gebhart/patrepeval huggingface dataset:
Bausteine von Oligosacchariden, LXXXVI. Glycosidierung mit Thioglycosiden von Oligosacchariden zu Segmenten von O‐Glycoproteinen (1988)

Abstract Thioglycoside von Mono‐, Di‐, Tri‐ und Tetrasacchariden, die 2‐Azido‐2‐desoxy‐ D ‐galactose als reduzierende Einheit enthalten, lassen sich bei Gegenwart von Dimethyl(methylthio)sulfoniumtriflat (DMTST) mit der Hydroxygruppe von selektiv blockierten Derivaten des L ‐Serins zu entsprechenden O‐Glycosiden umsetzen. In der Regel werden bevorzugt die α‐glycosidisch verknüpften Produkte gebildet. Auf diesem Wege wurde das Trisaccharid‐Glycosid 46 dargestellt, das die Core‐II‐Struktur der Mucine α‐glycosidisch gebunden an L ‐Serin darstellt. Methyltriflat ist als Promotor für die gleiche Thioglycosidierungsreaktion weniger effektiv als DMTST.
Analysis of quantitative PCR for the diagnosis of deletion and duplication carriers in the dystrophin gene. (1992)

A direct, non-radioactive method of quantitative PCR amplification has been investigated for the diagnosis of deletion and duplication carriers in the dystrophin gene. The simultaneous amplification of two loci, or several loci using multiplex PCR, allows for the direct comparison of relative amounts of products from normal homozygous loci and potentially heterozygous deleted/duplicated loci. Sufficient cycles of PCR are performed to enable visual analysis or densitometric quantification of products on ethidium bromide stained gels. The method has been verified in blind trials performed on known genotypes and by showing that under the conditions used the assay remains within the exponential phase of amplification.
Subject and Object Dependency Extraction Using Finite-State Transducers (1997)

We describe and evaluate an approach for fast automatic recognition and extraction of subject and object dependency relations from large French corpora, using a sequence of finite-state transducers. The extraction is performed in two major steps: incremental finite-state parsing and extraction of subject/verb and object/verb relations. Our incremental and cautious approach during the first phase allows the system to deal successfully with complex phenomena such as embeddings, coordination of VPs and NPs or non-standard word order. The extraction requires no subcategorisation information. It relies on POS information only. After describing the two steps, we give the results of an evaluation on various types of unrestricted corpora. Precision is around 90-97% for subjects (84-88% for objects) and recall around 86-92% for subjects (80-90% for objects). We also provide some error analysis; in particular, we evaluate the impact of POS tagging errors on subject/object dependency extraction.
Proton Relaxation Times in Paramagnetic Solutions. Effects of Electron Spin Relaxation (1961)

The proton relaxation time in solutions of paramagnetic ions depends, among other factors, on the relaxation time of the electron spins, τs. It is shown that the latter, for ions of the iron group, is determined mostly by the distortion of the hydrated complex by collisions with other water molecules. The theory provides a quantitative explanation for the decrease in T2 in Mn++ (and other) solutions in very high magnetic fields. The experimentally observed field and temperature dependence of the proton relaxation times, T1 and T2, for ions of the iron group is compared with theory and the features which depend on τs are stressed.
Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation (2016)

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m<sup>7</sup>GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N<sup>7</sup>-substituent of m<sup>7</sup>GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m<sup>7</sup>GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N<sup>7</sup>-methyl-guanosine (4a), N<sup>7</sup>-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N<sup>7</sup>-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents.
The Yorktown Simulation Engine: Introduction (1982)

The Yorktown Simulation Engine (YSE) is a special-purpose, highly-parallel programmable machine for the gate-level simulation of logic. It can simulate up to one million gates at a speed of over two billion gate simulations per second; it is estimated that the IBM 3081 processor could have been simulated on the YSE at a rate of 1000 instructions per second. This is far beyond the capabilities of existing register-level software simulators. The YSE has been designed and is being constructed at the IBM T. J. Watson Research Center. This paper introduces the YSE and describes its top-level architecture.
px+ipySuperfluid froms-Wave Interactions of Fermionic Cold Atoms (2008)

Two-dimensional (p(x)+ip(y)) superfluids or superconductors offer a playground for studying intriguing physics such as quantum teleportation, non-Abelian statistics, and topological quantum computation. Creating such a superfluid in cold fermionic atom optical traps using p-wave Feshbach resonance is turning out to be challenging. Here we propose a method to create a p(x)+ip(y) superfluid directly from an s-wave interaction making use of a topological Berry phase, which can be artificially generated. We discuss ways to detect the spontaneous Hall mass current, which acts as a diagnostic for the chiral p-wave superfluid.
Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma cells and myeloma (2007)

