Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer.

PURPOSE To evaluate the safety and pharmacokinetics of BCL-2 antisense oligonucleotide (G3139) administered by prolonged i.v. infusion in patients with advanced cancer. EXPERIMENTAL DESIGN A total of 35 patients was treated in cohorts of 3-6 with 0.6-6.9 mg/kg/day of BCL-2 antisense oligonucleotide as a continuous infusion for 14 or 21 days. Plasma levels of intact antisense oligonucleotide were measured in all patients. RESULTS G3139 was generally well tolerated. At the highest dose level examined in this study (6.9 mg/kg/day), fatigue and transient reversible elevations of serum transaminases (grades 2-3) became apparent after >or=7 days of treatment. Both reactions were believed to be drug related. Pharmacokinetic analyses showed that steady-state plasma concentrations of G3139 were reached approximately 10 h after starting the infusion and increased linearly across the range of doses administered <or=6.9 mg/kg/day. The terminal plasma half-life was approximately 2 h. Exploratory studies using Western blots, performed on peripheral blood mononuclear cells on selected patients, demonstrated a decline in bcl-2 protein levels during treatment. No major antitumor responses were observed. CONCLUSIONS BCL-2 antisense therapy is well tolerated. Relative to other dose-finding studies of G3139, fatigue was somewhat more prominent in this study, possibly because of the protracted i.v. infusion schedule of the antisense oligonucleotide. Current randomized trials are using the highest daily dose established in this study given by shorter infusion periods (i.e., 7 mg/kg/day for 5-7 days) to enhance the antitumor activity of standard cytotoxic drugs.
Immunoglobulin levels in workers exposed to hexachlorobenzene

The serum immunoglobulin (IgG, IgM and IgA) concentrations of 52 chlorinated-exposed workers were examined and compared with those of non-exposed, age- and sex-matched individuals. At the time of testing, the exposed population had mean hexachlorobenzene (HCB) blood levels of 3.84 mg/dl with a range of 0.1 to 16 mg/dl. Increased IgG and IgM levels were found in the HCB- exposed workers (P50.05 and P50.01, respectively). Hepatic function was evaluated by serum aspartate (AST) and alanine aminotransferase (ALT) activities, as well as by bilirubin levels. IgM concentrations were positively correlated with three of the studied parameters, namely, length of exposure (r=0.367) and the activities of both AST (r=0.367) and ALT (r=0.507).
Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study

This randomized, open-label, active-controlled, dose-finding phase IIb study evaluated the efficacy and safety of trabedersen (AP 12009) administered intratumorally by convection-enhanced delivery compared with standard chemotherapy in patients with recurrent/refractory high-grade glioma. One hundred and forty-five patients with central reference histopathology of recurrent/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) were randomly assigned to receive trabedersen at doses of 10 or 80 µM or standard chemotherapy (temozolomide or procarbazine/lomustine/vincristine). Primary endpoint was 6-month tumor control rate, and secondary endpoints included response at further timepoints, survival, and safety. Six-month tumor control rates were not significantly different in the entire study population (AA and GBM). Prespecified AA subgroup analysis showed a significant benefit regarding the 14-month tumor control rate for 10 µM trabedersen vs chemotherapy (p= .0032). The 2-year survival rate had a trend for superiority for 10 µM trabedersen vs chemotherapy (p = .10). Median survival for 10 µM trabedersen was 39.1 months compared with 35.2 months for 80 µM trabedersen and 21.7 months for chemotherapy (not significant). In GBM patients, response and survival results were comparable among the 3 arms. Exploratory analysis on GBM patients aged ≤55 years with Karnofsky performance status >80% at baseline indicated a 3-fold survival at 2 and 3 years for 10 µM trabedersen vs chemotherapy. The frequency of patients with related or possibly drug-related adverse events was higher with standard chemotherapy (64%) than with 80 µM trabedersen (43%) and 10 µM trabedersen (27%). Superior efficacy and safety for 10 µM trabedersen over 80 µM trabedersen and chemotherapy and positive risk–benefit assessment suggest it as the optimal dose for further clinical development in high-grade glioma.
Neural correlates of partial lexical activation

As a spoken word unfolds over time, it is temporarily consistent with the acoustic forms of multiple words. Previous behavioral research has shown that, in the face of temporary ambiguity about how a word will end, multiple candidate words are briefly activated. Here, we provide neural imaging evidence that lexical candidates only temporarily consistent with the input activate perceptually based semantic representations. An artificial lexicon and novel visual environment were used to target human MT/V5 and an area anterior to it which have been shown to be recruited during the reading of motion words. Participants learned words that referred to novel objects and to motion or color/texture changes that the objects underwent. The lexical items corresponding to the change events were organized into phonologically similar pairs differing only in the final syllable. Upon hearing spoken scene descriptions in a posttraining verification task, participants showed greater activation in the left hemisphere anterior extent of MT/V5 when motion words were heard than when nonmotion words were heard. Importantly, when a nonmotion word was heard, the level of activation in the anterior extent of MT/V5 was modulated by whether there was a phonologically related competitor that was a motion word rather than another nonmotion word. These results provide evidence of activation of a perceptual brain region in response to the semantics of a word while lexical competition is in process and before the word is fully recognized.
A Novel Intrusion Detection Method Using Deep Neural Network for In-Vehicle Network Security

