gebhart/patrepeval huggingface dataset:
MAP Inference via Block-Coordinate Frank-Wolfe Algorithm (2019)

We present a new proximal bundle method for Maximum-A-Posteriori (MAP) inference in structured energy minimization problems. The method optimizes a Lagrangean relaxation of the original energy minimization problem using a multi plane block-coordinate Frank-Wolfe method that takes advantage of the specific structure of the Lagrangean decomposition. We show empirically that our method outperforms state-of-the-art Lagrangean decomposition based algorithms on some challenging Markov Random Field, multi-label discrete tomography and graph matching problems.
Proteomics to display lovastatin-induced protein and pathway regulation in rat liver (2000)

Lovastatin is a lipid lowering agent that acts by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a key regulatory enzyme in cholesterol biosynthesis. In this study the pattern of gene network regulation induced in hepatic proteins as a response to lovastatin treatment was analyzed by proteomics. In livers of male F344 rats treated with 1.6 mg/kg/day lovastatin or 150 mg/kg/day lovastatin for seven days, 36 proteins were found to be significantly altered (p<0.001) in relation to treatment. The changed proteins were classified according to their cellular function and participation in biochemical pathways. The following observations were made: (i) inhibition of HMG-CoA reductase provoked a regulatory response in the cholesterol synthesis pathway including the induction of cytosolic HMG-CoA synthase and of isopentenyl-diphosphate delta-isomerase, (ii) manipulation of the lipid metabolism triggered alterations in key enzymes of the carbohydrate metabolism, and (iii) lovastatin treatment was associated with signs of toxicity as reflected by changes in a heterogeneous set of cellular stress proteins involved in functions such as cytoskeletal structure, calcium homeostasis, protease inhibition, cell signaling or apoptosis. These results present new insights into liver gene network regulations induced by lovastatin and illustrate a yet unexplored application of proteomics to discover new targets by analysis of existing drugs and the pathways that they regulate.
Experimental Respiratory Syncytial Virus Infection of Adults (1971)

Abstract Volunteers were inoculated with a low (102.7 pfu), or 200-fold higher dose (105.0 pfu) of respiratory syncytial virus (RSV). The low dose infected 100% of the men but did not produce illness; the level of virus replication and the magnitude of the subsequent antibody response were inversely correlated with the level of nasal secretory neutralizing antibody prior to infection. The high dose infected only 53% of the men (9 of 17); five of the infected men became ill. Two of the men who excreted virus apparently resisted experimental inoculation and acquired infection secondarily by contact with infected men. The differences in rates of infection between the two studies were minimized if only those men who had extensive infection (virus excretion τ; 102.5 pfu or significant antibody responses) were considered. Resistance to extensive infection in both studies, and resistance to illness in the second study, appeared to be correlated with high levels of nasal wash antibody, but not with the level of serum antibody.
Screening of High-k Layers in MIS and MIM Capacitors Using Aqueous Chemical Solution Deposition (2007)

Abstract not Available.
Six-Step Gram Scale Synthesis of the HIV Integrase Inhibitor Dolutegravir Sodium (2021)

A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was investigated. The convergent strategy developed herein starts from 3-(R)-amino-1- butanol and builds up the BC ring system in 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4- difluorobenzylamine was either performed from the carboxylic acid or through aminolysis of the corresponding ester precursor. Final salt formation afforded dolutegravir sodium in 48–51% isolated yield (HPLC-purity: 99.7–99.9%) over six linear steps.&lt;br&gt;
Human dendritic cells subsets as targets and vectors for therapy (2013)

The skin immune system includes a complex network of dendritic cells (DCs). In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms that maintain immune homeostasis and in pathogenic chronic inflammation in which immune responses are unrestrained. Harnessing DC function by directly targeting DC-derived molecules or by selectively modulating DC subsets is a novel strategy for ameliorating inflammatory diseases. In this short review, we discuss recent advances in understanding the functional specialization of skin DCs and the potential implication for future DC-based therapeutic strategies.
Bragg Cell Receivers (Optical Processors) (2005)

