Miracle-dz/UniFAR-FTUs huggingface dataset:
A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14

Objective More than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA. Methods 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations. Results 43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10−4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10−7). Such association appeared to be independent of HLA-B27. Conclusions We report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.
Challenges and opportunities for suicide bereavement research: the experience of ethical board review.

BACKGROUND While high-quality and ethically sound research is needed to better understand and respond to the needs of those bereaved by suicide, there is a concern that ethical boards internationally raise unreasonable objections to research with those bereaved by suicide. AIMS This pilot study was conducted to examine the issues faced by suicide bereavement and postvention researchers while obtaining ethical board approval. METHOD Suicide bereavement and postvention researchers from four continents were surveyed on their experiences of responding to ethical board challenges to research proposals and requests to amend their research as a result of ethical board concerns. RESULTS While ethical boards differ in their response to suicide bereavement research, eight of 19 researchers surveyed indicated they had had proposals challenged, with two of these eight researchers reporting having to make major changes to their proposals as a result. The researchers provided examples of how they responded to those concerns about perceived risks of their research by ethical board members. CONCLUSIONS There are strict guidelines regarding the treatment of research study participants, and ethical boards must ensure the proposed research procedures adhere to these guidelines. Yet, in the field of suicide bereavement research it would appear that some ethical boards place restrictions or raise concerns about research being conducted in an absence of sound knowledge about the safety of such research. This ultimately may influence the design of research being conducted. Such influence in turn shapes the data generated from the research and thus what is published in the literature. It is both timely and imperative for ethical board members to be well educated on what the risks of those who are bereaved by suicide may be prior to making recommendations on research project designs.
Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down.

OBJECTIVE Numerous neuroimaging studies have examined the function of the dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually are identified, it is unclear why some studies find too little activation and others too much. The authors' goal was to explore this phenomenon. METHOD They used the N-back working memory task and functional magnetic resonance imaging at 3 T to examine a group of 14 patients with schizophrenia and a matched comparison group of 14 healthy subjects. RESULTS Patients' performance was significantly worse on the two-back working memory task than that of healthy subjects. However, there were areas within the dorsolateral prefrontal cortex of the patients that were more active and areas that were less active than those of the healthy subjects. When the groups were subdivided on the basis of performance on the working memory task into healthy subjects and patients with high or low performance, locales of greater prefrontal activation and locales of less activation were found in the high-performing patients but only locales of underactivation were found in the low-performing patients. CONCLUSIONS These findings suggest that patients with schizophrenia whose performance on the N-back working memory task is similar to that of healthy comparison subjects use greater prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that other patients with schizophrenia fail to sustain the prefrontal network that processes the information, achieving even lower accuracy as a result. These findings add to other evidence that abnormalities of prefrontal cortical function in schizophrenia are not reducible to simply too much or too little activity but, rather, reflect a compromised neural strategy for handling information mediated by the dorsolateral prefrontal cortex.
Anterior shoulder instability in weight lifters

Occult instability is recognized as a major cause of shoulder dysfunction in throwing athletes. Few studies have characterized the findings of occult instability in nonthrowers. The purpose of this study was to examine shoulder instability in a group of weight lifters. The symptoms, physical findings, and results of treatment for 23 shoulders in 20 athletes are presented. All ath letes presented with a complaint of progressive inability to perform exercises with the upper extremity in the abducted, externally rotated position (the "at-risk" po sition) because of pain. One hundred percent of the athletes experienced posterior shoulder pain when the shoulder was placed in forced abduction and external rotation. Thirteen shoulders in 10 patients responded to conservative management including aggressive re habilitation and modification of technique to avoid the at-risk position. The other 10 shoulders, which did not respond to conservative treatment, required surgical treatment to alleviate the symptoms. All 20 patients have successfully returned to their previous weight lifting activities.
Progestin receptor is transiently expressed perinatally in neurons of the rat isocortex

