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Background The four co-circulating and immunologically interactive dengue virus serotypes (DENV1-4) pose a unique challenge to vaccine design because sub-protective immunity can increase the risk of severe dengue disease. Existing dengue vaccines have lower efficacy in DENV seronegative individuals but higher efficacy in DENV exposed individuals. There is an urgent need to identify immunological measures that are strongly associated with protection against viral replication and disease following sequential exposure to distinct serotypes. Methods/Design This is a phase 1 trial wherein healthy adults with neutralizing antibodies to zero (seronegative), one non-DENV3 (heterotypic), or more than one (polytypic) DENV serotype will be vaccinated with the live attenuated DENV3 monovalent vaccine rDEN3Δ30/31-7164. We will examine how pre-vaccine host immunity influences the safety and immunogenicity of DENV3 vaccination in a non-endemic population. We hypothesize that the vaccine will be safe and well tolerated, and all groups will have a significant increase in the DENV1-4 neutralizing antibody geometric mean titer between days 0 and 28. Compared to the seronegative group, the polytypic group will have lower mean peak vaccine viremia, due to protection conferred by prior DENV exposure, while the heterotypic group will have higher mean peak viremia, due to mild enhancement. Secondary and exploratory endpoints include characterizing serological, innate, and adaptive cell responses; evaluating proviral or antiviral contributions of DENV-infected cells; and immunologically profiling the transcriptome, surface proteins, and B and T cell receptor sequences and affinities of single cells in both peripheral blood and draining lymph nodes sampled via serial image-guided fine needle aspiration. Discussion This trial will compare the immune responses after primary, secondary, and tertiary DENV exposure in naturally infected humans living in non-endemic areas. By evaluating dengue vaccines in a new population and modeling the induction of cross-serotypic immunity, this work may inform vaccine evaluation and broaden potential target populations. Trial Registration NCT05691530 registered on January 20, 2023.

O objetivo da presente tese é avaliar a lógica de realização do setor terciário em Palmas (TO), para tanto, analisa, desde sua fundação, a dicotomia entre o planejado e o realizado, evidenciando as motivações e impactos de desvios e fissuras promovidos pelas atividades terciárias que, nas suas acepções tangível e intangível, induzem novas formas de vivenciar a cidade, ressignificando a vida cotidiana e potencializando a urbanidade. O método utilizado foi o da pesquisa bibliográfica, com revisão de literatura histórica e teórica, e trabalho de campo, com coleta de entrevistas/depoimentos de caráter qualitativo e pesquisa de caráter observacional. Foram investigados e discutidos: vínculos teóricos e empíricos das inter-relações e pré-disposições entre cidade, atividades terciárias e urbanidade; presença destas inter-relações e pré-disposições no ideário de cidade moderna, evidenciadas por algumas teorias urbanas e projetos paradigmáticos dos séculos XIX e XX; projeto concebido de Palmas (discurso e estratégias projetuais) em relações às problematizações do desenho urbano no arranjo de suas atividades que condicionam à realização do terciário; e o instrumento zoneamento – que tem sido aplicado tanto em cidades novas/planejadas como nas cidades seculares – quanto à sua efetividade na geração de espacialidades com mais urbanidade. Os resultados obtidos apontam para a comprovação da hipótese: quando uma cidade nova planejada (projeto e legislação) negligencia a lógica de realização das atividades terciárias na sua complexidade, estas passam a fissurar as restrições e determinações impostas, desviando localizações, reformulando o desenho urbano e transformando tipologias na busca de sua realização; moldando uma cidade mais diversa – projetual e legalmente – e com mais urbanidade. Para além da hipótese demonstrada, a pesquisa contribui, também, oferecendo subsídios para rever o processo de gestão de cidades, quer sejam novas/planejadas, quer sejam seculares, mas que são regidas por zoneamentos que não incorporam a complexidade de realização do terciário e, consequentemente, não facilitam o florescimento e mantenimento de urbanidade. The objective of this thesis is to evaluate the logic of realization of the tertiary sector in Palmas (TO). Tertiary services that, in their tangible and intangible meanings, induce new ways of experiencing the city, giving new meaning to everyday life and enhancing urbanity. The method used was bibliographic research, with a review of historical and theoretical literature, and field work, with the collection of qualitative interviews/depositions and observational research. The following were investigated and discussed: theoretical and empirical links of interrelationships and pre-dispositions between city, tertiary activities and urbanity; presence of these interrelations and pre- dispositions in the ideas of the modern city, evidenced by some urban theories and paradigmatic projects of the 19th and 20th centuries; project conceived by Palmas (discourse and design strategies) in relation to the problematization of urban design in the arrangement of its activities that condition the realization of the tertiary; and the zoning instrument – which has been applied both in new/planned cities and in secular cities – regarding its effectiveness in generating spatialities with more urbanity. The results obtained point to the confirmation of the hypothesis: when a new planned city (project and legislation) neglects the logic of carrying out tertiary activities in their complexity, they begin to crack the restrictions and determinations imposed, diverting locations, reformulating the urban design and transforming typologies in the search for their realization; shaping a more diverse city – both in terms of design and law – and with more urbanity. In addition to the demonstrated hypothesis, the research also contributes by offering subsidies to review the management process of cities, whether they are new/planned or secular, but which are governed by zoning that do not incorporate the complexity of tertiary development and, consequently, they do not facilitate the flourishing and maintenance of urbanity.

The upper Assam shelf is a self-slope basin in north-east India, filled with nearly 7 km of sedimentary rocks of tertiary period with the granite basement and various oil fields along the border of the Naga thrust. The major producing fields are structural and strati-structural. The study area is placed in between the Mikir hills and Naga thrust. The objective of the study is to identify potential hydrocarbon reservoir zones in the geologically complex south upper of the Assam shelf using estimates of acoustic impedance and porosity derived by 3D post-stack seismic inversion. Well data, such as sonic velocity and density logs, from two wells (namely, KA and TE) are used in the inversion and validation of results. Inversion results are used to build a geological model in the form of acoustic impedance from which we derive 3D porosity cube which are used for hydrocarbon potential in the Paleocene to lower Oligocene sands, and the Precambrian basement. Although the amplitude maps provide an indication of potential reservoirs, the extent of these zones are much better identified in the inverted impedance maps and the corresponding estimated high-porosity zones. The analysis predicted the potential reservoir rocks in the Sylhet, Kopili and Barail formations, in which the Sylhet and Kopili appear to have good potential zones. Near the vicinity of the Naga thrust belt, the proximity of potential reservoir is predicted in the Kopili, Sylhet formation and in the fractured basement, respectively.

