gebhart/patrepeval huggingface dataset:
Targeting NAD+ Biosynthesis Overcomes Panobinostat and Bortezomib-Induced Malignant Glioma Resistance (2020)

To improve therapeutic responses in patients with glioma, new combination therapies that exploit a mechanistic understanding of the inevitable emergence of drug resistance are needed. Intratumoral heterogeneity enables a low barrier to resistance in individual patients with glioma. We reasoned that targeting two or more fundamental processes that gliomas are particularly dependent upon could result in pleiotropic effects that would reduce the diversity of resistant subpopulations allowing convergence to a more robust therapeutic strategy. In contrast to the cytostatic responses observed with each drug alone, the combination of the histone deacetylase inhibitor panobinostat and the proteasome inhibitor bortezomib synergistically induced apoptosis of adult and pediatric glioma cell lines at clinically achievable doses. Resistance that developed was examined using RNA-sequencing and pharmacologic screening of resistant versus drug-naïve cells. Quinolinic acid phosphoribosyltransferase (QPRT), the rate-determining enzyme for <i>de novo</i> synthesis of NAD<sup>+</sup> from tryptophan, exhibited particularly high differential gene expression in resistant U87 cells and protein expression in all resistant lines tested. Reducing QPRT expression reversed resistance, suggesting that QPRT is a selective and targetable dependency for the panobinostat-bortezomib resistance phenotype. Pharmacologic inhibition of either NAD<sup>+</sup> biosynthesis or processes such as DNA repair that consume NAD<sup>+</sup> or their simultaneous inhibition with drug combinations, specifically enhanced apoptosis in treatment-resistant cells. Concomitantly, <i>de novo</i> vulnerabilities to known drugs were observed. IMPLICATIONS: These data provide new insights into mechanisms of treatment resistance in gliomas, hold promise for targeting recurrent disease, and provide a potential strategy for further exploration of next-generation inhibitors.
Prototype conflict alerting system for free flight (1997)

The development of a prototype alerting system for a conceptual free eight environment is discussed. The alerting logic is based on a probabilistic model of aircraft sensor and trajectory uncertainties that need not be Gaussian distributions. Monte Carlo simulations are used over a range of encounter situations to estimate coneict probability as a function of intruder position, heading, and speed, as determined through a datalink between aircraft. Additionally, the probability of coneict along potential avoidance trajectories is used to indicate whether adequate space is available to resolve a coneict. Intruder intent information, e.g., e ight plan, is not included in the modelbutcould beused toreducetheuncertaintyintheprojected trajectory. Fouralertstagesaredeenedbasedon the probability of cone ict and on the avoidance maneuvers that are availableto thee ight crew. Preliminary results from numerical evaluations and from a piloted simulator study at NASA Ames Research Center are summarized.
Does Sex Influence the Impact That Smoking, Treatment Interruption and Impaired Pulmonary Function Have on Outcomes in Limited Stage Small Cell Lung Cancer Treatment? (2005)

In LS-SCLC, women overall do better than men, with or without a negative variable. The largest quantifiable improvement in survival for women came from smoking cessation, and for men from avoidance of breaks during treatment.
Optimum design of chamfer distance transforms (1998)

The distance transform has found many applications in image analysis. Chamfer distance transforms are a class of discrete algorithms that offer a good approximation to the desired Euclidean distance transform at a lower computational cost. They can also give integer-valued distances that are more suitable for several digital image processing tasks. The local distances used to compute a chamfer distance transform are selected to minimize an approximation error. A new geometric approach is developed to find optimal local distances. This new approach is easier to visualize than the approaches found in previous work, and can be easily extended to chamfer metrics that use large neighborhoods. A new concept of critical local distances is presented which reduces the computational complexity of the chamfer distance transform without increasing the maximum approximation error.
Broad-Spectrum Antibacterial Peptide Kills Extracellular and Intracellular Bacteria Without Affecting Epithelialization (2021)

