gebhart/patrepeval huggingface dataset:
A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas (2016)

OBJECTIVE A randomized trial that compares clinical outcomes following microsurgery (MS) or stereotactic radiosurgery (SRS) for patients with small- and medium-sized vestibular schwannomas (VSs) is impractical, but would have important implications for clinical decision making. A matched cohort analysis was conducted to evaluate clinical outcomes in patients treated with MS or SRS. METHODS The records of 399 VS patients who were cared for by 2 neurosurgeons and 1 neurotologist between 2001 and 2014 were evaluated. From this data set, 3 retrospective matched cohorts were created to compare hearing preservation (21 matched pairs), facial nerve preservation (83 matched pairs), intervention-free survival, and complication rates (85 matched pairs) between cases managed with SRS and patients managed with MS. Cases were matched for age at surgery (± 10 years) and lesion size (± 0.1 cm). To compare hearing outcomes, cases were additionally matched for preoperative Class A hearing according to the American Academy of Otolaryngology-Head and Neck Surgery guidelines. To compare facial nerve (i.e., cranial nerve [CN] VII) outcomes, cases were additionally matched for preoperative House-Brackmann (HB) score. Investigators who were not involved with patient care reviewed the clinical and imaging records. The reported outcomes were as assessed at the time of the last follow-up, unless otherwise stated. RESULTS The preservation of preoperative Class A hearing status was achieved in 14.3% of MS cases compared with 42.9% of SRS cases (OR 4.5; p < 0.05) after an average follow-up interval of 43.7 months and 30.3 months, respectively. Serviceable hearing was preserved in 42.8% of MS cases compared with 85.7% of SRS cases (OR 8.0; p < 0.01). The rates of postoperative CN VII dysfunction were low for both groups, although significantly higher in the MS group (HB III-IV 11% vs 0% for SRS; OR 21.3; p < 0.01) at a median follow-up interval of 35.7 and 19.0 months for MS and SRS, respectively. There was no difference in the need for subsequent intervention (2 MS patients and 2 SRS patients). CONCLUSIONS At this high-volume center, VS resection or radiosurgery for tumors ≤ 2.8 cm in diameter was associated with low overall morbidity. The need for subsequent intervention was the same in both groups. SRS was associated with improved hearing and facial preservation rates and reduced morbidity, but with a shorter average follow-up period. Facial function was excellent in both groups. Since patients were not randomly selected for surgery, different clinical outcomes may be of different value to individual patients. Both anticipated medical outcomes and patient goals remain the drivers of treatment decisions.
Accessing human selenoproteins through chemical protein synthesis (2016)

The human body contains 25 selenoproteins, which contain in their sequence the twenty-first encoded amino acid, selenocysteine. About a dozen of these proteins remain functionally uncharacterized or poorly studied. Challenges in accessing these selenoproteins using traditional recombinant expressions have prevented biological characterization thus far. Chemical protein synthesis has the potential to overcome these hurdles. Here we report the first total chemical syntheses of two human selenoproteins, selenoprotein M (SELM) and selenoprotein W (SELW). The synthesis of the more challenging protein SELM was enabled using recent advances in the field of selenocysteine chemistry. This approach allows the preparation of selenoproteins in milligram quantities and in homogenous form, which should open new horizons for future studies to pursue a fuller biological understanding of their role in health and disease.
β-Amyloid Precursor Protein: Function in Stem Cell Development and Alzheimer's Disease Brain (2013)

Stem cell therapy may be a suitable approach for the treatment of many neurodegenerative diseases. However, one major impediment to the development of successful cell-based therapies is our limited understanding of the mechanisms that instruct neural stem cell behaviour, such as proliferation and cell fate specification. The β-amyloid precursor protein (APP) of Alzheimer's disease (AD) may play an important role in neural stem cell proliferation and differentiation. Our recent work shows that in vitro, APP stimulates neural stem or progenitor cell proliferation and neuronal differentiation. The effect on proliferation is mediated by an autocrine factor that we have identified as cystatin C. As cystatin C expression is also reported to inhibit the development of amyloid pathology in APP transgenic mice, our finding has implications for the possible use of cystatin C for the therapy of AD.
Insulin and dietary fructose induce stearoyl-CoA desaturase 1 gene expression of diabetic mice. (1994)

