Miracle-dz/UniFAR-FTUs huggingface dataset:
ADP-ribosylation factor 6 regulates insulin secretion through plasma membrane phosphatidylinositol 4,5-bisphosphate

ADP-ribosylation factor 6 (ARF6) is a small GTP-binding protein that regulates peripheral vesicular trafficking and actin cytoskeletal dynamics, and it has been implicated as critical to regulated secretion. Expression of a dominant-inhibitory ARF6 mutant, ARF6(T27N), impaired glucose-, depolarization-, and γ-thio-GTP-stimulated insulin secretion in the pancreatic β cell line, MIN6. In response to depolarization, MIN6 cells expressing ARF6(T27N) displayed an unaltered initial fast phase but an impaired subsequent slow phase of insulin secretion. Actin cytoskeletal disassembly with latrunculin A enhanced insulin secretion, whereas stabilization with jasplakinolide inhibited secretion, consistent with the actin cytoskeleton serving as a barrier to exocytosis in these cells. ARF6(T27N) led to a depolarization-dependent reduction in the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] with a time course that paralleled the inhibition of secretion. Moreover, blockade of PI(4,5)P2-dependent events by expression of a lipid-binding protein resulted in inhibition of depolarization-induced secretion in a manner identical to ARF6(T27N). These results indicate that ARF6 is required to sustain adequate levels of PI(4,5)P2 during periods of increased PI(4,5)P2 metabolism such as regulated secretion.
Neoadjuvant chemo-irradiation in un-resectable carcinoma of rectum.

BACKGROUND Rectal cancer is one of the most frequent gastrointestinal cancers. Conventionally surgery is the mainstay of treatment, however after surgery alone, local recurrence is high especially in locally advanced rectal cancer, i.e. tethered and fixed rectal cancer. This study was conducted to determine the role of neo-adjuvant (pre-operative) chemoirradiation in locally advanced carcinoma of the rectum to improve resectability, local control and survival. METHODS Study was conducted in Radiation Oncology department of Shaukat Khanum Memorial Cancer Hospital and Research Center from May 97-Oct 99. Thirteen patients with unresectable/locally advanced adenocarcinoma rectum received neo-adjuvant chemoirradiation, 50 Gray to pelvis by box technique on Cobalt-60 machine with concomitant 5-Flurouracil 500 mg/m2 for first three and last three days followed by abdomino-perineal/low anterior resection. RESULTS Neo-adjuvant chemoirradiation resulted in resectability rate of 92% and clinical down staging in 11/13 (84%) patients and pathological complete response in 2/13 (15%) patients and a local recurrence rate of 2/13 (15.38%). Non hematological toxicity (diarrhea grade 4--15%, erythema grade 3--23%, dysuria grade 1-2--38%) were main problems observed during neo-adjuvant chemoirradition. CONCLUSION Concomitant preoperative chemoirradiation for locally advanced rectal cancer is associated with considerable clinical and pathological down staging. Tumor resectability is improved with potential for improved local control and is relatively safe with acceptable morbidity.
Iterative deconvolution of simultaneous dual radionuclide projections for CdZnTe based cardiac SPECT

We propose a method of separating primary 99mTc and 201Tl photons in projections acquired on a SPECT camera based on CdZnTe detectors during a simultaneous dual radionuclide rest-stress myocardial perfusion scan. The method is based on a model of spectral and spatial distribution of counts in the measured projections. We use the Maximum Likelihood Expectation Maximisation (ML-EM) iterative algorithm to solve the model equations for the pure primary counts. The deconvolved primary count projections are then reconstructed using the standard OSEM algorithm. Considerable improvement of defect contrast can be observed in anthropomorphic phantom scans.
Isolated pseudo–RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition

