gebhart/patrepeval huggingface dataset:
Pro-Apoptotic Synergistic Interactions between ERK1/2 and Bcl-2 Inhibitors in Acute Myeloid Leukemia Cells. (2004)

Abstract We previously reported that activation of the Ras/MEK/ERK signaling pathway alone or in combination with high levels of Bcl-2 confers poor prognosis in patients with acute myeloid leukemias (AML). In this study, we investigated whether the simultaneous disruption of these two pathways by pharmacological inhibition of ERK1/2 and Bcl-2 utilizing novel small molecule inhibitors would induce pro-apoptotic activity in myeloid leukemic cells. For inhibition of ERK1/2 signaling, we utilized the MEK inhibitor CI-1040 (Pfizer Global Research and Development). Functional Bcl-2 inhibition was achieved by the novel BH3 peptide binding domain inhibitor A438744.7 (Abbott Laboratories). A dose-dependent increase in apoptosis as assessed by an increase in phosphatidylserine externalization was observed in OCI-AML3 cells after 24h incubation with CI-1040 or A438744.7 (both in a range between 0.25 and 2 μM). When these agents were used in combination at a fixed 1:1 ratio, a dramatic enhancement of cell killing was observed especially at lower concentrations (70.63%±9.95 Annexin V+ cells at 0.25 μM of each compound). Isobologram analysis (Chou and Talalay method) revealed a Combination Index (CI) < 1 (CI=0.114 and 0.436 at 0.25 μM and 2 μM, respectively) suggesting the strongly synergistic nature of these interactions. In addition, combined treatment with CI-1040 and A438744.7 resulted in a substantial increase of mitochondrial damage and caspase cleavage. Pre-incubation (1-hour) with a pan-caspase inhibitor (IDN-1965) was able to completely abrogate sensitivity to the inhibitors. We further demonstrated that bcl-2 overexpression prevented induction of apoptosis by low doses of both, MEK and BH3 inhibitors, whereas enforced Bcl-XL expression essentially abrogated the lethal effects of A438744.7, but not of CI-1040. Finally, to evaluate whether the combined strategy of ERK1/2 and Bcl-2 inhibition would be potentially applicable to leukemia patients, primary cells were isolated from AML samples and exposed to CI-1040 and A438744.7, as single agents or in combination at a 1:1 ratio for up to 96 hours. In each sample, drugs administrated individually were minimally toxic. Co-administration of CI-1040 and BH3 inhibitors displayed strong synergistic lethal effects toward primary cells from AML patients (CI=0.45±0.42 at 0.25 μM and CI=0.20±0.22 at 0.5 μM after 48h incubation). In conclusion, simultaneous exposure to nanomolar concentrations of MEK and bcl-2 inhibitors induced mitochondrial dysfunction, caspases activation and striking synergistic pro-apoptotic activity in myeloid leukemic cells. Similar synergistic interactions occured in primary AML samples. Together, these data strongly suggest that therapeutic strategies combining MEK and Bcl-2 inhibitors warrant further examination in AML.
[Substituted picolinic acids as DBH inhibitors. Inhibition of dopamine beta-hydroxylase and antihypertensive action]. (1983)

The authors determined the dissociation constant, the constant of copper complex formation, the inhibitory action on the catecholamine biosynthesis enzyme dopamine beta-hydroxylase (DBH; copper glycoprotein), as well as the antihypertensive effect on spontaneously hypertensive rats of a series of substituted picolinic or fusaric acids (FA; 5-n-butylpicolinic acids). The substances investigated may be characterized as weak to medium-strong acids which form stable copper(II) complexes in solution and in the solid state. The concentrations required for a 50% inhibition of DBH range between 10(-6) and 10(-5) mol/l. The picolinic acid structure is of greater importance to enzyme inhibition than the butylpyridine structure. From the inhibition type of FA it may be deduced that the mechanism of inhibition cannot be explained only by the complex formation of the enzyme copper. Most of these derivatives are of hypotensive activity; some others exert a hypertensive effect. A quantitative correlation between the action on blood pressure and the enzyme inhibition cannot be established without calculation (quantitative structure-activity analysis). The hypotensive activity is above all due to DBH inhibition in the angiovascular region and in the suprarenal gland.
Automated SAR measurements for compliance testing of cellular telephones (2002)

Determination of peak 1-g SAR is required for all new personal wireless devices to ensure that it complies with the RF safety guidelines approved by US Federal Communications Commission (FCC). We have developed an automated SAR measurement setup which uses a 3D stepper motor system to move the Narda Model 8021 implantable E-field probe to determine the SAR distributions inside a homogenous human phantom. The E-field probe was calibrated against the FDTD using a slab phantom and was checked to have good isotropy (/spl plusmn/0.23 dB) and a wide dynamic range (10 mW/kg to 10 W/kg) both at AMPS (840 MHz) and PCS (1900 MHz) frequencies. The system was validated using a sphere model and has been used for SAR testing of several commercial telephones with different operating frequencies and antenna structures, the agreement between the measurements and FDTD calculations of 1-g SARs is excelled and generally within /spl plusmn/25%.
A compact T/R switching circuit using quadrature couplers and drain-driven HPAs (2002)

