gebhart/patrepeval huggingface dataset:
Glucokinase activation repairs defective bioenergetics of islets of Langerhans isolated from type 2 diabetics (2011)

It was reported previously that isolated human islets from individuals with type 2 diabetes mellitus (T2DM) show reduced glucose-stimulated insulin release. To assess the possibility that impaired bioenergetics may contribute to this defect, glucose-stimulated respiration (Vo(2)), glucose usage and oxidation, intracellular Ca(2+), and insulin secretion (IS) were measured in pancreatic islets isolated from three healthy and three type 2 diabetic organ donors. Isolated mouse and rat islets were studied for comparison. Islets were exposed to a "staircase" glucose stimulus, whereas IR and Vo(2) were measured. Vo(2) of human islets from normals and diabetics increased sigmoidally from equal baselines of 0.25 nmol/100 islets/min as a function of glucose concentration. Maximal Vo(2) of normal islets at 24 mM glucose was 0.40 ± 0.02 nmol·min(-1)·100 islets(-1), and the glucose S(0.5) was 4.39 ± 0.10 mM. The glucose stimulation of respiration of islets from diabetics was lower, V(max) of 0.32 ± 0.01 nmol·min(-1)·100 islets(-1), and the S(0.5) shifted to 5.43 ± 0.13 mM. Glucose-stimulated IS and the rise of intracellular Ca(2+) were also reduced in diabetic islets. A clinically effective glucokinase activator normalized the defective Vo(2), IR, and free calcium responses during glucose stimulation in islets from type 2 diabetics. The body of data shows that there is a clear relationship between the pancreatic islet energy (ATP) production rate and IS. This relationship was similar for normal human, mouse, and rat islets and the data for all species fitted a single sigmoidal curve. The shared threshold rate for IS was ∼13 pmol·min(-1)·islet(-1). Exendin-4, a GLP-1 analog, shifted the ATP production-IS curve to the left and greatly potentiated IS with an ATP production rate threshold of ∼10 pmol·min(-1)·islet(-1). Our data suggest that impaired β-cell bioenergetics resulting in greatly reduced ATP production is critical in the molecular pathogenesis of type 2 diabetes mellitus.
Processing and characterization of nanocrystalline materials (2004)

Thanks to Evrim Yakut for sacrificing so much for the neverending X-RD runs. Thanks to Hasan Demir for his creative practical solutions and expertise on xls. Thanks to Sedat Akkurt for his exactingness and understanding. Thanks to Muhsin Çiftçioğlu for his trust. Very special thanks to Devrim Balköse for the mental support in a hard day’s morning. Nanocrystalline materials with grain sizes under 100 nm have been counted as a very promising class of ceramic materials. The decrease in grain size imparts superior structural properties to the ceramic materials like increased fracture toughness, wear resistance and superplastic deformation at high temperatures. So, nanocrystalline ceramics can be used as structural materials in a wide range of uses covering advanced engineering applications such as aircraft and automotive technologies as well as electronics, computation and material sciences. Nanocrystalline alumina has been a popular research subject for the last decade because of the superior structural properties of alumina besides lower cost compared to
Targeting Gut T Cell Ca2+ Release-Activated Ca2+ Channels Inhibits T Cell Cytokine Production and T-Box Transcription Factor T-Bet in Inflammatory Bowel Disease (2009)

Prolonged Ca(2+) entry through Ca(2+) release-activated Ca(2+) (CRAC) channels is crucial in activating the Ca(2+)-sensitive transcription factor NFAT, which is responsible for directing T cell proliferation and cytokine gene expression. To establish whether targeting CRAC might counteract intestinal inflammation, we evaluated the in vitro effect of a selective CRAC inhibitor on T cell cytokine production and T-bet expression by lamina propria mononuclear cells (LPMC) and biopsy specimens from inflammatory bowel disease (IBD) patients. The inhibitory activity of the CRAC blocker was investigated through patch-clamp experiments on rat basophilic leukemia cells and fluorometric imaging plate reader intracellular Ca(2+) assays using thapsigargin-stimulated Jurkat T cells and its detailed selectivity profile defined using a range of in vitro radioligand binding and functional assays. Anti-CD3/CD28-stimulated LPMC and biopsy specimens from 51 patients with IBD were cultured with a range of CRAC inhibitor concentrations (0.01-10 microM). IFN-gamma, IL-2, IL-8, and IL-17 were analyzed by ELISA. T-bet was determined by immunoblotting. We found that the CRAC blocker concentration-dependently inhibited CRAC current in rat basophilic leukemia cells and thapsigargin-induced Ca(2+) influx in Jurkat T cells. A concentration-dependent reduction in T-bet expression and production of IFN-gamma, IL-2, IL-17, but not IL-8, was observed in IBD LPMC and biopsy specimens treated with the CRAC inhibitor. In conclusion, we provide evidence that the suppression of CRAC channel function may dampen the increased T cell response in the inflamed gut, thus suggesting a promising role for CRAC inhibitor drugs in the therapeutic management of patients with IBD.
CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells (2014)

