Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2+ breast cancer

Abstract Morphine and other opioid analgesics are potent pain-relieving agents routinely used for pain management in patients with cancer. However, these drugs have recently been associated with a worse relapse-free survival in patients with surgical cancer, thus suggesting that morphine adversely affects cancer progression and relapse. In this study, we evaluated the impact of morphine on breast cancer progression, metastatic dissemination, and outgrowth of minimal residual disease. Using preclinical mouse models for metastatic invasive lobular and HER2+ breast cancer, we show that analgesic doses of morphine do not affect mammary tumor growth, angiogenesis, and the composition of tumor-infiltrating immune cells. Our studies further demonstrate that morphine, administered in the presence or absence of surgery-induced tissue damage, neither facilitates de novo metastatic dissemination nor promotes outgrowth of minimal residual disease after surgery. Together, these findings indicate that opioid analgesics can be used safely for perioperative pain management in patients with cancer and emphasize that current standards of “good clinical practice” should be maintained.
Phase II study of dose-intense temozolomide in recurrent glioblastoma.

2038 Background: Most GBM patients relapse within 1 year from diagnosis. Among patients who progress on standard temozolomide, the optimal therapy is unknown. Resistance to temozolomide is partially mediated by the DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT may be depleted by prolonged temozolomide administration, dose-intense schedules may overcome resistance in patients with recurrent GBM. METHODS This is a phase 2 single arm study of temozolomide 75-100 mg/m2/day for 21 days of each 28-day cycle. Patients have GBM in first recurrence following standard therapy, including at least 2 cycles of adjuvant temozolomide. The primary endpoint is 6-month progression-free survival (PFS6). RESULTS Forty-eight participants have been accrued, one of whom withdrew prior to treatment. There are 26 men (55%), median age 57 (range 25-74), median KPS 90 (range 60-100). Of 40 patients with MGMT methylation results, 7 are methylated (17.5%). There were 6 (13%) partial responses (PR). Eighteen patients (38%) achieved stable disease (SD). Median PFS was 10 weeks (95% CI: 8-17) and PFS6 23%. Median OS was 13 months (95% CI: 8-not reached). Patients with methylated MGMT had median PFS 7.4 months (95% CI 1.9-15.6), and unmethylated promoters 2 months (95% CI 1.9-3.8; p=0.08). Median OS in methylated patients was 16 months (95% CI 16-not yet reached), unmethylated 11.5 months (95% CI 8-not yet reached; p=0.05). The probability of achieving PR/SD was higher in patients with MGMT methylation (p=0.03). Response, PFS, and OS did not depend on the number of prior temozolomide cycles or the time off temozolomide. Treatment was well tolerated with limited Grade 3 neutropenia (n=3) or thrombocytopenia (n=4). CONCLUSIONS Dose-intense temozolomide on a 21/28 day schedule is a safe regimen for patients with GBM in first recurrence. Updated efficacy results will be presented.
Cbln1 Is Essential for Interaction-Dependent Secretion of Cbln3

ABSTRACT Cbln1 and the orphan glutamate receptor GluRδ2 are pre- and postsynaptic components, respectively, of a novel transneuronal signaling pathway regulating synapse structure and function. We show here that Cbln1 is secreted from cerebellar granule cells in complex with a related protein, Cbln3. However, cbln1- and cbln3-null mice have different phenotypes and cbln1 cbln3 double-null mice have deficits identical to those of cbln1 knockout mice. The basis for these discordant phenotypes is that Cbln1 and Cbln3 reciprocally regulate each other's degradation and secretion such that cbln1-null mice lack both Cbln1 and Cbln3, whereas cbln3-null mice lack Cbln3 but have an approximately sixfold increase in Cbln1. Unlike Cbln1, Cbln3 cannot form homomeric complexes and is secreted only when bound to Cbln1. Structural modeling and mutation analysis reveal that, by constituting a steric clash that is masked upon binding Cbln1 in a “hide-and-run” mechanism of endoplasmic reticulum retention, a single arginine confers the unique properties of Cbln3.
Blood Pressure and Cardiovascular Disease Risk in the Veterans Affairs Diabetes Trial