In this paper, we propose a novel intrusion detection technique using a deep neural network (DNN). In the proposed technique, in-vehicle network packets exchanged between electronic control units (ECU) are trained to extract low- dimensional features and used for discriminating normal and hacking packets. The features perform in high efficient and low complexity because they are generated directly from a bitstream over the network. The proposed technique monitors an exchanging packet in the vehicular network while the feature are trained off-line, and provides a real-time response to the attack with a significantly high detection ratio in our experiments.
Choosing people: the role of social capital in information seeking behaviour

It is an almost universal finding in studies investigating human information behaviour that people choose other people as their preferred source of information. An explanation for the use of people as information sources is that they are easier to approach than more formal sources and therefore are a least effort option. However there have been few studies that have investigated who the people chosen as information sources are and what their relationship to the information seeker is. This paper reports findings that come out of a larger investigation of the information seeking behaviour of a random sample of residents of Ulaanbaatar, Mongolia. Using the theory of social capital as a conceptual framework and the methods of social network analysis, this study investigated the relational factors associated with the choice of people as information sources. Results indicate that respondents chose people who had better resources than they had and were not well known by them. This suggests that respondents were deliberate in their choice of people information sources and therefore it is speculated that people are not necessarily the least effort option but may require considerable effort to seek out and consult.
The role of cerebral oedema in the pathogenesis of cerebral malaria

Abstract It has been suggested that sequestration of parasitized red blood cells might contribute to the pathogenesis of cerebral malaria (CM), by hypoxia causing either: (i) compensatory vasodilatation with a resultant increase in the brain volume; or (ii) enhancing cytokine-induced nitric oxide (NO) production via induction of inducible NO synthase (iNOS). Available evidence suggests that cerebral oedema is the initiating and probably the most important factor in the pathogenesis of murine CM. The relevance of this model in the study of the pathogenesis of CM has been questioned. However, a closer look at published reports on both human and murine CM, in this review, suggests that the pathogenesis of the murine model of CM might reflect more closely the CM seen in African children than that seen in Asian adults. It is also proposed that the role of iNOS induction during CM is protective: that the primary purpose of iNOS induction is to inhibit the side effects of brain indoleamine 2,3-dioxygenase (IDO) induction and quinolinic acid accumulation during hypoxia.
The [RNQ+] prion: A model of both functional and pathological amyloid

The formation of fibrillar amyloid is most often associated with protein conformational disorders such as prion diseases, Alzheimer disease and Huntington disease. Interestingly, however, an increasing number of studies suggest that amyloid structures can sometimes play a functional role in normal biology. Several proteins form self-propagating amyloids called prions in the budding yeast Saccharomyces cerevisiae. These unique elements operate by creating a reversible, epigenetic change in phenotype. While the function of the non-prion conformation of the Rnq1 protein is unclear, the prion form, [RNQ+], acts to facilitate the de novo formation of other prions to influence cellular phenotypes. The [RNQ+] prion itself does not adversely affect the growth of yeast, but the overexpression of Rnq1p can form toxic aggregated structures that are not necessarily prions. The [RNQ+] prion is also involved in dictating the aggregation and toxicity of polyglutamine proteins ectopically expressed in yeast. Thus, the [RNQ+] prion provides a tractable model that has the potential to reveal significant insight into the factors that dictate how amyloid structures are initiated and propagated in both physiological and pathological contexts.
A Feature-Based, Robust, Hierarchical Algorithm for Registering Pairs of Images of the Curved Human Retina

This paper describes a robust hierarchical algorithm for fully-automatic registration of a pair of images of the curved human retina photographed by a fundus microscope. Accurate registration is essential for mosaic synthesis, change detection, and design of computer-aided instrumentation. Central to the algorithm is a 12-parameter interimage transformation derived by modeling the retina as a rigid quadratic surface with unknown parameters. The parameters are estimated by matching vascular landmarks by recursively tracing the blood vessel structure. The parameter estimation technique, which could be generalized to other applications, is a hierarchy of models and methods, making the algorithm robust to unmatchable image features and mismatches between features caused by large interframe motions. Experiments involving 3,000 image pairs from 16 different healthy eyes were performed. Final registration errors less than a pixel are routinely achieved. The speed, accuracy, and ability to handle small overlaps compare favorably with retinal image registration techniques published in the literature.
The complete set of ASCA X-ray observations of non-magnetic cataclysmic variables

