Miracle-dz/UniFAR-FTUs huggingface dataset:
Run-to-run critical dimension and sidewall angle lithography control using the PROLITH simulator

We derive and investigate three different run-to-run (R2R) feedback controllers for the purpose of trying to minimize the detrimental effects of lithography process disturbances on critical resist profiles. Our controllers manipulate the dose and focus inputs and include Kalman filtering schemes that estimate the disturbances. The first controller adjusts the critical dimension (CD) and sidewall angle (SWA) of the resist profile. The second controller compensates for the print bias between isolated and dense lines. The third controller finds the best tradeoff between CD, SWA, and print bias. We tested the performance of the controllers using the lithography simulator PROLITH (v.7.0). The results showed a reduction of the effect of the disturbances on the CD, SWA, and print bias. Moreover, the results quantify the benefit of using focus, in addition to dose, as a control input for the purpose of controlling the resist profile.
Prophylactic window therapy with the clinical poly(ADP‐ribose) polymerase inhibitor olaparib delays BRCA1‐deficient mammary tumour formation in mice

Women with heterozygous germline mutations in the BRCA1 tumour suppressor gene are strongly predisposed to developing early‐onset breast cancer through loss of the remaining wild‐type BRCA1 allele and inactivation of TP53. Although tumour prevention strategies in BRCA1‐mutation carriers are still limited to prophylactic surgery, several therapeutic strategies have been developed to target the DNA repair defects (also known as ‘BRCAness’) of BRCA1‐deficient tumours. In particular, DNA‐damaging agents such as platinum drugs and poly(ADP‐ribose) polymerase (PARP) inhibitors show strong activity against BRCA1‐mutated tumours. However, it is unclear whether drugs that target BRCAness can also be used to prevent tumour formation in BRCA1‐mutation carriers, especially as loss of wild‐type BRCA1 may not be the first event in BRCA1‐associated tumourigenesis. We performed prophylactic treatments in a genetically engineered mouse model in which de novo development of BRCA1‐deficient mammary tumours is induced by stochastic loss of BRCA1 and p53. We found that prophylactic window therapy with nimustine, cisplatin or olaparib reduced the amount and size of mammary gland lesions, and significantly increased the median tumour latency. Similar results were obtained with intermittent prophylactic treatment with olaparib. Importantly, prophylactic window therapy with nimustine and cisplatin resulted in an increased fraction of BRCA1‐proficient mammary tumours, suggesting selective survival and malignant transformation of BRCA1‐proficient lesions upon prophylactic treatment with DNA‐damaging agents. Prophylactic therapy with olaparib significantly prolonged mammary tumour‐free survival without any significant increase in the fraction of BRCA1‐proficient tumours, warranting the evaluation of this PARP inhibitor in prophylactic trials in BRCA1‐mutation carriers. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Evolutionary History and Functional Characterization of Three Large Genes Involved in Sporulation in Bacillus cereus Group Bacteria

ABSTRACT The Bacillus cereus group of bacteria is a group of closely related species that are of medical and economic relevance, including B. anthracis, B. cereus, and B. thuringiensis. Bacteria from the Bacillus cereus group encode three large, highly conserved genes of unknown function (named crdA, crdB, and crdC) that are composed of 16 to 35 copies of a repeated domain of 132 amino acids at the protein level. Bioinformatic analysis revealed that there is a phylogenetic bias in the genomic distribution of these genes and that strains harboring all three large genes mainly belong to cluster III of the B. cereus group phylogenetic tree. The evolutionary history of the three large genes implicates gain, loss, duplication, internal deletion, and lateral transfer. Furthermore, we show that the transcription of previously identified antisense open reading frames in crdB is simultaneously regulated with its host gene throughout the life cycle in vitro, with the highest expression being at the onset of sporulation. In B. anthracis, different combinations of double- and triple-knockout mutants of the three large genes displayed slower and less efficient sporulation processes than the parental strain. Altogether, the functional studies suggest an involvement of these three large genes in the sporulation process.
Kinase conformations: A computational study of the effect of ligand binding

Protein function is often controlled by ligand‐induced conformational transitions. Yet, in spite of the increasing number of three‐dimensional crystal structures of proteins in different conformations, not much is known about the driving forces of these transitions. As an initial step toward exploring the conformational and energetic landscape of protein kinases by computational methods, intramolecular energies and hydration free energies were calculated for different conformations of the catalytic domain of CAMP‐dependent protein kinase (cAPK) with a continuum (Poisson) model for the electrostatics. Three protein kinase crystal structures for ternary complexes of cAPK with the peptide inhibitor PKI(5‐24) and ATP or AMP‐PNP were modeled into idealized intermediate and open conformations. Concordant with experimental observation, we find that the binding of PKI(5‐24) is more effective in stabilizing the closed and intermediate forms of cAPK than ATP. PKI(5‐24) seems to drive the final closure of the active site cleft from intermediate to closed state because ATP does not distinguish between these two states. Binding of PKI(5‐24) and ATP is energetically additive.
Tumor‐to‐tumor metastasis to the central nervous system