A seismic study was conducted to re-interpret the Qasab and Jawan oil field in northern Iraq, south of the city of Mosul, by reprocessing and interpreting many seismic sections of a number of field surveys that included the field area. Two reflectors are detected, represented by Hartha Formations which were deposited during the Cretaceous age and Euphrates Formation which was deposited during the Tertiary age in order to stabilize the structural image of this field. The study was achieved by reinterpreting seismic sections using the Petrel program, where time, velocity and depth maps were prepared for the two formations. The study showed that the Qasab and Jawan fields generally consist of a structural closure located at the wells of the northern dome. This closure extends to the south east and deviates towards the east in the form of a structural rift. The study concluded the existence of a transverse fault that cuts Qasab and Jawan structures, forming a structural trap that represents the southern part of Qasab structure.

Conducting needs analysis is a prevalent phenomenon in designing curriculum in language teaching and learning. This paper explored the English language needs of engineering students at the tertiary level of education in Bangladesh vis-à-vis four basic language skills. Moreover, this paper tried to shed some light on the gaps between learners’ present level of competence and target needs. This study followed the mixed approach (both quantitative approach and qualitative approach) to collect data through questionnaires, semi-structured interviews, and focus group discussions. Under the random stratified sampling method, the study collected data from 99 undergraduate engineering students and 15 EFL teachers from different universities in Bangladesh. The findings of the study revealed that engineering students felt the ardent need for all the four major language skills (listening, speaking, reading, and writing). The findings also addressed the needs of the subskills regarding each language skill. Additionally, the offered courses were not adequately addressing the language needs of the students. Moreover, the duration and number of English language classes were not sufficient to meet the needs of the engineering students. Based on the findings, this study made some recommendations to minimize the gaps between engineering students’ present and target needs of the English language.

A mixed-methods approach to understanding the effects of exposure to metacognitive prompts during research

The EtfAB components of two bifurcating flavoprotein systems, the crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase from the bacterium Megasphaera elsdenii and the menaquinone-dependent NADH:ferredoxin oxidoreductase from the archaeon Pyrobaculum aerophilum, have been investigated. With both proteins, we find that removal of the electron-transferring flavin adenine dinucleotide (FAD) moiety from both proteins results in an uncrossing of the reduction potentials of the remaining bifurcating FAD; this significantly stabilizes the otherwise very unstable semiquinone state, which accumulates over the course of reductive titrations with sodium dithionite. Furthermore, reduction of both EtfABs depleted of their electron-transferring FAD by NADH was monophasic with a hyperbolic dependence of reaction rate on the concentration of NADH. On the other hand, NADH reduction of the replete proteins containing the electron-transferring FAD was multiphasic, consisting of a fast phase comparable to that seen with the depleted proteins followed by an intermediate phase that involves significant accumulation of FAD⋅-, again reflecting uncrossing of the half-potentials of the bifurcating FAD. This is then followed by a slow phase that represents the slow reduction of the electron-transferring FAD to FADH-, with reduction of the now fully reoxidized bifurcating FAD by a second equivalent of NADH. We suggest that the crossing and uncrossing of the reduction half-potentials of the bifurcating FAD is due to specific conformational changes that have been structurally characterized.

Songbirds are the largest order of birds with 6456 species, making up more than half of every known bird species. The location and time of their emergence, as well as the method of their spreading, is debated. They are present in the Carpathian Basin from the beginning of the Neogene, with an increasing number of types and species. Due to their diverse ways of life and diets, their presence mirrors the environmental conditions of the given geological periods quite accurately.

Significance The Hv1 proton channel is an unusual voltage-gated ion channel with atypical architecture and stoichiometry. While functional as a monomer, Hv1 is usually expressed as a dimer of two voltage-sensing domains (VSDs). How the two VSDs arrange relative to each other is a matter of debate and the functional impact of VSD–VSD interactions is only partly understood. We show that the Hv1 dimer interface is formed by the S1 and S4 transmembrane segments of the VSD. We find this S1–S4 dimer interface to be a strong regulator of Hv1 gating. This interface therefore constitutes a promising target for the development of allosteric modulators for this class of channels critical for pH regulation and immunity., The voltage-gated proton channel Hv1 is a member of the voltage-gated ion channel superfamily, which stands out in design: It is a dimer of two voltage-sensing domains (VSDs), each containing a pore pathway, a voltage sensor (S4), and a gate (S1) and forming its own ion channel. Opening of the two channels in the dimer is cooperative. Part of the cooperativity is due to association between coiled-coil domains that extend intracellularly from the S4s. Interactions between the transmembrane portions of the subunits may also contribute, but the nature of transmembrane packing is unclear. Using functional analysis of a mutagenesis scan, biochemistry, and modeling, we find that the subunits form a dimer interface along the entire length of S1, and also have intersubunit contacts between S1 and S4. These interactions exert a strong effect on gating, in particular on the stability of the open state. Our results suggest that gating in Hv1 is tuned by extensive VSD–VSD interactions between the gates and voltage sensors of the dimeric channel.

The use of Right dihedral method, Lisle graph, and Mohr diagram allows the analysis of the paleostress. Fault slip data were measured for eighteen data of two stations located within Chia Gara structure in Dohuk area in the High Folded Zone, Northern Iraq. Depending on Mohr diagram, Bott equation, and vertical thickness, the magnitudes of the paleostress at the time of the tectonic activity were determined. Firstly, Georient Software was used to estimate the orientation of the paleostresses (σ1, σ2 and σ3). Secondly, using the rupture –friction law, taking into account the depth of the overburden, the vertical stress (σv) was calculated to determine the magnitude of the paleostresses in the study area. The values in station one (hinge area, eight data) were σ1=7100, σ2=4121.5, and σ3=1143 bars, whereas the values in station two (the north limb of structure, ten data) were σ1=3740, σ2=1585, and σ3=570 bars. The high magnitudes of the principal stress axes may refer to the active tectonic events which led to the deformation of the area during the Mesozoic Era and the Tertiary period. The study area shows the existence of two types of the faults, the first type is the reactivated faults, the poles of which lie between the sliding line and Mohr envelope. The second type is the inactive faults, with poles lying on the great circle of Mohr diagram

