gebhart/patrepeval huggingface dataset:
Protein misfolding in neurodegenerative diseases (2004)

A common pathogenic mechanism shared by diverse neurodegenerative disorders, like Alzheimer's disease, Parkinson's disease, Huntington's disease and transmissible spongiform encephalopathies, may be altered protein homeostasis leading to protein misfolding and aggregation of a wide variety of different proteins in the form of insoluble fibrils. Mutations in the genes encoding protein constituents of these aggregates have been linked to the corresponding diseases, thus a reasonable scenario of pathogenesis was based on misfolding of a neurone-specific protein that forms insoluble fibrils that subsequently kill neuronal cells. However, during the past 5 years accumulating evidence has revealed the neurotoxic role of prefibrillar intermediate forms (soluble oligomers and protofibrils) produced during fibril formation. Many think these may be the predominant neurotoxic species, whereas microscopically visible fibrillar aggregates may not be toxic. Large protein aggregates may rather be simply inactive, or even represent a protective state that sequesters and inactivates toxic oligomers and protofibrils. Further understanding of the biochemical mechanisms involved in protein misfolding and fibrillization may optimize the planning of common therapeutic approaches for neurodegenerative diseases, directed towards reversal of protein misfolding, blockade of protein oligomerization and interference with the action of toxic proteins.
Recent findings in phosphate homeostasis (2005)

Pi homeostasis depends on the activity of Na/Pi cotransporters in intestine and kidney. Na/Pi transporter activity is regulated by cellular and endocrine factors, among which fibroblast growth factor 23 plays a central role. Adequate control of Pi homeostasis is crucial, as a moderate increase in serum Pi concentration and polymorphisms in genes involved in Pi metabolism may influence the aging process and lifespan.
Glucocorticoid receptors in subpopulations of childhood acute lymphocytic leukemia. (1977)

In view of the known differences in sensitivity to glucocorticoids among functional subcategories of lympocytes in the mouse and the awareness that different subcategories of acute lymphocytic leukemia may represent proliferation of different clones of lymphoblasts, we examined lymphoblast populations with known surface markers for differences in specific cytoplasmic glucocorticoid receptor activity. Lymphoblasts were divided into those that formed sheep erythrocyte rosettes (T-lymphoblasts) and those that lacked all surface markers (null lymphoblasts). The latter were further subdivided by their ability to stimulate allogeneic donors in mixed lymphocyte culture (MLC). Lack of stimulation in MLC is a characteristic of mature T-cells. Eighteen patients had null lymphoblasts that did stimulate in MLC, and glucocorticoid binding sites in these ranged from 4,096 to 21,869 sites/cell (median, 7,571). Eighteen patients with T-lymphoblasts had binding sites ranging from 0 to 5,887 sites/cell (median, 2,173). This difference in specific glucocorticoid receptor levels is highly significant ( p < 0.001). Nine patients whose lymphoblasts lacked identifiable surface markers but failed to stimulate in MLC had intermediate values for receptor sites. Thus it appears that null lymphoblasts are more likely to have higher numbers of specific glucocorticoid receptor than T-lymphoblasts. The differential capacity of lymphoblasts to bind steroid may prove useful in designing therapeutic regimens for the different subcategories of acute lymphocytic leukemia.
Implications of High-Affinity Hybridization by Locked Nucleic Acid Oligomers for Inhibition of Human Telomerase (2002)

Oligonucleotides that contain locked nucleic acid (LNA) bases have remarkably high affinity for complementary RNA and DNA sequences. This increased affinity may facilitate the recognition of nucleic acid targets inside cells and thus improve our ability to use synthetic oligonucleotides for controlling cellular processes. Here we test the hypothesis that LNAs offer advantages for inhibiting human telomerase, a ribonucleoprotein that is critical for tumor cell proliferation. We observe that LNAs complementary to the telomerase RNA template are potent and selective inhibitors of human telomerase. LNAs can be introduced into cultured tumor cells using cationic lipid, with diffuse uptake throughout the cell. Transfected LNAs effectively inhibited intracellular telomerase activity up to 40 h post-transfection. Shorter LNAs of eight bases in length are also effective inhibitors of human telomerase. The melting temperatures of these LNAs for complementary sequences are superior to those of analogous peptide nucleic acid oligomers, emphasizing the value of LNA bases for high-affinity recognition. These results demonstrate that high-affinity binding by LNAs can be exploited for superior recognition of an intracellular target.
Migraine biomarkers in cerebrospinal fluid: A systematic review and meta-analysis (2016)

Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta-analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased β-endorphin (β-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and β-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, β-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine.
Chemiluminescent hybridization-ligation assays for delta F508 and delta I507 cystic fibrosis mutations (1996)

Chemiluminescent hybridization-ligation assays were devised to detect the delta F508 and delta I507 cystic fibrosis mutations in samples of human DNA that had been amplified by PCR. Two synthetic DNA oligomers were used in each assay. One of the oligomers was labeled with an acridinium ester and the other was immobilized on paramagnetic particles. The oligomers were hybridized to the samples and the target sequences discriminated by ligation with T4 or a thermostable DNA ligase. The performance of the assay was evaluated in a blind study of 30 samples. There was complete correspondence between the assignments based on the chemiluminescent assay and those made previously by gel electrophoresis, with one exception. The assignment of this discrepant sample by the chemiluminescent assay as a delta I507/normal heterozygote rather than a delta F508/normal heterozygote was confirmed by sequencing. The chemiluminescent hybridization-ligation assay provides a rapid and convenient means of discriminating DNA sequences differing by a single nucleotide.
High-dose mitoxantrone induces programmed cell death or apoptosis in human myeloid leukemia cells (1993)

Mitoxantrone has been shown in vitro to exhibit a steep dose-response relationship with respect to the clonogenic survival of acute myeloid leukemia cells. In this report, we show that 1-hour exposure of human myeloid leukemia HL-60 and KG-1 cells to mitoxantrone concentrations ranging between 0.1 and 10.0 mumol/L induced internucleosomal DNA fragmentation of approximately 200-bp integer multiples, characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Mitoxantrone-mediated PCD was associated with a steep inhibition of the clonogenic survival of the leukemic cells. In addition, intracellularly, mitoxantrone-induced PCD was associated with a marked induction of c-jun and significant repression of c-myc and BCL-2 oncogenes. Pretreatment with the protein kinase C stimulator phorbol myristate acetate enhanced mitoxantrone-induced internucleosomal DNA fragmentation, whereas protein kinase C inhibitors staurosporine and H7 had no effect. These findings suggest that PCD is a potential mechanism underlying the steep dose-response relationship of mitoxantrone to the inhibition of clonogenic survival of acute myeloid leukemia cells.
Annealing of CoFeB/MgO based single and double barrier magnetic tunnel junctions: Tunnel magnetoresistance, bias dependence, and output voltage (2009)

Co 40 Fe 40 B 20 / MgO single and double barrier magnetic tunnel junctions (MTJs) were grown using target-facing-target sputtering for MgO barriers and conventional dc magnetron sputtering for Co40Fe40B20 ferromagnetic electrodes. Large tunnel magnetoresistance (TMR) ratios, 230% for single barrier MTJs and 120% for the double barrier MTJs, were obtained after postdeposition annealing in a field of 800 mT. The lower TMR ratio for double barrier MTJs can be attributed to the amorphous nature of the middle Co40Fe40B20 free layer, which could not be crystallized during postannealing. A highly asymmetric bias voltage dependence of the TMR can be observed for both single and double barrier MTJs in the as-deposited states and after field annealing at low temperature. The asymmetry decreases with increasing annealing temperature and the bias dependence becomes almost symmetric after annealing at 350 °C. Maximum output voltages of 0.65 and 0.85 V were obtained for both single and double barrier MTJs, respectively, after annealing at 300 °C, a temperature which is high enough for large TMR ratios but insufficient to completely remove asymmetry from the TMR bias dependence.
Human Telomere Sequence DNA in Water-Free and High-Viscosity Solvents: G-Quadruplex Folding Governed by Kramers Rate Theory (2012)

Structures formed by human telomere sequence (HTS) DNA are of interest due to the implication of telomeres in the aging process and cancer. We present studies of HTS DNA folding in an anhydrous, high viscosity deep eutectic solvent (DES) comprised of choline choride and urea. In this solvent, the HTS DNA forms a G-quadruplex with the parallel-stranded ("propeller") fold, consistent with observations that reduced water activity favors the parallel fold, whereas alternative folds are favored at high water activity. Surprisingly, adoption of the parallel structure by HTS DNA in the DES, after thermal denaturation and quick cooling to room temperature, requires several months, as opposed to less than 2 min in an aqueous solution. This extended folding time in the DES is, in part, due to HTS DNA becoming kinetically trapped in a folded state that is apparently not accessed in lower viscosity solvents. A comparison of times required for the G-quadruplex to convert from its aqueous-preferred folded state to its parallel fold also reveals a dependence on solvent viscosity that is consistent with Kramers rate theory, which predicts that diffusion-controlled transitions will slow proportionally with solvent friction. These results provide an enhanced view of a G-quadruplex folding funnel and highlight the necessity to consider solvent viscosity in studies of G-quadruplex formation in vitro and in vivo. Additionally, the solvents and analyses presented here should prove valuable for understanding the folding of many other nucleic acids and potentially have applications in DNA-based nanotechnology where time-dependent structures are desired.
Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice (2003)

