Miracle-dz/UniFAR-FTUs huggingface dataset:
Feedback GAN (FBGAN) for DNA: a Novel Feedback-Loop Architecture for Optimizing Protein Functions

Generative Adversarial Networks (GANs) represent an attractive and novel approach to generate realistic data, such as genes, proteins, or drugs, in synthetic biology. Here, we apply GANs to generate synthetic DNA sequences encoding for proteins of variable length. We propose a novel feedback-loop architecture, called Feedback GAN (FBGAN), to optimize the synthetic gene sequences for desired properties using an external function analyzer. The proposed architecture also has the advantage that the analyzer need not be differentiable. We apply the feedback-loop mechanism to two examples: 1) generating synthetic genes coding for antimicrobial peptides, and 2) optimizing synthetic genes for the secondary structure of their resulting peptides. A suite of metrics demonstrate that the GAN generated proteins have desirable biophysical properties. The FBGAN architecture can also be used to optimize GAN-generated datapoints for useful properties in domains beyond genomics.
Molecular Characterization of Leading Edge Protrusions in the Absence of Arp2/3 Complex

Cells employ protrusive leading edges to navigate and promote their migration in diverse physiological environments. Classical models of leading edge protrusion rely on a treadmilling dendritic actin network that undergoes continuous assembly nucleated by the Arp2/3 complex, forming ruffling lamellipodia. Although the dendritic nucleation model has been rigorously evaluated in several computational studies, experimental evidence demonstrating a critical role for Arp2/3 in the generation of protrusive actin structures and cell motility has been far from clear. Most components of the pathway have been probed for their relevance by RNA interference or dominant-negative constructs. However, given that the Arp2/3 complex nucleates actin at nanomolar concentrations, even a dramatic knockdown could still leave behind a level sufficient to fully or partially support Arp2/3 complex-dependent functions.
Serum levels of testosterone and SHBG in association with body mass index improve the predictive capability of consolidate tumor biomarkers in pre- and postmenopausal breast cancer patients

Objective To investigate the contribution of serum levels of testosterone (TS) and sex hormone binding globulin (SHBG) in association with body mass index (BMI) as a surrogate marker of obesity, to the predictive capability of tumor size (T), lymph node (N) and estrogen receptor (ER) status and proliferative activity (TLI). Methods We investigated 120 women with primary breast cancer and median follow-up of 138 months. Serum levels of TS and SHBG and patient's BMI were evaluated before surgery. The contribution of TS, SHBG, their ratio (TS/SHBG) and BMI to the predictive capability of tumor-specific biomarkers was investigated by Harrell's c statistic. Results TS alone did not affect prognosis, whereas SHBG was protective in postmenopausal patients, in which BMI was associated with a progressive increase in the relapse-specific hazard ratio (HR). When in combination, TS, SHBG and BMI, affected prognosis in different ways depending on menopausal status. The best predictive capability (c = 0.78) was observed in postmenopausal patients when at the basic model (N + TLI) were added TS, BMI, TS * BMI interaction, with or without SHBG. In premenopause subgroup, the best predictive capability (c = 0.67) was provided by the basic model (N + TLI) plus TS and SHBG or their ratio, BMI and TS * BMI or TS/SHBG * BMI interaction. Conclusions Patient-associated features such as BMI and serum levels of TS and SHBG can improve the predictive capability of consolidate tumor-specific biomarkers in both pre- and postmenopause, thus providing a relevant contribution to the decision-making process.
X-ray Diffraction Analysis on the Surface Layer Grain Size of 45 Steel after High Energy Shot Peening

The surface of 45 medium carbon steel was treated by high energy shot peening technique first,and then the microstructures of the surface layer were characterized by means of X-ray diffraction(XRD). The practical and de-noising XRD spectrums were presented.The evolution of the grain size on the surface layer was investigated by the full width at half maximum and the average grain size was calculated.The results show that the mean grain size in the medium carbon steel surface with treatment of high energy shot peening is in the range of nanocystalline, and the average grain size is about 64.847 8 nm.The X-ray diffraction can be used to reveal the rnicrostructures of the nanocrystalline layer.
Recent Developments in Cannabis Chemistry

