Miracle-dz/UniFAR-FTUs huggingface dataset:
CryoEM structure of Hsp104 and its mechanistic implication for protein disaggregation

Hsp104 is a ring-forming AAA+ machine that recognizes both aggregated proteins and prion-fibrils as substrates and, together with the Hsp70 system, remodels substrates in an ATP-dependent manner. Whereas the ability to disaggregate proteins is dependent on the Hsp104 M-domain, the location of the M-domain is controversial and its exact function remains unknown. Here we present cryoEM structures of two Hsp104 variants in both crosslinked and noncrosslinked form, in addition to the structure of a functional Hsp104 chimera harboring T4 lysozyme within the M-domain helix L2. Unexpectedly, we found that our Hsp104 chimera has gained function and can solubilize heat-aggregated β-galactosidase (β-gal) in the absence of the Hsp70 system. Our fitted structures confirm that the subunit arrangement of Hsp104 is similar to other AAA+ machines, and place the M-domains on the Hsp104 exterior, where they can potentially interact with large, aggregated proteins.
Endovascular treatment of cerebral venous thrombosis: Contemporary multicenter experience

Endovascular therapy of cerebral venous thrombosis using modern approaches to intracranial recanalization, such as stent retrievers and aspiration thrombectomy, is not well described. We performed a retrospective review of data for consecutive patients with venous sinus thrombosis who underwent endovascular treatment between 1 January 2010 and 31 December 2013 at participating institutions. We identified a total of 13 patients with a diagnosis of cerebral venous thrombosis. The most frequently utilized type of endovascular intervention was the Penumbra aspiration system (Penumbra Inc., Alameda, California, USA) (nine cases), followed by local infusion of tissue plasminogen activator (bolus and/or drip in six cases) and stent retrievers (Solitaire FR (Covidien, Irvine, California, USA) in three cases and Trevo (Stryker, Kalamazoo, Michigan, USA) in one case). Overall, multimodality treatment (two or more different types of devices or approaches) was performed in 62% of cases. Follow-up data were available for 11 patients; of those, five had a favorable clinical outcome (defined as modified Rankin Scale score of 0–2) and three patients died. Various endovascular approaches are utilized in current clinical practice. A multimodal approach to endovascular therapy for the treatment of cerebral venous thrombosis resulted in partial or complete restoration of flow in all cases, yet the mortality rate of 27% indicates the need for improvement in recanalization strategies for this disorder.
DriftBoard: A Panning-Based Text Entry Technique for Ultra-Small Touchscreens

Emerging ultra-small wearables like smartwatches pose a design challenge for touch-based text entry. This is due to the "fat-finger problem," wherein users struggle to select elements much smaller than their fingers. To address this challenge, we developed DriftBoard, a panning-based text entry technique where the user types by positioning a movable qwerty keyboard on an interactive area with respect to a fixed cursor point. In this paper, we describe the design and implementation of DriftBoard and report results of a user study on a watch-size touchscreen. The study compared DriftBoard to two ultra-small keyboards, ZoomBoard (tapping-based) and Swipeboard (swiping-based). DriftBoard performed comparably (no significant difference) to ZoomBoard in the major metrics of text entry speed and error rate, and outperformed Swipeboard, which suggests that panning-based typing is a promising input method for text entry on ultra-small touchscreens.
Toxicity of Zinc Oxide Nanoparticles in Rats Treated by Two Different Routes: Single Intravenous Injection and Single Oral Administration

Toxicokinetics of zinc oxide nanoparticles (ZnONP) was studied in rats via a single intravenous (iv) injection and a single oral administration (3 mg/kg or 30 mg/kg), respectively. Blood concentrations of zinc (Zn) were monitored for 7 d and tissue distribution were determined in liver, kidneys, lung, spleen, thymus, brain, and testes. To ascertain the excretion of ZnONP, Zn levels in urine and feces were measured for 7 d. ZnONP were not readily absorbed from the gastrointestinal tract (GIT) after oral administration and were excreted mostly in feces. When the nanoparticles were injected iv to rats at a dose of 30 mg/kg, peak concentration appeared at 5 min but returned to normal range by d 2 (48 h after injection). ZnONP were distributed mainly to liver, kidneys, lung, and spleen, but not to thymus, brain, and testes. The distribution level was significantly decreased to normal by d 7. Feces excretion levels after iv injection supported biliary excretion of ZnONP. In rats injected iv with 30 mg/kg, mitotic figures in hepatocytes were significantly increased and multifocal acute injuries with dark brown pigment were noted in lungs, while no significant damage was observed in rats treated orally with the same dosage. Color versions of one or more of the figures in the article can be found online at www.tandfonline. com/uteh
House Prices and Housing Investment in Sweden and the United Kingdom: Econometric Analysis for the Period 1970-1998

