gebhart/patrepeval huggingface dataset:
Rapid desilylation of oligoribonucleotides at elevated temperatures: cleavage activity in ribozyme-substrate assays. (1995)

Treatment of 2'-O-silyl-oligoribonucleotides with triethylamine trihydrofluoride in DMF at 55 degrees C for 1 h effected complete desilylation. The product was isolated by a single addition of 1-butanol to the reaction mixture. The resulting RNA was found to be identical with that obtained by traditional desilylation methods as analyzed by HPLC, enzyme digest and ribozyme-substrate assays.
Application of Bivalent Bioisostere Concept on Design and Discovery of Potent Opioid Receptor Modulators (2019)

Here, we described the structural modification of previously identified μ opioid receptor (MOR) antagonist NAN, a 6α-<i>N</i>-7'-indolyl substituted naltrexamine derivative, and its 6β-<i>N</i>-2'-indolyl substituted analogue INTA by adopting the concept of "bivalent bioisostere". Three newly prepared opioid ligands, <b>25</b> (NBF), <b>31</b>, and <b>38</b>, were identified as potent MOR antagonists both in vitro and in vivo. Moreover, these three compounds significantly antagonized DAMGO-induced intracellular calcium flux and displayed varying degrees of inhibition on cAMP production. Furthermore, NBF produced much less significant withdrawal effects than naloxone in morphine-pelleted mice. Molecular modeling studies revealed that these bivalent bioisosteres may adopt similar binding modes in the MOR and the "address" portions of them may have negative or positive allosteric modulation effects on the function of their "message" portions compared with NAN and INTA. Collectively, our successful application of the "bivalent bioisostere concept" identified a promising lead to develop novel therapeutic agents toward opioid use disorder treatments.
268. Enhanced Gene Expression of Factor VIII by Ultrasound-Mediated Gene Delivery in Dogs (2015)

Previously we demonstrated that ultrasound (US)-mediated gene delivery (UMGD) can significantly enhance reporter gene transfer into the mouse and rat livers. This nonviral gene transfer strategy can bypass many obstacles encountered by viral gene therapy. Most significantly, we have achieved therapeutic levels of FVIII following UMGD into hemophilia A mice. Recently we have successfully developed prototype US systems including several unfocused and semi-focused transducers to treat large tissue volumes in canine and swine. In order to facilitate the translation of this technology to treat hemophilia, we have recently treated 2 normal dogs with UMGD of FVIII plasmids using an open surgery procedure. Four mg of a high-expressing, liver-specific pBS-HCRHPI-FVIIIA plasmid and 3 ml of Definity® MBs in 8 ml total PBS solution were injected via the segmental portal vein branch with simultaneous exposure of the target liver lobe to therapeutic US (1.1 MHz frequency, 20 cycle pulses, 50 Hz pulse repetition frequency) for 4 minutes using the large diameter transducers. A sham-treated dog received an equivalent pGL4/MB dose, but was not exposed to tUS. We used an apodized dual element unfocused transducer H105 at 2.5Mpa peak negative pressure (PNP) in the first dog experiment and observed low levels of hFVIII gene expression in the treated liver lobes. The second dog experiment was performed using a cylindrically 6.2 MPa at the focal area. One day following treatment, the treated liver lobes were sectioned, and representative sections were fixed and stained for FVIII expression by histochemical staining using a polyclonal anti-FVIII antibody. Untreated normal dog liver and human liver were used as negative and positive controls. Significant hFVIII gene expression was obtained in both treated liver lobes with the expression levels slightly lower than control human liver lobe. Furthermore, fairly homogeneous distribution of FVIII gene expression was observed in hepatocytes. Next, we performed Western blot analysis to confirm if the staining is specific to human FVIII protein. A heavy chain band specific to hFVIII was observed in treated dog plasma and positive hFVIII control, but not in control normal dog plasma and pre-bleed plasma sample from the dog before treatment. Significant enhancement of FVIII-specific clotting activity was also obtained in the second treated dog compared to pre-treatment and the first treated dog. In addition, transaminase levels and histology analysis indicated minimal tissue damage in treated dog livers. Enhancement of FVIII gene expression by UMGD is currently evaluated in hemophilia dogs. Our results sugges that UMGD has great potential for therapeutic treatment of hemophilia A.
On Polytopes with Linear Rank with respect to Generalizations of the Split Closure (2021)