A Bragg cell receiver has the potential of being used as an EW receiver. It can cover a wide instantaneous bandwidth of possibly over 1 GHz, and the frequency resolution can be very fine. However, to process short pulses, the frequency resolution is governed by the minimum PW of the input signals rather than by the performance of the Bragg cell. At present, the sensitivity and dynamic range of the Bragg cell receiver is limited by the photodetectors. With present detector technology, the dynamic range is rather low for EW receiver applications. Theoretically, the dynamic range of the Bragg cell receiver can be improved with the interferometric approach. However, further development is required to demonstrate the feasibility. A Bragg cell receiver can be considered a channelized receiver where the channelization is accomplished through optical means. One Bragg cell is equivalent to several hundred filters connected in parallel. In a power Bragg cell receiver, RF amplifiers cannot be added after the frequency channelization to improve the sensitivity, but light amplification may be added in front of the photodetectors to accomplish this. In an interferometric Bragg cell receiver, RF amplifiers can be added after channelization to improve the sensitivity of the receiver. Therefore, the interferometric Bragg cell receiver is very much like the channelized receiver discussed in Chapter 7. A Bragg cell receiver has potential performance characteristics that are very desirable for EW applications. Although the feasibility of the receiver has been demonstrated, extensive research and development, especially in the digitizing circuits, is critically needed to realize its full capability. To take the advantage of the small size of the optical bench, the digitizing circuits must be made small in size using VLSI circuit technology.
A Case Study of Glucose Levels During Sleep Using Multilevel Fast Function on Scalar Regression Inference (2023)

Continuous glucose monitors (CGMs) are increasingly used to measure blood glucose levels and provide information about the treatment and management of diabetes. Our motivating study contains CGM data during sleep for 174 study participants with type II diabetes mellitus measured at a 5-min frequency for an average of 10 nights. We aim to quantify the effects of diabetes medications and sleep apnea severity on glucose levels. Statistically, this is an inference question about the association between scalar covariates and functional responses observed at multiple visits (sleep periods). However, many characteristics of the data make analyses difficult, including (1) nonstationary within-period patterns; (2) substantial between-period heterogeneity, non-Gaussianity, and outliers; and (3) large dimensionality due to the number of study participants, sleep periods, and time points. For our analyses, we evaluate and compare two methods: fast univariate inference (FUI) and functional additive mixed models (FAMMs). We extend FUI and introduce a new approach for testing the hypotheses of no effect and time invariance of the covariates. We also highlight areas for further methodological development for FAMM. Our study reveals that (1) biguanide medication and sleep apnea severity significantly affect glucose trajectories during sleep and (2) the estimated effects are time invariant.
The Effect of Soluble P-Selectin in Coagulation (2008)

Abstract P-selectin, a member of the selectin family, is a vascular cell adhesion molecule. It is expressed and stored in alpha granules of platelets and in Weibel-Palade bodies of endothelial cells, and upon activation, P-selectin is translocated/transferred to the membrane surface. A key function of the P-selectin is to mediate leukocyte, lymphocyte and platelet interactions in inflammation and possibly in the thrombus formation. A soluble variant, S-Psel, comprising the extracellular domain of P-selectin, has been identified in healthy individuals, but is markedly elevated in patient with vascular disorders. Recent work on S-Psel suggested that S-Psel may play a role in hemostasis/coagulation through the generation of procoagulant TF-bearing microparticles (MP), and therefore, has potential in treating patients with the bleeding disorders, like hemophilia. The aim of this study is to verify studies reporting that S-Psel exhibits in vitro and in vivo pro-coagulant activity. S-Psel and S-Psel-Fc (IgG) fusion were purchased commercially or prepared at Novo Nordisk Research US (NNRUS) and their biological activity was verified by P-selectin/Pselectin glycoprotein ligand-1(PSGL-1) interaction in vitro. The clotting times of human whole blood and plasma treated with S-Psel or S-Psel-Fc, or with an irrelevant human IgG control protein, were measured by thromboelastography and aggregometry respectively. After up to 8 hours of incubation with S-Psel and S-Psel-Fc at a concentration of 15ug/ml, we found no significant difference between samples treated with S-Psel, S-Psel-Fc and the IgG controls. The ability of S-Psel to generate TF-bearing microparticles in human whole blood was examined in a FXa substrate cleavage assay; however, no significant difference in cleavage was observed. Finally, we evaluated S-Psel in vivo. Hemophilia A mice were injected with recombinant mouse S-Psel-IgG or S-Psel-Fc (IgG) at the concentration of 1.2 mg/Kg body weight and human IgG was used as control. As suggested from published results, the effect of S-Psel was determined 6 h after the treatment. Contrary to previous reports, the results revealed no significant difference in bleed time and blood loss between the experimental and control group. In conclusion, we were unable to demonstrate the procoagulant activity of S-Psel in our laboratory either in vitro or in vivo.
Final results of a phase II trial of weekly nab-paclitaxel with GM-CSF as chemoimmunotherapy for platinum-resistant epithelial ovarian cancer. (2012)

