gebhart/patrepeval huggingface dataset:
Accelerating self-consistent field theory of block polymers in a variable unit cell (2017)

Self-consistent field theory (SCFT) is one of the most widely used tools to study the equilibrium phase behavior of block polymers. We have extended an existing version of the Anderson-mixing iteration scheme to solve the highly nonlinear SCFT equations while simultaneously optimizing the unit-cell dimensions. This improved scheme substantially increases the computational efficiency compared to existing schemes.
The phosphotransferase VanU represses expression of four qrr genes antagonizing VanO-mediated quorum-sensing regulation in Vibrio anguillarum (2011)

Vibrio anguillarum utilizes quorum sensing to regulate stress responses required for survival in the aquatic environment. Like other Vibrio species, V. anguillarum contains the gene qrr1, which encodes the ancestral quorum regulatory RNA Qrr1, and phosphorelay quorum-sensing systems that modulate the expression of small regulatory RNAs (sRNAs) that destabilize mRNA encoding the transcriptional regulator VanT. In this study, three additional Qrr sRNAs were identified. All four sRNAs were positively regulated by σ(54) and the σ(54)-dependent response regulator VanO, and showed a redundant activity. The Qrr sRNAs, together with the RNA chaperone Hfq, destabilized vanT mRNA and modulated expression of VanT-regulated genes. Unexpectedly, expression of all four qrr genes peaked at high cell density, and exogenously added N-acylhomoserine lactone molecules induced expression of the qrr genes at low cell density. The phosphotransferase VanU, which phosphorylates and activates VanO, repressed expression of the Qrr sRNAs and stabilized vanT mRNA. A model is presented proposing that VanU acts as a branch point, aiding cross-regulation between two independent phosphorelay systems that activate or repress expression of the Qrr sRNAs, giving flexibility and precision in modulating VanT expression and inducing a quorum-sensing response to stresses found in a constantly changing aquatic environment.
Cervical cancer suppressor gene is within 1 cM on 6p23 (2000)

We previously showed loss of heterozygosity at 6p to be a common genetic alteration in cervical cancer and cervical intraepithelial neoplasia. To characterize this critical area of deletion in chromosome 6, we evaluated 107 invasive cervical cancers, using 23 polymorphic markers. Genomic DNA from microdissected frozen or paraffin-embedded cervical tumors and corresponding normal tissue was analyzed. Fifty-three percent (57/107) of the cervical tumors showed loss in 6p. Deletions were found in all stages and histologic types. Ninety-one percent (52/57) of these tumors had a loss at 6p23. One tumor defined the distal area of deletion at marker D6S429. Two tumors defined the proximal area of deletion at marker D6S1578. Genotyping of parental DNA was done on 16 cases to evaluate the origin of chromosomal loss. The deletion occurred in the paternal chromosome in 10 tumors and in the maternal in six. Within each tumor, the same parental chromosome was lost at all tested heterozygous 6p markers. The order of the polymorphic markers and estimate of distances in the critical region were confirmed by generation of a yeast artificial chromosome (YAC) contig and pulse-field gel electrophoresis. Our data strongly suggest that a gene important in cervical cancer tumorigenesis is located within a 1-cM region of 6p23, and it is not imprinted. Genes Chromosomes Cancer 27:373–379, 2000. © 2000 Wiley-Liss, Inc.
A cloud-based system for automatic glaucoma screening (2015)

In recent years, there has been increasing interest in the use of automatic computer-based systems for the detection of eye diseases including glaucoma. However, these systems are usually standalone software with basic functions only, limiting their usage in a large scale. In this paper, we introduce an online cloud-based system for automatic glaucoma screening through the use of medical image-based pattern classification technologies. It is designed in a hybrid cloud pattern to offer both accessibility and enhanced security. Raw data including patient's medical condition and fundus image, and resultant medical reports are collected and distributed through the public cloud tier. In the private cloud tier, automatic analysis and assessment of colour retinal fundus images are performed. The ubiquitous anywhere access nature of the system through the cloud platform facilitates a more efficient and cost-effective means of glaucoma screening, allowing the disease to be detected earlier and enabling early intervention for more efficient intervention and disease management.
A randomized trial of ethyl lauroyl arginate‐containing mouthrinse in the control of gingivitis (2015)

