Miracle-dz/UniFAR-FTUs huggingface dataset:
Aldoxorubicin: a tumor-targeted doxorubicin conjugate for relapsed or refractory soft tissue sarcomas

Despite available therapies after initial systemic therapy, prognosis remains poor in relapsed or refractory soft tissue sarcomas (STS). The rational and clinical development of novel agents to improve outcomes in this area of high unmet need is desperately warranted. Aldoxorubicin is a prodrug of doxorubicin that binds to serum albumin immediately after administration through an acid-sensitive hydrazone linker and is subsequently transported to tumor tissues where the acidic environment cleaves the linker and facilitates delivery of a tumor-targeted drug payload. In clinical studies to date, there has been evidence of efficacy and mitigated cardiac toxicity. In this review, we comprehensively detail the clinical development of aldoxorubicin in STS to date. Specifically, we highlight available data on the pharmacokinetics and efficacy from Phase I, Phase II, and Phase III trials in advanced or metastatic STS. We conclude with considerations for future directions of investigation for this promising antitumor agent.
Synthetic CpG oligonucleotides induce a genetic profile ameliorating murine myocardial I/R injury

We previously demonstrated that pre‐conditioning with CpG oligonucleotide (ODN) 1668 induces quick up‐regulation of gene expression 3 hours post‐murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the “black box” beyond these first 3 hours. C57BL/6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed‐chest model, followed by reperfusion for 24 hours. RNA was extracted from hearts, and labelled cDNA was hybridized to gene microarrays. Data analysis was performed with BRB ArrayTools and Ingenuity Pathway Analysis. Functional groups mediating restoration of cellular integrity were among the top up‐regulated categories. Genes known to influence cardiomyocyte survival were strongly induced 24 hours post‐I/R. In contrast, proinflammatory pathways were down‐regulated. Interleukin‐10, an upstream regulator, suppressed specifically selected proinflammatory target genes at 24 hours compared to 3 hours post‐I/R. The IL1 complex is supposed to be one regulator of a network increasing cardiovascular angiogenesis. The up‐regulation of numerous protective pathways and the suppression of proinflammatory activity are supposed to be the genetic correlate of the cardioprotective effects of CpG 1668 pre‐conditioning.
Towards High Performance Dynamic Cloud Environments

The advent of the Internet of Things, sensor and social networks, to mention just a few examples, all contribute towards the solid establishment of the Big Data era. High Performance Computing (HPC) becomes necessary for the efficient processing of the massive amounts of data our society generates, and cloud computing is a critical component to deliver this processing power to a broader audience that cannot afford to acquire and maintain such complex computing systems themselves. However, HPC specific technology and performance is not yet apt to be delivered efficiently over highly flexible and dynamic environments, as typically are the virtualized cloud infrastructures. In this thesis, we address challenges that arise in high performance dynamic cloud environments, that are equipped with HPC specific technology, in the context of networking and virtualization. We use InfiniBand, a high performance lossless interconnection network as the basis of our research, and first show that lossless networks pose prime challenges when the nature of the infrastructure is very dynamic, i.e. exhibits continuous changes. Then we propose a network I/O virtualization architecture, the InfiniBand vSwitch architecture, that can make lossless network technologies more favorable in the cloud. Moreover, we propose different network reconfiguration methods to enable performance-driven reconfigurations in very large network topologies that are commonly found in data centers. Performance-driven reconfigurations are frequently needed to adapt to unpredictable workload changes resulting from the shared and on-demand nature of a cloud platform, or when cloud providers employ live migration of virtual machines to optimize the resource usage of their infrastructure. Last but not least, we propose a new Quality-of-Service metric, called delay, to capture the directly observable service degradation in consolidated cloud environments. We suggest that the delay can be used as a direct service level agreement metric between cloud providers and cloud tenants.
Method of op-amp speeding increase, basing on introduction of the nonlinear differentiating circuit

