Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of 2G12 Fab2 in Complex with Soluble and Fully Glycosylated HIV-1 Env by Negative-Stain Single-Particle Electron Microscopy

ABSTRACT The neutralizing anti-HIV-1 antibody 2G12 is of particular interest due to the sterilizing protection it provides from viral challenge in animal models. 2G12 is a unique, domain-exchanged antibody that binds exclusively to conserved N-linked glycans that form the high-mannose patch on the gp120 outer domain centered on a glycan at position N332. Several glycans in and around the 2G12 epitope have been shown to interact with other potent, broadly neutralizing antibodies; therefore, this region constitutes a supersite of vulnerability on gp120. While crystal structures of 2G12 and 2G12 bound to high-mannose glycans have been solved, no structural information that describes the interaction of 2G12 with gp120 or the Env trimer is available. Here, we present a negative-stain single-particle electron microscopy reconstruction of 2G12 Fab2 in complex with a soluble, trimeric Env at ∼17-Å resolution that reveals the antibody's interaction with its native and fully glycosylated epitope. We also mapped relevant glycans in this epitope by fitting high-resolution crystal structures and by performing neutralization assays of glycan knockouts. In addition, a reconstruction at ∼26 Å of the ternary complex formed by 2G12 Fab2, soluble CD4, and Env indicates that 2G12 may block membrane fusion by induced steric hindrance upon primary receptor binding, thereby abrogating Env's interaction with coreceptor(s). These structures provide a basis for understanding 2G12 binding and neutralization, and our low-resolution model and glycan assignments provide a basis for higher-resolution studies to determine the molecular nature of the 2G12 epitope. IMPORTANCE HIV-1 is a human virus that results in the deaths of millions of people around the world each year. While there are several effective therapeutics available to prolong life, a vaccine is the best long-term solution for curbing this global epidemic. Here, we present structural data that reveal the viral binding site of one of the first HIV-1-neutralizing antibodies isolated, 2G12, and provide a rationale for its effectiveness. These structures provide a basis for higher-resolution studies to determine the molecular nature of the 2G12 epitope, which will aid in vaccine design and antibody-based therapies.
Geldpolitik in einer real divergierenden Währungsunion: Ein kritischer Blick auf die „Performance“ der EZB

1 Einführung | 35 2 Externe Faktoren: eine Lanze für die Europäische Zentralbank? | 36 3 Performance der EZB – Wasser in den Wein | 40 3.1 Makroökonomische Kriterien – Inflation und Wirtschaftswachstum | 40 3.2 Risiken der Geldpolitik der EZB für die Finanzstabilität | 47 3.3 Mangelnde Effektivität der unkonventionellen Geldpolitik | 48 3.4 Rechtliche Probleme der unkonventionellen Geldpolitik | 49 3.5 Gleichgewichtige Realzinsen und säkulare Stagnation | 50 3.6 Ausstieg aus unkonventioneller Geldpolitik dringend angezeigt | 51 3.7 Unbestimmtes „counterfactual“ | 54 3.8 Internationale Übertragungseffekte der Geldpolitik | 55 3.9 „Trump“ – Ein Problem für die EZB | 55 3.10 Der „Two-handed approach“ als Leitbild makroökonomischer EU-Governance | 56 3.11 Die Eurozone in der Target-Falle | 57 3.12 Zwischenfazit | 58 4 Ausblick und ordnungspolitische Implikationen | 58
The development of anger management program based on acceptance and commitment therapy for youth taekwondo players

This study aimed to develop an intervention program based on acceptance and commitment therapy (ACT) for youth taekwondo players. Eight sessions of the ACT program were provided to nine youth taekwondo players. The content analysis was conducted for the activities, activity sheets, assignments, and program evaluations. First of all, the results showed that the ACT program changed the participants’ diverse psychological inflexibility a flexible and value-oriented state, which was supported by their positive mood changes after each session. Secondly, ‘walking meditation,’ ‘a bus driver and a passenger role play,’ and ‘writing a letter to the self’ were positively evaluated according to the analysis on the feedbacks and evaluations on each session and activity. Lastly, overall evaluation on the ACT program indicated that there were changes in a positive attitude, thoughts, and feelings (anger and irritation) toward taekwondo. The most memorable activities were ‘eating meditation,’ ‘breath-counting meditation,’ and ‘welcoming the beggar’ exercise. These results suggest that an intervention program based on the ACT may have a positive impact on anger management for youth.
A 32-bit RISC-V AXI4-lite bus-based microcontroller with 10-bit SAR ADC

