gebhart/patrepeval huggingface dataset:
Capturing Vulnerability Variations for Register Files (2013)

Soft error rates are estimated based on worst-case architectural vulnerability factor (AVF). Therefore, it makes tracking real-time accurate AVF very attractive to computer designers: more accurate AVF numbers will allow turning on more features at runtime while keeping the promised SDC and DUE rates. This paper presents a hardware mechanism based on linear regressions to estimate the AVF (SDC and DUE) of the register file for out-of-order cores. Our results show that we are able to have a high correlation factor at low cost.
Enabling Ligand Screening for Palladium‐Catalysed Enantioselective Aza‐Michael Addition Reactions (2007)

In the paper by P. H. Phua, A. J. P. White, J. G. de Vries and K. K. Hii in Issue 4+5, 2006, pp. 587–592 (DOI: 10.1002/adsc.200505404), the structural formula of (R)-Difluorphos in Figure 1 on page 589 is incorrect. The correct structure is given below.1 The compound was procured commerically (Strem) for this work. The synthesis of this ligand and its application in asymmetric catalysis was first reported by Genet and coworkers [S. Jeulin, S. Duprat de Paule, V. Ratovelomanana-Vidal, J.-P. Genet, N. Champion, and P. Dellis, Angew. Chem. Int. Ed. 2004, 43, 320–325]. We are grateful to Professor J.-P. Genet for pointing out the error.
Analytic versus adaptive image formation using optical phased arrays (2009)

Current optical phased arrays produce images by adaptively phasing the output of several telescopes on a common focal plane. Image based phasing techniques such as Phase Diversity, are used to maintain the phasing in real time. This requires both a computationally intensive algorithm for estimating the phasing errors as well as a means for rapidly adjusting the optical path length through each telescope. In this paper we will compare the adaptive technique of phasing multiple telescopes with the analytic technique of digital holography. Digital holography provides a means of digitally estimating and correcting the phasing errors between the multiple telescopes. The process can occur long after the data has been acquired which relaxes the requirements on the stability of the phased array as well as the mechanical complexity. Experimental results will be shown for adaptive and analytical image formation in remote sensing applications.
15-Gbit/in2recording on a DWDD disc using a land/groove substrate with a red laser enabled by a side-wall annealing process (2003)

We developed a side-wall-annealing technique for land/groove substrates. By applying this technique to our Domain Wall Displacement Detection (DWDD) Magneto-Optical (MO) recording stack formed on a land/groove substrate, even with an NA of 0.6 and a wavelength of 660 nm, we realized a density of 15 Gbit/in<sup>2</sup> with a sufficiently wide recording tolerance. This density corresponds to a capacity of 4.7 GB mm disc like MiniDisc.
In‐vitro and in‐vivo pharmacology of a novel TRPV1 receptor antagonist: JNJ38748021 (2008)

TRPV1 is a polymodal nociceptor that plays a critical role in modulating sensory thresholds and is an attractive target for analgesia and inflammatory disorders. Here we report a novel tetrahydropyrimidoazepine, JNJ38748021 that attenuated capsaicin activation of the recombinant TRPV1 receptor with a pIC 50 of 7.2 ± 0.05 against both the rat and the human isoforms (FLIPR). Likewise, JNJ38748021 was also an equipotent antagonist against both pH and anandamide‐induced activation of rat and human TRPV1. The compound also displaced resiniferatoxin in a binding assay with a pK i of 7.2 (rat) and 7.7 (human). Against the native form of TRPV1, JNJ38748021 blocked capsaicin‐induced rat bladder contractility with a pK B of 7.1 (isometric contraction of isolated tissue) and a pIC 50 of 6.8 in isolated rat DRG cultured neurons (whole‐cell patch clamp). JNJ38748021 was modestly orally bioavailable (35%) in rats at 10 mg/kg with a C max of about 1 μM. The clearance and half‐life of the compound was 2.2 l/hr/kg and 1.43 hr, respectively in rats. In a pharmacodynamic model of capsaicin‐induced hypotension, the plasma concentration for half effect (Cp 50 ) was 1 μM. JNJ38748021 (10 and 30 mg/kg, p.o) was efficacious in reversing carrageen‐induced thermal hyperalgesia in rats. In conclusion, JNJ38748021 is a novel TRPV1 antagonist with analgesic properties.
Comparing the Cervista HPV HR Test and Hybrid Capture 2 Assay in a Dutch Screening Population: Improved Specificity of the Cervista HPV HR Test by Changing the Cut-Off (2014)