In this paper we study the rank of polytopes contained in the 0-1 cube with respect to $t$-branch split cuts and $t$-dimensional lattice cuts for a fixed positive integer $t$. These inequalities are the same as split cuts when $t=1$ and generalize split cuts when $t &gt; 1$. For polytopes contained in the $n$-dimensional 0-1 cube, the work of Balas implies that the split rank can be at most $n$, and this bound is tight as Cornuéjols and Li gave an example with split rank $n$. All known examples with high split rank -- i.e., at least $cn$ for some positive constant $c &lt; 1$ -- are defined by exponentially many (as a function of $n$) linear inequalities. For any fixed integer $t &gt; 0$, we give a family of polytopes contained in $[0,1]^n$ for sufficiently large $n$ such that each polytope has empty integer hull, is defined by $O(n)$ inequalities, and has rank $Ω(n)$ with respect to $t$-dimensional lattice cuts. Therefore the split rank of these polytopes is $Ω(n)$. It was shown earlier that there exist generalized branch-and-bound proofs, with logarithmic depth, of the nonexistence of integer points in these polytopes. Therefore, our lower bound results on split rank show an exponential separation between the depth of branch-and-bound proofs and split rank.
Activation of endoplasmic reticulum stress response during the development of ischemic heart disease (2006)

Endoplasmic reticulum (ER) stress has been found to be associated with neurodegenerative diseases and diabetes mellitus. Whether ER stress is involved in the development of heart disease is not known. Cardiac-specific expression of monocyte chemoattractant protein-1 (MCP-1) in mice causes the development of ischemic heart disease. Here we report that microarray analysis of gene expression changes in the heart of these transgenic mice revealed that a cluster of ER stress-related genes was transcriptionally activated in the heart during the development of ischemic heart disease. The gene array results were verified by quantitative real-time PCR that showed highly elevated transcript levels of genes involved in unfolded protein response such as ER and cytoplasmic chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER-associated degradation system such as ubiquitin. Immunoblot analysis confirmed the expression of chaperones, PDI, and ubiquitin. Immunohistochemical analyses showed that ER stress proteins were associated mainly with the degenerating cardiomyocytes. A novel ubiquitin fold modifier (Ufm1) that has not been previously associated with ER stress and not found to be induced under any condition was also found to be upregulated in the hearts of MCP mice (transgenic mice that express MCP-1 specifically in the heart). The present results strongly suggest that activation of ER stress response is involved in the development of ischemic heart disease in this murine model.
Dietary fiber content influences soluble carbohydrate levels in ruminal fluids (2012)

The soluble carbohydrate concentration of ruminal fluid, as affected by dietary forage content (DFC) and/or ruminally undegradable intake protein content (UIPC), was determined. Four ruminally cannulated steers, in a 4 × 4 Latin square design, were offered diets containing high (75 % of DM) or low (25 % of DM) DFC and high (6 % of DM) or low (5 % of DM) UIPC, in a 2 × 2 factorial arrangement. Zinc-treated SBM was the primary UIP source. Soluble hexose concentration (145.1 μM) in ruminal fluid (RF) of steers fed low DFC diets exhibited a higher trend (P = 0.08) than that (124.5 μM) of steers fed high DFC diets. UIPC did not modulate (P = 0.54) ruminal soluble hexose concentrations. Regardless of diet, soluble hexose concentration declined immediately after feeding and did not rise until 3 h after feeding (P < 0.0001). Cellobiose (≈90 %) and glucose (≈10 %) were the major soluble hexoses present in RF. Maltose was not detected. Soluble glucose concentration (13.0 μM) was not modified by either UIPC (P = 0.40) nor DFC (P = 0.61). However, a DFC by post-prandial time interaction was detected (P = 0.02). Pentose concentrations were greater (P = 0.02) in RF of steers fed high DFC (100.2 μM) than steers fed low DFC (177.0 μM). UIPC did not influence (P = 0.35) soluble pentose concentration. The identity of soluble pentoses in ruminal fluid could not be determined. However, unsubstituted xylose and arabinose were excluded. These data indicate that: (i) soluble carbohydrate concentrations remain in ruminal fluid during digestion and fermentation; (ii) slight diurnal changes began after feeding; (iii) DFC influences the soluble carbohydrate concentration in RF; and (iv) UIPC of these diets does not affect the soluble carbohydrate concentration of RF.
New Findings in Security Printing and Imaging (2009)

