gebhart/patrepeval huggingface dataset:
O2–02–03: Linkage–based full genome scan for late onset Alzheimer's disease in a genetically isolated population (2006)

We studied late onset Alzheimer's disease (LOAD) in a young, genetically isolated population from the Southwest of the Netherlands. Extensive genealogy was collected, resulting in a complex pedigree containing 103 LOAD patients and their 4,645 relatives. This genealogy provides a unique opportunity to identify LOAD loci. However, utilization of such a pedigree in multipoint linkage analysis is computationally challenging. (1) To develop a new algorithm to cut the entire pedigree into computable sub–units and (2) conduct genome–wide linkage analysis of LOAD. For cutting the entire pedigree, we propose a two–step procedure accomplished by first identifying homogeneous sub–clusters followed by reconstructing pedigrees with reasonable sizes that are suitable for linkage analysis. For the linkage analysis, we assumed a dominant mode of inheritance, modeled the disease penetrance in an age dependent manner, and estimated the allele frequencies based on 72 unaffected, elderly individuals from the same area. The algorithm developed clustered all patients into 35 sub–pedigrees, which accounted for 87.5% of the complete genealogic information. We confirmed four known loci on chromosomes 1q23 (LOD = 4.2 between D1S498 and D1S484), 6p21 (LOD = 2.9 between D6S1610 and D6S257), 10q23 (LOD = 2.6 between D10S1686 and D10S185) and 12q11 (LOD = 1.7 between D12S345 and D12S85). APOE showed only mild evidence of linkage in a two–point analysis (LOD = 1.5). We did not confirm a recently reported linkage on 9q22 where the UBQLIN1 gene is located. We also identified two novel loci on chromosome 3q23 (LOD = 4.3 at D3S1569) and 7p13 (LOD = 3.2 between D7S484 and D7S510). These linkage signals are currently under further investigation by fine mapping. We developed an algorithm that can split large pedigrees into manageable sub–units and preserves maximum information about relationships. The ability to identify known loci in an isolated population provides a strong proof of principle. Furthermore, we suggest two novel LOAD loci on chromosomes 3q23 and 7p13.
High-throughput functional variant screens via in vivo production of single-stranded DNA (2021)

Creating and characterizing individual genetic variants remains limited in scale, compared to the tremendous variation both existing in nature and envisioned by genome engineers. Here we introduce retron library recombineering (RLR), a methodology for high-throughput functional screens that surpasses the scale and specificity of CRISPR-Cas methods. We use the targeted reverse-transcription activity of retrons to produce single-stranded DNA (ssDNA) in vivo, incorporating edits at >90% efficiency and enabling multiplexed applications. RLR simultaneously introduces many genomic variants, producing pooled and barcoded variant libraries addressable by targeted deep sequencing. We use RLR for pooled phenotyping of synthesized antibiotic resistance alleles, demonstrating quantitative measurement of relative growth rates. We also perform RLR using the sheared genomic DNA of an evolved bacterium, experimentally querying millions of sequences for causal variants, demonstrating that RLR is uniquely suited to utilize large pools of natural variation. Using ssDNA produced in vivo for pooled experiments presents avenues for exploring variation across the genome.
Influence Of Solder Joint Shape On The Thermo-Mechanical Reliability Of CSP's (2004)

Not only the stand-off height but also the shape of a solder joint has a strong influence on the joint reliability under temperature cycling. The shape determines the size of the local stress and strain concentrations. It is therefore very important to know well the joint shape after reflow. In a previous paper closed analytical expressions were derived for liquid bump shapes, as a function of pad size and bump height [1]. The bump deformation as a function of the chip weight could be derived from the force constant. In the present paper closed analytical expressions are derived for the force constant for liquid bumps having unequal spherical pad sizes. It turns out that the force constant for compression can be optimized as a function of the ratio of those pad sizes. The shape of the bump and especially the contact angle is of interest for modeling activities where geometrical effects do play a role. Furthermore from the variation in bumps heights on a chip an estimate can be made of the tilt of the chip after assembly. The solder profile estimation by the analytical expressions is validated by experimental results. Also a comparison with the solder profile estimation by the simulation software Surface Evolver is done. Both comparisons showed that the analytical estimation of the standoff height is very good as long as the gravitation energy contributed by the chip weight is less than 10% of the total energy. Finally, an example is shown where the analytical model and Surface Evolver are the geometrical input for a finite element model. The example considers a CSP assembled at both sides of the printed circuit board.
Curvature Based Triangle Mesh Segmentation with Boundary Rectification (2003)