We estimate quarterly dynamic housing demand and investment supply models for Sweden and the UK for the sample period 1970-1998, using an Error Correction Method (ECM). To facilitate comparisons of results between Sweden and the UK we model both countries identically with approximately almost the similar type of exogenous variables. The long run income elasticities for Sweden and the UK are constrained to be 1.0 respectively. The long runs semi-elasticity for interest rates are 2.1 and 0.9 for Sweden and the UK. The speed of adjustment on the demand side is 0.12 and 0.23 while on the supply side is 0.06 and 0.48 for Sweden respectively the UK. Granger causality tests indicate that income Granger causes house prices for Sweden, while for the UK there is also a feedback from house prices to income. House prices Granger cause financial wealth for Sweden, while for the UK it's vice versa. House prices cause household debt for Sweden, while for UK there is a feedback from debt. Interest rates Granger cause house prices for the UK and Sweden. In both countries Tobin’s q Granger cause housing investment. Generally the diagnostic tests indicate that the model specifications were satisfactory to the unknown data generating process.
Physical-Layer Secrecy for OFDM Transmissions Over Fading Channels

This paper considers the information theoretic secrecy rates that are achievable by an orthogonal frequency-division multiplexing (OFDM) transmitter/receiver pair in the presence of an eavesdropper that might either use an OFDM structure or choose a more complex receiver architecture. The analysis is made possible by modeling the system as a particular instance of a high dimensional multiple-input multiple-output wiretap channel. The secrecy capacity is formulated as a maximization problem under a trace constraint, and simple expressions are given for its high signal-to-noise (SNR) limit. The low rate limit of the secrecy outage probability is also evaluated under a fading channel model. As for the finite SNR case, the secrecy rates that can be achieved with particular inputs are considered. Numerical results are provided under a Rayleigh fading channel model and under dependence of the main and eavesdropper channels. The secrecy loss due to the OFDM structure constraints, and the information gain for an eavesdropper that uses a more complex receiver, are also considered.
New Functions for Unsupervised Asymmetrical Paraphrase Detection

Monolingual text-to-text generation is an emerging research area in Natural Language Processing. One reason for the interest in such generation systems is the possibility to automatically learn text-to-text generation strategies from aligned monolingual corpora. In this context, paraphrase detection can be seen as the task of aligning sentences that convey the same information but yet are written in different forms, thereby building a training set of rewriting examples. In this paper, we propose a new type of mathematical functions for unsupervised detection of paraphrases, and test it over a set of standard paraphrase corpora. The results are promising as they outperform stateof-the-art functions developed for similar tasks. We consider two types of paraphrases symmetrical and asymmetrical entailed and show that although our proposed functions were conceived and oriented toward the asymmetrical detection, they perform rather well for symmetrical sentence pairs identification.
Mathematical formula recognition using virtual link network

We propose a new method of recognizing mathematical formulae. The method is robust against the recognition errors of characters and the variation of the printing styles of the documents. The outline is as follows: we first construct a network with vertices representing the characters (symbols), linked with each other by several edges with labels and costs representing the possible relations of the pair of characters. The network has multiple edges with different labels and costs representing the ambiguity of the decision of the relation of character pairs. Then, we output the spanning tree of the network with minimum cost which corresponds to the recognition result of the structure of the mathematical formula, using not only the local costs initially attached to the network but the costs reflecting global structure of the formula. The advantage of this method is that local errors of the recognition are recovered automatically by the total cost of the recognition tree.
Comparison of the Effect of Mutant and Wild-Type p53 on Global Gene Expression

