Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of recombinant IgG antibodies against the leucine-33 form of the platelet β3 integrin (HPA-1a) on platelet function

Summary Recombinant HPA-1a antibodies with Fc, mutated to remove destructive effector functions, have been developed as a potential therapy for fetomaternal alloimmune thrombocytopenia (FMAIT), via blockade of binding of human HPA-1a polyclonal antibodies to fetal HPA-1a1b platelets. We have assessed the effect of the IgG1 HPA-1a antibody B2G1 and two mutated derivatives in various functional assays in resting and agoniststimulated platelets of the three HPA-1 genotypes. With HPA-1a1b platelets (fetal genotype), the antibodies did not activate signalling or CD62P expression in resting platelets, did not change in vitro bleeding time (IVBT), and did not inhibit platelet adhesion to collagen in flowing blood. Adhesion of HPA-1a1b platelets to fibrinogen was reduced by 20%, and aggregation induced by ADP by 50%, but collagen-related peptide (CRP-XL)-induced aggregation was normal. With HPA-1a1a platelets, aggregation to both ADP and CRP-XL was inhibited, with total blockade of adhesion to fibrinogen and of IVBT responses. Interestingly, a monovalent antibody fragment with identical specificity had no inhibitory effect on aggregation. In static adhesion assays using human αIIbβ3 or αVβ3 transfectants of HPA-1a (Leu33) phenotype, attachment to fibrinogen of the latter but not of the former was completely blocked by the HPA-1a antibodies. These observations are best explained by antibody-mediated blockade of the RGD binding site on β3 by a mechanism of steric hindrance. As the effect on platelet function is modest with HPA-1a1b (fetal type) platelets, the mutated HPA-1a antibodies described here could be developed further for FMAIT therapy.
Cardiovascular actions of angiotensin‐(1–12) in the hypothalamic paraventricular nucleus of the rat are mediated via angiotensin II

The role of the hypothalamic paraventricular nucleus (PVN) in cardiovascular regulation is well established. In this study, it was hypothesized that the PVN may be one of the sites of cardiovascular actions of a newly discovered angiotensin, angiotensin‐(1–12). Experiments were carried out in urethane‐anaesthetized, artificially ventilated, adult male Wistar rats. The PVN was identified by microinjections of NMDA (10 mm). Microinjections (50 nl) of angiotensin‐(1–12) (1 mm) into the PVN elicited increases in mean arterial pressure, heart rate and renal sympathetic nerve activity. The tachycardic responses to angiotensin‐(1–12) were attenuated by bilateral vagotomy. The cardiovascular responses elicited by angiotensin‐(1–12) were attenuated by microinjections of an angiotensin II type 1 receptor (AT1R) antagonist (losartan), but not an angiotensin II type 1 receptor (AT2R) antagonist (PD123319), into the PVN. Combined inhibition of angiotensin‐converting enzyme and chymase in the PVN abolished angiotensin‐(1–12)‐induced responses. Angiotensin‐(1–12)‐immunoreactive cells and fibres were more numerous in the middle and caudal regions of the PVN. Angiotensin‐(1–12) was present in many, but not all, vasopressinergic PVN cells. This peptide was also present in some non‐vasopressinergic PVN cells, but not in oxytocin‐containing PVN cells. These results can be summarized as follows: (1) microinjections of angiotensin‐(1–12) into the PVN elicited increases in mean arterial pressure, heart rate and renal sympathetic nerve activity; (2) heart rate responses were mediated via both sympathetic and vagus nerves; (3) both angiotensin‐converting enzyme and chymase were needed to convert angiotensin‐(1–12) to angiotensin II in the PVN; and (4) AT1Rs, but not AT2Rs, in the PVN mediated angiotensin‐(1–12)‐induced responses. It was concluded that the cardiovascular actions of angiotensin‐(1–12) in the PVN are mediated via its conversion to angiotensin II.
Extracellular Cyclophilin A Activates Platelets Via EMMPRIN (CD147) and PI3K/Akt Signaling, Which Promotes Platelet Adhesion and Thrombus Formation In Vitro and In Vivo

