gebhart/patrepeval huggingface dataset:
Water Ring Structure at DNA Interfaces: Hydration and Dynamics of DNA-Anthracycline Complexes (1994)

In crystallographic structures of biological macromolecules, one can observe many hydration rings that originate at one water molecule, pass via hydrogen bonds through several others, and return to the original water molecule. Five-membered water rings have been thought to occur with greater frequency than other ring sizes. We describe a quantitative assessment of relationships between water ring size and frequency of occurrence in the vicinity of nucleic acid interfaces. This report focuses on low-temperature X-ray crystallographic structures of two anthracyclines, adriamycin (ADRI) and daunomycin (DAUN), bound to d(CGATCG) and on several DNA structures published previously by others. We have obtained excellent low-temperature (-160 degrees C, LT) X-ray intensity data for d(CGATCG)-adriamycin and d(CGATCG)-daunomycin with a multiwire area detector. The LTX-ray data sets contain 20% (daunomycin, LT-DAUN) and 35% (adriamycin, LT-ADRI) more reflections than were used to derive the original room-temperature (15 degrees C) structures [Frederick, C.A., Williams, L.D., Ughetto, G., van der Marel, G. A., van Boom, J.H., Rich, A., & Wang, A.H.-J. (1990) Biochemistry 29, 2538-2549]. The results show that five-membered water rings are not preferred over other ring sizes. This assessment is consistent with our observation of broad dispersion W-W-W angles (sigma = 20 degrees). In addition, we report that the thermal mobility, distinct from the static disorder, of the amino sugar of daunomycin and adriamycin is significantly greater than that of the rest of the complex. This mobility implies that if the central AT base pair is switched to a CG base pair, there should be a low energy cost in avoiding the guanine amino group. The energy difference (for the sugar-binding preference) between d(CGTACG) and d(CGCGCG) could be considerably less than 20 kcal/mol, a value proposed previously from computation.
A Data-Parallel Implementation of the Adaptive Fast Multipole Algorithm 1 (1993)

Given an ensemble of n bodies in space whose interaction is governed by a potential function, the N-body problem is to calculate the force on each body in the ensemble that results from its interaction with all other bodies. An efficient algorithm for this problem is critical in the simulation of molecular dynamics, turbulent fluid flow, intergalactic matter and other problems. The fast multipole algorithm (FMA) developed by Greengard approximates the solution with bounded error in time O(n ). For non-uniform distributions of bodies, an adaptive variation of the algorithm is required to maintain this time complexity. The parallel execution of the FMA poses complex implementation issues in the decomposition of the problem over processors to reduce communication. As a result the 3D Adaptive FMA has, to our knowledge, never been implemented on a scalable parallel computer. This paper describes several variations on the parallel adaptive 3D FMA algorithm that are expressed using the datapa...
ChemInform Abstract: A New Convenient Synthetic Method and Preliminary Pharmacological Characterization of Triazinediones as Prokineticin Receptor Antagonists. (2014)

Abstract A new improved synthetic methodology to form triazinediones as potential antagonists for prokineticin receptors is described.
Probing the electrical properties of highly-doped Al:ZnO nanowire ensembles (2010)

The analysis of transparent conducting oxide nanostructures suffers from a lack of high throughput yet quantitatively sensitive set of analytical techniques that can properly assess their electrical properties and serve both as characterization and diagnosis tools. This is addressed by applying a comprehensive set of characterization techniques to study the electrical properties of solution-grown Al-doped ZnO nanowires as a function of composition from 0 to 4 at. % Al:Zn. Carrier mobility and charge density extracted from sensitive optical absorption measurements are in agreement with those extracted from single-wire field-effect transistor devices. The mobility in undoped nanowires is 28 cm2/V s and decreases to ∼14 cm2/V s at the highest doping density, though the carrier density remains approximately constant (1020 cm−3) due to limited dopant activation or the creation of charge-compensating defects. Additionally, the local geometry of the Al dopant is studied by nuclear magnetic resonance, showing the occupation of a variety of dopant sites.
Design of instrumentation for probing changes in electrospray droplets via the Stern–Volmer relationship (2004)

Electrospray ionization (ESI) is a proven method for introducing large intact molecules into the gas phase. However, the processes that occur within this ion source are poorly understood. We have developed instrumentation and methodology to probe the evolution of droplets within the electrospray plume. Using emission lifetime spectroscopy, excited-state lifetimes of [Ru(bpy)3]2+ with and without a known quencher, 2,3,5,6-tetramethyl-p-phenlyenediamine, present were observed. Lifetimes were shown to decrease as quencher concentration increased, as expected. Rate constants (with and without quencher present) were determined and correlated with quencher concentration using the Stern–Volmer relationship. Stern–Volmer plots reveal the linearity of the quenching reaction and can be used to determine the concentrations of species within the electrosprayed droplets. The evolution of the ESI droplets can be probed by comparing the concentration of a species at different locations within the plume.
Channel Aligned Beamforming in Two-Way Multi-Pair Decode-and-Forward Relay Down-Link Channels (2012)