International audience
High-Q Nanocavity-Based Raman Laser Fabricated on a (100) SOI Substrate with a 45-Degree-Rotated Top Silicon Layer (2018)

We report a low-threshold Raman laser based on nanocavities fabricated on an improved (100) SOI substrate with a 45-degree-rotated top silicon layer. We consider that this SOI substrate enables mass production of silicon Raman lasers.
Resonant Beam Communications With Echo Interference Elimination (2020)

Resonant beam communications (RBCom) is capable of providing wide bandwidth when using light as the carrier. Besides, the RBCom system possesses the characteristics of mobility, high signal-to-noise ratio (SNR), and multiplexing. Nevertheless, the channel of the RBCom system is distinct from other light communication technologies due to the echo interference issue. In this article, we reveal the mechanism of the echo interference and propose the method to eliminate the interference. Moreover, we present an exemplary design based on frequency shifting and optical filtering, along with its mathematic model and performance analysis. The numerical evaluation shows that the channel capacity is greater than 15 b/s/Hz.
Stable Germylenes Derived from 1,2-Bis(arylimino)acenaphthenes (2004)

Metal exchange reactions of the magnesium complexes (dpp-BIAN)Mg(THF)n, (dtb-BIAN)Mg(THF)n, and (bph-BIAN)Mg(THF)n with GeCl2(dioxane) afford the stable germylenes (dpp-BIAN)Ge (1), (dtb-BIAN)Ge(Et2O) (2), and (bph-BIAN)Ge (3), respectively (dpp-BIAN = 1,2-[(2,6-iPr2C6H3)N]2C12H6, dtb-BIAN = 1,2-[(2,5-tBu2C6H3)N]2C12H6, bph-BIAN = 1,2-[(2-PhC6H4)N]2C12H6). Compound 1 is also obtained from (dpp-BIAN)Na4 and GeCl4 in Et2O. The germylenes 1−3 were characterized by elemental analyses, 1H NMR, 13C NMR, and IR spectroscopy, and X-ray crystal structure analyses. In the monomeric molecules the two imino nitrogen atoms coordinate the germanium atom. The aryl(N) groups are arranged rather orthogonal to the acenaphthenediimine plane. Compound 3 shows an anti geometry with the ortho phenyl substituents of both N-phenyl rings positioned on opposite sides of the acenaphthenediimine plane. The bite angles N−Ge−N are 85.2° (1) and 85.0° (3), respectively. The Ge−N bond distances in 1−3 range from 1.878 to 1.915 Å.
Geometrical and Electronic Structure of the Pt7 Cluster:  A Density Functional Study (2004)

We present a study on the structural and electronic properties of the Pt7 cluster by using density functional theory within the generalized gradient approximation for the exchange and correlation. The structures, relative stabilities, and vibrational frequencies of various isomers are calculated and compared with the well-studied Au7 cluster. The ground state of the Pt7 cluster favors a three-dimensional geometrytwo-dimensional local minima are not locatedwhereas for its neighbor, gold heptamer, a two-dimensional geometry is favored. The most stable isomer of Au7 is found to be an edge-capped rhombus structure and an edge-capped tetrahedron structure is found to be the most stable three-dimensional local minimum. The ground state of the Pt7 cluster is found to be a coupled tetragonal pyramid structure with the quintet state in contrast to a pentagonal bipyramid structure obtained by semiempirical molecular dynamics calculation. The natural orbital analysis shows that the overall charge transfer is from 6s to 5d orbitals in the Pt7 cluster, whereas in Au7 cluster it is from 5d to 6s. The molecular orbital picture shows that the bonding orbitals are due to the hybridization between 5d and 6s molecular orbitals in Pt7 cluster, and the nonbonding and antibonding orbitals lie close to the highest occupied molecular orbital. This may be compared with the Au7 electronic structure, where the nonbonding and antibonding orbitals mainly consists of 5d6s hybridized molecular orbitals.
The Central Hip Vertical Axis (2010)