Objective— Cyclophilin A (CyPA) is secreted under inflammatory conditions by various cell types. Whereas the important role of intracellular CyPA for platelet function has been reported, the effect of extracellular CyPA on platelet function has not been investigated yet. Approach and Results— Inhibition of extracellular CyPA through a novel specific inhibitor MM284 reduced thrombus after ferric chloride–induced injury in vivo. In vitro extracellular CyPA enhanced thrombus formation even in CyPA−/− platelets. Treatment of isolated platelets with recombinant CyPA resulted in platelet degranulation in a time- and dose-dependent manner. Inhibition of the platelet surface receptor extracellular matrix metalloproteinase inducer (cluster of differentiation 147) by an anticluster of differentiation 147 monoclonal antibody significantly reduced CyPA-dependent platelet degranulation. Pretreatment of platelets with CyPA enhanced their recruitment to mouse carotid arteries after arterial injury, which could be inhibited by an anticluster of differentiation 147 monoclonal antibody (intravital microscopy). The role of extracellular CyPA in adhesion could be confirmed by infusing CyPA−/− platelets in CyPA+/+ mice and by infusing CyPA+/+ platelets in CyPA−/− mice. Stimulation of platelets with CyPA induced phosphorylation of Akt, which could in turn be inhibited in the presence of phosphoinositid-3-kinase inhibitors. Akt-1−/− platelets revealed a markedly decreased degranulation on CyPA stimulation. Finally, ADP-induced platelet aggregation was attenuated by MM284, as well as by inhibiting paracrine-secreted CyPA without directly affecting Ca2+-signaling. Conclusions— Extracellular CyPA activates platelets via cluster of differentiation 147–mediated phosphoinositid-3-kinase/Akt-signaling, leading to enhanced adhesion and thrombus formation independently of intracellular CyPA. Targeting extracellular CyPA via a specific inhibitor may be a promising strategy for platelet inhibition without affecting critical functions of intracellular CyPA.
Cramer-Rao Bounds for source localization in shallow ocean with generalized Gaussian noise

Localization of underwater acoustic sources is a problem of great interest in the area of ocean acoustics. There exist several algorithms for source localization based on array signal processing. It is of interest to know the theoretical performance limits of these estimators. In this paper we develop expressions for the Cramer-Rao-Bound (CRB) on the variance of direction-of-arrival (DOA) and range-depth estimators of underwater acoustic sources in a shallow range-independent ocean for the case of generalized Gaussian noise. We then study the performance of some of the popular source localization techniques, through simulations, for DOA/range-depth estimation of underwater acoustic sources in shallow ocean by comparing the variance of the estimators with the corresponding CRBs.
Quantitative Ecological and Taphonomic Patterns in Late Cenozoic Mollusk-Dominated Marine Fossil Assemblages

Applications in paleontological research are far from being limited to taxonomic collection and identification. Nor is such research limited to working solely on fossil data. Actualistic paleontology is the study of modern or recent organisms and processes to better understand those of the past. The bulk of this body of research falls under the category of actualistic paleontology, and examines geochronological methods and error biases in dating biological specimens ranging in age from modern to thousands of years old. Although such methods are arguably not perfect, error rates of ± a few hundred to few thousand years can be extremely important when considering ecological relationships among both Holocene taxa and time-averaged paleocommunities, but quite diminished when considering implications on more traditional dating techniques for ancient strata. Regardless, understanding implications of time resolution is important in analyses of and comparisons between any biological dataset. The following chapters are united by quantitative and statistical management of data with varying levels of temporal resolution, and represent four manuscripts that either are in press or soon to be submitted for publication.
Evidence that the supE44 Mutation of Escherichia coli Is an Amber Suppressor Allele of glnX and that It Also Suppresses Ochre and Opal Nonsense Mutations