5082^ Background: Ovarian cancer patients with an anti-tumor immune response have a prolonged survival, suggesting that augmenting anti-tumor immunity may be therapeutic. We hypothesized that weekly nab paclitaxel (nabP) followed by GM-CSF may enhance anti tumor immunity and prolong time to progression (TTP). Methods: Eligible subjects had platinum resistant ovarian, primary peritoneal or fallopian tube cancer, and an elevated CA125. Conditional power estimate after 11 subjects showed 22 subjects had 80% power to show a response rate (RR) &gt;21% if the true study RR is 35%. Study end points were RR and TTP. Progression (DP) was doubling of CA125 above the nadir. Complete response (CR) was a decline of CA125 below institutional normal. Partial response (PR) was a decline of &gt;50% from baseline. Stable disease (SD) was all other scenarios. Subjects received nabP, 100mg/m 2 days 1,8,15 followed by GM-CSF 250mcg days 16-26 of a 28 day cycle until progression or 6 cycles were complete. Responding subjects received up to 6 more cycles of GM-CSF on days 14-28. Results: 21 subjects received at least one dose of study medications. Median age was 61 (30-91) and had a median of 3 (1-13) prior regimens. Among those completing the study, the median TTP was 132 days vs. 272 days on the prior platinum regimen. 9/21 (43%) had a PR and 4/21 (19%) had a CR. Subjects with a response had a median TTP of 140 days. Assay of serial T-lymphocyte counts against CEA, MUC1, CA125 and tt and influenza controls are planned. Conclusions: Weekly nabP with GM-CSF had manageable toxicity and induced a high response rate (62% by CA125) in patients with platinum resistant ovarian cancer, however this regimen did not prolong the TTP beyond the TTP observed in the prior platinum regimen.
WOMBAT: World of Molecular Bioactivity (2005)

This chapter contains sections titled: Introduction – Brief History of the WOMBAT Project WOMBAT 2004.1 Overview WOMBAT Database Structure WOMBAT Quality Control Uncovering Errors from Literature Data Mining with WOMBAT Conclusions and Future Challenges
Beta subunit coexpression and the alpha1 subunit domain I-II linker affect piperidine block of neuronal calcium channels (1996)

The effects of local anesthetics were examined on a family of transiently expressed neuronal calcium channels. Fomocaine, a local anesthetic containing a morpholine ring, preferentially blocked alpha1E channels (Ki = 100 microM), and had a lower affinity (3- to 15-fold) for alpha1A, alpha1B, and alpha1C channels. Block was incompletely reversible, followed 1:1 kinetics, and did not affect steady-state inactivation properties. Fomocaine block was sensitive to the concentration of permeant ion and enhanced in the presence of external pore blockers, suggesting a site of action in the conducting pathway. Flecainide, which carries a piperidine ring, and the diphenylbutylpiperidine antipsychotic, penfluridol, caused qualitatively similar block, suggesting that morpholine rings are compatible with the piperidine receptor site. In contrast, procaine, which contains an alkyl chain, caused reversible low affinity block of the different calcium channels (Kd values between 2 and 5 mM) and was least effective on alpha1E and did not compete with fomocaine, suggesting that local anesthetics interact with at least two distinct receptor sites. Compared to coexpression with the Ca channel beta1b subunit, block at the piperidine receptor site was significantly weakened with the beta2a subunit suggesting that the nature of the beta subunit contributes to drug binding. Amino acid changes in the cytoplasmic linker between domains I and II resulted in decreased fomocaine and penfluridol blocking affinity. Furthermore, the blocking affinity observed with alpha1B, was conferred on alpha1A by substitution of the domain I-II linker of alpha1B into alpha1A. Taken together, the data suggest that beta subunit binding and the domain I-II linker contribute to the piperidine receptor site on neuronal calcium channels.
Laboratory Diagnosis of 37 Cases of Bartonella Endocarditis Based on Enzyme Immunoassay and Real-Time PCR (2021)