OBJECTIVE Blood pressure ranges associated with cardiovascular disease (CVD) events in advanced type 2 diabetes are not clear. Our objective was to determine whether baseline and follow-up (On-Study) systolic blood pressure (SBP), diastolic blood pressure (DBP), and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial (VADT). RESEARCH DESIGN AND METHODS Participants in the VADT (n = 1,791) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in standard and intensive glycemic treatment groups. Blood pressure levels of all subjects at baseline and On-Study were analyzed to detect associations with CVD risk. The primary outcome was the time from randomization to the first occurrence of myocardial infarction, stroke, congestive heart failure, surgery for vascular disease, inoperable coronary disease, amputation for ischemic gangrene, or CVD death. RESULTS Separated SBP ≥140 mmHg had significant risk at baseline (hazards ratio [HR] 1.508, P < 0.001) and On-Study (HR 1.469, P = 0.002). DBP <70 mmHg increased CVD events at baseline (HR 1.482, P < 0.001) and On-Study (HR 1.491, P < 0.001). Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP <70 mmHg at baseline (HR 1.785, P = 0.03) and On-Study (HR 2.042, P = 0.003) and nearly all SBP with DBP <70 mmHg. CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension. Increased risk with DBP <70 mmHg, even when combined with SBP in guideline-recommended target ranges, supports a new finding in patients with type 2 diabetes. The results emphasize that DBP <70 mmHg in these patients was associated with elevated CVD risk and may best be avoided.
GFR estimation using standardized serum cystatin C in Japan.

BACKGROUND Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed glomerular filtration rate (GFR)-estimating equations based on standardized serum cystatin C (CKD-EPI(cys)) and standardized serum creatinine plus standardized serum cystatin C (CKD-EPI(cr-cys)). We developed new GFR-estimating equations based on standardized cystatin C for a Japanese population and compared their accuracy with the CKD-EPI equations. STUDY DESIGN Accuracy of diagnostic test study. SETTING & PARTICIPANTS 413 (development data set) and 350 individuals (validation data set). INDEX TEST CKD-EPI(cys); CKD-EPI(cr-cys); modifications to CKD-EPI(cys) and CKD-EPI(cr-cys) using Japanese coefficients; and newly developed Japanese eGFR equations based on standardized serum cystatin C (Eq(cys)), cystatin C with a nonrenal factor reflecting hypothesized extrarenal elimination (Eq(cys+nonrenal)), and creatinine in combination with cystatin C (Eq(cr-cys)). Standardized cystatin C values were determined by a colloidal gold immunoassay traceable to the international certified reference material ERM-DA471/IFCC. REFERENCE TEST Measured GFR by inulin renal clearance. RESULTS In a development data set, we calculated Japanese coefficients for CKD-EPI(cys) and CKD-EPI(cr-cys) of 0.977 (95% CI, 0.853-1.002) and 0.908 (95% CI, 0.889-0.928), respectively. In a validation data set, we compared CKD-EPI(cys), Eq(cys), and Eq(cys+nonrenal) with each other. Bias and accuracy were not significantly different among the 3 equations. The precision of CKD-EPI(cys) was significantly better than for Eq(cys) (P = 0.007) and not significantly different from Eq(cys+nonrenal) (P = 0.6). We then compared 0.908 × CKD-EPI(cr-cys), Eq(cr-cys), and Eq(average) (the average value of Eq(cr) [previous Japanese equation based on standardized serum creatinine] and Eq(cys+nonrenal)) with each other in the validation data set. Bias and accuracy were not significantly different among the 3 equations. The precision of 0.908 × CKD-EPI(cr-cys) was significantly better than for Eq(cr-cys) (P = 0.004) and not significantly different from Eq(average) (P = 0.06). LIMITATIONS Limited number of participants with measured GFR >90 mL/min/1.73 m(2). Extrarenal elimination of cystatin C was not measured. CONCLUSIONS CKD-EPI(cys) performed well in Japanese individuals, suggesting that equations based on serum cystatin C could be used in patients with different races without modification. Accounting for extrarenal elimination of cystatin C may improve the performance of estimating equations.
Improved action recognition by combining multiple 2D views in the bag-of-words model