The transcription and mRNA levels of murine liver stearoyl-CoA desaturase 1 (SCD1) are induced 11- and 45-fold, respectively, by feeding fasted normal mice with a fat-free, high carbohydrate diet (Ntambi, J. M. (1992) J. Biol. Chem. 267, 10925-10930). In this study, we used streptozotocin-induced diabetic mice to study the regulatory role of carbohydrate and insulin on expression of the SCD1 gene in liver. Fructose administration to fasted diabetic mice induced a 2-fold increase in SCD1 mRNA within 6 h and a 23-fold increase within 24 h. Similarly, insulin administration to diabetic mice induced SCD1 mRNA from 4-fold within 4 h to 22-fold within 24 h. Insulin plus fructose, however, achieved full induction, with a 45-fold increase of SCD1 mRNA and a 10-fold increase in SCD1 transcription within 24 h. Additionally, the effect of insulin on SCD1 mRNA was inhibited 75% with dibutyryl-cAMP and theophylline administration and 70% by cycloheximide administration. Synthesis of liver albumin mRNA showed little change upon dietary manipulation or insulin treatment. Our data demonstrate that insulin and dietary fructose or a metabolite of fructose positively regulate the expression of the SCD1 gene in mouse liver.
<i>In Planta</i> Mutagenesis Determines the Functional Regions of the Wheat Puroindoline Proteins (2009)

In planta analysis of protein function in a crop plant could lead to improvements in understanding protein structure/function relationships as well as selective agronomic or end product quality improvements. The requirements for successful in planta analysis are a high mutation rate, an efficient screening method, and a trait with high heritability. Two ideal targets for functional analysis are the Puroindoline a and Puroindoline b (Pina and Pinb, respectively) genes, which together compose the wheat (Triticum aestivum L.) Ha locus that controls grain texture and many wheat end-use properties. Puroindolines (PINs) together impart soft texture, and mutations in either PIN result in hard seed texture. Studies of the PINs' mode of action are limited by low allelic variation. To create new Pin alleles and identify critical function-determining regions, Pin point mutations were created in planta via EMS treatment of a soft wheat. Grain hardness of 46 unique PIN missense alleles was then measured using segregating F(2):F(3) populations. The impact of individual missense alleles upon PIN function, as measured by grain hardness, ranged from neutral (74%) to intermediate to function abolishing. The percentage of function-abolishing mutations among mutations occurring in both PINA and PINB was higher for PINB, indicating that PINB is more critical to overall Ha function. This is contrary to expectations in that PINB is not as well conserved as PINA. All function-abolishing mutations resulted from structure-disrupting mutations or from missense mutations occurring near the Tryptophan-rich region. This study demonstrates the feasibility of in planta functional analysis of wheat proteins and that the Tryptophan-rich region is the most important region of both PINA and PINB.
Minimally Invasive Randomization for Collecting Unbiased Preferences from Clickthrough Logs (2006)

Clickthrough data is a particularly inexpensive and plentiful resource to obtain implicit relevance feedback for improving and personalizing search engines. However, it is well known that the probability of a user clicking on a result is strongly biased toward documents presented higher in the result set irrespective of relevance. We introduce a simple method to modify the presentation of search results that provably gives relevance judgments that are unaffected by presentation bias under reasonable assumptions. We validate this property of the training data in interactive real world experiments. Finally, we show that using these unbiased relevance judgments learning methods can be guaranteed to converge to an ideal ranking given sufficient data.
Quantitative Ultrasound Assessment of the Rat Cervix (2006)