ABSTRACT Translational readthrough of nonsense codons is seen not only in organisms possessing one or more tRNA suppressors but also in strains lacking suppressors. Amber suppressor tRNAs have been reported to suppress only amber nonsense mutations, unlike ochre suppressors, which can suppress both amber and ochre mutations, essentially due to wobble base pairing. In an Escherichia coli strain carrying the lacZU118 episome (an ochre mutation in the lacZ gene) and harboring the supE44 allele, suppression of the ochre mutation was observed after 7 days of incubation. The presence of the supE44 lesion in the relevant strains was confirmed by sequencing, and it was found to be in the duplicate copy of the glnV tRNA gene, glnX. To investigate this further, an in vivo luciferase assay developed by D. W. Schultz and M. Yarus (J. Bacteriol. 172:595-602, 1990) was employed to evaluate the efficiency of suppression of amber (UAG), ochre (UAA), and opal (UGA) mutations by supE44. We have shown here that supE44 suppresses ochre as well as opal nonsense mutations, with comparable efficiencies. The readthrough of nonsense mutations in a wild-type E. coli strain was much lower than that in a supE44 strain when measured by the luciferase assay. Increased suppression of nonsense mutations, especially ochre and opal, by supE44 was found to be growth phase dependent, as this phenomenon was only observed in stationary phase and not in logarithmic phase. These results have implications for the decoding accuracy of the translational machinery, particularly in stationary growth phase.
Smoking, alcohol consumption and denture use in patients with oral mucosal lesions.

BACKGROUND Epidemiologic researches about oral mucosal lesions have been performed in different populations. But, in dermatology outpatients, oral mucosal lesions have not been investigated previously. OBJECTIVE We aimed to determine the prevalence of oral mucosal lesions among dermatology outpatients and the relationship between OML and smoking, alcohol intake, denture and dental filling use and skin diseases. METHODS Randomly selected 1041 dermatology outpatients were examined for dermatological diseases and oral mucosal lesions. All of the patients were questioned about smoking, alcohol intake, denture and dental filling use. RESULTS In 235 patients, oral mucosal lesions were recorded. 268 (25.7%) of the patients had history of smoking, 42 (4%) drinking alcohol and 180 (17.3%) denture and dental filling. 32 (64%) of the smokers, 54 (30%) of denture users and 10 (23.8%) alcohol consumers had at least one OML. Age and smoking were found as significant risk factors for oral mucosal lesions. Fissured tongue was the most common oral lesion and it was seen significantly higher in patients with denture. Smoking was risk factor for coated tongue and linea alba. CONCLUSIONS Oral mucosa should be examined carefully even if the patients do not attend with the complaint of oral lesions, especially in elderly patients, smokers and denture users.
HIV-1 RNAs are Not Part of the Argonaute 2 Associated RNA Interference Pathway in Macrophages

Background MiRNAs and other small noncoding RNAs (sncRNAs) are key players in post-transcriptional gene regulation. HIV-1 derived small noncoding RNAs (sncRNAs) have been described in HIV-1 infected cells, but their biological functions still remain to be elucidated. Here, we approached the question whether viral sncRNAs may play a role in the RNA interference (RNAi) pathway or whether viral mRNAs are targeted by cellular miRNAs in human monocyte derived macrophages (MDM). Methods The incorporation of viral sncRNAs and/or their target RNAs into RNA-induced silencing complex was investigated using photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP) as well as high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP), which capture Argonaute2-bound miRNAs and their target RNAs. HIV-1 infected monocyte-derived macrophages (MDM) were chosen as target cells, as they have previously been shown to express HIV-1 sncRNAs. In addition, we applied small RNA deep sequencing to study differential cellular miRNA expression in HIV-1 infected versus non-infected MDMs. Results and Conclusion PAR-CLIP and HITS-CLIP data demonstrated the absence of HIV-1 RNAs in Ago2-RISC, although the presence of a multitude of HIV-1 sncRNAs in HIV-1 infected MDMs was confirmed by small RNA sequencing. Small RNA sequencing revealed that 1.4% of all sncRNAs were of HIV-1 origin. However, neither HIV-1 derived sncRNAs nor putative HIV-1 target sequences incorporated into Ago2-RISC were identified suggesting that HIV-1 sncRNAs are not involved in the canonical RNAi pathway nor is HIV-1 targeted by this pathway in HIV-1 infected macrophages.
A definition of general weighted fairness and its support in explicit rate switch algorithms

We give a general definition of weighted fairness and discuss how a pricing policy can be mapped to general weighted (GW) fairness. The GW fairness can be achieved by calculating the excess fairshare (weighted fairshare of the left over bandwidth) for each VC. We show how a switch algorithm can be modified to support the GW fairness by using the excess fairshare term. We use ERICA+ as an example switch algorithm and show how it can be modified to achieve the general fairness. Simulations results are presented to demonstrate that, the modified switch algorithm achieves GW fairness. An analytical proof for convergence of the modified ERICA+ algorithm is given in the appendix.
Consequences of Cathodal Stimulation for Behavior: When Does It Help and When Does It Hurt Performance?

