Miracle-dz/UniFAR-FTUs huggingface dataset:
De novo design of a model peptide sequence to examine the effects of single amino acid substitutions in the hydrophobic core on both stability and oligomerization state of coiled-coils.

A model peptide sequence was de novo designed to investigate the hydrophobicity, stability and oligomerization state resulting from single amino acid substitutions in the hydrophobic core a position of the central heptad of a five heptad coiled-coil. This involved selecting a hydrophobic core consisting of Val and Leu at a and d positions, respectively, known to form both two- and three-stranded coiled-coils. In addition, the sequence provided the correct overall coiled-coil stability and maximized the hydrophobicity surrounding the substitution site by having Leu in the hydrophobic core above and below the site of substitution. To control oligomerization state we exploited differential placement of an interhelical disulfide-bridge, which was placed in the coiled-coil hydrophobic core at the C-terminal d position, or alternatively outside of the core at the N-terminal via a Cys-Gly-Gly linker. We found that the Cys-Gly-Gly linker allowed assessment of both relative stability and oligomerization state after extensive biophysical characterization of the models by circular dichroism, sedimentation equilibrium, sedimentation velocity and finally high-performance size-exclusion chromatography (HPSEC) under both benign and denaturing conditions. The Cys-Gly-Gly linker was found to be unique in allowing the inherent two- or three-stranded oligomerization state to be observed in benign medium, while also allowing the stability to be determined by concentration independent chemical denaturation of a two-stranded coiled-coil. This entails a two-state transition from a folded disulfide-bridged two-stranded coiled-coil (monomeric state) to the unfolded monomer, even for analogs where the coiled-coil is a trimer of disulfide-bridged peptides in benign medium. We also developed novel HPSEC methodology for monitoring the chemical denaturation of a folded monomeric protein in fast exchange with the corresponding unfolded protein, which elutes as a single peak throughout the denaturation process.
Choroidal thickness maps from spectral domain and swept source optical coherence tomography: algorithmic versus ground truth annotation

Background/aims The purpose of the study was to create a standardised protocol for choroidal thickness measurements and to determine whether choroidal thickness measurements made on images obtained by spectral domain optical coherence tomography (SD-OCT) and swept source (SS-) OCT from patients with healthy retina are interchangeable when performed manually or with an automatic algorithm. Methods 36 grid cell measurements for choroidal thickness for each volumetric scan were obtained, which were measured for SD-OCT and SS-OCT with two methods on 18 eyes of healthy volunteers. Manual segmentation by experienced retinal graders from the Vienna Reading Center and automated segmentation on >6300 images of the choroid from both devices were statistically compared. Results Model-based comparison between SD-OCT/SS-OCT showed a systematic difference in choroidal thickness of 16.26±0.725 μm (p<0.001) for manual segmentation and 21.55±0.725 μm (p<0.001) for automated segmentation. Comparison of automated with manual segmentations revealed small differences in thickness of −0.68±0.513 μm (p=0.1833). The correlation coefficients for SD-OCT and SS-OCT measures within eyes were 0.975 for manual segmentation and 0.955 for automatic segmentation. Conclusion Choroidal thickness measurements of SD-OCT and SS-OCT indicate that these two devices are interchangeable with a trend of choroidal thickness measurements being slightly thicker on SD-OCT with limited clinical relevance. Use of an automated algorithm to segment choroidal thickness was validated in healthy volunteers.
Back Injuries among Nursing Personnel

Reducing the total number of work related back injuries among nurses is important, but reducing those injuries that are severe enough to result in lost time and/or disability is critical. Results of this study indicate that female nurses in the early phases of assignment on long term care units are at greatest risk for back injury, but risk factors that relate significantly to the severity of the injury are tour of duty (evening) and weight of the nurse (200 + pounds). Recommendations suggested by this study include: evaluation of lifting techniques and practices; orientation whenever assignments are changed; accurate assessment of nurse, client, and situation; and the regular use of an assessment tool which incorporates all of these factors.
Long‐range transcriptional regulation of breast cancer genes

