gebhart/patrepeval huggingface dataset:
Estimates of the Rate and Distribution of Fitness Effects of Spontaneous Mutation in Saccharomyces cerevisiae (2001)

The per-genome, per-generation rate of spontaneous mutation affecting fitness (U) and the mean fitness cost per mutation (s) are important parameters in evolutionary genetics, but have been estimated for few species. We estimated U and sh (the heterozygous effect of mutations) for two diploid yeast strains differing only in the DNA mismatch-repair deficiency used to elevate the mutation rate in one (mutator) strain. Mutations were allowed to accumulate in 50 replicate lines of each strain, during 36 transfers of randomly chosen single colonies (approximately 600 generations). Among wild-type lines, fitnesses were bimodal, with one mode showing no change in mean fitness. The other mode showed a mean 29.6% fitness decline and the petite phenotype, usually caused by partial deletion of the mitochondrial genome. Excluding petites, maximum-likelihood estimates adjusted for the effect of selection were U = 9.5 x 10(-5) and sh = 0.217 for the wild type. Among the mutator lines, the best fit was obtained with 0.005 < or = U < or = 0.94 and 0.049 > or = sh > or = 0.0003. Like other recently tested model organisms, wild-type yeast have low mutation rates, with high mean fitness costs per mutation. Inactivation of mismatch repair increases the frequency of slightly deleterious mutations by approximately two orders of magnitude.
Utility and Feasibility of a Center Surround Event Camera (2022)

Standard dynamic vision sensor (DVS) event cameras output a stream of spatially-independent log-intensity brightness change events so they cannot suppress spatial redundancy. Nearly all biological retinas use an antagonistic center-surround organization. This paper proposes a practical method of implementing a compact, energy-efficient Center Surround DVS (CSDVS) with a surround smoothing network that uses compact polysilicon resistors for lateral resistance. The paper includes behavioral simulation results for the CSDVS (see sites.google.com/view/csdvs/home). The CSDVS would significantly reduce events caused by low spatial frequencies, but amplify the informative high frequency spatiotemporal events.
Thermal Lability of Beta Galactosidase from Pink Salmon Liver (1969)

The effect of heat on the stability of a protein isolated from a cold-water fish was tested by following the decrease in enzymatic activity of beta galactosidase, purified from livers of Pacific pink salmon. The thermal stability is pH-dependent; it is highest at pH 4 and lowest at neutral pH, where only 30 percent of the activity remains after 10 minutes at 40 degrees C. Comparative experiments demonstrate greater thermal stability of beta galactosidase from rat liver.
Multi-Combilipases: Co-Immobilizing Lipases with Very Different Stabilities Combining Immobilization via Interfacial Activation and Ion Exchange. The Reuse of the Most Stable Co-Immobilized Enzymes after Inactivation of the Least Stable Ones (2020)

The lipases A and B from Candida antarctica (CALA and CALB), Thermomyces lanuginosus (TLL) or Rhizomucor miehei (RML), and the commercial and artificial phospholipase Lecitase ultra (LEU) may be co-immobilized on octyl agarose beads. However, LEU and RML became almost fully inactivated under conditions where CALA, CALB and TLL retained full activity. This means that, to have a five components co-immobilized combi-lipase, we should discard 3 fully active and immobilized enzymes when the other two enzymes are inactivated. To solve this situation, CALA, CALB and TLL have been co-immobilized on octyl-vinyl sulfone agarose beads, coated with polyethylenimine (PEI) and the least stable enzymes, RML and LEU have been co-immobilized over these immobilized enzymes. The coating with PEI is even favorable for the activity of the immobilized enzymes. It was checked that RML and LEU could be released from the enzyme-PEI coated biocatalyst, although this also produced some release of the PEI. That way, a protocol was developed to co-immobilize the five enzymes, in a way that the most stable could be reused after the inactivation of the least stable ones. After RML and LEU inactivation, the combi-biocatalysts were incubated in 0.5 M of ammonium sulfate to release the inactivated enzymes, incubated again with PEI and a new RML and LEU batch could be immobilized, maintaining the activity of the three most stable enzymes for at least five cycles of incubation at pH 7.0 and 60 °C for 3 h, incubation on ammonium sulfate, incubation in PEI and co-immobilization of new enzymes. The effect of the order of co-immobilization of the different enzymes on the co-immobilized biocatalyst activity was also investigated using different substrates, finding that when the most active enzyme versus one substrate was immobilized first (nearer to the surface of the particle), the activity was higher than when this enzyme was co-immobilized last (nearer to the particle core).
An Improved Decoding Scheme for Emergency Alert Wake-Up Bits in ATSC 3.0 (2019)