The 0.15% LAE-containing mouthrinse was well tolerated and significantly reduced plaque, gingivitis and bleeding when used as an adjunct to tooth brushing for 4 weeks.
Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers (2021)

Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Importantly, we show that this resistance can be overcome through targeting AKT and we find that AKT inhibitors are superior to pan-PI3K inhibition in the context of PTEN loss. However, in the presence of wild-type PTEN and PIK3CA-activating mutations, p110α-dependent signaling is dominant and selectively inhibiting p110α is therapeutically superior to AKT inhibition. These discoveries reveal a more nuanced understanding of PI3K isoform dependency and unveil novel strategies to selectively target PI3K signaling nodes in a context-specific manner.
Rationale for the combination of veliparib with platinum-based chemotherapy. (2015)

2556 Background: Owing to the role of PARPs in DNA damage repair, PARP inhibitors (PARPi) are under clinical investigation as anticancer therapies with a focus on tumors with impaired homologous recombination or regimens containing DNA damaging chemotherapies. Pre-clinical evidence indicates that PARPi potentiate the cytotoxicity of platinums. A recent Phase II study suggested evidence of a benefit in both progression and survival when veliparib was added to carboplatin and paclitaxel in the treatment of advanced NSCLC. Methods: In vitroefficacy was evaluated in GFP-overexpressing cell lines cultured as 3D spheroids. In vivo efficacy was determined in xenograft tumor-bearing SCID mice. PARP1 trapping was evaluated by cellular fractionation and immunoblotting. Bone marrow toxicity was determined with CFU assays. Results: We have developed a method to monitor the growth of 3D spheroids in vitro in real time. In this system, veliparib potentiated the activity of platinums in numerous models. Likewise, veliparib potentiated the activity of platinums in multiple xenograft models in vivo. PARP trapping was undetectable when PARPi were combined with cisplatin. PARPi differed in the extent to which catalytic inhibition and trapping could be resolved. PARPi with more potent trapping activity induced greater cytotoxicity in bone marrow CFU assays than equipotent inhibitors with weaker trapping activity. Conclusions: Veliparib potentiates the activity of platinum agents in vitro and in vivo; however the mechanisms underlying this activity remain unclear. PARP trapping is a recently characterized mechanism central to the synergistic cytotoxicity of PARPi and temozolomide. In contrast, our results suggest that PARP trapping is not required for the combination activity of PARPi and cisplatin. Our observation that potent trapping activity is associated with cytotoxicity towards myeloid and erythroid progenitors suggests that trapping may contribute to the anemia and myelosuppression observed in patients treated with PARPi. As such, PARPi capable of catalytic inhibition at concentrations where trapping is undetectable may be more suitable for combination regimens in which trapping is not required for activity.
Mass Spectrometric Studies of Vapor-Phase Crystal Growth (1972)

A mass spectrometer has been coupled to an open‐tube, vapor‐phase, crystal growth apparatus in order to study vapor‐phase processes leading to the deposition of crystals. Studies of the and Cl2 reactions with gallium showed that is the only gallium chloride formed. Studies of decomposition showed that very little decomposes under given experimental conditions, but this can be changed by the presence of W and Pt. Thermochemical data were collected or calculated for all species detected in the system. The reaction mechanisms leading to the deposition of are discussed. It is concluded that the reaction controlling the deposition of can be written as
The clinical academic workforce of the future: a cross-sectional study of factors influencing career decision-making among clinical PhD students at two research-intensive UK universities (2017)