<i>Bartonella</i> spp., mostly <i>Bartonella quintana</i> and <i>B. henselae</i>, are a common cause of culture-negative endocarditis. Serology using immunofluorescence assay (IFA) and PCR performed on cardiac tissues are the mainstays of diagnosis. We developed an enzyme immunoassay (EIA) and a novel multiplex real-time PCR assay, utilizing <i>Bartonella</i> genus-specific, <i>B. henselae</i>-specific, and <i>B. quintana</i>-specific SimpleProbe probes, for diagnosis of <i>Bartonella</i> endocarditis. We aimed to evaluate the performance of these assays. Thirty-seven patients with definite endocarditis, 18 with <i>B. henselae</i>, 18 with <i>B. quintana</i>, and 1 with <i>B. koehlerae</i>, were studied. Diagnosis was confirmed by conventional PCR and DNA sequencing of surgical cardiac specimens. Similar to the case with IFA, anti-<i>Bartonella</i> IgG titers of ≥1:800 were found in 94% of patients by EIA; cross-reactivity between <i>B. henselae</i> and <i>B. quintana</i> precluded species-specific serodiagnosis, and frequent (41%) but low-titer cross-reactivity between <i>Coxiella burnetii</i> antibodies and <i>B. henselae</i> antigen was found in patients with Q fever endocarditis. Low-titer (1:100) cross-reactivity was uncommonly found also in patients with brucellosis and culture-positive endocarditis, particularly <i>Enterococcus faecalis</i> endocarditis. Real-time PCR performed on explanted heart valves/vegetations was in complete agreement with results of sequence-based diagnosis with characteristic melting curves. The genus-specific probe identified five additional endocarditis-associated <i>Bartonella</i> spp. at the genus level. In conclusion, EIA coupled with a novel real-time PCR assay can play an important role in <i>Bartonella</i> endocarditis diagnosis and expand the diagnostic arsenal at the disposal of the clinical microbiologist. Since serology remains a major diagnostic tool, recognizing its pitfalls is essential to avoid incorrect diagnosis.
Advances in One-Pot Synthesis through Borrowing Hydrogen Catalysis (2018)

The borrowing hydrogen (BH) principle, also called hydrogen auto-transfer, is a powerful approach which combines transfer hydrogenation (avoiding the direct use of molecular hydrogen) with one or more intermediate reactions to synthesize more complex molecules without the need for tedious separation or isolation processes. The strategy which usually relies on three steps, (i) dehydrogenation, (ii) intermediate reaction, and (iii) hydrogenation, is an excellent and well-recognized process from the synthetic, economic, and environmental point of view. In this context, the objective of the present review is to give a global overview on the topic starting from those contributions published prior to the emergence of the BH concept to the most recent and current research under the term of BH catalysis. Two main subareas of the topic (homogeneous and heterogeneous catalysis) have been identified, from which three subheadings based on the source of the electrophile (alkanes, alcohols, and amines) have been considered. Then the type of bond being formed (carbon-carbon and carbon heteroatom) has been taken into account to end-up with the intermediate reaction working in tandem with the metal-catalyzed hydrogenation/dehydrogenation step. The review has been completed with the more recent advances in asymmetric catalysis using the BH strategy.
Real-time transient elastography on standard ultrasound using mechanically induced vibration: System design and initial results (2011)

Tissue elasticity can be deduced from the study of the propagation of shear waves. Transient elastography by means of mechanical vibration has been well established in the literature as a means of assessing the elasticity of the soft tissue and shown to be useful in different clinical applications. Previous studies have focused mainly on custom single element ultrasound transducers and ultrafast ultrasound scanners. In this work, we report the design and implementation of a transient elastography system on a standard ultrasound scanner that enables quantitative assessment of tissue elasticity in real-time. We presents the actuator design as well as the proposed data acquisition schemes that enable imaging of transient shear waves both in 1D and 2D in addition to the reconstruction algorithms for estimating the Young's modulus from these 1D and 2D wave images. The performance of the system is validated experimentally using a commercial elasticity phantom. In both 1D and 2D imaging modes, a good agreement was observed between the Young's modulus reported by the phantom manufacturer and the Young's modulus estimated by our system.
Glycan modulation and sulfoengineering of anti–HIV-1 monoclonal antibody PG9 in plants (2015)