The diagnostic performance of the widely-used Cervista HPV HR test was compared to the Hybrid Capture 2 (HC2) test in a Dutch population-based cervical cancer screening program. In 900 scrapings of women with normal cytomorphology, specificity was 90% (95%CI: 87.84-91.87) for the Cervista HPV HR test and 96% (95%CI: 94.76-97.37) for the HC2 test with 93% agreement between both tests (κ = 0.5, p<0.001). The sensitivity for CIN2+ using 65 scrapings of women with histological-confirmed CIN2+ was 91% (95%CI: 80.97-96.51) for the Cervista HPV HR test and 92% (95%CI: 82.94-97.43) for the HC2 test with 95% agreement between both tests (κ = 0.7, p<0.001). Fifty-seven of 60 HC2 negative/Cervista positive cases tested HPV-negative with PCR-based HPV assays; of these cases 56% were defined as Cervista triple-positive with FOZ values in all 3 mixes higher than the second cut-off of 1.93 (as set by manufacturer). By setting this cut-off at 5.0, specificity improved significantly without affecting sensitivity. External validation of this new cut-off at 5.0 in triple-positive scrapings of women selected from the SHENCCASTII database revealed that 22/24 histological normal cases now tested HPV-negative in the Cervista HPV HR test, while CIN2+ lesions remained HPV-positive. The intra-laboratory reproducibility of the Cervista HPV HR test (n = 510) showed a concordance of 92% and 93% for cut-off 1.93 and 5.0 (κ = 0.83 and κ = 0.84, p<0.001) and inter-laboratory agreement of the Cervista HPV HR test was 90% and 93% for cut-off 1.93 and 5.0 (κ = 0.80 and κ = 0.85, p<0.001). In conclusion, the specificity of the Cervista HPV HR test could be improved significantly by increasing the second cut-off from 1.93 to 5.0, without affecting the sensitivity of the test in a population-based screening setting.
3D optical imagery for motion compensation in a limb ultrasound system (2016)

Conventional processes for prosthetic socket fabrication are heavily subjective, often resulting in an interface to the human body that is neither comfortable nor completely functional. With nearly 100% of amputees reporting that they experience discomfort with the wearing of their prosthetic limb, designing an effective interface to the body can significantly affect quality of life and future health outcomes. Active research in medical imaging and biomechanical tissue modeling of residual limbs has led to significant advances in computer aided prosthetic socket design, demonstrating an interest in moving toward more quantifiable processes that are still patient-specific. In our work, medical ultrasonography is being pursued to acquire data that may quantify and improve the design process and fabrication of prosthetic sockets while greatly reducing cost compared to an MRI-based framework. This paper presents a prototype limb imaging system that uses a medical ultrasound probe, mounted to a mechanical positioning system and submerged in a water bath. The limb imaging is combined with three-dimensional optical imaging for motion compensation. Images are collected circumferentially around the limb and combined into cross-sectional axial image slices, resulting in a compound image that shows tissue distributions and anatomical boundaries similar to magnetic resonance imaging. In this paper we provide a progress update on our system development, along with preliminary results as we move toward full volumetric imaging of residual limbs for prosthetic socket design. This demonstrates a novel multi-modal approach to residual limb imaging.
Increasing FcγRIIa affinity of an FcγRIII-optimized anti-EGFR antibody restores neutrophil-mediated cytotoxicity (2013)