In this paper a complete implementation and design of a fully-synthesized 32-bit microcontroller in a 130nm CMOS technology is presented. This is the first microcontroller featuring the open source RISC-V instruction set all mounted through AXI4-Lite and APB buses for communication process. The microcontroller contains a 10-bit SAR ADC, a 12-bit DAC, an 8-bit GPIO module, a 4kB-RAM, an SPI AXI slave interface for output verification, and an SPI APB slave interface for checking the correct behavioral of the APB bridge. All peripherals are controlled by a RISC-V and an SPI AXI master interface that is used for programming the device and checking the data flowing through all the slaves. A total power density is reported as 167μW/MHz and the area for this RISC-V microcontroller has a reduced footprint of 798μm×484μm.
Matrix converter two-step commutation method limitations

The paper describes the basic knowledge about the matrix converter two-step commutation method that was realized on our department. This commutation strategy was implemented in VHDL for FPGA and was simulated in Simulink/Modelsim (cosimulation). The new developed two-step commutation method is two-time faster than the formerly implemented four-step commutation method. But the cosimulation in MatLab and Modelsim has proved that it includes some limitations not respected in theoretical analysis.
Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2.

INTRODUCTION Episodic ataxias (EAs) are rare dominantly inherited neurological disorders characterized by recurrent episodes of ataxia lasting minutes to hours. The most common subtype is EA type 2 (EA2) caused by pathogenic variants of calcium voltage-gated channel subunit alpha1 A gene (CACNA1A) on chromosome 19p13. SUBJECTS AND METHODS We examined a Slovak three-generation family. Genomic DNA of the family members was extracted from peripheral blood and amplified by polymerase chain reaction. CACNA1A variants were screened by Sanger sequencing. RESULTS We identified four family members with recurrent episodes of ataxia. Complex differential diagnosis was performed. Genetic analysis with direct sequencing revealed a novel heterozygous variant of CACNA1A - c.5264A>G (p.Glu1755Gly) located in the pore loop of domain IV of calcium channel alpha-1A subunit. CONCLUSION We identified a novel missense variant of a voltage-dependent P/Q-type calcium channel alpha-1A subunit in a Slovak three-generation family with recurrent episodes of ataxia. The heterozygous missense variant resulted in changing a highly conserved glutamic acid within the pore loop of domain IV.
Effect of finishing and polishing procedures on surface roughness, gloss and color of resin-based composites.

PURPOSE To evaluate the effects of different finishing and polishing procedures on surface roughness, gloss and color of five resin composites: two experimental microhybrid composites - FZ-Dentin (FZD) and FZ-Enamel (FZE), one commercial microhybrid composite - Esthet-X (EX), and two microfilled composites - Heliomolar (HM) and Renamel Microfill (RM). METHODS Surface roughness, gloss and color of the disc-shaped specimens (10 mm in diameter and 2-mm thick) were measured as Mylar (baseline), 16-fluted carbide bur and polishing were completed. Sixteen specimens of each composite were randomized to four groups of four. After finishing with a 16-fluted finishing bur, each group was polished by a different system: 1. Astropol (A), 2. Sof-lex disc (S), 3. Po-Go (P), 4. Enhance (E). Average surface roughness (Ra) was measured with a profilometer. Gloss measurements were performed using small-area glossmeter, while color coordinate values were recorded using a spectrophotometer. A deltaE*ab< or =1 was considered to be the limit of perceptibility. RESULTS The order of surface roughness ranked according to polishing system (for all five composites together) was: P < S < E < A. The order of surface roughness ranked according to composites was: RM < FZD < FZ < HM < EX. The order of gloss ranked according to polishing system (for all five composites together) was: P > E > A > S. The order of gloss values for the polished composites (for each of four polishing systems) was: RM > FZD > FZE > HM > EX. Fisher's PLSD intervals at the 0.05 level of significance for comparisons of means of surface roughness among five composites and four polishing systems were 0.01 and 0.01 microm, respectively. Fisher's PLSD intervals at the 0.05 level of significance for comparisons of means of gloss among five composites and four polishing systems were 6 and 5 GU, respectively. Color differences (deltaE*ab) among five composites and four polishing methods were found to range from 0.2 to 1.1.
Herpes zoster: an early manifestation of HIV infection.