Intracellular therapeutic targets that define tumor immunosuppression in both tumor cells and T cells remain intractable. Here, we have shown that administration of a covalently linked siRNA to an aptamer (apt) that selectively binds cytotoxic T lymphocyte-associated antigen 4 (CTLA4(apt)) allows gene silencing in exhausted CD8⁺ T cells and Tregs in tumors as well as CTLA4-expressing malignant T cells. CTLA4 expression was upregulated in CD8⁺ T cells in the tumor milieu; therefore, CTLA4(apt) fused to a STAT3-targeting siRNA (CTLA4(apt)-STAT3 siRNA) resulted in internalization into tumor-associated CD8⁺ T cells and silencing of STAT3, which activated tumor antigen-specific T cells in murine models. Both local and systemic administration of CTLA4(apt)-STAT3 siRNA dramatically reduced tumor-associated Tregs. Furthermore, CTLA4(apt)-STAT3 siRNA potently inhibited tumor growth and metastasis in various mouse tumor models. Importantly, CTLA4 expression is observed in T cells of patients with blood malignancies, and CTLA4(apt)-STAT3 siRNA treatment of immunodeficient mice bearing human T cell lymphomas promoted tumor cell apoptosis and tumor growth inhibition. These data demonstrate that a CTLA4(apt)-based siRNA delivery strategy allows gene silencing in both tumor-associated T cells and tumor cells and inhibits tumor growth and metastasis.
Systemic gene transfer reveals distinctive muscle transduction profile of tyrosine mutant AAV-1, -6, and -9 in neonatal dogs (2014)

The muscular dystrophies are a group of devastating genetic disorders that affect both skeletal and cardiac muscle. An effective gene therapy for these diseases requires bodywide muscle delivery. Tyrosine mutant adeno-associated virus (AAV) has been considered as a class of highly potent gene transfer vectors. Here, we tested the hypothesis that systemic delivery of tyrosine mutant AAV can result in bodywide muscle transduction in newborn dogs. Three tyrosine mutant AAV vectors (Y445F/Y731F AAV-1, Y445F AAV-6, and Y731F AAV-9) were evaluated. These vectors expressed the alkaline phosphatase reporter gene under transcriptional regulation of either the muscle-specific Spc5-12 promoter or the ubiquitous Rous sarcoma virus promoter. Robust skeletal and cardiac muscle transduction was achieved with Y445F/Y731F AAV-1. However, Y731F AAV-9 only transduced skeletal muscle. Surprisingly, Y445F AAV-6 resulted in minimal muscle transduction. Serological study suggests that the preexisting neutralization antibody may underlie the limited transduction of Y445F AAV-6. In summary, we have identified Y445F/Y731F AAV-1 as a potentially excellent systemic gene transfer vehicle to target both skeletal muscle and the heart in neonatal puppies. Our findings have important implications in exploring systemic neonatal gene therapy in canine models of muscular dystrophy.
Neurologic Complications of Cancer (2008)

Abstract This resource reviews the impact of cancer on the nervous system. It examines the diagnosis and management of neurological complications of specific types of cancer, as well as the side effects of oncological treatments.
Antioxidant role of human haptoglobin (2004)

