Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous

Injection of a new gene therapy vector into the easily accessible vitreous transduced the entire retina and rescued disease phenotypes. New Eye Pod Gene therapy mediated by adeno-associated virus (AAV) vectors has been clinically successful for the treatment of certain inherited diseases of the retina—the light-sensitive structure at the back of the eye that houses the photoreceptor cells (rods and cones). These degenerative disorders arise from mutated genes that either fail to express an essential protein or express harmful proteins that drive structural breakdown, cell death, and, ultimately, blindness. Current gene therapy regimens require damaging injections of gene-carrying vectors into the space between the rod and cone photoreceptors and the retinal pigment epithelium. By this route, the genetic material is delivered to only part of the retina. Now, Dalkara et al. show that delivery of a new vector into the eye’s easily accessible vitreous humour transduces the entire retina and rescues degenerative eye disease phenotypes. The authors used in vivo–directed evolution to fashion an AAV vector that delivers wild-type versions of defective genes throughout the retina after noninjurious injection into the eye’s easily accessible vitreous humour—the gel-like liquid between the lens and the retina. The newly engineered gene therapy systems rescued disease phenotypes in two mouse models of inherited eye diseases (X-linked retinoschisis and Leber’s congenital amaurosis) and transduced photoreceptor cells in nonhuman primates when delivered via the vitreous. Development of these next-generation therapeutic “eye pods” suggests that gene therapy vectors can be designed to penetrate dense tissues, which currently constitute barriers to gene delivery. Inherited retinal degenerative diseases are a clinically promising focus of adeno-associated virus (AAV)–mediated gene therapy. These diseases arise from pathogenic mutations in mRNA transcripts expressed in the eye’s photoreceptor cells or retinal pigment epithelium (RPE), leading to cell death and structural deterioration. Because current gene delivery methods require an injurious subretinal injection to reach the photoreceptors or RPE and transduce just a fraction of the retina, they are suitable only for the treatment of rare degenerative diseases in which retinal structures remain intact. To address the need for broadly applicable gene delivery approaches, we implemented in vivo–directed evolution to engineer AAV variants that deliver the gene cargo to the outer retina after injection into the eye’s easily accessible vitreous humor. This approach has general implications for situations in which dense tissue penetration poses a barrier for gene delivery. A resulting AAV variant mediated widespread delivery to the outer retina and rescued the disease phenotypes of X-linked retinoschisis and Leber’s congenital amaurosis in corresponding mouse models. Furthermore, it enabled transduction of primate photoreceptors from the vitreous, expanding its therapeutic promise.
The Financial Sector Reforms and Their Effect on the Nigerian Economy

This paper examines the financial sector reforms and its effect on the Nigerian Economy. The financial sector is without no doubt a very essential part of the economy of a nation and any reforms carried out in it extend to other parts of the economy representing a transformational moment for the economy and its people. This study employs the ordinary least square method in carrying out this research. The study covers the period 1980-2008. It can be seen that the financial sector developments that were experienced in Nigeria`s economy at one point or the other had effect on the activities of the economy. However, this does not imply that the reforms in the financial sector are solely responsible for the sector being better off. In this research study, an improvement in financial intermediation was considered a necessary condition for stimulating investment, raising productive capacity and fostering economic growth. It is therefore recommended that there should be macroeconomic stability, as the activities in all other sectors affect this or is affected by it. Also there should be political stability as this also affects the effective operation of the financial sector.
Diagnosis of Cattle Brucellosis by PCR and Serological Methods: Comparison of Diagnostic Tests

