gebhart/patrepeval huggingface dataset:
The evolution of heterogeneous integration and packaging for the age of chiplets (2023)

Ever since IBM pioneered microelectronics packaging, IBM Research has continued to innovate to ensure that packaging and heterogeneous integration technology is available to satisfy the needs for performance, complexity, and memory and logic density with regard to high performance computing systems. In this era of ever-expanding need for high-performance computing and ever-pervasive artificial intelligence, traditional scaling economics headwinds combined with the need for versatility and fast product development mandate a system-level approach to generate the efficiencies the industry has been able to provide in the past through more traditional scaling approaches. This system-level approach renders imperative the use of chiplet-based architectures and the use of heterogeneous integration and advanced packaging to achieve the disaggregation with best-performing and most efficient IP components to sustain a viable economic model while achieving performance targets. In this talk we will discuss several key process and integration considerations that drive the use of various horizontal and vertical interconnection technology elements that must be implemented to enable the successful realization of efficient and cost-effective high-performance systems in the AI era. Future progress on these technology fronts will depend on disruptive innovation in two critical areas: (a) wafer-level and die-level processes, such as lithographic patterning, wafer-wafer bonding and debonding, bond and assembly processes, etc. that can enable packaging of these heterogeneous structures without compromising performance and reliability, (b) commensurate improvements and enablement of adequate metrology and inspection solutions to address the challenges stemming from these new chiplet-interconnecting methods and the associated topographic implications.
A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression (2019)

Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features transdifferentiation of tissue-resident pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, a process induced by PDAC cells but of unclear significance for PDAC progression. Here, we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state. Specifically, stroma-derived lysophosphatidylcholines support PDAC cell synthesis of phosphatidylcholines, key components of cell membranes, and also facilitate production of the potent wound-healing mediator lysophosphatidic acid (LPA) by the extracellular enzyme autotaxin, which is overexpressed in PDAC. The autotaxin-LPA axis promotes PDAC cell proliferation, migration, and AKT activation, and genetic or pharmacologic autotaxin inhibition suppresses PDAC growth <i>in vivo</i>. Our work demonstrates how PDAC cells exploit the local production of wound-healing mediators to stimulate their own growth and migration. SIGNIFICANCE: Our work highlights an unanticipated role for PSCs in producing the oncogenic LPA signaling lipid and demonstrates how PDAC tumor cells co-opt the release of wound-healing mediators by neighboring PSCs to promote their own proliferation and migration.<i>See related commentary by Biffi and Tuveson, p. 578</i>.<i>This article is highlighted in the In This Issue feature, p. 565</i>.
System-level interconnect architecture exploration for custom memory organizations (2001)

For data dominated applications, power consumption and memory bandwidth bottlenecks can be significantly alleviated with a custom memory organization. However, this potentially entails complex memory interconnections and a large routing overhead. This is undesirable for area cost, power consumption, and layout design complexity. By exploiting time-multiplexing opportunities over the long memory buses, this overhead can be significantly reduced. This paper proposes a system-level methodology for automated exploration of the interconnect architecture, which finds the optimal trade-off points for memory bus time-multiplexing. Experiments performed on real-life applications using our prototype tool show that even for very distributed memory organizations, the interconnect complexity can be significantly reduced to a cost-efficient, manageable level.
Correction: Thermochemical wastewater valorization via enhanced microbial toxicity tolerance (2021)

Correction for ‘Thermochemical wastewater valorization via enhanced microbial toxicity tolerance’ by Lahiru N. Jayakody et al. , Energy Environ. Sci. , 2018, 11 , 1625–1638, DOI: 10.1039/C8EE00460A.
Intramolecular signal transmission in a tetrameric repressor of the IclR family (2011)