Significance Serine/arginine (SR) proteins are key regulators of eukaryotic gene expression and have been associated with multiple human diseases including cancers. Several members of this protein family contain a noncanonical RNA recognition motif (RRM), the pseudo-RRM, for which the mode of RNA recognition is unknown. Here, we solved the structure of SRSF1 pseudo-RRM bound to RNA. It reveals the RNA motif recognized and a very unusual mode of interaction, which is conserved for all the SR proteins containing pseudo-RRMs. Finally, we show that the pseudo-RRM in isolation often is sufficient to regulate splicing, and we reveal its mechanism of action. Serine/arginine (SR) proteins, one of the major families of alternative-splicing regulators in Eukarya, have two types of RNA-recognition motifs (RRMs): a canonical RRM and a pseudo-RRM. Although pseudo-RRMs are crucial for activity of SR proteins, their mode of action was unknown. By solving the structure of the human SRSF1 pseudo-RRM bound to RNA, we discovered a very unusual and sequence-specific RNA-binding mode that is centered on one α-helix and does not involve the β-sheet surface, which typically mediates RNA binding by RRMs. Remarkably, this mode of binding is conserved in all pseudo-RRMs tested. Furthermore, the isolated pseudo-RRM is sufficient to regulate splicing of about half of the SRSF1 target genes tested, and the bound α-helix is a pivotal element for this function. Our results strongly suggest that SR proteins with a pseudo-RRM frequently regulate splicing by competing with, rather than recruiting, spliceosome components, using solely this unusual RRM.
Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts

Secreted PCSK9 binds to cell surface LDL receptor (LDLR) and directs the receptor for lysosomal degradation. PCSK9 is potent at inducing LDLR degradation in cultured liver-derived cells, but it is considerably less active in immortalized fibroblasts. We examined PCSK9 trafficking in SV-589 human skin fibroblasts incubated with purified recombinant wild-type PCSK9 or gain-of-function mutant PCSK9-D374Y with increased LDLR binding affinity. Despite LDLR-dependent PCSK9 uptake, cell surface LDLR levels in SV-589 fibroblasts were only modestly reduced by wild-type PCSK9, even at high nonphysiological concentrations (20 µg/ml). Internalized 125I-labeled wild-type PCSK9 underwent lysosomal degradation at high levels, indicating its dissociation from recycling LDLRs. PCSK9-D374Y (2 µg/ml) reduced cell surface LDLRs by approximately 50%, but this effect was still blunted compared with HepG2 hepatoma cells. Radioiodinated PCSK9-D374Y was degraded less efficiently in SV-589 fibroblasts, and Alexa488-labeled PCSK9-D374Y trafficked to both lysosomes and endocytic recycling compartments. Endocytic recycling assays showed that more than 50% of internalized PCSK9-D374Y recycled to the cell surface compared with less than 10% for wild-type PCSK9. These data support that wild-type PCSK9 readily dissociates from the LDLR within early endosomes of SV-589 fibroblasts, contributing to PCSK9-resistance. Although a large proportion of gain-of-function PCSK9-D374Y remains bound to LDLR in these cells, degradative activity is still diminished.
Antimurine antibody formation following OKT3 therapy.

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants. (ABSTRACT TRUNCATED AT 400 WORDS)
[Polish version of the Groningen Social Disabilities Schedule II (GSDS II)--assessment of validity].

INTRODUCTION Precise and adequate assessment of social functioning and disability is a subject of major interest and concern of the researchers. Until now, no instrument with confirmed psychometric properties was established as a supportive measure of disability in the framework of the rehabilitation process with the participation of the National Insurance Agency. A potentially useful instrument for this purpose is the Groningen Social Disabilities Schedule II (GSDSII). AIM Aim of the study was the evaluation of usefulness of the Polish version of GSDSII as a social disabilities measure in the population of psychiatric inpatients. METHOD 130 persons with a broad range of diagnoses (schizophrenia, mood disorders, anxiety disorders) were interviewed. For estimation of convergent validity, the following reference tools were selected: Global Assessment of Functioning (GAF), Social Assessment of Functioning scale (SOFAS), Global Assessment of Relational Functioning (GARF), World Health Organization Disability Assessment Schedule II (WHO-DASII). For criterion validity the Brief Psychiatric Rating Scale (BPRS) 24-item version was applied. RESULTS. The sufficient and good validity indices were obtained for concurrent validity of GSDSII. There was also a significant interrelation between psychopathology assessed with BPRS and disability measured by GSDSII. CONCLUSIONS Results allow for the supplication of the GSDSII in the research on psychosocial disability in Poland.
A pulse oximetry system with motion artifact reduction based on Fourier analysis

