Miracle-dz/UniFAR-FTUs huggingface dataset:
A —244-dB FOM High-Frequency Piezoelectric Resonator-Based Cascaded Fractional-N PLL With Sub-ppb-Order Channel-Adjusting Technique

This paper proposes a cascaded fractional-N phase-locked loop (PLL) based on a high-frequency piezoelectric resonator (PZR). Sub-ppb-order frequency resolution is achieved by a channel adjustment technique. Besides its small form factor, a high- ${Q}$ PZR at gigahertz frequencies realizes a very low phase-noise synthesizer for RF applications. However, three fundamental issues remain to be solved: the narrow tuning range and large process variation of PZR-based oscillators, the low-frequency resolution of a PLL referenced to gigahertz-order frequencies, and the undesirable harmonic oscillation caused by the inductance of the CMOS-PZR bonding wire. To overcome these issues, we propose a channel-adjusting technique (CAT) that adaptively sets the division ratio of two PLLs to maintain constant output frequency of the second PLL while varying the PZR oscillator frequency, hence permitting the narrow tuning range and wide process variation of the PZR oscillator. The first PLL in our PLL architecture determines the output frequency resolution and the second reduces the power consumption of the delta–sigma modulator. We also suppress the harmonic oscillations in the PZR oscillator. The prototype PLL is fabricated in a 65-nm CMOS and achieves an 8.484–8.912-GHz output, 180-fs rms jitter, and −244-dB FOM while consuming 12.7-mW power. We developed a cascaded fractional-N PLL based on a high-frequency PZR with a sub-ppb-order CAT, which overcomes the narrow tuning range problem in gigahertz PZRs. A prototype PLL fabricated in a 65-nm CMOS consumed 12.7 mWand output 8.484–8.912 GHz with 180-fs rms jitter.
Up-Regulation of Pain Behavior and Glial Activity in the Spinal Cord after Compression and Application of Nucleus Pulposus onto the Sciatic Nerve in Rats

Study Design Experimental animal study. Purpose To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. Overview of Literature Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. Methods The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. Results Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). Conclusions Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
Weight Maintenance with Litramine (IQP-G-002AS): A 24-Week Double-Blind, Randomized, Placebo-Controlled Study

Background. Litramine (IQP-G-002AS) was shown to be effective and safe for weight loss in overweight and obese subjects. However, long-term effectiveness on maintenance of body weight loss has yet to be ascertained. Objective. To assess effect of Litramine on maintenance of body weight loss. Methods. A double-blind, randomised, placebo-controlled trial on overweight and obese patients was conducted over two sites in Germany for 24 weeks. Subjects with documented previous weight loss of 3% over the last 3–6 months were randomised to groups given either Litramine (3 g/day) or a matching placebo. Primary endpoints were difference of mean body weight (kg) between baseline and end of study and maintenance of initially lost body weight in verum group, where maintenance is defined as ≤1% weight gain. Results. Subjects who were taking Litramine lost significantly more body weight compared to the subjects taking placebo who gained weight instead (−0.62 ± 1.55 kg versus 1.62 ± 1.48 kg, p < 0.001). More importantly, 92% of subjects in Litramine group were able to maintain their body weight after initial weight loss, versus 25% in placebo group. No serious adverse events were reported throughout. Conclusion. Litramine is effective and safe for long-term body weight maintenance. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT01505387.
Appetite Regulation In Relation To Energy Provision.

Background Appetite control is a very complex process which influences the short term feeding behaviour and a long term adaptive process that responds to the energy input. Appetite control and food intake is influenced by a combination of behavioural, psychological and neuro-endocrine influences. METHODS For identification of articles search engines of the databases EMBASE, OVID, Pub med and MEDLINE were used for papers published from 2002 to 2015 in English language. RESULTS The higher endogenous peptide YY (PYY) and cholecystokinin (CCK) and lower ghrelin levels are not always associated with subjective feelings of fullness or hunger and a decreased energy intake which highlights the fact that appetite control and food intake is a very intricate process. CONCLUSIONS When food is ingested, numerous physiological, hormonal, social and psychological processes are triggered in an intricate manner. Therefore, it can be said that ghrelin, PYY and CCK are just few pieces, which contributes to the process of appetite control and energy intake.
DIVERSIFICATION IN SEXUAL AND ASEXUAL ORGANISMS