Brucellosis is one of the most widespread zoonotic diseases globally. This chronic, contagious disease mainly transmitted from cattle, sheep, goats, pigs and camels through direct contact with blood, placenta, fetuses or uterine secretions or through consumption of contaminated raw animal products such as unpasteurized milk or cheese. Brucellosis is endemic in Iran. The aim of this study was to compare the molecular and serological tests for detection of brucellosis. In a cross-sectional study, the blood specimens were collected from 92 unvaccinated cattle during the time period September 2014 to July, 2015. The serum samples were aliquoted and stored at −20°C until tested. The brucellosis diagnosis was established by indirect ELISA (iELISA), Rose Bengal, 2ME, Wright and polymerase chain reaction (PCR) method. In this investigation frequency of brucellosis by using Wright, 2ME, Rose Bengal, and iELISA methods were 42.3% (n= 39), 50% (n= 71), 78.2% (n=72), 75% (n=69), 86.2% (n=76), respectively. The specificity and sensitivity of iELISA was higher than the other tests. The 72 positive Rose Bengal samples in PCR were shown to be positive by both genes and 20 negative Rose Bengal samples were shown negative by both samples. Prevention of brucellosis mainly involves education, food quality and personal hygiene. Efforts should be made by responsible authorities. The results of this study showed specificity and sensitivity of indirect ELISA (iELISA) test is more than other methods. So, brucellosis diagnosis using of this test is recommended.
Cardiovascular effects of nitrergic system of the pedunculopontine tegmental nucleus in anesthetized rats

Objective(s): Nitric oxide (NO) is an important neurotransmitter in central nervous system involved in central cardiovascular regulation. The presence of NO in the pedunculopontine tegmental (PPT) nucleus has been shown, but its cardiovascular effect has not been determined. In the present study, the cardiovascular effect of NO in the PPT nucleus was evaluated. Materials and Methods: After induction of anesthesia, a polyethylene catheter (PE-50) filled with heparinized saline inserted into the femoral artery, and the blood pressure (BP) and heart rate (HR) were continuously recorded. Animals were then placed in a stereotaxic apparatus and maximum changes of mean arterial pressure (∆MAP) and heart rate (∆HR) after microinjection of two doses of NG-nitro-L-arginine methyl ester (L-NAME, 30 and 90 nmol), L-arginine (L-Arg 10 and 50 nmol) and sodium nitroprusside (SNP, 9 and 27 nmol) into the PPT were provided and compared with control group (One-way ANOVA). Results: Both doses of L-NAME significantly increased ∆MAP compared to control (P<0.05 and P<0.01, respectively). ∆HR only in higher dose (90 nmol) significantly increased compared to control (P<0.05). Two doses of L-Arg (10 and 50 nmol/150 nl) had no significant effect on ∆MAP or ∆HR. Higher dose of SNP (27 nmol) significantly decreased ∆MAP (P<0.05) and its both doses significantly decreased ∆HR compared to control (P<0.05 and P<0.001, respectively). Effect of higher dose on ∆HR was significantly higher than the lower dose (P<0.05). Conclusion: Our results show an inhibitory effect of the nitrergic system of the PPT on central cardiovascular system.
Why do simulation? Towards a working epistemology for practitioners of the dark arts

The purpose of this paper is to argue for clarity of methodology in social science simulation. Simulation is now at a stage in the social sciences where it is important to be clear why simulation should be used and what it is intended to achieve. The paper goes on to discuss a particularly important source of opposition to simulation in the social sciences which arises from perceived threats to the orthodox hard-core. This is illustrated by way of a couple of case studies. The paper then goes on to discuss defences to standard criticisms of simulation and the various positive reasons for using simulation in preference to other methods of theorising in particular situations.
Apprendre à l'université

Que signifie apprendre a l'universite ? Comment doit-on y apprendre et pourquoi le faire ? Pourquoi tant d'etudiants echouent-ils a apprendre a l'universite ? Cet ouvrage rend compte des resultats d'une enquete qualitative sur les relations differenciees a l'acte d'apprendre des etudiants a l'universite, en mobilisant pour cette analyse un nombre important de recherches internationales et francaises. Le propos est pense a la confluence de trois registres. L'auteur envisage d'abord la place centrale de la question du sens dans la relation a l'apprendre chez les etudiants. Le second registre est relatif au fait de concevoir l'acte d'apprendre en tant qu'acte situe dans un contexte pedagogique et au sein d'une matrice disciplinaire qui exercent une influence indeniable dans la mobilisation intellectuelle des etudiants. Enfin, le troisieme registre prend en compte la qualite de leur apprentissage. Cette distinction s'explique par les specificites et les enjeux de l'apprentissage universitaire, qui doit preparer les etudiants a confronter les defis d'un monde en mutation permanente. C'est dans l'optique d'une sociologie de l'education que l'auteur se propose d'analyser l'experience universitaire des jeunes et leur engagement vis-a-vis de l'acte d'apprendre. Il a cherche a saisir de l'interieur le point de vue de l'etudiant, en realisant des entretiens dans cinq universites francaises. Un portait bouleversant du monde etudiant qui est tout sauf homogene. Cet ouvrage est destine aux enseignants-chercheurs, ainsi qu'aux differents acteurs de la pedagogie universitaire. Il s'adresse aussi aux etudiants interesses par la question de l'apprentissage universitaire.
Fevers and abnormal blood and cerebrospinal fluid studies after pediatric cerebral hemispherectomy: impact of etiology and age at surgery.

