gebhart/patrepeval huggingface dataset:
Analysis and Optimization of Star-Structured Switched-Capacitor Equalizers for Series-Connected Battery Strings (2017)

Due to the adjacent cell-to-cell equalization, the classical switched-capacitor equalizer (SCE) has seriously low balancing speed and efficiency for a long battery string. Therefore, a series of star-structured switched-capacitor equalizers are proposed to achieve high balancing speed and efficiency independent of the cell number and the cell voltage distribution without significant influences on the size, cost, control, and reliability compared with the classical SCE. The proposed topologies use the least mosfets and capacitors to achieve the most direct balancing paths between any two cells, being the optimal switched-capacitor structures. An analysis method for the slow switching limit and the fast switching limit impedances of the proposed equalizers is proposed to provide a theoretical guidance for the selection of the switching frequency. The inherent advantages of the proposed systems are the small size, low cost, simple control, high efficiency, fast speed, easy modularization, and high reliability. A prototype for four lithium-ion battery cells is set up. Experimental results show improved balancing performances with strong robustness. Moreover, the measured peak balancing efficiency is about 93.1% despite faster balancing speed.
Identification of Phosphorylation Sites in PHF-TAU from Patients with Guam Amyotrophic Lateral Sclerosis/Parkinsonism-dementia Complex (1996)

Guam Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (Guam ALS/PDC) is a progressive neurodegenerative disorder characterized by abundant neurofibrillary tangles (NFTs) composed of aggregated paired helical filaments (PHFs). These abnormal filaments resemble the PHFs in neurofibrillary lesions of classic Alzheimer's disease (AD), and recent studies demonstrated that tau in Guam ALS/PDC is aberrantly phosphorylated and biochemically similar to the abnormal tau proteins (PHFtau) in classic AD. However, unlike PHFtau in AD, there is little information on the specific sites of phosphorylation in PHFtau from Guam ALS/PDC. Thus, to address this important issue, we examined tangle-rich Guam ALS/PDC and AD brains by Western blot, immunoelectron microscopy and immunohistochemistry using 13 antibodies to defined phosphate-dependent or -independent epitopes distributed throughout AD PHFtau. These studies identified 7 previously unknown sites of phosphorylation in PHFtau from Guam ALS/PDC (i.e. Thr181, Thr231, Ser262, Ser396, Ser404, Ser422, and the site defined by monoclonal antibody AT10), all of which also are found in AD PHFtau. Indeed, the Western blot, light and immunoelectron microscopic data suggest that NFTs, PHFs and PHFtau in Guam ALS/PDC are very similar to their counterparts in classic AD. Thus, insights into mechanisms leading to the accumulation of neurofibrillary lesions in Guam ALS/PDC may advance understanding of the pathogenesis and biological consequences of these lesions in classic AD.
Optimized Electroactive Polymer Supercapacitors (2014)

The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information.
Factors involved in guanine/cytosine (G/C) selectivity of DNA-binding drugs: a molecular modelling study of ligand interactions with a tyrT DNA sequence (1993)

Molecular modelling studies are reported on the interactions of two analogues of the bis(amidinium) drug berenil with an extended DNA sequence, the 60 base-pair sequence from the tyrT promoter. These analogues have the hydrogen bond-donating amidinium groups of this agent replaced by hydrogen bond-accepting carbonyl moieties. Since the amidinium functions facilitate binding of the parent drug to AT-rich sequences of DNA, one goal of this study has been to examine the potential for the modified analogues to interact with GC-rich regions in the minor groove of DNA. The molecular modelling strategy involves screw-type translation of the ligand molecules along the length of the duplex DNA sequence at 0.05 nm intervals and energy minimisation using an all-atom force-field. The contributions to the binding interaction are examined in terms of the van der Waals and electrostatic non-bonded energy components and the induced perturbation terms. It is found that conversion of one amidinium group to an amide function is insufficient to produce GC-binding selectivity, whereas conversion of both terminal groups does confer some selectivity for G · C base-pairs, although at the expense of reduced overall DNA binding affinity. The roles played by the various contributors to the binding energy and the factors that influence possible recognition of G · C base-pairs are analysed in detail.
Production, isolation and structure determination of a novel .BETA.-glucosidase inhibitor, cyclophellitol, from Phellinus sp. (1990)