Antibody-dependent cell-mediated cytotoxicity (ADCC) has been suggested as an essential mechanism for the in vivo activity of cetuximab, an epidermal growth factor receptor (EGFR)-targeting therapeutic antibody. Thus, enhancing the affinity of human IgG1 antibodies to natural killer (NK) cell-expressed FcγRIIIa by glyco- or protein-engineering of their Fc portion has been demonstrated to improve NK cell-mediated ADCC and to represent a promising strategy to improve antibody therapy. However, human polymorphonuclear (PMN) effector cells express the highly homologous FcγRIIIb isoform, which is described to be ineffective in triggering ADCC. Here, non-fucosylated or protein-engineered anti-EGFR antibodies with optimized FcγRIIIa affinities demonstrated the expected benefit in NK cell-mediated ADCC, but did not mediate ADCC by PMN, which could be restored by FcγRIIIb blockade. Furthermore, eosinophils and PMN from paroxysmal nocturnal hemoglobinuria patients that expressed no or low levels of FcγRIIIb mediated effective ADCC with FcγRIII-optimized anti-EGFR antibody. Additional experiments with double FcγRIIa/FcγRIII-optimized constructs demonstrated enhanced PMN-mediated ADCC compared with single FcγRIII-optimized antibody. In conclusion, our data demonstrate that FcγRIIIb engagement impairs PMN-mediated ADCC activity of FcγRIII-optimized anti-EGFR antibodies, while further optimization of FcγRIIa binding significantly restores PMN recruitment.
Improved Itaconate Production with Ustilago cynodontis via Co-Metabolism of CO2-Derived Formate (2022)

In recent years, it was shown that itaconic acid can be produced from glucose with <i>Ustilago</i> strains at up to maximum theoretical yield. The use of acetate and formate as co-feedstocks can boost the efficiency of itaconate production with Ustilaginaceae wild-type strains by reducing the glucose amount and thus the agricultural land required for the biotechnological production of this chemical. Metabolically engineered strains (<i>U. cynodontis</i> Δ<i>fuz7</i> Δ<i>cyp3</i> ↑P<sub>ria1</sub> and <i>U. cynodontis</i> Δ<i>fuz7</i> Δ<i>cyp3</i> P<sub>etef</sub><i>mttA</i> ↑P<sub>ria1</sub>) were applied in itaconate production, obtaining a titer of 56.1 g L<sup>-1</sup> and a yield of 0.55 g<sub>itaconate</sub> per g<sub>substrate</sub>. Both improved titer and yield (increase of 5.2 g L<sup>-1</sup> and 0.04 g<sub>itaconate</sub> per g<sub>substrate</sub>, respectively) were achieved when using sodium formate as an auxiliary substrate. By applying the design-of-experiments (DoE) methodology, cultivation parameters (glucose, sodium formate and ammonium chloride concentrations) were optimized, resulting in two empirical models predicting itaconate titer and yield for <i>U. cynodontis</i> Δ<i>fuz7</i> Δ<i>cyp3</i> P<sub>etef</sub><i>mttA</i> ↑P<sub>ria1</sub>. Thereby, an almost doubled itaconate titer of 138 g L<sup>-1</sup> was obtained and a yield of 0.62 g<sub>itaconate</sub> per g<sub>substrate</sub> was reached during confirmation experiments corresponding to 86% of the theoretical maximum. In order to close the carbon cycle by production of the co-feed via a "power-to-X" route, the biphasic Ru-catalysed hydrogenation of CO<sub>2</sub> to formate could be integrated into the bioprocess directly using the obtained aqueous solution of formates as co-feedstock without any purification steps, demonstrating the (bio)compatibility of the two processes.
Assessment of VoIP quality over Internet backbones (2003)

As the Internet evolves into a ubiquitous communication infrastructure and provides various services including telephony, it has to stand up to the toll quality standards set by traditional telephone companies. Our objective is to assess to what extent today's Internet meets this expectation. Our assessment is based on delay and loss measurements taken over wide-area backbone networks, considers realistic VoIP scenarios and uses quality measures appropriate for voice. Our findings indicate that although voice services can be adequately provided by some ISPs, a significant number of paths lead to poor performance even for excellent VoIP end-systems. This makes a strong case for special handling of voice traffic on those paths. Even on the good paths, rare loss events can occasionally cause perceptible degradation of voice quality. Finally, the appropriate choice of the playout buffer scheme for each path was found to be of critical importance for the perceived quality.
System-level data-flow transformations for power reduction in image and video processing (2002)

Application studies in the domain of image and video processing systems indicate that up to 80% of the power and area cost in customized architectures for such data-dominant processing is due to storage and transfers for multi-dimensional (M-D) data. This paper has two main contributions. First, to reduce this dominant cost, we propose a formalized methodology of data-flow transformations which address the system-level storage organization. Secondly, we will demonstrate the usefulness of the stages in this novel approach based on realistic test-vehicles, i.e. crucial modules in a complex H.263 video decoder system for teleconferencing.
Apolipoprotein E: Essential Catalyst of the Alzheimer Amyloid Cascade (2012)