Herpes zoster, also known as shingles, is a reactivation of a previous infection with the herpes varicella-zoster virus. A person's first encounter with the virus causes chicken pox, usually in children. Once the chicken pox has healed, the virus remains in the posterior root ganglion of the spinal cord for the rest of the person's life. If a person's immunity is reduced for any reason, the virus can be reactivated, travel down one of the sensory nerves to the skin and cause herpes zoster. Herpes zoster cannot be contracted from someone who has it, for the infection always comes from one's own spinal cord. However, chicken pox can be caught from someone with herpes zoster. Before signs of herpes zoster become apparent on the skin, there is pain along the course of one of the sensory nerves of the skin. A rash then appears 2-3 days later, beginning with grouped vesicles either confined to 1 dermatome or spread over 2 adjacent dermatomes. The vesicles will later crust over before healing in 3-4 weeks. The rash remains painful until it has healed. Herpes zoster-related problems at the eye, tongue, chest and abdomen, and bladder and bowel are noted. In Africa, the presentation of a patient with herpes zoster should always lead the clinician to suspect HIV infection, for since the beginning of the AIDS pandemic, herpes zoster has often been the first manifestation of HIV infection. Various treatments with analgesics and topical and antiretroviral agents are described.
Testosterone Induction of Male-like Vocalizations in Female Budgerigars (Melopsittacus undulatus)

Budgerigars possess a complex learned vocal repertoire that includes a long rambling song called warble. While both males and females can warble, there are marked sex differences in the amount of song produced. Males generally warble daily at a high rate, while females rarely sing. Both the quantity and the quality of male warble are influenced by circulating levels of testosterone. Males have higher circulating levels of testosterone than females. In this study we asked whether administering testosterone to adult female budgerigars would activate male-like vocal behavior. Four females were implanted with 8-mm Silastic implants filled with testosterone and recorded before and after implantation. Within 10-14 days, all four birds showed: (1) changes in there color to the male-like condition (blue), (2) male-typical patterns of precopulatory behavior, and (3) an increase in their rate of warbling to male-like levels. Sound analysis revealed that the acoustic structure of the testosterone-induced female warble is similar to the male warble. These data indicate that sex differences in budgerigar vocal behavior are not based on early organizational effects of steroid hormones, but rather are probably the result of adult sex differences in circulating testosterone levels.
Bacteria Inhibit Biosynthesis of Bone Matrix Proteins in Human Osteoblasts

The effect of extracts from Staphylococcus aureus and Staphylococcus epidermidis on bone matrix production were assessed by analyzing the biosynthesis of osteocalcin and Type I collagen in a human osteoblastic osteosarcoma cell line (MG-63). In MG-63 cells, extracts from Staphylococcus aureus and Staphylococcus epidermidis decreased 1,25(OH)2-vitamin D3 stimulated osteocalcin biosynthesis, and insulinlike growth factor I induced production of Type I collagen in a concentration dependent manner. The basal rate of osteocalcin and Type I collagen formation was unaffected by the bacterial extracts. The inhibitory effect of the bacteria on osteocalcin biosynthesis was seen after 24 hours of treatment and was maintained for at least 96 hours. The extracts of Staphylococcus aureus and Staphylococcus epidermidis enhanced prostaglandin E2 formation in the MG-63 cells. Abolition of the prostaglandin E2 response by treatment with indomethacin and flurbiprofen did not affect bacteria induced inhibition of osteocalcin production. Stimulation of osteocalcin biosynthesis by 1,25(OH)2-vitamin D3 was associated with a decreased rate of cell proliferation. The inhibitory action of the bacterial extracts was not linked to any inhibition of [3H]-thymidine incorporation into deoxyribonucleic acid. These data show that extracts of Staphylococcus aureus and Staphylococcus epidermidis have the ability to inhibit the biosynthesis of bone matrix proteins by a nonprostaglandin and noncytotoxic dependent mechanism and suggest that bone loss in inflammatory processes containing Staphylococcus aureus or Staphylococcus epidermidis may not be caused only by enhanced bone resorption but also by decreased bone formation.
Frequency-Reconfigurable Microstrip Patch-Slot Antenna