Recent experimental evidence shows that vaccination with amyloid-beta peptide (Abeta) of transgenic mouse models of Alzheimer's disease protects from the pathological accumulation of amyloid within the CNS. Phase I/II clinical trials of Abeta vaccination in mild to moderate Alzheimer's disease have been undertaken. Un expectedly, one of these trials has been suspended because 15 patients showed clinical signs consistent with CNS inflammation. Here, we show that C57BL/6 mice immunized with Abeta1-42 peptide develop an inflammatory disease of the CNS characterized by the presence both in the brain and spinal cord of perivenular inflammatory foci containing macrophages, T and B cells, and immunoglobulins. The experimental disease was observed only when pertussis toxin, an agent known to favour autoimmune processes, was co-administered. The immune-mediated CNS reaction was associated to Abeta-induced CD4(+) cells showing a Th1-type cytokine expression profile and to elevated levels of circulating anti-Abeta immunoglobulins. Our results indicate that vaccination with Abeta could determine, under certain circumstances, an aberrant autoimmune-type reaction to Abeta resulting in a perivenular inflammatory encephalomyelitis.
GradNorm: Gradient Normalization for Adaptive Loss Balancing in Deep Multitask Networks (2017)

Deep multitask networks, in which one neural network produces multiple predictive outputs, can offer better speed and performance than their single-task counterparts but are challenging to train properly. We present a gradient normalization (GradNorm) algorithm that automatically balances training in deep multitask models by dynamically tuning gradient magnitudes. We show that for various network architectures, for both regression and classification tasks, and on both synthetic and real datasets, GradNorm improves accuracy and reduces overfitting across multiple tasks when compared to single-task networks, static baselines, and other adaptive multitask loss balancing techniques. GradNorm also matches or surpasses the performance of exhaustive grid search methods, despite only involving a single asymmetry hyperparameter $α$. Thus, what was once a tedious search process that incurred exponentially more compute for each task added can now be accomplished within a few training runs, irrespective of the number of tasks. Ultimately, we will demonstrate that gradient manipulation affords us great control over the training dynamics of multitask networks and may be one of the keys to unlocking the potential of multitask learning.
Reprocessing and Recycling of Highly Cross-Linked Ion-Conducting Networks through Transalkylation Exchanges of C–N Bonds (2015)

Exploiting exchangeable covalent bonds as dynamic cross-links recently afforded a new class of polymer materials coined as vitrimers. These permanent networks are insoluble and infusible, but the network topology can be reshuffled at high temperatures, thus enabling glasslike plastic deformation and reprocessing without depolymerization. We disclose herein the development of functional and high-value ion-conducting vitrimers that take inspiration from poly(ionic liquid)s. Tunable networks with high ionic content are obtained by the solvent- and catalyst-free polyaddition of an α-azide-ω-alkyne monomer and simultaneous alkylation of the resulting poly(1,2,3-triazole)s with a series of difunctional cross-linking agents. Temperature-induced transalkylation exchanges of C-N bonds between 1,2,3-triazolium cross-links and halide-functionalized dangling chains enable recycling and reprocessing of these highly cross-linked permanent networks. They can also be recycled by depolymerization with specific solvents able to displace the transalkylation equilibrium, and they display a great potential for applications that require solid electrolytes with excellent mechanical performances and facile processing such as supercapacitors, batteries, fuel cells, and separation membranes.
Detecting Ransomware with Honeypot Techniques (2016)

Attacks of Ransomware are increasing, this form of malware bypasses many technical solutions by leveraging social engineering methods. This means established methods of perimeter defence need to be supplemented with additional systems. Honeypots are bogus computer resources deployed by network administrators to act as decoy computers and detect any illicit access. This study investigated whether a honeypot folder could be created and monitored for changes. The investigations determined a suitable method to detect changes to this area. This research investigated methods to implement a honeypot to detect ransomware activity, and selected two options, the File Screening service of the Microsoft File Server Resource Manager feature and EventSentry to manipulate the Windows Security logs. The research developed a staged response to attacks to the system along with thresholds when there were triggered. The research ascertained that witness tripwire files offer limited value as there is no way to influence the malware to access the area containing the monitored files.
A facile Huckel molecular orbital solution of Buckminsterfullerene using chemical graph theory (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA facile Huckel molecular orbital solution of Buckminsterfullerene using chemical graph theoryJerry Ray Dias Cite this: J. Chem. Educ. 1989, 66, 12, 1012Publication Date (Print):December 1, 1989Publication History Received3 August 2009Published online1 December 1989Published inissue 1 December 1989https://doi.org/10.1021/ed066p1012RIGHTS & PERMISSIONSArticle Views456Altmetric-Citations38LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
Protein-Directed Assembly of Arbitrary Three-Dimensional Nanoporous Silica Architectures (2011)