In the course of our screening of beta-glucosidase inhibitor, a culture filtrate of a mushroom, Phellinus sp. strongly inhibited the enzyme activity. The active substance was isolated through charcoal separation, column chromatography and crystallization. Spectroscopic and crystallographic analysis revealed that it had a novel cyclitol structure, (1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4,1,0]heptane-2,3,4-tri ol, and we named it cyclophellitol. It inhibited almond-derived beta-glucosidase with an IC50 of 0.8 micrograms/ml.
Modulation of Estrogen Receptor-α Transcriptional Activity by the Coactivator PGC-1 (2000)

A transcriptional coactivator of the peroxisome proliferator-activated receptor-gamma (PPARgamma), PPARgamma-coactivator-1(PGC-1) interacts in a constitutive manner with the hinge domain of PPARgamma and enhances its transcriptional activity. In this study we demonstrate that PGC-1 is a coactivator of estrogen receptor-alpha (ERalpha)-dependent transcriptional activity. However the mechanism by which PGC-1 interacts with ERalpha is different from that of PPARgamma. Specifically, it was determined that the carboxyl terminus of PGC-1 interacts in a ligand-independent manner with the ERalpha hinge domain. In addition, an LXXLL motif within the amino terminus of PGC-1 was shown to interact in an agonist-dependent manner with the AF2 domain within the carboxyl terminus of ERalpha. The ability of PGC-1 to associate with and potentiate the transcriptional activity of an ERalpha-AF2 mutant that is unable to interact with the p160 class of coactivators suggests that this coactivator may have a unique role in estrogen signaling. It is concluded from these studies that PGC-1 is a bona fide ERalpha coactivator, which may serve as a convergence point between PPARgamma and ERalpha signaling.
DOZ047.51: Swallowing and pulmonary diagnoses in children with EA and TEF (2019)

Abstract Introduction Children with repaired congenital esophageal atresia/tracheoesophageal fistula (EA/TEF) are at high risk of aerodigestive morbidity. We hypothesized that age and coexisting pulmonary diagnoses are associated with dysphagia in this population. Methods Retrospective review of children with EA/TEF seen in the aerodigestive program between 2011 and 2015 was carried out and comorbidities, video fluoroscopic swallow studies (VFSS), chest CT, and bronchoscopy results were reviewed. VFSS was considered abnormal if there was aspiration, deep laryngeal penetration, significant residue, or delayed initiation. Mann–Whitney U test was used to examine VFSS results by age. Fisher's exact test was used to assess the relationship between VFSS result and comorbidities. Results Ninety VFSS were performed on 44 children with EA/TEF (median 2 studies per patient, range: 0–7). Fifty three percent (23/39) children had at least one abnormal VFSS. Seventeen children had VFSS change between normal and abnormal over time, with 11 normal on their most recent VFSS. Younger children (Mdn = 1.57 years) were more likely to have an abnormal test result than older children (Mdn = 3.55 years) (p = 0.001). Children with severe tracheomalacia (&gt;90% tracheal collapse visualized on flexible bronchoscopy) had a higher incidence of abnormal VFSS (14/20; 70%) than the other children with EA/TEF (9/24; 38%) (P = 0.04). Children with other pulmonary and airway comorbidities, including gestation age &lt;36 weeks (P = 0.24), vocal fold immobility (P = 0.1), abnormal chest CT (P = 0.1), tended to have an increased incidence of abnormal VFSS but did not reach statistical significance in this cohort. Discussion Dysphagia was prevalent in this cohort and related to age and severe tracheomalacia. This reinforces the need for a multidisciplinary evaluation including feeding and swallowing evaluation. In this rare disease, we must collaborate between sites to improve our understanding of aerodigestive diagnoses and disease outcomes.
Efficient and Stable Perovskite Solar Cells Using Molybdenum Tris(dithiolene)s as p-Dopants for Spiro-OMeTAD (2017)