A novel T/R switching circuit is proposed for microwave T/R modules. It consists of balanced high-power amplifiers with quadrature couplers, and a low-noise amplifier which is connected to the isolation port of the coupler. In RX-mode, the HPAs are switched off by controlling drain voltage of FETs. A prototype C- to Ku-band T/R switching circuit has been fabricated, and the validity of the switching method has been confirmed experimentally.
ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease (2021)

Key recommendations of these guidelines include the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. Future critical research priorities are also identified.
How to ask for permission (2012)

We employed gentamicin-sensitive and -resistant derivatives of Escherichia coli in a macrophage phagocytosis assay that compared lambda bacteriophage and gentamicin as extracellular bactericidal agents. Colony counts and direct microscopic examination of phagocytized E. coli supported the conclusion that gentamicin entered macrophages, even at low concentrations, and contributed to their bactericidal activity. Also, two E. coli strains differing in the ability to express the adhesin of type 1 pili (FimH) were distinguishably different in intracellular survival when lambda was used as the extracellular killing agent but were indistinguishable when gentamicin was employed.
Decontaminating the polymerase chain reaction. (1991)

Template DNA, which was added to a modified polymerase chain reaction mixture to simulate contamination, was inactivated by restriction enzyme digestion. After inactivation of the restriction enzymes, additional template, buffer and Taq polymerase were added to the reaction and the polymerase chain reaction proceeded. Results are presented using several different restriction enzymes with four base recognition sequences. The limitations of the method are discussed to indicate the tactics to be used for other DNA sequences.
Expression of Mitochondrial Capsule Selenoprotein mRNA Increases with Aging, but Decreases by Selenium Deficiency in the Mouse Testis. (1997)

Mitochondrial capsule selenoprotein (MCS) has been known as a structural protein of the mitochondrial sheath in spermatozoa. In this study, to investigate whether or not the expression of MCS mRNA in testes is affected by aging or selenium (Se) deficiency, the cDNA clone of MCS was isolated from the testes of 8-week-old ICR mice by reverse transcription-polymerase chain reaction. The nucleic acid sequence analysis confirmed that the cloned cDNA is an open reading frame of the MCS and contains 3 in-phase TGA codons that recognize specifically the selenocysteine in selenoprotein. According to Northern blot analysis, the MCS mRNA in testes greatly increased at 8 weeks old and then began to increase with aging. As compared with that of 8-week-old mice, the signal increased about 2.4-fold in the testes of 80-week-old mice. On the other hand, we generated Se-deficient and Se-sufficient mice by feeding weanling male mice (3 weeks old) with either a Se-deficient or a Se-sufficient diet for 11 weeks. MCS mRNA decreased about 21-fold in the testes of Se-deficient animals as compared with that of Se-sufficient animals. The present study provides a novel evidence that MCS mRNA level in testes increases with aging, but remarkably decreases due to Se deficiency.
The eye in stroke: amaurosis fugax, ischaemic optic neuropathy and chronic ocular ischaemia. (1988)

The problems of the eye associated with amaurosis fugax, ischaemia optic neuropathy and chronic ocular ischaemia are presented and the possibility of treatment is discussed.
Leveraging Backscatter for Ultra-low Power Wireless Sensing Systems (2021)

Continuous scaling of CMOS has been the major catalyst in miniaturization of integrated circuits (ICs) and crucial for global socio-economic progress. However, continuing the traditional way of scaling to sub-20nm technologies is proving to be very difficult as MOSFETs are reaching their fundamental performance limits [1] and interconnection bottleneck is dominating IC operational power and performance [2]. Migrating to 3-D, as a way to advance scaling, has been elusive due to inherent customization and manufacturing requirements in CMOS architecture that are incompatible with 3-D organization. Partial attempts with die-die [3] and layer-layer [4] stacking have their own limitations [5]. We propose a new 3-D IC fabric technology, Skybridge [6], which offers paradigm shift in technology scaling as well as design. We co-architect Skybridge’s core aspects, from device to circuit style, connectivity, thermal management, and manufacturing pathway in a 3-D fabric-centric manner, building on a uniform 3-D template. Our extensive bottom-up simulations, accounting for detailed material system structures, manufacturing process, device, and circuit parasitics, carried through for several designs including a designed microprocessor, reveal a 30-60x density, 3.5x performance/watt benefits, and 10x reduction in interconnect lengths vs. scaled 16-nm CMOS [6]. Fabric-level heat extraction features are found to be effective in managing IC thermal profiles in 3-D. This 3-D integrated fabric proposal overcomes the current impasse of CMOS in a manner that can be immediately adopted, and offers unique solution to continue technology scaling in the 21<sup>st</sup> century.
On-chip Microring Resonator Based Electro-optic Full Adder for Optical Computing (2017)