The method of the high speed increase and the transients for the large signal in operational amplifier (Op-Amp) is considered. Base structure of Op-Amp, which is classical, contains the basic correcting condenser, providing stability of Op-Amp, the compensating capacity driver (DCc∗) and the buffer amplifier. For increase on 1–3 order of the slew rate (SR) of the output voltage increase in such Op-Amp the nonlinear differentiating circuit is introduced. This circuit is realized on the basis of the additional differential stage (DS2) and differentiating capacity. Thus DS2 practically don't influence on some static and small-signal dynamic parameters of Op-Amp, but on the large signal in during leading edge of the input signal, when basic differential stage of Op-Amp enters into a nonlinear mode, he differentiates input voltage and forms the large recharge current of the basic correction capacity. As consequence, SR of Op-Amp essentially raises. Feature of Op-Amp of the given class is the opportunity of the differential stage to work in the micocurrents mode. The decision of the nonlinear differential equation describing transients in Op-Amp is received. This decision allows designing the concrete circuit-technical decisions of Op-Amp within the framework of modern microelectronic technologies, including BJT, SiGe, CMOS, BiJFet, etc. The results of computer simulation confirming of the efficiency of the suggested circuit-technical decisions are given. So, in the micro-powerful BiJFet operational amplifier admitting the work at low temperatures and influence of a penetrating radiation, maximal SR of the output voltage increase increases up to 3000–4000 V/μs.
Contemporary genetic structure of an endemic freshwater turtle reflects Miocene orogenesis of New Guinea

The island of New Guinea lies in one of the most tectonically active regions in the world and has long provided outstanding opportunity for studies of biogeography. Several chelid turtles, of clear Gondwanal origin, occur in New Guinea; all species except one, the endemic Elseya novaeguineae, are restricted to the lowlands south of the Central Ranges. Elseya novaeguineae is found throughout New Guinea. We use mitochondrial and nuclear gene variation among populations of E. novaeguineae throughout its range to test hypotheses of recent extensive dispersal versus more ancient persistence in New Guinea. Its genetic structure bears the signature of Miocene vicariance events. The date of the divergence between a Birds Head (Kepala Burung) clade and clades north and south of the Central Ranges is estimated to be 19.8 Mya [95% highest posterior density (HPD) interval of 13.3–26.8 Mya] and the date between the northern and southern clades is estimated to be slightly more recent at 17.4 Mya (95% HPD interval of 11.0–24.5 Mya). The distribution of this endemic species is best explained by persistent occupation (or early invasion and dispersal) and subsequent isolation initiated by the dramatic landform changes that were part of the Miocene history of the island of New Guinea, rather than as a response to the contemporary landscape of an exceptionally effective disperser. The driving influence on genetic structure appears to have been isolation arising from a combination of: (1) the early uplift of the Central Ranges and establishment of a north-south drainage divide; (2) development of the Langguru Fold Belt; (3) the opening of Cenderawasih Bay; and (4) the deep waters of the Aru Trough and Cenderawasih Bay that come close to the current coastline to maintain isolation of the Birds Head through periods of sea level minima (−135 m). The dates of divergence of turtle populations north and south of the ranges predate the telescopic uplift of the central ranges associated with oblique subduction of the Australian Plate beneath the Pacific Plate. Their isolation was probably associated with earlier uplift and drainage isolation driven by the accretion of island terranes to the northern boundary of the Australian craton that occurred earlier than the oblique subduction. The opening of Cenderawasih Bay is too recent (6 Mya) to have initiated the isolation of the Birds Head populations from those of the remainder of New Guinea, although its deep waters will have served to sustain the isolation through successive sea level changes. The molecular evidence suggests that the Birds Head docked with New Guinea some time before the Central Ranges emerged as a barrier to turtle dispersal. Overall, deep genetic structure of the species complex reflects events and processes that occurred during Miocene, whereas structure within each clade across the New Guinea landscape relates to Pliocene and Pleistocene times. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111, 192–208.
The Effects on Parapatric Divergence of Linkage between Preference and Trait Loci versus Pleiotropy

