gebhart/patrepeval huggingface dataset:
Rett syndrome and the MECP2 gene (2001)

First described by Andreas Rett in 1966,1 Rett syndrome is a severe neurodevelopmental disorder which almost exclusively affects females. A genetic aetiology was suggested by MZ twin concordance and a case of vertical transmission of the disorder.2 Although the prevalence is between 1 in 10 000 and 1 in 15 000 female births,3 >95% of cases arise de novo so the disorder has been considered to be an X linked dominant which is lethal in hemizygous males. The few familial cases are almost invariably connected through the female line

The uncertainty of diagnosis associated with the occasional presence of apparently affected males has always been complicated by the wide clinical spectrum presented by females, which ranges from the severely affected “classical” cases through a wide range of disability to a milder forme fruste. This variable severity has been partly ascribed to the degree to which skewing of X inactivation favours expression of the normal X chromosome. This, however, may not explain the specific variants such as the more mildly affected girls with retained speech or the more severe congenitally affected cases with early seizures.

Classically, Rett syndrome may be diagnosed when an affected girl has developed normally for about the first 6 to 18 months of life. At about this age her development begins to slow down and then regresses, with loss of skills already gained, such as speech and purposeful movement of the hands. Affected girls become subject to gross developmental delay, severe mental handicap, stereotyped hand movements such as hand wringing and flapping, an apraxic gait, and autistic behaviour.4 There may also be acquired microcephaly, periods of hyperventilation, and difficulties with swallowing.5 Finally, the regression period plateaus and affected girls survive into adulthood without further deterioration. Table 1 summarises the criteria by which a clinical …
Characterization and Control of Adosorbates of Nitrogen Mono-oxide on Tin Dioxide Surface (1996)

The adso1ption of NO on the suace of SnO2was investigated by combining the measurement of electcal resistance with a temperature programmed de80rption techniue Four types of adsorbates of NO were recognizedom desotion temperaturesieL(30C)(2000C)(280C)and Y(3800C)These were estimated to be cationic dinBr of NO(L)anionic nitro1(SnNO())cationic nitrosyl(SnNO())and anionic nitrito(SnO-NO(Y)) It was)und that the )rmation or distribution of the latter three adsorbates drastically changed depending on the relox state of SnO2surfacethe presence of additives and the coexistence ofoxygen gasBecause ofthe competition ofthree adsorbatesa sensor element using SnO2showed con4)lex behavior upon expo8ure to NO in aiL The addition of an alkali metal oxide such as K20to SnO2wevercould improve the NO nsing Properties signicantly This is attributed to the ndication of adsorption behavior ofNOIt seems that these additives modify the SnO2suce to be more favorable totype adsorption 11NTRODUCTION Recent global issues on environnnt are deding vadous investigations to solve environmentrelatedproblemsDevelopment ofcopactsen80rstodetect2pollutmtsis includedinthiscategolyEspeciallythe detection of NO and NO20ften called NOx COlleCtiVelyin enVirOnment aS Well aS in conustion exhausts is an urgent suect For this purposethe use of semiconducting oxides8eemstobeprosingbecausebothNO an(l NO2tend to be adsorbed rather strongly onetal oxides In facta lot of studies on semicon(luctor sensors fbr NOx have alrea(ly been reporei119)but these approaches are Deptment of Matenals Science and
Synthesis of Nucleoside Analogues Bearing the Five Naturally Occurring Nucleic Acid Bases Built on a 2-Oxabicylo[3.1.0]hexane Scaffold (2005)

Hitherto unknown nucleoside analogues incorporating the five naturally occurring nucleic acid bases built on a 2-oxabicyclo[3.1.0]hexane template were synthesized. The synthesis of these new conformationally restricted nucleoside analogues involved the preparation of a suitable sugar precursor bearing the 2-oxabicyclo[3.1.0]hexane scaffold. This sugar was readily obtained from [(3aS,6aS)-2,2-dimethyl-3a,6a-dihydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether (4) following a Simons-Smith-type cyclopropanation reaction. Finally, glycosylation reactions and deprotection provided the nucleoside analogues. Using nucleoside 14 bearing thymine base as a model, we found that the conformation of such nucleoside analogue was restricted toward a (0)T(1) conformation.
Tailoring DNA Structure To Increase Target Hybridization Kinetics on Surfaces (2010)