Cathodal Transcranial Direct Current Stimulation (C-tDCS) has been reported, across different studies, to facilitate or hinder performance, or simply to have no tangible effect on behavior. This discrepancy is most prominent when C-tDCS is used to alter a cognitive function, questioning the assumption that cathodal stimulation always compromises performance. In this study, we aimed to study the effect of two variables on performance in a simple cognitive task (letter Flanker), when C-tDCS was applied to the left prefrontal cortex (PFC): (1) the time of testing relative to stimulation (during or after), and (2) the nature of the cognitive activity during stimulation in case of post-tDCS testing. In three experiments, we had participants either perform the Flanker task during C-tDCS (Experiment 1), or after C-tDCS. When the Flanker task was administered after C-tDCS, we varied whether during stimulation subjects were engaged in activities that posed low (Experiment 2) or high (Experiment 3) demands on the PFC. Our findings show that the nature of the task during C-tDCS has a systematic influence on the outcome, while timing per se does not.
Evaluation of Potential Relay Locations in a Urban Macro-Cell Scenario with Applicability to LTE-A

Relay base stations are expected to play an important role in extending coverage for beyond 3G networks, such as LTE-A. However, the signal quality experienced on the backhaul link between the macro-cell and the relay node has a major impact on the performance of the multi-hop transmission. This paper presents a measurement-based study focusing on the performance evaluation of the relay backhaul link for different potential relay locations and antenna configurations in a real urban macro-cell scenario. Based on the assumption that a similar network deployment would apply for LTE-A, a fully operational 3G network has been used for measuring both received signal strength and Signal-to-Interference-Ratio (SIR). Furthermore, the results have been used to estimate the performance of the multi-hop transmission under simplifying assumptions. The experimental results show that by increasing the relay height from 2.4 m to 5 m, the received signal strength improves on average by 1.7 dB for omnidirectional antennas. When a directional antenna is mounted at 5 m and pointed towards the serving macro cell, significant SIR gains (around 5.9 dB) and throughput improvements are achieved at the locations where the relay node and the macro-cell are in Line-of-Sight (LOS).
Is the long‐term outcome of children following febrile convulsions favorable?

The study comprised 80 children aged 6 to 9 years with a history of febrile convulsions. A neurological examination, an interview to assess psychiatric anomalies, and a series of neuropsychological tests were performed on patients with previous febrile convulsions and on matched healthy controls. Children with non‐febrile seizures or CNS infections were excluded. Recurrence of febrile seizures in the study group was 41% (N=33), 18 children (22%) had prolonged febrile convulsions, six (7.5%) patients and two controls showed discrete neurological abnormalities. Behavioral anomalies were exhibited by 22% of the patients and 6% of the healthy children. The neuropsychological test results did not demonstrate significant differences between the children with febrile convulsions and the healthy controls. However, in children with prolonged febrile convulsions, non‐verbal intelligence was found to be significantly lower as compared with children with simple febrile seizures and with controls. None of the other parameters tested yielded any differences between patients and controls. Children with multiple recurrences of febrile convulsions performed poorer in all tests when compared with children with only one febrile seizure or with controls. Other factors such as a positive family history of epilepsy, age at onset of febrile convulsions, or duration of the seizure were not found to be of prognostic significance.
Variation of Topology in Magnetic Bubbles in a Colossal Magnetoresistive Manganite

The emergence of zero-bias bubbles (≈100 nm in diameter) with various Bloch lines and their triangular lattice is revealed in a colossal magnetoresistive material, La1-x Srx MnO3 , by means of Lorentz transmission electron microscopy (LTEM). The magnetization dynamics, and accompanying changes of the topological number of bubbles via the field-driven motion of the Bloch lines, are demonstrated by in situ LTEM observations.
The extracellular matrix and blood vessel formation: not just a scaffold

