gebhart/patrepeval huggingface dataset:
The <i>Polycomb</i>-Group Gene<i>Ezh2</i> Is Required for Early Mouse Development (2001)

Polycomb-group (Pc-G) genes are required for the stable repression of the homeotic selector genes and other developmentally regulated genes, presumably through the modulation of chromatin domains. Among the Drosophila Pc-G genes, Enhancer of zeste [E(z)] merits special consideration since it represents one of the Pc-G genes most conserved through evolution. In addition, the E(Z) protein family contains the SET domain, which has recently been linked with histone methyltransferase (HMTase) activity. Although E(Z)-related proteins have not (yet) been directly associated with HMTase activity, mammalian Ezh2 is a member of a histone deacetylase complex. To investigate its in vivo function, we generated mice deficient for Ezh2. The Ezh2 null mutation results in lethality at early stages of mouse development. Ezh2 mutant mice either cease developing after implantation or initiate but fail to complete gastrulation. Moreover, Ezh2-deficient blastocysts display an impaired potential for outgrowth, preventing the establishment of Ezh2-null embryonic stem cells. Interestingly, Ezh2 is up-regulated upon fertilization and remains highly expressed at the preimplantation stages of mouse development. Together, these data suggest an essential role for Ezh2 during early mouse development and genetically link Ezh2 with eed and YY1, the only other early-acting Pc-G genes.
A Collagen-based Scaffold Delivering Exogenous MicroRNA-29B to Modulate Extracellular Matrix Remodeling (2014)

Directing appropriate extracellular matrix remodeling is a key aim of regenerative medicine strategies. Thus, antifibrotic interfering RNA (RNAi) therapy with exogenous microRNA (miR)-29B was proposed as a method to modulate extracellular matrix remodeling following cutaneous injury. It was hypothesized that delivery of miR-29B from a collagen scaffold will efficiently modulate the extracellular matrix remodeling response and reduce maladaptive remodeling such as aggressive deposition of collagen type I after injury. The release of RNA from the scaffold was assessed and its ability to silence collagen type I and collagen type III expression was evaluated in vitro. When primary fibroblasts were cultured with scaffolds doped with miR-29B, reduced levels of collagen type I and collagen type III mRNA expression were observed for up to 2 weeks of culture. When the scaffolds were applied to full thickness wounds in vivo, reduced wound contraction, improved collagen type III/I ratios and a significantly higher matrix metalloproteinase (MMP)-8: tissue inhibitor of metalloproteinase (TIMP)-1 ratio were detected when the scaffolds were functionalized with miR-29B. Furthermore, these effects were significantly influenced by the dose of miR-29B in the collagen scaffold (0.5 versus 5 μg). This study shows a potential of combining exogenous miRs with collagen scaffolds to improve extracellular matrix remodeling following injury.
Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma (2020)

Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against B-cell malignancies, yet marked vulnerability to antigen escape and tumor relapse exists. Here we report the rational design and optimization of bispecific CAR-T cells with robust activity against heterogeneous multiple myeloma (MM) that is resistant to conventional CAR-T cell therapy targeting B-cell maturation antigen (BCMA). We demonstrate that BCMA/CS1 bispecific CAR-T cells exhibit superior CAR expression and function compared to T cells that co-express individual BCMA and CS1 CARs. Combination therapy with anti-PD-1 antibody further accelerates the rate of initial tumor clearance in vivo, while CAR-T cell treatment alone achieves durable tumor-free survival even upon tumor re-challenge. Taken together, the BCMA/CS1 bispecific CAR presents a promising treatment approach to prevent antigen escape in CAR-T cell therapy against MM, and the vertically integrated optimization process can be used to develop robust cell-based therapy against novel disease targets.
Asphalt Oxidation Mechanisms and the Role of Oxidation Products on Age Hardening Revisited (2011)