Defects in apoptosis mechanisms play important roles in malignancy and autoimmunity. Orphan nuclear receptor Nur77/TR3 has been demonstrated to bind antiapoptotic protein Bcl-2 and convert it from a cytoprotective to a cytodestructive protein, representing a phenotypic conversion mechanism. Of the 6 antiapoptotic human Bcl-2 family members, we found that Nur77/TR3 binds strongest to Bcl-B, showing selective reactivity with Bcl-B, Bcl-2, and Bfl-1 but not Bcl-X(L), Mcl-1, or Bcl-W. Nur77 converts the phenotype of Bcl-B from antiapoptotic to proapoptotic. Bcl-B is prominently expressed in plasma cells and multiple myeloma. Endogenous Bcl-B associates with endogenous Nur77 in RPMI 8226 myeloma cells, where RNA interference experiments demonstrated dependence on Bcl-B for Nur77-induced apoptosis. Furthermore, a Nur77-mimicking peptide killed RPMI 8226 myeloma cells through a Bcl-B-dependent mechanism. Because Bcl-B is abundantly expressed in plasma cells and some myelomas, these findings raise the possibility of exploiting the Nur77/Bcl-B mechanism for apoptosis for eradication of autoimmune plasma cells or myeloma.
Studies on the melanin affinity of selegiline (deprenyl) and other amphetamine derivatives. (1988)

The main aim of our study was to assess the melanin affinity of selegiline as well as the pharmacologic and pharmacokinetic aspects of its binding. The in vivo melanin binding of [14C] selegiline was studied by the method of whole body autoradiography. Extensive accumulation was observed in the pigmented mouse eye while in the albino animal uptake was low in the corresponding tissues. Our in vitro investigations demonstrated that the amphetamine derivatives tested can be taken up by melanins. Scatchard analysis of selegiline binding to the dopamine melanin (structurally similar to the neuromelanin) and beef eye melanin showed that more than one class of binding sites may be implicated. The total binding capacity of the beef-eye melanin was higher than that of the dopamine melanin. The selegiline inhibition of the [3H] MPP+ (the neurotoxic metabolite of MPTP) binding to dopamine melanin was also investigated. In the studied concentration range, the binding of [3H] MPP+ was depressed to about 70 per cent of the original maximum value. In conclusion, as a result of its melanin affinity, which is demonstrated in this study, selegiline may most probably accumulate in the pigmented nerve cells. The observed melanin affinity may contribute to the application of this compound for the treatment of Parkinson's disease or may play a role in its protective effect against MPTP neurotoxicity.
Glucocorticoid receptor up-regulation in early rheumatoid arthritis treated with low dose prednisone or placebo. (2003)

The GR number in the PBMC of early RA patients did not predict which patients would be prednisone responders based on clinical or radiological parameters. However, the up-regulation of the GR number in PBMC in early RA patients towards the GR number of healthy subjects during the first two years of their disease course seems to reflect a recovery or compensatory mechanism as a response to an ongoing inflammatory process. This recovery may be not enough to efficiently control the inflammatory situation.
Entdeckung und Nutzbarmachung von stillem Wissen in heterogenen Expertengemeinschaften – das Projekt AWAKE (Uncovering and Utilization of Tacit Knowledge in Heterogeneous Expert Communities) (2003)

Zusammenfassung In diesem Beitrag beschreiben wir die in dem AWAKE – Networked Awareness for Knowledge Discovery - Projekt entwickelten Ansätze, Lösungen und Prototypen zur empirischen Untersuchung der Frage, wie implizite Wissensstrukturen in unterschiedlichen Expertengemeinschaften entdeckt, visualisiert und für diese nutzbar gemacht werden können. Der Schwerpunkt liegt dabei auf dem entwickelten Modell sowie dem System zur Erstellung und kollaborativen Nutzung von personalisierten Wissenskarten und kollaborativen Begriffsnetzen. Zu den Anwendungsszenarien gehören die automatische Generierung von personalisierten Wissensportalen, kollaborative semantische Exploration von komplexen Informationsräumen und der Aufbau von gemeinschaftlichen Terminologienetzwerken in formalisierten Ontologien. Die entwickelten Prototypen verbinden automatische Textanalyse mit maschinellem Lernen und Nutzerschnittstellen zur Visualisierung von Kontexten und Beziehungen sowie zum Aufbau neuer Wissensstrukturen. Als Entwicklungskontext und empirische Testumgebung diente die Internetplattform netzspannung.org, ein Wissensportal das digitale Kunst, Kultur und Informationstechnologie verbindet.
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade (2016)