Attempts to uncover the genetic basis of female mating preferences and male signals involved in reproductive isolation have discovered intriguing cases in which loci contributing to these traits co-localize in their chromosomal positions. Such discoveries raise the question of whether alleles at certain loci contribute pleiotropically to male and female components of premating reproductive isolation, versus whether these loci are merely tightly linked. Here we use population genetic models to assess the degree to which these alternatives affect both short term and equilibrium patterns of trait (signal) and preference divergence. We take advantage of the fact that in the case of secondary contact between populations exchanging migrants, patterns of divergence across the range of preference strengths differ markedly when preferences and traits are controlled by the same locus (the case of phenotype matching) versus when they are on separate chromosomes. We find that tight linkage between preference and trait loci can mimic the pleiotropic pattern for many generations (roughly the reciprocal of the recombination rate), but that any recombination ultimately results in equilibrium patterns of divergence far more similar to those found when preferences and traits are on separate chromosomes. In general, our finding that pleiotropy results in quite different long-term patterns from tight linkage highlights the importance of distinguishing between these possibilities in empirical systems.
Lesions of the perirhinal cortex but not of the frontal, medial prefrontal, visual, or insular cortex block fear-potentiated startle using a visual conditioned stimulus

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and 1–2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3–4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory.
Lightweighted and energy-aware MIKEY-Ticket for e-health applications in the context of internet of things

To secure e-health communications, key management protocols play a vital role in the security process. Nevertheless, current e-health systems are unable to run existing standardised key management protocols due to their limited energy power and computational capabilities. In this paper, we introduce two solutions to tailor MIKEY-Ticket protocol to a such constrained environment. Firstly, we propose a new header compression scheme to reduce the size of MIKEY's header from 12 Bytes to 3 Bytes in the best compression case. Secondly, we present a new exchange mode to reduce the number of exchanged messages from 6 to 4. We use a formal validation tool to evaluate and validate the security properties of our tailored MIKEY-Ticket protocol. In addition, we evaluate both communication and computational costs to demonstrate the energy gain. The results show a decrease in MIKEY-Ticket overhead and a considerable energy gain without compromising its security properties.
New Challenges in Neural Computation NC 2 – 2010

The revival of NNs surprised some, including me. Back then I considered NNs problematic especially because of their ‘representational limitations’ in comparison to the explicit structure that can be represented (and learned), e.g., with graphical models, or probabilistic relational models, or representing functions indirectly via optimization or planning problems, as often done in robotics. In fact, the limitation seemed not only w.r. t. representational capacity, but also w.r. t. the computational operations on such representations. It is however interesting to see that ‘Representation Learning’ became, again, a central research topic in the NN community. I introduce the talk discussing this controversy between the (perhaps feasible? ) dream of learning everything in a generic, essentially ‘no-prior’ substrate (‘end-to-end learning’) versus the tough science of trying to identify what we believe is essential problem structure and learning relative to such priors. I mention some older work of mine as well as some newer that might seem to move away from the ‘representation issue’, but never really has. Machine Learning Reports http://www.techfak. uni-bielefeld.de/∼fschleif/mlr/mlr.html Keynote talk: Neural Simpletrons Minimalistic Deep Neural Networks for Probabilistic Learning with Few
MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3’UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.
Cell Selection with Deep Reinforcement Learning in Sparse Mobile Crowdsensing

Sparse Mobile CrowdSensing (MCS) is a novel MCS paradigm where data inference is incorporated into the MCS process for reducing sensing costs while its quality is guaranteed. Since the sensed data from different cells (sub-areas) of the target sensing area will probably lead to diverse levels of inference data quality, cell selection (i.e., choose which cells of the target area to collect sensed data from participants) is a critical issue that will impact the total amount of data that requires to be collected (i.e., data collection costs) for ensuring a certain level of quality. To address this issue, this paper proposes a Deep Reinforcement learning based Cell selection mechanism for Sparse MCS, called DR-Cell. We properly model the key concepts in reinforcement learning including state, action, and reward, and then propose to use a deep recurrent Q-network for learning the Q-function that can help decide which cell is a better choice under a certain state during cell selection. Experiments on various real-life sensing datasets verify the effectiveness of DR-Cell over the state-of-the-art cell selection mechanisms in Sparse MCS by reducing up to 15% of sensed cells with the same data inference quality guarantee.
Gene delivery using human cord blood-derived CD34+cells into inflamed glomeruli in NOD/SCID mice.