Quantitative ultrasound predicted cervical ripening in the rat cervix, but before use in humans, quantitative ultrasound will need to predict gestational age in the later days of gestation with more precision.
Study on spatial and temporal mobility pattern of urban taxi services (2010)

The analysis of human behavior is the basis of understanding many social phenomena. Based on a large database of taxi billing system, this paper provides an analysis of human mobility data in an urban area of using taxi services in Shanghai. By studying the spatial temporal data of taxi services, it shows that the distribution of running time interval is approximated by Power-law distribution. And it also reflects that the taxi services may have the short-time and small-scaled characteristics, which seems to be consistent with human travel patterns.
Inhibition of Histone Deacetylase 6 Acetylates and Disrupts the Chaperone Function of Heat Shock Protein 90 (2005)

The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated alpha-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and alpha-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and alpha-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors.
C1q inhibitor (C1qINH): functional properties and possible relationship to a lymphocyte membrane-associated C1q precipitin. (1981)

Abstract A serum inhibitor of C1q (ClqINH) was isolated and its functional properties were studied. ClqINH was found to abrogate the C1q hemolytic activity in a dose-dependent fashion requiring an incubation period of 20 min for optimal inhibition. Quantitiative precipitin studies showed that C1q inhibitor binds to and precipitates isolated C1q forming a C1q-C1qlNH complex with a peak of precipitation at the zone of equivalence. Preincubation of NHS containing 0.01 M EDTA with C1qINH resulted in a marked decrease (60%) when the mixture was tested for hemolytic activity in the presence of calcium. However, no effect was observed when the inhibitor was preincubated with NHS without EDTA, suggesting that C1qINH binds to free C1q in serum but not when it is in complex with C1r and C1s. The uptake of 125IC1q by lymphocytes was also abrogated when the C1q was first preincubated with the inhibitor. Since C1q binds to lymphocyte receptors and to the C1r-Ca++-C1s complex by its collagenous tail, it is inferred that C1q inhibitor may also bind to the collagenous portion of C1q, thereby abrogating its capacity to initiate the complement cascade and attach to C1q receptors on lymphocytes. In addition, an activity that is inhibitory to the C1q-dependent biologic functions was solubilized from the membranes of peripheral blood lymphocytes. The membrane-associated material was found to abrogate C1q hemolytic activity, to bind free C1q in EDTA-treated serum, and to precipitate isolated C1q when analyzed by double immunodiffusion techniques. These results demonstrate that the serum C1qINH can control C1q-dependent immune reactions and tend to suggest that C1qINH might be identical with or related to the inhibitor isolated from lymphocyte membranes. This could mean that C1qINH might be synthesized by lymphocytes and carried as a C1q receptor, which is partly shed into the blood stream as new receptors are synthesized.
Geometric camera calibration using systems of linear equations (2003)

Geometric camera calibration is the process of determining a mapping between points in world coordinates and the corresponding image locations of the points. In previous methods, calibration typically involved the iterative solution to a system of nonlinear equations. A method is presented for performing camera calibration that provides a complete, accurate solution, using only linear systems of equations. By using two calibration planes, a line-of-sight vector is defined for each pixel in the image. The effective focal point of a camera can be obtained by solving the system that defines the intersection point of the line-of-sight vectors. Once the focal point has been determined, a complete camera model can be obtained with a straightforward least-squares procedure. This method of geometric camera calibration has the advantages of being accurate, efficient, and practical for a wide variety of applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
HoloGAN: Unsupervised Learning of 3D Representations From Natural Images (2019)