Tumor‐to‐tumor metastasis is a well‐recognized phenomenon. Meningioma is the most common intracranial host tumor, with the breast and lung being the most common primary sites. We report herein two such cases of metastasis from pulmonary adenocarcinoma and malignant melanoma (MM) of vulva, respectively. Case 1: a 69‐year‐old female smoker who had a history of right upper lobectomy of lung for adenocarcinoma presented with a headache and altered mental status, and was found to have a left temporal contrast‐enhancing mass with massive surrounding edema on MRI. The resection specimen revealed foci of metastatic adenocarcinoma within a microcystic meningioma. Case 2: a 75‐year‐old woman with a history of radical vulvectomy for MM died of widespread systemic metastasis of MM. At autopsy, a 2.5 × 2 × 2 cm firm nodule attached to the falx was incidentally found, with focal black discoloration at the periphery of the mass. Histologic examination showed a fibroblastic meningioma with a focus of metastatic MM. Case 1 is the first case report describing a microcystic variant of meningioma harboring metastatic carcinoma. Although MM is one of the most common metastatic brain tumors, MM‐to‐meningioma metastasis is reportedly extremely rare, but can occur.
The Histone Chaperone Asf1 Increases the Rate of Histone Eviction at the Yeast PHO5 and PHO8 Promoters*

Eukaryotic gene expression starts off from a largely obstructive chromatin substrate that has to be rendered accessible by regulated mechanisms of chromatin remodeling. The yeast PHO5 promoter is a well known example for the contribution of positioned nucleosomes to gene repression and for extensive chromatin remodeling in the course of gene induction. Recently, the mechanism of this remodeling process was shown to lead to the disassembly of promoter nucleosomes and the eviction of the constituent histones in trans. This finding called for a histone acceptor in trans and thus made histone chaperones likely to be involved in this process. In this study we have shown that the histone chaperone Asf1 increases the rate of histone eviction at the PHO5 promoter. In the absence of Asf1 histone eviction is delayed, but the final outcome of the chromatin transition is not affected. The same is true for the coregulated PHO8 promoter where induction also leads to histone eviction and where the rate of histone loss is reduced in asf1 strains as well, although less severely. Importantly, the final extent of chromatin remodeling is not affected. We have also presented evidence that Asf1 and the SWI/SNF chromatin remodeling complex work in distinct parallel but functionally overlapping pathways, i.e. they both contribute toward the same outcome without being mutually strictly dependent.
Effects of Simulation Versus Traditional Tutorial-Based Training on Physiologic Stress Levels Among Clinicians: A Pilot Study

Introduction: Emotionality and heightened anxiety during medical simulation encounters have been hypothesized to contribute to improved cognition and learning, but the overall stress “dose response curve” of experiential learning remains unclear. We sought to (1) identify the degree and time course of physiologic stress induced in physicians by simulation-based training (SBT), when compared with a traditional tutorial-based interactive-education training (IET) and (2) compare differences in stress responses to simulation activities among pediatric provider groups. Method: Twenty-seven gastroenterology physicians were randomized among six crisis resource management courses taught by SBT versus IET. Eleven RNs and four technicians participated in the SBT exercises. Heart rate (HR) and salivary cortisol (SC) levels were measured in all participants at four time points before, during, and after participation in the SBT sessions and at two time points before and after the IET sessions. Results: Physicians who underwent SBT (n = 13) demonstrated increased tachycardia at the end of the session (+17 beats/min), when compared with those in the IET group (n = 14) who demonstrated an overall negative response (−4 beats/min, P = 0.001). Similarly, physicians in the SBT group demonstrated increased SC (+0.140 &mgr;g/dL, 70% over baseline), when compared with physicians in the IET group who had a median decrease in SC (−0.015 &mgr;g/dL, 20% under baseline, P = 0.001). There were similar increases in HR in all participants after SBT, but technicians experienced a relatively smaller increase in SC compared with physicians and nurses. Conclusions: After high-fidelity SBT within the gastroenterology suite, clinicians independent of their role demonstrated increased physiologic stress levels—as measured by HR and SC levels—compared with traditional IET sessions. The study provides novel calibration data compared with a traditional baseline for future investigations aimed at further understanding the dose-response curve of simulation-based experiences to optimize emotionality, cognition, and learning.
Type 2 Diabetes Prevention in the Real World