Abstract Human plasma haptoglobin (Hp) is classified according to three phenotypes: Hp 1‐1, 2‐1, and 2‐2 attributed by their two common alleles 1 and 2. Clinically, the 2–2 phenotype is associated with the risk of cardiovascular diseases and diabetes mellitus in patients. In this study, we demonstrate that Hp is an extremely potent antioxidant, which directly protects low density lipoprotein from Cu 2+ ‐induced oxidation. Its potency was markedly superior to probucol (one of the most potent antioxidants). Ranking of the IC 50 of antioxidant activity was as follows: Hp 1‐1 ≳ Hp 2‐1 ≳ Hp 2‐2 ≳ probucol ≳ vitamin E. Blockage of disulfide linkages between Hp subunits, not only abolished the α‐helical content but also diminished the ability of Hp to form a complex with hemoglobin. The modified Hp subunits exerted almost 4 times greater antioxidant activity than that of native Hp. To investigate the antioxidant role of Hp on the cellular level, the cDNA of Hp 1‐1 was cloned, introduced into the pcDNA3.0 vector which contains the cytomega lovirus promoter and transfected into chinese hamster ovary (CHO)‐K1 cells. Following transfection, CHO cells were able to express Hp 1–1 protein and significantly ( p < 0.001) elevated cell tolerance against oxidative stress. Transfected cells showed 2‐fold higher resistance to hydrogen peroxide exposure for 24 h compared to control cells. Thus, Hp plays a provocative antioxidant role as demonstrated by our in vitro and ex vivo studies.
Enantioselective Synthesis of α‐Amino Acetals and α‐Amino Acids by Nucleophilic 1,2‐Addition to Diethoxyacetaldehyde SAMP Hydrazone (1993)

The nucleophilic 1,2-addition of organocerium compounds to α-SAMP/RAMP hydrazone acetals 1 is the basis of a new, highly enantioselective route to synthetically versatile α-amino acetals 2 and α-amino acids 3. R = Me, Et, nPr, iPr, nBu, tBu, Ph.
Simultaneous Up-regulation of Viral Receptor Expression and DNA Synthesis Is Required for Increasing Efficiency of Retroviral Hepatic Gene Transfer (1998)

To understand the relative contribution of viral receptor expression and cell proliferation in retroviral gene transfer, we created human hepatocyte-derived HuH-7.MCAT-1 cell lines. These cells constitutively express the murine ecotropic retroviral receptor MCAT-1 without changes in morphology or proliferation states. The MCAT-1 receptor is also a cationic amino acid transporter, and the HuH-7.MCAT-1.7 cells showed increased Vmax of uptake and steady-state accumulation of the cationic amino acids L-arginine and L-lysine. In HuH-7.MCAT-1 cells, L-arginine uptake was significantly up-regulated by norepinephrine and dexamethasone, and hepatocyte growth factor also increased L-arginine uptake along with cellular DNA synthesis. Gene transfer was also markedly increased in HuH-7. MCAT-1.7 cells incubated with an ecotropic LacZ retrovirus, and this further increased with hormones and hepatocyte growth factor. To define whether viral receptor up-regulation by itself increased gene transfer, cell cycling was inhibited by a recombinant adenovirus expressing the Mad transcription factor (AdMad), which is a dominant-negative c-Myc regulator. This restricted cells in G0/G1, without attenuating MCAT-1 activity, as shown by flow cytometry and L-arginine uptake analysis, respectively. When asynchronously cycling HuH-7.MCAT-1.7 cells were first infected with the AdMad virus and then exposed to the ecotropic LacZ virus, gene transfer was virtually abolished. The data indicate that while up-regulation of viral receptors can greatly enhance retrovirally mediated gene transfer, DNA synthesis remains an absolute requirement for hepatic gene therapy with this approach.
Algorithms for intersecting parametric and algebraic curves I (1994)

The problem of computing the intersection of parametric and algebraic curves arises in many applications of computer graphics and geometric and solid modeling. Previous algorithms are based on techniques from elimination theory or subdivision and iteration. The former is, however, restricted to low-degree curves. This is mainly due to issues of efficiency and numerical stability. In this article we use elimination theory and express the resultant of the equations of intersection as matrix determinant. The matrix itself rather than its symbolic determinant, a polynomial, is used as the representation. The problem of intersection is reduced to that of computing the eigenvalues and eigenvectors of a numeric matrix. The main advantage of this approach lies in its efficency and robustness . Moreover, the numerical accuracy of these operations is well understood. For almost all cases we are able to compute accurate answers in 64-bit IEEE floating-point arithmetic.
Airborne in‐situ OH and HO<sub>2</sub> observations in the cloud‐free troposphere and lower stratosphere during SUCCESS (1998)

