Miracle-dz/UniFAR-FTUs huggingface dataset:
This item is the archived peer-reviewed author-version of: Bio-inspired materials in drug delivery: exploring the role of pulmonary surfactant in sIRNA inhalation therapy

Many pathologies of the respiratory tract are inadequately treated with existing small moleculebased therapies. The emergence of RNA interference (RNAi) enables the post-transcriptional silencing of key molecular disease factors that cannot readily be targeted with conventional small molecule drugs. Pulmonary administration of RNAi effectors, such as small interfering RNA (siRNA), enables direct delivery into the lung tissue, hence reducing systemic exposure. Unfortunately, the clinical translation of RNAi is severely hampered by inefficient delivery of siRNA therapeutics toward the cytoplasm of the target cells. In order to have a better control of the siRNA delivery process, both extraand intracellular, siRNAs are typically formulated in nanosized delivery vehicles (nanoparticles, NPs). In the lower airways, which is the targeted site of action for multiple pulmonary disorders, these siRNA-loaded NPs will encounter the pulmonary surfactant (PS) layer, covering the entire alveolar surface. The interaction between the instilled siRNA-loaded NPs and the PS at this nano-bio interface results in the adsorption of PS components onto the surface of the NPs. The formation of this so-called biomolecular corona conceals the original NP surface and will therefore profoundly determine the biological efficacy of the NP. Though this interplay has initially been regarded as a barrier towards efficient siRNA delivery to the respiratory target cell, recent reports have illustrated that the interaction with PS might also be beneficial for local pulmonary siRNA delivery.
Jump-landing biomechanics and knee-laxity change across the menstrual cycle in women with anterior cruciate ligament reconstruction.

CONTEXT Of the individuals able to return to sport participation after an anterior cruciate ligament(ACL) injury, up to 25% will experience a second ACL injury. This population may be more sensitive to hormonal fluctuations, which may explain this high rate of second injury. OBJECTIVE To examine changes in 3-dimensional hip and knee kinematics and kinetics during a jump landing and to examine knee laxity across the menstrual cycle in women with histories of unilateral noncontact ACL injury. DESIGN Controlled laboratory study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 20 women (age = 19.6 ± 1.3 years, height = 168.6 ± 5.3 cm, mass = 66.2 ± 9.1 kg) with unilateral, noncontact ACL injuries. INTERVENTION(S) Participants completed a jump-landing task and knee-laxity assessment 3 to 5 days after the onset of menses and within 3 days of a positive ovulation test. MAIN OUTCOME MEASURE(S) Kinematics in the uninjured limb at initial contact with the ground during a jump landing, peak kinematics and kinetics during the loading phase of landing, anterior knee laxity via the KT-1000, peak vertical ground reaction force, and blood hormone concentrations (estradiol-β-17, progesterone, free testosterone). RESULTS At ovulation, estradiol-β-17 (t = -2.9, P = .009), progesterone (t = -3.4, P = .003), and anterior knee laxity (t = -2.3, P = .03) increased, and participants presented with greater knee-valgus moment (Z = -2.6, P = .01) and femoral internal rotation (t = -2.1, P = .047). However, during the menses test session, participants landed harder (greater peak vertical ground reaction force; t = 2.2, P = .04), with the tibia internally rotated at initial contact (t = 2.8, P = .01) and greater hip internal-rotation moment (Z = -2.4, P = .02). No other changes were observed across the menstrual cycle. CONCLUSIONS Knee and hip mechanics in both phases of the menstrual cycle represented a greater potential risk of ACL loading. Observed changes in landing mechanics may explain why the risk of second ACL injury is elevated in this population.
Properties of presympathetic neurones in the rostral ventrolateral medulla in the rat: an intracellular study "in vivo'.