The marijuana plant Cannabis sativa contains a bewildering array of organic chemicals. As is true with other botanic species, there are representatives of almost all chemical classes present, including monoand sesquiterpenes, carbohy-drates, aromatics, and a variety of nitrogenous compounds. Interest in the study of this plant has centered primarily on the resinous fraction, as it is this material that is invested with the pharmacological activity that is peculiar to the plant. This resin is secreted by the female plant as a protective agent during seed ripening, although it can be found as a microscopic exudate through the aerial portions of plants of either sex. The pure resin, hashish or charas, is the most potent fraction of the plant, and has served as the source material for most of the chemical studies. The family of chemicals that has been isolated from this source has been referred to as the cannabinoid group. It is unique amongst psychotropic materials from plants in that there are no alkaloids present. The fraction is totally nitro-gen-free. Rather, the set of compounds can be considered as analogs of the parent compound cannabinol (I), a fusion product of terpene and a substituted resorcinol. Beyond the scope of this present review are such questions as the distribution of these compounds within the plant, the bo-tanic variability resulting from geographic distribution, the diversity of pharmacological action assignable to the several distinct compounds present, and the various preparations and customs of administration. This presentation will be limited to chemical structure and synthesis, with only passing com-ments on the topics of biosynthesis and human use.
A reference-free time difference of arrival source localization using a passive sensor array

Least squares source position estimation techniques from time difference of arrival measurements are based on choosing a reference sensor. Selecting different reference sensors may affect the positioning accuracy by a considerable amount. We suggest a closed-form least squares position estimation using all the available distinct time differences, which does not involve the selection of a reference sensor. The nonlinear terms, associated with the distances between the sensors and the source, are eliminated with an orthogonal projection matrix. Simulation results show that the proposed approach outperforms previous closed-form least squares solutions.
Cascades of Homeostatic Dysregulation Promote Incubation of Cocaine Craving

In human drug users, cue-induced drug craving progressively intensifies after drug abstinence, promoting drug relapse. This time-dependent progression of drug craving is recapitulated in rodent models, in which rats exhibit progressive intensification of cue-induced drug seeking after withdrawal from drug self-administration, a phenomenon termed incubation of drug craving. Although recent results suggest that functional alterations of the nucleus accumbens (NAc) contribute to incubation of drug craving, it remains poorly understood how NAc function evolves after drug withdrawal to progressively intensify drug seeking. The functional output of NAc relies on how the membrane excitability of its principal medium spiny neurons (MSNs) translates excitatory synaptic inputs into action potential firing. Here, we report a synapse-membrane homeostatic crosstalk (SMHC) in male rats, through which an increase or decrease in the excitatory synaptic strength induces a homeostatic decrease or increase in the intrinsic membrane excitability of NAc MSNs, and vice versa. After short-term withdrawal from cocaine self-administration, despite no actual change in the AMPA receptor-mediated excitatory synaptic strength, GluN2B NMDA receptors, the SMHC sensors of synaptic strength, are upregulated. This may create false SMHC signals, leading to a decrease in the membrane excitability of NAc MSNs. The decreased membrane excitability subsequently induces another round of SMHC, leading to synaptic accumulation of calcium-permeable AMPA receptors and upregulation of excitatory synaptic strength after long-term withdrawal from cocaine. Disrupting SMHC-based dysregulation cascades after cocaine exposure prevents incubation of cocaine craving. Thus, cocaine triggers cascades of SMHC-based dysregulation in NAc MSNs, promoting incubated cocaine seeking after drug withdrawal. SIGNIFICANCE STATEMENT Here, we report a bidirectional homeostatic plasticity between the excitatory synaptic input and membrane excitability of nucleus accumbens (NAc) medium spiny neurons (MSNs), through which an increase or decrease in the excitatory synaptic strength induces a homeostatic decrease or increase in the membrane excitability, and vice versa. Cocaine self-administration creates a false homeostatic signal that engages this synapse-membrane homeostatic crosstalk mechanism, and produces cascades of alterations in excitatory synapses and membrane properties of NAc MSNs after withdrawal from cocaine. Experimentally preventing this homeostatic dysregulation cascade prevents the progressive intensification of cocaine seeking after drug withdrawal. These results provide a novel mechanism through which drug-induced homeostatic dysregulation cascades progressively alter the functional output of NAc MSNs and promote drug relapse.
MAFB enhances oncogenic Notch signaling in T cell acute lymphoblastic leukemia