This paper proposes an improved decoding scheme of emergency alert wake-up bits in Advanced Television Systems Committee (ATSC) 3.0. When a broadcast service is being provided, a bootstrap signal of ATSC 3.0 includes the minimal essential information that does not change at least for two consecutive physical layer frames. Then, the received signal can be further assumed to be binary modulated according to each wake-up bit, so as to achieve the improved decoding performance as well as reduced decoding complexity. The simulation results show that the proposed decoding scheme of wake-up bits can obtain signal-to-noise ratio (SNR) gains of approximately 1.6 dB and 2.5 dB at bit error rate (BER) of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> compared to the conventional decoding scheme under fixed and mobile reception environments, respectively. In addition, the analysis on the computational complexity of the proposed decoding scheme is provided.
On kernel methods for relational learning (2003)

Kernel methods have gained a great deal of popularity in the machine learning community as a method to learn indirectly in highdimensional feature spaces. Those interested in relational learning have recently begun to cast learning from structured and relational data in terms of kernel operations. We describe a general family of kernel functions built up from a description language of limited expressivity and use it to study the benefits and drawbacks of kernel learning in relational domains. Learning with kernels in this family directly models learning over an expanded feature space constructed using the same description language. This allows us to examine issues of time complexity in terms of learning with these and other relational kernels, and how these relate to generalization ability. The tradeoffs between using kernels in a very high dimensional implicit space versus a restricted feature space, is highlighted through two experiments, in bioinformatics and in natural language processing. 1.
Oestrogen-Induced Changes in the Synaptology of the Monkey (Cercopithecus aethiops) Arcuate Nucleus During Gonadotropin Feedback (2001)

To assess their role in the regulation of gonadotropin secretion in primates, we determined the number of synaptic connections on gondotropin releasing hormone (GnRH)- and non-GnRH neurones of the arcuate nucleus of ovariectomized (OVX) and OVX plus oestradiol benzoate-treated African green monkeys. After 24 h (day 1), 48 h (day 2) and 8 days (day 8), we performed immunostaining for GnRH. Using electron microscopy, synapses on GnRH- and randomly selected non-GnRH neurones were counted and characterized according to the classification of Gray (symmetric/inhibitory or asymmetric/excitatory). Serum concentrations of oestradiol (OVX) needed to 232 pg/ml on day 1, 63 pg/ml on day 2 and 45 pg/ml on day 8. Concentrations of luteinizing hormone (LH) fell after ovariectomy to 9 microg/ml on day 1, surged to 93 microg/ml on day 2 and declined again by day 8. (a) Ten days after ovariectomy, there were no synapses on GnRH neurones, whereas non-GnRH cells received substantial inhibitory innervation and moderate excitatory input. (b) On day 1, GnRH neurones had highest numbers of inhibitory synapses, while inhibitory synapses on non-GnRH neurones decreased, whereas numbers of excitatory synapses remained relatively unchanged compared to OVX monkeys. (c) By day 2, synapses on GnRH neurones decreased, while synapses increased on non-GnRH cells compared to day 1. (d) On day 8, the most pronounced alteration on GnRH cells was an elevated inhibitory input while non-GnRH neurones received the fewest synapses compared to day 2. We conclude that during an oestrogen-induced LH surge, synapses on GnRH- and mixed non-GnRH neurones are differentially regulated. These findings suggest that oestrogen modulation of arcuate nucleus synapses may be important in the regulation of gonadotropin secretion in monkeys.
Operational Resource Theory of Nonclassicality and the Mach-Zehnder Interferometer (2019)

The nonclassical properties of quantum states are of tremendous interest due to their potential applications in future technologies. It has recently been realized that the concept of a theory is a powerful approach to quantifying and understanding nonclassicality. An important goal in this endeavor is to find resource theoretic measures of nonclassicality that are operational, meaning that they also quantify the ability of quantum states to provide enhanced performance for specific tasks, such as precision sensing. Here we present such a measure: it satisfies the necessary requirements of a resource-theoretic measure, and has the closest possible relationship to precision measurement: it quantifies the quantum-enhanced precision for pure states and is a tight upper bound on this precision for mixed states. We also show that a balanced Mach-Zehnder Interferometer provides a way to experimentally extract this measure, and we examine how the measure quantifies the concept of macroscopicity.
Statistical Mechanics of Coal Treated as a Densely Cross-Linked Network (1997)