ABSTRACT The correlation between asphalt viscosity increase on oxidative aging and the carbonyl compounds formed (almost exclusively ketones) has been well established; however, the effect of sulfoxide formation on physical properties during age hardening has received little attention. Evidence is presented in this paper that shows that the alcohols, which are formed concurrently with the sulfoxides from the same hydroperoxide precursors as the ketones, have a similar effect on asphalt viscosity increase as does the ketones. These alcohols are the main contributors to oxidative age hardening of high sulfur asphalts. Analysis of the kinetic data for ketone and sulfoxide formation during asphalt oxidation also provides additional evidence for the validity of the dual asphalt oxidation mechanism previously reported.
Vascular endothelial growth factor, soluble fms‐like tyrosine kinase 1 and genistein‐induced changes in the vascular reactivity of rat's aorta (2014)

The results suggest that genistein may help overcome the vasospasm in PE. It may be a promising therapeutic approach to PE.
Analyzing the properties of smoothing methods for language models (2002)

The authors discuss the properties of several frequent smoothing methods for language models. Because of the data sparseness problem, smoothing methods are employed to estimate the probability for each n-gram (including all the seen and unseen events). There are several well-known smoothing methods: Additive discount, Good-Turing, Witten-Bell, Katz and Absolute discount. We propose a set of properties to evaluate the statistical behaviors of these methods. Furthermore, a smoothing scheme, Huang-Yu method, is presented, which complies with all the proposed properties.
Surface-Enhanced Raman Spectroscopy: A New Modality for Cancer Imaging (2015)

Although surface-enhanced Raman scattering (SERS) spectroscopy has traditionally been used as an in vitro analytic tool, in the past few years the first reports of the feasibility of in vivo imaging of cancer with biocompatible SERS probes have emerged. SERS imaging has great potential in the field of medical imaging because it offers several major advantages over other molecular imaging methods. Medical imaging using SERS nanoprobes can yield higher sensitivity and higher signal specificity than other imaging modalities, while also offering multiplexing capabilities that allow for unique applications. This article reviews the principles of SERS and highlights recent advances for in vivo cancer imaging. To present the abilities of this method as accurately as possible, the discussion is limited to studies in which the imaging data were confirmed by histological correlation.
Prevalence and Abundance of Latently Transcribed Varicella-Zoster Virus Genes in Human Ganglia (2006)

In human ganglia latently infected with varicella-zoster virus (VZV), sequence analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66) are transcribed. However, their comparative prevalence and abundance are unknown. Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for RNA corresponding to the five virus genes known to be transcribed in latently infected human ganglia. The most prevalent transcript found was VZV gene 63 (78%), followed by gene 66 (43%), gene 62 (36%), and gene 29 (21%). No gene 21 transcripts were detected in any of the 28 ganglia. VZV gene 63 RNA was also the most abundant (3,710 +/- 6,895 copies per 1 microg of mRNA) transcript detected in latently infected human ganglia, followed by VZV gene 29 (491 +/- 594), VZV gene 66 (117 +/- 85), and VZV gene 62 (64 +/- 38). Thus, the repeated detection and high abundance of VZV gene 63 transcripts in latently infected ganglia suggests that VZV gene 63 may be more important for the maintenance of virus latency than the less abundantly transcribed and randomly detected VZV genes 21, 29, 62, and 66.
Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene (1993)

The TSH receptor (TSHr) is one of the most important thyroid differentiation markers. The binding of the TSH hormone to its receptor is an essential step in the modulation of thyroid function and differentiation. Here we report that the thyroid transcription factor 1 (TTF1), a transcription factor essential for thyroid-specific gene expression, binds to the TSHr minimal promoter. The promoter, when mutated at this binding site, shows a decreased activity in thyroid cells. In cotransfection experiments in nonthyroid cells, TTF1 is able to trans-activate the TSHr minimal promoter. This finding strengthens the importance of TTF1 in the maintenance of thyroid differentiation. The promoters of the main thyroid differentiation markers thyroglobulin, thyroperoxidase, and now TSHr, are regulated by TTF1
Operating room noise at Johns Hopkins Hospital (2006)