Background: Little is known about the combined impact of increasing ultrasound usage by clinical disciplines outside radiology and technical advances in other specialised radiological modalities on the role of ultrasound in tertiary-level radiology departments.Objectives: The aim of this study was to evaluate temporal trends in ultrasound utilisation in a tertiary-level radiology department.Method: An institutional review board-approved retrospective descriptive study in the radiology department of Tygerberg Hospital (TBH). The nature and number of ultrasound performed in 2013 and 2019 were retrieved from the TBH radiology information system (RIS). These were compared, expressed as a proportion of the overall annual radiology workload and stratified by location (ultrasound suite, interventional suite, mammography suite). Ultrasound suite examinations were analysed by body part and age (0–13 years; 13 years) and interventional suite workload by procedure.Results: The overall radiology workload decreased by 8%, reflecting the interplay between decreased plain radiography (–19%) and general fluoroscopy (–0.3%) and increased computed tomography (27%), magnetic resonance (23%) and fluoroscopically guided procedures (22%).There was a 12% increase in ultrasound utilisation. Ultrasound remained the second most common specialised imaging investigation throughout, after computed tomography. Ultrasound suite services were stable (–1%) representing a balance between decreased abdominal (–22%) and arterial (–16%) scans, and increased musculoskeletal (67%), small part (65%) and neonatal brain scans (41%). There were substantial increases in interventional (90%) and mammography suite (199%) services.Conclusion: Ultrasound remains a key modality in the tertiary-level radiology department, with an evolving pattern of clinical applications.

ObjectivesEmergency caesarean sections (ECS) are time-sensitive procedures. Multiple factors may affect team efficiency but their relative importance remains unknown. This study aimed to identify the most important predictors contributing to quality of care during ECS in terms of the arrival-to-delivery interval.DesignA retrospective cohort study. ECS were classified by urgency using emergency categories one/two and three (delivery within 30 and 60 min). In total, 92 predictor variables were included in the analysis and grouped as follows: ‘Maternal objective’, ‘Maternal psychological’, ‘Fetal factors’, ‘ECS Indication’, ‘Emergency category’, ‘Type of anaesthesia’, ‘Team member qualifications and experience’ and ‘Procedural’. Data was analysed with a linear regression model using elastic net regularisation and jackknife technique to improve generalisability. The relative influence of the predictors, percentage significant predictor weight (PSPW) was calculated for each predictor to visualise the main determinants of arrival-to-delivery interval.Setting and participantsPatient records for mothers undergoing ECS between 2010 and 2017, Nordsjællands Hospital, Capital Region of Denmark.Primary outcome measuresArrival-to-delivery interval during ECS.ResultsData was obtained from 2409 patient records for women undergoing ECS. The group of predictors representing ‘Team member qualifications and experience’ was the most important predictor of arrival-to-delivery interval in all ECS emergency categories (PSPW 25.9% for ECS category one/two; PSPW 35.5% for ECS category three). In ECS category one/two the ‘Indication for ECS’ was the second most important predictor group (PSPW 24.9%). In ECS category three, the second most important predictor group was ‘Maternal objective predictors’ (PSPW 24.2%).ConclusionThis study provides empirical evidence for the importance of team member qualifications and experience relative to other predictors of arrival-to-delivery during ECS. Machine learning provides a promising method for expanding our current knowledge about the relative importance of different factors in predicting outcomes of complex obstetric events.

ImportanceIn an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care.ObjectiveTo examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital.Design, Setting, and ParticipantsThis retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks’ gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022.ExposuresHospital of birth at 22 to 29 weeks’ gestation.Main Outcomes and MeasuresBirthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (ResultsA total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B– or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B–level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B– or C-level NICUs decreased by 9.2% (95% CI, −10.3% to −8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks’ gestation occurred at hospitals with high-volume B– or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B– or C-level NICUs decreased by 10.9% [95% CI, −14.0% to −7.8%) in the East North Central region and by 21.1% (95% CI, −24.0% to −18.2%) in the West South Central region.Conclusions and RelevanceThis retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks’ gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes.

This study explored and analyzed the EFL writing at tertiary level (university level) in Palestine. Therefore, the researcher analyzed fifteen essays of Palestinian EFL students at the university level. The analysis was in terms of four writing measures: complexity, accuracy, fluency, and lexical density. For the sake of analysis, means, standard deviations, and Pearson���s Correlation Coefficient were used. The results showed that the students��� essays lacked accuracy, fluency, complexity, and lexical density. Further, the correlation between complexity and fluency was strong. However, the relationship between accuracy and fluency was weak. These results imply that the writing skill at tertiary level is low and unconvincing. Therefore, the researcher recommended improving fluency through power writing, accuracy through reading longer reading texts and avoids reading blogs, Facebook entries, and tweets, complexity through having more in class and home practice and activities, and lexical density through encouraging the students to read Wikipedia, news articles, fiction, and general prose. The decision makers, universities, curricula designers, and teacher are also advised to set plans, which pay more attention to writing and even prioritize witting as a must.

Photosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.

Background Health Management Information Systems (HMIS) are being adopted increasingly in tertiary hospitals in developing countries like Pakistan, with the aim of improving physician and patient convenience. However, the perception of healthcare professionals regarding HMIS should be thoroughly assessed in order to achieve effective utilization and implementation of this system. Objective To assess the perception of physicians regarding the newly implemented HMIS in a tertiary setting hospital in Pakistan. Materials and methods A cross-sectional study was conducted in all the departments of Ghurki Trust Teaching Hospital (GTTH), Lahore. Total 145 physicians of varying specialty units, fulfilling the inclusion and exclusion criteria, were included and data were collected over a span of six months between July 2020 and December 2020. Data was collected by using a structured questionnaire. The SPSS software version 22 was used for data analysis. Results are presented in the form of frequencies and tables. Results The sample population consisted of 80 males (55.2%) and 65 females (44.8%), with the majority of the respondents having 1-5 years of clinical experience. Of the total, 61.4% (n = 89) knew about the term HMIS, while 71.7% (n = 104) of participants responded that no formal training was provided to them before the implementation of HMIS. Overall, 77.9% of respondents agreed that formal training should have been conducted before the implementation of this system. In total, 77.2% of respondents considered the ease to review patients’ history (ERPH) as the biggest advantage of HMIS, while 54.5% considered being paper-free (PF), and 53.1% considered facilitation of data analysis (FDA) as the next two major advantages. As for the disadvantages, 75.9% of respondents considered HMIS to be more time-consuming (TC) and 57.2% considered it to be a hindrance to smooth running (HSR) of clinical work in case of overloading of patients. Conclusions While implementation of HMIS was found to have significant advantages in the opinion of physicians, such as ease in reviewing patients' medical records, data analysis, and providing paperless patient care, it should nevertheless be preceded by formal training of all physicians regarding its use. Many physicians consider HMIS to be more TC, especially in circumstances where the patient load is overwhelming.

