Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of BRCA1 Status in Patients with Breast Cancer Using Estrogen Receptor and Basal Phenotype

Purpose: To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
Controls on the geometry of potholes in bedrock channels

Potholes (circular depressions carved into bedrock) are the dominant roughness elements in many bedrock channels. Here we show, using data from previous studies and new data from the Smith River, Oregon, that pothole depths increase in proportion to both the mean pothole radius (such that the most common pothole depth‐to‐radius ratio is 2) and the diameter of the largest clasts episodically stored in potholes. We present a theory for these observations based on computational fluid dynamics and sediment transport modeling of vortices in cylindrical cavities of different shapes and sizes. We show that the shear stress at the bottom of a pothole (which controls the rate of pothole growth) is maximized for potholes with a depth‐to‐radius ratio of approximately 1 and decreases nonlinearly with increasing depth‐to‐radius ratio such that potholes with depth‐to‐radius ratios larger than 3 are uncommon. Our model provides a mechanistic explanation for pothole shapes and sizes.
Rap 1 b facilitates NK cell functions via IQGAP 1-mediated signalosomes

The Rockefeller University Press $30.00 J. Exp. Med. www.jem. org/cgi/doi/10.1084/jem.20100040 Cite by DOI: 10.1084/jem.20100040 of 6 The Ras-mediated Raf–MEK–ERK activation pathway controls many fundamental cellular processes. Rap1 belongs to the Ras superfamily, and their role in regulating NK cell development and functions is not understood. Rap1a and Rap1b isoforms are able to regulate cell proliferation, differentiation, adhesion, and polarization (Stork and Dillon, 2005). These two share >95% amino acid homology (Rousseau-Merck et al., 1990). Conversion of inactive Rap1-GDP to active Rap1-GTP is regulated by multiple guanine nucleotide exchange factors such as C3G, RasGRP/CalDAG-GEFs, and EPACs (Gotoh et al., 1995; de Rooij et al., 1998; Kawasaki et al., 1998). Rap1 signaling is terminated by GTPase-activating proteins (GAPs) such as SPA-1 and RapGAPs (Rubinfeld et al., 1991; Kurachi et al., 1997). Rap1 regulates diverse downstream effectors including B-Raf and C-Raf, whose phosphorylation depends on active Rap1-GTPase and play a critical role in the sequential activation of MEK1/2 and their substrates ERK1/2 (Jin et al., 2006; Romano et al., 2006). Recent studies have shown that scaffolding proteins such as IQGAP (1, 2, and 3), KSR1, MP1, or Paxillin can function as signal processing centers by bringing together GTPases, kinases, and their substrates (Sacks, 2006). IQGAP1 can bind to both Rap1a and Rap1b (Jeong et al., 2007). IQGAP1 is widely expressed in multiple tissues including lymphocytes. The N-terminal calponin homology domain of IQGAP1 binds to actin and the IQ domain recruits calmodulin (Joyal et al., 1997). The C-terminal end of IQGAP1 engages with Cdc42-GTP (Joyal et al., 1997), Rac1GTP (Hart et al., 1996), E-cadherin (Kuroda et al., 1998), -catenin (Li et al., 1999), and APC (Watanabe et al., 2004). IQGAP1 also has the ability to bind to B-Raf (Ren et al., 2007), MEK1/2 (Roy et al., 2005), and ERK1/2 (Roy et al., 2004). Irrespective of these findings, IQGAP1-mediated signalosome formation and its relevance in regulating lymphocyte functions have not been investigated. Recently, we generated Rap1a and Rap1b gene knockout mice (Chrzanowska-Wodnicka CORRESPONDENCE Subramaniam Malarkannan: subra.malar@bcw.edu
Efficient implementations of the sum-product algorithm for decoding LDPC codes

