gebhart/patrepeval huggingface dataset:
Short Communication Molecular Cloning of a Chick Cochlea cDNA Encoding a Subunit of DNA Replication Factor C/Activator 1 (1994)

A chick cochlea cDNA library was constructed to clone molecules involved in peripheral auditory transduction and in the maintenance and regeneration of the sensory neuroepithelium following damage. Characterization of the library showed it to be of high complexity, to contain a high proportion of full-length cDNA inserts, and to contain a representative proportion of clones derived from hair cell transcripts. A cDNA clone encoding the chick homolog of the 40-kD subunit of the human replication factor C (also called activator 1) was isolated and the complete cDNA sequence determined. The predicted amino acid sequence is about 90% identical to that of the human homolog. Expression of the message for this replication factor was detected in brain and liver as well as in the cochlea. Expression levels in the brain are relatively high and are similar in developing and adult chicken nervous tissue. This suggests that replication factor C message expression, unlike that for the functionally associated factor proliferating cell nuclear antigen (PCNA), may be constitutive rather than cell cycle dependent. Although likely to be involved in DNA replication within the receptor neuroepithelium, expression of this replication factor message is not likely to constitute a marker for proliferation.
Presence of ED-A containing fibronectin in human articular cartilage from patients with osteoarthritis and rheumatoid arthritis. (1996)

EDA+Fn generally accumulates in the surface zone of OA cartilage, where it may play a role in extracellular matrix remodelling. Its presence was more abundant in SF and in cartilage from patients with RA.
Viral Vectors and Delivery Strategies for CNS Gene Therapy (2010)

This review aims to provide a broad overview of the targets, challenges and potential for gene therapy in the CNS, citing specific examples. There are a broad range of therapeutic targets, with very different requirements for a suitable viral vector. By utilizing different vector tropisms, novel routes of administration and engineered promoter control, transgenes can be targeted to specific therapeutic applications. Viral vectors have proven efficacious in preclinical models for several disease applications, spurring several clinical trials. While the field has pushed the limits of existing adeno-associated virus-based vectors, a next generation of vectors based on rational engineering of viral capsids should expand the application of gene therapy to be more effective in specific therapeutic applications.
Nucleophosmin (NPM1/B23) Interacts with Activating Transcription Factor 5 (ATF5) Protein and Promotes Proteasome- and Caspase-dependent ATF5 Degradation in Hepatocellular Carcinoma Cells (2012)

Nucleophosmin (NPM1/B23) and the activating transcription factor 5 (ATF5) are both known to subject to cell type-dependent regulation. NPM1 is expressed weakly in hepatocytes and highly expressed in hepatocellular carcinomas (HCC) with a clear correlation between enhanced NPM1 expression and increased tumor grading and poor prognosis, whereas in contrast, ATF5 is expressed abundantly in hepatocytes and down-regulated in HCC. Re-expression of ATF5 in HCC inhibits cell proliferation. We report here that using an unbiased approach, tandem affinity purification (TAP) followed with mass spectrometry (MS), we identified NPM1 as a novel ATF5-interacting protein. Unlike many other NPM1-interacting proteins that interact with the N-terminal oligomerization domain of NPM1, ATF5 binds via its basic leucine zipper to the C-terminal region of NPM1 where its nucleolar localization signal is located. NPM1 association with ATF5, whose staining patterns partially overlap in the nucleoli, promotes ATF5 protein degradation through proteasome-dependent and caspase-dependent pathways. NPM1-c, a mutant NPM1 that is defective in nucleolar localization, failed to stimulate ATF5 polyubiquitination and was unable to down-regulate ATF5. NPM1 interaction with ATF5 displaces HSP70, a known ATF5-interacting protein, from ATF5 protein complexes and antagonizes its role in stabilization of ATF5 protein. NPM1-promoted ATF5 down-regulation diminished ATF5-mediated repression of cAMP-responsive element-dependent gene transcription and abrogates ATF5-induced G(2)/M cell cycle blockade and inhibition of cell proliferation in HCC cells. Our study establishes a mechanistic link between elevated NPM1 expression and depressed ATF5 in HCC and suggests that regulation of ATF5 by NPM1 plays an important role in the proliferation and survival of HCC.
Highly conductive metal gate fill integration solution for extremely scaled RMG stack for 5 nm & beyond (2017)