TRAAK is a mechanosensitive two-pore domain K+ (K2P) channel localized to nodes of Ranvier in myelinated neurons. TRAAK deletion in mice results in mechanical and thermal allodynia, and gain-of-function mutations cause the human neurodevelopmental disorder FHEIG. TRAAK displays basal and stimulus-gated activities typical of K2Ps, but the mechanistic and structural differences between these modes are unknown. Here, we demonstrate that basal and mechanically gated openings are distinguished by their conductance, kinetics, and structure. Basal openings are low conductance, short duration, and due to a conductive channel conformation with the interior cavity exposed to the surrounding membrane. Mechanically gated openings are high conductance, long duration, and due to a channel conformation in which the interior cavity is sealed to the surrounding membrane. Our results explain how dual modes of activity are produced by a single ion channel and provide a basis for the development of state-selective pharmacology with the potential to treat disease.

Eolian material within pelagic North Pacific Ocean (NPO) sediments contains considerable information about paleoclimate evolution in Asian dust source areas. Eolian signals preserved in NPO sediments have been used as indices for enhanced Asian interior aridity. We here report a detailed eolian dust record, with chemical index of alteration (CIA) and Rb/Sr variations, for NPO sediments from Ocean Drilling Program Hole 885A over the past 4.0 m.y. CIA and Rb/Sr co-vary with the dust signal carried by combined eolian hematite and goethite concentrations. Changes in CIA around the intensification of Northern Hemisphere glaciation (iNHG) event at ca. 2.75 Ma indicate that dust production in source areas was associated mostly with physical and chemical weathering before and after the iNHG event, respectively. We here attribute the eolian flux increase into the NPO across the iNHG event mainly to increased availability of wind-erodible sediment in dust source areas derived from snow and glacial meltwater runoff, which resulted from glacial expansion and enhanced snowfall in the mountains surrounding the Tarim region in response to global cooling. Our results provide a deeper understanding of Asian interior environmental changes in response to global paleoclimate changes, where dust source areas became intermittently moister rather than more arid in response to global cooling., This study was supported by the National Key R&D Program of China (2016YFA0601903); the National Natural Science Foundation of China (NSFC 41430962); the NSFC-Shandong Joint Fund for Marine Science Research Centers (U1606401); the National Program on Global Change and Air-Sea Interaction (GASI-GEOGE-03); the Australia-New Zealand International Ocean Discovery Program Consortium (ANZIC), which provided Legacy/Special Analytical Funding (ANZIC is supported by the Australian government through the Australian Research Council's LIEF funding scheme [LE140100047], the Australian and New Zealand consortium of universities and government agencies); and the Ocean Drilling Program, which was sponsored by the U.S. National Science Foundation (NSF) and participating countries under management of Joint Oceanographic Institutions (JOI), Inc.

The study of pore characteristics is of great importance in reservoir evaluation, especially in deeply buried sandstone. It controls the storage mechanism and reservoir fluid properties of the permeable horizons. The first member of Eocene Shahejie Formation (Es1) sandstone is classified as feldspathic litharenite and lithic arkose. The present research investigates the pore characteristics and reservoir features of the deeply buried sandstone reservoir of Es1 member of Shahejie Formation. The techniques including thin-section petrography, mercury injection capillary pressure (MICP), scanning electron microscopy and laser scanning confocal microscope images were used to demarcate the pores including primary intergranular pores and secondary intergranular, intragranular, dissolution and fracture pores. Mercury injection test and routine core analysis were led to demarcate the pore network characteristics of the studied reservoir. Pore size and pore throat size distribution are acquired from mercury injection test. Porosity values range from 0.5% to 30%, and permeability ranges 0.006–7000 mD. Pore radii of coarse-grained sandstone and fine-grained sandstone range from 0.2 to > 4 µm and 1 nm to 1.60 µm, respectively, by MICP analysis. The mineral composition also plays an important role in protecting the pores with pressure from failure. Fractured sandstone and coarse-grained sandstone consist of large and interconnected pores that enhance the reservoir porosity and permeability, whereas fine-grained sandstone and siltstone consist of numerous pores but not well interconnected, and so they consist of high porosity with low permeability.

This article examines the development and the contents of the library of Ignacy Oginski, appointed elder of the Darsūniškis and Vaiguva communities; his collection of books is discussed with an emphasis on how the sense of self as well as geneological and religious identity are expressed. The library of I.Oginski is discussed within the context of the history of his family and closest relatives as well as his connections with the Bernardines of Trakai. The bibliographical and provenance analysis is founded on I. Oginski’s books, which are stored in Vilnius University Library (10 specimens); also published at the end of this paper is a list of books bestowed by I. Oginski to the Trakai Bernardine Monastery, which itself was added into the 1787 catalogue of the monastery’s library. It was determined that I. Oginski belonged to the third order of the Franciscan tertiaries and was a financial affairs trustee (i.e., a syndic, Lat. Sindicus Apostolicus) of the Trakai Bernardine Monastery, which he, together with his mother Antonina Oginska, had amply sponsored and to which he bequeathed upon death a sum of 7 thousand Lithuanian Zloty. I. Oginski bestowed his personal library, which consisted of 201 volume, to the Bernardines on March 29, 1786 based on a testament written in Kruonis. It contained not only the more traditional printed materials but also some sheet music characteristic of courtly culture, ledgers, and silva rerum manuscripts. Noteworthy is the prayer “On the Appeal for a Fulfilling Life” (Pol. O uproszenie stanu życia przyzwoitego), handwritten by I. Oginski himself. A large part of the library consisted of ascetic lectures, spiritual exercises, and sermons typical of the Bernardine monks, but the collection was not limited in this aspect, as it also had some secular French works from the Enlightenment period and textbooks printed by the publishing house of the Vilnius Piarists. The considerable number of historical works and books containing dedications with references to the merits of the Oginskis to the state and the Church shows that I. Oginski was particularly attentive of his family history. Generally, the library demonstrates quite clearly a promotional-religious aspect of I. Oginski’s genealogical sense of self and identity. And here, too, the ascetic literature supplements the data from other sources regarding I. Oginski’s piety and his belonging to the tertiary community. The carried out study of I. Oginski’s identity and his personal library’s development and the relevant associations confirms the available possibilities of using the approaches and methodologies of cultural anthropology and social communication in book science studies.