We propose a novel generative adversarial network (GAN) for the task of unsupervised learning of 3D representations from natural images. Most generative models rely on 2D kernels to generate images and make few assumptions about the 3D world. These models therefore tend to create blurry images or artefacts in tasks that require a strong 3D understanding, such as novel-view synthesis. HoloGAN instead learns a 3D representation of the world, and to render this representation in a realistic manner. Unlike other GANs, HoloGAN provides explicit control over the pose of generated objects through rigid-body transformations of the learnt 3D features. Our experiments show that using explicit 3D features enables HoloGAN to disentangle 3D pose and identity, which is further decomposed into shape and appearance, while still being able to generate images with similar or higher visual quality than other generative models. HoloGAN can be trained end-to-end from unlabelled 2D images only. Particularly, we do not require pose labels, 3D shapes, or multiple views of the same objects. This shows that HoloGAN is the first generative model that learns 3D representations from natural images in an entirely unsupervised manner.
Partially Bridge-Fluorinated Dimethyl Bicyclo[1.1.1]pentane-1,3-dicarboxylates:  Preparation and NMR Spectra (2001)

Direct fluorination of dimethyl bicyclo[1.1.1]pentane-1,3-dicarboxylate, obtained from [1.1.1]propellane prepared by an improved synthetic procedure, furnished esters of 14 of the 15 possible bridge-fluorinated bicyclo[1.1.1]pentane-1,3-dicarboxylic acids, isolated by preparative GC. Calculated geometries reflect the substitution pattern in a regular fashion compatible with Bent's rules. Considerable additional strain is introduced into the bicyclo[1.1.1]pentane cage by polyfluorination; it is calculated to be as high as 33-35 kcal/mol for hexasubstitution. Three arrangements of the fluorine substituents are especially strain-rich: geminal, proximate, and W-related. The (1)H, (13)C, and (19)F NMR spectra exhibit a striking variety of chemical shifts and long-range coupling constants. These are in good agreement with results calculated with neglect of the bridgehead substituents for all of the chemical shifts by the GIAO-RHF/6-31G//RHF/6-31G and GIAO-RHF/6-31G//MP2/6-31G methods and for many of the coupling constants by the EOM-CCSD/6-311G//MP2/6-311G method. The proximate (4)J(FF) constants are particularly large (50-100 Hz) and show an inverse linear dependence on the calculated F-F distance in the range 2.43-2.58 A.
Linear and nonlinear optical susceptibilities of Maxwell Garnett composites: Dipolar spectral theory (1999)

A theory of linear and nonlinear optical susceptibilites of disordered composites consisting of nanospheres in a dielectric host (Maxwell Garnett composites) is developed. The theory is based on a spectral representation in the dipole approximation. Numerical computations are performed in the framework of the dipolar spectral theory to obtain the linear dielectric function and third-order hypersusceptibility. For the fill factors f (from 0.001 to 0.12) considered, our spectral function agrees within the expected 10% error with the previously published function. We have introduced a material independent spectral representation for hypersusceptibilities. The third-order hypersusceptibility ${\ensuremath{\chi}}_{c}^{(3)}$ shows regions of strong enhancement (by up to four orders of magnitude for a silver composite). The mean-field theory provides a reasonable approximation only at very low fill factors $(f\ensuremath{\lesssim}{10}^{\ensuremath{-}3}).$ For $f\ensuremath{\gtrsim}0.04,$ the mean-field theory fails dramatically almost everywhere, except for distant wings of the spectral contour (very far from optical resonances). A physical effect responsible for the failure of the mean-field theories and contributing to the resonant enhancement of nonlinear susceptibilities is large fluctuations of local fields in the resonant region.
Single-chain site-specific mutations of fluorescein-amino acid contact residues in high affinity monoclonal antibody 4-4-20 (1991)