OBJECT The object of this study was to determine if etiology and age at surgery were linked with fevers and altered white blood cell and CSF laboratory values after cerebral hemispherectomy. METHODS Seizure etiologies (n = 76) were classified into hemimegalencephaly (HME), cortical dysplasia (CD), infarcts (stroke), Rasmussen encephalitis (RE), history of infections, and Sturge-Weber syndrome (SWS) and were compared with clinical variables, maximum daily temperature (Tmax), and blood and CSF studies through Day 12 posthemispherectomy. RESULTS The Tmax on Days 2-4 and 9-12 postsurgery were higher for HME and RE cases than for stroke cases. Patients with RE showed positive correlations, whereas those with SWS had negative correlations between Tmax and age at surgery. Blood WBC counts on postsurgery Days 3, 6, and 9-12 were higher in the HME and CD cases than in the stroke and RE cases. The percentage of blood polymorphonuclear cells (%bloodPMNs) was higher in the RE cases than in the HME, CD, and SWS cases. The RE, HME, and CD cases showed positive correlations between %bloodPMNs and age at surgery. The percentage of blood monocytes (%bloodMono) was higher in the patients with HME than in those with stroke or RE. The HME and CD cases showed negative correlations between %bloodMono and age at surgery. The CSF red blood cell counts were higher in the RE than in the CD and stroke cases. The percentage of CSF monocytes was higher in patients with CD than in those with stroke and RE. The percentage of CSF lymphocytes positively correlated with age at surgery. CONCLUSIONS Seizure etiology and age at surgery were associated with developing fevers and altered blood and CSF values after pediatric cerebral hemispherectomy. These findings indicate that besides infections, other clinical variables have an impact on developing fevers and abnormal laboratory values posthemispherectomy. Cultures appear to be the most reliable predictor of infections.
Differences in citation impact across countries

Using a large data set, indexed by Thomson Reuters, consisting of 4.4 million articles published in 1998–2003 with a 5‐year citation window for each year, this article studies country citation distributions for a partitioning of the world into 36 countries and two geographical areas in eight broad scientific fields and the all‐sciences case. The two key findings are the following. First, country citation distributions are highly skewed and very similar to each other in all fields. Second, to a large extent, differences in country citation distributions can be accounted for by scale factors. The Empirical situation described in the article helps to understand why international comparisons of citation impact according to (a) mean citations and (b) the percentage of articles in each country belonging to the top 10% of the most cited articles are so similar to each other.
Automatic Assessment of Infants' Levels-of-Distress from the Cry Signals

It has long been an attractive prospect to monitor and assess infants' physical and emotional well-being by analyz- ing their cries. The feasibility of such an approach depends on the introduction of modern computer signal processing technology into infant cry research. In this paper, we first discuss the issue of quantifying the distress level of infants. We propose the use of a single item-the level of distress (L0D)-to describe parents' perceptual assess- ment of infants' distress situation from cry sounds. Then, we introduce the concept of cry modes and cry mode sequences to efficiently represent the time-frequency characteristics of infant cries. With the introduction of the cry mode representation scheme, a composite parameter-the H -value-is established as a descrip- tor of the LOD. The H-value can be derived from the cry sound signal. In our experiment, the H-value showed strong consistency with the parents' LOD rating. Finally, an automatic cry analysis system based on hidden Markov models (HMM's) is explained. This system automatically estimates the W-value from a cry sound signal. Testing with 58 different cries uttered by infants under various degrees of stimulation has shown that this HMM-based system is able to give assessments of the distress level of infants consistent with the perceptions of experienced parents. This work provides the basis for the design of automated devices for the monitoring and evaluation of cries of normal and sick infants.
RIP2 contributes to Nod signaling but is not essential for T cell proliferation, T helper differentiation or TLR responses