An analysis of the statistical mechanics of a densely cross-linked system is presented. It is argued that for such systems fluctuations of the cross-link points will be severely inhibited and the assumption of affine deformation should be reasonable. It is first demonstrated that the usual result obtained by classical theories can be obtained by an alternative method without assuming Gaussian statistics or the Langevin approximation for the partition function. For values of N, the number of “statistical segments” (freely hinged and rotating) between cross-link points, ≤2, the Gaussian results cannot apply. For small deformations of networks with N ≥ 3, the Gaussian approximation is shown to be valid. This latter result will be employed in studies of the deformation of swollen coal gels in future work.
Decreased plasma adiponectin concentration in patients with essential hypertension (2003)

Adipocytes secrete several biologically active substances that are presumed to be involved in obesity-related hypertension. There are no reports that deal with the relationship between plasma adiponectin concentration and blood pressure (BP). To evaluate the role of adiponectin in essential hypertension 33 patients with essential hypertensive (EHP) (12 women, 21 men) and 33 body mass index-matched normotensive healthy subjects (NHS) (13 women, 20 men) were studied. In EHP plasma adiponectin concentration was significantly lower than in NHS (9.1 +/- 4.5 v 13.7 +/- 5.2 microg/mL, respectively). In all subjects a significant negative correlation was found between plasma adiponectin concentration and mean, systolic, and diastolic BP, suggesting that adiponectin contributes to the clinical course of essential hypertension.
Response Surface Techniques for Diffuser Shape Optimization (2000)

The design of incompressible diffusers for maximum pressure recovery is used to demonstrate the utility of response surface approximations for design optimization of flow devices. Two examples involving two and five design variables are treated, with the diffuser wall shapes described by polynomials and B-splines. In both cases monotonicity conditions drastically reduce the design space. In this irregularly shaped space, a pool of designs is selected by a D-optimality criterion and analyzed by a finite volume computational fluid dynamics (CFD) code. Quadratic polynomial response surfaces are then fitted to the pressure recovery coefficients. To improve the prediction accuracy, uncertain regressor terms and possible outlier design points are excluded based on statistical tests. A standard optimization algorithm is used to find the optimal diffuser design from the response surface approximations. The optimum diffusers exhibit minimal flow separation and yield similar wall shapes for the two parameterizations. A main asset of the response surface optimization approach lies in the smoothing of noisy response functions. Therefore, the issue of numerical noise in CFD results based on the use of two different analysis codes is addressed.
Improving Osteosarcoma Treatment: Comparative Oncology in Action (2022)

Osteosarcoma (OSA) is the most common pediatric malignant bone tumor. Although surgery together with neoadjuvant/adjuvant chemotherapy has improved survival for localized OSA, most patients develop recurrent/metastatic disease with a dismally poor outcome. Therapeutic options have not improved for these OSA patients in recent decades. As OSA is a rare and "orphan" tumor, with no distinct targetable driver antigens, the development of new efficient therapies is still an unmet and challenging clinical need. Appropriate animal models are therefore critical for advancement in the field. Despite the undoubted relevance of pre-clinical mouse models in cancer research, they present some intrinsic limitations that may be responsible for the low translational success of novel therapies from the pre-clinical setting to the clinic. From this context emerges the concept of comparative oncology, which has spurred the study of pet dogs as a uniquely valuable model of spontaneous OSA that develops in an immune-competent system with high biological and clinical similarities to corresponding human tumors, including in its metastatic behavior and resistance to conventional therapies. For these reasons, the translational power of studies conducted on OSA-bearing dogs has seen increasing recognition. The most recent and relevant veterinary investigations of novel combinatorial approaches, with a focus on immune-based strategies, that can most likely benefit both canine and human OSA patients have been summarized in this commentary.
Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients (2021)

Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: NCT02029443, NCT02475681, NCT02970318 and NCT02337829). Acalabrutinib was given orally at total daily doses of 100-400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32-89]; median follow-up: 25.9 months [range, 0-58.5]) were analyzed. Cardiac AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with highrisk CLL (clinicaltrials gov. Identifier: NCT02477696) prospectively assess differences in CV toxicity between the two agents.
Determinants for Substrate Phosphorylation by p21-Activated Protein Kinase (γ-PAK) (1997)