Human serum albumin (HSA) constitutes the primary transporter of fatty acids, bilirubin, and other plasma compounds. The binding, transport, and release of its cargos strongly depend on albumin conformation, which is affected by bound ligands induced by physiological and pathological conditions. HSA is both highly oxidized and heavily loaded with fatty acids and bilirubin in chronic liver disease. By employing small-angle X-ray scattering we show that HSA from the plasma of chronic liver disease patients undergoes a distinct opening compared to healthy donors. The extent of HSA opening correlates with clinically relevant variables, such as the model of end-stage liver disease score, bilirubin, and fatty acid levels. Although the mild oxidation of HSA in vitro does not alter overall structure, the alteration of patients’ HSA correlates with its redox state. This study connects clinical data with structural visualization of albumin dynamicity in solution and underlines the functional importance of albumin’s inherent flexibility., Paar et al. propose a SAXS-based approach to study conformations of human serum albumin (HSA) from patients with liver disease and a structural understanding of HSA dynamicity and its correlation with clinical variables are provided. Using it on real clinical samples, this study has concrete practical implications too.

The rapid increase in the number of proteins in sequence databases and the diversity of their functions challenge computational approaches for automated function prediction. Here, we introduce DeepFRI, a Graph Convolutional Network for predicting protein functions by leveraging sequence features extracted from a protein language model and protein structures. It outperforms current leading methods and sequence-based Convolutional Neural Networks and scales to the size of current sequence repositories. Augmenting the training set of experimental structures with homology models allows us to significantly expand the number of predictable functions. DeepFRI has significant de-noising capability, with only a minor drop in performance when experimental structures are replaced by protein models. Class activation mapping allows function predictions at an unprecedented resolution, allowing site-specific annotations at the residue-level in an automated manner. We show the utility and high performance of our method by annotating structures from the PDB and SWISS-MODEL, making several new confident function predictions. DeepFRI is available as a webserver at https://beta.deepfri.flatironinstitute.org/., The rapid increase in the number of proteins in sequence databases and the diversity of their functions challenge computational approaches for automated function prediction. Here, the authors introduce DeepFRI, a Graph Convolutional Network for predicting protein functions by leveraging sequence features extracted from a protein language model and protein structures.

Significance Light-driven rhodopsin proteins pump ions across cell membranes. They have applications in optogenetics and can potentially be used to develop solar energy–harvesting devices. A detailed understanding of rhodopsin dynamics and functions may therefore assist research in medicine, health, and clean energy. This time-resolved crystallography study carried out with X-ray free-electron lasers reveals detailed dynamics of chloride ion–pumping rhodopsin (ClR) within 100 ps of light activation. It shows the dissociation of Cl− from the Schiff base binding site upon light-triggered retinal isomerization. This Cl− dissociation is followed by diffusion toward the intracellular direction. The results hint at a common ion-pumping mechanism across rhodopsin families., Chloride ion–pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl− into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation–diffusion process upon light-triggered retinal isomerization.

Activation of voltage-gated ion channels is regulated by conformational changes of the voltage sensor domains (VSDs), four water- and ion-impermeable modules peripheral to the central, permeable pore domain. Anomalous currents, defined as ω-currents, have been recorded in response to mutations of residues on the VSD S4 helix and associated with ion fluxes through the VSDs. In humans, gene defects in the potassium channel Kv7.2 result in a broad range of epileptic disorders, from benign neonatal seizures to severe epileptic encephalopathies. Experimental evidence suggests that the R207Q mutation in S4, associated with peripheral nerve hyperexcitability, induces ω-currents at depolarized potentials, but the fine structural details are still elusive. In this work, we use atom-detailed molecular dynamics simulations and a refined model structure of the Kv7.2 VSD in the active conformation in a membrane/water environment to study the effect of R207Q and four additional mutations of proven clinical importance. Our results demonstrate that the R207Q mutant shows the most pronounced increase of hydration in the internal VSD cavity, a feature favoring the occurrence of ω-currents. Free energy and kinetics calculations of sodium permeation through the native and mutated VSD indicate as more favorable the formation of a cationic current in the latter. Overall, our simulations establish a mechanistic linkage between genetic variations and their physiological outcome, by providing a computational description that includes both thermodynamic and kinetic features of ion permeation associated with ω-currents.

Tetramethylenedisulfotetramine (TETS) is a so-called "caged" convulsant that is responsible for thousands of accidental and malicious poisonings. Similar to the widely used GABA receptor type A (GABAA) antagonist picrotoxinin, TETS has been proposed to bind to the noncompetitive antagonist (NCA) site in the pore of the receptor channel. However, the TETS binding site has never been experimentally mapped, and we here set out to gain atomistic level insights into how TETS inhibits the human α 2 β 3 γ 2 GABAA receptor. Using the Rosetta molecular modeling suite, we generated three homology models of the α 2 β 3 γ 2 receptor in the open, desensitized, and closed/resting state. Three different ligand-docking algorithms (RosettaLigand, Glide, and Swissdock) identified two possible TETS binding sites in the channel pore. Using a combination of site-directed mutagenesis, electrophysiology, and modeling to probe both sites, we demonstrate that TETS binds at the T6' ring in the closed/resting-state model, in which it shows perfect space complementarity and forms hydrogen bonds or makes hydrophobic interactions with all five pore-lining threonine residues of the pentameric receptor. Mutating T6' in either the α 2 or β 3 subunit reduces the IC50 of TETS by ∼700-fold in whole-cell patch-clamp experiments. TETS is thus interacting at the NCA site in the pore of the GABAA receptor at a location that is overlapping but not identical to the picrotoxinin binding site. SIGNIFICANCE STATEMENT: Our study identifies the binding site of the highly toxic convulsant tetramethylenedisulfotetramine (TETS), which is classified as a threat agent by the World Health Organization. Using a combination of homology protein modeling, ligand docking, site-directed mutagenesis, and electrophysiology, we show that TETS is binding in the pore of the α2β3γ2 GABA receptor type A receptor at the so-called T6' ring, wherein five threonine residues line the permeation pathway of the pentameric receptor channel.

Resum.