Members of the IclR family control bacterial genes involved in a number of physiological processes. The IclR-family member TtgV crystallizes as a tetramer, with each TtgV monomer consisting of two domains--a DNA binding domain and an effector recognition domain, which are interconnected by an extended α-helix. When bound to DNA, a kink is introduced so that the extended helix is split in two α-helices (helix-4 and -5). Differential scanning calorimetry studies revealed that TtgV unfolds in a single event, suggesting that the two domains unfold cooperatively. When mutations are introduced in helix-5 that disrupt interactions between Arg98 and Glu102, the thermal unfolding of the TtgV domains becomes uncoupled without compromising effector binding. Two of these mutants (TtgVE102R and TtgVE102A) showed impaired release from target DNA, suggesting that these mutations alter signal transmission. By combining various mutants, we found that the mutations in the connecting α-helix exhibited a dominant effect over mutations in DNA binding and effector binding domains. We propose a model in which the loss of cooperativity of unfolding of TtgV reflects perturbed interdomain communication, and that the transition from the continuous to discontinuous helix may mediate interdomain communication necessary for the proper functioning of TtgV.
Optimal Spatial Signal Design for mmWave Positioning under Imperfect Synchronization (2021)

We consider the problem of spatial signal design for multipath-assisted mmWave positioning under limited prior knowledge on the user's location and clock bias. We propose an optimal robust design and, based on the low-dimensional precoder structure under perfect prior knowledge, a codebook-based heuristic design with optimized beam power allocation. Through numerical results, we characterize different position-error-bound (PEB) regimes with respect to clock bias uncertainty and show that the proposed low-complexity codebook-based designs outperform the conventional directional beam codebook and achieve near-optimal PEB performance for both analog and digital architectures.
Activation studies with amines and amino acids of the β-carbonic anhydrase encoded by theRv3273gene from the pathogenic bacteriumMycobacterium tuberculosis (2018)

The activation of a β-class carbonic anhydrase (CAs, EC 4.2.1.1) from Mycobacterium tuberculosis, encoded by the gene Rv3273 (mtCA 3), was investigated using a panel of natural and non-natural amino acids and amines. mtCA 3 was effectively activated by D-DOPA, L-Trp, dopamine and serotonin, with K<sub>A</sub>s ranging between 8.98 and 12.1 µM. L-His and D-Tyr showed medium potency activating effects, with K<sub>A</sub>s in the range of 17.6-18.2 µM, whereas other amines and amino acids were relatively ineffective activators, with K<sub>A</sub>s in the range of 28.9-52.2 µM. As the physiological roles of the three mtCAs present in this pathogen are currently poorly understood and considering that inhibition of these enzymes has strong antibacterial effects, discovering molecules that modulate their enzymatic activity may lead to a better understanding of the factors related to the invasion and colonisation of the host during Mycobacterium tuberculosis infection.
Purification and some properties of a thermostable acidic endo-Î²-1,4-d-mannanase fromSclerotium(Athelia)rolfsii (1999)

The phytopathogenic fungus Sclerotium (Athelia) rolfsii forms one major endo-β-1,4-d-mannanase (EC 3.2.1.78) under non-induced and derepressed conditions, i.e. after depletion of glucose which was used as the only carbohydrate substrate for its cultivation. This mannanase was purified to electrophoretic homogeneity by ammonium sulfate precipitation, hydrophobic interaction chromatography, anion exchange chromatography and gel filtration. The enzyme is a glycoprotein with a molecular mass of 46.5±2 kDa (SDS-PAGE), an isoelectric point of 2.75, and a pH optimum of 3.0–3.5. The enzyme is especially stable in the acidic region with an exceptional half-life of activity of 41 days at pH 4.5 and 50°C. It exerts activity on β-1,4-mannan from ivory nut, which is hydrolyzed mainly to mannobiose and mannotriose, as well as on glucomannan, galactomannan, galactoglucomannan, and mannooligosaccharides not smaller than mannotetraose. The main end-products mannotriose and to a lesser extent mannobiose inhibit its activity moderately.
An optimal topology for a static P2P live streaming network: Analysis and real-world results (2011)