We report a method for increasing the rate of target hybridization on DNA-functionalized surfaces using a short internal complement DNA (sicDNA) strand. The sicDNA causes up to a 5-fold increase in association rate by inducing a conformational change that extends the DNA away from the surface, making it more available to bind target nucleic acids. The sicDNA-induced kinetic enhancement is a general phenomenon that occurred with all sequences and surfaces investigated. Additionally, the process is selective and can be used in multicomponent systems to controllably and orthogonally "turn on" specific sequences by the addition of the appropriate sicDNA. Finally, we show that sicDNA is compatible with systems used in gene regulation, intracellular detection, and microarrays, suggesting several potential therapeutic, diagnostic, and bioinformatic applications.
Robust Global Stabilization of an Underactuated Airship with Parameter Uncertainties and Flight Experiments(Mechanical Systems) (2010)

This paper considers the problem of controlling both the planar position and the orientation of an underactuated airship with a reduced number of actuators. The airship is a nonholonomic system described by a set of nonlinear equations and the dynamics are subject to bounded uncertainties. A smooth and time-varying coordinate transformation is utilized to reduce the robust stabilization problem of the airship to that of a linear time-invariant system. A new robust feedback controller is obtained for global stabilization of both the position and the orientation of the underactuated airship with parameter uncertainties. The proposed design method is simple and straightforward. Experiments are performed to validate the effectiveness of the proposed controller.
Phenome-wide association studies (PheWAS) across large “real-world data” population cohorts support drug target validation (2017)

Abstract Phenome-wide association studies (PheWAS), which assess whether a genetic variant is associated with multiple phenotypes across a phenotypic spectrum, have been proposed as a possible aid to drug development through elucidating mechanisms of action, identifying alternative indications, or predicting adverse drug events (ADEs). Here, we evaluate whether PheWAS can inform target validation during drug development. We selected 25 single nucleotide polymorphisms (SNPs) linked through genome-wide association studies (GWAS) to 19 candidate drug targets for common disease therapeutic indications. We independently interrogated these SNPs through PheWAS in four large “real-world data” cohorts (23andMe, UK Biobank, FINRISK, CHOP) for association with a total of 1,892 binary endpoints. We then conducted meta-analyses for 145 harmonized disease endpoints in up to 697,815 individuals and joined results with summary statistics from 57 published GWAS. Our analyses replicate 70% of known GWAS associations and identify 10 novel associations with study-wide significance after multiple test correction (P&lt;1.8x10 -6 ; out of 72 novel associations with FDR&lt;0.1). By leveraging directionality and point estimate of the effect sizes, we describe new associations that may predict ADEs, e.g., acne, high cholesterol, gout and gallstones for rs738409 (p.I148M) in PNPLA3 ; or asthma for rs1990760 (p.T946A) in IFIH1 . We further propose how quantitative estimates of genetic safety/efficacy profiles can be used to help prioritize candidate targets for a specific indication. Our results demonstrate PheWAS as a powerful addition to the toolkit for drug discovery. One Sentence Summary Matching genetics with phenotypes in 800,000 individuals predicts efficacy and on-target safety of future drugs.
TU‐C‐ValB‐02: Patient Specific Differences in Setup Error Variability and Its Effect On Treatment Margins in Fractioned Radiotherapy (2006)

Purpose: It is often assumed that geometric error distributions in radiotherapy differ from patient to patient. It is however, problematic to substantiate this assumption because, generally, limited measurements are available per patient, giving a high uncertainty in the estimate of the standard deviation (SD). Our aim is to develop a simple method to estimate the true distribution variability based on statistical data analysis of a large patient population and to investigate the effect of detected variability on population based PTV‐margins. Method and Materials: Setup error data of 470 prostate cancer patients (11 portal imaging measurements per patient, used for off‐line corrections), were analyzed for random errors. The SD of the setup error was computed for each patient. The RMS‐values of these numbers estimate the random uncertainty in the patient population. Next, the SD of the SD per patient is computed, containing the real distribution variability diluted by “measurement error in the SD” due to the limited number of samples. To estimate the true distribution variability, a correction is applied for this “measurement error”. Finally, that margin was calculated that encloses the CTV with the 95% isodose for 90% of the population. Results: The true inter‐patient variability is 26% of the SD, found after correcting for a “measurement error” of 18% (11 samples). Inter‐patient distribution variability leads to larger PTV‐margins, partly because the range of dose blurring becomes patient dependent. Assuming normality and the same SD variability in random and systematic errors, the margin for systematic errors increases from 2.5SD to 2.8SD, maintaining the same margin for random errors. Conclusion: Inter‐patient distribution variability exists but only slightly exceeds its measurement error and it is therefore difficult to detect for individual patients. By grouping many patients, it can be detected. A variable distribution requires slightly larger margins than a homogenous one.
Peptide Mapping by Two-Dimensional Thin-Layer Electrophoresis-Thin-Layer Chromatography (2003)