Abstract Sexual reproduction has long been proposed as a major factor explaining the existence of species and species diversity. Yet, the importance of sex for diversification remains obscure because of a lack of critical theory, difficulties of applying universal concepts of species and speciation, and above all the scarcity of empirical tests. Here, we use genealogical theory to compare the relative tendency of strictly sexual and asexual organisms to diversify into discrete genotypic and morphological clusters. We conclude that asexuals are expected to display discrete clusters similar to those found in sexual organisms. Whether sexuals or asexuals display stronger clustering depends on a number of factors, but in at least some scenarios asexuals should display a stronger pattern. Confounding factors aside, the only explanation we identify for stronger patterns of diversification in sexuals than asexuals is if the faster rates of adaptive change conferred by sexual reproduction promote greater clustering. Quantitative comparisons of diversification in related sexual and asexual taxa are needed to resolve this issue. The answer should shed light not only on the importance of the different stages leading to diversification, but also on the adaptive consequences of sex, still largely unexplored from a macroevolutionary perspective.
Elastic constants of cancellous bone

Cancellous bone is a porous type of tissue mainly found near the ends of long bones and in vertebral bodies. In long bones, it distributes the mechanical loads from the articular surfaces to the cortical shaft, whereas in vertebral bodies it is the main load-carrying constituent. Bone fractures due to conditions such as osteoporosis usually occur in cancellous bone regions. Diseases in the skeleton, such as osteoarthritis, might be related to the mechanical properties of the subchondral bone under the affected cartilage and that of the cancellous bone supporting it. Hence, the mechanical quality of cancellous bone is an important parameter for bone fracture risk and integrity.
Atribute Match Discovery in Information Integration: Exploiting Multiple Facets of Metadata

Automating semantic matching of attributes for the purpose of information integration is challenging, and the dynamics of the Web further exacerbate this problem. Believing that many facets of metadata can contribute to a resolution, we present a framework for multifaceted exploitation of metadata in which we gather information about potential matches from various facets of metadata and combine this information to generate and place confidence values on potential attribute matches. To make the framework apply in the highly dynamic Web environment, we base our process on machine learning when sufficient applicable data is available and base it otherwise on empirically observed rules. Experiments we have conducted are encouraging, showing that when the combination of facets converges as expected, the results are highly reliable.
Matrix factorization-based data fusion for drug-induced liver injury prediction

Traditional studies of liver toxicity involve screening compounds through in vivo and in vitro tests. They need to distinguish between compounds that represent little or no health concern and those with the greatest likelihood to cause adverse effects in humans. High-throughput and toxicogenomic screening methods coupled with a plethora of circumstantial evidence provide a challenge for improved toxicity prediction and require appropriate computational methods that integrate various biological, chemical and toxicological data. We report on a data fusion approach for prediction of drug-induced liver injury potential in humans using microarray data from the Japanese Toxicogenomics Project (TGP) as provided for the contest by CAMDA 2013 Conference. Our aim was to investigate if the data from different TGP studies could be fused together to boost prediction accuracy. We were also interested if in vitro studies provided sufficient information to refrain from studies in animals. We show that our recently proposed matrix factorization-based data fusion provides an elegant computational framework for integration of the TGP and related data sets, 29 data sets in total. Fusion yields a high cross-validated accuracy (AUC of 0.819 for in vivo assays), which is above the accuracy of the established machine learning procedure of stacked classification with feature selection. Our data analysis shows that animal studies may be replaced with in vitro assays (AUC = 0.799) and that liver injury in humans can be predicted from animal data (AUC = 0.811). Our principal contribution is a demonstration that analysis of toxicogenomic data can substantially benefit from data fusion with directly and circumstantially related data sets.
Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity

The specificity and function of T helper (Th) immune responses underlying the induction, progression, and resolution of experimental autoimmune myocarditis (EAM) in A/J mice are unclear. Published data suggest involvement of both Th1 and Th2 responses in EAM; however, the previous inability to assess antigen-specific in vivo and in vitro T-cell responses in cardiac myosin-immunized animals has confounded our understanding of this important model of autoimmune myocarditis. The goal of our study was to develop an alternative model of EAM based on a recombinant fragment of cardiac myosin, in hopes that the recombinant protein will permit measurement of functional T-cell responses that is not possible with purified native protein. A/J mice immunized with a recombinant fragment of cardiac myosin spanning amino acids 1074–1646, termed Myo4, developed severe myocarditis characterized by cardiac hypertrophy, massive mononuclear cell infiltration and fibrosis, three weeks post-immunization. The mice also developed an IgG1 dominant humoral immune response specific for both Myo4 and purified cardiac myosin. The in vitro stimulation of splenocytes harvested from Myo4-immunized animals with Myo4 resulted in cellular proliferation with preferential production of the Th1- and Th17-associated cytokines, IFN-γ, IL-17, and IL-6, respectively. Production of IL-4 was negligible by comparison. This study describes a new model of EAM, inducible by immunization with a specific fragment of cardiac myosin, from which antigen-specific analyses reveal an importance for both Th1 and Th17 immunity.
Bone formation of the porous layer formed of Ti-Ag mesh for GBR membrane applications

본 연구의 목적은 마이크로 표면 위에 나노 단위의 다공성 구조를 갖는 티타늄-은 메쉬를 제작하고 메쉬의 골 형성능을 평가하는데 있다. 우선 시편 제작을 위해 cp-Ti에 비해 부식저항성이 뛰어난 티타늄-은 합금을 은 2.0 at%을 첨가시켜 제작하였다. 그리고 표면에 다공성 구조를 형성하기 위해 알루미나 입자를 사용하여 시편을 블라스팅 처리한 뒤 0.5% 불산 전해액에서 60분 동안 20 V 전압을 가하여 양극산화 처리하였다. 시편의 표면 형태는 주사전자현미경을 통해 관찰하였다. 골 형성능을 평가하기 위해 토끼의 두개골을 천공한 뒤 파절편을 제거하고 그 위에 시편을 식립하였다. 각각 2주와 4주 뒤 메쉬 주위의 골 조직 형태를 3D 스캔 이미지로 관찰하였고 생성된 골의 부피를 측정하였다. 시편 표면 형상 관찰 결과 마이크로 단위의 반구 형태 구조 위에 나노 단위의 다공성 구조를 관찰할 수 있었고, 골 형성능 결과에서는 대조군으로 메쉬를 식립하지 않은 경우에서 보다 티타늄-은 합금 메쉬를 식립한 경우에서 2주와 4주 모두 유의하게 더 많은 골 형성량을 보였다(p<0.05). 따라서 이 연구 결과로 미루어 보아 티타늄-은 합금에 마이크로 표면 위에 나노 다공성 구조를 형성할 수 있었으며 골 형성능 역시 우수하여 골유도 재생술을 위한 메쉬로서 유용하게 사용할 수 있을 것이라고 사료된다.
Self-rating makes the difference: Identifying palliative care needs of patients feeling severely affected by multiple sclerosis

Abstract Objective: People feeling severely affected by multiple sclerosis (MS) comprise a heterogeneous group, and this heterogeneity leads to very distinct needs and makes planning for needs difficult. To provide optimal care, it is important to identify specific needs in specific subgroups. Our objective was to identify the specific palliative care (PC) needs of patients who felt severely affected by the disease by analyzing their feeling (1) more or (2) less severely affected and their possible differences in expressed care needs. Method: A self-report questionnaire with 25 needs categories including 7 categories pertaining to care was applied to patients who felt severely affected by MS. An additional single question identified patients feeling more (≥7, median-split) and less (<7) severely affected. Differences were analyzed by chi-squared and Mann–Whitney U tests. The sample (N = 573) was composed of respondents who replied to an invitation by the German Multiple Sclerosis Society to participate in a survey on unmet needs of severely affected patients. Results: Of 573 patients (median age 51), 358 (62.48%) felt more severely affected. Compared to patients feeling less severely affected, they found the stress on their next of kin to be higher (p < 0.001), were in greater need of home visitation (p < 0.001), did not have permanent neurologists (p = 0.016), and felt that they visited them too rarely (p < 0.0001). They also needed more emotional support from their nursing care service (p = 0.006). Significance of results: A self-rating scale can identify two groups of patients with different care needs. These data may help shaping patient-centered support structures. Palliative care, with its multidisciplinary approach, might be one further option to meet the specific needs of patients and their relatives.
Popliteal Artery Aneurysm Repair in the Endovascular Era