The CHVA is more reproducible and showed better intra- and interobserver agreement, when compared with the CSVL for the identification of the lumbar modifier. The CHVA can be easily computed in 3D and represents the physiologic center of balance of the spino-pelvic unit because it takes into account femoral head support. We recommend keeping the CSVL for 2-dimensional measurement to adapt the measures relative to the CSVL to the proposed CHVA axis and adopting CHVA as the reference axis for 3D evaluation of idiopathic scoliosis.
Physical experimentation with prefetching helper threads on Intel's hyper-threaded processors (2004)

Pre-execution techniques have received much attention as an effective way of prefetching cache blocks to tolerate the ever-increasing memory latency. A number of pre-execution techniques based on hardware, compiler, or both have been proposed and studied extensively by researchers. They report promising results on simulators that model a simultaneous multithreading (SMT) processor. We apply the helper threading idea on a real multithreaded machine, i.e., Intel Pentium 4 processor with hyper-threading technology, and show that indeed it can provide wall-clock speedup on real silicon. To achieve further performance improvements via helper threads, we investigate three helper threading scenarios that are driven by automated compiler infrastructure, and identify several key challenges and opportunities for novel hardware and software optimizations. Our study shows a program behavior changes dynamically during execution. In addition, the organizations of certain critical hardware structures in the hyper-threaded processors are either shared or partitioned in the multithreading mode and thus, the tradeoffs regarding resource contention can be intricate. Therefore, it is essential to judiciously invoke helper threads by adapting to the dynamic program behavior so that we can alleviate potential performance degradation due to resource contention. Moreover, since adapting to the dynamic behavior requires frequent thread synchronization, having light-weight thread synchronization mechanisms is important.
ChemInform Abstract: Amidyl and Carbamyl Radicals by Stannane‐Mediated Cleavage of O‐ Benzoyl Hydroxamic Acid Derivatives. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Anab initiocalculation of the ideal tensile strength of β-silicon nitride (2001)

In this study, the ideal strength of \ensuremath{\beta}-silicon nitride was calculated using a first-principles molecular dynamics method. The stress-strain curve of \ensuremath{\beta}-silicon nitride was calculated from simulations of uniaxial extension in the [100] and [001] axial directions, and an ideal tensile strength of \ensuremath{\sim}72.2 and \ensuremath{\sim}75.0 GPa, respectively, was obtained. In addition, the elastic constants were determined, along the two principle axial directions, [100] and [001], and values of \ensuremath{\sim}559 and \ensuremath{\sim}403 GPa, respectively, were obtained. The elastic constant results were found to be in reasonable agreement with existing data.
Implant- and anesthesia-related factors affecting cardiopulmonary threshold intensities for vagus nerve stimulation (2021)