The amyloid cascade hypothesis remains a robust model of AD neurodegeneration. However, amyloid deposits contain proteins besides Aβ, such as apolipoprotein E (apoE). Inheritance of the apoE4 allele is the strongest genetic risk factor for late-onset AD. However, there is no consensus on how different apoE isotypes contribute to AD pathogenesis. It has been hypothesized that apoE and apoE4 in particular is an amyloid catalyst or "pathological chaperone". Alternatively it has been posited that apoE regulates Aβ clearance, with apoE4 been worse at this function compared to apoE3. These views seem fundamentally opposed. The former would indicate that removing apoE will reduce AD pathology, while the latter suggests increasing brain ApoE levels may be beneficial. Here we consider the scientific basis of these different models of apoE function and suggest that these seemingly opposing views can be reconciled. The optimal therapeutic target may be to inhibit the interaction of apoE with Aβ rather than altering apoE levels. Such an approach will not have detrimental effects on the many beneficial roles apoE plays in neurobiology. Furthermore, other Aβ binding proteins, including ACT and apo J can inhibit or promote Aβ oligomerization/polymerization depending on conditions and might be manipulated to effect AD treatment.
Percolation, tie-molecules, and microstructural origins of charge transport in semicrystalline conjugated polymers (Presentation Recording) (2015)

Semiconducting polymers play an important role in a wide range of optical and electronic material applications. Polymer thin films that result in the highest performance typically have a complex semicrystalline morphology, indicating that considerable device improvement can be achieved through optimization of microstructural properties. However, the connection between molecular ordering and device performance is difficult to predict due to the current need for a mathematical theory of the physics that dictates charge transport in semiconducting polymers. It is experimentally suggested that efficient transport in such films occurs via connected networks of crystallites. We present an analytical and computational description of semicrystalline conjugated polymer materials that captures the impact of polymer conformation on charge transport in heterogeneous thin films. We first develop an analytical theory for the statistical behavior of a polymer emanating from a crystallite and predict the average distance to the first kink in the chain that traps a charge. We use this analysis to define the conditions for percolation and the consequent efficient transport through a semicrystalline material. We then establish a charge transport model using Monte Carlo simulations that predicts the multi-scale charge transport and crystallite connections. We approximate the thin film as a two-dimensional grid of crystallites embedded in amorphous polymer. The chain conformations in the amorphous region are determined by the wormlike chain model, and the crystallites are assigned fixed mobilities. We use this model to identify limits of charge transport at various time scales for varying fraction of crystallinity.
Megatrends (2023)

Understanding megatrends allows individuals and organizations to align with and benefit from the richness of trending technologies.
Arthroscopic Suture‐Bridge Repair for Small to Medium Size Supraspinatus Tear: Healing Rate and Retear Pattern (2012)

Level IV, therapeutic case series.
Sequence-specific DNA sensing based on silicon nanowires (2004)

Highly sensitive, sequence-specific and label-free DNA sensors were demonstrated by monitoring the electronic conductance of silicon nanowires with chemically bonded single stranded (ss) DNA or peptide nucleic acid (PNA) probe molecules. For a 12-mer oligonucleotide, tens of pM of target ss-DNA in solution was recognized when the complementary DNA oligonucleotide probe was attached to the SiNW surfaces. In contrast, ss-DNA samples of 1000x concentration with single base mismatch only produce a weak signal due to nonspecific binding.
Abstract B20: A genome-scale RNA interference screen for resistance mechanisms to BRAF inhibition in melanoma (2012)