New antibacterial drugs with novel modes of action are urgently needed as antibiotic resistance in bacteria is increasing and spreading throughout the world. In this study, we aimed to explore the possibility of using APIM-peptides targeting the bacterial β-clamp for treatment of skin infections. We selected a lead peptide, named betatide, from five APIM-peptide candidates based on their antibacterial and antimutagenic activities in both G<sup>+</sup> and G<sup>-</sup> bacteria. Betatide was further tested in minimal inhibitory concentration (MIC) assays in ESKAPE pathogens, in <i>in vitro</i> infection models, and in a resistance development assay. We found that betatide is a broad-range antibacterial which obliterated extracellular bacterial growth of methicillin-resistant <i>Staphylococcus epidermidis</i> (MRSE) in cell co-cultures without affecting the epithelialization of HaCaT keratinocytes. Betatide also reduced the number of intracellular <i>Staphylococcus aureus</i> in infected HaCaT cells. Furthermore, long-time exposure to betatide at sub-MICs induced minimal or no increase in resistance development compared to ciprofloxacin and gentamicin or ampicillin in <i>S. aureus</i> and <i>Escherichia coli</i>. These properties support the potential of betatide for the treatment of topical skin infections.
Structuring Local Identity: Nation, Province and County in Shanxi During the 1990s (2002)

One of the more interesting aspects of politics in the People's Republic of China during the 1990s was the attempt by many provincial leaders to create a specifically provincial discourse of development that entailed the reformulation of provincial identity. Both inside and outside the People's Republic of China, provincialism has often been held to challenge the unity of the Chinese state. However, an examination of the provincial discourse of development in Shanxi during the 1990s suggests that provincial and indeed more local identity politics are more complex and finely nuanced than might at first seem to be the case. Shanxi's new provincial identity was neither exclusive nor opposed to other identities, but one of a series of multiple and overlapping identities, structured within a hierarchy of place and identity that reached down to and interacted with the more local levels of county and village, as well as up to the national level. At the same time it is clear that the appeal to localism has started to influence the ways in which provincial leaders participate in national politics. Moreover, there is some indication that the emphasis on localism may have resulted in the county and the town or city becoming more significant locales for identity formation than the province, though the consequences of this for provincial and local politics remain unclear.
Analysis of T-cell-dependent and -independent antigens of Rickettsia conorii with monoclonal antibodies (1987)

Four monoclonal antibodies from euthymic mice and two monoclonal antibodies from athymic mice were directed against antigens of Rickettsia conorii, as shown by both indirect immunofluorescence and an enzyme immunoassay. There was extensive cross-reactivity with other spotted fever group rickettsiae. Euthymic monoclonal antibodies 3-2 and 9-2 (immunoglobulin G2a [IgG2a]) and 27-10 (IgG1) distinctly outlined the acetone-fixed rickettsial surface, as determined by indirect immunofluorescence; only monoclonal antibody 3-2 reacted with the intact rickettsial surface, as determined by colloidal gold-protein A negative-stain electron microscopy. Athymic monoclonal antibodies 32-2 and 35-3 (IgM) and euthymic monoclonal antibody 31-15 (IgG3) all demonstrated an irregular, extrarickettsial morphology, as determined by immunofluorescence, and ultrastructural cell wall blebs that were readily shed from the rickettsial surface. Monoclonal antibody 3-2, the only antibody to confer protection in lethally challenged mice, reacted with a high-molecular-weight protein in Western immunoblots. Monoclonal antibodies 31-15, 32-2, and 35-3 reacted with a "ladder" of proteinase K-resistant, lipopolysaccharidelike antigens. None of the monoclonal antibodies stabilized the ultrastructural rickettsial slime layer, but both athymic and euthymic polyclonal antibodies to R. conorii did. This is, to the best of our knowledge, the first report of the production of monoclonal antibodies to R. conorii and their use for antigenic analysis.
Starch Branching Enzymes from Maize (1985)