The transcription factor MAFB epigenetically facilitates Notch1-induced T cell leukemia. New targets, better mouse model for leukemia T cell acute lymphoblastic leukemias (T-ALLs) are often caused by mutations in the gene encoding Notch1, which mediates cell-cell contact signaling in embryonic development and adult tissue maintenance. However, mice expressing these mutants frequently fail to develop T-ALL. Pajcini et al. found that the transcription factors MAFB and ETS2 increased the expression of Notch1 target genes in mouse and human T-ALL cells by recruiting histone acetyltransferases. Expressing MAFB enhanced the development of Notch1-mutant T-ALL in mice. Because Notch1 is critical for the maintenance of various healthy adult tissues, developing a way to inhibit MAFB or its interacting partners may be a more targeted therapy for leukemia patients. Activating mutations in the gene encoding the cell-cell contact signaling protein Notch1 are common in human T cell acute lymphoblastic leukemias (T-ALLs). However, expressing Notch1 mutant alleles in mice fails to efficiently induce the development of leukemia. We performed a gain-of-function screen to identify proteins that enhanced signaling by leukemia-associated Notch1 mutants. The transcription factors MAFB and ETS2 emerged as candidates that individually enhanced Notch1 signaling, and when coexpressed, they synergistically increased signaling to an extent similar to that induced by core components of the Notch transcriptional complex. In mouse models of T-ALL, MAFB enhanced leukemogenesis by the naturally occurring Notch1 mutants, decreased disease latency, and increased disease penetrance. Decreasing MAFB abundance in mouse and human T-ALL cells reduced the expression of Notch1 target genes, including MYC and HES1, and sustained MAFB knockdown impaired T-ALL growth in a competitive setting. MAFB bound to ETS2 and interacted with the acetyltransferases PCAF and P300, highlighting its importance in recruiting coactivators that enhance Notch1 signaling. Together, these data identify a mechanism for enhancing the oncogenic potential of weak Notch1 mutants in leukemia models, and they reveal the MAFB-ETS2 transcriptional axis as a potential therapeutic target in T-ALL.
A semantic scene model for multitemporal detection of Urban villages in mega city regions of China

Urban villages (UVs) are a special type of urban settlements in China. Their spatial evolution in recent years has a close relationship with urban planning and economic development. However, the remote sensing community pays little attention to UVs. This paper presents a new semantic scene model based on primitive indexes for detecting UVs using high resolution remotely sensed imagery. The model represents scenes as characteristics histograms of primitive objects. In the experiments, UVs in the main urban areas of Shenzhen over 2003-2012 were mapped. The proposed model outperformed conventional scene models quantitatively and visually, and showed good transferability across multitemporal images.
Pre-existing malignancy results in increased prevalence of distinct populations of CD4+ T cells during sepsis

The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age-matched non-cancer controls were then subjected to CLP. Splenocytes were harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression Analysis of Density-normalized Events) were used to analyze populations of CD4+ cells most different between the two groups. Results indicated that relative to non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more activated CD4+ effectors, and fewer naïve CD4+ T cells during sepsis, suggesting that the CD4+ T cell compartment in cancer septic hosts is one of increased activation and differentiation. Moreover, cancer septic animals exhibited expansion of two distinct subsets of CD4+ T cells relative to previously healthy septic controls. Specifically, we identified increases in both a PD-1hi population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic animals. By combining phenotypic analysis of exhaustion markers with functional analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape of cancer septic animals is characterized by both increased CD4+ T cell activation and exhaustion, findings that may underlie the observed increased mortality in mice with pre-existing malignancy following sepsis.
A self-report scale to help make psychiatric diagnoses: the Psychiatric Diagnostic Screening Questionnaire.

BACKGROUND The Psychiatric Diagnostic Screening Questionnaire (PDSQ) is a brief, psychometrically strong, self-report scale designed to screen for the most common DSM-IV Axis I disorders encountered in outpatient mental health settings. In the present report, we describe the diagnostic performance (sensitivity, specificity, and positive and negative predictive values) of the PDSQ in an outpatient setting. METHODS Six hundred thirty psychiatric outpatients presenting for treatment were evaluated with the Structured Clinical Interview for DSM-IV after completing the PDSQ. Patients arrived approximately 20 minutes before the scheduled time of the appointment to complete the scale. Diagnostic raters were blind to responses on the scale. RESULTS The PDSQ's subscales' diagnostic performance varied in a predictable manner according to the cutoff score-as the threshold for case identification increased, subscale sensitivity decreased and specificity increased. Mean subscale sensitivities of 80%, 85%, and 90% resulted in mean subscale specificities of 78%, 73%, and 66%, respectively, and negative predictive values of 95%, 96%, and 97%. Receiver operating curves were determined for each subscale and all areas under the curve were significant. CONCLUSIONS The PDSQ is a diagnostic aid designed to be used in clinical practice to facilitate the efficiency of conducting initial diagnostic evaluations. From a clinical perspective, it is most important that a diagnostic aid have good sensitivity, so that most cases are detected, and high negative predictive value, so that most noncases on the measure are indeed noncases. Our results indicate that most of the PDSQ subscales were able to achieve this goal.
Influence of Organizational Citizenship Behavior on Hotel Employees’ Job Satisfaction and Subjective Well-Being