We present the complete set of 34 ASCA observations of non-magnetic cataclysmic variables. Timing analysis reveals large X-ray flux variations in dwarf novae in outburst (Z Cam, SS Cyg and SU UMa) and orbital modulation in high inclination systems (including OY Car, HT Cas, U Gem, T Leo). We also found episodes of unusually low accretion rate during quiescence (VW Hyi and SS Cyg). Spectral analysis reveals broad temperature distributions in individual systems, with emission weighted to lower temperatures in dwarf novae in outburst. Absorption in excess of interstellar values is required in dwarf novae in outburst, but not in quiescence. We also find evidence for subsolar abundances and X-ray reflection in the brightest systems. LS Peg, V426 Oph and EI UMa have X-ray spectra that are distinct from the rest of the sample and all three exhibit candidate X-ray periodicities. We argue that they should be reclassified as intermediate polars. In the case of V345 Pav we found that the X-ray source had been previously misidentified. Ke yw ords: stars: dwarf novae ‐ novae, cataclysmic variables ‐ X-rays: stars.
Peering through the Dust: Evidence for a Supermassive Black Hole at the Nucleus of Centaurus A from VLT Infrared Spectroscopy

We used the near-infrared spectrometer ISAAC at the ESO Very Large Telescope to map the velocity field of Cen A (NGC 5128) at several position angles and locations in the central 20'' of the galaxy. The high spatial resolution (~0.″5) velocity fields from both ionized and molecular gas (Paβ, [Fe II], Brγ, and H2) are not compromised by either excitation effects or obscuration. We identify three distinct kinematical systems: (1) a rotating "nuclear disk" of ionized gas, confined to the inner 2'', the counterpart of the Paα feature previously revealed by HST/NICMOS imaging; (2) a ringlike system with a ~6'' inner radius detected only in H2 likely the counterpart of the 100 pc scale structure detected in CO by other authors; (3) a normal extended component of gas rotating in the galactic potential. The nuclear disk is in Keplerian rotation around a central mass concentration, dark (M/L > 20 M☉/LK☉) and pointlike at the spatial resolution of the data (R < 0.″25-4 pc). We interpret this mass concentration as a supermassive black hole. Its dynamical mass based on the line velocities and disk inclination (i > 15°) is MBH = 2 × 108 M☉. The ringlike system is probably characterized by noncircular motions; a "figure of 8" pattern observed in the H2 position-velocity diagram might provide kinematical evidence for the presence of a nuclear bar.
Alliance Experience and Accommodation in the Choice of Alliance Governance Structure

This paper explores a less-recognized aspect of alliance management capabilities, accommodation, which occurs when a firm refrains from applying its bargaining power, agreeing to terms that address their partner’s concerns or interests to a greater degree than their own. Despite its potential importance, the strategy and marketing literatures provide few insights into when and how accommodation occurs in alliances. We propose that firms with greater alliance experience are more likely to accommodate their partner’s concerns through the choice of governance structure, relying on their accumulated alliance capabilities to mitigate their own governance concerns. We find evidence to support our propositions in innovation alliances initiated between target and client firms in the biotechnology and pharmaceutical industries. In addition to formally introducing the concept of accommodation into the literature on the governance of alliances, we establish that there are boundary conditions for accommodation to occur; in our case, sufficient alliance experience. Moreover, we provide evidence in support of the transaction value perspective, which - while intellectually appealing - has been difficult to test empirically. Lastly, we demonstrate the value of considering the (possibly conflicting) concerns and preferences of all partners in the alliance, rather than focusing on the hazards faced by a focal partner.
A rollover indicator based on a tire stiffness backstepping observer: Application to an All-Terrain Vehicle

Lateral rollover is the leading cause of fatal accidents in light all-terrain vehicles (e.g. quad bikes), especially in the agricultural area. The estimation and prediction of hazardous situations are preliminary steps in the design of active security devices. If numerous metrics have already been defined for on-road vehicles, few approaches are suitable for fast motions in a natural environment (mainly due to tire/ground contact specificity and variability). This paper proposes an algorithm dedicated to the estimation and prediction of one metric, namely lateral load transfer (LLT), in order to anticipate rollover situations on an irregular and natural ground. It is based on a vehicle dynamic model, used jointly with a backstepping observer. It allows to take into account tire/ground contact nonlinearities and variability, which impact the rollover tendency. The efficiency of the metric is investigated through advanced simulations and full scale experiments on a Kymco quad bike.
Privacy and Access Control for Outsourced Personal Records