Palynological contents of organic-rich Tertiary sediments of the Hongsa coalfield, Xayabouly Province, north-western Lao PDR, were investigated. Palynomorphs that were used to reconstruct the palaeovegetation and palaeoclimate, were extracted from a sediment drill core from the central part of the Hongsa coal mine. Three pollen zones from bottom to top (Hongsa I zone, Hongsa II zone, and Hongsa III zone) were divided based on the quantitative change of the palynological assemblages. They indicate the change of climate from subtropical to temperate during the deposition of the Hongsa coal. The Hongsa vegetation composes of subtropical to warm temperate broad-leaved forests. Quercus, Fagus, castanoids, Salix, Fabaceae, and Myrtaceae were the dominant trees and shrubs, and ferns were commonly found on the forest floor. The palynological assemblages from the Hongsa Basin are different from the Oligocene and Miocene from northern Thailand; however, they are similar to the middle to late Miocene of southwest China.

Resum.

The red soils spread over South Sumatra are generally derived from the materials of the late Tertiary Period, are more than 1 million years old, and have fully developed and ultimately weathered. Thus, these soils commonly have weatherable minerals and chemical properties with low values. The eruption of Mount Krakatau, more than a hundred years ago, brought about the spreading of fresh volcanic materials particularly to the surface horizons of the soils. Therefore, it is expected that the weatherable minerals and chemical properties of the soils in South Sumatra will increase. The aim of this research is to study the weatherable minerals and some chemical properties of the red soils distributed in the southern part of Sumatra Island due to their exposure to the Krakatau eruption of 1883. The results show that all the soils have colors of 10YR to 10R; and thus, they can be classified as red soils. The eruption of Mount Krakatau has significantly increased the percentage of weatherable minerals and the CEC of the clay in the surface horizons of the soils in the southern part of Sumatra Island.

Membrane protein biogenesis in the endoplasmic reticulum (ER) is complex and failure-prone. The ER membrane protein complex (EMC), comprising eight conserved subunits, has emerged as a central player in this process. Yet, we have limited understanding of how EMC enables insertion and integrity of diverse clients, from tail-anchored to polytopic transmembrane proteins. Here, yeast and human EMC cryo-EM structures reveal conserved intricate assemblies and human-specific features associated with pathologies. Structure-based functional studies distinguish between two separable EMC activities, as an insertase regulating tail-anchored protein levels and a broader role in polytopic membrane protein biogenesis. These depend on mechanistically coupled yet spatially distinct regions including two lipid-accessible membrane cavities which confer client-specific regulation, and a non-insertase EMC function mediated by the EMC lumenal domain. Our studies illuminate the structural and mechanistic basis of EMC’s multifunctionality and point to its role in differentially regulating the biogenesis of distinct client protein classes., eLife digest Cells are surrounded and contained by a plasma membrane consisting of a double layer of fats and proteins. These proteins monitor and facilitate the movement of food, oxygen and messages in and out of the cell, and help neighboring cells communicate. Membrane proteins are manufactured in a cell compartment called the endoplasmic reticulum. Cellular machines called ribosomes visit this compartment’s membrane to manufacture proteins that need to be secreted or embedded into the cell’s membranes. As these proteins are made, they are pulled into the endoplasmic reticulum so they can be folded correctly and inserted in the membrane. A cellular machine in this compartment’s membrane that aids this process is the endoplasmic reticulum membrane protein complex (EMC). Many steps can go wrong during protein assembly, so to control protein quality, the EMC has to accommodate the variety of complex physical features that proteins can have. To explore the activity of the EMC, Miller-Vedam, Bräuning, Popova et al. studied the normal structure of the EMC in both yeast and human cells grown in the lab. These snapshots of the complex in different species had a lot in common, including how the complex was arranged within and around the membrane. Next, Miller-Vedam, Bräuning, Popova et al. generated 50 mutant versions of the EMC in human cells to determine how changing different parts of the complex affected the production of three proteins that rely on the EMC to fold correctly. These proteins were an enzyme called squalene synthase, a signaling protein called the beta adrenergic receptor and sigma intracellular receptor 2, a protein involved in the regulation of cholesterol levels. Mutations in the section of the EMC outside of the endoplasmic reticulum, within the main cellular compartment, negatively impacted the stability of squalene synthase. This section of the EMC provides a platform where proteins can associate before entering the membrane. The part of EMC that spans the membrane contains both a fat-filled cavity and a cavity with a ‘door’ that is either open or closed. Mutations in this section disrupted the insertion of both squalene synthase and the beta adrenergic receptor into the membrane, a role performed by the cavity with the door. The specific role of the fat-filled cavity is still not fully understood, but a mutation affecting this cavity disrupts the correct production of all three proteins studied. The largest section of the complex, which sits inside the endoplasmic reticulum, protected proteins as they folded, ensuring they were not destroyed for being folded incorrectly before they were fully formed. Mutations in this part of the EMC negatively impacted the stability of sigma intracellular receptor 2 without negatively affecting the other proteins. This molecular dissection of the activity of the EMC provides insights into how membrane proteins are manufactured, stabilized, coordinated, and monitored for quality. These findings could contribute towards the development of new treatments for certain congenital diseases. For example, cystic fibrosis, retinitis pigmentosa, and Charcot-Marie-Tooth disease are all thought to be caused by mutations within membrane proteins that require the EMC during their production.

The isolation of novel microbes from environmental samples continues to be a key strategy for the discovery of new metabolic capacities for the degradation and transformation of lignocellulose. We report the draft genome sequence of a new strain of Brevibacillus borstelensis isolated from a sorghum-adapted microbial community derived from a compost sample.

A new fossil species, Protanthomyza grimaldiisp. nov. (Diptera, Anthomyzidae), is described from Baltic amber (Eocene, 48–34 Ma) based on two (male and female) inclusions. It is the ninth species of the †genus Protanthomyza Hennig, 1965 and †subfamily Protanthomyzinae Roháček, 1998. Adult morphology of P. grimaldiisp. nov. revealed that the rich chaetotaxy of the thoracic pleuron, two anal veins and presence of the anteroventral process of the epandrium are plausibly shared by all species of Protanthomyza. Relationships of the new species, which belongs to a group lacking the ctenidial spine on the fore femur, are discussed.