Very little reliable information exists on the sound levels present in an operating room environment. In an attempt to remedy this situation, rigorous acoustic testing of the operating rooms in Johns Hopkins Hospital was conducted. Sound levels in each of the operating rooms was recorded for a period of 24 h. The data were analyzed to determine background sound levels, average equivalent sound levels (Leq’s), and frequency distribution. With the assistance of Johns Hopkins Hospital, we were able to match each surgery to the period of noise it produced and to associate sound levels with particular types of surgeries. This data was used to determine the average sound-pressure level for classes of surgery (e.g., orthopedic, neurological, etc.). Averaging over many surgeries, orthopedic surgery was found to have the highest Leq at approximately 66 dB(A). Urology, cardiology, gastrointestinal, and neurosurgery followed closely, ranging from 62 to 65 dB(A).
Conduit and cable installation for a centralized network with logical star-star topology (1995)

Addresses a comprehensive design issue of a centralized communication network with logical star-star topology: each established hub is connected to the center node via its own cable route which may pass through a number of sites, and so is the connection from a user to its destination hub. The study distinguishes itself from other network design studies in the literature by explicitly addressing the reality that the cable can be installed only in the conduit, and some hub devices such as line concentrators and multiplexers, if properly installed, would provide more economical cable paths. A cost minimization model is first made to cover three types of decisions in one setting: locating hubs, placing conduit system, and installing cable therein. It is then formulated as a variant of classical network design model, allowing the incorporation of the well-known dual-ascent solution strategy. Despite the complexity inherent to the design problem, the performance of the proposed solution heuristic is shown via the extensive computational experiments with large-scale test problems to be very satisfactory in both speed and quality of the solutions generated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
3.2 GHz 6.4 Gb/s per wire signaling in 0.18 μm CMOS (2002)

Simultaneous bidirectional signaling provides 6.4 Gb/s/wire with random data on a 22 b point-to-point bus over 15 cm on a PCB. The signaling rate decreases to 2.4 Gb/s/wire over 122 cm through 2 connectors. The I/O circuits have closed-loop slew rate control and are part of a 6.6 M transistor router component that consumes 21 W, packaged in a 31/spl times/31 mm/sup 2/ OLGA substrate.
Regulation of alternative splicing by short non-coding nuclear RNAs (2010)

Recent results from deep-sequencing and tiling array studies indicated the existence of a large number of short, metabolically stable, non-coding RNAs. Some of these short RNAs derive from known RNA classes like snoRNA or tRNAs. There are intriguing similarities between short non-coding nuclear RNAs and oligonucleotides used to change alternative splicing events, which usually target a disease-relevant RNA. We review the current knowledge of this emerging class of RNAs and discuss evidence that some of these short RNAs could function in alternative splice site selection.
Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory. (1991)

We have examined secretory antibody and cell-mediated immune responses to oral cholera vaccine in the human gastrointestinal mucosa. Freshly isolated peripheral blood lymphocytes and intestinal lymphocytes obtained by enzymatic dispersion of duodenal biopsies were assayed for numbers of total and vaccine specific immunoglobulin-secreting cells by enzyme-linked immunospot assay (ELISPOT) techniques; the frequency of cells secreting interferon-gamma (IFN-gamma) was also examined by a new modification of the ELISPOT technique. After booster immunizations with oral cholera vaccine, large numbers of cholera toxin-specific antibody-secreting cells (ASC) appeared in the small intestine. The responses were dominated by IgA ASC. A single immunization, performed 5 mo after the initial vaccinations, gave rise to an ASC response similar to that seen after the first booster immunization, with respect to both magnitude and isotype distribution. Each of the immunizations also evoked an ASC response in blood which was of lower magnitude than that seen in the small intestine, and comprised similar proportions of IgA and IgG ASC. A booster immunization also resulted in increased frequencies of IFN-gamma-secreting cells, but this increase was confined to the duodenal mucosa. This study establishes the feasibility of studying, at the single-cell level, intestinal immune reactivity in humans. Furthermore, it indicates that the small intestinal mucosa is an enriched source of IFN-gamma. It also demonstrates marked differences between intestinal and peripheral blood immune responses after enteric immunization, and confirms the notion that the mucosal immune system in humans displays immunological memory.
Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats (2018)