The hydroxyl (OH) and hydroperoxyl (HO 2 ) radicals were measured for the first time throughout the troposphere and in the lower stratosphere with a new instrument aboard the NASA DC‐8 aircraft during the 1996 SUCCESS mission. Typically midday OH was 0.1‐0.5 pptv and HO 2 was 3‐15 pptv. Comparisons with a steady‐state model yield the following conclusions. First, even in the lower stratosphere OH was sensitive to the albedo of low clouds and distant high clouds. Second, although sometimes in agreement with models, observed OH and HO 2 were more than 4 times larger at other times. Evidence suggests that for the California upper troposphere on 10 May this discrepancy was due to unmeasured HO x sources from Asia. Third, observed HO 2 /OH had the expected inverse dependence with NO, but was inexplicably higher than modeled HO 2 /OH by an average of 30%. Finally, small‐scale, midday OH and HO 2 features were strongly linked to NO variations.
A Parallel Tempering algorithm for probabilistic sampling and multimodal optimization (2013)

Abstract Non-linear inverse problems in the geosciences often involve probabilistic sampling of multimodal density functions or global optimization and sometimes both. Efficient algorithmic tools for carrying out sampling or optimization in challenging cases are of major interest. Here results are presented of some numerical experiments with a technique, known as Parallel Tempering, which originated in the field of computational statistics but is finding increasing numbers of applications in fields ranging from Chemical Physics to Astronomy. To date, experience in use of Parallel Tempering within earth sciences problems is very limited. In this paper, we describe Parallel Tempering and compare it to related methods of Simulated Annealing and Simulated Tempering for optimization and sampling, respectively. A key feature of Parallel Tempering is that it satisfies the detailed balance condition required for convergence of Markov chain Monte Carlo (McMC) algorithms while improving the efficiency of probabilistic sampling. Numerical results are presented on use of Parallel Tempering for trans-dimensional inversion of synthetic seismic receiver functions and also the simultaneous fitting of multiple receiver functions using global optimization. These suggest that its use can significantly accelerate sampling algorithms and improve exploration of parameter space in optimization. Parallel Tempering is a meta-algorithm which may be used together with many existing McMC sampling and direct search optimization techniques. It's generality and demonstrated performance suggests that there is significant potential for applications to both sampling and optimization problems in the geosciences.
RNA−Protein Interactions in the Tat−<i>trans</i>-Activation Response Element Complex Determined by Site-Specific Photo-Cross-Linking (1998)

Transcriptional regulation in human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all HIV transcripts. We have used a site-specific cross-linking method based on 6-thioguanosine (6-thioG) photochemistry to determine the conformation of TAR RNA and its interaction with Tat protein under physiological conditions. Two different TAR RNA constructs with a single photoactive nucleoside (6-thioG) at position 21 or 26 were synthesized. Upon UV irradiation, 6-thioG at both positions formed interstrand covalent cross-links in TAR RNA. Determination of cross-link sites by RNA sequencing revealed that 6-thioG at position 21 contacts U42, while a 6-thioG at position 26 cross-links to C39. The addition of arginine did not alter the site of RNA-RNA cross-links; however, the yields of 6-thioG26-C39 cross-link were decreased. In the presence of a Tat fragment, Tat(38-72), UV irradiation of RNA modified with 6-thioG at position 21 resulted in RNA-protein cross-links but no RNA-RNA cross-links were observed. 6-thioG at position 26 formed both RNA-RNA and RNA-protein cross-links in the presence of Tat(38-72). Our results provide direct evidence that, during RNA-protein recognition, Tat is in close proximity to O6 of G21 and G26 in the major groove of TAR RNA.
Gas–liquid phase-transfer catalysis: Wittig–Horner reaction in heterogeneous conditions (1987)