Abstract Mutation of the serine/threonine protein kinase BRAF is observed in approximately 50% of melanomas. This leads to enhanced activation of the kinase, stimulation of the MAPK pathway and aberrant cell proliferation and tumorigenesis. Small molecule inhibitors such as vemurafenib (PLX4032) block BRAF-mediated cell proliferation and recent clinical trials show an overall response rate of about 50%. Evidently, some patients do not respond to the drug or go on to develop resistance while on treatment. Therefore, we designed an RNA interference screen to identify loss of function events that could drive resistance to growth-inhibitory concentrations of PLX4720. We used a pooled lentiviral shRNA library consisting of approximately 90,000 hairpins targeting over 16,500 genes. shRNA-infected cells were split into two groups, one treated with DMSO, the other treated with PLX4720. Following a period in culture, the abundance of each hairpin was assessed by PCR amplification of barcoded hairpin DNA followed by massively parallel paired-end sequencing. RIGER was used to rank the individual hairpins and identify candidate genes that were required for survival of A375 cells in the presence of DMSO, compared to an early time point control. Strikingly, BRAF emerged as the most depleted and therefore most essential gene, validating our screening approach. We then identified those hairpins that were enriched in the presence of PLX4720 compared to DMSO. A small number of genes were identified as candidate ‘resistance suppressors’, which when knocked down, conferred a survival advantage to BRAF inhibitor-treated cells. Validation of these genes in secondary assays and characterization of the resistance mechanism(s) will be presented. By integrating these findings with other genomic and functional studies we aim to identify clinically relevant genetic events that cause RAF-inhibitor resistance in melanoma.
Low radiation loss, broadband distribution feedback optical filter (2003)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.
INVEX—a web-based tool for integrative visualization of expression data (2013)

Freely available at http://www.invex.ca.
Mouse APOBEC1 cytidine deaminase can induce somatic mutations in chromosomal DNA (2019)

At an experimental level mouse APOBEC1 is remarkable among 12 mammalian A1 enzymes in that it represents a source of somatic mutations in mouse genome, potentially fueling oncogenesis. While the order Rodentia is bereft of A3A and A3B like enzymes it seems that APOBEC1 may well substitute for it, albeit remaining much less active. This modifies the paradigm that APOBEC3 and AID enzymes are the sole endogenous mutator enzymes giving rise to off-target editing of mammalian genomes.
A QoS framework for heavy-tailed traffic over the wireless Internet (2003)

In this paper, we propose a QoS framework for wireless data applications that accounts for the heavy-tailed nature of Internet traffic. Instead of the conventional wisdom of provisioning more conservatively for such traffic, we investigate scheduling strategies that implicitly penalize the long transactions (e.g., long file transfers) that contribute to the heavy tails, while providing good performance to short transactions (e.g., a short Web page download). The proposed framework is illustrated by the simple model of a bottleneck link, at which transactions (e.g., TCP connections) whose lengths follow a heavy-tailed distribution begin according to a Poisson process. The link scheduler we investigate is the foreground-background (FB) scheduler, which serves, in each transmission slot, the transaction that has received the least service thus far. Comparing the conventional round robin (RR) scheduler with the FB scheduler, we find that the FB scheduler requires much fewer network resources to attain a given QoS. After showing the efficacy of the FB scheduler for a single bottleneck link, we consider a wireless link shared by multiple users, where further gains are obtained by using multiuser diversity, exploiting the differences in the qualities of the channel seen by different users. We generalize our notion of QoS for this scenario, in a manner consistent with the notion of proportional fairness (PF), and investigate scheduling using an appropriate combination of PF across users, and FB across transactions for a given user.
CoRAL: predicting non-coding RNAs from small RNA-sequencing data (2013)

The surprising observation that virtually the entire human genome is transcribed means we know little about the function of many emerging classes of RNAs, except their astounding diversities. Traditional RNA function prediction methods rely on sequence or alignment information, which are limited in their abilities to classify the various collections of non-coding RNAs (ncRNAs). To address this, we developed Classification of RNAs by Analysis of Length (CoRAL), a machine learning-based approach for classification of RNA molecules. CoRAL uses biologically interpretable features including fragment length and cleavage specificity to distinguish between different ncRNA populations. We evaluated CoRAL using genome-wide small RNA sequencing data sets from four human tissue types and were able to classify six different types of RNAs with ∼80% cross-validation accuracy. Analysis by CoRAL revealed that microRNAs, small nucleolar and transposon-derived RNAs are highly discernible and consistent across all human tissue types assessed, whereas long intergenic ncRNAs, small cytoplasmic RNAs and small nuclear RNAs show less consistent patterns. The ability to reliably annotate loci across tissue types demonstrates the potential of CoRAL to characterize ncRNAs using small RNA sequencing data in less well-characterized organisms.