Coronaviridae is a peculiar viral family, with a very large RNA genome and characteristic appearance, endowed with remarkable tendency to transfer from animals to humans. Since the beginning of the 21st century, three highly transmissible and pathogenic coronaviruses have crossed the species barrier and caused deadly pneumonia, inflicting severe outbreaks and causing human health emergencies of inconceivable magnitude. Indeed, in the past two decades, two human coronaviruses emerged causing serious respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV-1) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV), causing more than 10,000 cumulative cases, with mortality rates of 10 % for SARS-CoV-1 and 34.4 % for MERS-CoV. More recently, the severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) has emerged in China and has been identified as the etiological agent of the recent COVID-19 pandemic outbreak. It has rapidly spread throughout the world, causing nearly 22 million cases and ∼ 770,000 deaths worldwide, with an estimated mortality rate of ∼3.6 %, hence posing serious challenges for adequate and effective prevention and treatment. Currently, with the exception of the nucleotide analogue prodrug remdesivir, and despite several efforts, there is no known specific, proven, pharmacological treatment capable of efficiently and rapidly inducing viral containment and clearance of SARS-CoV-2 infection as well as no broad-spectrum drug for other human pathogenic coronaviruses. Another confounding factor is the paucity of molecular information regarding the tendency of coronaviruses to acquire drug resistance, a gap that should be filled in order to optimize the efficacy of antiviral drugs. In this light, the present review provides a systematic update on the current knowledge of the marked global efforts towards the development of antiviral strategies aimed at coping with the infection sustained by SARS-CoV-2 and other human pathogenic coronaviruses, displaying drug resistance profiles. The attention has been focused on antiviral drugs mainly targeting viral protease, RNA polymerase and spike glycoprotein, that have been tested in vitro and/or in clinical trials as well as on promising compounds proven to be active against coronaviruses by an in silico drug repurposing approach. In this respect, novel insights on compounds, identified by structure-based virtual screening on the DrugBank database endowed by multi-targeting profile, are also reported. We specifically identified 14 promising compounds characterized by a good in silico binding affinity towards, at least, two of the four studied targets (viral and host proteins). Among which, ceftolozane and NADH showed the best multi-targeting profile, thus potentially reducing the emergence of resistant virus strains. We also focused on potentially novel pharmacological targets for the development of compounds with anti-pan coronavirus activity. Through the analysis of a large set of viral genomic sequences, the current review provides a comprehensive and specific map of conserved regions across human coronavirus proteins which are essential for virus replication and thus with no or very limited tendency to mutate. Hence, these represent key druggable targets for novel compounds against this virus family. In this respect, the identification of highly effective and innovative pharmacological strategies is of paramount importance for the treatment and/or prophylaxis of the current pandemic but potentially also for future and unavoidable outbreaks of human pathogenic coronaviruses.

Purpose: The cornea is the most significant refractive medium in the eye. Pathologies affecting the cornea usually have a great impact on vision. The etiology of corneal disorder varies from one geographical location to another. The objective of this study was to determine the pattern of corneal disorders at Ekiti State University Teaching Hospital, Ado-Ekiti. Materials and Methods: A retrospective study of case records of patients with cornea disorders over a 5-year period was carried out. Demographic characteristics, presenting visual acuity, and risk factor for cornea disorders were retrieved. Data were entered into the Statistical Package for the Social Sciences version 20, and statistical significance was inferred at P < 0.05. Results: Corneal disorders accounted for 3.3% of the eye disorders seen during the period of study. The median age was 37 years. Males outnumbered females giving a ratio of 1.9:1 and the age range from 0.25 to 92 years. There were more females than males in the 11–20 years’ age group. Students (84, 25.4%) and artisans (62, 18.8%) were the two leading occupational groups. Infectious cases constituted 27.2% of the cases. Visual acuity at presentation was

We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.

Samira Ben-Menni Schuler was granted a predoctoral grant (F.P.U. program) from the Spanish Government. Hammadi Hamza was granted by a postdoctoral fellowship (Erasmus Mundus-Al Idrisi II scholarship) from the European Union. The authors thank all those people and institutions that facilitated or helped in the collection of samples (in alphabetical order: angel Banares, Antonio Delgado, Brother Anthony, Government of Ireland, Elizabeth Ojeda, Emer Ni Dhuill, Gobierno de Canarias, Ibai Olariaga-Ibarguren, Inaki Sanz-Azkue, Junta de Andalucia, Kristyna Hanuova, Miguel Perez-Gutierrez, Parque Nacional de Garajonay, Ranger Brian Duffy, Sito Chinea, Yves Krippel). We also thank Ana Garcia-Garcia for technical assistance in SDM analysis. This research was funded by the Regional Andalusian Government, grant number P10-RNM-6198., Fern phylogeographic studies have mostly focused on the influence of the Pleistocene climate on fern distributions and the prevalence of long-distance dispersal. The effect of pre-Pleistocene events on the distributions of fern species is largely unexplored. Here, we elucidate a hypothetical scenario for the evolutionary history of Vandenboschia speciosa, hypothesised to be of Tertiary palaeotropical flora with a peculiar perennial gametophyte. We sequenced 40 populations across the species range in one plastid region and two variants of the nuclear gapCp gene and conducted time-calibrated phylogenetic, phylogeographical, and species distribution modelling analyses. Vandenboschia speciosa is an allopolyploid and had a Tertiary origin. Late Miocene aridification possibly caused the long persistence in independent refugia on the Eurosiberian Atlantic and Mediterranean coasts, with the independent evolution of gene pools resulting in two evolutionary units. The Cantabrian Cornice, a major refugium, could also be a secondary contact zone during Quaternary glacial cycles. Central European populations resulted from multiple post-glacial, long-distance dispersals. Vandenboschia speciosa reached Macaronesia during the Pliocene–Pleistocene, with a phylogeographical link between the Canary Islands, Madeira, and southern Iberia, and between the Azores and northwestern Europe. Our results support the idea that the geological and climate events of the Late Miocene/Early Pliocene shifted Tertiary fern distribution patterns in Europe., Spanish Government European Commission, (Erasmus Mundus-Al Idrisi II scholarship) from the European Union - Regional Andalusian Government P10-RNM-6198

The photosynthesis machinery in chloroplast thylakoid membranes is comprised of multiple protein complexes and supercomplexes(1,2). Here, we show a novel supramolecular organization of photosystem I (PSI) in the moss Physcomitrella patens by single-particle cryo-electron microscopy. The moss-specific light-harvesting complex (LHC) protein Lhcb9 is involved in this PSI supercomplex, which has been shown to have a molecular density similar to that of the green alga Chlamydomonas reinhardtii(3). Our results show that the structural organization is unexpectedly different—two rows of the LHCI belt exist as in C. reinhardtii(4), but the outer one is shifted toward the PsaK side. Furthermore, one trimeric LHC protein and one monomeric LHC protein position alongside PsaL/K, filling the gap between these subunits and the outer LHCI belt. We provide evidence showing that Lhcb9 is a key factor, acting as a linkage between the PSI core and the outer LHCI belt to form the unique supramolecular organization of the PSI supercomplex in P. patens.