Blocking Programmed Death-1 (PD-1) can reinvigorate exhausted CD8 T cells (T<sub>EX</sub>) and improve control of chronic infections and cancer. However, whether blocking PD-1 can reprogram T<sub>EX</sub> into durable memory T cells (T<sub>MEM</sub>) is unclear. We found that reinvigoration of T<sub>EX</sub> in mice by PD-L1 blockade caused minimal memory development. After blockade, reinvigorated T<sub>EX</sub> became reexhausted if antigen concentration remained high and failed to become T<sub>MEM</sub> upon antigen clearance. T<sub>EX</sub> acquired an epigenetic profile distinct from that of effector T cells (T<sub>EFF</sub>) and T<sub>MEM</sub> cells that was minimally remodeled after PD-L1 blockade. This finding suggests that T<sub>EX</sub> are a distinct lineage of CD8 T cells. Nevertheless, PD-1 pathway blockade resulted in transcriptional rewiring and reengagement of effector circuitry in the T<sub>EX</sub> epigenetic landscape. These data indicate that epigenetic fate inflexibility may limit current immunotherapies.
Selective Roles of Retinoic Acid Receptor and Retinoid X Receptor in the Suppression of Apoptosis by All-trans-retinoic Acid (2001)

Retinoic acids exert profound effects on many biological processes including cell proliferation, differentiation, and morphogenesis. We previously reported that all-trans-retinoic acid (t-RA) protected mesangial cells from H(2)O(2)-triggered apoptosis by suppressing the activator protein 1 (AP-1) pathway. It was via inhibition of c-fos and c-jun expression and suppression of c-Jun N-terminal kinase (JNK) activation. In this report, we investigated the involvement of retinoic acid receptor (RAR) and retinoid X receptor (RXR) in the antiapoptotic effect of t-RA in H(2)O(2)-exposed cells. We found that pretreatment with RAR pan-antagonist (AGN193109) or RXR pan-antagonist (HX531) attenuated the antiapoptotic effect of t-RA. Similarly, transient transfection with a dominant-negative mutant of RAR or a dominant-negative RXR diminished the antiapoptotic effect of t-RA. Both RAR and RXR antagonists reversed the suppressive effect of t-RA on AP-1 activity. However, the roles of RAR and RXR in the suppression of AP-1 components by t-RA were found to be different. RAR antagonist reversed the suppressive effect of t-RA on both c-fos and c-jun, whereas RXR antagonist reversed the effect of t-RA on c-fos but not c-jun. Furthermore, suppression of JNK activation by t-RA was observed even in the presence of RAR and RXR antagonists. Consistently, suppression of JNK by t-RA was not affected by overexpression of either the dominant-negative RAR or the dominant-negative RXR. These data elucidated that the antiapoptotic effect of t-RA is mediated by both nuclear receptor-dependent and -independent mechanisms.
Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation (2011)

The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson's disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted.
Comparison of Prostatic Cancer Tissue Dihydrotestosterone Levels at the Time of Relapse Following Orchiectomy or Estrogen Therapy (1984)

Dihydrotestosterone concentrations have been measured in prostatic tissue from patients with recurrent advanced prostatic cancer after 1.0 to 5.0 mg. diethylstilbestrol per day or castration with or without estrogen therapy. Although medical or surgical castration usually leads to tissue dihydrotestosterone concentrations of less than 2.4 ng./gm. 2 of 20 surgically castrated and 4 of 9 estrogen-treated patients had values above this level. The difference between the number of patients with dihydrotestosterone levels greater than 2.4 ng./gm. in the surgical castrated and estrogen-treated groups was statistically significant by a chi-square test. These differences suggest that 1) increased tissue dihydrotestosterone levels in diethylstilbestrol-treated patients may be caused by inadequate dosage or decreased compliance, and 2) increased tissue dihydrotestosterone concentrations greater than 2.4 ng./gm. in castrated patients suggest an adrenocortical androgen contribution to the prostatic dihydrotestosterone level. Therefore, patients who are castrated or treated with diethylstilbestrol should have plasma testosterone and tissue dihydrotestosterone measurements at the time of relapse. If plasma and tissue dihydrotestosterone levels are at castrate levels (plasma levels less than 0.5 ng./ml. and tissue levels less than 2.4 ng./gm.) then further hormonal therapy is not indicated. Otherwise, adrenocortical suppression should be done if plasma testosterone is at castrate levels and tissue dihydrotestosterone is elevated. When plasma testosterone is above castrate levels titration with hormonal therapy should be done while plasma testosterone is monitored to achieve plasma testosterone levels below 0.5 ng./ml.
Encapsulation "The Future of Probiotics"-A Review (2009)