OBJECTIVE We study the effectiveness of the GOAL Lifestyle Implementation Trial at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352, type 2 diabetes risk score FINDRISC = 16.2 ± 3.3, BMI 32.6 ± 5.0 kg/m2) received six lifestyle counseling sessions over 8 months. Measurements were at baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS Statistically significant risk reduction at 12 months was maintained at 36 months in weight (−1.0 ± 5.6 kg), BMI (−0.5 ± 2.1 kg/m2), and serum total cholesterol (−0.4 ± 1.1 mmol/l). CONCLUSIONS Maintenance of risk reduction in this “real world” trial proves the intervention's potential for significant public health impact.
High Frequencies of Functionally Competent Circulating Tax-Specific CD8+ T Cells in Human T Lymphotropic Virus Type 2 Infection

Human T lymphotropic virus type 2 (HTLV-2) is characterized by a clinically asymptomatic persistent infection in the vast majority of infected individuals. In this study, we have characterized for the first time ex vivo specific CTL responses against the HTLV-2 Tax protein. We could detect CTL responses only against a single HLA-A*0201-restricted Tax2 epitope, comprising residues 11–19 (LLYGYPVYV), among three alleles screened. Virus-specific CTLs could be detected in most evaluated subjects, with frequencies as high as 24% of circulating CD8+ T cells. The frequency of specific CTLs had a statistically significant positive correlation with proviral load levels. The majority of virus-specific CD8+ T cells exhibited an effector memory/terminally differentiated phenotype, expressed high levels of cytotoxicity mediators, including perforin and granzyme B, and lysed in vitro target cells pulsed with Tax2(11–19) synthetic peptide in a dose-dependent manner. Our findings suggest that a strong, effective CTL response may control HTLV-2 viral burden and that this may be a significant factor in maintaining persistent infection and in the prevention of disease in infected individuals.
Identifying Real World Concepts in Social Media

The bene ts of mining social media are rapidly increasing with social media's increasing popularity and the increasing amount of social media data available. Mining social media presents new di culties, however, because users' posts are informal and often do not even claim to be authoritative. Users often describe concepts using lay phrases that cannot be mapped to an existing knowledge base, users often change the word choices and constructions in these phrases rather than treating them as a precise vocabulary, and users often post anecdotes or reactions to news stories that must be separated from users' descriptions of their experiences. Many types of social media mining require that these di culties be addressed. Users' vocabularies must be mapped onto a knowledge base before a system can determine how concepts expressed by one user relate to concepts expressed by another, and many types of mining are intended to be performed only on posts describing users' rst person experiences. In this dissertation I propose and evaluate methods for overcoming these di culties. I propose a synonym discovery method for discovering equivalent lay phrases and mapping between lay phrases and expert terms in a knowledge base; I show this method performs substantially better than comparable previously proposed synonym discovery methods (i.e., methods that do not require query logs or parallel corpora). I propose several concept extraction methods that use a thesaurus to identify variations of known lay phrases, as are often created when users speak informally. These methods outperform existing concept extraction methods as measured by both F1 and Precision. I then describe an architecture for identifying real world trends using
Three-dimensional endoscopy in sinus surgery

Purpose of reviewSurgical endoscopy revolutionized the management of disease in nearly every surgical field, including rhinology. Endoscopy offered several advantages for the surgical management of rhinologic disease. However, it had a distinct disadvantage compared to direct vision, namely loss of binocular vision. Two-dimensional (2D) endoscopy limited depth perception, widely regarded as an important parameter for accurate and efficient movements during surgery. Three-dimensional (3D) endoscopic visualization has been actively pursued for decades by endoscopic surgeons in multiple surgical specialties. However, its clinical role has been limited due to technical limitations as well as successful adaptation by endoscopic surgeons to monocular cues offered by 2D technology. Recent findingsUntil recently, stereoscopic technology included variations of dual channel video, dual chip-on-the-tip, and shutter mechanism, as well as various 3D displays. Over the past decade a novel 3D endoscopic technology was introduced. This technology used a lenticular array of lenses in front of a single video chip at the distal end of an endoscope to generate a stereoscopic view of the surgical field. Also known as the ‘insect eye’ technology since it mimics the compound eye of arthropods, this endoscope has reinvigorated the field of 3D endoscopic surgery. SummaryRecent developments in 3D endoscopy hold much promise for all surgical subspecialties, particularly endoscopic sinus and skull-base surgery.
A 4-channel 10.3Gb/s transceiver with adaptive phase equalizer for 4-to-41dB loss PCB channel