Heavy oil and bitumens have been exploited in Italy during the past, in particular over the Maiella Mountain’s northwest flank (Central Italy), where relatively undeformed, hydrocarbon-bearing carbonate-ramp reservoirs of the Bolognano Formation crop out. These reservoirs represent the exhumed analog of a wider petroleum system that has been investigated also in the subsurface by exploration activities, both onshore and offshore (Central Adriatic). Here we present, for the first time, a historical data set composed of 180 shallow wells drilled over the area in 1942 by a company named Azienda Lavorazione Bitumi Asfalti; we digitally reconstructed this data set, integrating it with field observations, laboratory measurements, and thin-section analysis. Using Petrel (mark of Schlumberger) three-dimensional software, we modeled the reservoir and the hydrocarbon distribution, also calculating volumes of hydrocarbons in place. In our work, we demonstrate the presence of these quite homogeneous, porous carbonate reservoirs over the whole region, and we identify internal reservoir geometries characterized by clinoforms, likely resulting from a large-scale depositional cross-bedding and progradation. We also infer a different function of faults in the hydrocarbon accumulations: major faults were able to create independent compartments during migration, whereas minor, more recent elements did not control hydrocarbon accumulation, likely postdating a main lower-Pliocene migration phase. We believe that the observations derived from our work can represent a good analog for carbonate-ramp reservoirs elsewhere, may help in identifying appropriate modeling solutions, and can be used as calibration for future renewed exploration efforts in the region, both onshore and offshore.

The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE) 30 nM and activating at (IDE) 30 nM. Only an activating effect is observed in a yeast mutant locked in the "open" conformation (i.e., the alpha-3 Delta N 20S), envisaging a possible role of IDE as modulator of the 20S "open"-"closed" allosteric equilibrium. Protein-protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S alpha-3 subunit which regulates the gate opening of the 20S.

For many decades, there has been speculation about when the Alpine Fault first became a major regional structure. This paper presents a summary of recently published data, especially U–Pb ages, tha...

La zona metropolitana del Valle de México ocupa el territorio de tres entidades federales: Distrito Federal, Estado de México, e Hidalgo, lo que hace que sea difícil un Planea miento conjunto. Para entender cómo es este territorio se parte de un encuadre histórico de la zona. Se explican los problemas que ha sufrido su economía con la desindustrialización, lo que ha dado lugar a una especialización terciaria de la ciudad con dos sectores: formal, e informal, que absorbe el desempleo del primero, pero genera pobreza, delincuencia y diferenciación zonal de la ciudad., The metropolitan zone in the Mexico Valley settles the territory of three federal organizations: Federal District, State of Mexico, and Hidalgo, which causes difficulties to make a joint Planning. In order to understand how this territory is, an historical frame of the zone is related. The problems that its economy has suffered by the disindustrialization are explained. It has caused to a tertiary specialization of the city in two sectors: formal, and informal. The informal sector absorbs the unemployment of informal, but that generates poverty, delinquency and zonal differentiation of the city

The aim of the study was to investigate the effect of Task Base Language Teaching (TBLT) on tertiary ESOL learners’ academic writing achievement in tertiary level. Therefore, the experimental research was applied to this study. The control group was taught through Classical Method (CM) while the experiment group was taught through Task Based Language Teaching (TBLT) method. Furthermore, the pre-test and post-test were administered to students in control group and experiment group (30 students in each group). The data were tabulated by employing t-test in Statistical Package for Social Science (SPSS) version 21. Based on the data analysis, the result indicated that the null hypothesis (Ho) was rejected and the alternative hypothesis (Ha) was accepted. It can be concluded that there was a significant effect of Task Based Language Teaching (TBLT) method on tertiary ESOL learners’ writing achievement compared to Classical Method (CM) of teaching.

The interactome of arzanol was investigated by MS-based chemical proteomics, a pioneering technology for small molecule target discovery. Brain glycogen phosphorylase (bGP), a key regulator of glucose metabolism so far refractory to small molecule modulation, was identified as the main high-affinity target of arzanol. Competitive affinity-based proteomics, DARTS, molecular docking, surface plasmon resonance and in vitro biological assays provided molecular mechanistic insights into the arzanol-enzyme interaction, qualifying this positive modulator of bGP for further studies in the realm of neurodegeneration and cancer.

The beetle family Ptilodactylidae contains more than 500 extant species, however, its fossil record is scarce and remains understudied. In this study, we describe a new species of Ptilodactylidae, Ptilodactyla eocenica Kundrata, Bukejs and Blank, sp. nov., based on a relatively well-preserved specimen from Baltic amber. We use X-ray microcomputed tomography to reconstruct its morphology since some of the principal diagnostic characters have been obscured by opaque bubbles. It is the third ptilodactylid species described from Baltic amber, and the first one belonging to the subfamily Ptilodactylinae. Additionally, we summarize the classification, diversity, and distribution of both extinct and extant Ptilodactylidae.

Khabbaz oilfield has a symmetrical subsurface anticline with a length of 20 km and a width of 4 km. Despite the fact that Khabbaz oilfield has a small size structure, it is known as one of the massive Oilfields in Iraq. The reservoirs of Khabbaz oilfield are produced by both Cretaceous and Tertiary rocks. The Upper Qamchuqa reservoir is the most productive reservoir of the Khabbaz oilfield with thickness ranges between 138 to 170 m. This formation is subdivided into two units, from the top is Unit A with a thickness of 67 m and from the bottom is Unit B with a thickness of 84.5 m. From a full set of log data of three wells (Kz-1, Kz-13 and Kz-14), the petrophysical properties of Khabbaz oilfield has been evaluated. The wireline log data includes gamma-ray log, sonic log, neutron log, density log and resistivity logs, both Rxo and Rt logs. This study revealed that Unit A represents the best reservoir characteristics where Unit A is subdivided into six reservoir subunits named (1-A, 2-A, 3-A, 4-A, 5-A and 6-A). They are separated by five non-reservoir subunits named 1-N, 2-N, 3-N, 4-N and 5-N. In addition to a less porous reservoir unit that is called Unit B, which has been divided into four reservoir subunits named 1-B, 2-B, 3-B and 4-B. These are separated by five non-reservoir units named 1-N, 2-N, 3-N, 4-N and 5-N. It has been recognized that both reservoir units A and B are clean formations and have minimum shale volume with high porosity in limestone and dolomite to dolomitic limestone lithology with high oil saturation and low water saturation. Based on the above reservoir characteristics it can be concluded that the reservoir units of the Khabbaz oilfield contain a massive commercial hydrocarbon accumulation.