Breast cancer is a major health problem and understanding the genetic basis of this disease is crucial for predicting risk and developing effective targeted therapeutics. Several breast cancer predisposing genes have been identified, but mutations in the coding regions of these genes only accounts for a small proportion of risk. Research now suggests that combinations of multiple non‐coding changes in breast cancer susceptibility genes, which cause moderate alterations in gene expression, will be responsible for the remaining inherited risk. These non‐coding changes will include variants in proximal and distal transcriptional and post‐transcriptional regulatory elements and may affect the levels and function of trans‐acting factors, including proteins and RNAs, which act on these elements. Somatic changes in such elements and factors have also been associated with breast cancer progression. With the recent advent of techniques allowing the detection of long‐range DNA interactions spanning the human genome, it has become increasingly clear that long‐range regulatory elements constitute an important mechanism for gene regulation. Recent studies have identified several such elements that are important for regulating genes involved in breast cancer, raising the possibility that defects in these sequences may contribute to breast cancer predisposition and progression. In this review, we discuss the emerging functions of cis‐regulatory elements and a subset of trans‐acting factors in breast tumorigenesis. We also discuss some recent progress in our understanding of how dysregulation in these transcriptional components may contribute to breast cancer, and the potential implications for molecular diagnosis, prognosis prediction, and the treatment of this disease. © 2012 Wiley Periodicals, Inc.
Response of Estradiol and Inhibin to Experimentally Reduced Luteinizing Hormone During Follicle Deviation in Mares1

Abstract The increase in LH concentrations at the time of the decrease in FSH concentrations during follicle deviation in mares was studied to determine the role of LH in the production of estradiol and immunoreactive inhibin (ir-inhibin). Ten days after ovulation, all follicles ≥6 mm were ablated, prostaglandin F2α was given, and either 0 mg (control group, n = 15) or 100 mg of progesterone in safflower oil (treated group, n = 16) was given daily for 14 days, encompassing the day of diameter deviation. The follicular and hormonal data were normalized to the expected day of the beginning of diameter deviation when the largest follicle first reached ≥20 mm (Day 0). The experimentally induced decrease in LH concentrations during follicle deviation beginning on Day −4 delayed and stunted the increase in circulating concentrations of ir-inhibin and estradiol beginning on Days −3 and −1, respectively, but did not alter the predeviation FSH surge and the initiation of diameter deviation between the two largest follicles. Combined for both groups, the interval to the expected day of deviation was 16.6 days after ovulation when the largest follicle was a mean of 21.6 mm. After deviation, the largest follicle started to regress in the treated group beginning on Day 1 and was associated with decreased concentrations of ir-inhibin and estradiol, and increased concentrations of FSH. The negative influence of the dominant follicle on the postdeviation decrease in FSH observed in the control group was alleviated and concentrations resurged in the treated group. Apparently this is the first in vivo evidence that the increase in LH that precedes follicle deviation has a positive effect in supporting the production of inhibin during diameter deviation. It was concluded that the increase in LH concentrations before diameter deviation played a role in the production of estradiol and inhibin by the largest follicle during deviation.
Concomitant changes in cross‐sectional area and water content in skeletal muscle after resistance exercise

This study investigated how one bout (1EX) and three bouts (3EX) of strenuous resistance exercise affected the cross‐sectional area (CSA) and water content (WC) of the quadriceps muscle and patella tendon (PT), 4 h and 52 h after the last exercise bout. Ten healthy untrained male subjects performed 1EX with one leg and 3EX with the other leg. CSA and WC were measured with magnetic resonance imaging 10, 20 and 30 cm proximal to the tibia plateau (TP) for the muscle, and at the proximal, central and distal site for the PT prior to exercise, and 4 h and 52 h after the last exercise bout. Ten centimeter above the TP, muscle CSA was significantly increased at 4 h (1EX: 13 ± 5%; 3EX: 13 ± 4%) and 52 h (1EX: 16 ± 5%; 3EX: 16 ± 5%) compared with baseline. Muscle WC was significantly increased at 4 h (1EX: 7 ± 1%; 3EX: 6 ± 2%) and 52 h (1EX: 8 ± 2%; 3EX: 8 ± 3%) compared to baseline. PT central CSA was significantly reduced at 52 h (3EX: 14 ± 2%) compared with baseline and (3EX: 13 ± 1%) compared with 4 h. Present data demonstrate that strenuous resistance exercise results in an acute increase in muscle WC and underlines the importance of ensuring sufficient time between the last exercise bout and the determination of anatomical dimensions in muscles.
Optimal Unlimited Free-Replacement Warranty Strategy using Reconditioned Products