Broadly neutralizing anti-HIV-1 monoclonal antibodies, such as PG9, and its derivative RSH hold great promise in AIDS therapy and prevention. An important feature related to the exceptional efficacy of PG9 and RSH is the presence of sulfated tyrosine residues in their antigen-binding regions. To maximize antibody functionalities, we have now produced glycan-optimized, fucose-free versions of PG9 and RSH in Nicotiana benthamiana. Both antibodies were efficiently sulfated in planta on coexpression of an engineered human tyrosylprotein sulfotransferase, resulting in antigen-binding and virus neutralization activities equivalent to PG9 synthesized by mammalian cells ((CHO)PG9). Based on the controlled production of both sulfated and nonsulfated variants in plants, we could unequivocally prove that tyrosine sulfation is critical for the potency of PG9 and RSH. Moreover, the fucose-free antibodies generated in N. benthamiana are capable of inducing antibody-dependent cellular cytotoxicity, an activity not observed for (CHO)PG9. Thus, tailoring of the antigen-binding site combined with glycan modulation and sulfoengineering yielded plant-produced anti-HIV-1 antibodies with effector functions superior to PG9 made in CHO cells.
Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins (2010)

Several neurodegenerative diseases involve the selective damage of neuron cells resulting from the accumulation of amyloid fibril formation. Considering that the formation of amyloid fibrils as well as their precursor oligomers is cytotoxic, the agents that prevent the formation of oligomers and/or fibrils might allow the development of a novel therapeutic approach to neurodegenerative diseases. Here, we show pyrroloquinoline quinone (PQQ) inhibits the amyloid fibril formation of the amyloid proteins, amyloid beta (1-42) and mouse prion protein. The fibril formation of mouse prion protein in the presence of PQQ was dramatically prevented. Similarly, the fibril formation of amyloid beta (1-42) also decreased. With further advanced pharmacological approaches, PQQ may become a leading anti-neurodegenerative compound in the treatment of neurodegenerative diseases.
Electric Propulsion Research and Development at NASA (2018)

Electric propulsion (EP) is an important technology for NASA. It has played a major role on three missions, namely Deep Space 1, Dawn and Space Technology 7, and it is planned for use on many more. The ion propulsion system for the ongoing Dawn mission has achieved several notable accomplishments, including providing a total velocity change (delta-V) of over 11 km/s to the spacecraft. As a result of these successes, solar electric propulsion (SEP) is now broadly recognized as an essential technology for both robotic and human exploration. NASA is currently conducting many projects focused on research and development of EP for a variety of applications. All three of NASA's mission directorates that deal directly with space exploration are actively engaged in supporting work in this area. This paper describes these projects in more detail, including the specific engineering activities being conducted at NASA's main centers for EP technology development, namely Glenn Research Center (GRC) and the Jet Propulsion Laboratory (JPL).
ChemInform Abstract: One‐Pot Ketone Synthesis with Alkylzinc Halides Prepared from Alkyl Halides Via a Single Electron Transfer (SET) Process: New Extension of Fukuyama Ketone Synthesis. (2016)

Abstract The method is elaborated for late‐stage coupling reactions in the convergent synthesis of complex molecules, including the fully protected scaffold (I) containing all carbons of the marine natural product Eribulin.
Toward Unseating the Unsafe C Programming Language (2021)

Reflecting on content that I taught in a recent security course about software-based vulnerabilities, I wondered: Am I giving too much focus to the C programming language? C-based examples get straight to the point, allowing compact illustrations of the concepts underlying stack-and heap-based buffer overruns and return-oriented programming, aside from integer-based vulnerabilities, related to arithmetic underflow, conversions between signed and unsigned values, and errors due to the compiler promotion of short-integer data types in arithmetic expressions.1 But are these relevant for today's students, given the wide availability of modern languages with strong language safety properties? Unfortunately, the answer is still yes.