1. Intracellular recordings were made in pentobarbitone‐anaesthetized rats from sixty‐eight neurones located in the rostral ventrolateral medulla (RVLM), which responded with inhibition (latency, 33.6 +/‐ 9.3 ms) after stimulation of the aortic depressor nerve with short bursts of pulses. This inhibition was due to chloride‐ and voltage‐dependent IPSPs. 2. Seventeen neurones could be excited antidromically after stimulation in the T2 spinal segment (conduction velocity 1.9‐8.5 m.s‐1) and were classified as RVLM presympathetic vasomotor neurones. 3. ‘Spontaneously’ active neurones (n = 29) displayed a largely irregular pattern of firing, with no clear relationship between the level of the membrane potential and cycles of phrenic nerve activity at end‐tidal CO2 < 5.0%. Cardiac cycle‐related shifts of the membrane potential were not considered indicative of baroreceptor input as they could be due to movement artifacts. 4. All neurones displayed large synaptic activity (EPSPs and IPSPs, peak‐to‐peak amplitude > 5.0 mV). The depolarizing IPSPs observed during injection of chloride and/or negative current consisted of a phasic and a tonic component. 5. The on‐going activity of these neurones resulted from synaptic inputs, with individual action potentials usually preceded by identifiable fast EPSPs. 6. No evidence was found for the presence of gradual depolarizations (autodepolarizations) between individual action potentials, and therefore under these experimental conditions the activity of RVLM presympathetic neurones did not depend on intrinsic pacemaker properties. 7. These results are consistent with the ‘network’ hypothesis for the generation of sympathetic vasomotor tone.
Metcalfe's Law as a Model for Bitcoin's Value

This paper demonstrates that bitcoin’s medium- to long-term price follows Metcalfe’s law. Bitcoin is modeled as a token digital currency, a medium of exchange with no intrinsic value that is transacted within a defined electronic network. Per Metcalfe’s law, the value of a network is a function of the number of pairs transactions possible, and is proportional to n-squared. A Gompertz curve is used to model the inflationary effects associated with the creation of new bitcoin. The result is a parsimonious model of supply (number of bitcoins) and demand (number of bitcoin wallets), with the conclusion bitcoin’s price fits Metcalfe’s law exceptionally well. Metcalfe’s law is used to investigate Gandal’s et.al. [2018] assertion of price manipulation in the Bitcoin ecosystem during 2013-2014.
Job stress and satisfaction among clinical radiologists.

AIMS Consultant radiologists appear to be at greater risk of burnout than consultants working in other specialties. The aim of this study was to examine sources of stress and satisfaction at work for radiologists and hospital consultants in other specialties in order to try to understand this difference. MATERIALS AND METHODS A postal questionnaire survey of psychiatric morbidity (12-item General Health Questionnaire), burnout (Maslach Burnout Inventory) and sources of job stress and satisfaction (study-specific questionnaires) was carried out among a random sample of 882 hospital consultants working in radiology and three other specialties (surgery, gastroenterology and oncology). RESULTS The most stressful aspect of work for radiologists was work overload. Inadequacies in current staffing and facilities and concerns about funding were also major sources of stress, as were impositions made on radiologists by other clinicians. The most important sources of satisfaction for radiologists were their relationships with patients and being perceived to do their job well by colleagues. Importantly, radiologists reported less satisfaction than the other specialists from many of the aspects of work measured. A greater proportion of radiologists than other specialists felt insufficiently trained in communication skills [80% (n = 168) vs 47% (n = 310);P < 0.001] and management skills [84% (n = 179) vs 76% (n = 506);P < 0.05]. CONCLUSION These data highlight aspects of radiologists' work which need to be tackled in order to reduce their stress and increase their satisfaction, and thereby their risk of burnout.
Tumors and Fibrinogen

Abstract: The progression of a tumor from benign and localized to invasive and metastatic growth is the major cause of poor clinical outcome in cancer patients. Much like in a healing wound, the deposition of fibrin(ogen), along with other adhesive glycoproteins, into the extracellular matrix (ECM) serves as a scaffold to support binding of growth factors and to promote the cellular responses of adhesion, proliferation, and migration during angiogenesis and tumor cell growth. Inappropriate synthesis and deposition of ECM constituents is linked to altered regulation of cell proliferation, leading to tumor cell growth and malignant transformation. Fibrin deposition occurs within the stroma of a majority of tumor types. In contrast, abundant FBG, not fibrin, is present within the stroma of breast cancers. It is thought to originate from exudation of plasma FBG and subsequent deposition into the tumor stroma and not endogenous synthesis and secretion of FBG by breast tumor cells. However, we show that MCF‐7 human breast cancer cells synthesize and secrete FBG polypeptides, suggesting that the origin of FBG in the stroma of breast carcinoma may be due to endogenous synthesis and deposition. Moreover, FBG assembles into ECM as conformationally altered FBG, not as fibrin. Studies in our laboratory demonstrate that FBG alters the ability of breast cancer cells to migrate. Together, the results of studies from our laboratory, as well as the laboratories of others, indicate that the presence of fibrin(ogen) within the tumor stroma likely affects the progression of tumor cell growth and metastasis. This review focuses on FBG within tumors and its relationship with other tumor constituents, ultimately focusing on the role of FBG in breast cancer.
Low Power Asynchronous Data Acquisition Front End for Wireless Body Sensor Area Network