The long-term sustainability of our resources is dependent on reducing the consumption of virgin resources, and one method of achieving this goal is product remanufacturing. It is already established that the production of remanufactured products costs less than that of creating a new one, however the effects of this on warranty costs are now considered. Due to consumer perceptions of the quality of remanufactured products, it cannot be sold for the same price as a new product. In addition, the warranty costs the manufacturer incurs will also be higher. This paper proposes a mathematical model for the optimal one-dimensional unlimited free-replacement warranty policy with replacements carried out with reconditioned products. Numerical optimization is used to compute the optimal warranty and production parameters which maximize the total profit.
The function of neutrophils in sepsis

Purpose of review Neutrophils are an essential arm of the innate immune response. In patients with sepsis, reprogramming of neutrophil occurs, manifest by impaired recruitment of neutrophils to sites of infection, abnormal accumulation of neutrophils to remote sites, and dysregulation of neutrophil effector responses. This review examines the mechanisms underlying dysregulated neutrophil trafficking and function during sepsis. Recent findings Mechanisms governing neutrophil function in sepsis are complex. Bacterial products, cytokines/chemokines, leukotrienes, and immunomodulatory hormones can modulate neutrophil migratory responses during sepsis via induction of cytoskeletal changes, disruption of polymorphonuclear leukocyte (PMN)–endothelial cell interactions, and alterations in G-protein-coupled receptor expression or signaling. Impaired chemotactic responses and alterations in neutrophil function can occur as a result of dysregulated PMN G-protein-coupled receptor and Toll-like receptor expression and/or signaling. As sepsis evolves, neutrophil gene expression is altered, leading to suppression of proinflammatory and immunomodulatory genes, as well as decreased production of reactive oxygen species. Neutrophil extracellular traps are produced to contain and kill invading pathogens, but can paradoxically promote further tissue damage. Summary Neutrophil migration is a coordinated process that is altered at multiple stages during sepsis. In combination with impaired neutrophil function, these alterations culminate in defective innate immunity in septic patients. Defining the mechanisms involved and strategies to interrupt these deleterious responses requires further investigation.
New glycemic targets for patients with diabetes from the Japan Diabetes Society

In the ‘Evidence‐based Practice Guideline for the Treatment for Diabetes in Japan 2013’, a new concept of the glycemic control in patients with diabetes in Japan has been declared from the Japan Diabetes Society. The main objective value of HbA1c was set to <7% from the perspective of preventing microvascular complications. On the other hand, the objective in cases where objectives can be attained by appropriate dietary or exercise therapy, or during pharmacotherapy without the occurrence of side effects such as hypoglycemia was set to <6%, and the objective in cases where intensification of treatment was considered difficult due to side effects such as hypoglycemia or for other reasons was set to <8%. Treatment objectives should be established individually, in consideration of age, duration of disease, organ damage, risk of hypoglycemia, support structure, and etc.
An Experimental Music Theory

In man, the size of the trunk is proportionate to the lower portions. and as a man grows up it becomes much smaller in proportion. In infancy the reverse is found. In other words, all children are dwarfs. The whole groups of birds and fishes are dwarflike. This is why all animals are less intelligent than man. And the reason, as aforesaid, is that in very many of them the principle of the soul is sluggish and corporeal. And if the heat which raises the organism up wanes still further while the earthy matter waxes, then the animals’ bodies wane, and they will be many-footed; and finally they lose their feet altogether and lie full length on the ground. Proceeding a little further in this way, they actually have their principal part down below, and finally the part which answers to a head comes to have neither motion nor sensation; at this stage the creature becomes a plant.1
Enhancing Research Ethics Capacity in the Middle East: Experience and Challenges of a Fogarty-Sponsored Training Program