In this paper, a system that records photoplethysmography and performs motion artifact reduction is proposed. In order to calculate SpO2, accurate amplitude of PPG is essential. As a matter of fact that the PPG signal is acquired through an optical sensor, it is prone to be affected by motion artifact. As a result, noise cancellation is a major issue in the calculation of SpO2. In the calculation of SpO2, the exact waveform is not the key point, whereas the amplitude plays the important role. Therefore, Fourier analysis is adopted to perform the noise cancellation. In the proposed system, data acquisition and analog filtering are done on a printed circuit board which is controlled by an FPGA. The acquired data are sent to a computer, where Fourier analysis is done to cancel motion artifact. Experiments have been done to demonstrate the performance of the proposed algorithm. The proposed system performs PPG signal acquisition, motion artifact reduction and SpO2 calculation.
Evolutionary algorithm for a genetic robot’s personality

This paper proposes a new concept of the genetic robot which has its own robot genome, in which each chromosome consists of many genes that contribute to defining the robotpsilas personality. The large number of genes also allows for a highly complex system, however it becomes increasingly difficult and time-consuming to ensure reliability, variability and consistency for the robotpsilas personality while manually initializing values for the individual genes. To overcome this difficulty, this paper proposes an evolutionary algorithm for a genetic robotpsilas personality (EAGRP). EAGRP evolves a gene pool that customizes the robotpsilas genome so that it closely matches a simplified set of features desired by the user. It does this using several new techniques. It acts on a 2 dimensional individual upon which a new masking method, the Eliza-Meme scheme, is used to derive a plausible individual given the restricted preference settings desired by the user. The proposed crossover method allows reproduction for the 2-dimensional genome. Finally, the evaluation procedure for individuals is carried out in a virtual environment using tailored perception scenarios.
Power Allocation for SC-FDE-Based CR Systems Under Explicit Primary User Protection

In this letter, we consider the power allocation for a single-carrier (SC)-based secondary user (SU) transmitter (Tx), which transmits concurrently with an SC or multicarrier (MC) primary user (PU) over the same frequency band. A rate maximization problem for the SU system is formulated subject to an SU-Tx power constraint and an explicit rate loss constraint for the PU system. Due to the nonconvexity of the resulting problem, we propose a successive convex approximation approach to solve the problem where in each iteration closed-form solutions are derived for the power allocation variables of the SU-Tx. We further prove that the proposed algorithm is guaranteed to converge to a local optimum of the original nonconvex problem. Simulation results are provided to show the efficacy of the proposed approach.
Structural and functional alterations in the β2‐adrenoceptor are caused by a point mutation in patients with atopic eczema

Abstract: The density of β2‐adrenoceptors is significantly decreased in both keratinocytes and peripheral blood lymphocytes from patients with atopic eczema. Furthermore both cell types showed a sixfold increase in the KD for the specific binding of the non‐specific antagonists (–)‐[3H]CGP 12177 and [125 I]CYP to keratinocytes and lymphocytes respectively compared with healthy controls. Based on these results polymorphism in the β2‐adrenoceptor gene was suspected. Consequently the entire intronless β2‐adrenoceptor gene was isolated from whole blood and by RT‐PCR from keratinocyte extracts of nine patients with atopic eczema and four healthy controls. DNA sequence analysis of nine atopic eczema patients confirmed a substitution in codon (1618) GCC (Ala119) to GAC (Asp119). This point mutation is expressed on the third transmembrane helix only 13Å away from the established agonist/antagonist binding site at Asp113. Computer modelling of this third transmembrane helix revealed substantial structural changes in the mutant compared with the wild type. Epidermal keratinocytes were established from one patient with atopic eczema (homozygote), the mother (heterozygote) and one age‐matched healthy control. Cells were grown in media containing different concentrations of l‐phenylalanine and receptor densities were determined. The results showed that cells with atopic eczema showed an increased sensitivity to l‐phenylalanine concentrations with a narrow homeostasis compared with healthy controls. The heterozygous mother was only 50% as sensitive as the child. In summary, the results indicate that atopic eczema is associated with a single point mutation in the β2‐adrenoceptor gene leading to an impaired adrenergic response in the epidermis of these patients.
A TELSA School Leaders’ Self-Assessment Application: A Case of Private Schools in Albania