This paper describes replacement-metal-gate (RMG) fill integration solutions with a cobalt-reflow process combined with a thin barrier layer for future node FinFET and gate-all-around technology. As CMOS scaling continues, the conventional tungsten CVD for RMG runs out of room to fill in a scaled gate trench. The lack of low resistivity W fill causes gate conductance degradation and negatively impacts CMOS performance. A unique Co-fill process combined with scaled barrier thickness is proposed as a new RMG solution. The Co fill significantly improves gate conductance at sub-15nm CD by seam-free gap fill and low resistivity, while achieving target threshold voltage.
Interim analysis of a phase II trial of 5-azacitidine (5AC) and entinostat (SNDX-275) in relapsed advanced lung cancer (NSCLC) (2009)

8055 Background: Epigenetic gene silencing mediated through aberrant DNA methylation and histone deacetylation is a key contributor to lung carcinogenesis. Pre-clinical studies suggest that combining inhibitors of DNA methyltransferase (DNMT) with inhibitors of histone deacetylase (HDAC) synergistically induce re-expression of epigenetically-silenced tumor suppressor genes. Clinical studies at our institution combining the DNMT inhibitor, 5AC, with the HDAC inhibitor, entinostat, in hematologic malignancies have shown remarkable clinical activity. We hypothesized a similar effect would be seen in lung cancer. This study aims to assess the response rate and time to progression of 5AC and entinostat in NSCLC. Methods: Patients (pts) include adults with histologically confirmed recurrent NSCLC and progressive disease after ≥1 prior chemotherapy regimen. 40 mg/m 2 of 5AC is administered SQ days 1–6 and 8–10 with 7 mg of entinostat PO days 3 and 10 of a 28 day cycle. A standard Simon two stage design is being used. The sample size is calculated with a power of 90% and a two-sided type 1 error allowance of 5%. Stage 1 included 18 pts, with subsequent expansion to a total of 32. Results: 25 pts have enrolled to date. Demographic characteristics include: mean age (range) - 63 (46- 80); M:F - 1:2; 80% former smokers; 80% adenocarcinomas; mean # of previous therapies - 3. One pt. has had a complete response. She remained on therapy for 14 m and came off therapy due to a new nodule which was resected. Molecular analysis suggests a second primary stage I NSCLC. She remains disease free at 20 m. Another man has stabilization of disease (SD) for ≥16 m with marked symptomatic improvement. Another pt had SD for 4 months. The remaining pts have progressed after 2 cycles of therapy. Main toxicities included injection site reactions, nausea/vomiting, constipation, fatigue, and hematologic toxicities. Conclusions: The combination of 5AC and entinostat is safe and well tolerated in advanced NSCLC pts. 2 pts have had durable benefit from treatment, including a complete response. Pharmacodynamic and pharmacokinetic analyses are being conducted to identify characteristics of the subset of pts responding to this novel therapy. [Table: see text]
Substituent effects on the turn-on kinetics of rhodamine-based fluorescent pH probes (2013)

Fluorescent turn-on probes based on a rhodamine spirolactam (RSL) structure have recently become a popular means of detecting pH, metal ions, and other analytes of interest. RSLs are colorless and non-fluorescent until the target analyte induces opening of the spirocyclic ring system, revealing the fully conjugated and highly fluorescent rhodamine dye. Among RSLs opened by acid, we have observed wide variation in the kinetics of the fluorescence turn-on process such that some probes would not be usable in situations where a rapid reading is desired or the pH fluctuates temporally. Herein we present a systematic investigation of the fluorescence turn-on kinetics of RSLs to probe the hypothesis that the reaction rates are influenced by the electronic properties of the spirolactam ring system. A series of 8 aniline-derived RSLs with para substituents ranging from electron-donating to electron-withdrawing was prepared from rhodamine B. The fluorescence turn-on rates are observed to increase by a factor of four as the substituent is tuned from methoxy to nitro. This effect is explained in terms of the destabilization of the reaction intermediate by the substituent. As the reaction rates increase across the series, a concomitant increase in fluorescence intensity is also observed. This result is attributed to an increase in the concentration of the fluorescent form of the dye and is consistent with the expected equilibrium properties of this system. These findings are applied to the design of a faster-reacting and more intensely fluorescent RSL pH probe.
THE EFFECT OF THE HEPTAPEPTIDE (2-8) AND HEXAPEPTIDE (3-8) FRAGMENTS OF ANGIOTENSIN II ON ALDOSTERONE SECRETION1 (1971)