In the past three NIP conferences, we have presented novel techniques for embedding security information into the variable data printing (VDP) for labels, documents and packaging. Recently, we have discovered that fundamental assumptions in other fields&#x2014;error correcting code (ECC), classification and the use of color, for three examples&#x2014;are not necessarily valid when functional security is the goal of the printing. It will be shown herein that the assumptions behind default ECC do not hold for 2D or color 2D barcodes with mobile image capture. Alternatives to ECC are suggested. When security-related tasks are the end goals of the printing and imaging, the deployment optimization for image classification is fundamentally altered. Tuning the classification engine to the security aim, rather than the image features as in traditional classification, provides significant improvement in both image throughput and classification accuracy for security-related tasks&#x2014;such as inspection, authentication and forensic imaging. It will, finally, be shown that there are significant new security approaches either only possible or else greatly enhanced by the printing of color, rather than grayscale or binary, images. These broad results indicate that applied research in security printing requires new basic research in the related image processing fields.
Generation of Long-Term T-Lymphoid Cell Lines With Specific Cytotoxic Reactivity for a Syngeneic Murine Lymphoma<xref ref-type="fn" rid="FN2">2</xref> (1982)

The long-term in vitro growth in T-cell growth factor (TCGF) of murine cytotoxic T-lymphoid cells directed against syngeneic tumor antigens was investigated. C57BL/6 mice were immunized to syngeneic FBL-3 lymphoma by two ip injections of irradiated FBL-3 lymphoma cells. Splenocytes from these animals were injected into mice with disseminated lethal FBL-3 tumor. The injection of cyclophosphamide (Cy) plus immunized lymphocytes significantly improved survival with cure of 53% of 38 animals. In comparison, treatment with Cy alone resulted in 0 of 31 cured and treatment with Cy plus unimmunized cells resulted in 0 of 40 cured (P less than 0.0005). These in vivo immunized lymphocytes were reexposed to FBL-3 tumor in vitro for 5 days in lectin-free TCGF (LF-TCGF). Although in vivo and in vitro sensitized lymphocytes exhibited no cytotoxicity toward fresh FBL-3 tumor cells in an 18-hour 51Cr release assay, expansion of appropriately sensitized cells in LF-TCGF resulted in significant lysis of fresh FBL-3 tumor cells. This significant lysis was specific and lysed syngeneic FBL-3 but not syngeneic MCA-103 fresh tumor targets. This maximal specific cytotoxicity was maintained for 2.5 months. A screening assay was developed that permitted rapid identification and isolation of low-frequency cytotoxic clones with reactivity specific for FBL-3 tumor. Several of these cloned cells were grown for almost 3 months with maintenance of high degrees of specific lysis (as much as 4,500 lytic U/10(6) cells). These cytotoxic lines and clones will be of value for the study of tumor-host immunologic interactions and perhaps for use in adoptive immunotherapy.
Tail asymptotics for processor-sharing queues (2004)

The basic queueing system considered in this paper is the M/G/1 processor-sharing queue with or without impatience and with finite or infinite capacity. Under some mild assumptions, a criterion for the validity of the reduced-service-rate approximation is established when service times are heavy tailed. This result is applied to various models based on M/G/1 processor-sharing queues.
ChemInform Abstract: Preparation of 7‐Alkyl‐2,3,6,7‐tetrahydro‐4‐alkyl‐2‐oxo‐1H‐1,3‐diazepine‐5‐carboxylates by Ring Expansion Nucleophilic Addition. (1986)

Abstract The reaction of the pyrimidine derivatives (I) with the Grignard reagents (II) proceeds under ring expansion and nucleophilic addition to yield the title compounds (III).
Verminderte Hydrophobizität der Darmmukosa bei Colitis ulcerosa im Vergleich zu M. Crohn und gesunden Kontrollen: Hinweis auf einen Barrieredefekt (2008)

Hintergrund: Es mehren sich die Hinweise, dass ein Defekt der mukosalen Barriere in der Ätiopathogenese chronisch entzündlicher Darmerkrankungen einen wichtigen Stellenwert einnimmt. Ziel der vorliegenden Arbeit war es, einen solchen Barrieredefekt sowohl bei Colitis ulcerosa als auch bei M. Crohn durch Bestimmung der Oberflächenhydrophobizität der Darmmukosa biophysikalisch zu definieren und zu quantifizieren.
Hydroxymethylnitrofurazone (NFOH) decreases parasitaemia, parasitism and tissue lesion caused by infection with the Bolivia Trypanosoma cruzi type I strain in Swiss and C57BL/6 mice (2022)