Action recognition is a hard problem due to the many degrees of freedom of the human body and the movement of its limbs. This is especially hard when only one camera viewpoint is available and when actions involve subtle movements. For instance, when looked from the side, checking one's watch may look very similar to crossing one's arms. In this paper, we investigate how much the recognition can be improved when multiple views are available. The novelty is that we explore various combination schemes within the robust and simple bag-of-words (BoW) framework, from early fusion of features to late fusion of multiple classifiers. In new experiments on the publicly available IXMAS dataset, we learn that action recognition can be improved significantly already by only adding one viewpoint. We demonstrate that the state-of-the-art on this dataset can be improved by 5% - achieving 96.4% accuracy - when multiple views are combined. Cross-view invariance of the BoW pipeline can be improved by 32% with intermediate-level fusion.
Some aspects of handling velocity inversion and hidden layer problems in seismic refraction work

There are two types of masked layers in seismic refraction work: the velocity reversal (low-velocity layer) and the hidden layer (insufficient velocity contrast or layer thickness). On the basis of an analytical formulation of the general case of a masked layer under an overburden of plane and parallel multiple refractors the two limiting cases are discussed: the solution resulting from an uncritical interpretation of the measured time-distance curve and the blind zone solution. Between these two limiting cases there is a variety of possible masked layer solutions. These no-blind zone solutions—as well as the blind zone solution itself—are formulated separately for the velocity inversion and the hidden layer case. For the evaluation of some no-blind zone solution a diagram is presented which can be used for any case of multiple refractors in the overburden of the masked layer. However, it is only for the three- and the four-layer case that a blind zone interpretation by use of diagrams is advisable. Such diagrams are presented together with the basic sets of formulae which contain as parameters only ratios of velocities and layer thicknesses. As the velocity of the masked layer is usually unknown the diagrams are principally constructed to show the dependence on the masked layer velocity. This is useful for estimation of the largest possible error.
Genetic diversity and population structure of Arabidopsis thaliana along an altitudinal gradient

In this study Tyagi et al. determined the genetic diversity and population structure of the model plant, Arabidopsis thaliana. These populations inhabit west Himalaya, an undersampled region. Using 19 genomic SSR and 11 chloroplast markers they determined that these populations are highly structured and genetically distinct from the rest of the world populations. They also observed that the populations were structured at the altitudinal level. Additionally their molecular clock analysis showed that these populations are not recent introductions and have inhabited the Himalayan region for about 130,000 years.
Comparison of multiple models for remote sensing of carbon exchange using MODIS data in conifer-dominated forests

Boreal forests in the northern hemisphere provide important sinks for storing carbon dioxide (CO2). However, the size and distribution of these sinks remain uncertain. In particular, many remote-sensing models show a strong bias in the simulation of carbon fluxes for evergreen needleleaf forest. The objective of this study is to improve these predictive models for accurately quantifying temporal changes in the net ecosystem exchange (NEE) of conifer-dominated forest solely based on satellite remote sensing, including the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra daytime land-surface temperature (LST), night-time LST′, enhanced vegetation index (EVI), land–surface water index (LSWI), fraction of absorbed photosynthetically active radiation (FPAR), and leaf area index (LAI). Considering that the component fluxes, gross primary production (GPP), and ecosystem respiration (Re), are strongly influenced by vegetation phenology, seasonality information was extracted from time-series MODIS EVI data based on non-linear least-squares fits of asymmetric Gaussian model functions with a software package for analysing the time-series of satellite sensor data (TIMESAT). The results indicated that models directly incorporating phenological information failed to improve their performance for temperate deciduous forest. Instead, three methods to retrieve the component fluxes – GPP and Re – including direct estimates, models incorporating the phenological information, and models developed based on the threshold value (LST 273 K), were explored respectively. All methods improved NEE estimates markedly and models developed based on the threshold value performed best, and provided a future framework for accurate remote sensing of NEE in evergreen forest.
Neutral composition measurements by the Pioneer Venus Neutral Mass Spectrometer during Orbiter re‐entry