Efficient implementations of the sum-product algorithm (SPA) are presented for decoding low-density parity-check (LDPC) codes using log-likelihood ratios (LLR) as messages between symbol and parity-check nodes. Various reduced-complexity derivatives of the LLR-SPA are proposed. Both serial and parallel implementations are investigated, leading to trellis and tree topologies, respectively. Furthermore, by exploiting the inherent robustness of LLRs, it is shown, via simulations, that coarse quantization tables are sufficient to implement complex core operations with negligible or no loss in performance. The unified treatment of decoding techniques for LDPC codes presented here provides flexibility in selecting the appropriate design point in high-speed applications from a performance, latency and computational complexity perspective.
Maintaining a focus on user requirements throughout the development of clinical workstation software

Establishing user requirements is well recognized as a critical step in the development of useful and usable systems (e.g., [5]). Recent innovations in human-computer interaction design address new methods for effective requirements gathering, such as Participatory Design and Contextual Inquiry (e.g., [7], [9]). However, even when projects use these methods successfully to collect vrdid requirement descriptions, it remains a challenge to establish a process that makes direct use of those descriptions during software development [11]. Valuable requirements information can be lost as it is reinterpreted during the development of functional specifications and the implementation of the proposed system. We describe the several steps we have taken to keep an ongoing and evolving understanding of user requirements under consideration by system designers and developers as they face the “real” (to them) requirements of adapting function to the constraints of computer platforms, project cost, and delivery schedule. The specific work reported here applies to the design of software for a clinical workstation used to review medical information. However, we believe the lessons we learned, maintaining the influence of user requirements throughout the development process, will apply in other practical system development situations.
Learning robust independent bases for accurate scene categorization

Due to the importance of feature extraction and scene representation in classification tasks, this paper presents an approach for unsupervised feature learning using Independent Subspace Analysis. The optimization process of feature bases is incorporated into the framework of incremental learning to cope with the learning difficulty with large or dynamic samples. The proposed method could automatically learn image features and accomplish scene classification with Spatial Pyramid Matching model. Also, the influence of related parameters in optimization and classification is discussed. Experiment shows the proposed method constructs efficient scene description and outperforms several previous methods in classification on OT scene dataset.
Identification of Malignancy-Associated Changes in Histologically Normal Tumor-Adjacent Epithelium of Patients with HPV-Positive Oropharyngeal Cancer

The incidence of HPV-positive oropharyngeal cancer (HPV+ OPC) is increasing, thus presenting new challenges for disease detection and management. Noninvasive methods involving brush biopsies of diseased tissues were recently reported as insufficient for tumor detection in HPV+ OPC patients, likely due to differences between the site of tumor initiation at the base of involuted crypts and the site of brush biopsy at the crypt surface. We hypothesized that histologically normal surface epithelial cells in the oropharynx contain changes in nuclear morphology that arise due to tumor proximity. We analyzed the nuclear phenotype of matched tumor, tumor-adjacent normal, and contralateral normal tissues from biopsies of nine HPV+ OPC patients. Measurements of 89 nuclear features were used to train a random forest-based classifier to discriminate between normal and tumor nuclei. We then extracted voting scores from the trained classifier, which classify nuclei on a continuous scale from zero (“normal-like”) to one (“tumor-like”). In each case, the average score of the adjacent normal nuclei was intermediate between the tumor and contralateral normal nuclei. These results provide evidence for the existence of phenotypic changes in histologically normal, tumor-adjacent surface epithelial cells, which could be used as brush biopsy-based biomarkers for HPV+ OPC detection.
Social Interaction Effects and Choice Under Uncertainty. An Experimental Study

Extensive field evidence shows individuals’ decisions in settings involving choice under uncertainty (e.g. savings and investment choices) depend on the decisions of their peers. One hypothesized cause of peer group effects is social interaction effects: an individual’s utility from an action is enhanced by others taking the same action. We employ a series of controlled laboratory experiments to study the causes of peer effects in choice under uncertainty. We find strong peer group effects in the laboratory. Allowing feedback about others’ choices increases group polarization and reduces the likelihood that subjects will choose risky or ambiguous gambles. We observe spillover effects, as observing another’s choice of one risky (safe) gamble makes all risky (safe) gambles more likely to be chosen. Our design allows us to eliminate social learning, social norms, group affiliation, and complementarities as possible causes for the observed peer group effects, leaving social interaction effects as the likely cause. We use a combination of theory and empirical analysis to show that preferences including “social regret” are more consistent with the data than preferences including a taste for conformity.
Structural Characterization of Minor Ampullate Spidroin Domains and Their Distinct Roles in Fibroin Solubility and Fiber Formation