The chemical hydroxymethylation of the antimicrobial nitrofurazone leads to the prodrug NFOH, also increases the anti-T. cruzi activities (in vitro and in vivo), as well as showed non-genotoxic (Ames and micronucleus assays). In the present study, we assessed the anti-T. cruzi effect of the NFOH In vivo - in acute Swiss and C57Bl/6 experimental Chagas models. The treatment started at 5 days post-infection during 20 consecutive days (orally, once day, 150mg/kg), and the parasitaemia as well as histopathology analysis were performed. In both experimental murine models, NFOH was able to reduce parasitemia blood avoiding parasitic reactivation, during immunosuppression period (dexamethasone 5mg/kg, 14 days), in 100% of the mice, and decrease tissue parasite nests, demonstrating absence of amastigote forms in all organs (100%) analyzed, data similar to benznidazole (BZN). Therefore, the results shown here pointing to the NFOH as promising compound for further preclinical studies, being a high potential drug to effective and safe chemotherapy to Chagas disease.
Fast Microwave-Assisted Synthesis of Wells-Dawson-Type 18-Tungsto-2-Phosphate [P2W18O62]6− (2019)

We report on a fast microwave-assisted synthetic procedure of the Wells-Dawson-type 18-tungsto-2-phosphate [P2W18O62]6− with a 35% yield in 24 h, rather than a week using conventional heating.
Mechanically Robust, Rapidly Actuating, and Biologically Functionalized Macroporous Poly(N-isopropylacrylamide)/Silk Hybrid Hydrogels (2010)

A route toward mechanically robust, rapidly actuating, and biologically functionalized polymeric actuators using macroporous soft materials is described. The materials were prepared by combining silk protein and a synthetic polymer (poly(N-isopropylacrylamide) (PNIAPPm)) to form interpenetrating network materials and macroporous structures by freeze-drying, with hundreds of micrometer diameter pores and exploiting the features of both polymers related to dynamic materials and structures. The chemically cross-linked PNIPAAm networks provided stimuli-responsive features, while the silk interpenetrating network formed by inducing protein β-sheet crystallinity in situ for physical cross-links provided material robustness, improved expansion force, and enzymatic degradability. The macroporous hybrid hydrogels showed enhanced thermal-responsive properties in comparison to pure PNIPAAm hydrogels, nonporous silk/PNIPAAm hybrid hydrogels, and previously reported macroporous PNIPAAm hydrogels. These new systems reach near equilibrium sizes in shrunken/swollen states in less than 1 min, with the structural features providing improved actuation rates and stable oscillatory properties due to the macroporous transport and the mechanically robust silk network. Confocal images of the hydrated hydrogels around the lower critical solution temperature (LCST) revealed macropores that could be used to track changes in the real time morphology upon thermal stimulus. The material system transformed from a macroporous to a nonporous structure upon enzymatic degradation. To extend the utility of the system, an affinity platform for a switchable or tunable system was developed by immobilizing biotin and avidin on the macropore surfaces.
Isoforms of Atopic Allergens with Reduced Allergenicity but Conserved T Cell Antigenicity: Possible Use for Specific Immunotherapy (1997)

Based on these findings, we propose a new form of specific immunotherapy using hypoallergenic recombinant allergen isoforms.
Spectral Induced Polarization Measurements On Unsaturated, Unconsolidated Sediments (2002)

Understanding the Spectral Induced Polarization (SIP) response to saturation is required&lt;br&gt;to improve application of this geophysical technique in the vadose zone. SIP measurements (0.1-&lt;br&gt;1000 Hz) were conducted on three unconsolidated sediments during evaporative drying. Sample&lt;br&gt;grain size distribution was determined from laser particle size diffraction measurements. The&lt;br&gt;dependence of the real and imaginary conductivity components on frequency and degree of&lt;br&gt;saturation was determined. Both conductivity components exhibit an Archie-type power law&lt;br&gt;dependence on saturation. However, the imaginary conductivity is less dependent on saturation.&lt;br&gt;We find that, for each sample, the low frequency imaginary (surface) conductivity saturation&lt;br&gt;exponent is approximately about half the low frequency real (bulk) conductivity exponent. The&lt;br&gt;dependence of the imaginary conductivity exponent on frequency depends on sample type. For a&lt;br&gt;fine sample, the imaginary saturation exponent is effectively frequency independent. For a coarse&lt;br&gt;sample, the imaginary conductivity saturation dependence decreases above 10 Hz. This is&lt;br&gt;tentatively related to the difference in the size of polarizable pores within each sample.
Abstract 17680: Association of Lipid Accumulation Product with All-Cause, Cardiovascular or Ischemic Heart Disease Mortality: The National Health and Nutrition Examination Survey (2012)