The aim of the present study is to analyze the influence of organizational citizenship behavior (OCB) of employees working for the accommodation business on their job satisfaction (JS) and subjective well-being (SWB). For this purpose, data were collected from 2,051 employees in various five-star accommodation enterprises located in Antalya, the most important tourism destination in Turkey. The analysis of the data showed that organizational citizenship behavior and its subdimensions correlate positively with job satisfaction and subjective well-being and influence them positively. It was also found that job satisfaction mediates the relationship between organizational citizenship behavior and subjective well-being. Employees with organizational citizenship behavior were found to have higher levels of job satisfaction and subjective well-being. The results showed that organizational citizenship behavior is a stronger predictor for the job satisfaction of the employees than subjective well-being. The findings offer useful and important implications for business managers when hiring employees.
Twitter tsunami early warning network : a social network analysis of Twitter information flows

In the aftermath of earthquakes, tsunamis, such as the 2011 Great East Japan Tsunami, caused enormous damage around the world. With the extreme disaster events of the past, nations improved disaster preparedness and response through sensors and tsunami early warning systems. Even with system usage, however, governments still need to warn the targeted citizens – who may be anywhere within the vulnerable areas – of predicted tsunami and ordered mass evacuations within a very limited lead time. While social media research is on the rise outside the domain of social networking, very little is written about Twitter use for tsunami early warning. In this research, therefore, we examined the utility of Twitter as a tsunami early warning network, which engages citizens and disaster management agencies in diffusing disaster information. We conducted a social network analysis of Twitter information flows among the central disaster warning agency’s Twitter followers during the 2012 Indonesia Earthquake.
Low-noise biasing of voltage-controlled oscillators by means of resonant inductive degeneration

Many of the existing theories on phase-noise generation in oscillators are concerned with the noise originating from the active part and the resonator, while the contribution of the biasing noise is usually neglected. However, some recent theories have enlightened that the contribution of the biasing noise to the overall phase noise of the oscillator, actually, overwhelms all the other contributors together. Therefore, the concept of biasing to minimize the noise contribution of the oscillator's tail-current source is described in this paper. The procedure followed in the noise optimization of the inductively-degenerated low-noise amplifier scheme is here applied to the tail-current source. Noise at close to double the oscillating frequency is identified as the main contributor of biasing-noise to the over-all oscillator phase noise, and a design procedure is developed accordingly. The presented analysis gives full insight into the performances of the low-noise biasing scheme, i.e., the resonant inductive degeneration of the current source, proving that this topology is an excellent trade-off between design effort and phase-noise performance.
Analysis of plasmons and homogenization in a flat-layered photonic crystals and hyperbolic metamaterials

The dispersion equation and the analysis and homogenization in periodic and quasiperiodic plane layered structures with alternating dielectric layers of metal and dielectric layers, as well as a graphene sheet and SiO2 layers have been investigated. The cases are considered when these patterns become the properties of hyperbolic metamaterials, i.e., having different signs of the real parts of the tensor components of the effective dielectric constant. It is shown that usage only dielectric layers is perspective in reducing losses.
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer

BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease‐free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two‐sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3‐year rate of disease‐free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease‐free survival rate for a 6‐month duration of therapy was superior to that for a 3‐month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P = 0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower‐risk subgroup. (Funded by the National Cancer Institute and others.)
Effects of knee loading on obesity‐related non‐alcoholic fatty liver disease in an ovariectomized mouse model with high‐fat diet

Hormonal and nutritional disorders are the main causes of obesity and non‐alcoholic fatty liver disease, especially in the elderly and in postmenopausal women. Although physical activity might alleviate these disorders, the elderly may often have difficulty in carrying out physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptoms of obesity and fatty liver.