Cloud storage has rapidly become a cornerstone of many IT infrastructures, constituting a seamless solution for the backup, synchronization, and sharing of large amounts of data. Putting user data in the direct control of cloud service providers, however, raises security and privacy concerns related to the integrity of outsourced data, the accidental or intentional leakage of sensitive information, the profiling of user activities and so on. Furthermore, even if the cloud provider is trusted, users having access to outsourced files might be malicious and misbehave. These concerns are particularly serious in sensitive applications like personal health records and credit score systems. To tackle this problem, we present GORAM, a cryptographic system that protects the secrecy and integrity of outsourced data with respect to both an untrusted server and malicious clients, guarantees the anonymity and unlink ability of accesses to such data, and allows the data owner to share outsourced data with other clients, selectively granting them read and write permissions. GORAM is the first system to achieve such a wide range of security and privacy properties for outsourced storage. In the process of designing an efficient construction, we developed two new, generally applicable cryptographic schemes, namely, batched zero-knowledge proofs of shuffle and an accountability technique based on chameleon signatures, which we consider of independent interest. We implemented GORAM in Amazon Elastic Compute Cloud (EC2) and ran a performance evaluation demonstrating the scalability and efficiency of our construction.
Are the most durable shelly taxa also the most common in the marine fossil record?

Abstract This paper tests whether the most common fossil brachiopod, gastropod, and bivalve genera also have intrinsically more durable shells. Commonness was quantified using occurrence frequency of the 450 most frequently occurring genera of these groups in the Paleobiology Database (PBDB). Durability was scored for each taxon on the basis of shell size, thickness, reinforcement (ribs, folds, spines), mineralogy, and microstructural organic content. Contrary to taphonomic expectation, common genera in the PBDB are as likely to be small, thin-shelled, and unreinforced as large, thick-shelled, ribbed, folded, or spiny. In fact, only six of the 30 tests we performed showed a statistically significant relationship between durability and occurrence frequency, and these six tests were equally divided in supporting or contradicting the taphonomic expectation. Thus, for the most commonly occurring genera in these three important groups, taphonomic effects are either neutral with respect to durability or compensated for by other factors (e.g., less durable taxa were more common in the original communities). These results suggest that biological information is retained in the occurrence frequency patterns of our target groups.
The gap between human's attitude towards robots in general and human's expectation of an ideal everyday life robot

Acceptance, trust and a successful deployment of robots in human's everyday life depends both on technical implementation and on psychological aspects. The current work identifies essential features and characteristics that have the potential to increase the acceptance of robots, reduce prejudices and improve the development of appropriate and suitable robots with target-group specific features and characteristics. We present the first part of a major research project that aims to develop a valid and reliable toolkit for an encompassing measurement of human's attitude towards robots. By means of the Semantic Differential Scale a comparison of human's attitude towards robots in general and human's expectation of an ideal, personal everyday life robot has been performed. Results reveal major differences between these two concepts and the demand of robots adapted to human's requirements.
Correlates of Scholarly Recognition in the Field of Higher Education

This study examines the correlates that distinguish between editors and noneditors in the field of higher education. The correlates examined are research productivity, the allocation of time for research and teaching, professional contacts of faculty, membership in professional associations, and characteristics of the scholars’ doctoral training program. The conceptual perspective is drawn from the literature on scholarly recognition; editorial board appointments are defined as one form of scholarly recognition. Data are reported for matched pairs of editors and noneditors drawn from the ASHE Directory and conclusions are drawn about correlates that differentiate between the two groups.
Truths and controversies concerning the role of miRNAs in atherosclerosis and lipid metabolism

Purpose of review Better tools are sorely needed for both the prevention and treatment of cardiovascular diseases, which account for more than one-third of the deaths in Western countries. MicroRNAs typically regulate the expression of several mRNAs involved in the same biological process. Therapeutic manipulation of miRNAs could restore the expression of multiple players within the same physiologic pathway, and ideally offer better curative outcomes than conventional approaches that target only one single player within the pathway. This review summarizes available studies on the prospective value of targeting miRNAs to prevent dyslipidemia and atherogenesis. Recent findings Silencing the expression of miRNAs that target key genes involved in lipoprotein metabolism in vivo with antisense oligonucleotides results in the expected de-repression of target mRNAs in liver and atherosclerotic plaques. However, the consequences of long-term antimiRNA treatment on both circulating lipoproteins and athero-protection are yet to be established. Summary A number of studies have demonstrated the efficacy of miRNA mimics and inhibitors as novel therapeutic tools for treating dyslipidemia and cardiovascular diseases. Nevertheless, concerns over unanticipated side-effects related to de-repression of additional targets should not be overlooked for miRNA-based therapies.