Measurements by the Pioneer Venus Orbiter Neutral Mass Spectrometer (ONMS) instrument during Orbiter re-entry have been made from 18–24 hours local solar time, above 170 km, of He, and from midnight to 4.5 hours below 200 km of He, N, O, CO, N2, and CO2. Preliminary results indicate that in the post-midnight sector He is the dominant species above 170 km, O the dominant species from 140–170 km and CO2 the dominant species below 140 km. Estimated scale height temperatures for He, O and CO2 of about 105–120 K are similar to those observed in 1978–80 at higher solar activity. The densities at 1 am local solar time and at 150 km are within 35% of those measured earlier. The He bulge is also similar to that observed in 1978–80 confirming that thermosphere superrotation is still present. Comparison with the results of a Venus Thermosphere General Circulation Model suggests the nightside is not sensitive to changes in solar activity due to the isolation of the day and night thermospheres. Apparently, the relatively small changes in the dayside thermosphere with solar activity have little impact on the nightside thermosphere.
A temporal matching method for pitch determination from noisy speech signals

A new method based on temporal matching is presented in this paper for pitch determination from noisy speech signals. At first, a variable-length average magnitude sum function (VLAMSF) that exhibits a periodicity similar to the pitch period of the voiced speech, has been proposed. We argue that the discrete cosine transform (DCT) power spectrum of the VLAMSF is capable of revealing an estimate of a pitch-harmonic (PH) more accurately even in a heavy noisy scenario. Then, exploiting the extracted PH, we formulate an impulse train with a variable-period that is used to temporally match the periodicity of the proposed VLAMSF for pitch determination. It has been shown through extensive simulations using the Keele database that our new approach consistently outperforms the other existing methods especially at low signal-to-noise ratios (SNRs).
The Use of Dynamic Segment Scoring for Language-Independent Question Answering

This paper presents a novel language-independent question/answering (Q/A) system based on natural language processing techniques, shallow query understanding, dynamic sliding window techniques, and statistical proximity distribution matching techniques. The performance of the proposed system using the latest Text REtrieval Conference (TREC-8) data was comparable to results reported by the top TREC-8 contenders.
A search for high-redshift molecular absorption lines towards millimetre-loud, optically faint quasars

We describe initial results of a search for redshifted molecular absorption towards four millimetre-loud, optically faint quasars. A wide frequency bandwidth of up to 23 GHz per quasar was scanned using the Swedish-ESO Submillimetre Telescope at La Silla. Using a search list of commonly detected molecules, we obtained nearly complete redshift coverage up to z a b s = 5. The sensitivity of our data is adequate to have revealed absorption systems with characteristics similar to those seen in the four known redshifted millimetre-band absorption systems, but none were found. Our frequency-scan technique nevertheless demonstrates the value of wide-band correlator instruments for searches such as these. We suggest that a somewhat larger sample of similar observations should lead to the discovery of new millimetre-band absorption systems.
Emerging options for the management of age-related macular degeneration with stem cells

Age-related macular degeneration (AMD) is a devastating retinal disease that occurs in later life as the retinal pigment epithelium (RPE) cells die, with subsequent photoreceptor degeneration. In the past, RPE transplant surgeries gave evidence that AMD was potentially treatable, but it involved limited amounts of ocular tissue, and the complication rate was high. Then, stem cell transplants offered an unlimited supply of retinal precursors for endogenous repair and exogenous cell replacement. Debate continues as to which type of stem cell is most appropriate for treating AMD. The prospects include adult-derived progenitor stem cells (including progenitor cells from ocular tissues), hematopoietic stem cells, embryonic stem cells, and induced pluripotent stem cells. Now the therapy is expanding into phase I human trials. This review examines the collective research contributions toward a clinical model of AMD management with stem cells.
Filtering revolution