Wireless body sensor area networks (WBAN) is one of the key technologies to solve the rising healthcare costs through early detection, and point-of-care diagnosis and health management. However there is a stringent power requirement on individual sensor nodes in such networks. Consequently traditional signal chain of amplify-digitize-transmit generates large amounts of data that cannot be sustained due to limited energy and bandwidth. In this paper we propose an asynchronous data acquisition platform that provides inherent digitization and compression at the source. The proposed implementation consists of low noise front-end amplifier (AFE) with tunable bandwidth and an asynchronous clockless analog-to-digital converter (ADC). Data compression is achieved by the inherent signal dependent sampling of the asynchronous architecture. The AFE and ADC were fabricated in a 0. 18μm CMOS technology and consume a total of 79μW. Measured results for asynchronous ECG signal acquisition are presented.
Temperature-Dependent Demography of Chilades pandava peripatria (Lepidoptera: Lycaenidae)

ABSTRACT Chilades pandava peripatria Hsu and its host plant Cycas taitungensis Shen, Hill, Tsou & Chen are both endemic species to Taiwan. Ch. pandava peripatria has a specific association with buds and soft leaves of cycad plants. The introduced species, Cy. revoluta, have prolonged budding periods and extensive auxiliary buds that extensively contribute to the outbreak of Ch. pandava peripatria. An in-depth knowledge of the development, survival, and fecundity of Ch. pandava peripatria under different environmental conditions is necessary to understand the population growth of Ch. pandava peripatria. The demography of Ch. pandava peripatria was studied based on the age-stage, two-sex life table at 20, 23, 25, 28, and 31°C, 70% RH, and a photoperiod of 16:8 (L:D) h under laboratory conditions. Ch. pandava peripatria completed its development under tested temperatures but did not produce offsprings at 23°C Because of the high egg mortality at 20°C, the data at this given temperature were excluded from this study. The intrinsic rate of increase (r) under these tested temperatures was 0.1846, 0.2919, and 0.1412 d-1, respectively. The net reproductive rate (R0) was 165.47, 262.32, and 56.68 offsprings per individual and the mean generation time (T) was 27.72, 19.10, and 28.67 d, respectively. Our results indicated that Ch. pandava peripatria is highly adaptable to environments where temperature ranges from 25 to 31°C.
Autoantibodies to glucosylated proteins in the plasma of patients with diabetes mellitus.

Nonenzymatic glucosylation interferes with recognition of low density lipoprotein (LDL) by its receptor and markedly decreases the rate of plasma clearance of glucosylated LDL, both in experimental animals and in normal human subjects. However, in selected diabetic subjects we have observed a paradoxical increase in the clearance of glucosylated LDL, suggesting the possibility of immune-mediated clearance. Immunoassay demonstrated antibodies specific for glucosylated LDL in the preinjection plasma of each of four such diabetic subjects studied. These antibodies cross-react with other glucosylated proteins and recognize specifically the glucosylated lysine epitope--i.e., glucitollysine . These data suggest that nonenzymatic glucosylation of plasma or structural proteins may render them immunogenic and result in production of autoantibodies that recognize not only the particular immunogen but also many other glucosylated proteins, including glucosylated tissue proteins. These findings may be relevant to the increased prevalence of immune complexes in plasma of diabetic subjects and the late complications of diabetes mellitus.
Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains

ABSTRACT While hypoxia-inducible factor (HIF) is a major actor in the cell survival response to hypoxia, HIF also is associated with cell death. Several studies implicate the HIF-induced putative BH3-only proapoptotic genes bnip3 and bnip3l in hypoxia-mediated cell death. We, like others, do not support this assertion. Here, we clearly demonstrate that the hypoxic microenvironment contributes to survival rather than cell death by inducing autophagy. The ablation of Beclin1, a major actor of autophagy, enhances cell death under hypoxic conditions. In addition, the ablation of BNIP3 and/or BNIP3L triggers cell death, and BNIP3 and BNIP3L are crucial for hypoxia-induced autophagy. First, while the small interfering RNA-mediated ablation of either BNIP3 or BNIP3L has little effect on autophagy, the combined silencing of these two HIF targets suppresses hypoxia-mediated autophagy. Second, the ectopic expression of both BNIP3 and BNIP3L in normoxia activates autophagy. Third, 20-mer BH3 peptides of BNIP3 or BNIP3L are sufficient in initiating autophagy in normoxia. Herein, we propose a model in which the atypical BH3 domains of hypoxia-induced BNIP3/BNIP3L have been designed to induce autophagy by disrupting the Bcl-2-Beclin1 complex without inducing cell death. Hypoxia-induced autophagy via BNIP3 and BNIP3L is clearly a survival mechanism that promotes tumor progression.
Share Price Reaction to Dividend Announcements: A Case of Pakistani Banking Sector

The relationship between dividend policy and stock prices has been researched extensively in the developed countries. Their relationship has also been checked in emerging countries especially in Pakistan. However, despite the far-reaching literature on dividend policy still no unanimity on a general dividend theory had been achieved that either explains the process of dividend decision making or forecast an ideal dividend policy. At this point one is compelled to accept the term “Dividend Puzzle” introduced by (Black, 1976) by saying, “The harder we look at the dividend picture, the more it seems like a puzzle, with pieces that just don’t fit together”. This paper is in attempt to analyze the relationship between dividend policy and stock prices in the context of Pakistani banking sector. During the conduct of the research, for the achievement of desired objectives, a standard event study has been used to find the unexpected returns for the three types of announcements i.e. cash dividends, bonus issues (stock dividend), simultaneous cash and bonus announcements using the dividend announcements data of 21 banks as a sample over a period 2005-2013. The analysis of the data reveals that beta values of individual securities do matter and thus convey important information to the outsiders in Pakistani banking sector thereby supporting the dividend signaling hypothesis. Since most of the returns on events dates are negative thereby transmitting bad news to the investors, it might be due to the dividend decrease events, as the study analyzed the aggregate dividend events without differentiating the dividend-increase firms from dividend-decrease companies. so the managers are required to revise their corporate practices to overcome these negative returns or if it is due having certain projects with positive net present values or due to tax reasons, they have to properly educate the investors with the future prospects of such decisions.
Exploring Ideation: Knowledge Development in Science through the Lens of Semantic and Social Networks

In this paper, we explore changes in both structural and semantic characteristics of a scientific social network. We trace the emergence of knowledge, what we refer to as ideation, through publication data from two conferences in a sub-field of Computer Science. Social network analysis is used to determine structural characteristics of the co-authorship networks, and we perform semantic network analysis on title words of articles to trace content of topics over time. We find that the emergence of new topics is accompanied by a tendency toward less dense and transitive, but more evenly distributed, social networks. We show that ideation is fostered in a relatively loose environment, as the field does not cling to one particular topic with all authors contributing to it. On the contrary, there is enough 'slack' for new knowledge topics to emerge and consolidate over time. Findings contribute to research on social network antecedents, innovation and science studies.
New Gene Cassettes for Trimethoprim Resistance,dfr13, and Streptomycin-Spectinomycin Resistance,aadA4, Inserted on a Class 1 Integron