<i>Objective.</i>Vagus nerve stimulation (VNS) is typically delivered at increasing stimulus intensity until a neurological or physiological response is observed ('threshold') for dose calibration, preclinically and therapeutically. Factors affecting VNS thresholds have not been studied systematically. In a rodent model of VNS we measured neural and physiological responses to increasing VNS intensity, determined neurological and physiological thresholds and examined the effect of implant- and anesthesia-related factors on thresholds.<i>Approach.</i>In acute and chronic vagus implants (45 and 20 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake conditions. Evoked compound action potentials (CAPs) were recorded and activation of different fiber types was extracted. Elicited physiological responses were registered, including changes in heart rate (HR), breathing rate (BR), and blood pressure (BP). CAP and physiological thresholds were determined.<i>Main results</i>. The threshold for evoking discernable CAPs (>10<i>µ</i>V) (CAP threshold) is significantly lower than what elicits 5%-10% drop in heart rate (heart rate threshold, HRT) (25<i>µ</i>A ± 1.8 vs. 80<i>µ</i>A ± 5.1, respectively; mean ± SEM). Changes in BP and small changes in BR (bradypnea) occur at lowest intensities (70<i>µ</i>A ± 8.3), followed by HR changes (80<i>µ</i>A ± 5.1) and finally significant changes in BR (apnea) (310<i>μ</i>A ± 32.5). HRT and electrode impedance are correlated in chronic (Pearson correlation<i>r</i>= 0.47;<i>p</i>< 0.001) but not in acute implants (<i>r</i>= -0.34;<i>p</i>NS); HRT and impedance both increase with implant age (<i>r</i>= 0.44;<i>p</i>< 0.001 and<i>r</i>= 0.64;<i>p</i>< 0.001, respectively). HRT is lowest when animals are awake (200<i>µ</i>A ± 35.5), followed by ketamine-xylazine (640<i>µ</i>A ± 151.5), and isoflurane (1000<i>µ</i>A ± 139.5). The sequence of physiological responses with increasing VNS intensity is the same in anesthetized and awake animals. Pulsing frequency affects physiological responses but not CAPs.<i>Significance</i>. Implant age, electrode impedance, and type of anesthesia affect VNS thresholds and should be accounted for when calibrating stimulation dose.
Technologies to address antimicrobial resistance (2018)

Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.
Additive stimulatory action of glucocorticoids and androgens on basal and estrogen-repressed apolipoprotein-D messenger ribonucleic acid levels and secretion in human breast cancer cells. (1992)

Recent elucidation of the amino acid sequence of the progesterone-binding protein GCDFP-24, the major protein found in human breast gross cystic disease fluid, reveals that this glycoprotein corresponds to apolipoprotein-D (apo-D), a member of the alpha 2-microglobulin superfamily which binds small hydrophobic ligands. The present study describes the multiple hormonal control of apo-D mRNA levels, intracellular protein content, as well as secretion compared to cell proliferation in human ZR-75-1 breast cancer cells. In these cells, exposure to the synthetic glucocorticoid dexamethasone (DEX) markedly decreases basal as well as 17 beta-estradiol (E2)-induced cell proliferation while causing a maximal 10-fold stimulation of apo-D secretion in the presence or absence of E2. Incubation with 500 nM DEX or 10 nM dihydrotestosterone (DHT), alone and in combination, markedly increased apo-D mRNA/actin mRNA ratios by 16-, 22-, and 28-fold, respectively. Exposure to 1 nM E2 decreased the apo-D mRNA/actin mRNA ratio by 65%. In E2-treated cells, simultaneous exposure to DHT, DEX, and DHT plus DEX markedly increased the apo-D mRNA/actin mRNA ratios by 50-, 35-, and 105-fold, respectively. The stimulatory effect of DEX on intracellular apo-D content and secretion was also additive to that of the androgen DHT in the presence or absence of E2. The present study provides the first data describing the hormonal regulation of apo-D mRNA levels and intracellular protein content and demonstrates the effect of glucocorticoids alone as well as their interaction with androgens and estrogens on these parameters as well as on apo-D secretion. As shown in the present data, the effects of steroids on apo-D gene expression, intracellular apo-D protein content, and secretion are opposite their respective specific effects on cell proliferation in human ZR-75-1 breast cancer cells.
State of Charge Node Planning with Segmented Traffic Information (2018)

Battery State of Charge (SOC) planning is crucial for the minimization of fuel consumption in Plug-in Hybrid Electric Vehicles (PHEVs). Generally, the charge depleting and charge sustaining strategy is no longer optimal when the required trip energy is greater than the energy stored in a battery. The optimal SOC trajectory depends on the traffic information or the speed profile of the entire trip. In this paper, crude traffic information about the velocity profile, similar to the type of information available in mobile navigation applications, is considered for the SOC planning. Specifically, we propose an effective method of determining the optimal sequence of SOC values at nodes between each segment of a route using segmented sparse traffic information. These SOC node values can be used as boundary conditions or a terminal condition for low-level vehicle energy management with more accurate traffic information available locally. Results from approximate one-hour trip shows that the proposed approach achieves similar fuel consumption improvements (within 2.5%) when compared to solutions from dynamic programming using detailed velocity profiles (with time step every 1 sec). Our proposed method for SOC planning with sparse traffic information improves computation time: from hours to less than a minute.
Inter- and Intramolecular Mechanisms for Chlorine Rearrangements in Trimethyl-Substituted N-Chlorohydantoins (2012)