Steroid hormones influence the development of numerous brain regions, including some that are not classically considered steroid‐sensitive. For example, nuclear receptors for both androgen and estrogen have been detected in neonatal cortical cells. High levels of progestin binding and progestin receptor (PR) mRNA have also been reported in early perinatal isocortex. PR expression coincides with high levels of de novo progesterone produced within the cortex, suggesting that PR and its ligand influence the important developmental cortical processes occurring shortly after birth. In order to better understand the role PR plays in cortical development, we used the cellular‐level resolution of immunohistochemistry and in situ hybridization (ISH) to characterize changes in perinatal PR expression within specific cortical lamina. PR immunoreactivity (PR‐ir) was examined at embryonic days (E) 18, 20, 21, 22, and postnatal days (P) 1, 3, 6, 9, 13, and 27. We find that PR‐ir is transiently expressed in specific lamina of frontal, parietal, temporal, and occipital cortex. PR‐ir was observed in subplate cells on E18, in increasingly superficial lamina (primarily lamina V, then II/III) during early postnatal development, and was absent by P27. Double‐labeling immunohistochemistry indicated that PR‐ir colocalizes with the neuronal marker, microtubule associated protein‐2, but not with the glial marker, nestin, nor with γ‐aminobutyric acid. These results suggest that specific subpopulations of cortical neurons may be transiently sensitive to progesterone, and that progesterone and its receptor may play a critical role in the fundamental mechanisms underlying normal cortical development. J. Comp. Neurol. 512:124–139, 2009. © 2008 Wiley‐Liss, Inc.
A very low area ADC for 3-D stacked CMOS image processing system

This paper presents a very small circuit area analog-to-digital converter (ADC) for three-dimensional (3-D) stacked CMOS image processing system. To realize high-speed image sensor, we have proposed a block-parallel signal processing with 3-D stacked structure. The proposed block-parallel analog signal processing elements contains CMOS image sensor, correlated double sampling (CDS) array, and ADC array. Each circuit layer is vertically stacked and electrically connected by through-Si vias (TSVs), which can improve sensor performance. On the other hand, the block-parallel system requires ADC with extremely low-power and small circuit area. Therefore, the trade-off among area, power dissipation and conversion speed is important factor, and critical challenge. To achieve extremely low circuit area and low power dissipation, ADC designed in the prototype chip for fundamental evaluation employed the time interleaved charge-redistribution successive approximation (SAR) method. An implemented 9-bit prototype in a 90 nm CMOS technology occupies 100×100 μm2, achieves an ENOB of 7.28 bit at a conversion rate of 4 MS/s. The power dissipation is 381μW with supply voltage of 1.0V and 4 MS/s conversion rate.
Single embryo and oocyte lipid fingerprinting by mass spectrometry[S]

Methods used for lipid analysis in embryos and oocytes usually involve selective lipid extraction from a pool of many samples followed by chemical manipulation, separation and characterization of individual components by chromatographic techniques. Herein we report direct analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) of single and intact embryos or oocytes from various species. Biological samples were simply moisturized with the matrix solution and characteristic lipid (represented by phosphatidylcholines, sphingomyelins and triacylglycerols) profiles were obtained via MALDI-MS. As representative examples, human, bovine, sheep and fish oocytes, as well as bovine and insect embryos were analyzed. MALDI-MS is shown to be capable of providing characteristic lipid profiles of gametes and embryos and also to respond to modifications due to developmental stages and in vitro culture conditions of bovine embryos. Investigation in developmental biology of the biological roles of structural and reserve lipids in embryos and oocytes should therefore benefit from these rapid MALDI-MS profiles from single and intact species.
Knockdown of estrogen receptor‐α induces autophagy and inhibits antiestrogen‐mediated unfolded protein response activation, promoting ROS‐induced breast cancer cell death

Approximately 70% of all newly diagnosed breast cancers express estrogen receptor (ER)‐α. Although inhibiting ER action using targeted therapies such as fulvestrant (ICI) is often effective, later emergence of antiestrogen resistance limits clinical use. We used antiestrogen‐sensitive and ‐resistant cells to determine the effect of antiestrogens/ERα on regulating autophagy and unfolded protein response (UPR) signaling. Knockdown of ERα significantly increased the sensitivity of LCC1 cells (sensitive) and also resensitized LCC9 cells (resistant) to antiestrogen drugs. Interestingly, ERα knockdown, but not ICI, reduced nuclear factor (erythroid‐derived 2)‐like (NRF)‐2 (UPR‐induced antioxidant protein) and increased cytosolic kelch‐like ECH‐associated protein (KEAP)‐1 (NRF2 inhibitor), consistent with the observed increase in ROS production. Furthermore, autophagy induction by antiestrogens was prosurvival but did not prevent ERα knockdown‐mediated death. We built a novel mathematical model to elucidate the interactions among UPR, autophagy, ER signaling, and ROS regulation of breast cancer cell survival. The experimentally validated mathematical model explains the counterintuitive result that knocking down the main target of ICI (ERα) increased the effectiveness of ICI. Specifically, the model indicated that ERα is no longer present in excess and that the effect on proliferation from further reductions in its level by ICI cannot be compensated for by increased autophagy. The stimulation of signaling that can confer resistance suggests that combining autophagy or UPR inhibitors with antiestrogens would reduce the development of resistance in some breast cancers. —Cook, K. L. , Clarke, P. A. G. , Parmar, J., Hu, R. , Schwartz‐Roberts, J. L. , Abu‐Asab, M. , Wärri, A. , Baumann, W. T. , Clarke, R. Knockdown of estrogen receptor‐α induces autophagy and inhibits antiestrogen‐mediated unfolded protein response activation, promoting ROS‐induced breast cancer cell death. FASEB J. 28, 3891‐3905 (2014). www.fasebj. org
Noisy Softmax: Improving the Generalization Ability of DCNN via Postponing the Early Softmax Saturation