The aim of this work was to prepare and optimize a solid self-nanoemulsifying drug delivery system pre-concentrate (SSP) containing water-insoluble flurbiprofen (FL) using a novel pseudo-ternary phase diagram. The pseudo-ternary phase diagram, composed of FL as the drug and dispersion core, Kollisolv MCT 70 as the oil phase, and TPGS (tocopherol polyethylene glycol 1000 succinate) as the surfactant, was constructed for the determination of the SSP region. SSP was investigated in terms of particle size, physical state by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), in vitro dissolution and oral pharmacokinetics in rats. The determined SSP (FL/Kollisolv MCT 70/TPGS = 10/10/80, weight %) in the pseudo-ternary phase diagram had the melting point of 32.37 °C and uniform mean particle size of below 30 nm without any precipitation of FL in the dispersion. In the dissolution test, the SSP exhibited 95.70 ± 3.40% of release at 15 min, whereas the raw FL showed poor dissolution (i.e., 6.75 ± 1.30%) at that time point. In addition, the SSP showed the enhanced oral absorption (i.e., 1.93-fold increase in AUCinfinite) as compared to the suspension group of raw FL. Therefore, the developed SSP would be a promising drug delivery system with excellent solubilization, dissolution, and bioavailability for FL.
Performance of raw and regenerated multi- and single-walled carbon nanotubes in xylene removal from aqueous solutions (2012)

Aims: The ability of raw and recycled multi- and single-walled carbon nanotubes (MWCNT and SWCNT) for xylene adsorption from aqueous solutions was evaluated. Materials and Methods: Batch adsorption experiments were conducted in 110 ml glass bottles. Gas chromatography-mass spectrometry was used for xylene measurement and the carbon nanotube characteristics were evaluated with the help of a transmission electron microscope. Results: With a carbon nanotube dose of 1 g/l, xylene concentration of 10 mg/l, pH 7, and a contact time of 10 minutes, the equilibrium adsorption capacity (q e (mg/g)) of SWCNT was 9.2 mg/g, which was higher than that for MWCNT (8.9 mg/g). The SWCNT revealed a better performance for xylene sorption than the MWCNT. Results of a desorption study showed that xylene adsorbed onto the SWCNT and MWCNT can be easily desorbed at 105 ± 2°C.Conclusions: It is concluded that recycled carbon nanotubes on heating for the first time, show a better performance for xylene adsorption than when they are raw. The SWCNT are efficient as xylene adsorbents in an environmental pollution cleanup.
<i>Chlamydia</i> co‐opts the rod shape‐determining proteins MreB and Pbp2 for cell division (2012)

Chlamydiae are obligate intracellular bacterial pathogens that have extensively reduced their genome in adapting to the intracellular environment. The chlamydial genome contains only three annotated cell division genes and lacks ftsZ. How this obligate intracellular pathogen divides is uncharacterized. Chlamydiae contain two high-molecular-weight (HMW) penicillin binding proteins (Pbp) implicated in peptidoglycan synthesis, Pbp2 and Pbp3/FtsI. We show here, using HMW Pbp-specific penicillin derivatives, that both Pbp2 and Pbp3 are essential for chlamydial cell division. Ultrastructural analyses of antibiotic-treated cultures revealed distinct phenotypes: Pbp2 inhibition induced internal cell bodies within a single outer membrane whereas Pbp3 inhibition induced elongated phenotypes with little internal division. Each HMW Pbp interacts with the Chlamydia cell division protein FtsK. Chlamydiae are coccoid yet contain MreB, a rod shape-determining protein linked to Pbp2 in bacilli. Using MreB-specific antibiotics, we show that MreB is essential for chlamydial growth and division. Importantly, co-treatment with MreB-specific and Pbp-specific antibiotics resulted in the MreB-inhibited phenotype, placing MreB upstream of Pbp function in chlamydial cell division. Finally, we showed that MreB also interacts with FtsK. We propose that, in Chlamydia, MreB acts as a central co-ordinator at the division site to substitute for the lack of FtsZ in this bacterium.
Ultrasensitive Fluorogenic Reagents for Neuraminidase Titration (2017)