Abstract To compare outcomes of popliteal artery aneurysm (PAA) repair by endovascular treatment, great saphenous vein (GSV) bypass, and prosthetic bypass. Single center retrospective analysis of patients presenting PAA from 2000 to 2013. Patients were divided into endovascular treatment (group A); GSV bypass (group B); and prosthetic graft bypass (group C). Outcomes were technical success, perioperative mortality, and morbidity. Survival, primary and secondary patency, and freedom from reintervention rate were estimated. Differences in ankle-brachial index (ABI), in-hospital length of stay (InH-Los), red blood cell (RBC) transfusion, and limb loss were reported. Mean follow-up was 49 (median: 35; 1–145; SD 42) months. Sixty-seven patients were included; 25 in group A, 28 in group B, and 14 in group C. PAA was symptomatic in 23 (34%) cases. Technical success was 100%. No perioperative death occurred. Three (4.5%) perioperative complications were reported with no significant difference between groups (P = 0.866). Five-years estimated survival was 78%. Estimated 5-years primary patency for groups A, B, and C was 71%, 81%, and 69%, respectively (P = 0.19). Estimated 5-years secondary patency for groups A, B, and C was 88%, 85%, and 84% (P = 0.85). Estimated 5-years freedom from reintervention for groups A, B, and C was 62%, 84%, and 70%, respectively (P = 0.16). A significant difference between preoperative ABI versus postoperative ABI was observed (P = 0.001). InH-LoS was significantly shorter in group A (P < 0.001). RBC transfusions were required significantly less in group A when compared to group C (P = 0.045). Overall limb salvage was achieved in all but 1 patient. PAA repair has good early and long-term outcomes with different treatment options. Endovascular treatment was not inferior to surgical repair with a reduced InH-LoS and RBC transfusion. It can be successfully employed even in nonelective setting. A randomized controlled trial with long-term follow-up and appropriate patient inclusion criteria is necessary to compare these 3 treatment options.
Evidence for an association between JC virus and colorectal neoplasia.

To the Editor: Newcomb et al. ([1][1]) have attempted to confirm the presence of JC virus (JCV) DNA in colorectal cancers and have failed to do so. They reached their negative conclusion, although other groups have been able show JCV in colonic epithelium and colorectal neoplasia ([2][2][-4][3]).
Genetic Interaction between Arabidopsis Qpm3.1 Locus and Bacterial Effector Gene hopW1-1 Underlies Natural Variation in Quantitative Disease Resistance to Pseudomonas Infection

Wide quantitative variation in plant disease resistance across Arabidopsis wild populations has been documented and the underlying mechanisms remain largely unknown. To investigate the genetic and molecular basis of this variation, Arabidopsis recombinant inbred lines (RILs) derived from Aa-0 × Col-0 and Gie-0 × Col-0 crosses were constructed and used for inoculation with Pseudomonas syringae pathovars maculicola ES4326 (ES4326) and tomato DC3000 (DC3000). Bacterial growth assays revealed continuous distribution across the large differences between the most and the least susceptible lines in the RILs. Quantitative trait locus (QTL) mapping analyses identified a number of QTLs underpinning the variance in disease resistance, among which Qpm3.1, a major QTL on chromosome III from both Aa-0 and Gie-0 accessions, preferentially restricted the growth of ES4326. A genetic screen for the ES4326 gene selectively leading to bacterial growth inhibition on accession Aa-0 uncovered the effector gene hopW1-1. Further QTL analysis of disease in RILs inoculated with DC3000 carrying hopW1-1 showed that the genetic interaction between Qpm3.1 and hopW1-1 determined Arabidopsis resistance to bacterial infection. These findings illustrate the complexity of Arabidopsis-Pseudomonas interaction and highlight the importance of pathogen effectors in delineating genetic architectures of quantitative variation in plant disease resistance.
Genetic analysis of mecA gene and detection of homologue pbpD in Stahylococcus sciuri group