Over the past few years, softmax and SGD have become a commonly used component and the default training strategy in CNN frameworks, respectively. However, when optimizing CNNs with SGD, the saturation behavior behind softmax always gives us an illusion of training well and then is omitted. In this paper, we first emphasize that the early saturation behavior of softmax will impede the exploration of SGD, which sometimes is a reason for model converging at a bad local-minima, then propose Noisy Softmax to mitigating this early saturation issue by injecting annealed noise in softmax during each iteration. This operation based on noise injection aims at postponing the early saturation and further bringing continuous gradients propagation so as to significantly encourage SGD solver to be more exploratory and help to find a better local-minima. This paper empirically verifies the superiority of the early softmax desaturation, and our method indeed improves the generalization ability of CNN model by regularization. We experimentally find that this early desaturation helps optimization in many tasks, yielding state-of-the-art or competitive results on several popular benchmark datasets.
FPGA-based strong PUF with increased uniqueness and entropy properties

Physical unclonable functions (PUFs), are a type of physical security primitive which enable identification and authentication of hardware devices, such as field programmable gate arrays (FPGAs) and application specific integrated circuits (ASICs). Arbiter PUFs were the first proposed Strong PUF and are also widely studied. However, these designs often suffer from poor uniqueness and reliability characteristics leaving them vulnerable to modeling attacks, as well as being difficult to implement on FPGAs due to the physical layout restrictions. Some more recent designs based around non-linear voltage transfer characteristics, or non-linear currents improve the resistance against modeling attacks. However they can only be implemented on ASICs due to their voltage/current requirements. To address this problem, we propose a new PUF circuit that offers a significantly higher theoretical entropy than the traditional Arbiter PUF construction, and which is specifically designed for FPGAs. The proposed work is verified on a low-cost Nexys4 board which contains a Xilinx Artix-7 FPGA fabricated at 28nm. The experimental results give a uniqueness of 20 %, considerably higher than the reported 9 % of a traditional Arbiter PUF design, and an expected reliability of ≈ 96% over an environmental temperature range of 0° C to 75° C, with a reliability of ≈ 92 % with ±10 % variation in supply voltage.
Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women.

Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (< 0.05-1.15) IU/l and 0.06 (< 0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (> 15 mm) in these patients. (ABSTRACT TRUNCATED AT 250 WORDS)
The effect of medicaments used in endodontic regeneration on root fracture and microhardness of radicular dentine.

AIM To investigate the effect of medicaments used in endodontic regeneration on root fracture resistance and microhardness of radicular dentine. METHODOLOGY The root canals of mandibular premolars (n = 180) were instrumented and randomized into three treatment groups and an untreated control group. Each treatment group received either triple antibiotic paste (TAP), double antibiotic paste (DAP) or calcium hydroxide paste [Ca(OH)₂] intracanal medicament. Teeth were kept in saline for 1 week, 1 month or 3 months. After each time-point, 15 teeth were randomly selected from each group and two root cylinders were obtained from each tooth. One cylinder was subjected to a fracture resistance test, and the other cylinder was used for a microhardness test. Two-way ANOVA and Tukey's pairwise comparisons were used for statistical analysis. RESULTS For the microhardness test, the two-way interaction between group and time was significant (P < 0.001). The intracanal application of TAP and DAP caused significant and continuous decrease in root dentine microhardness after one (P < 0.05) and 3 months (P < 0.001), respectively. The three-month intracanal application of Ca(OH)₂ significantly increased the microhardness of root dentine (P < 0.05). The time factor had a significant effect on fracture resistance (P < 0.001). The three intracanal medicaments caused significant decreases in fracture resistance ranging between 19% and 30% after 3-month application compared to 1-week application. CONCLUSION In this laboratory study, the 3-month application of triple antibiotic paste, double antibiotic paste or calcium hydroxide paste medicaments significantly reduced the root fracture resistance of extracted teeth compared to a 1-week application.
In vitro and in vivo biofilm adhesion to esthetic coated arch wires and its correlation with surface roughness.