Metal halide perovskite solar cells have now reached efficiencies of over 22%. To date, the most efficient perovskite solar cells have the n-i-p device architecture and use 2,2′,7,7′-tetrakis(N,N′-di-p-methoxyphenylamine)-9,9′-spirobifluorene or poly(triarylamine) as the hole transport material (HTM), which are typically doped with lithium bis((trifluomethyl)sulfonyl)amide (Li-TFSI). Li-TFSI is hygroscopic and detrimental to the long-term performance of the solar cells, limiting its practical use. In this work, we successfully replace Li-TFSI by molybdenum tris(1-(methoxycarbonyl)-2-(trifluoromethyl)ethane-1,2-dithiolene), Mo(tfd-CO2Me)3, or molybdenum tris(1-(trifluoroacetyl)-2-(trifluoromethyl)ethane-1,2-dithiolene), Mo(tfd-COCF3)3. With these two dopants, we achieve stabilized power conversion efficiencies up to 16.7% and 15.7% with average efficiencies of 14.8% ± 1.1% and 14.4% ± 1.2%, respectively. Moreover, we observe a significant enhancement of the long-term stability of perovskite solar cells under 85 °C thermal stressing in air.
Discovery of 2-{3-[2-(1-Isopropyl-3-methyl-1H-1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β-Sparing Phosphoinositide 3-Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity (2013)

Dysfunctional signaling through the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway leads to uncontrolled tumor proliferation. In the course of the discovery of novel benzoxepin PI3K inhibitors, we observed a strong dependency of in vivo antitumor activity on the free-drug exposure. By lowering the intrinsic clearance, we derived a set of imidazobenzoxazepin compounds that showed improved unbound drug exposure and effectively suppressed growth of tumors in a mouse xenograft model at low drug dose levels. One of these compounds, GDC-0032 (11l), was progressed to clinical trials and is currently under phase I evaluation as a potential treatment for human malignancies.
Discovery of Potent and Selective Methylenephosphonic Acid CD73 Inhibitors (2021)

Solid tumors are often associated with high levels of extracellular ATP. Ectonucleotidases catalyze the sequential hydrolysis of ATP to adenosine, which potently suppresses T-cell and NK-cell functions via the adenosine receptors (A<sub>2a</sub> and A<sub>2b</sub>). The ectonucleotidase CD73 catalyzes the conversion of AMP to adenosine. Thus, increased CD73 enzymatic activity in the tumor microenvironment is a potential mechanism for tumor immune evasion and has been associated with poor prognosis in the clinic. CD73 inhibition is anticipated to restore immune function by skirting this major mechanism of adenosine generation. We have developed a series of potent and selective methylenephosphonic acid CD73 inhibitors via a structure-based design. Key binding interactions of the known inhibitor adenosine-5'-(α,β-methylene)diphosphate (AMPCP) with hCD73 provided the foundation for our early designs. The structure-activity relationship study guided by this structure-based design led to the discovery of <b>4a</b>, which exhibits excellent potency against CD73, exquisite selectivity against related ectonucleotidases, and a favorable pharmacokinetic profile.
Comparison of microscopic versus molecular approaches in classifying the relatedness of synchonous and metachronous cancers. (2010)

e21091 Background: Oncologists are increasingly challenged with resolving whether separate cancers discovered synchronously or metachronously in patients represent metastasis or second primaries. This dilemma confounds proper patient care. Comparative mutational profiling (CMP) can address this need. We reviewed medical records to define the status of how this issue is currently managed and compared these findings with the results of CMP. Methods: We reviewed clinical records and pathology reports on 126 unselected, problematic patients with greater than 1 cancer, sent to us to determine the cancers' relatedness. Based on pathology reports, we assigned each cancer pair to 1 of 4 groups of relatedness: metastasis, independent primaries, unknown, or not stated in report. We performed quantitative CMP (RedPath PathFinderTG) using 17 markers on the DNA from cellular targets dissected from routine tissue or cytology slides. Results: CMP showed 63 of 126 (50%) patients had new primary cancers; 63 (50%), recurrent disease. Pathology reports did not state a relationship in 65 of 126 (52%) patients; 28 of these 65 (22%) reports nevertheless staged the lesion pathologically as a new primary. 36 of 126 (29%) reports expressly stated that the microscopic analysis was indeterminate. The remaining 25 (20%) reports classified the relatedness; however, CMP reclassified the relationship in 9 (36%). 14 (11%) patients with metachronous cancers had latency intervals exceeding 5 years; CMP showed 6 (43%) of these patients had recurrent disease including 2 with intervals of 13 and 17 years. Conclusions: Optimal patient management requires correct pathologic staging and definitive discrimination between cancer recurrence and new cancer formation. Traditional microscopic methods often fail, especially for small specimens or for origin from a single organ. Quantitative CMP fills this void. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration RedPath Integrated Pathology RedPath Integrated Pathology
Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer (2017)