The mechanisms for “gain-of-function” phenotypes produced by mutant p53s such as enhanced proliferation, resistance to transforming growth factor-β–mediated growth suppression, and increased tumorigenesis are not known. One theory is that these phenotypes are caused by novel transcriptional regulatory events acquired by mutant p53s. Another explanation is that these effects are a result of an imbalance of functions caused by the retention of some of the wild-type transcriptional regulatory events in the context of a loss of other counterbalancing activities. An analysis of the ability of DNA-binding domain mutants A138P and R175H, and wild-type p53 to regulate the expression levels of 6.9 × 103 genes revealed that the mutants retained only <5% of the regulatory activities of the wild-type protein. A138P p53 exhibited mostly retained wild-type regulatory activities and few acquired novel events. However, R175H p53 possessed an approximately equal number of wild-type regulatory events and novel activities. This is the first report that, after examination of the regulation of a large unfocused set of genes, provides data indicating that remaining wild-type transcriptional regulatory functions existing in the absence of counterbalancing activities as well as acquired novel events both contribute to the gain-of-function phenotypes produced by mutant p53s. However, mutant p53s are likely to be distinct in terms of the extent to which each mechanism contributes to their gain-of-function phenotypes.
RankSQL: query algebra and optimization for relational top-k queries

This paper introduces RankSQL, a system that provides a systematic and principled framework to support efficient evaluations of ranking (top-k) queries in relational database systems (RDBMS), by extending relational algebra and query optimization. Previously, top-k query processing is studied in the middleware scenario or in RDBMS in a "piecemeal" fashion, i.e., focusing on specific operator or sitting outside the core of query engines. In contrast, we aim to support ranking as a first-class database construct. As a key insight, the new ranking relationship can be viewed as another logical property of data, parallel to the "membership" property of relational data model. While membership is essentially supported in RDBMS, the same support for ranking is clearly lacking. We address the fundamental integration of ranking in RDBMS in a way similar to how membership, i.e., Boolean filtering, is supported. We extend relational algebra by proposing a rank-relational model to capture the ranking property, and introducing new and extended operators to support ranking as a first-class construct. Enabled by the extended algebra, we present a pipelined and incremental execution model of ranking query plans (that cannot be expressed traditionally) based on a fundamental ranking principle. To optimize top-k queries, we propose a dimensional enumeration algorithm to explore the extended plan space by enumerating plans along two dual dimensions: ranking and membership. We also propose a sampling-based method to estimate the cardinality of rank-aware operators, for costing plans. Our experiments show the validity of our framework and the accuracy of the proposed estimation model.
Long-term pegylated interferon monotherapy following 72 weeks of pegylated interferon and ribavirin in hepatitis C virus genotype-1-infected slow responders.

OBJECTIVE Slow responders to pegylated interferon (Peg-IFN) and ribavirin (RBV) among patients infected with hepatitis C virus (HCV) genotype 1 may benefit from an extended treatment course. The aim of this study was to determine the efficacy of persistent negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy. METHODS A total of 46 HCV genotype 1-infected slow responders were treated for 72 weeks with Peg-IFN and RBV combination therapy alone (n=25) or additional long-term biweekly treatment with 90 μg of Peg-IFN-α2a (n=21). The criterion for the completion of long-term Peg-IFN monotherapy was defined as the attainment of constantly negative HCV RNA in the serum over 96 weeks during IFN treatment. RESULTS The patients with sustained negative serum HCV RNA during 96 weeks of IFN treatment had a higher rate of sustained virological response (SVR) than those without (81 vs. 40%, p=0.012). A multivariate analysis identified sustained negativity of serum HCV RNA over 96 weeks of IFN treatment to be a predictive factor for SVR. CONCLUSION In the present study, sustained negative serum HCV RNA over 96 weeks during long-term Peg-IFN monotherapy following 72 weeks of combination therapy of Peg-IFN and RBV resulted in beneficial virological outcomes among HCV genotype 1-infected slow responders.
SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis

Suppressor of Cytokine Signaling‐2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. This has been classically demonstrated by the overgrowth phenotype of SOCS2−/− mice, which has normal systemic insulin‐like growth factor 1 (IGF‐1) levels. The local effects of GH on bone growth are equivocal, and therefore this study aimed to understand better the SOCS2 signaling mechanisms mediating the local actions of GH on epiphyseal chondrocytes and bone growth. SOCS2, in contrast to SOCS1 and SOCS3 expression, was increased in cultured chondrocytes after GH challenge. Gain‐ and loss‐of‐function studies indicated that GH‐stimulated chondrocyte STATs‐1, ‐3, and ‐5 phosphorylation was increased in SOCS2−/− chondrocytes but not in cells overexpressing SOCS2. This increased chondrocyte STAT signaling in the absence of SOCS2 is likely to explain the observed GH stimulation of longitudinal growth of cultured SOCS2−/− embryonic metatarsals and the proliferation of chondrocytes within. Consistent with this metatarsal data, bone growth rates, growth plate widths, and chondrocyte proliferation were all increased in SOCS2−/− 6‐week‐old mice as was the number of phosphorylated STAT‐5–positive hypertrophic chondrocytes. The SOCS2−/− mouse represents a valid model for studying the local effects of GH on bone growth. © 2012 American Society for Bone and Mineral Research.
On Esscher Transforms in Discrete Finance Models