Spider silk is protein fibers with extraordinary mechanical properties. Up to now, it is still poorly understood how silk proteins are kept in a soluble form before spinning into fibers and how the protein molecules are aligned orderly to form fibers. Minor ampullate spidroin is one of the seven types of silk proteins, which consists of four types of domains: N-terminal domain, C-terminal domain (CTD), repetitive domain (RP) and linker domain (LK). Here we report the tertiary structure of CTD and secondary structures of RP and LK in aqueous solution, and their roles in protein stability, solubility and fiber formation. The stability and solubility of individual domains are dramatically different and can be explained by their distinct structures. For the tri-domain miniature fibroin, RP-LK-CTDMi, the three domains have no or weak interactions with one another at low protein concentrations (<1 mg/ml). The CTD in RP-LK-CTDMi is very stable and soluble, but it cannot stabilize the entire protein against chemical and thermal denaturation while it can keep the entire tri-domain in a highly water-soluble state. In the presence of shear force, protein aggregation is greatly accelerated and the aggregation rate is determined by the stability of folded domains and solubility of the disordered domains. Only the tri-domain RP-LK-CTDMi could form silk-like fibers, indicating that all three domains play distinct roles in fiber formation: LK as a nucleation site for assembly of protein molecules, RP for assistance of the assembly and CTD for regulating alignment of the assembled molecules.
HIV health information access using spoken dialogue systems: Touchtone vs. speech

This paper presents our work in the design of a SDS for the provision of health information to caregivers of HIV positive children. We specifically address the frequently debated question of input modality in speech systems; touchtone versus speech input, in a new context of low literacy users and a health information service. We discuss our experiences and fieldwork which includes needs assessment interviews, focus group sessions, and user studies in Botswana with semi and low-literate users. Our results indicate user preference for touchtone over speech input although both systems were comparable in performance based on objective metrics.
A new classification of the Chirostyloidea (Crustacea: Decapoda: Anomura)

The high level classification of the Chirostyloidea Ortmann, 1892, is reviewed. Eumunididae Milne-Edwards & Bouvier, 1900, is resurrected for two genera formerly placed in the Chirostylidae Ortmann, 1892, Eumunida Smith, 1883, and Pseudomunida Haig, 1979, based on shared characteristics such as the dorsal carapace striation, presence of supraocular spines of the rostrum, dentition of the mandible, presence of an epipod and an annulated exopod flagellum of maxilliped 1. Three families are now included in the Chirostyloidea: Chirostylidae, Eumunididae and Kiwaidae. Diagnoses are provided for each family as well as a key to the families. The fossil record of the Chirostyloidea is discussed, with putative records of Eumunida in the fossil record referred to the galatheid genus Sadayoshia Baba, 1969.
Multiplexed Nanopore Sequencing of HLA-B Locus in Māori and Pacific Island Samples

The human leukocyte antigen (HLA) system encodes the human major histocompatibility complex (MHC). HLA-B is the most polymorphic gene in the MHC class I region and many HLA-B alleles have been associated with adverse drug reactions (ADRs) and disease susceptibility. The frequency of such HLA-B alleles varies by ethnicity, and therefore it is important to understand the prevalence of such alleles in different population groups. Research into HLA involvement in ADRs would be facilitated by improved methods for genotyping key HLA-B alleles. Here, we describe an approach to HLA-B typing using next generation sequencing (NGS) on the MinION™ nanopore sequencer, combined with data analysis with the SeqNext-HLA software package. The nanopore sequencer offers the advantages of long-read capability and single molecule reads, which can facilitate effective haplotyping. We developed this method using reference samples as well as individuals of New Zealand Māori or Pacific Island descent, because HLA-B diversity in these populations is not well understood. We demonstrate here that nanopore sequencing of barcoded, pooled, 943 bp polymerase chain reaction (PCR) amplicons of 49 DNA samples generated ample read depth for all samples. HLA-B alleles were assigned to all samples at high-resolution with very little ambiguity. Our method is a scaleable and efficient approach for genotyping HLA-B and potentially any other HLA locus. Finally, we report our findings on HLA-B genotypes of this cohort, which adds to our understanding of HLA-B allele frequencies among Māori and Pacific Island people.
Evolution of Locomotion on a Physical Tensegrity Robot