Findings suggest that urging predoctoral clinicians to gain varied research experience while ensuring availability of opportunities, and introducing more flexible recruitment criteria for CL appointments, would foster CACs. As CL posts are often only open to those still in training, the many postdoctoral clinicians who have completed training, or nearly done so, do not currently gain the opportunity the post offers to develop as independent researchers. Better opportunities should be accompanied by enhanced career support for clinical doctoral students (eg, to increase knowledge of CLs). Finally, ways to increase the number of senior clinical academic appointments should be explored since their lack seems to significantly influence career decisions.
Cutoff wavelength of ridge waveguide near field transducer for disk data storage (2008)

The electromagnetic eigenmodes of and light transmission through a C-aperture to the far field, and to a storage medium, have been studied based on the full vectorial finite difference method. It is found that the cutoff wavelength of C-aperture waveguides in a gold film is much longer than that in a perfect electric conductor, and the fundamental mode is confined in the gap and polarized with the electric field along the gap. The light transmission resonance through C-apertures to far field and to a storage medium occurs at wavelengths below the waveguide cutoff wavelength. Measurements on the fabricated C-apertures confirm the mode confinement and transmission resonance.
Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose (2015)

Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulinproducing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo.
Engineered, highly reactive substrates of microbial transglutaminase enable protein labeling within various secondary structure elements (2017)

Microbial transglutaminase (MTG) is a practical tool to enzymatically form isopeptide bonds between peptide or protein substrates. This natural approach to crosslinking the side-chains of reactive glutamine and lysine residues is solidly rooted in food and textile processing. More recently, MTG's tolerance for various primary amines in lieu of lysine have revealed its potential for site-specific protein labeling with aminated compounds, including fluorophores. Importantly, MTG can label glutamines at accessible positions in the body of a target protein, setting it apart from most labeling enzymes that react exclusively at protein termini. To expand its applicability as a labeling tool, we engineered the B1 domain of Protein G (GB1) to probe the selectivity and enhance the reactivity of MTG toward its glutamine substrate. We built a GB1 library where each variant contained a single glutamine at positions covering all secondary structure elements. The most reactive and selective variants displayed a >100-fold increase in incorporation of a recently developed aminated benzo[a]imidazo[2,1,5-cd]indolizine-type fluorophore, relative to native GB1. None of the variants were destabilized. Our results demonstrate that MTG can react readily with glutamines in α-helical, β-sheet, and unstructured loop elements and does not favor one type of secondary structure. Introducing point mutations within MTG's active site further increased reactivity toward the most reactive substrate variant, I6Q-GB1, enhancing MTG's capacity to fluorescently label an engineered, highly reactive glutamine substrate. This work demonstrates that MTG-reactive glutamines can be readily introduced into a protein domain for fluorescent labeling.
Isolation of signal from stationary microbubbles adhered to vessel walls using an adaptive regression filtering technique (2010)

The singular value filter (SVΓ) is proposed for isolation of adherent microbubble signal in ultrasound-based targeted molecular imaging. The SVF method involves signal decomposition of complex echo data such that ensembles are reexpressed along a new basis determined from principal component analysis (PCA) using the singular value decomposition (SVD) method. In contrast to many previously proposed PCA-based approaches, filter coefficients in SVF are dictated by a weighting function allowing for non-binary coefficients and based upon a signal model of the underlying source signals. The weighting function allows for filter coefficients to be determined adaptively from the shape of the singular value spectra of local regions of echo data, which is quantified using a parameter called the normalized singular spectrum area (NSSA). Simulations in FIELD II are performed to quantify the effects of acoustic scatterer motion characteristics, such as motion and decorrelation, on NSSA. Results confirm that the singular value spectrum flattens, and thus NSSA increases, monotonically with increased axial shift of scatterers between A-lines and increased differential motion. The SVF filter is validated experimentally in an ex vivo porcine artery with adherent microbubbles collecting on the lower wall due to application of acoustic radiation force. SVF was compared to a low-pass infinite impulse response (IIR) filter operating on pulse inversion (PI) data. Results from our ex vivo experiments indicate that signal from adherent microbubbles exhibits higher dimensionality and thus higher NSSA than signal from vessel wall and free microbubbles. SVF provided >; 40dB contrast of adherent microbubble signal over vessel wall and >; 32dB contrast of adherent microbubble over free microbubble signal.
The β2-adrenergic receptor in the apical membrane of intestinal enterocytes senses sugars to stimulate glucose uptake from the gut (2023)