In this paper we present a P2P live streaming topology which performs near the optimum under common constraints. We assume two types of nodes: viewers that consume the entire media, and amplifiers which are non-viewing nodes utilized for their upstream bandwidth. We analytically derive the minimum needed server upload, for any topology, under the constraint of limited total peer upload. Under this constraint, we prove that a 2-level topology for the amplifiers is optimal. Then, by running experiments on RayV's real-world commercial system, we demonstrate that in such a 2-level system the server upload is indeed near the minimum.
Structure–activity Relationships of Glutathione Peroxidase 4 Inhibitor Warheads (2020)

&lt;p&gt;Direct inhibition of GPX4 requires covalent modification of the active-site selenocysteine. While phenotypic screening has revealed that activated alkyl chlorides and masked nitrile-oxides can inhibit GPX4 covalently, a systematic assessment of potential electrophilic warheads with the capacity to inhibit cellular GPX4 has been lacking. Here we survey more than 25 electrophilic warheads across several distinct GPX4-targeting scaffolds. Surprisingly, we find that electrophiles with attenuated reactivity compared to chloroacetamides are unable to target GPX4. The highly reactive propiolamide warheads we uncover in this study highlight the potential need for masking strategies similar to those we have described for nitrile-oxide-based GPX4 inhibitors. Finally, our observations that there are spatial requirements between warhead and scaffold for achieving optimal GPX4 targeting and that certain low-molecular-weight analogs inhibit GPX4 with selectivity suggest that rational design of GPX4 inhibitors may be a productive approach. The generation of ligand-bound crystal structures to facilitate such studies should therefore be prioritized by the field. &lt;/p&gt;
Stories from the Trenches (2012)

I will not follow where the path may lead, but I will go where there is no path, and I will leave a trail.
Wideband Probe-Type Waveguide-To-Microstrip Transition for 28 GHz Applications (2018)

A design of a broadband probe-type waveguide-to-microstrip transition operating in the 26-30.5 GHz band is presented. The transition is based on a combination of a simple low-profile waveguide adapter with the WR28 flange and a PCB containing a printed probe, a microstrip line and a short Substrate Integrated Waveguide (SIW) section in-between that is used for impedance matching improvement. The transition is formed only on the top dielectric layer of a multilayer hybrid PCB which consists of a high frequency material Rogers RO4350B with the thickness of 0.168 mm and four layers of traditional low-frequency and low-cost FR4 material. Performance of the designed transition was optimized using full-wave electromagnetic simulations and experimentally verified on two back-to-back test structures each containing two designed transitions separated by a microstrip line with the length of 20 and 30 mm. Measurement results show that the designed waveguide-to-microstrip transition has the bandwidth of 26-30.5 GHz for the -15 dB level of the reflection coefficient with the insertion loss less than 0.8 dB.
Acid-mediated topological control in a functionalized foldamer (2016)

Induced conformational change provides a powerful mechanism to modulate the structure and function of molecules. Here we describe the synthesis of chiral, surface-functionalized oligomeric pyridine/imidazolidin-2-one foldamers, and interrogate their acid-mediated transition between linear and helical topologies.
Abstract 983: Integrative analysis of androgen receptor regulated long non-coding RNA in prostate cancer (2016)