Reporting bias – the media’s tendency to systematically underreport or overreport certain types of events – is a persistent problem for participants and observers of armed conflict. We argue that the nature of reporting bias depends on how news organizations navigate the political context in which they are based. Where government pressure on the media is limited – in democratic regimes – the scope of reporting should reflect conventional media preferences toward novel, large-scale, dramatic developments that challenge the conventional wisdom and highlight the unsustainability of the status quo. Where political constraints on reporting are more onerous – in non-democratic regimes – the more conservative preferences of the state will drive the scope of coverage, emphasizing the legitimacy and inevitability of the prevailing order. We test these propositions using new data on protest and political violence during the 2011 Libyan uprising and daily newspaper coverage of the Arab Spring from 113 countries. We uncover evidence of a status-quo media bias in non-democratic states, and a revisionist bias in democratic states. Media coverage in non-democracies underreported protests and nonviolent collective action by regime opponents, largely ignored government atrocities, and overreported those caused by rebels. We find the opposite patterns in democratic states.
Early production of radicals from charged particle tracks in water.

An overview is presented of the early production of water radicals due to the passage of fast charged particles. It starts with energy deposition in tracks followed by the time scale of events of importance to radiation chemistry and radiobiology. Primary radical yields and reaction schemes, considered independent of particle LET but functions of the phase of the medium, are discussed within the framework of diffusion kinetics. Taking these primary G values (i.e., 100-eV yield) of OH, e-aq, and H as 5.70, 4.78, and 0.62, respectively, in liquid water, simple examples are provided for the evolution of the radical species. Finally, attention is drawn to some special physical features of fast, heavy charged particle tracks.
Deformation mechanisms and rheology: why marble is weaker than quartzite

When deformed together in nature, calcite rocks invariably appear weaker and more ductile than quartz rocks. This can be reconciled with experimental flow data only by taking into account grain-size-sensitive (GSS) flow in calcite rocks, which is predicted to dominate even at grain sizes on the order of 1mm at middle metamorphic grades. Using new experimental data that demonstrate the transition between intracrystalline plastic and GSS flow of quartz rocks, we predict that unnaturally small grain sizes at temperatures of 700°C or higher are required for GSS flow of quartz in nature. Thus natural flow of quartzite is expected to occur by intracrystalline plastic processes, even after recrystallization to a fine grain size.
Learning to Filter with Predictive State Inference Machines

Latent state space models are a fundamental and widely used tool for modeling dynamical systems. However, they are difficult to learn from data and learned models often lack performance guarantees on inference tasks such as filtering and prediction. In this work, we present the PREDICTIVE STATE INFERENCE MACHINE (PSIM), a data-driven method that considers the inference procedure on a dynamical system as a composition of predictors. The key idea is that rather than first learning a latent state space model, and then using the learned model for inference, PSIM directly learns predictors for inference in predictive state space. We provide theoretical guarantees for inference, in both realizable and agnostic settings, and showcase practical performance on a variety of simulated and real world robotics benchmarks.
A new procedure for developing UMTS filters based on periodic structures

A new method for developing UMTS filters for upload and download bands is proposed. The filters are based on a periodical resonator called the H-type resonator. Simulation results show that the relative mean error is less than 1.5%. The filter designed by this method has an insertion loss less than 1dB and provides low return loss in the bandpass. A periodic network analysis was used for designing the H-type resonator. We have also derived a lumped-element circuit model for the filter whose element's values are found by using genetic algorithms. It is shown that the filter has a suitable frequency response, and that it can be applied quite well in telecommunication systems.