Prostate cancer is driven by androgen stimulation of the androgen receptor (AR). The next-generation AR antagonist, enzalutamide, prolongs survival, but resistance and lethal disease eventually prevail. Emerging data suggest that the glucocorticoid receptor (GR) is upregulated in this context, stimulating expression of AR-target genes that permit continued growth despite AR blockade. However, countering this mechanism by administration of GR antagonists is problematic because GR is essential for life. We show that enzalutamide treatment in human models of prostate cancer and patient tissues is accompanied by a ubiquitin E3-ligase, AMFR, mediating loss of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2), which otherwise inactivates cortisol, sustaining tumor cortisol concentrations to stimulate GR and enzalutamide resistance. Remarkably, reinstatement of 11β-HSD2 expression, or AMFR loss, reverses enzalutamide resistance in mouse xenograft tumors. Together, these findings reveal a surprising metabolic mechanism of enzalutamide resistance that may be targeted with a strategy that circumvents a requirement for systemic GR ablation.
Bacteria and bacterial rRNA genes associated with the development of colitis in IL-10−/− Mice (2008)

The negative associations of these 2 phylotypes (GpC2 and Gp66) suggest that these bacteria were being immunologically targeted, consistent with prior findings that the Lachnospiraceae bacterium A4 bears a prevalent flagellar antigen for disease-associated immunity in murine immune colitis and human Crohn's disease. Identification of these associations suggests that the experimental approach used in this study will have considerable utility in elucidating the host-microbe interactions underlying IBD.
Secure Quantum Communication Technologies and Systems: From Labs to Markets (2020)

We provide a broad overview of current quantum communication by analyzing the recent discoveries on the topic and by identifying the potential bottlenecks requiring further investigation. The analysis follows an industrial perspective, first identifying the state or the art in terms of protocols, systems, and devices for quantum communication. Next, we classify the applicative fields where short- and medium-term impact is expected by emphasizing the potential and challenges of different approaches. The direction and the methodology with which the scientific community is proceeding are discussed. Finally, with reference to the European guidelines within the Quantum Flagship initiative, we suggest a roadmap to match the effort community-wise, with the objective of maximizing the impact that quantum communication may have on our society.
Stimulation of Glucose-Dependent Insulin Secretion by a Potent, Selective sst3 Antagonist (2012)

This letter provides the first pharmacological proof of principle that the sst3 receptor mediates glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. To enable these studies, we identified the selective sst3 antagonist (1R,3R)-3-(5-phenyl-1H-imidazol-2-yl)-1-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-β-carboline (5a), with improved ion channel selectivity and mouse pharmacokinetic properties as compared to previously described tetrahydro-β-carboline imidazole sst3 antagonists. We demonstrated that compound 5a enhances GSIS in pancreatic β-cells and blocks glucose excursion induced by dextrose challenge in ipGTT and OGTT models in mice. Finally, we provided strong evidence that these effects are mechanism-based in an ipGTT study, showing reduction of glucose excursion in wild-type but not sst3 knockout mice. Thus, we have shown that antagonism of sst3 represents a new mechanism with potential in treating type 2 diabetes mellitus.
Applications of nanophotonics to classical and quantum information technology (2006)