The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (<i>β</i> <sub>2</sub>-AR) at the enterocyte apical membrane and reveal its role in stimulating glucose uptake from the gut by the sodium/glucose-linked transporter, SGLT1. Upon heterologous expression in different reporter systems, the <i>β</i> <sub>2</sub>-AR responds to multiple sugars in the mM range, consistent with estimated gut sugar levels after a meal. Most adrenergic receptor antagonists inhibit sugar signaling, while some differentially inhibit epinephrine and sugar responses. However, sugars did not inhibit binding of I<sup>125</sup>-cyanopindolol, a <i>β</i> <sub>2</sub>-AR antagonist, to the ligand-binding site in cell-free membrane preparations. This suggests different but interdependent binding sites. Glucose uptake into everted sacs from rat intestine was stimulated by epinephrine and sugars in a <i>β</i> <sub>2</sub>-AR-dependent manner. STD-NMR confirmed direct physical binding of glucose to the <i>β</i> <sub>2</sub>-AR. Oral administration of glucose with a non-bioavailable <i>β</i> <sub>2</sub>-AR antagonist lowered the subsequent increase in blood glucose levels, confirming a role for enterocyte apical <i>β</i> <sub>2</sub>-ARs in stimulating gut glucose uptake, and suggesting enterocyte <i>β</i> <sub>2</sub>-AR as novel drug target in diabetic and obese patients. Future work will have to reveal how glucose sensing by enterocytes and neuroendocrine cells is connected, and whether <i>β</i> <sub>2</sub>-ARs mediate glucose sensing also in other tissues.
Evaluating and Enhancing Intel® Stratix® 10 FPGAs for Persistent Real-Time AI (2019)

Interactive intelligent services (e.g., smart web search) are becoming essential datacenter workloads. They rely on data-intensive artificial intelligence (AI) algorithms that do not use batch computation due to their tight latency constraints. Since off-chip data accesses have higher latency and energy consumption than on-chip accesses, a persistent AI approach with the entire model stored in on-chip memory is becoming the new norm for real-time AI. This approach is the cornerstone of Microsoft's Brainwave FPGA-based AI cloud and was recently added to Nvidia's cuDNN library. In this work, we implement, optimize and evaluate a Brainwave-like neural processing unit (NPU) on a large Stratix-10 FPGA. We benchmark it against a large Nvidia Volta GPU running cuDNN persistent AI kernels. Across real-time persistent RNN, GRU, and LSTM workloads, we show that Stratix-10 offers ~3× (FP32) and ~10× (INT8) better latency than GPU (FP32), which uses only ~6% of its peak throughput. Then, we propose TensorRAM, an ASIC chiplet for persistent AI that is 2.5D integrated with an FPGA in the same package. TensorRAM enhances the on-chip memory capacity and bandwidth, with enough multi-precision INT8/4/2/1 throughput to match that bandwidth. Multiple TensorRAMs can be integrated with Stratix-10. Our evaluation shows that a small 32-mm2 TensorRAM on 10nm offers 64MB of SRAMs with 32TB/s on-chiplet bandwidth and 64 TOP/s (INT8). A small Stratix-10 with a TensorRAM (INT8) offers 16× better latency and 34× energy efficiency compared to GPU (FP32). Overall, Stratix-10 with TensorRAM offers compelling and scalable persistent AI solutions.
UWB LNAs using LC ladder and transformers for input matching networks (2006)