Due to their high strength-to-weight ratio, robustness and deformability, tensegrity structures are an appealing platform for the emerging field of soft robotics, with applications ranging from search-and-rescue to field-deployable structures. Unfortunately, these properties also make tensegrities challenging to control through conventional means. In this paper we describe a novel means of vibration-based tensegrity actuation which allows for the manual control of a physical tensegrity robot in the plane as well as state-machine based target following. We demonstrate the evolution of effective gaits using only physical evaluations of the robot, and further demonstrate how a combination of the state-machine with the hill climber allows for the hands-off automation of the evolutionary process. We conclude with a description of how this can lead to a bootstrapping effect, with the potential to significantly accelerate and automate the physical evolution of our tensegrity robot.
Plasmodium vivax dhfr Mutations among Isolates from Malarious Areas of Iran

The use of sulfadoxine and pyrimethamine (SP) for treatment of vivax malaria is uncommon in most malarious areas, but Plasmodium vivax isolates are exposed to SP because of mixed infections with other Plasmodium species. As P. vivax is the most prevalent species of human malaria parasites in Iran, monitoring of resistance of the parasite against the drug is necessary. In the present study, 50 blood samples of symptomatic patients were collected from 4 separated geographical regions of south-east Iran. Point mutations at residues 57, 58, 61, and 117 were detected by the PCR-RFLP method. Polymorphism at positions 58R, 117N, and 117T of P. vivax dihydrofolate reductase (Pvdhfr) gene has been found in 12%, 34%, and 2% of isolates, respectively. Mutation at residues F57 and T61 was not detected. Five distinct haplotypes of the Pvdhfr gene were demonstrated. The 2 most prevalent haplotypes were F57S58T61S117 (62%) and F57S58T61N117 (24%). Haplotypes with 3 and 4 point mutations were not found. The present study suggested that P. vivax in Iran is under the pressure of SP and the sensitivity level of the parasite to SP is diminishing and this fact must be considered in development of malaria control programs.
Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus

Background: Alzheimer’s disease (AD) pathology in idiopathic normal pressure hydrocephalus (iNPH) contributes to poor shunt responses. Amyloid-β 1– 42 (Aβ42) toxic conformer was recently identified with features of rapid oligomerization, strong neurotoxicity and synaptotoxicity. Objective: This observational study points to Aβ42 toxic conformer as a biomarker for AD pathology and for poor postoperative prognosis in patients with iNPH. Methods: The first cohort consisted of patients with AD (n = 17) and iNPH (n = 17), and cognitively normal individuals (CN, n = 12). The second cohort, consisted of 51 patients with iNPH, was divided into two groups according to phosphorylated Tau (pTau) level (low- and high-pTau groups); the low-pTau group was further subdivided according to one-year postoperative change in Aβ42 toxic conformer ratio (%) [Aβ42 toxic conformer/Aβ42×100] (decreased- and increased-conformer subgroups). Enzyme-linked immunosorbent assay was used to measure pTau, Aβ42, and Aβ42 toxic conformer in cerebrospinal fluid. Outcomes were evaluated using neuropsychological tests one- and two-years postoperatively. Results: In the first cohort, Aβ42 toxic conformer ratio in the iNPH group (10.8%) was significantly higher than that in the CN group (6.3%) and significantly lower than that in the AD group (17.2%). In the second cohort, the high-pTau group showed cognitive decline two-years postoperatively compared to baseline. However, the low-pTau group showed favorable outcomes one-year postoperatively; furthermore, the increased-conformer subgroup showed cognitive decline two-years postoperatively while the decreased-conformer subgroup maintained the improvement. Conclusions: Change in Aβ42 toxic conformer ratio predicts long-term cognitive outcome in iNPH, even in the low-pTau group.
Gemini and Chandra Observations of Abell 586, A Relaxed Strong-lensing Cluster