A frequency-reconfigurable microstrip patch switchable to slot antenna is proposed. The antenna is capable of frequency switching at nine different frequency bands between 1.98 and 3.59 GHz. The patch is resonating at 3.59 GHz, while the slot produces eight different operating frequencies between 1.98 and 3.41 GHz. Five RF p-i-n diode switches are positioned in the slot to achieve frequency reconfigurability. Simulated and measured results are used to demonstrate the performance of the antenna. The simulated and measured return losses, together with the radiation patterns, are presented.
HTLV-1 inserts an ectopic CTCF-binding site into the human genome

Significance The retrovirus human T-lymphotropic virus type 1 (HTLV-1) causes inflammatory and malignant diseases in humans. To maintain latency and avoid immune detection in vivo, HTLV-1 minimizes expression of genes on the plus-strand of the integrated provirus but allows constitutive expression of the minus-strand gene, which maintains clonal persistence. It is not understood how this gene expression is regulated. We show that CTCF, a master regulator of chromatin structure and gene expression, binds to HTLV-1, forms loops between the provirus and host genome, and alters expression of proviral and host genes. Because a typical HTLV-1–infected host carries >104 infected T-cell clones, each containing a provirus integrated in a different genomic site, CTCF binding gives HTLV-1 the potential to cause widespread abnormalities in the human genome. Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes malignant and inflammatory diseases in ∼10% of infected people. A typical host has between 104 and 105 clones of HTLV-1–infected T lymphocytes, each clone distinguished by the genomic integration site of the single-copy HTLV-1 provirus. The HTLV-1 bZIP (HBZ) factor gene is constitutively expressed from the minus strand of the provirus, whereas plus-strand expression, required for viral propagation to uninfected cells, is suppressed or intermittent in vivo, allowing escape from host immune surveillance. It remains unknown what regulates this pattern of proviral transcription and latency. Here, we show that CTCF, a key regulator of chromatin structure and function, binds to the provirus at a sharp border in epigenetic modifications in the pX region of the HTLV-1 provirus in T cells naturally infected with HTLV-1. CTCF is a zinc-finger protein that binds to an insulator region in genomic DNA and plays a fundamental role in controlling higher order chromatin structure and gene expression in vertebrate cells. We show that CTCF bound to HTLV-1 acts as an enhancer blocker, regulates HTLV-1 mRNA splicing, and forms long-distance interactions with flanking host chromatin. CTCF-binding sites (CTCF-BSs) have been propagated throughout the genome by transposons in certain primate lineages, but CTCF binding has not previously been described in present-day exogenous retroviruses. The presence of an ectopic CTCF-BS introduced by the retrovirus in tens of thousands of genomic locations has the potential to cause widespread abnormalities in host cell chromatin structure and gene expression.
Consequences of the inhibition of Hdm2 expression in human osteosarcoma cells using antisense oligonucleotides.

The present study was performed to identify a potent and sequence-specific antisense oligonucleotide (ASO), to inhibit Hdm2 expression in human cancer cell lines and to study the downstream consequences. Ten chimeric 2'-O-methoxyethyl (MoE)-modified hemimers were synthesized that targeted various regions from the 5'- to the 3'-end of Hdm2 mRNA. The IC50 of the most potent ASO, NCH-4401, was subsequently determined and compared to the IC50 of a 2'-MoE-modified ASO, with a complete phosphorothioate backbone (NCH-4668), and to a 3 bp mismatched ASO (NCH4529). NCH4401 inhibited Hdm2 expression in SJSA-1 cells with an IC50 of 120 nm, whereas NCH-4668 was less potent with an IC50 of 180 nm. The mismatched control ASO was completely inactive, indicating a sequence-dependent mechanism of action of NCH-4401. NCH4401 was subsequently used to study the consequences of inhibiting Hdm2 expression in human osteosarcoma cells. NCH-4401 completely inhibited Hdm2 protein expression in SJSA-1 cells at a concentration of 300 nm, already 4 h after start of ASO treatment. At an ASO concentration of 300 nM, p53 protein was induced 12.5-fold and p21 was induced 8-fold over background levels, 24 h after start of ASO treatment. The dramatic induction of p53 in SJSA-1 cells prompted us to investigate whether the accumulation of p53 in these cells was followed by induction of apoptosis. However, no signs for apoptosis were detected in SJSA-1 cells, following induction of wild-type p53 using the Yopro method and the induction of caspase-3 activity. SJSA-1 cells were subsequently treated with NCH-4401 at different concentrations in combination with two well-known DNA-damaging agents, i.e. carboplatin and mitomycin C. Apoptosis induction following treatment of cells with DNA-damaging agents and NCH4401 was determined in parallel by measuring caspase-3 activation and uptake of the DNA dye Yopro. Carboplatin and mitomycin C together only slightly induced apoptosis in SJSA-1 cells to a factor of approximately 2-fold, as measured by the induction of caspase-3 activity. The downregulation of Hdm2 expression by NCH4401 did not induce apoptosis on its own and did not potentiate the mitomycin C/carboplatin-induced programmed cell death.
Portugol IDE v3.x: A new environment to teach and learn computer programming