Introduction: The lipid accumulation product (LAP) has been proposed as an alternative continuous index of lipid accumulation, but the predictive role of LAP on mortality has not been adequately studied. LAP is based on a combination of waist circumference (WC) in cm and serum triglyceride (TG) in SI units: [LAP = (WC − 65) × TG for men and (WC − 58) × TG for women]. Objective: We examined association between LAP and risk of all-cause, cardiovascular (CVD) and ischemic heart disease (IHD) mortality in a nationally representative cohort. Methods: Participants between ages 30 and 74 enrolled in the National Health and Nutrition Examination Survey (NHANES) III study from 1988 to 1994 had known CVD risk factors (age, sex, race, BMI, diabetes, hypertension, smoking history, triglycerides, history of CVD, family history of CVD and medication use) measured. All-cause, CVD and IHD mortality through 2006 were obtained via linkage with the National Death Index. Cox proportional hazards model was used to estimate ha...
On Discarding, Caching, and Recalling Samples in Active Learning (2012)

We address challenges of active learning under scarce informational resources in non-stationary environments. In real-world settings, data labeled and integrated into a predictive model may become invalid over time. However, the data can become informative again with switches in context and such changes may indicate unmodeled cyclic or other temporal dynamics. We explore principles for discarding, caching, and recalling labeled data points in active learning based on computations of value of information. We review key concepts and study the value of the methods via investigations of predictive performance and costs of acquiring data for simulated and real-world data sets.
A practical microgripper by fine alignment, eutectic bonding and SMA actuation (1995)

A silicon microgripper with a large gripping force, a relatively rigid structural body, and flexibility in functional design is presented. The actuation is generated by Ni-Ti-Cu shape memory alloy (SMA) films and the stress induced can deflect each side of the microgripper up to 55 {mu}m for a total gripping motion of 110 {mu}m. When fully open, the force exerted by the film corresponds to a 40 mN gripping force on the tip of the gripper.
Image representation and enhancement on elastic manifolds (2008)

Enhancing detail and contours of objects in low resolution noisy natural images is still one of the most outstanding challenges in image processing. This study is devoted to a new approach to adaptive image enhancement, based on the application of a damped elastic deformation process to single images. The proposed approach results in a Telegraph-Diffusion (TeD) denoising-and-sharpening filtering scheme which enhances fine details in images. Three efficient numerical schemes are presented. Advantages of the algorithm are discussed with reference to computational results.
Safety, immunogenicity, and tolerability of three influenza vaccines in older adults (2013)

To determine if newer influenza vaccines can safely improve seroprotection rates of older adults, we compared three licensed trivalent inactivated vaccines (TIVs) in a randomized, controlled trial with evaluator blinding. Participants were non-frail adults ≥ 65 y old, annually TIV-immunized. Study vaccines included intradermal (IDV), MF59-adjuvanted (ADV) and subunit (TIV) formulations of equal potency and strain composition. Blood was obtained before vaccination (V1) and 21 (V2) and 180 d (V3) afterward and tested by hemagglutination inhibition (HAI) assay. Safety diaries were completed daily by participants and specific tolerability questions were posed regarding injections and symptoms. In total, 911 participants were immunized and 887 (97.4%) completed V3. Groups had similar demographics. General symptom rates post-vaccination were similar among groups. Rates of injection site redness after IDV/ADV/TIV were 75%/13%/13% and rates of pain were 29%/38%/20%, respectively, but each vaccine was well tolerated, with symptoms causing little bother. Baseline antibody titers did not differ significantly among groups but B/Brisbane titers were too high for meaningful response assessments. At V2, seroprotection rates (HAI titer ≥ 40) were highest after ADV, the rate advantage over IDV and TIV being significant at 11.8% and 11.4% for H3N2 and 10.2% and 12.5% for H1N1, respectively. At day 180, seroprotection rates had declined ~25% and no longer differed significantly among groups. While IDV and TIV were also well tolerated, ADV induced modestly higher antibody titers in seniors to influenza A strains at 3 weeks but not 6 mo post-vaccination. Immune responses to IDV and TIV were similar in this population.
Preface of the “Symposium on multi-scale mathematical and numerical analysis of involution-constrained PDEs” (2015)

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