Oxacillin/methicillin-resistance is related to the mecA and its regulatory genes mecR1 and mecI. Its origin is still unknown, although evidences support that it is related to CNS, once mecA and a homologue gene, pbpD, were both detected in Staphylococcus sciuri species group. The present work evaluated 210 samples of skin and ear swabs from rodents and 60 nasal swabs from equines of Army Biologic Institute, Rio de Janeiro. Pheno- and genotypic characterization provided 59.52% (25/42) and 78.57% (11/14) S. lentus and S. sciuri, respectively. It was observed that although all S. sciuri isolates tested positive for pbpD, there was no correlation with oxacillin-resistance. On the other hand, isolates tested positive for mecA gene also presented phenotypic oxacillin-resistance in at least one assay. The alignment of the mecA gene showed that the nucleotide sequences were sorted into 2 different groups, one comprising the bovine strains and the other containing human and equine strains.
Restoring miR122 in human stem-like hepatocarcinoma cells, prompts tumor dormancy through Smad-independent TGF-β pathway

miR122 is the prevalent miRNA in adult healthy liver and it is responsible for liver stem cell differentiation towards hepatocyte lineage. Its expression is frequently lost in hepatocellular carcinoma (HCC). We studied the effects of restoring miR122 expression in a distinctive cell line derived from human HCC-BCLC9 cells-with a solid stem-like cell profile, high tumor initiating ability and undetectable miR122 expression. We generated a stable BCLC9 cell line that expresses miR122 (BCLC9-miR122). Restitution of miR122 in BCLC9 cells, decreases cell proliferation rate and reduces significantly tumor size in vivo. BCLC9-miR122 cells down-regulate expression of MYC, KLF4, FOXM1, AKT2 and AKT3 genes and up-regulate FOXO1 and FOXO3A gene expression. In addition, miR122 transfected cells decreased AKT2 kinase activation while decreased FOXO1 and FOXO3A protein inactivation. Reduction in tumor size in BCLC9-miR122 associated with an increase in p38MAPK protein expression and activation leading to a low phospho-ERK1/2 to phospho-p38 ratio. Treatment of miR122 positive cells with an inhibitor of TGFBR1 activation, abolished tumor dormancy program and recovered cell proliferation rate through a Smad-independent TGF-β response. HCC stem-like cells can be directed towards cell differentiation and tumor dormancy by restoring miR122 expression. We demonstrate, for the first time, that dormancy program is achieved through a Smad-independent TGF-β pathway. Reestablishing miR122 expression is a promising therapeutic strategy that would work concurrently reducing tumor aggressiveness and decreasing disease recurrence.
Cancers with Higher Density of Tumor-Associated Macrophages Were Associated with Poor Survival Rates

Background: Macrophages are a component of a tumor’s microenvironment and have various roles in tumor progression and metastasis. This study evaluated the relationships between tumor-associated macrophage (TAM) density and clinical outcomes in 14 different types of human cancers. Methods: We investigated TAM density in human tissue microarray sections from 14 different types of human cancers (n = 266) and normal thyroid, lung, and breast tissues (n = 22). The five-year survival rates of each cancer were obtained from the 2011 Korea Central Cancer Registry. Results: Among 13 human cancers, excluding thyroid cancer, pancreas, lung, and gallbladder cancers had the highest density of CD163-positive macrophages (7.0±3.5%, 6.9±7.4%, and 6.9 ± 5.5%, respectively). The five-year relative survival rates of these cancers (pancreas, 8.7%; lung, 20.7%; gallbladder, 27.5%) were lower than those of other cancers. The histological subtypes in thyroid cancer exhibited significantly different CD163-positive macrophages densities (papillary, 1.8 ± 1.6% vs anaplastic, 22.9 ± 17.1%; p < .001), but no significant difference between histological subtypes was detected in lung and breast cancers. Moreover, there was no significant difference in CD163-positive macrophages densities among the TNM stages in lung, breast, and thyroid cancers. Conclusions: Cancers with higher TAM densities (pancreas, lung, anaplastic thyroid, and gallbladder) were associated with poor survival rate.