Teaching of programming is crucial in every engineering course and particularly in computer courses. Students failure in this domain has led to the development of Portugol IDE, a tool for teaching/learning algorithms. This tool allows algorithms to be coded in mother tongue of portuguese students (portugol) or in flow diagrammatic language (flowchart) and its automatic execution. This paper presents generation 3.x of this tool and describes the advancements therein.
Enrollment without Learning: Teacher Effort, Knowledge, and Skill in Primary Schools in Africa

School enrollment has universally increased over the last 25 years in low-income countries. Enrolling in school, however, does not assure that children learn. A large share of children in low-income countries complete their primary education lacking even basic reading, writing, and arithmetic skills. Teacher quality is a key determinant of student learning, but not much is known about teacher quality in low-income countries. This paper discusses an ongoing research program intended to help fill this void. We use data collected through direct observations, unannounced visits, and tests from primary schools in seven sub-Saharan African countries to answer three questions: How much do teachers teach? What do teachers know? How well do teachers teach?
Making Sense of Risk: An Interpretative Phenomenological Analysis of Vulnerability to Heart Disease

This study investigates perceptions of familial hypercholesterolaemia (FH) and its genetic basis in patients diagnosed with, and receiving treatment for, FH. Semi-structured interviews were conducted with seven patients. Transcripts were analysed using interpretative phenomenological analysis (IPA). Participants reported engaging in an active process of seeking causes for their FH. FH was invariably attributed to genes. In some cases diet and stress were also considered as causes of FH. Causal attributions appear to be both a determinant and a result of behavioural strategies to reduce risk. On the whole, FH was perceived as unproblematic, a perception that appeared to reflect downward social comparison processes. Nonetheless, participants reported acting in ways consonant with the perception of an increased risk of heart attack, in particular, being vigilant to symptoms of a possible heart attack.
Laser ablated 48 GHz ZOR CRLH antenna on alumina substrate

The paper presents a zeroth order resonance (ZOR) Composite Right / Left-Handed (CRLH) coplanar waveguide (CPW) antenna on AlSiMag 614 alumina substrate. The device was designed, microprocessed by laser ablation and tested for millimeter wave frequency range (48 GHz). Experimental results for two antenna samples show return loss of -21.98 dB at 48.01 GHz and -20.42 dB at 48.17 GHz respectively. The -3 dB beamwidth of the transversal radiation lobe for two antenna samples are 57° and 54°, respectively. The gain measured at 48 GHz using the De Friis method was 8.98 dBi.
Axonal Target Choice and Dendritic Development of Ferret Beta Retinal Ganglion Cells

We have investigated the relationship between axon targeting and dendritic morphology in beta retinal ganglion cells in the postnatal ferret. Axonal projections were assessed by making separate injections of different fluorescent retrograde tracers into either the superior colliculus or lateral geniculate nucleus in viva The dendritic morphology of retrogradely labelled cells was revealed by the in vitro intracellular injection of Lucifer yellow in fixed retina. In this way, 405 retinal ganglion cells were triple‐ or double‐labelled and characterized by their dendritic branching styles. Both the distinct dendritic morphology of beta cells and the characteristic restriction of their adult axonal terminals to the lateral geniculate nucleus emerge postnatally. Beta cell dendritic morphology is established between postnatal days 5 and 9. As in the cat (Ramoa et al, 1989), beta cells extend and then retract a projection to the superior colliculus as part of their normal development. Transient beta axonal collaterals to the superior colliculus persist beyond the period of cell death, but nearly all are withdrawn by postnatal day 15. No dendritically distinct beta cell projects to the superior colliculus alone, at any age.