical relevance.
Characterization of CO2precipitated Kraft lignin to promote its utilization (2009)

Converting pulp mills into forest biorefineries to produce biopower and biomaterials can decrease their environmental impact and increase feasibility at the same time. One of the key challenges to reach this goal is the recovery of lignin from process streams for subsequent utilization in a variety of innovative green processes. This study examines the fundamental chemical structure of lignin recovered from Kraft pulping streams by an acid precipitation/washing methodology. Functional group analysis and molecular weight profiles were determined by NMR and SEC with promising results for future conversions; such as low hydroxyl (oxygen) contents and low molecular weights (∼3000 g mol−1).
Intranasal Civamide for the Acute Treatment of Migraine Headache (2000)

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.
Switch from perforin‐expressing to perforin‐deficient CD8+ T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo (2009)

Although CD8(+) cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8(+) CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8(+) T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8(+) cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8(+) CTL have two killing strategies.
Incorporation of Pain in Dreams of Hospitalized Burn Victims (2002)

It has been shown that realistic, localized painful sensations can be experienced in dreams either through direct incorporation or from past memories of pain. Nevertheless, the frequency of pain dreams in healthy subjects is low. This prospective study was designed to evaluate the occurrence and frequency of pain in the dreams of patients suffering from burn pain. Twenty-eight nonventilated burn victims were interviewed for 5 consecutive mornings during the first week of hospitalization. A structured-interview protocol was used to collect information on dream content, quality of sleep, and pain intensity and location. Patients were also administered the Impact of Event Scale to assess posttraumatic symptoms. Thirty-nine percent of patients reported 19 pain dreams on a total of 63 dreams (30%). Patients with pain dreams showed evidence of worse sleep, more nightmares, higher intake of anxiolytic medication, and higher scores on the Impact of Event Scale than did patents reporting dreams with no pain content. Moreover, patients with pain dreams also had a tendency to report more intense pain during therapeutic procedures. Although more than half of our sample did not report pain dreams, these results suggest that pain dreams do occur at a greater frequency in suffering populations than in normal volunteers. More importantly, dreaming about pain may be an added stress for burn patents and may contribute to both poor sleep and higher pain intensity, which could evolve into a cycle of pain-anxiety-sleeplessness.
Are n-3 fatty acids still cardioprotective? (2012)

The question of the extent to which n-3 fatty acid supplementation reduces risk for cardiovascular disease remains open. Future studies must be properly powered, use doses of n-3 fatty acids significantly higher than those provided in background diets, focus on patient populations with low n-3 fatty acid tissue levels, treat for longer periods of time, and consider the effects of these agents in the great majority of patients who are not on guideline-directed therapeutic regimens. The strong evidence-base from prospective cohort studies and the ever-deepening understanding of the cellular effects of long-chain n-3 fatty acids together support the need for these nutrients in reducing cardiovascular risk. Short-term findings from randomized controlled trials need to be interpreted in the light of all the evidence.
Cell Culture of the Intervertebral Disc of Rats (1991)

To establish cell culture of the nucleus pulposus and anulus fibrosus of rat intervertebral disc, the effects of culture conditions on the growth of cells and the synthesis of DNA, proteoglycan, and collagen were studied. For cell culture of the nucleus pulposus, the use of 3-week-old rats and a medium adjusted to pH 7.0 was optimal. There was almost no difference in growth between cells in Ham's F12 medium and those in Dulbecco's Modified Eagle Medium. In cells isolated from the anulus fibrosus, a medium adjusted to pH 7.0-7.6 was preferable, but irrespective of rat age. Culture cells of the nucleus pulposus were composed of large cells with vacuoles and small polygonal cells. These cells had a slight growth activity and a fair capability of proteoglycan and collagen synthesis. Culture cells of the anulus fibrosus were composed of polygonal and spindle-shape cells, and the growth was more vigorous with the potentials for proteoglycan and collagen synthesis than the nucleus cells.
Aurora‐A induces cell survival and chemoresistance by activation of Akt through a p53‐dependent manner in ovarian cancer cells (2006)

Aurora-A is frequently altered in epithelial malignancies. Overexpressing Aurora-A induces centrosome amplification and G2/M cell cycle progression. We have previously shown elevated level of Aurora-A in ovarian cancer and activation of telomerase by Aurora-A in human mammary and ovarian epithelia. Here we report that Aurora-A protects ovarian cancer cells from apoptosis induced by chemotherapeutic agent and activates Akt pathway in a p53-dependent manner. Ectopic expression of Aurora-A renders cells resistant to cisplatin (CDDP), etoposide and paclitaxel-induced apoptosis and stimulates Akt1 and Akt2 activity in wild-type p53 but not p53-null ovarian cancer cells. Aurora-A inhibits cytochrome C release and Bax conformational change induced by CDDP. Knockdown of Aurora-A by RNAi sensitizes cells to CDDP-induced apoptosis and decreases phospho-Akt level in wild-type p53 cells. Reintroduction of p53 decreases Akt1 and Akt2 activation and restores CDDP sensitivity in p53-null but not p53-null-Aurora-A cells. Inhibition of Akt by small molecule inhibitor, API-2, overcomes the effects of Aurora-A-on cell survival and Bax mitochondrial translocation. Taken collectively, these data indicate that Aurora-A activates Akt and induces chemoresistance in a p53-dependent manner and that inhibition of Akt may be an effective means of overcoming Aurora-A-associated chemoresistance in ovarian cancer cells expressing wild-type p53.