We analyze the mass content of the massive strong-lensing cluster Abell 586 (z = 0.17). We use optical data (imaging and spectroscopy) obtained with the Gemini Multi-Object Spectrograph (GMOS) mounted on the 8 m Gemini North telescope, together with publicly available X-ray data taken with the Chandra space telescope. Employing different techniques—velocity distribution of galaxies, weak gravitational lensing, and spatially resolved X-ray spectroscopy—we derive mass and velocity dispersion estimates from each of them. All estimates agree well with each other, within a 68% confidence level, indicating a velocity dispersion of 1000-1250 km s-1. The projected mass distributions obtained through weak lensing and X-ray emission are strikingly similar, having nearly circular geometry. We suggest that Abell 586 is probably a truly relaxed cluster whose last major merger occurred more than ~4 Gyr ago.
Plug-and-Play ADMM for Image Restoration: Fixed-Point Convergence and Applications

Alternating direction method of multiplier (ADMM) is a widely used algorithm for solving constrained optimization problems in image restoration. Among many useful features, one critical feature of the ADMM algorithm is its modular structure, which allows one to plug in any off-the-shelf image denoising algorithm for a subproblem in the ADMM algorithm. Because of the plug-in nature, this type of ADMM algorithms is coined the name “Plug-and-Play ADMM. ” Plug-and-Play ADMM has demonstrated promising empirical results in a number of recent papers. However, it is unclear under what conditions and by using what denoising algorithms would it guarantee convergence. Also, since Plug-and-Play ADMM uses a specific way to split the variables, it is unclear if fast implementation can be made for common Gaussian and Poissonian image restoration problems. In this paper, we propose a Plug-and-Play ADMM algorithm with provable fixed-point convergence. We show that for any denoising algorithm satisfying an asymptotic criteria, called bounded denoisers, Plug-and-Play ADMM converges to a fixed point under a continuation scheme. We also present fast implementations for two image restoration problems on superresolution and single-photon imaging. We compare Plug-and-Play ADMM with state-of-the-art algorithms in each problem type and demonstrate promising experimental results of the algorithm.
Interleukin-18 expression and the response to treatment in patients with psoriasis

Introduction The aim of the study was to demonstrate interleukin-18 (IL-18) expression in keratinocytes from psoriatic lesions in comparison to keratinocytes from uninvolved skin and to study the change of expression after therapeutic interventions. Material and methods This study included 16 patients of different clinical subtypes of psoriasis. Interleukin-18 gene expression analysis was performed using real time quantitative PCR. Three biopsies were obtained from each patient. Two were taken from the lesional psoriatic skin and from uninvolved skin before starting treatment. A third lesional skin biopsy was taken at the end of 2 months of treatment. The treatment was in the form of topical steroids or oral systemic methotrexate. Results Of all 16 studied patients, significantly increased IL-18 expression was noted in keratinocytes from psoriatic lesions before and after treatment when compared to keratinocytes from uninvolved skin (p = 0.001 and p = 0.002 respectively). The IL-18 expression in the skin lesions after treatment was significantly lower than lesional skin before treatment (p = 0.023). In psoriatic skin lesions of all studied patients IL-18 expression was significantly correlated with disease duration (r = 0.40 and p = 0.01) and clinical severity of psoriasis (r = 0.72 and p = 0.001). Conclusions Increased IL-18 expression in keratinocytes from psoriatic lesions of our patients and its correlation with disease duration and severity supported the concept of psoriasis as a T cell mediated autoimmune disease. This could establish therapeutic and preventive approaches for psoriasis that ultimately lead to improved outcomes for patients.