We consider the down-link of multi-pair two-way decode-and-forward (DaF) relay channel with multiple antennas at all the nodes. We propose schemes composed of relay pre-coder and user receive beam-formers to support 2M degrees of freedom when M antennas are employed at the relay. A channel aligning technique, where the channel vectors of a pair are forced to be aligned, is introduced so that we can use, at the relay, the well-known pre-coder like zero forcing (ZF) or the regularized channel inversion (RI) from the cellular down-link channels. Alternation based optimization of the pre-coder and the beam-formers searches the channel aligned vector space to further enhance the performance of the scheme in the low and mid SNR range.
ChemInform Abstract: A CONVENIENT SYNTHESIS AND REACTIONS OF SPIRO(3H‐INDOLE‐3,2′‐THIAZOLIDINE)‐2,4′(1H)‐DIONES (1982)

Abstract Durch Reaktion von Isatin (I) mit den Aminen (II) und Mercaptoessigsäure (III) werden die Spiroverbindungen (IV) erhalten.
Randomized phase II trial of weekly squalamine, carboplatin, and paclitaxel as first line therapy for advanced non-small cell lung cancer (2004)

7109 Background:Squalamine is an anti-angiogenic aminosterol that acts directly within activated endothelial cells and has acivity in cancer and eye angiogenesis models. Previously a Phase I/II trial in advanced non-small cell lung cancer (NSCLC) of a once every three weeks regimen of squalamine (given as a five day infusion at doses of 100 to 400 mg/m2/day) combined with carboplatin (AUC=6) and paclitaxel (225 mg/m2) was reported to give a response rate of 28% in 43 patients, with median survival of 10.0 months and one year survival of 40%. In the current study a weekly “metronomic” dosing approach of the squalamine, carboplatin, and paclitaxel regimen was evaluated. Methods:45 patients with Stage IIIB NSCLC with pleural effusion or Stage IV disease were enrolled. The drug regimen was a weekly three hour infusion of squalamine (patients randomly assigned 1:1 to a dose of 100 or 200 mg/m2)combined with weekly carboplatin (AUC=2) and paclitaxel (75 mg/m2), for 12 weeks. Patients were eligible to receive additional chemotherapy if tolerating therapy well and experiencing continued clinical benefit. Results:Two patients were withdrawn for intercurrent illness before receiving any study medication. Objective responses occurred in 23% of the patients (10 of 43; 1 complete and 9 partial responses), with five responses in each of the two dose groups. There were less serious adverse events than with the three weekly regimen. Survival data is maturing and will be available at the time of the presentation. Conclusions:The weekly regimen of squalamine combined with carboplatin and paclitaxel was better tolerated than the three week regimen, but this “metronomic” dosing approach did not improve efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genaera Corp. Genaera Corp. Genaera Corp.
Modeling technology impact on cluster microprocessor performance (2003)

The growing speed gap between transistors and wire interconnects is forcing the development of distributed, or clustered, architectures. These designs partition the chip into small regions with fast intracluster communication. Longer latency is required to communicate between clusters. The hardware and/or software are responsible for scheduling instructions to clusters such that critical path communication occurs within a cluster. This paper presents GENEric SYstems Simulator (GENESYS), a technology modeling tool that captures a broad range of materials, device, circuit, and interconnect parameters across current and future semiconductor technology. This tool is used to explore the relationship between key technology parameters (intercluster wire delay and transistor switching delay) and key architecture parameters (superscalar versus multithreaded instruction dispatch, and value prediction support). GENESYS is used to predict intercluster latencies as VLSI technology advances. The study provides quantitative data showing how conventional superscalar performance is degraded with increasing wire latency. Threaded designs are more tolerant to wire delay. Optimal thread size changes with advancing VLSI technology, suggesting a highly adaptive architecture. Value prediction is shown to be useful in all cases, but provides more benefit to the multithreaded design.
Discovery of PI-1840, a Novel Noncovalent and Rapidly Reversible Proteasome Inhibitor with Anti-tumor Activity (2014)

The proteasome inhibitor bortezomib is effective in hematologic malignancies such as multiple myeloma but has little activity against solid tumors, acts covalently, and is associated with undesired side effects. Therefore, noncovalent inhibitors that are less toxic and more effective against solid tumors are desirable. Structure activity relationship studies led to the discovery of PI-1840, a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nm) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μm) activities of the proteasome. Furthermore, PI-1840 is over 100-fold more selective for the constitutive proteasome over the immunoproteasome. Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor, nutlin, and to the pan-Bcl-2 antagonist BH3-M6. Finally, in vivo, PI-1840 but not bortezomib suppresses the growth in nude mice of human breast tumor xenografts. These results warrant further evaluation of a noncovalent and rapidly reversible proteasome inhibitor as potential anticancer agents against solid tumors.
The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner. (1993)