The effect of local adrenal arterial infusion of the heptapeptide (2-8) and hexapeptide (3-8) fragments of angiotensin 11 on a aldosterone secretion was examined. The heptapeptide (2-8) resembled the octapeptide in activity and stimulated aldosterone whereas the hexapeptide (3-8) had no effect.
Darbepoetin alfa: a new approach to the treatment of chemotherapy-induced anaemia (2003)

Chemotherapy-induced anaemia has important consequences on the quality of life and social function of cancer patients. The finding of erythropoietin (EPO) deficiency in these patients led to the therapeutic development of erythropoietic proteins. Darbepoetin alfa (Aranesp), Amgen Inc, Thousand Oaks, California), a new erythropoietic growth factor, has eight more sialic acids than epoetin alfa. The increased sialic acid content confers a three-fold longer half-life and allows the drug to be administered less frequently than epoetin alfa. Darbepoetin alfa affects the same early haematopoietic cells as epoetin alfa and the endogenous hormone EPO. Preclinical pharmacokinetic studies suggest that the intrinsic pharmacological properties of darbepoetin alfa are comparable to those of epoetin alfa, but that the increased sialic acid content allows for less-frequent administration with superior performance. Darbepoetin alfa has been shown to have safe clinical efficacy in a variety of tumour settings and with several types of chemotherapy.
A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice. (1993)

The human apolipoprotein (apo) E and apoC-I genes are located 5 kilobases apart in the same transcriptional orientation on chromosome 19, and they are expressed at high levels in the liver with lower levels of expression in selected other tissues. Analysis of a series of overlapping human apoE and apoC-I genomic fragments in transgenic mice revealed that the expression of these transgenes in the liver requires a common cis-acting regulatory domain. This hepatic control region (HCR) was localized to a 764-base pair region that is located about 18 kilobases downstream of the apoE promoter and about 9 kilobases downstream of the apoC-I promoter. All the transgenic animals that had been prepared with a construct that contained this region had relatively high levels of transgene expression in the liver, whereas constructs that lacked this region showed no expression in the liver. In situ hybridization studies showed that the HCR directed apoE and apoC-I transgene expression in hepatocytes. When the HCR from the apoE/C-I gene locus was ligated proximal to a human apoA-IV gene fragment, which is not normally expressed in the liver, the resulting apoA-IV/HCR fusion construct was expressed at high levels in the liver, indicating that the HCR could direct high level liver expression of a heterologous promoter/gene construct. Expression of the apoE transgene in the liver and kidney, and perhaps other tissues, required the presence of a nonspecific proximal enhancer element in the apolipoprotein E gene promoter, located between 161 and 141 bp relative to the transcription initiation site. However, the proximal apoE gene promoter, including this enhancer element, contained no sequences capable of directing hepatocyte expression in the absence of the HCR. Thus, the far-downstream HCR appears to contain all of the sequences necessary for determining high level liver-specific gene expression.
P2X7 purinoceptor expression in Xenopus oocytes is not sufficient to produce a pore‐forming P2Z‐like phenotype (1997)

The purinergic rP2X7 receptor expressed in a number of heterologous systems not only functions as a cation channel but also gives rise to a P2Z‐like response, i.e. a reversible membrane permeabilization that allows the passage of molecules with molecular masses of ≥300 Da. We investigated the properties of rP2X7 receptors expressed in Xenopus oocytes. In two‐electrode voltage‐clamp experiments, ATP or BzATP caused inward currents that were abolished or greatly diminished when NMDG + or choline + replaced Na + as the principal external cation. In fluorescent dye experiments, BzATP application did not result in entry of the fluorophore YO‐PRO‐1 2+ . Thus, rP2X7 expression in Xenopus oocytes does not by itself give rise to the pore‐forming P2Z phenotype, suggesting that ancillary factors are involved.
Micropreconcentrator for Enhanced Trace Detection of Explosives and Chemical Agents (2006)