Moore's Law has set great expectations that the performance/price ratio of commercially available semiconductor devices will continue to improve exponentially at least until the end of the next decade. Although the physics of nanoscale silicon transistors alone would allow these expectations to be met, the physics of the metal wires that connect these transistors will soon place stringent limits on the performance of integrated circuits. We will describe a Si-compatible global interconnect architecture - based on chip-scale optical wavelength division multiplexing - that could precipitate an "optical Moore's Law" and allow exponential performance gains until the transistors themselves become the bottleneck. Based on similar fabrication techniques and technologies, we will also present an approach to an optically-coupled quantum information processor for computation beyond Moore's Law, encouraging the development of practical applications of quantum information technology for commercial utilization. We present recent results demonstrating coherent population trapping in single N-V diamond color centers as an important first step in this direction.
Identity management tools for protecting online privacy (2011)

We use the Internet for shopping, staying in contact with friends, paying our bills, and declaring our taxes -- for almost everything. Thereby we emit a lot of sensitive information that is exchanged, processed, and stored at many different places. Sometimes we release our information voluntarily and consciously but quite often also unconsciously and unnoticed. In any case, once released, we can impossibly control the dispersal of this information, let alone remain aware where the information about us is stored and processed. However, the press reports daily on incidents where sensitive information has been lost, stolen, or misused -- often even information originally collected by large and reputable organizations. This situation puts our privacy and security at risk.
Numerical modeling of fin-and-tube condenser with wet-wall desuperheating. (2018)

Current heat exchanger simulation models typically divide the condenser into three regimes (desuperheating, two-phase and subcooled) and assume that condensation does not start until the bulk refrigerant flow reaches a state of saturated vapor. However, plenty of experiments have verified that condensation can occur much earlier than that when the tube wall surface temperature drops below the dew point of refrigerant even though the bulk flow is still superheated. This phenomenon is called wet-wall desuperheating (also referred to as wet-desuperheating, or condensation from desuperheated vapor in some publications). Wet-wall desuperheating is rarely modelled in the extant heat exchanger simulations due to lack of understanding in its physical process. However, neglecting this important phenomenon may lead to substantial performance prediction errors. This paper proposes a new fin-and-tube condenser heat exchanger model to bridge the research gap. In the proposed model, the heat exchanger is divided into four regimes: dry-wall desuperheating, wet-wall desuperheating, two-phase condensation and subcooled. The existence of dry-wall desuperheating and the onset point of wet-wall desuperheating are determined by rigorous algorithms. Boundaries between different flow regimes are captured to eliminate numerical discontinuities. A tube-by-tube analysis is adopted to allow for the simulation of complex tube circuitries. Simulation studies are performed to demonstrate the capabilities of the proposed model. The results show that wet-wall desuperheating always exists in the condenser with refrigerant vapor entering at the inlet, and neglecting the phenomenon can lead to significant under prediction for heat exchanger performance.
Covert preleukemia driven by MLL gene fusion (2008)

Abstract Acute leukemia is considered to be a two‐ or multiple‐step process. Although there is a considerable knowledge regarding the character of the “first hit,” the nature of the “second hit” remains unanswered in most of the cases including leukemias with MLL gene rearrangement. We demonstrate here a striking sequence of events, which include a covert, protracted preleukemic phase characterized by a dominant MLL/FOXO3A clone with intact myeloid differentiation and the subsequent acquisition of a secondary genetic abnormality, leading to overt lymphoblastic leukemia. Backtracking of the secondary acute lymphoblastic leukemia (sALL) with the MLL rearrangement showed no blasts in the bone marrow (BM) during the protracted preleukemic phase. However, at the same time (more than 1 year before the sALL diagnosis) the MLL/FOXO3A was present in up to 90% of BM cells including myeloid lineage, suggesting that the fusion arose in a multipotent progenitor. To identify potential “second hit” precipitating sALL we compared DNA in preleukemic versus fully leukemic samples. The analysis revealed a 10 Mb gain on 19q13.32 in the sALL, absent in the preleukemic specimen. These data provide insight into the dynamics of leukemogenesis in secondary leukemia with MLL rearrangement. © 2008 Wiley‐Liss, Inc.