The Wittig–Horner synthesis of alkenes has been carried out under gas–liquid phase-transfer catalysis (g.l.–p.t.c.) conditions. With this technique the carbonyl compound and the phosphonate flow, under pressure, through solid potassium carbonate contained in a thermostatted column where the conditions (temperature and pressure) are such as to ensure that the reactants are gaseous. The alkene so produced was cooled and collected at the column outlet. Reaction yields were higher when the solid potassium carbonate was coated with poly(ethylene glycol)–Carbowax 6000. The function of the poly(ethylene glycol) is discussed. Aromatic aldehydes react successfully with triethyl phosphonoacetate and diethyl (cyanomethyl)phosphonate; ketones react only with diethyl (cyanomethyl)phosphonate. Reaction conversions (based on the purity of the recovered alkene) are always high, while yields (measured on the basis of the actual amount of pure alkene recovered, with respect to the reacting carbonyl compound) are lower.
A modular system for ion exchange waste water treatment and recycling in the electroplating industry (1988)

SummaryRecent developments in plant design and in ion exchange resins have produced modern ion exchange systems which are reliable, efficient, economic and simple to operate. For water purification and recovery a mixture of cation exchange resins (usually containing a sulphonic acid, carboxylic acid or phosphonic acid group) and an anionic exchange resin (usually containing a quaternary ammonium, secondary amine, or tertiary amine active group) is employed. The skeletal structure of the resin used, although inactive with respect to the ion exchange behaviour, determines the life and stability of the resin in actual use.
Attention Enhances the Retrieval and Stability of Visuospatial and Olfactory Representations in the Dorsal Hippocampus (2009)

A key question in the analysis of hippocampal memory relates to how attention modulates the encoding and long-term retrieval of spatial and nonspatial representations in this region. To address this question, we recorded from single cells over a period of 5 days in the CA1 region of the dorsal hippocampus while mice acquired one of two goal-oriented tasks. These tasks required the animals to find a hidden food reward by attending to either the visuospatial environment or a particular odor presented in shifting spatial locations. Attention to the visuospatial environment increased the stability of visuospatial representations and phase locking to gamma oscillations--a form of neuronal synchronization thought to underlie the attentional mechanism necessary for processing task-relevant information. Attention to a spatially shifting olfactory cue compromised the stability of place fields and increased the stability of reward-associated odor representations, which were most consistently retrieved during periods of sniffing and digging when animals were restricted to the cup locations. Together, these results suggest that attention selectively modulates the encoding and retrieval of hippocampal representations by enhancing physiological responses to task-relevant information.
T1 Maps by K-Space Reduced Snapshot-FLASH MRI (1992)

The T1 maps evaluated from k-space reduced Snapshot fast low angle shot (FLASH) images provide high contrast parameter images for tissue characterization in vivo of any body region. An algorithm for computing T1 values that allows a fast and reliable evaluation of T1 maps and yields reproducible values of tissue parameters in MR imaging is presented. The algorithm combined with the Snapshot FLASH inversion recovery imaging sequence permits a precise determination of T1 values, even for T1 times as low as 50 ms. Comparison with a spectroscopical inversion recovery method on identical phantoms demonstrates the accuracy of this technique. With its total acquisition time of approximately 2 s, IR Snapshot FLASH is fast enough to be used in monitoring fast T1 dynamics.
Coordinated fractional frequency reuse (2007)

In recent years, Orthogonal Frequency Division Multiple Access (OFDMA) has become an attractive transmission technology, which is part of various emerging system standards for broadband cellular communications. Examples include the 3GPP Long Term Evolution (LTE) and 802.16e WiMAX. In OFDMA, mobile terminals are multiplexed in time and frequency. A major problem in these systems is the inter-cell interference, which is caused by neighboring cells when transmitting on the same time and frequency slots. This problem can be solved by using beamforming antennas and coordinating the transmissions among base stations. This is known as interference coordination. In this paper, we present a distributed algorithm for interference coordination, which enhances the cell edge performance with global information provided by a central coordinator. The signaling delay during the communication with the central coordinator can be on the order of seconds, while an additional local interference coordination in each base station ensures a high performance even in dynamic environments. This combination of global and local coordination enhances the overall spectral efficiency by 50% compared to a Reuse 3 system while maintaining the same cell edge performance.