The principle behind peptide mapping is straightforward: If two proteins have the same primary structures, then cleavage of each protein with a specific protease or chemical cleavage reagent will yield identical peptide fragments. However, if the proteins have different primary structures, and then the cleavage will generate unrelated peptides. The similarity or dissimilarity of the proteins’ primary structure is reflected in the similarity or dissimilarity of the peptide fragments. Separation of peptides by 2-D thin-layer electrophoresis-thin-layer chromatography (2-D TLE-TLC) results in very high resolution of the peptides, making subtle comparisons possible. There are four phases to the 2-D TLE-TLC peptide mapping process:
Antigenic Drift Defines a New D4 Subgenotype of Measles Virus (2017)

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes.<b>IMPORTANCE</b> Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution.
Low-noise InGaAs APD based on micro-scaled photonic structures for low light imaging application (2022)

In this work, we designed an InGaAs APD with a higher photocurrent to dark current ratio than a regular APD. The improvement is based on optical confinement in an optical resonator, which is able to increase the optical intensity in the detector volume and thus its quantum efficiency. With optical confinement, the absorbing layer can be 20 times thinner than the regular APD, reducing the dark current by the same amount and still be able to produce 90.9% of the photocurrent. The Ip/Id ratio can thus be increased by 18.2 times in concomitant with a lower operating voltage. Higher photocurrent can also be obtained using a thicker absorber. To further increase the detection sensitivity, we designed an efficient InGaAsP LED having the similar resonator geometry. The resonator geometry enables more collimated emission and increases the optical power theoretically by more than 36 times compared with a regular LED. Integrating the resonant APD and LED together will yield a powerful SWIR transceiver for various low light, LIDAR, and 3-dimensional imaging applications.
Diamond — A quantum engineer's best friend (2016)

Diamond possesses remarkable physical and chemical properties, and in many ways is the ultimate engineering material. For example, it is transparent from the ultra-violet to infrared, has a high refractive index (n = 2.4), strong optical nonlinearity (Kerr and Raman) and a wide variety of light-emitting defects. These properties make diamond a highly desirable material for many applications, including those in quantum and nonlinear photonics, high power optics and optomechanics.
Design of broadband beamformers for microphone arrays using variably-weighted least squares (2008)

Various criteria of broadband beamformer design for microphone arrays have been proposed in the literature. However, weighting functions used in these criteria are usually fixed as some constants. Instead, this paper fully exploits the degrees of freedom in weighting functions to design broadband beamformers by using the variably-weighted least squares method. By doing so, we demonstrate that efficient and flexible broadband beamforming can be achieved with passband shaping characteristics while keeping a minimal stopband level. Several design examples are presented to demonstrate the performance of the proposed algorithm.
High-Order Waveguide Modes in ZnO Nanowires (2007)

We use tapered silica fibers to inject laser light into ZnO nanowires with diameters around 250 nm to study their waveguiding properties. We find that high-order waveguide modes are frequently excited and carry significant intensity at the wire surface. Numerical simulations reproduce the experimental observations and indicate a coupling efficiency between silica and ZnO nanowires of 50%. Experimentally, we find an emission angle from the ZnO nanowires of about 90 degrees , which is in agreement with the simulations.
Preoperative Coronary Angiographic Prediction of Bypass Flow and Short‐Term Patency (1975)

A quantitative preoperative coronary angiographic index was defined in 148 patients undergoing coronary revascularization. Each diseased vessel was scored 0-3, for both diameter and quality of run-off. The sum of the scores for diameter and run-off constituted the numerical index for the diseased vessel. Correlations between the index and graft flow measured by electromagnetic flow meter at surgery were established in 259 bypassed vessels. The highest scores (5-6) were associated with higher flows, and the lower scores (0-4) with the lower flows (P less than 0.005). Repeat angiography performed 2 wk postoperatively in 110 patients demonstrated 174 graft patencies and 15 graft closures. Mean flow in open grafts was 82 +/- 41 ml/mn vs. 60 +/- 23ml/mn in closed grafts (P less than 0.005). It is concluded that graft flow is predictable from preoperative Coronary Angiographic Index and that higher flow and index scores are more likely to be associated with graft patency than low flows and index scores.
Synthesis of Halogen-Substituted Pyridyl and Pyrimidyl Derivatives of [3,2-c]Pyrazolo Corticosteroids:  Strategies for the Development of Glucocorticoid Receptor Mediated Imaging Agents (2002)