Through precise control of nanoscale building blocks, such as proteins and polyamines, silica condensing microorganisms are able to create intricate mineral structures displaying hierarchical features from nano- to millimeter-length scales. The creation of artificial structures of similar characteristics is facilitated through biomimetic approaches, for instance, by first creating a bioscaffold comprised of silica condensing moieties which, in turn, govern silica deposition into three-dimensional (3D) structures. In this work, we demonstrate a protein-directed approach to template silica into true arbitrary 3D architectures by employing cross-linked protein hydrogels to controllably direct silica condensation. Protein hydrogels are fabricated using multiphoton lithography, which enables user-defined control over template features in three dimensions. Silica deposition, under acidic conditions, proceeds throughout protein hydrogel templates via flocculation of silica nanoparticles by protein molecules, as indicated by dynamic light scattering (DLS) and time-dependent measurements of elastic modulus. Following silica deposition, the protein template can be removed using mild thermal processing yielding high surface area (625 m(2)/g) porous silica replicas that do not undergo significant volume change compared to the starting template. We demonstrate the capabilities of this approach to create bioinspired silica microstructures displaying hierarchical features over broad length scales and the infiltration/functionalization capabilities of the nanoporous silica matrix by laser printing a 3D gold image within a 3D silica matrix. This work provides a foundation to potentially understand and mimic biogenic silica condensation under the constraints of user-defined biotemplates and further should enable a wide range of complex inorganic architectures to be explored using silica transformational chemistries, for instance silica to silicon, as demonstrated herein.
Interferon and ribavirin versus interferon and amantadine in interferon nonresponders with chronic hepatitis C (2000)

OBJECTIVE: The aim of this study was to compare the potential efficacy and safety of a combination of interferon and ribavirin with that of interferon and amantadine in patients who had previously failed to respond to interferon monotherapy. METHODS: A total of 29 patients were randomized to 3 million units of α-interferon three times weekly with 1000 mg of ribavirin daily (group A, n = 14) or an identical dose of α-interferon and amantadine hydrochloride given in a dose of 200 mg daily (group B, n = 15). Patients were treated for 24 wk and observed for 24 wk posttreatment. RESULTS: The treatment groups were evenly matched with respect to gender, frequency of genotype 1, presence of fibrosis, as well as baseline alanine aminotransferase (ALT) and HCV RNA levels. At the end of therapy, five of 14 or 36% of patients in group A versus 0 of 15 in group B had both normal serum ALT and nondetectable HCV RNA by polymerase chain reaction (p = 0.017). A complete response was sustained, however, in only two of 13 patients (15%) in group A who completed 24 wk of observation posttreatment. CONCLUSIONS: A substantial proportion of interferon nonresponders have an end-of-treatment biochemical and virological response to a combination of interferon and ribavirin, and sustained responses are possible. The addition of amantadine to interferon, in contrast, does not seem to enhance the antiviral effectiveness of interferon in patients who have previously failed to respond.
Systemic chemotherapy for HIV-associated lymphoma in the era of highly active antiretroviral therapy (2000)

Treatment of AIDS-associated non-Hodgkin lymphoma poses a complex and multifaceted challenge for the physician. Treatment responses to cytotoxic chemotherapy are relatively poor, relapse rates are high, and AIDS progression continues to be a major concern in patients receiving dose-intensive antilymphoma therapy. The recent advances in anti-HIV therapy have not seen a clear counterpart in improved antilymphoma therapy, but trials are underway that may help move this field forward. For patients who achieve a complete and durable response to antilymphoma therapy, potent antiretroviral therapy may help improve the prognosis from AIDS progression. Major questions persist, however, on the role of chemotherapy dose intensity, the best use of antiretroviral therapy during the administration of lymphoma therapy, and the optimal design of studies that can address these questions.
Images on the Internet: enhanced user access (1994)

Practical tips on how to retrieve and view images, with a description of image file formats and the requirements for viewing and decompression software. Then, explore on your own with a list of sample resources available.