BACKGROUND Bone marrow reconstitution using genetically-modified hematopoietic stem cells has been reported to confer resistance to inflammation and prevent renal injury in glomerulonephritis. Although this strategy has potentials for clinical use, taking hematopoietic stem cells from bone marrow is highly stressful for patients. In this regard, umbilical cord blood may be a useful alternative and, therefore, we focused on their suitability as a source of hematopoietic stem cells for transplantation-based therapy for glomerulonephritis. METHODS CD34+ cells were obtained from human umbilical cord blood, retrovirally transduced with human beta-glucuronidase (HBG) gene, and transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After confirming the successful chimerism, these mice were treated with lipopolysaccharide (LPS), and local HBG expression in glomeruli was examined using immunohistochemical analysis, HBG bioassay, and Western blot analysis. RESULTS Clonogenic assay showed that 88.4 +/- 5.9% burst-forming unit-erythroid (BFU-E), 79.7 +/- 11.4% in colony-forming unit-macrophage (CFU-M), and 81.1 +/- 14.1% in colony-forming unit-granulocyte (CFU-G), respectively, possessed the transgene after transfection, suggesting that precommited cells were susceptible to retroviral infection. Flow cytometric analysis revealed that 24.1 +/- 14.5% of bone marrow cells in these chimera mice expressed human lymphocyte antigen (HLA) 8 weeks after transplantation. Also, clonogenic assay showed that a sustained engraftment of human hematopoietic cells expressed HBG. CD14-positive cells were recruited into the glomeruli upon LPS treatment and they secreted bioactive HBG, suggesting that cord blood-derived CD34+cells may differentiate into monocyte lineage while maintaining the expression of the transgene. CONCLUSION These data indicate that umbilical cord blood cells can be utilized as a source of hematopoietic stem cells for the transplantation-based therapy of glomerulonephritis.
Fruit fly scale robots can hover longer with flapping wings than with spinning wings

Hovering flies generate exceptionally high lift, because their wings generate a stable leading edge vortex. Micro flying robots with a similar wing design can generate similar high lift by either flapping or spinning their wings. While it requires less power to spin a wing, the overall efficiency depends also on the actuator system driving the wing. Here, we present the first holistic analysis to calculate how long a fly-inspired micro robot can hover with flapping versus spinning wings across scales. We integrate aerodynamic data with data-driven scaling laws for actuator, electronics and mechanism performance from fruit fly to hummingbird scales. Our analysis finds that spinning wings driven by rotary actuators are superior for robots with wingspans similar to hummingbirds, yet flapping wings driven by oscillatory actuators are superior at fruit fly scale. This crossover is driven by the reduction in performance of rotary compared with oscillatory actuators at smaller scale. Our calculations emphasize that a systems-level analysis is essential for trading-off flapping versus spinning wings for micro flying robots.
The Weight Distribution of Quasi-quadratic Residue Codes

We investigate a family of codes called quasi-quadratic residue (QQR) codes . We are interested in these codes mainly for two reasons: Firstly, they have close relations with hyperelliptic curves and Goppa's Conjecture, and serve as a strong tool in studying those objects. Secondly, they are very good codes. Computational results show they have large minimum distances when \begin{document}$p\equiv 3 \pmod 8$\end{document} . Our studies focus on the weight distributions of these codes. We will prove a new discovery about their weight polynomials, i.e. they are divisible by \begin{document}$(x^2 + y^2)^{d-1}$\end{document} , where \begin{document}$d$\end{document} is the corresponding minimum distance. We also show that the weight distributions of these codes are asymptotically normal. Based on the relation between QQR codes and hyperelliptic curves, we will also prove a result on the point distribution on hyperelliptic curves.