We propose a ripple-carry electro-optic full adder using microring resonators, taking advantage of unique properties of light on chip. This proposed design with larger bandwidth and lower power consumption paves the way to future optical computing.
Emoji and Emoticon in Tweet Sentiment Classification (2020)

Indonesian Twitter's user tends to use emoji or emoticon when tweeting. Emoji and emoticon can help them for conveying their message efficiently. It is used for expressing their sentiment about a certain topic. For analyzing sentiment with classification technique, the use of emoji and emoticon might take into consideration. In this paper, we knew that Indonesian Twitter's User not only uses emoji in their tweets but also emoticon although emoji used is dominating tweets than emoticon. In some cases, both of them are used simultaneously in a tweet. Emoji and emoticon affect classification model performance positively so that emoji and emoticon might not remove in-text pre-processed and include in classification features. For included in classification feature emoji and emoticon convert into its Unicode Name, but this conversion slightly below classification model from conversion emoji and emoticon into its lexicon sentiment. Conversion emoji and emoticon into its lexicon sentiment make classification model performance more stable. But considering emoticon and emoji cannot simply be interpreted into certain sentiment class so conversion into Unicode Name is encouraging. SVM produces the best performance followed by Bernoulli Naïve Bayes and the last one is Multinomial Naïve Bayes.
Tip for scanning tunneling microscopy made of monocrystalline, semiconducting, chemical vapor deposited diamond (1992)

A tip for scanning tunneling microscopy (STM) was fabricated from semiconducting, chemical vapor deposited (CVD) diamond, epitaxially grown on a natural diamond substrate. Extremely high, p-type conductivity was realized by heavy boron doping. A sharp tip was obtained by conventional diamond polishing in such a way that the ultimate tip (radius&lt;12 nm) is situated in the electrically conductive CVD layer. Atomic resolution on graphite surfaces could easily be obtained under normal operating conditions for STM in air. The feasibility of using the diamond tip to create nanostructures on surfaces was also investigated.
Personalized temporal medical alert system (2013)

The continuous increasing needs in telemedicine and healthcare, accentuate the need of well-adapted medical alert systems. Such alert systems may be used by a variety of patients and medical actors, and should allow monitoring a wide range of medical variables. This paper proposes Tempas, a personalized temporal alert system. It facilitates customized alert configuration by using linguistic trends. The trend detection algorithm is based on data normalization, time series segmentation, and segment classification. It improves state of the art by treating irregular and regular time series in an appropriate way, thanks to the introduction of an observation variable valid time. Alert detection is enriched with quality and applicability measures. They allow a personalized tuning of the system to help reducing false negatives and false positives alerts.
Technological and nutritional aspects of milk chocolate enriched with grape pomace products (2020)

Abstract The French paradox is the observation of low heart disease death rates despite high intake of cholesterol and saturated fat, possibly related to the consumption of red wine containing polyphenols. Those are also found in pomace and affect health as radical catchers inhibiting cancer, inflammations and arteriosclerosis. European cocoa regulation allows incorporating up to 40% of added foodstuffs into chocolate, so grape pomace can be used. Cocoa itself is known as a very good source of phenolic compounds, and consequently dark chocolate is considered to have similar health benefits as red wine. Milk chocolates contain only little fat-free cocoa dry matter; therefore, grape pomace is considered most beneficial here. Entire pomace or flour from seeds have been tested to evaluate technical aspects as well as the impact on chocolate properties like particle size distribution, flow properties, total phenol content, antioxidative capacity and sensory perception. Initial trials revealed that additional drying and also pre-grinding was necessary before pomace can be used as an ingredient. Various samples were produced by the coarse conching process, which uses a ball mill for size reduction below 30 µm. A difficulty arises when some tough particles slip through without being properly ground; D99-values can be used to better control this issue. Grape pomace contains almost as many polyphenols as cocoa liquor, so it can serve as a substitute. Its content and thus quality depends on gentle drying. Finally, adding, e.g., just 3.5% was able to significantly increase the polyphenol contents of milk chocolate.
Large-scale active measurements of DNS entries related to e-mail system security (2015)