Spleen cells from mice immunized with starch branching enzymes were fused with cells from the mouse myeloma Sp2/0-AG14 cell line to form hybridomas. Those hybridomas producing antibodies against the branching enzyme were screened by the enzyme-linked immunosorbent assay using purified branching enzyme as the antigen. Three monoclonal cell lines (1A1D7, 1A1C3 and 4D2A9D8) were found to produce antibodies which showed positive enzyme-linked immunosorbent assay reactions with maize branching enzyme I in addition to branching enzymes IIa and IIb. Three other monoclonal cell lines (4D2D10, 4D2F9, and 2A6C12) were also selected which were found to produce antibodies showing positive enzyme-linked immunosorbent assay reactions with branching enzymes IIa and IIb only.Amino acid composition and peptide maps obtained after trypsin or chymotrypsin digestion show that there is no difference between branching enzyme IIa and IIb but they are significantly different from branching enzyme I which, along with immunological data, suggests that only two forms of starch branching enzyme may be present in maize kernels.Immunological cross-reaction was also found between the starch branching enzyme from maize kernels and the glycogen branching enzyme from Escherichia coli using polyclonal antibodies against starch branching enzyme I or IIa and IIb or E. coli glycogen branching enzyme, suggesting some immunological similarities between maize starch branching enzymes and E. coli glycogen branching enzyme.
A Bypass-Switching SAR ADC With a Dynamic Proximity Comparator for Biomedical Applications (2018)

A bypass-switching successive approximation (BSSA) register analog-to-digital converter (ADC) employing a newly proposed dynamic proximity comparator is presented in this paper. By exploiting the current characteristics of a current correlator, the proposed comparator generates the bypass signal directly along with the polarity comparison result. The bypass window size can be adjusted to optimize the power reduction for different sensing applications with low-voltage sensitivity. A BSSA logic circuit is adopted with reduced number of logic gates as well as switching power. A prototyped chip including a proposed ADC has been designed and fabricated in a 0.18-μm CMOS process occupying an area of 0.041 mm2. With a supply voltage of 0.6 V and at a sampling rate of 50 kS/s, the measured signal-to-noise-distortion ratio (SNDR) and spurious free dynamic range (SFDR) are 56.9 and 68.7 dB, respectively, achieving an effective number of bits (ENoB) of 9.16. The ADC consumes power of 114 nW while digitizing sinusoidal inputs. With a bypass window size of ±32 LSBs, the designed ADC consumes only 76 nW when quantizing full-scale electrocardiography signals that are generated from a certified commercial simulator, exhibiting a figure-of-merit (FoM) of 2.66 fJ/conversion-step. Besides ECG signals, the ADC is also demonstrated by digitizing electromyography and electrooculography signals from human bodies.
Chemokine receptors and HIV (1997)

The discovery that chemokine receptors are the human cofactors required along with CD4 for fusion and infection by HIV has opened new directions in AIDS research on mechanisms of viral entry, tropism, and pathogenesis. A possible mechanism of co-receptor function has been demonstrated that involves the formation of a complex on the cell surface between the HIV-1 envelope, CD4, and the coreceptor. Functional studies indicate that this interaction is structurally complex, that it probably involves multiple domains of the coreceptor, and that different virus isolates interact with coreceptors in distinct ways. Other immunodeficiency viruses including simian immunodeficiency virus and feline immunodeficiency virus also utilize chemokine receptors for entry. The identification of genetic polymorphisms helps explain why some people, with alterations in the CCR5 gene that prevent expression, are protected from HIV-1 infection. The discovery of specific HIV-1 fusion coreceptor molecules has not only provided new insights into the mechanisms of viral entry and tropism, but also led to new avenues of investigation on strategies to block HIV infection.
Reversible σ‐Borane‐to‐Borylene Transformation: A Little Something For Everyone (2009)