The object of our study is where each Sn is a m-dimensional stochastic (real valued) vector, i.e. denned on a probability space (Ω, , P) and adapted to a filtration (n)0≤n≤N with 0 being the σ-algebra consisting of all null sets and their complements. In this paper we interpret as the value of some financial asset k at time n. Remark: If the asset generates dividends or coupon payments, think of as to include these payments (cum dividend process). Think of dividends as being reinvested immediately at the ex-dividend price. Definition 1 (a) A sequence of random vectors where is called a trading strategy. Since our time horizon ends at time N we must always have ϑN ≡ 0. The interpretation is obvious: stands for the number of shares of asset k you hold in the time interval [n,n + 1). You must choose ϑn at time n. (b) The sequence of random variables where Sn stands for the payment stream generated by ϑ (set ϑ−1 ≡ 0).
Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

OBJECTIVES To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD). DESIGN Systematic review and meta-analysis. SETTINGS Outpatient clinics. SUBJECTS Adults, aged 18 years and older, with MDD receiving an initial treatment attempt with SGA. INTERVENTIONS Any CAM or exercise intervention compared with an SGA. OUTCOME MEASURES Treatment response, remission, change in depression rating, adverse events, treatment discontinuation, and treatment discontinuation due to adverse events. RESULTS We found 22 randomized controlled trials for direct comparisons and 127 trials for network meta-analyses, including trials of acupuncture, omega-3 fatty acids, S-adenosyl methionine, St. John's wort, and exercise. For most treatment comparisons, we found no differences between treatment groups for response and remission. However, the risk of bias of these studies led us to conclude that the strength of evidence for these findings was either low or insufficient. The risk of treatment harms and treatment discontinuation attributed to adverse events was higher for selective serotonin receptor inhibitors than for St. John's wort. CONCLUSIONS Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the available evidence base tempers any conclusions that we might draw from those trials. Future trials should incorporate patient-oriented outcomes, treatment expectancy, depressive severity, and harms assessments into their designs; antidepressants should be administered over their full dosage ranges; and larger trials using methods to reduce sampling bias are needed.
Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

BACKGROUND Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. METHODS AND RESULTS In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). CONCLUSION Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.
Drug Actions Interactions & Reactions

Rational use of gentamicin in the neonate and young infant ·is promoted in an editorial by Mccraken and Nelson in Am. ]. Dis. Child. 124: 13-14 (July) 1972. Reference is made to the resistance now being encountered by kanamycin and streptomycin in treating sepsis and meningitis. The use of gentamicin in these cases as well as in P11e11clomona11 cultured infections was encouraged. A review of dosing schedules, adequate . ~erum and spinal fluid levels, and variances according to infants age were made for both the IM and IV routes of administration. The authors also mentioned intrathecal or intraventricular dosing schedules. It was pointed out that gentamicin in minary tract infections required smaller doses (I mg/kg '8 h) due to the large amounts of drug excreted in the urine. With any form of administration no accumulation has been cited in dosing for seven to ten days. C.A:o. :nACE K. BnETTSCHNEH>En
Comparison of state occupation, entry, exit and waiting times in two or more groups based on current status data in a multistate model

We propose mean absolute distance‐based nonparametric bootstrap tests comparing the occupation probabilities, entry, exit and waiting times in a given state in two or more groups in a multistate model. The state occupied is determined at a single inspection time for each individual. Nonparametric monotonic regression and smoothing are used to uniquely define the various marginal estimators for each group which are then compared via a mean absolute distance criterion. A detailed simulation study shows that the proposed tests all have close to nominal size and reasonable power. An illustrative application to a pubertal development data set obtained from the NHANES III (Analytic and Reporting Guidelines: The Third National Health and Nutrition Examination Survey (1988–94). Hyattsville, MD: National Center for Health Statistics, Centers for Disease Control and Prevention, 1997) is also presented. Copyright © 2010 John Wiley & Sons, Ltd.