Influenza viral neuraminidase plays a crucial role during infections. It is a major target for the development of anti-influenza drugs and is also attracting increasing attention as a vaccine target as evidence accumulates that neuraminidase-neutralizing antibodies contribute to protection. However, no method currently exists to accurately and efficiently measure concentrations of active neuraminidase in virus samples or other crude mixtures, which hampers development on both fronts. In this report, we describe the development of a selective and sensitive active-site titration reagent for neuraminidase that can quantify viral neuraminidases down to sub-nanomolar levels in crude samples, with no background from non-viral neuraminidases. By using this reagent, we determined accurate k<sub>cat</sub> values for six influenza A and two influenza B neuraminidases for the first time. We also quantified the neuraminidase content in a commercial influenza vaccine, thus demonstrating that this titration reagent opens the possibility for better vaccine analysis.
Sub 100 nW Volatile Nano-Metal-Oxide Memristor as Synaptic-Like Encoder of Neuronal Spikes (2018)

Advanced neural interfaces mediate a bioelectronic link between the nervous system and microelectronic devices, bearing great potential as innovative therapy for various diseases. Spikes from a large number of neurons are recorded leading to creation of big data that require online processing under most stringent conditions, such as minimal power dissipation and on-chip space occupancy. Here, we present a new concept where the inherent volatile properties of a nano-scale memristive device are used to detect and compress information on neural spikes as recorded by a multielectrode array. Simultaneously, and similarly to a biological synapse, information on spike amplitude and frequency is transduced in metastable resistive state transitions of the device, which is inherently capable of self-resetting and of continuous encoding of spiking activity. Furthermore, operating the memristor in a very high resistive state range reduces its average in-operando power dissipation to less than 100 nW, demonstrating the potential to build highly scalable, yet energy-efficient on-node processors for advanced neural interfaces.
Smoking and Risk of All-cause Deaths in Younger and Older Adults (2016)

Cigarette smoking is the leading preventable cause of death worldwide. Few studies, however, have examined the modified effects of age on the association between smoking and all-cause mortality.In the current study, the authors estimated the association between smoking and age-specific mortality in adults from Beijing, China. This is a large community-based prospective cohort study comprising of 6209 Beijing adults (aged ≥40 years) studied for approximately 8 years (1991-1999). Hazard ratios (HRs) and attributable fractions associated with smoking were estimated by Cox proportional hazard models, adjusting for age, sex, alcohol intake, body mass index, systolic blood pressure, hypertension, and heart rate.The results showed, compared with nonsmokers, the multivariable-adjusted HRs for all-cause mortality were 2.7(95% confidence interval (CI):1.56-4.69) in young adult smokers (40-50 years) and 1.31 (95% CI: 1.13-1.52) in old smokers (>50 years); and the interaction term between smoking and age was significant (P = 0.026). Attributable fractions for all-cause mortality in young and old adults were 63% (95% CI: 41%-85%) and 24% (95% CI: 12%-36%), respectively. The authors estimated multivariate adjusted absolute risk (mortality) by Poisson regression and calculated risk differences and 95% CI by bootstrap estimation. Mortality differences (/10,000 person-years) were 15.99 (95% CI: 15.34-16.64) in the young and 74.61(68.57-80.65) in the old. Compared with current smokers, the HRs of all-cause deaths for former smokers in younger and older adults were 0.57 (95% CI: 0.23-1.42) and 0.96 (95% CI: 0.73-1.26), respectively.The results indicate smoking significantly increases the risks of all-cause mortality in both young and old Beijing adults from the relative and absolute risk perspectives. Smoking cessation could also reduce the excess risk of mortality caused by continuing smoking in younger adults compared with older individuals.
Nanodiamonds in dusty low-pressure plasmas (2009)

Dusty plasmas composed of carbon, hydrogen, and oxygen have been evidenced by optical emission spectroscopy and microwave interferometry, due to the increase in electron energy and the decrease in electron density. These plasmas allow homogeneous synthesis of nanodiamond grains composed of either pure diamond nanocrystals only (2–10 nm in size) or of diamond nanocrystals and some sp2-hybridized carbon entities. The control of their size and their microstructure could open ways for a wide range of fields. Their formation from a plasma-activated gaseous phase is also attractive because the formation of nanodiamonds in the universe is still a matter of controversy.