Since its early beginnings, e-mail has been one of the most successful Internet services as it was the first to offer global, asynchronous and almost instant message delivery. However, at the same time e-mail has not been designed with strong security considerations in mind, leading to various problems related to unsolicited messages. In order to mitigate this situation, since the mid 2000s, domain-based message authentication mechanisms have been standardized and deployed which mostly rely on their specific entries in the DNS. In our present paper, we provide the results our measurements of such entries for the SPF, ADSP and DMARC technologies for the Top 1 Million Alexa sites over a period of four months in 2014. While we have found many expected types of entries, we were also surprised at the non-negligible number of either too lax or too strict policy configurations, which we comment upon in detail, along with analyzing interesting correlations in cross-technology configurations. After providing valuable insights into the current status and the trends in SPF, ADSP and DMARC, we conclude the present paper with an outlook on our future work.
Honey as a topical treatment for wounds (2015)

It is difficult to draw overall conclusions regarding the effects of honey as a topical treatment for wounds due to the heterogeneous nature of the patient populations and comparators studied and the mostly low quality of the evidence. The quality of the evidence was mainly downgraded for risk of bias and imprecision. Honey appears to heal partial thickness burns more quickly than conventional treatment (which included polyurethane film, paraffin gauze, soframycin-impregnated gauze, sterile linen and leaving the burns exposed) and infected post-operative wounds more quickly than antiseptics and gauze. Beyond these comparisons any evidence for differences in the effects of honey and comparators is of low or very low quality and does not form a robust basis for decision making.
Clonal expansion of lung V delta 1+ T cells in pulmonary sarcoidosis. (1993)

Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for gamma/delta T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular gamma/delta T cell receptors. An abnormally high percentage of gamma/delta cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing alpha/beta receptors. Furthermore, as in normals, the circulating gamma/delta cells in patients predominantly expressed V gamma 9/V delta 2 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of gamma/delta cells expressing V delta 1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V delta 1+ cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus.
High-Resolution Structural Characterization of a New Adeno-associated Virus Serotype 5 Antibody Epitope toward Engineering Antibody-Resistant Recombinant Gene Delivery Vectors (2018)

Adeno-associated virus serotype 5 (AAV5) is being developed as a gene delivery vector for several diseases, including hemophilia and Huntington's disease, and has a demonstrated efficient transduction in liver, lung, skeletal muscle, and the central nervous system. One limitation of AAV gene delivery is preexisting neutralizing antibodies, which present a significant challenge for vector effectiveness in therapeutic applications. Here, we report the cryo-electron microscopy (cryo-EM) and image-reconstructed structure of AAV5 in complex with a newly generated monoclonal antibody, HL2476, at 3.1-Å resolution. Unlike other available anti-AAV5 capsid antibodies, ADK5a and ADK5b, with epitopes surrounding the 5-fold channel of the capsid, HL2476 binds to the 3-fold protrusions. To elucidate the capsid-antibody interactions, the heavy and light chains were sequenced and their coordinates, along with the AAV5 viral protein, assigned to the density map. The high resolution of the complex enabled the identification of interacting residues at the 3-fold protrusions of the capsid, including R483, which forms two hydrogen bonds with the light chain of HL2476. A panel of AAV5 variants was generated and analyzed by native dot immunoblot and transduction assays. This identified variants with antibody escape phenotypes that maintain infectivity.<b>IMPORTANCE</b> Biologics based on recombinant AAVs (rAAVs) are increasingly becoming attractive human gene delivery vehicles, especially after the approval of Glybera in Europe and Luxturna in the United States. However, preexisting neutralizing antibodies against the AAV capsids in a large percentage of the human population limit wide-spread utilization of these vectors. To circumvent this problem, stealth vectors must be generated that are undetectable by these antibodies. This study details the high-resolution characterization of a new antigenic region on AAV5, a vector being developed for numerous delivery applications. The structure of AAV5 complexed with HL2476, a novel antibody, was determined by cryo-EM to 3.1-Å resolution. The resolution of the density map enabled the identification of interacting residues between capsid and antibody and the determinants of neutralization. Thus, the information obtained from this study can facilitate the generation of host immune escape vectors.
Ultra Low Contact Resistivities for CMOS Beyond 10-nm Node (2013)

Contact resistances are directly measured for contacts with sizes from 25 to 330 nm using e-beam based nano-TLM devices. Record low contact resistivities <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">${\sim}1.5\times 10^{-9}~\Omega\cdot~{\rm cm}^{2}$</tex></formula> are extracted from Ni(Pt) silicide contacts on in situ boron-doped <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">${\rm Si}_{0.7}{\rm Ge}_{0.3}$</tex></formula> with a chemical boron-doping density of <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$2\times 10^{21}/{\rm cm}^{3}$</tex></formula> . This is very promising for pMOS applications beyond the 10-nm node. A clear dependence of contact resistance on the silicide thickness has also been found.