OBJECTIVE To evaluate the in vitro ability of esthetic coated rectangular arch wires to retain oral biofilms and in vivo biofilm formation on these wires after 4 and 8 weeks of clinical use and to correlate the findings with the surface roughness of these wires. MATERIALS AND METHODS Three brands of esthetic coated nickel-titanium (NiTi) arch wires were selected. Arch wires retrieved after 4 and 8 weeks of intraoral use were obtained from 30 orthodontic patients. Surface roughness (SR) was assessed with an atomic force microscope. In vitro adhesion assays were performed using Streptococcus mutans (MS), Staphylococcus aureus, and Candida albicans. The amount of bacterial adhesion was quantified using the colony-count method. Paired t-test, analysis of variance, post hoc Tukey's test, and Pearson's correlation coefficient test were used for statistical analysis at the . 05 level of significance. RESULTS In vitro bacterial adhesion showed significant differences between wires in terms of MS adhesion (P = .01). All wires showed significant increases in SR (P = .001 after 4 weeks and .007 after 8 weeks) and biofilm adhesion (P = .0001 after 4 weeks and .045 after 8 weeks) after intraoral exposure. A significant positive correlation (P = .001 after 4 weeks and .05 after 8 weeks) was observed between these two variables in vivo, but the correlation was not significant for in vitro bacterial adhesion. CONCLUSIONS SR and biofilm adhesion increased after intraoral use at all time intervals. There was a positive correlation between SR and biofilm adhesion in vivo only.
Biochemical Evaluation of Running Workouts Used in Training for the 400-m Sprint

Saraslanidis, PJ, Manetzis, CG, Tsalis, GA, Zafeiridis, AS, Mougios, VG, and Kellis, SE. Biochemical evaluation of running workouts used in training for the 400-m sprint. J Strength Cond Res 23(8): 2266-2271, 2009-A 400-m runner relies primarily on the lactate system for energy production. Although several running distances and schemes are used in training for this event, it is not clear which one(s) causes maximal activation of the lactate system so as to optimize adaptations of the lactic capacity. This study examined the effect of 4 running workouts differing in distance (300 vs. 400 m) and mode of execution (continuous/single vs. intermittent) on stimulation of the lactate system and biochemical markers of metabolism and muscle damage. Twelve young men performed 4 runs at maximal effort: 300, 3 × 100, 400, and 2 × 200 m. Blood was drawn before and after exercise for the measurement of lactate, glucose, creatinine, and creatine kinase (CK). Average speed was higher (p < 0.001) in the 300- vs. 400-m tests (7.52 ± 0.50 vs. 7.08 ± 0.59 m·s−1) and in the intermittent vs. continuous tests (7.45 ± 0.50 vs. 7.15 ± 0.58 m·s−1). Lactate was higher in the intermittent vs. continuous tests (16.3 ± 2.2 vs. 15.0 ± 2.0 mmol·L−1, p < 0.05). Serum glucose, creatinine, and CK increased after exercise (p ≤ 0.001), and glucose was higher in the 400- vs. 300-m trials (5.76 ± 0.46 vs. 5.33 ± 0.30 mmol·L−1, p = 0.032). In conclusion, although all 4 running regimens greatly stimulated the lactate system, it appears that the intermittent workouts are superior compared with continuous ones of the same total distance in increasing the ability for energy production via the lactate system. Thus, intermittent workouts can be successfully used by 400-m athletes to develop specific (speed) endurance and should be considered to precede the continuous runs of racing distance within a macrocycle.
Cembranoid diterpenes and a briarane diterpene from corals

Two new cembrane diterpenes (+)-polydactylide (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (2) together with (+)-sarcophine (3) and (+)-sarcophytoxide (4) have been isolated from the soft coral Sinularia polydactyla. The new cembrane diterpene (−)-7β-hydroxy-8α-methoxydeepoxysarcophine (5) has been obtained from the soft coral Sarcophyton trocheliophorum and the known briarane diterpene briaexcavatolide W (6) from the gorgonian coral Briareum sp. The structures were determined primarily by NMR spectroscopy. The assignment of NMR signals was performed by means of 1H–1H COSY, ROESY, HMQC and HMBC experiments.