Previous crystallographic studies of high affinity anti-fluorescein monoclonal antibody 4-4-20 (Ka = 1.7 x 10(10) M-1) complexed with fluorescyl ligand resolved active site contact residues involved in binding. For better definition of the relative roles of three light chain antigen contact residues (L27dhis, L32tyr and L34arg), four site-specific mutations (L27dhis to L27lys, L32tyr to L32phe, and L34arg to L34lys and L34his) were generated and expressed in single-chain antigen binding derivatives of monoclonal antibody 4-4-20 containing two different polypeptide linkers (SCA 4-4-20/205c, 25 amino acids and SCA 4-4-20/212, 14 amino acids). Results showed that L27dhis and L32tyr were necessary for wild type binding affinities, however, were not required for near-wild type Qmax values (where Qmax is the maximum fluoroscein fluorescence quenching expressed as percent). Tyrosine L32 which hydrogen bonds with ligand was also characterized at the haptenic level through the use of 9-hydroxyphenylfluoron which lacks the carboxyl group to which L32 tyrosine forms a hydrogen bond. Results demonstrated that wild type SCA and mutant L32phe possessed similar HPF binding characteristics. Active site contact residue L34arg was important for fluorescein quenching maxima and binding affinity (L34his mutant), however, substitution of lysine for arginine at L34 did not have a significant effect on observed Qmax value. In addition, substitutions had no effect on structural and topological characteristics, since all mutants retained similar idiotypic and metatypic properties. Finally, two linkers were comparatively examined to determine relative contributions to mutant binding properties and stability. No linker effects were observed. Collectively, these results verified the importance of these light chain fluorescein contact residues in the binding pocket of monoclonal antibody 4-4-20.
Enantioselective Copper‐Catalysed Allylic Alkylation of Cinnamyl Chlorides by Grignard Reagents using Chiral Phosphine‐Phosphite Ligands (2010)

Abstract The copper(I)‐catalysed S N 2′‐type allylic substitution of E ‐3‐aryl‐allyl chlorides (cinnamyl chlorides) using Grignard reagents represents a powerful method for the synthesis of compounds carrying a benzylic stereocentre. By screening a small library of modular chiral phosphine‐phosphite ligands a new copper(I)‐based catalyst system was identified which allows the performance of such reactions with exceptional high degrees of regio‐ and enantioselectivity. Best results were obtained using TADDOL‐derived ligands (3 mol%), copper(I) bromide⋅dimethyl sulfide (CuBr⋅SMe 2 ) (2.5 mol%) and methyl tert ‐butyl ether (MTBE) as a solvent. Various (1‐alkyl‐allyl)benzene derivatives were prepared with up to 99% ee (GC) in isolated yields of up to 99%. In most cases the product contained less than 3% of the linear regioisomer (except for ortho ‐substituted substrates). Both electron‐rich and electron‐deficient cinnamyl chlorides were successfully employed. The absolute configuration of the products was assigned by comparison of experimental and calculated CD spectra. The substrates were prepared from the corresponding alcohols by reaction with thionyl chloride. Initially formed mixtures of regioisomeric allylic chlorides were homogenised by treatment with CuBr⋅SMe 2 (2.5 mol%) in the presence of triphenyl phosphine (PPh 3 ) (3 mol%) in MTBE at low temperature to give the pure linear isomers. In reactions with methylmagnesium bromide (MeMgBr) an ortho ‐diphenylphosphanyl‐arylphosphite ligand with an additional phenyl substituent in ortho′ ‐position at the aryl backbone proved to be superior. In contrast, best results were obtained in the case of higher alkyl Grignard reagents (such as ethyl‐, n ‐butyl‐, isopropyl‐, and 3‐butenylmagnesium bromides) with a related ligand carrying an isopropyl substituent in ortho′ ‐position. The method was tested on a multi‐mmol scale and is suited for application in natural product synthesis.
Mechanical Properties of Unidirectional Carbon-Coated HI-NICALON Fiber-Reinforced SiC Matrix Composites (1995)

The SiC matrix composites reinforced with carboncoated HI-NICALON were investigated. Samples hotpressed at 1750°C had a maximum strength and KIC of 490 MPa and 11 MPa √m at room temperature, respectively. The strength at 1300°C was higher than that at room temperature. However, the strength decreased above 1400°C. There might be an amorphous phase in the matrix which softens the samples at high temperatures, resulting in plastic behaviour at high temperatures.