We describe the research ethics capacity needs of the countries from the Middle East region. Against this background, we relate the experience of an international training program focused on providing long-term training in research ethics to individuals from low- and middle-income countries in the Middle East area. We describe our pedagogical approach to training, program changes to address challenges faced, and accomplishments of trainees. Many former trainees developed research ethics curricula in their home institutions, established or enhanced their institutions' research ethics committees, provided leadership to national research ethics systems, and conducted research in research ethics. Based on our analysis, we make recommendations for how trainees can further address current regional research ethics needs in the Middle East and conduct future research. This paper is part of a collection of papers analyzing the Fogarty International Center's International Research Ethics Education and Curriculum Development program.
Clinical instructor's behavior: Nursing student's perception toward effective clinical instructor's characteristics

Background and Aim: Clinical training as the core of nursing education is a significant and essential component for development of professional nurses. The quality of clinical instructor’s behavior plays a significant role in the learning process of the students, especially in clinical practice. The aim of the study was to assess the clinical instructor’s behaviors and nursing students’ perceptions toward effective clinical instructor's characteristics that facilitate learning process. Methods: Setting: The current study was conducted at Faculty of Nursing, Cairo University. Design: Descriptive, correlational design was utilized for the current study. Sample: A convenient sample of 333 was drawn from nursing students in different levels of baccalaureate nursing programs who had finished at least two clinical rotations with patient care. Tools: The Nursing Clinical Teacher Effective Inventory (NCTEI) was used for data collection. Results: Findings of the current study revealed that the highest ranked clinical instructor’s behavior as reported by the student’s was teaching ability category followed by evaluation and nursing competence respectively. Regarding effective clinical instructor’s characteristics as perceived by students, the highest ranked one was teaching ability category followed by nursing competence and evaluation respectively. The personality and interpersonal relationship among nursing student set as the fourth and fifth factors that affect learning process in the clinical settings. Conclusions: Effective clinical instructor's characteristics that affect learning process as perceived by nursing student include matching clinical teaching abilities, nursing competence and evaluation to student understanding and experience. Also, the nursing students considered the personality and interpersonal relationship is very important characteristics to provide support and encouragement to the student during clinical practice. Recommendation: Workshops/seminars should be organized and also orientation program for all newly clinical instructors on their roles in clinical teaching. These findings may help faculty to be pleased about students’ views and acknowledge the areas of success as well as areas that needs improvement.
Positive selection in the egg receptor for abalone sperm lysin

The mechanism of speciation is a central problem in evolutionary biology. In free-spawning animals with no complex mating behavior, prezygotic reproductive isolation (speciation) could result from the rapid divergence of genes coding for sperm and egg proteins that bind each other during fertilization. In abalone, sperm lysin evolves rapidly by positive Darwinian selection. The egg vitelline envelope receptor for lysin had previously been shown to evolve neutrally and be subjected to concerted evolution. Several mathematical simulations predict that both male and female reproductive proteins should evolve rapidly by positive selection. Here we report that the sequence diversity of the amino-terminal end of the egg vitelline envelope receptor for lysin has been promoted by positive Darwinian selection. These data provide molecular support for theoretical models showing that the two sexes are locked in a “coevolutionary chase” that could be driven by processes such as sexual selection, sexual conflict, or microbial attack (pathogen avoidance). The result of this continuous coevolution of the gamete recognition system could be the splitting of one population into two that are reproductively isolated (speciation).
An Initial Study of Modifiable and Non-Modifiable Factors for Late-Life Psychosis