• Introduction • ECM: composition and structure ‐ Collagen ‐ Laminin ‐ Fibronectin ‐ Elastin ‐ Nidogen ‐ Glycosaminoglycans ‐ Perlecan ‐ Syndecans ‐ Receptors for ECM molecules • Evaluation of ECM molecules and their modulators in vessel formation ‐ Determination of essential ECM components of vessel formation ‐ Collagen‐I and laminins are important for vessel structural integrity and provide contrasting signals in angiogenesis ‐ The function of collagens in the blood vessel basement membrane ‐ Laminin α4 is a key molecule in basement membrane assembly, microvessel stability and maturation ‐ Fibronectin is essential for vascular development ‐ Perlecan and syndecans modulate growth factors in angiogenesis ‐ Fragments of ECM proteins regulate angiogenic processes ‐ Proteins involved in signalling through ECM molecules ‐ Thrombospondins ‐ CCN proteins • ECM signalling in vessel formation: what next?
Further Validation of the Pillbox Test in a Mixed Clinical Sample

Objective: The purpose of this research was to provide further criterion and construct validation of the Pillbox Test, a brief, ecologically valid measure designed to assess executive functioning(EF). Method: Participants were 179 older male veterans who completed the Pillbox Test as part of a neuropsychological evaluation. Results: Performance on the Pillbox Test differed significantly between patients with and without dementia, with total error scores of ≥5 and ≥7 showing similar levels of sensitivity and specificity at 67% and at or near 70%, respectively. Hierarchical multiple regression analysis revealed that measures of EF predicted performance on the Pillbox Test above and beyond measures of processing speed, but not above and beyond measures in other cognitive domains. Conclusions: Findings suggest the Pillbox Test is a promising new performance-based measure of executive functioning that can discriminate between patients with and without dementia.
Lingual Kinematics in Dysarthric and Nondysarthric Speakers with Parkinson's Disease

Articulatory dysfunction is recognised as a major contributor to the speech disturbances seen in Parkinson's disease (PD). The present study aimed to compare lingual kinematics during consonant production within a sentence in eight dysarthric (DPD) and seven nondysarthric (NDPD) speakers with PD with those of eleven nonneurologically impaired normal participants. The tongue tip and tongue back movements of the participants during sentence production were recorded using electromagnetic articulography (EMA). Results showed that both the DPD and NDPD had deviant articulatory movement during consonant production that resulted in longer duration of consonant production. When compared with the NDPD group, the DPD group primarily exhibited increased range of lingual movement and compatible duration of production with an accompanying increase in maximum velocity, maximum acceleration, and maximum deceleration. These findings are contrary to proposed theories that suggest articulatory imprecision in dysarthric speakers with PD is the outcome of reduced range of articulatory movement.
Links as a service (LaaS): Guaranteed tenant isolation in the shared cloud

The most demanding tenants of shared clouds require complete isolation from their neighbors, in order to guarantee that their application performance is not affected by other tenants. Unfortunately, while shared clouds can offer an option whereby tenants obtain dedicated servers, they do not offer any network provisioning service, which would shield these tenants from network interference. In this paper, we introduce Links as a Service (LaaS), a new abstraction for cloud service that provides isolation of network links. Each tenant gets an exclusive set of links forming a virtual fat-tree, and is guaranteed to receive the exact same bandwidth and delay as if it were alone in the shared cloud. Consequently, each tenant can use the forwarding method that best fits its application. Under simple assumptions, we derive theoretical conditions for enabling LaaS without capacity over-provisioning in fat-trees. New tenants are only admitted in the network when they can be allocated hosts and links that maintain these conditions. LaaS is implementable with common network gear, tested to scale to large networks and provides full tenant isolation at the worst cost of a 10% reduction in the cloud utilization.
Radar‐based subglacial lake classification in Antarctica

Subglacial lakes in East Antarctica can be separated into four categories specified by radar reflection properties. Definite lakes are brighter than their surroundings by at least 2 dB (relatively bright) and both are consistently reflective (specular) and have a reflection coefficient greater than −10 dB (absolutely bright). Dim lakes are relatively bright and specular but not absolutely bright, indicating nonsteady ice dynamics. Fuzzy lakes are both relatively and absolutely bright, but not specular, and may indicate saturated sediments or “swamps. ” Indistinct lakes are absolutely bright and specular but no brighter than their surroundings. Lakes themselves and the different classes of lakes are not arranged randomly throughout Antarctica but are clustered around ice divides, ice stream onsets, and prominent bedrock troughs, with each cluster demonstrating a different characteristic lake classification distribution. The lake classification algorithm expands on previous studies and demonstrates a novel way to characterize ice‐water interactions in East Antarctica.