The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappa B DNA motifs. Bcl-3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappa B (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined I kappa B, which maintains heterodimeric NF-kappa B p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, I kappa B-related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52.
Clinical significance of HIV DNA in polymorphonuclear neutrophils from patients with HIV infection. (1993)

HIV DNA was detected by the polymerase chain reaction technique in polymorphonuclear neutrophils (PMNs) in 11 of 37 (29.7%) HIV-infected patients. A detectable level of HIV DNA in PMNs was more common in symptomatic than asymptomatic HIV infected patients (46.7% and 18.2%, respectively; p < 0.05). HIV DNA in PMNs was detected most frequently in patients with recurrent bacterial pneumonia or Pneumocystis carininii pneumonia. An association between HIV DNA in PMNs and a low CD4/8 ratio as well as high levels of immunoglobulins in the sera was noted. Detectable HIV DNA was found more frequently in patients with neutropenia than in those with a normal level of neutrophils in peripheral blood (44.4% and 28.0%, respectively; p < 0.05). These data suggest that infection of PMNs by HIV may be associated with PMN impairment during HIV infection.
On Green Energy Powered Cognitive Radio Networks (2014)

Green energy powered cognitive radio (CR) network is capable of liberating the wireless access networks from spectral and energy constraints. The limitation of the spectrum is alleviated by exploiting cognitive networking in which wireless nodes sense and utilize the spare spectrum for data communications, while dependence on the traditional unsustainable energy is assuaged by adopting energy harvesting (EH) through which green energy can be harnessed to power wireless networks. Green energy powered CR increases the network availability and thus extends emerging network applications. Designing green CR networks is challenging. It requires not only the optimization of dynamic spectrum access but also the optimal utilization of green energy. This paper surveys the energy efficient cognitive radio techniques and the optimization of green energy powered wireless networks. Existing works on energy aware spectrum sensing, management, and sharing are investigated in detail. The state of the art of the energy efficient CR based wireless access network is discussed in various aspects such as relay and cooperative radio and small cells. Envisioning green energy as an important energy resource in the future, network performance highly depends on the dynamics of the available spectrum and green energy. As compared with the traditional energy source, the arrival rate of green energy, which highly depends on the environment of the energy harvesters, is rather random and intermittent. To optimize and adapt the usage of green energy according to the opportunistic spectrum availability, we discuss research challenges in designing cognitive radio networks which are powered by energy harvesters.
Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle (2007)

MyoD is a myogenic master transcription factor that plays an essential role in muscle satellite cell (muscle stem cell) differentiation. To further investigate the function of MyoD in satellite cells, we examined the transplantation of satellite cell-derived myoblasts lacking the MyoD gene into regenerating skeletal muscle. After injection into injured muscle, MyoD(-/-) myoblasts engrafted with significantly higher efficiency compared with wild-type myoblasts. In addition, MyoD(-/-) myoblast-derived satellite cells were detected underneath the basal lamina of muscle fibers, indicating the self-renewal property of MyoD(-/-) myoblasts. To gain insights into MyoD gene deficiency in muscle stem cells, we investigated the pathways regulated by MyoD by GeneChip microarray analysis of gene expression in wild-type and MyoD(-/-) myoblasts. MyoD deficiency led to down-regulation of many muscle-specific genes and up-regulation of some stem cell markers. Importantly, in MyoD(-/-) myoblasts, many antiapoptotic genes were up-regulated, whereas genes known to execute apoptosis were down-regulated. Consistent with these gene expression profiles, MyoD(-/-) myoblasts were revealed to possess remarkable resistance to apoptosis and increased survival compared with wild-type myoblasts. Forced expression of MyoD or the proapoptotic protein Puma increased cell death in MyoD(-/-) myoblasts. Therefore, MyoD(-/-) myoblasts may preserve stem cell characteristics, including their resistance to apoptosis, expression of stem cell markers, and efficient engraftment and contribution to satellite cells after transplantation. Furthermore, our data offer evidence for improved therapeutic stem cell transplantation for muscular dystrophy, in which suppression of MyoD in myogenic progenitors would be beneficial to therapy by providing a selective advantage for the expansion of stem cells.
Growth Differentiation Factor-9 Stimulates Rat Theca-Interstitial Cell Androgen Biosynthesis1 (2000)

Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the theca layer. Theca cells provide the androgen substrate for aromatization and estrogen production by granulosa cells. Using biologically active recombinant GDF-9 (rGDF-9) and an androgen-producing immortalized theca-interstitial cell (TIC) line or primary TIC, we have examined the action of this paracrine hormone on theca cell steroidogenesis. The effect of GDF-9 on TIC progesterone synthesis was marginal and inconsistent in the primary cultures. In immortalized theca cells, GDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanced both basal and stimulated androstenedione accumulation in the primary and transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preovulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte product, on TIC androgen production suggests a regulatory role of the oocyte on theca cell function and hence on follicle development and differentiation. This direct effect of GDF-9 on thecal steroidogenesis is consistent with its recently demonstrated actions on thecal cell recruitment and differentiation.
The Sparse Abstract Machine (2022)

We propose the Sparse Abstract Machine (SAM), an abstract machine model for targeting sparse tensor algebra to reconfigurable and fixed-function spatial dataflow accelerators. SAM defines a streaming dataflow abstraction with sparse primitives that encompass a large space of scheduled tensor algebra expressions. SAM dataflow graphs naturally separate tensor formats from algorithms and are expressive enough to incorporate arbitrary iteration orderings and many hardware-specific optimizations. We also present Custard, a compiler from a high-level language to SAM that demonstrates SAM's usefulness as an intermediate representation. We automatically bind from SAM to a streaming dataflow simulator. We evaluate the generality and extensibility of SAM, explore the performance space of sparse tensor algebra optimizations using SAM, and show SAM's ability to represent dataflow hardware.
Exact Solutions for the Carrier–Vehicle Traveling Salesman Problem (2017)

Carrier–vehicle systems generally consist of a slow carrier (e.g., a ship) with a long operational range and a faster vehicle (e.g., an aircraft) with a limited operational range. The carrier has the role of transporting the faster vehicle and of deploying, recovering, and servicing it. The goal of the carrier–vehicle traveling salesman problem (CVTSP) is to permit the faster vehicle to visit a given collection of targets in the shortest time while using the carrier as a base for possible multiple trips. As a consequence, the carrier and vehicle should be synchronized. The visiting sequence of the targets is not given a priori. We present a mixed-integer, second-order conic programming (MISOCP) formulation for the CVTSP. Computational results are shown for the resolution of the model with commercial solvers. The MISOCP structure and the relationship to the traveling salesman problem are exploited for developing a ranking-based solution algorithm that outperforms the commercial solvers.
ChemInform Abstract: Further Intramolecular Reactions of 1,2,4‐Triazines. Synthesis of Furo‐[2,3‐b]pyridines and Dihydropyrano[2,3‐b]pyridines. (1986)

Abstract Die Diketone (I) und S‐Methyl‐thiosemicarbazid (II) liefern die Methylthiotriazine (III), die zu den Sultonen (IV) oxidiert werden.
Column-Parallel ADCs for CMOS Image Sensors and Their FoM-Based Evaluations (2018)

This paper reviews architectures and topologies for column-parallel analog-to-digital converters (ADCs) used for CMOS image sensors (CISs) and discusses the performance of CISs using column-parallel ADCs based on figures-of-merit (FoM) with considering noise models which behave differently at low/middle and high pixel-rate regions. Various FoM considering different performance factors are defined. The defined FoM are applied to surveyed data on reported CISs using column-parallel ADCs which are categorized into 4 types; single slope, SAR, cyclic and delta-sigma ADCs. The FoM defined by (noise)2(power)/(pixel-rate) separately for low/middle and high pixel-rate regions well explains the frontline of the CIS' performance in all the pixel rates. Using the FoM defined by (noise)2(power)/(intrascene dynamic range)(pixel-rate), the effectiveness of recently-reported techniques for extended-dynamic-range CISs is clarified.
Phosphatidylinositol 3-Kinase p110δ Isoform Regulates CD8+ T Cell Responses during Acute Viral and Intracellular Bacterial Infections (2016)

The p110δ isoform of PI3K is known to play an important role in immunity, yet its contribution to CTL responses has not been fully elucidated. Using murine p110δ-deficient CD8(+) T cells, we demonstrated a critical role for the p110δ subunit in the generation of optimal primary and memory CD8(+) T cell responses. This was demonstrated in both acute viral and intracellular bacterial infections in mice. We show that p110δ signaling is required for CD8(+) T cell activation, proliferation and effector cytokine production. We provide evidence that the effects of p110δ signaling are mediated via Akt activation and through the regulation of TCR-activated oxidative phosphorylation and aerobic glycolysis. In light of recent clinical trials that employ drugs targeting p110δ in certain cancers and other diseases, our study suggests caution in using these drugs in patients, as they could potentially increase susceptibility to infectious diseases. These studies therefore reveal a novel and direct role for p110δ signaling in in vivo CD8(+) T cell immunity to microbial pathogens.