Abstract Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer. AR regulates a large repertoire of genes; however, the effect of androgen signaling on the regulation of long non-coding RNAs (lncRNA) remains incompletely understood. Using transcriptome sequencing (RNA-seq) of AR-positive cell lines VCaP and LNCaP treated with dihydroxytestosterone (DHT), we identified genes, including lncRNAs, which were strongly regulated by AR. To confirm direct regulation by AR, we interrogated AR-ChIP-seq data from VCaP and LNCaP cells, identifying the lncRNAs with direct AR binding. Existence of these lncRNAs in prostate cancer tissue samples was confirmed by analysis of RNA-seq data from prostate tumors, and the degree of differential expression in prostate tumors (localized and castration resistant metastases) versus benign was determined. The most highly overexpressed lncRNA in this analysis was a 2.7kb multi-exonic transcript present on chromosome 16 called ARlnc1. RACE was utilized to determine the exact exon structure of this gene, and its expression levels in various prostate cancer cell lines as well as independent prostate cancer tissue cohorts was assessed. Further, knockdown of ARlnc1 in AR dependent cell lines inhibited cell proliferation and induced apoptosis. Knockdown of ARlnc1 affected molecular signatures related to cell cycle, mitosis and DNA damage. Interestingly, ARlnc1 knockdown also suppressed global androgen signaling as determined by Gene set enrichment analysis using AR gene signature. Upon investigation of the mechanism through which PRCAT47 regulate AR signaling, we discovered that ARlnc1 regulates AR at the level of translation. Taken together, our data suggests that many lncRNAs are regulated by androgen signaling, and we identify one such lncRNA that is involved in a protein-lncRNA positive feedback loop. Citation Format: Rohit Malik, Yajia Zhang, Marcin Cieslik, Yashar S. Niknafs, Sethuramasundaram Pitchiaya, Yasuyuki Hosono, Shruthi Subramaniam, Sahr Yazdani, Xuhong Cao, Dan Robinson, Arul Chinnaiyan. Integrative analysis of androgen receptor regulated long non-coding RNA in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 983.
Analyzing Visual Mappings of Traditional and Alternative Music Notation (2018)

In this paper, we postulate that combining the domains of information visualization and music studies paves the ground for a more structured analysis of the design space of music notation, enabling the creation of alternative music notations that are tailored to different users and their tasks. Hence, we discuss the instantiation of a design and visualization pipeline for music notation that follows a structured approach, based on the fundamental concepts of information and data visualization. This enables practitioners and researchers of digital humanities and information visualization, alike, to conceptualize, create, and analyze novel music notation methods. Based on the analysis of relevant stakeholders and their usage of music notation as a mean of communication, we identify a set of relevant features typically encoded in different annotations and encodings, as used by interpreters, performers, and readers of music. We analyze the visual mappings of musical dimensions for varying notation methods to highlight gaps and frequent usages of encodings, visual channels, and Gestalt laws. This detailed analysis leads us to the conclusion that such an under-researched area in information visualization holds the potential for fundamental research. This paper discusses possible research opportunities, open challenges, and arguments that can be pursued in the process of analyzing, improving, or rethinking existing music notation systems and techniques.
Donepezilium oxalate trihydrate, a therapeutic agent for Alzheimer's disease (2006)

Donepezil, a cholinesterase inhibitor with good central nervous system penetration, has been crystallized as a tertiary amine salt with a disordered oxalate anion to give the title compound, (R,S)-1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl]piperidinium hydrogen oxalate trihydrate, C24H30NO3+.C2HO4-.3H2O. The indanone and piperidine ring planes are inclined at an angle of 33.4 (1) degrees. A comparison is made with the piperidinium cation bound in acetylcholinesterase in the solid state. The methylene units bridging the indanone-piperidine-benzyl groups determine the molecular shape and conformational features. The structure is stabilized mainly by O-H...O and N-H...O hydrogen bonds, with water molecules mediating interactions between oxalate anions and donepezilium cations.
Plasma Spraying of Lanthanum Silicate Electrolytes for Intermediate Temperature Solid Oxide Fuel Cells (ITSOFCs) (2009)

Abstract This study investigates the feasibility of manufacturing lanthanum silicate coatings for solid oxide fuel cells by atmospheric plasma spraying. The coatings produced are cohesive, relatively dense, and contain no secondary phases. Test results show that the starting composition of the powder is maintained after spraying and that particle velocity depends primarily on the plasma gas mixture. Due to the relatively high melting temperature of the particles, dense apatite coatings with few microstructural defects are obtained.
Regularized learning framework in the estimation of reflectance spectra from camera responses (2007)