Ligands for the glucocorticoid receptor labeled with high-energy isotopes are highly desired for their potential applications in nuclear medical studies of the brain where the dysregulation of this receptor system is thought to be involved in various neurodegenerative disorders. Analogues of the glucocorticoid cortivazol have previously been prepared as target compounds for labeling with high-energy isotopes. However, the phenyl rings of arylpyrazoles of this type are not sufficiently activated for nucleophilic substitution reactions that are generally required for the synthesis of radiohalogenated analogues. Since suitably substituted aromatic nitrogen heterocyclic groups are amenable to nucleophilic substitution, the goal of this study was the synthesis of pyridylpyrazolo and pyrimidylpyrazolo analogues similar to cortivazol that could be labeled with radiohalogens in the pyridine or pyrimidine rings. We describe the synthesis of several [3,2-c]pyrazolo steroids containing pyridyl, halopyridyl, and pyrimidyl substituents at the 2' position of the pyrazole ring. These compounds were tested for binding to the glucocorticoid receptor and for biological activity in glucocorticoid responsive HeLa cells grown in tissue culture. Of the pyridyl and pyrimidyl derivatives, 2'-(3-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole showed superior activity in both assays and it was used as the basis for the synthesis of several analogues that were halogenated in the pyridine ring. These halogenated compounds were all tested for their binding to the glucocorticoid receptor and for their biological activity. One, a fluorinated compound 2'-(2-fluoro-5-pyridyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxopregn-4-eno[3,2-c]pyrazole had excellent activity, considerably better than the potent glucocorticoid dexamethasone. Most importantly, fluorination was achieved using a nucleophilic exchange reaction, a method that is adaptable to radiolabeling with the positron-emitting isotope fluorine-18. Thus, considering its superior biological activity and adaptability for facile radiosynthesis, this target compound has the potential for imaging of glucocorticoid receptor containing tissues using positron emission tomography.
Deep profiling of single T cell receptor repertoire and phenotype with targeted RNA-seq (TECH2P.927) (2015)

Abstract Analysis of TCR repertoires is useful for monitoring T cell responses. Integrating TCR sequencing with expression of targeted genes at the single cell level allows comprehensive analysis of T cell function and specificity. RT-PCR reactions of single T cells were performed using 76 primers from VJC regions and 136 primers for targeted T cell genes. A series of nested PCR reactions incorporated with barcodes and adapters for pooled amplicons sequencing. A bioinformatics pipeline was used data analysis. 2880 single T cells were collected and tested. TCR sequences were obtained in up to 90% of the wells. Based on the CDR3 region, multiple dominant TCR clones were identified. 52 of 68 target genes were validated with sorted target-specific T cells. FOXP3, IL10, PRF1, IL13, and RUNX3 were highly expressed in memory activated cells. The specific CD8+ T cells had high frequency of CCR9, LAG3, CD8, CD62L, and IFNG expression. TGFB, TNFA, IL12, FOXP3, PD1, TBET, CTLA4, MKI67, RUNX1, and GATA3 were major biomarkers in the specific CD4 cells. The gene expression patterns were often associated with TCR repertoire CDR3 variations and/or the TCRβ and TCRα chain usage although the same TCRα/β sequences may have different target genes expressed. We expanded a method enabling sequencing of TCR repertoire and multiple functional genes in single, sorted, T cells through targeted RNA-seq technology. This approach could reveal important insights into T cell functions and clonal development.
<title>Characterization of elastic wave propagation in soil</title> (2002)

To optimize a landmine detection system currently being developed at Georgia Tech that uses both electromagnetic and elastic waves, wave propagation in soils has been studied to evaluate propagation characteristics and to identify nonlinear mechanisms. The system under development generates elastic waves in the soil using a surface-contacting transducer designed to preferentially excite Rayleigh waves, thus interrogating the surface layers of the soil. These waves propagate through the region of interest and interact with buried landmines and typical clutter objects (i.e., rocks, sticks, and man-made objects). Surface displacements are measured using a non-contact radar sensor that is scanned over the region of interest. To characterize the wave propagation effects as a function of drive amplitude and as a function of input signal type, a series of experiments was conducted using the radar sensor, accelerometers, and geophones at two test sites, the experimental model at Georgia Tech and a field test site at the Georgia Tech Research Institute's Cobb County Research Facility in suburban Atlanta. The two test sites presented different soils as the experimental model uses damp, compacted sand as a soil surrogate while the field test site has a well-weathered mixture of sand, silt, and clay. Surface displacement measurements were made using the radar sensor while both surface and subsurface measurements were made using triaxial accelerometers and geophones. Linear and nonlinear dispersion, wave speed changes, and nonlinear saturation were observed in the measured data.