A reaction with many facets: The facile dehydrogenative synthesis of a borylene complex (left in scheme) from a dihydroborane (right), proceeds reversibly at room-temperature. The implications of this reaction for the fields of inorganic, main-group, and hydrogen-storage chemistry are covered in this Highlight.
19.3: Electronic Structure Calculation and QSPR Analysis of Eu 2+ ‐doped Oxide Phosphors: Relationship between Emission Wavelength and Crystal Structure (2009)

Abstract In this study, we have computationally revealed the relationship between crystal structure and emission wavelength for Eu 2+ ‐doped oxide phosphors. The quantum chemistry calculations and quantitative analysis of structure‐property relationship suggested that both O and alkaline‐earth (A) atoms around the Eu atom in phosphors are of importance for emission wavelength. This extension of the consideration range for interaction of A atoms gave the simple guideline for the emission wavelength control of Eu 2+ ‐doped phosphors: 1) The host materials which have many A atoms and shorter/longer A‐A/A‐O distances are suitable to get longer Eu 2+ emission wavelength, 2) The host materials which have less A atoms and longer/shorter A‐A/A‐O distances are suitable to get shorter Eu 2+ emission wavelength.
Metabolic engineering of cyanobacteria for ethanol production (2009)

Development of renewable energy is rapidly being embraced by our society and industry to achieve the nation's economic growth goals and to help address the world's energy and global warming crises. Currently most of the bioethanol production is from the fermentation of agricultural crops and residues. There is much debate concerning the cost effectiveness and energy efficiency of such biomass based ethanol production processes. Here, we report the creation of a Synechocystis sp. PCC 6803 strain that can photoautotrophically convert CO2 to bioethanol. Transformation was performed using a double homologous recombination system to integrate the pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adh) genes from obligately ethanol producing Zymomonas mobilis into the Synechocystis PCC 6803 chromosome under the control of the strong, light driven psbAII promoter. PCR based assay and ethanol production assay were used to screen for stable transformants. A computerized photobioreactor system was established for the experimental design and data acquisition for the analysis of the cyanobacterial cell cultures and ethanol production. The system described here shows an average yield of 5.2 mmol OD730 unit−1 litre−1 day−1 with no required antibiotic/selective agent.
Quadratic placement revisited (1997)

The "quadratic placement" methodology is rooted in [Module Placement Based on Resistive Network Optimization, Proud: A Sea-Of-Gate Placement Algorithm, A Combined Force and Cut Algorithm for Hierarchical VLSI Layout]and is reputedly used in many commercial and in-house tools forplacement of standard-cell and gate-array designs. The methodologyiterates between two basic steps: solving sparse systems oflinear equations, and repartitioning. This work dissects the implementationand motivations for quadratic placement. We firstshow that (i) Krylov subspace engines for solving sparse systemsof linear equations are more effective than the traditional successiveover-relaxation (SOR) engine [A Unified Approach to Partitioning and Placement] and (ii) order convergence criteriacan maintain solution quality while using substantially fewersolver iterations. We then discuss the motivations and relevanceof the quadratic placement approach, in the context of past and futurealgorithmic technology, performance requirements, and designmethodology. We provide evidence that the use of numerical linearsystems solvers with quadratic wirelength objective may be due tothe pre-1990's weakness of min-cut partitioners, i.e., numerical engineswere needed to provide helpful hints to min-cut partitioners.Finally, we note emerging methodology drivers in deep-submicrondesign that may require new placement approaches to the placement problem.
Development of a Sodium Ion Secondary Battery (2013)