In multi-Gb/s wireline communications, equalizers are used to compensate for channel-induced signal distortion in order to stretch the maximum distance of transmission. Both amplitude and phase can be distorted in a channel. Amplitude distortion is a frequency-dependent attenuation due to skin effect and dielectric loss, causing inter-symbol-interference (ISI). A transmitter (TX) discrete-time pre-emphasis (PE) filter, a receiver (RX) continuous-time Linear Equalizer (LE), and an RX Decision-Feedback Equalizer (DFE) are generally used to cancel ISI. At 10Gb/s or higher data rate, equalizers for up to 33 to 39dB Nyquist loss and up to 20 to 25dB adapted loss range were reported [1–3]. On the other hand, how to compensate phase distortion is not clearly understood in practical circuit design. Theoretically, if a channel has minimum-phase-likecharacteristics, phase distortion is automatically co-equalized with amplitude distortion by a minimum-phase equalizer [4]. While this is the case for high-speed cables [5], it is not for PCB traces, because a non-minimum-phase equalizer, e.g., a PE with a pre-cursor tap, produces lower BER over a high-loss PCB channel than a minimum-phase equalizer, e.g., a PE without a pre-cursor tap. Thus the IEEE 10Gb Ethernet standard for backplanes adopted 3-tap PE with a precursor tap [6]. However, adaptive phase equalization in hardware has not been reported in the literature.
Visual saliency landmark detection algorithm based on DNN feature extraction

The integrated navigation pattern that is formed by the scene matching navigation and the inertial navigation or the satellite navigation is an important development direction of UAV autonomous navigation technology. As for the error identification problem of matching area in the process of scene matching landmark detection, the algorithm of visual saliency landmark detection for scene matching based on deep neural network for feature extraction is proposed. The experiments illustrated that the algorithm can effectively solve the problem of landmark detection in different environments and improve the robustness and effectiveness of landmark detection.
Replication Advantage and Host Factor-Independent Phenotypes Attributable to a Common Naturally Occurring Capsid Mutation (I97L) in Human Hepatitis B Virus

ABSTRACT Mutations of human hepatitis B virus (HBV) occur frequently within the capsid (core) protein in natural infections. The most frequent mutation of the core protein in HBV from Southeast Asia occurs at amino acid 97, changing an isoleucine (I) to a leucine (L). In our systematic study of virus-host interactions, we have examined the replication efficiency of a site-directed mutant, I97L, and its parental wild-type HBV in several different hepatoma cell lines. Interestingly, we found that this capsid variant replicated in human Huh7 hepatoma cells approximately 4.8-fold better than its parental wild-type HBV. A similar phenomenon was observed in another hepatoma cell line, J3. In addition, the level of encapsidated RNA pregenome in mutant I97L was about 5.7-fold higher than that of the wild-type HBV in Huh7 cells. Unlike Huh7 cells, no significant difference in viral DNA replication between the same I97L mutant and its parental wild-type HBV was observed in HepG2, a human hepatoblastoma cell line. This finding of a profound replication advantage for mutant I97L in Huh7 and J3 cells but not in HepG2 cells may have important implications for the emergence of this mutant in chronic HBV carriers. We speculate here that the mutation confers a host factor-independent growth advantage for the survival of HBV variants in gradually dedifferentiating hepatocytes and thus helps prolong viral persistence.
Probing the structure of F-actin: cross-links constrain atomic models and modify actin dynamics.

Cross-links between protomers in F-actin can be used as a very sensitive probe of both the dynamics and structure of F-actin. We have characterized filaments formed from a previously described yeast actin Q41C mutant, where disulfide bonds can be formed between the Cys41 that is introduced into subdomain-2 and Cys374 on an adjacent protomer. We find that the distribution of cross-linked n-mers shows no cooperativity and corresponds to a random probability cross-linking reaction. The random distribution suggests that disulfide formation does not cause a significant perturbation of the F-actin structure. Consistent with this lack of perturbation, three-dimensional reconstructions of extensively cross-linked filaments, using a new approach to helical image analysis, show very small structural changes with respect to uncross-linked filaments. This finding is in conflict with refined models but in agreement with the original Holmes et al. model for F-actin. Under conditions where 94 % of the protomers are linked by disulfide bonds, the distribution of filament twist becomes more heterogeneous with respect to control filaments. A molecular model suggests that strain, introduced by the disulfide, is relieved by increasing the twist of the long-pitch actin helices. Disulfide formation makes yeast actin filaments approximately three times less flexible in terms of bending and similar, in this respect, to vertebrate skeletal muscle F-actin. These observations support previous reports that the rigidity of F-actin can be controlled by the position of subdomain-2, and that this region is more flexible in yeast F-actin than in skeletal muscle F-actin.
Sensitivity of Energy System Investments to Policy Regulation Changes: Application of the Blue Sky Catastrophe

In this paper we argue, that the interaction of technology and economic policy regulations in the energy sector may be described by the so-called slow-fast class of dynamical systems. It is known that such systems may exhibit the blue sky catastrophe, a special type of bifurcation. Application of this result allows us to argue that caution is needed when updating economic policies in the energy sector to avoid the onset of catastrophic developments in the system's transformation, when energy system dynamics becomes unresponsive to policy updates.