Objective: To determine rates of psychotic symptoms and associated modifiable and non-modifiable factors among elderly long term nursing home residents without prior history of psychiatric illness. Method: A cross-sectional design using the Scale for the Assessment of Positive Symptoms (SAPS) to measure psychotic symptoms, the Folstein's Mini-Mental State Exam (MMSE), and Mattis Dementia Rating Scale (DRS) to evaluate cognitive impairment. Frequency and rates of global psychotic symptoms and hallucinations, delusions, formal thought disorder, and bizarre behavior were calculated. Logistic regression was used to examine modifiable (e.g., medication use) and non-modifiable clinical characteristics (e.g., older age) associated with late-life psychosis. Results: There were 15.9% of subjects reporting delusions and 7.3% reporting hallucinations. History of stroke, poorer cognition, and receiving multiple medications showed significant association with late-life psychosis. Only stroke (OR=9.12; 95% CI: 1.58–52.74) and receiving different classes of medications (benzodiazepines, neuroleptics, and antidepressants) (OR=13.17; 95% CI: 2.10–85.82) remained significantly associated with psychosis after adjusting for Mattis DRS total score. Further analyses excluding subjects with MMSE scores of 24 or lower (n = 24) showed essentially the same results but subjects with better cognitive function suffered a less severe form of psychosis, essentially constituted by one symptom type (i.e., visual hallucinations). Conclusions: Rates of late-life psychosis in this sample of nursing home residents without previous psychiatric history were high. Simultaneous use of medications including antidepressants, sedatives, and stimulants may be a clinically relevant modifiable factor to be targeted in prevention studies. Severity and type of psychosis is dependent on the severity of cognitive impairment.
Facial Averageness and Attractiveness in an Isolated Population of Hunter-Gatherers

Average faces possess traits that are common to a population. Preferences for averageness have been found in several types of study of both real and computer-manipulated faces. Such preferences have been proposed to be biologically based and thus should be found across human populations, though cross-cultural evidence to date has been limited. In this study we examined preferences for averageness in both the West and in an isolated hunter-gatherer society, the Hadza of Northern Tanzania in Africa. We show that averageness is generally preferred across faces and cultures, but there were no significant preferences for averageness in European faces by Hadza judges. The different visual experience of the two cultures may explain the differences in preferences. While Westerners have visual experience of both European and African faces, the Hadza are limited in their experience of European faces, potentially leading to a lack of preference for averageness in this group because of the lack of a representation of the ‘norm’ of European faces.
The Epstein-Barr Virus-encoded G Protein-coupled Receptor BILF1 Hetero-oligomerizes with Human CXCR4, Scavenges Gαi Proteins, and Constitutively Impairs CXCR4 Functioning*

Cells express distinct G protein-coupled receptor (GPCR) subtypes on their surface, allowing them to react to a corresponding variety of extracellular stimuli. Cross-regulation between different ligand-GPCR pairs is essential to generate appropriate physiological responses. GPCRs can physically affect each other's functioning by forming heteromeric complexes, whereas cross-regulation between activated GPCRs also occurs through integration of shared intracellular signaling networks. Human herpesviruses utilize virally encoded GPCRs to hijack cellular signaling networks for their own benefit. Previously, we demonstrated that the Epstein-Barr virus-encoded GPCR BILF1 forms heterodimeric complexes with human chemokine receptors. Using a combination of bimolecular complementation and bioluminescence resonance energy transfer approaches, we now show the formation of hetero-oligomeric complexes between this viral GPCR and human CXCR4. BILF1 impaired CXCL12 binding to CXCR4 and, consequently, also CXCL12-induced signaling. In contrast, the G protein uncoupled mutant BILF1-K3.50A affected CXCL12-induced CXCR4 signaling to a much lesser extent, indicating that BILF1-mediated CXCR4 inhibition is a consequence of its constitutive activity. Co-expression of Gαi1 with BILF1 and CXCR4 restored CXCL12-induced signaling. Likewise, BILF1 formed heteromers with the human histamine H4 receptor (H4R). BILF1 inhibited histamine-induced Gαi-mediated signaling by H4R, however, without affecting histamine binding to this receptor. These data indicate that functional cross-regulation of Gαi-coupled GPCRs by BILF1 is at the level of G proteins, even though these GPCRs are assembled in hetero-oligomeric complexes.