SUMITOMO KAGAKU 2013 couples that have the function of maintaining charge neutrality for cathodes. In research and development for the next generation of secondary batteries, known as post-lithium ion secondary batteries, extensive investigations are being carried out on batteries that do not use rare metals. One of the candidates for the next generation of secondary batteries that has been proposed to meet this demand for large power supplies is the sodium ion secondary battery that uses sodium instead of lithium as the charge carrier and iron, manganese and other transition metals instead of cobalt for redox couples, and such batteries are being investigated.1), 2) If sodium ion secondary batteries can be made practical, there will be an approximately three digit relaxation in the constraints on reserves accompanying this, and we can expect that the environmental impact and cost will be greatly reduced. On the other hand as shown in Table 1, sodium has a normal electrode potential of approximately 0.3V higher or, in terms of ion volume, twice or greater than lithium and an atomic weight that is three times greater.3) Therefore the guidelines for searching for electrode active materials for lithium ion secondary batteries cannot be appropriated for sodium ion secondary batteries. Development of a Sodium Ion Secondary Battery
Data from Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Method:&lt;/b&gt; Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines &lt;i&gt;IL1A&lt;/i&gt; (rs1800587), &lt;i&gt;IL1B&lt;/i&gt; (rs16944, rs1143627), &lt;i&gt;IL1RN&lt;/i&gt; (rs454078), &lt;i&gt;IL2&lt;/i&gt; (rs2069762), &lt;i&gt;IL6&lt;/i&gt; (rs1800795, rs1800797), &lt;i&gt;IL10&lt;/i&gt; (rs1800890, rs1800896), &lt;i&gt;TNF&lt;/i&gt; (rs1800629), &lt;i&gt;LTA&lt;/i&gt; (rs909253), and &lt;i&gt;CARD15&lt;/i&gt; (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Obesity (BMI ≥ 30 kg/m&lt;sup&gt;2&lt;/sup&gt;) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02–1.73], as was &lt;i&gt;TNF-308GA+AA&lt;/i&gt; (OR = 1.24; 95% CI, 1.07–1.44). Together, being obese and &lt;i&gt;TNF-308GA+AA&lt;/i&gt; increased DLBCL risk almost 2-fold relative to those of normal weight and &lt;i&gt;TNF-308GG&lt;/i&gt; (OR = 1.93; 95% CI, 1.27–2.94), with a RERI of 0.41 (95% CI, −0.05–0.84; &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;interaction&lt;/sub&gt; = 0.13). For FL and CLL/SLL, no associations with obesity or &lt;i&gt;TNF-308GA+AA&lt;/i&gt;, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and &lt;i&gt;TNF-308GA+AA&lt;/i&gt; may interact to increase DLBCL risk.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Impact:&lt;/b&gt; Studies using better measures of adiposity are needed to further investigate the interactions between obesity and &lt;i&gt;TNF-308G&gt;A&lt;/i&gt; in the pathogenesis of lymphoma. &lt;i&gt;Cancer Epidemiol Biomarkers Prev; 24(7); 1061–70. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Upstream/Downstream Real Time Surveillance and Optimization Systems: Two Sides of the Same Coin, or Never the Twain Shall Meet (2013)

Abstract Downstream Refineries and Chemical Plants have benefited from real time optimization systems (RTO) for the last 30 years. Downstream RTO is a well established and permanent fixture in many plants – the "way we do things ‘round here!". Upstream E&amp;P operations have "come to this party" much more recently and are using RTO more sparingly, even though the economic and HSSE benefits can be very significant. There are key differences between downstream and upstream. For example, downstream facilities do not deal with sub-surface uncertainties, multiphase flow and isolated/harsh environments; while upstream operations do not usually have to deal with complex chemical processes. Integrated Oil Companies run upstream and downstream operations and integration of tools/practices across both regimes is often perceived to be of significant value. Hence, the purpose of this paper is to compare and contrast downstream and upstream RTO learnings with a view to identifying and describing: similarities in production unit operations e.g. fluid separation, compression etc.; key differences between production unit operations; cultural differences between operations; RTO activities from a technical perspective; RTO business benefits and how these might be leveraged and sustained in both directions. What will emerge from this analysis will be a comparison, highlighting points of commonality and differences, leading to a better understanding of how RTO can be more effectively exploited in the upstream business – the cheapest oil available! Specifically, it is concluded that RTO in upstream operations is feasible and lucrative, but is relatively rare with sustainability a challenge. Downstream RTO is more common and sustainable, significantly less lucrative, but a "must do" to compete in a highly competitive, margin constrained business.