2 Abstract: In the recent past, there has been an explosion of probiotic health-based products. Many reports indicated that there is poor survival of probiotic bacteria in these products. Further, the survival of these bacteria in the human gastro-intestinal system is questionable. Providing probiotic living cells with a physical barrier against adverse environmental conditions is therefore an approach currently receiving considerable interest. The technology of microencapsulation of probiotic bacterial cells evolved from the immobilized cell culture technology used in the biotechnological industry. The use of encapsulated ingredients has increased markedly over the past few years. This increase has been the result of several factors, but the primary factor has been the increased awareness on the part of the food industry of the real advantages offered by encapsulated ingredients. Clearly, they do not offer a panacea for all the problems, but they do offer properties, which cannot be achieved by other routes and should be in the repertoire of those charged with the development of new and better products. Added convenience and reduced packaging costs may also be used to offset the cost of encapsulating one or more ingredients. Encapsulated forms of ingredients achieve longer shelf life of the product.
Contacting More of the Barnett Shale through an Integration of Real-Time Microseismic Monitoring, Petrophysics and Hydraulic Fracture Design (2007)

Abstract Horizontal wells represent a growing percentage of the rig count in unconventional gas wells in the United States. With effective stimulation techniques they have been shown to have favorable economics compared to vertical wells in the same reservoir. This is because of the large hydraulic fracture surface area that can be created from horizontal wells if effective stimulation techniques are employed. The Barnett Shale formation is the reservoir that has seen the largest growth using this technique in recent years. Estimated to extend over 54,000 square miles, the Barnett Shale formation displays different reservoir characteristics and properties in its different regions. The heterogeneous nature of this unconventional play makes standardization of the completion process problematic. One technology that has been used with increasing regularity to understand complex fracture geometry is microseismic (MS) fracture mapping1. Recent technology advances have made it possible for an onsite computer to process the thousands of seismic traces and deliver MS events hypocentral locations in a matter of seconds to a viewer in the fracturing treatment vehicle. Microseismic mapping used in conjunction with wellbore images and sonic logs has shed considerable light on the challenges faced in this reservoir. Massive water fracs are currently used to create complex hydraulic fracture networks. This stimulation technique, while successful, often leaves behind unstimulated sections of the reservoir. In order to achieve optimum horizontal well stimulation the lateral section must be characterized so that geologically different intervals can be identified and the proper stimulation technique employed. Technology has progressed to the point that microseismic monitoring of hydraulic fracture stimulation can efficiently provide extensive diagnostic information on fracture development and geometry in real-time. The case studies in this paper show how the use of real-time fracture mapping allows for on-the-fly changes in fracture design. Mapping also impacts the perforation strategy and restimulation designs to maximize the Effective Stimulation Volume (ESV). ESV is defined as the reservoir volume that has been effectively contacted by the stimulation treatment as determined by microseismic event locations and density. This paper further correlates MS activity to log data and illustrates how logs can be used to estimate fracture geometry. This data is then used to design a fit-for-purpose stimulation that has the greatest chance of maximizing the ESV and production.
Ca2+-dependent Antifreeze Proteins (1996)

The antifreeze proteins (AFPs) are structurally diverse molecules that share an ability to bind to ice crystals and inhibit their growth. The type II fish AFPs of Atlantic herring and smelt are unique among known AFPs in their requirement of a cofactor for antifreeze activity. These AFPs are homologous with the carbohydrate-recognition domains of Ca2+-dependent (C-type) lectins and require Ca2+ for their activity. To investigate the role of metal ions in the structure and function of type II AFPs, the binding of Ca2+ and other divalent cations to herring AFP was investigated. Binding studies using 45Ca2+ demonstrated that the AFP has a single Ca2+-binding site with a Kd of 9 microM. Proteolysis protection studies and measurement of antifreeze activity revealed a conformational change from a protease-sensitive and inactive apoAFP to a protease-resistant active AFP upon Ca2+ binding. Other divalent metal ions including Mn2+, Ba2+, and Zn2+ bind at the Ca2+-binding site and induce a similar change. A saturatable increase in tryptophan emission intensity at 340 nm also occurred upon Ca2+ addition. Whereas antifreeze activity appeared normal when Ca2+ or Mn2+ were bound, it was much lower in the presence of other metal ions. When Ba2+ was bound to the AFP, ice crystals showed a distinct difference in morphology. These studies demonstrate that herring AFP specifically binds Ca2+ and, consequently, adopts a conformation that is essential for its ice-binding activity.