For digital cameras, device-dependent pixel values describe the camera's response to the incoming spectrum of light. We convert device-dependent RGB values to device- and illuminant-independent reflectance spectra. Simple regularization methods with widely used polynomial modeling provide an efficient approach for this conversion. We also introduce a more general framework for spectral estimation: regularized least-squares regression in reproducing kernel Hilbert spaces (RKHS). Obtained results show that the regularization framework provides an efficient approach for enhancing the generalization properties of the models.
Computing Environments for Data Analysis III: Programming Environments (1988)

This is the third in a series of papers on aspects of modern computing environments that are relevant to statistical data analysis. In this paper, we discuss programming environments. In particular, we argue that integrated programming environments (for example, Lisp and Smalltalk environments) are more appropriate as a base for data analysis than conventional operating systems (for example, Unix).
Inactivation of the dual Bmp/Wnt inhibitor Sostdc1 enhances pancreatic islet function (2012)

Current endeavors in the type 2 diabetes (T2D) field include gaining a better understanding of extracellular signaling pathways that regulate pancreatic islet function. Recent data suggest that both Bmp and Wnt pathways are operative in pancreatic islets and play a positive role in insulin secretion and glucose homeostasis. Our laboratory found the dual Bmp and Wnt antagonist Sostdc1 to be upregulated in a mouse model of islet dysmorphogenesis and nonimmune-mediated lean diabetes. Because Bmp signaling has been proposed to enhance β-cell function, we evaluated the role of Sostdc1 in adult islet function using animals in which Sostdc1 was globally deleted. While Sostdc1-null animals exhibited no pancreas development phenotype, a subset of mutants exhibited enhanced insulin secretion and improved glucose homeostasis compared with control animals after 12-wk exposure to high-fat diet. Loss of Sostdc1 in the setting of metabolic stress results in altered expression of Bmp-responsive genes in islets but did not affect expression of Wnt target genes, suggesting that Sostdc1 primarily regulates the Bmp pathway in the murine pancreas. Furthermore, our data indicate that removal of Sostdc1 enhances the downregulation of the closely related Bmp inhibitors Ctgf and Gremlin in islets after 8-wk exposure to high-fat diet. These data imply that Sostdc1 regulates expression of these inhibitors and provide a means by which Sostdc1-null animals show enhanced insulin secretion and glucose homeostasis. Our studies provide insights into Bmp pathway regulation in the endocrine pancreas and reveal new avenues for improving β-cell function under metabolic stress.
Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase (2021)

The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
Dissecting a population genome for targeted screening of disease mutations (2001)

Compared to mixed populations, population isolates such as Finland show distinct differences in the prevalence of disease mutations. However, little information exists of the differences on the prevalence of different disease alleles in regional populations with different history of multiple bottlenecks. We constructed a DNA-array and monitored the prevalence of 31 rare and common disease mutations underlying 27 clinical phenotypes in a large population-based study sample. Over 64 000 genotypes were assigned in 2151 samples from four geographical areas representing early and late settlement regions of Finland. Each sample was analyzed in duplicate and a total of 142 000 array-derived genotyping calls were made. On average one in three individuals was found to be a carrier of one of the 31 monitored mutations. This should remove fears of the stigmatizing effect of a carrier-screening program monitoring multiple diseases. Regional differences were found in the prevalence of mutations, providing molecular evidence for the deviating population histories of regional subisolates. The mutations introduced early into the population revealed relatively even distribution in different subregions. More recently introduced rare mutations showed local clustering of disease alleles, indicating the persistence of population subisolates and the effect of multiple bottlenecks in molding the population gene pool. Regional differences were observed also for common disease alleles. Such precise information of the carrier frequencies could form the basis for targeted genetic screens in this population. Our approach describes a general paradigm for large-scale carrier-screening programs also in other populations.