gamma-PAK, originally designated PAK I and subsequently identified as a member of the p21-activated protein kinase family, has been shown to have cytostatic properties and to be involved in maintaining cells in a nondividing state [Rooney, R. D., et al., (1996) J. Biol. Chem. 271, 21498-21504]. The determinants for phosphorylation of substrates by gamma-PAK have been identified by examining the kinetics of phosphorylation of a series of synthetic peptides patterned after the sequence KKRKSGL, which is the site phosphorylated by gamma-PAK in the Rous sarcoma virus nucleocapsid protein NC in vivo and in vitro. With these peptides, the recognition sequence for gamma-PAK has been shown to contain two basic amino acids in the -2 and -3 positions, as represented by (K/R)RXS, in which the -2 position is an arginine, the -3 position is an arginine or a lysine, and X can be an acidic, basic, or neutral amino acid. A basic amino acid in the -1 or -4 position improves the rate of phosphorylation by increasing the Vmax and decreasing the Km. An acidic amino acid in the -1 position increases the rate (2.5-fold), as does an acidic residue in the -4 position, although to a lower extent (1.6-fold). Proline in the -1 or +1 position has a deleterious effect and inhibits phosphorylation by gamma-PAK. The substrate requirements of protein kinases that recognize basic amino acids on the N-terminal side of the phosphorylatable residue such as cAMP-dependent protein kinase (PKA) and Ca2+/phospholipid-dependent protein kinase (PKC) have been compared with gamma-PAK using the same peptides. An acidic residue in the -1 position negatively affects PKA and PKC; thus, peptides containing the sequence KRES can be used to identify gamma-PAK.
Reduced complexity ML multiuser sequence detection with per-survivor interference cancellation (2002)

In order to reduce the complexity of the optimum ML multiuser sequence detector, which grows exponentially with the number of users, we propose suboptimum MLSE algorithms to detect DS/CDMA signals where the likelihood computations are based on reduced-state trellises. Thus, the number of complex arithmetic computations per detected symbol can be significantly reduced. We propose the use of single or multiple trellises. In both cases, tentative decisions based on the surviving paths are used to approximate the desired likelihood function. Simulation results show that the algorithm proposed can achieve significant complexity reduction with marginal performance degradation.
EUV multilayer defect compensation (MDC) by absorber pattern modification: from theory to wafer validation (2011)

According to the ITRS roadmap, mask defects are among the top technical challenges to introduce extreme ultraviolet (EUV) lithography into production. Making a multilayer defect-free extreme ultraviolet (EUV) blank is not possible today, and is unlikely to happen in the next few years. This means that EUV must work with multilayer defects present on the mask. The method proposed by Luminescent is to compensate effects of multilayer defects on images by modifying the absorber patterns. The effect of a multilayer defect is to distort the images of adjacent absorber patterns. Although the defect cannot be repaired, the images may be restored to their desired targets by changing the absorber patterns. This method was first introduced in our paper at BACUS 2010, which described a simple pixel-based compensation algorithm using a fast multilayer model. The fast model made it possible to complete the compensation calculations in seconds, instead of days or weeks required for rigorous Finite Domain Time Difference (FDTD) simulations. Our SPIE 2011 paper introduced an advanced compensation algorithm using the Level Set Method for 2D absorber patterns. In this paper the method is extended to consider process window, and allow repair tool constraints, such as permitting etching but not deposition. The multilayer defect growth model is also enhanced so that the multilayer defect can be "inverted", or recovered from the top layer profile using a calibrated model.
Data from Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death <i>In vitro</i> (2023)

&lt;div&gt;Abstract&lt;p&gt;microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid–based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most up-regulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma &lt;i&gt;in situ&lt;/i&gt;. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by &lt;i&gt;in situ&lt;/i&gt; hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target down-regulation (&lt;i&gt;P&lt;/i&gt; = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer. [Cancer Res 2009;69(11):4851–60]&lt;/p&gt;&lt;/div&gt;
Dynamic and Noise Properties of PLL Circuits in GNSS Receivers (2019)

Different dynamic and noise characteristics of hardware-software systems of phase lock loops (PLL) within global navigation satellite systems (GNSS) receivers capable of operating under strong dynamic external effects have been considered in the present paper. Most operations in hardware-software systems are performed in processor at relatively low rate of time discretization, the signals of many satellite channels being successively processed by the processor. In the other, hardware part of the receiver, its own simultaneously operating channels correspond to each PLL system. A theoretical analysis of the considered PLL systems has been carried out by methods based on z-transformations. Then, these PLL systems were compared to each other with the help of simulation modeling in conditions of different dynamic impacts. In conclusion, some recommendations on selection of PLL systems of one or other type depending on GNSS receiver user's requirements have been given. These recommendations reflect the authors' previous experience in developing and designing commercial GNSS receivers.