The design, fabrication, and testing of a sorbent-coated microfabricated preconcentrator device in complementary metal-oxide-semiconductor is presented. As a sorbent-coated device, the preconcentrator is used to collect, concentrate, and deliver analyte sampled from air for analysis with a detector. The preconcentrator in this paper is based on a perforated flowthrough microhotplate structure that is coated with a sorbent layer to maximize vapor trapping efficiency. The coating sorbs the analytes of interest during the collection phase at ambient temperatures. A thermal desorption cycle is then used to rapidly heat the preconcentrator to 180 degC in 40 ms to release a concentrated wave of analyte. A finite-volume method was used to simulate the temperature distribution on a microhotplate and to model the time to reach the steady-state temperature. The experimental electrical measurements of the device were found to be in good agreement with the predicted values obtained using the finite-volume method. The preconcentrator device was demonstrated by interfacing to the front end of a handheld chemical agent detector and a handheld trace explosives detector. The preliminary results showed signal enhancement for the detection of the nerve agent simulant dimethylmethylphosphonate and the explosive 2,4,6-trinitrotoluene
3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features. (1999)

Our findings evidence a strong correlation between 3q21q26 chromosomal aberrations, abnormalities of megakaryocytopoiesis and lack of response to conventional chemotherapy and support the diagnostic and prognostic relevance of chromosome characterization in the classification of AML.
An H7N1 Influenza Virus Vaccine Induces Broadly Reactive Antibody Responses against H7N9 in Humans (2014)

Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses--including H7--are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested the in vivo potency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improved in vivo virus clearance in a passive-transfer H7N9 challenge mouse model.
Replay by Re-execution (1994)

article Free Access Share on Replay by Re-execution: A Paradigm for Asynchronous Collaboration via Record and Replay of Interactive Multimedia Sessions Authors: Nelson R. Manohar University of Michigan at Ann Arbor University of Michigan at Ann ArborView Profile , Atul Prakash University of Michigan at Ann Arbor University of Michigan at Ann ArborView Profile Authors Info & Claims ACM SIGOIS BulletinVolume 15Issue 2Dec. 1994 pp 32–34https://doi.org/10.1145/192611.1023978Published:01 December 1994Publication History 8citation95DownloadsMetricsTotal Citations8Total Downloads95Last 12 Months9Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
[Reduction of the period of treatment for leg lengthening. Technique and advantages]. (2001)

Multiple-segment lengthening using an automatic lengthening procedure set at 1 mm per day in four times provides an important reduction in the treatment delays since distraction is performed more rapidly and fewer steps are needed. Automatic high-frequency lengthening with the Ilizarov method provides optimal conditions for tissue regeneration: Treatment periods are shorter and anatomic and functional outcome is very satisfactory. Stimulation by extemporaneous compression of the regeneration zone allows a significant reduction in the duration of consolidation. Shorter delays to consolidation help avoid device-related complications.
Modified ELTRAN&#x00AE; &#x2014; A game changer for Monolithic 3D (2015)

It is well recognized that dimensional scaling has reached its diminishing return phase and the industry is now looking to monolithic 3D to be the future technology driver. This was clearly voiced in the Qualcomm keynote at DAC 2014 and follow-on presentation at ISPD 2015. This paper will present a novel use of the ELTRAN® process developed by Canon Inc. about 20 years ago primarily for SOI applications. Using ELTRAN techniques, a substrate could be prepared enabling any fab to simply integrate a monolithic 3D device without the need to change the current frontline fab process. This flow is further simplified and could be integrated with the game changing monolithic 3D flow introduced last year which leverages the emerging precision bonders, such as EVG's Gemini® XT FB. This flow provides a natural path for product innovation and an unparalleled competitive edge. In addition, this game-changer breakthrough offers a very cost competitive flow.
The new melanoma staging system (2003)

The new melanoma staging system from The American Joint Committee on Cancer (AJCC) is described. This major revision includes new criteria for staging the primary tumor (T), metastatic nodes (N) and distant metastases (M) as well as stage groupings. These criteria more accurately reflect those prognostic features of the primary and metastatic melanoma that correlate with survival outcome. Physicians managing melanoma should use this staging system in their clinical practice and in the conduct of melanoma clinical trials.
Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC) (2017)

Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9. In HCT116 cells, it selectively degrades CDK9 while sparing other CDK family members. This is the first example of a PROTAC that selectively degrades CDK9.
Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats (2006)

Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non-nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO-A and MAO-B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO-A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO-B inhibitor; 4 mg/kg) and the beta-carboline norharmane hydrochloride (reversible MAO-B inhibitor; 5 mg/kg/day) treatments on nicotine self-administration (30 microg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed-ratio schedule (FR5) of reinforcement. When a progressive-ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO-A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta-carboline, may also play an important role in sustaining smoking behavior in humans.