The antimicrobial compounds 1-chloro-3,5,5-trimethylhydantoin and 3-chloro-1,5,5-trimethylhydantoin (1 and 2, respectively) have been synthesized and examined via a joint experimental and computational study. The measured rate of loss of oxidative chlorine in the absence and presence of exposure to UVA irradiation determined 2 to be less stable than 1. An interesting migration reaction was observed during UVA irradiation that featured the production of chlorine rearrangement and dechlorinated compounds. Two novel hydrogen atom transfer reaction (HATR) mechanisms have been proposed: (1) an intramolecular process in which a hydrogen atom undergoes a series of sigmatropic shifts, and (2) an intermolecular pathway in which a radical abstracts a hydrogen atom from a neighboring molecule. Density functional theory (DFT) calculations at the UB3LYP/6-311G++(2d,p) theory level have been employed to elucidate the preferred reaction pathway. Both proposed HATR mechanisms predicted 2 to possess a lower free energy of activation, ΔG(‡), relative to 1 in accordance with the experimental stability measurements. However, the intermolecular route had an overall lower absolute ΔG(‡) and was more consistent with measured product ratios in solution. The intermolecular reaction pathway, unlike the intramolecular route, also predicted the lack of formation of a migration product featuring a Cl covalently bonded to a methylene group at the 5-position of the hydantoin moiety, which was verified by NMR experiments.
Metabolic Syndrome Mediates ROS-miR-193b-NFYA–Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction (2021)

In heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCβ1 expression. Adeno-associated virus-mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCβ1-cGMP signaling and ameliorate EIPH.
A Bargaining-Based Solution to the Team Mobility Planning Game (2017)

Despite extensive research on mobility planning, a situation in which multiple travellers participate in a cooperative endeavor to help each other optimize their objectives has not been investigated. Furthermore, due to the inherent multi-participant nature of the mobility problem, the existing solutions fail to produce ground-truth optimal mobility plans in the practical sense despite their claimed and well-proven theoretical optimality. This paper presents a team mobility trip-planning solution. The solution comes in the form of a game theoretic treatment of the planning problem. The solution allows multiple participants to engage in a collective solution-finding endeavor. The game theoretic solution utilizes the bargaining game to allow for the drivers to negotiate using their chosen strategies. This paper provides mathematical formulations of the team-planning problem, the developed solution, and the bargaining game. Furthermore, various aspects of the described game, such as game solution existence and game balancedness, are investigated. Simulation results are reported to demonstrate the efficiency of the developed game theoretic formulation under various scenarios.
PMD and CD sensitivity enhancement in directly modulated transmission systems through RZ DM-DPSK (2005)

We compare PMD and CD tolerances of 10 Gb/s directly-modulated transmission formats, including directly-modulated RZ-DPSK, RZ-OOK and NRZ-OOK, using a 1.55 μm commercially-available DML. Along with an increased receiver sensitivity of 3 dB, we show experimentally that RZ DM-DPSK is more robust than directly-modulated RZ-OOK and NRZ-OOK to both PMD and CD. (2 pages)
Development of Semiconductor Manufacturing System Integrating Wafer Process and Packaging Process Using a Half-Inch Sized Package (2018)

We have developed a semiconductor manufacturing system integrating a wafer process and a packaging process by using a half-inch sized package. The developed packaging tools are compatible with the tool-standard of Minimal Fab that we have already developed for half-inch wafer process. We have also developed a model process of a BGA package using the integrated system. We confirmed that MOSFET devices packaged in the BGA package worked electrically.