Competition in private schooling of our fast changing and globalized world demands higher qualities, at least significant development, not to fall behind and consequently lose the challenge. Schools play a crucial role in everybody’s life and families demand better education and outcomes for their children’s future. School leaders are the ones who can lead the development by keeping in touch with improvements and (inter)national requirements of success. All developments start with assessing the current state and making plans accordingly. However, leaders should start assessment from themselves. Especially in last twenty years, there have been more efforts to set standards for school leadership, their professional assessment and development. Self-assessments are formative assessments which can help leaders to develop their leadership knowledge, skills and practice if necessary steps are taken. Training and Educational Leader Self-Assessment (TELSA) as a free and thrust-worthy assessment tool with various dimensions can serve for the purpose as it is used as a school leaders’ self-assessment tool in this research. The purpose of this research is to find out how school leaders in Albanian private schools assess themselves, their strongest and weakest leadership development fields. The research focuses on three subdivisions as gender, educational background and work experience to classify their strongest and weakest points from the point of self-development. The results provide some cautionary signals to remind the school leaders of modern-world leadership concepts and advances.
Real-Time 3D Ball Tracking with CPU-GPU Acceleration Using Particle Filter with Multi-command Queues and Stepped Parallelism Iteration

3D ball tracking is a critical function in manyapplications such as game and players behavior analysis, andreal time implementation has become increasingly importantfor it can be used for live broadcast and TV contents. To reacha high accuracy, algorithms usually are time consuming due toa large set of calculations which is challenging to meet realtime demanding. This paper proposes multiple commandqueues, tactical threads allocation and stepped iterativeaddition to empower such a capacity on the CPU-GPUplatform. Multiple command queues achieves a parallelismbetween tasks in the algorithm. Secondly, the tactical threadsallocation helps mapping the algorithm into GPU andenhances synchronism between threads. And this paperproposes stepped iterative addition to achieve partialparallelism in a sequential operation. This work implements inan Intel Core i7-6700 GPU and AMD Radeon R9 FURY GPU.Tracking speed of our work increases 37.8 times from original431ms to 11.7ms while the success rate of the algorithm retainsover 99%. This result fully meets the requirement of 16.6msper frame for 60fps video real-time tracking.
Using uterine activity to improve fetal heart rate variability analysis for detection of asphyxia during labor

During labor, uterine contractions can cause temporary oxygen deficiency for the fetus. In case of severe and prolonged oxygen deficiency this can lead to asphyxia. The currently used technique for detection of asphyxia, cardiotocography (CTG), suffers from a low specificity. Recent studies suggest that analysis of fetal heart rate variability (HRV) in addition to CTG can provide information on fetal distress. However, interpretation of fetal HRV during labor is difficult due to the influence of uterine contractions on fetal HRV. The aim of this study is therefore to investigate whether HRV features differ during contraction and rest periods, and whether these differences can improve the detection of asphyxia. To this end, a case-control study was performed, using 14 cases with asphyxia that were matched with 14 healthy fetuses. We did not find significant differences for individual HRV features when calculated over the fetal heart rate without separating contractions and rest periods (p > 0.30 for all HRV features). Separating contractions from rest periods did result in a significant difference. In particular the ratio between HRV features calculated during and outside contractions can improve discrimination between fetuses with and without asphyxia (p < 0.04 for three out of four ratio HRV features that were studied in this paper).
Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.
Calcium-dependent Modulation of Poly(ADP-ribose) Polymerase-1 Alters Cellular Metabolism and DNA Repair*

After genotoxic stress poly(ADP-ribose) polymerase-1 (PARP-1) can be hyperactivated, causing (ADP-ribosyl)ation of nuclear proteins (including itself), resulting in NAD+ and ATP depletion and cell death. Mechanisms of PARP-1-mediated cell death and downstream proteolysis remain enigmatic. β-lapachone (β-lap) is the first chemotherapeutic agent to elicit a Ca2+-mediated cell death by PARP-1 hyperactivation at clinically relevent doses in cancer cells expressing elevated NAD(P)H:quinone oxidoreductase 1 (NQO1) levels. β-lap induces the generation of NQO1-dependent reactive oxygen species (ROS), DNA breaks, and triggers Ca2+-dependent γ-H2AX formation and PARP-1 hyperactivation. Subsequent NAD+ and ATP losses suppress DNA repair and cause cell death. Reduction of PARP-1 activity or Ca2+ chelation protects cells. Interestingly, Ca2+ chelation abrogates hydrogen peroxide (H2O2), but not N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced PARP-1 hyperactivation and cell death. Thus, Ca2+ appears to be an important co-factor in PARP-1 hyperactivation after ROS-induced DNA damage, which alters cellular metabolism and DNA repair.