Receptor‐interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses and innate immunity as a mediator in TLR signaling and nucleotide‐binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined both innate and adaptive immune responses in RIP2‐deficient mice on the C57BL/6 background. Despite the up‐regulation of RIP2 after T cell activation, we could not detect any defect in T cell proliferation or Th1/Th2 responses in RIP2‐KO mice. Furthermore, we found that TLR responses in RIP2‐deficient macrophages were normal. However, our analysis showed that Nod signaling was impaired in macrophages from RIP2‐deficient mice. In conclusion, our data demonstrate a critical role for RIP2 in Nod signaling, while T cell proliferation, T helper differentiation and TLR responses were unaffected by the absence of RIP2.
Feeding by Didelphis albiventris on treegum in the Northeastern Atlantic Forest of Brazil

White-eared opossums, Didelphis albiventris (Didelphidae, Marsupialia) are widely distributed in Brazil (Emmons and Feer, 1997), and are very common in the urban region of the State of Pernambuco. Most available information on the biology of this species in Brazil comes from studies conducted in patches of forests in the southern part of the country (e.g., Caceres, 2000; Caceres and Monteiro-Filho, 2001), and little is known of its biology in highly-modified environments although the species appears to be well adapted to urban habitats (Alessio, unpub. data) Based on mark-recapture studies it has been shown that white-eared opossums present a very generalist feeding habit, and that the inclusion of a variety of food items appear to be opportunistic (Eisenberg, 1989; Rodriguez and Barque, 1992; Santori et al., 1995; Leite et al., 1996; Malcolm, 1997; Carvalho et al., 1999; Caceres and Monteiro-Filho, 2001; Caceres, 2002). Another species of mammals that has adapted well to live in patchy environments where semi natural and urban habitats mingle in north-eastern Brazil is the Tufted-eared marmoset Callithrix jacchus, Callithrichidae, Primates (Alonso and Langguth, 1989; Mendes Pontes and Monteiro da Cruz, 1995; Roda and Mendes Pontes, 1998); this species is sympatric with the white-eared opossums and shows a fairly similar diet composed of fruits, insects, invertebrates, and small vertebrates (e.g., Stevenson and Rylands, 1988; Alonso and Langguth, 1989). Tufted-eared marmosets have developed the ability to actively exploit the exudates of a number of tree species by scratching off tree trunks and thus inducing the flow of tree gum; especially in the dry season this activity may take more than 70% of their foraging time (Fonseca and Lacher, 1984; Rylands, 1984; Silva and Monteiro da Cruz, 1993). Alonso and Langguth (1989) have also showed that Tufted-eared marmosets usually scratch the tree trunk at dusk and return to feed on the gum exudates in the first hours of the following morning. In this study we show for the first time that White-eared opossums (Didelphis albiventris) FEEDING BY DIDELPHIS ALBIVENTRIS ON TREE GUM IN THE NORTHEASTERN ATLANTIC FOREST OF BRAZIL
SPECIFICITY OPERATORS IN SpecDP

In this paper I argue that a common noun phrase DP contains a small clause, including both a predicate (headed by the common noun) and an abstract subject position. DPs that are specific (in the sense of EnG 1991) are argued to have an operator in SpecDP, which A-bar binds the abstract subject position of the DP-internal small clause. This analysis forms the basis of an account of the Specificity Effect on extraction from DP, as well as some other facts concerning the internal structure of DP. The analysis also predicts that while specific nominal predicates are DPs, non-specific nominal predicates are not. The two kinds of nominal predicate differ distributionally, and it is shown that these differences follow from the proposed analysis.
EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells

Systemic sclerosis (SSc) is characterised by a progressive microangiopathy that contributes significantly to the morbidity of patients with SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers of endothelial precursor cells (EPCs) might also contribute to the vascular pathogenesis of SSc. However, different protocols for isolation, enrichment, culture and quantification of EPCs are currently used, which complicate comparison and interpretation of the results from different studies. The aim of the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) group expert panel was to provide recommendations for standardisation of future research on EPCs. Consensus statements and recommendations were developed in a face to face meeting by an expert panel of the basic science working group of EUSTAR. The findings were: cardiovascular risk factors and medications such as statins should be described in detail. A detailed description of methods considering isolation, culture, enrichment and detection of EPCs should be given. For in vitro culture of EPCs, no protocol has been shown to be superior to another, but coating with laminin and type IV collagen would resemble most closely the situation in vivo. The endothelial phenotype should be confirmed in all in vitro cultures at the end of the culture period. We recommend using CD133, vascular endothelial growth factor type 2 receptor (VEGFR2) and CD34 in combination with a viability marker for quantification of EPCs in the blood. Finally, exact standard operating procedures for fluorescence-activated cell sorting (FACS) analysis are given that should be strictly followed. In summary, the EUSTAR recommendations will help to unify EPC research and allow better comparison between the results of different studies.
Effect of aquatic exercise on mental health, functional autonomy, and oxidative dysfunction in hypertensive adults

ABSTRACT The aquatic exercise is an effective non-pharmacological therapy for prevention and control of hypertension. The objective of the present study was to investigate the effect of aquatic exercise on mental health, functional autonomy, and oxidative dysfunction in hypertensive adults. Methodologically 29 adults (mean age 53 ± 7.5 years) were included in the study, and were randomly grouped as hypertensive (n = 16) and non-hypertensive (n = 13). Both groups underwent low-intensity aquatic exercise program for 12 weeks. Outcomes were evaluated at week 0 and 12. The values for the following parameters decreased in the hypertensive group post training: anxiety (−6.2 ± 2 score; 60%), Timed Up and Go test (−7.4 ± 0.3 sec; 30%), protein carbonylation (−0.15 ± 0.03 nmol/mg protein; 50%), nitric oxide (12.4 ± 6 nmol/mg protein; 62%), interleukin-6 (−27.6 ± 5.7 pg/mg protein; 46%), and tissue necrosis factor-alpha (−52.4 ± 3.8 pg/mg protein; 40%); however, the values of the following parameters increased before training: Berg score (56 ± 2; 7.8%), flexibility (27 ± 1 cm; 71%); glutathione (3.1 ± 1.3 nmol/mg protein; 138%), and superoxide dismutase (1.6 ± 0.4 nmol/mg; 166%). In conclusion, we suggest that low-intensity aquatic exercise program improved anxiety, functional autonomy, and oxidative dysfunction in hypertensive adults.
File placement mechanisms for improving write throughputs of cloud storage services based on Ceph and HDFS

Cloud storage services are pervasive nowadays. Many cloud storage services use distributed file systems as their backend storage systems. Some research results on file-size distribution of file systems show that file systems contain lots of small files. Therefore, this paper proposed a hybrid distributed file system based on Ceph and HDFS that can deliver satisfactory write throughputs for a cloud storage system with 80–90% small files and 10–20% large files. The experimental results show that the file allocation mechanism without RAM disk caching can improve the write throughputs of Ceph and HDFS by approximately 10% to 50%. While the one with RAM disk caching can have up to 200% write throughputs improvement.
Compression Behaviour of Reconstituted Soils at High Initial Water Contents

Oedometer tests starting from a very small effective vertical stress of 0·5 kPa were performed on three reconstituted clays with different liquid limits. The soils were prepared at various initial water contents, ranging from 0·7 to 2·0 times their corresponding liquid limits. It is observed that the e–log σ ′ v compression curves show an inverse ‘S' shape due to suction pressure resisting deformation, similar to that of soft natural clays caused by consolidation yield stress. The suction pressure σ ′ s of the reconstituted clays can be correlated with the ratio of initial void ratio to void ratio at liquid limit e0/eL. The suction pressure curve defined by a unique relationship between suction pressure σ ′ s and the normalised void ratio at suction pressure es/eL is also proposed to distinguish between the pre-suction and the post-suction states. In addition, Burland's concept of the intrinsic compression line is adopted for correlating the compression curves of various reconstituted clays at high initia.