The most efficient technique, based on LC ladder filtering, providing wide input matching in UWB LNA is first reviewed. Implemented with integrated inductors in a cascode topology, the circuit covers the 6 to 10 GHz upper frequency of European UWB and achieves an 8 dB maximum gain and 7.5 dB minimum noise figure for a 9 mW power consumption. A transformer implementation of this Inductive Degeneration LC Filtering cascode architecture is also proposed. It leads to reduce by 50% the number of integrated inductors. Providing a 13 dB maximum gain from 3 to 5 GHz, the lower band of UWB, the circuit exhibits a 4 dB minimum NF under 9 mW power consumption.
Oxygen-coupled Redox Regulation of the Skeletal Muscle Ryanodine Receptor/Ca2+ Release Channel (RyR1) (2013)

In mammalian skeletal muscle, Ca(2+) release from the sarcoplasmic reticulum (SR) through the ryanodine receptor/Ca(2+)-release channel RyR1 can be enhanced by S-oxidation or S-nitrosylation of separate Cys residues, which are allosterically linked. S-Oxidation of RyR1 is coupled to muscle oxygen tension (pO2) through O2-dependent production of hydrogen peroxide by SR-resident NADPH oxidase 4. In isolated SR (SR vesicles), an average of six to eight Cys thiols/RyR1 monomer are reversibly oxidized at high (21% O2) versus low pO2 (1% O2), but their identity among the 100 Cys residues/RyR1 monomer is unknown. Here we use isotope-coded affinity tag labeling and mass spectrometry (yielding 93% coverage of RyR1 Cys residues) to identify 13 Cys residues subject to pO2-coupled S-oxidation in SR vesicles. Eight additional Cys residues are oxidized at high versus low pO2 only when NADPH levels are supplemented to enhance NADPH oxidase 4 activity. pO2-sensitive Cys residues were largely non-overlapping with those identified previously as hyperreactive by administration of exogenous reagents (three of 21) or as S-nitrosylated. Cys residues subject to pO2-coupled oxidation are distributed widely within the cytoplasmic domain of RyR1 in multiple functional domains implicated in RyR1 activity-regulating interactions with the L-type Ca(2+) channel (dihydropyridine receptor) and FK506-binding protein 12 as well as in "hot spot" regions containing sites of mutation implicated in malignant hyperthermia and central core disease. pO2-coupled disulfide formation was identified, whereas neither S-glutathionylated nor sulfenamide-modified Cys residues were observed. Thus, physiological redox regulation of RyR1 by endogenously generated hydrogen peroxide is exerted through dynamic disulfide formation involving multiple Cys residues.
Decentralized microservice workflows for coalition environments (2017)

Workflow systems provide a convenient means of specifying distributed data and computing control dependencies amongst services. However, typical workflow system require a centralized management entity to coordinate the flow. In this paper, we explore the notion of fully decentralized workflows, composed using microservices. To this end, we take the approach of exposing service descriptions that have self learning properties wherein services are capable of learning which workflows they can participate in. In addition, we enable matching services to offer themselves up based on best utility, in terms of cost of transaction (processing power), cost of data access and, in coalition environments, security policy.
Semantically ordered parallel execution of multiprocessor programs (2016)

Nondeterministic execution of conventional, multithreaded programs complicates multiprocessor programming and system use in general. To eliminate nondeterminism from multiprocessor programs, we propose an ordered approach. It performs totally ordered execution of parallel algorithms expressed as programs with ordered semantics. We present a runtime system to implement this approach. The runtime provides APIs to express such programs and incorporates mechanisms to parallelize their execution. The runtime reaps the available parallelism by using dataflow and disciplined speculative execution. Further, it uses the program’s task sequence to provide an appearance of total order. We evaluate the ordered approach for expressiveness and performance, by implementing a range of parallel algorithms using it. Experiments on stock machines show that the developed programs, although semantically ordered, can match multithreaded programs in expressing parallelism. They can also match multithreaded programs in performance, in all but cases of very small task sizes and highly nondeterministic algorithms. This work is in collaboration with Gagan Gupta for his Ph.D. thesis.