ABSTRACT In a previous survey of 357 trimethoprim-resistant isolates of aerobic gram-negative bacteria from commensal fecal flora, hybridization experiments showed that 25% (90 of 357) of the isolates failed to hybridize to specific oligonucleotide probes for dihydrofolate reductase types 1, 2b, 3, 5, 6, 7, 8, 9, 10, and 12. Subsequent cloning and sequencing of a plasmid-borne trimethoprim resistance gene from one of these isolates revealed a new dihydrofolate reductase gene, dfr13, which occurred as a cassette integrated in a site-specific manner in a class 1 integron. The gene product shared 84% amino acid identity with dfr12 and exhibited a trimethoprim inhibition profile similar to that ofdfr12. Gene probing experiments with an oligonucleotide probe specific for this gene showed that 12.3% (44 of 357) of the isolates which did not hybridize to probes for other dihydrofolate reductases hybridized to this probe. Immediately downstream ofdfr13, a new cassette, an aminoglycoside resistance gene of the class AADA [ANT(3")(9)-I], which encodes streptomycin-spectinomycin resistance, was identified. This gene shares 57% identity with the consensus aadA1(ant(3")-Ia) and has been called aadA4(ant(3")-Id). The 3′ end of the aadA4 cassette was truncated by IS26, which was contiguous with a truncated form of Tn3. On the same plasmid, pUK2381, a second copy of IS26 was associated with sul2, which suggests that both integrase and transposase activities have played major roles in the arrangement and dissemination of antibiotic resistance genesdfr13, aadA4, blaTEM-1, and sul2.
Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol

Objective. To provide information on pregnancy outcomes in women receiving certolizumab pegol (CZP). Methods. The UCB Pharma safety database was searched for pregnancies through to September 1, 2014. Reports for maternal and paternal CZP exposure were included and outcomes examined, and data on CZP exposure, pregnancy, comorbidities, and infant events were extracted by 2 independent reviewers. Concomitant medications and disease activity were reviewed for clinical trial patients. Results. Of 625 reported pregnancies, 372 (59.5%) had known outcomes. Paternal exposure pregnancies (n = 33) reported 27 live births, 4 miscarriages, 1 induced abortion, and 1 stillbirth. Maternal exposure pregnancies (n = 339) reported 254 live births, 52 miscarriages, 32 induced abortions, and 1 stillbirth. Almost all reported pregnancies had exposure to CZP in the first trimester, when organogenesis takes place, and a third of them continued the drug into the second and/or third trimesters. The most frequent indications for maternal CZP use were Crohn disease (192/339) and rheumatic diseases (118/339). Twelve cases of congenital malformation and a single neonatal death were reported. Conclusion. Analysis of pregnancy outcomes after exposure to CZP supports previous reports, suggesting a lack of harmful effect of maternal CZP exposure on pregnancy outcomes. However, additional data from a larger number of outcomes after exposure and studies including an unexposed comparison group are required to fully evaluate CZP safety and tolerability in pregnancy.
Web 2.0–In Your Hand

Web 2.0 presents both a challenge and an opportunity for smart-phone vendors. The combination of HTML and JavaScript is becoming an increasingly powerful application platform. The W3C and some of the most important mobile browser developers, including Apple, Google, Opera, and Nokia, are actively involved in this evolution. Web 2.0 applications have already begun to come to mobile phones. Web widgets based on the WebKit core are already an important part of the iPhone and S60 platforms. Mobile-application developers is drawn to HTML and JavaScript as these new features are added to the various mobile browsers and Web toolkits.
Priority based Performance Improved Algorithm for Meta-task Scheduling in Cloud environment

Computing in Cloud is a topical skill that disquiet with allocation of computing resources and services on pay- per- use basis. To access remote computers, scheduling is a key task. Scheduling of task is a NP-complete problem. It is additional obscure in cloud computing atmosphere. To achieve improved performance of cloud resource, successful and proficient scheduling methodologies are needed. This paper proposes, a Meta-task Scheduling algorithm, Priority based Performance Improved Algorithm. It considers the user priority of meta-tasks. The high priority meta-task set is scheduled based on Min-Min algorithm and then the normal priority meta-task set is scheduled based on Max-Min algorithm. The proposed algorithm gives minimum makespan and better resource utilization.
The analysis of image motion by the rabbit retina

1. Micro‐electrode recordings were made from rabbit retinal ganglion cells or their axons. Of particular interest were direction‐selective units; the common on—off type represented 20·6% of the total sample (762 units), and the on‐type comprised 5% of the total.