Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct targeting pathways for the membrane insertion of tail-anchored (TA) proteins

Tail-anchored (TA) proteins are characterised by a C-terminal transmembrane region that mediates post-translational insertion into the membrane of the endoplasmic reticulum (ER). We have investigated the requirements for membrane insertion of three TA proteins, RAMP4, Sec61β and cytocrome b5. We show here that newly synthesised RAMP4 and Sec61β can accumulate in a cytosolic, soluble complex with the ATPase Asna1 before insertion into ER-derived membranes. Membrane insertion of these TA proteins is stimulated by ATP, sensitive to redox conditions and blocked by alkylation of SH groups by N-ethylmaleimide (NEM). By contrast, membrane insertion of cytochrome b5 is not found to be mediated by Asna1, not stimulated by ATP and not affected by NEM or an oxidative environment. The Asna1-mediated pathway of membrane insertion of RAMP4 and Sec61β may relate to functions of these proteins in the ER stress response.
Overview of Brain Microdialysis

The technique of microdialysis enables sampling and collecting of small‐molecular‐weight substances from the interstitial space. It is a widely used method in neuroscience and is one of the few techniques available that permits quantification of neurotransmitters, peptides, and hormones in the behaving animal. More recently, it has been used in tissue preparations for quantification of neurotransmitter release. This unit provides a brief review of the history of microdialysis and its general application in the neurosciences. The authors review the theoretical principles underlying the microdialysis process, methods available for estimating extracellular concentration from dialysis samples (i.e., relative recovery), the various factors that affect the estimate of in vivo relative recovery, and the importance of determining in vivo relative recovery to data interpretation. Several areas of special note, including impact of tissue trauma on the interpretation of microdialysis results, are discussed. Step‐by‐step instructions for the planning and execution of conventional and quantitative microdialysis experiments are provided. Curr. Protoc. Neurosci. 47:7.1. 1‐7.1. 28. © 2009 by John Wiley & Sons, Inc.
Fast and Accurate Online Video Object Segmentation via Tracking Parts

Online video object segmentation is a challenging task as it entails to process the image sequence timely and accurately. To segment a target object through the video, numerous CNN-based methods have been developed by heavily finetuning on the object mask in the first frame, which is time-consuming for online applications. In this paper, we propose a fast and accurate video object segmentation algorithm that can immediately start the segmentation process once receiving the images. We first utilize a part-based tracking method to deal with challenging factors such as large deformation, occlusion, and cluttered background. Based on the tracked bounding boxes of parts, we construct a region-of-interest segmentation network to generate part masks. Finally, a similarity-based scoring function is adopted to refine these object parts by comparing them to the visual information in the first frame. Our method performs favorably against state-of-the-art algorithms in accuracy on the DAVIS benchmark dataset, while achieving much faster runtime performance.
A User-Centric Diversity by Design Recommender System for the Movie Application Domain

Recommender systems (RS) have seen widespread adoption across the Internet. However, by emphasizing personalization through the optimization of accuracy-focused metrics, over - personalization may emerge, with negative effects on the user experience. A countermeasure to the problem is to diversify recommendations. In this paper, we present a solution that addresses the problem in the context of a movie application domain. The solution enhances diversity on four related dimensions, namely global coverage, local coverage, novelty, and redundancy. The proposed solution is designed to diversify users profiles, modeled on categorical preferences, within the same group in the recommendation filtering. We evaluate our approach on the Movielens dataset and show that our algorithm yields better results compared to random selection distant neighbors and performs comparably to one of the current state of the art solutions.
Tobacco Smoking, Alcohol Drinking, Diabetes, Low Body Mass Index and the Risk of Self-Reported Symptoms of Active Tuberculosis: Individual Participant Data (IPD) Meta-Analyses of 72,684 Individuals in 14 High Tuberculosis Burden Countries

Background The effects of multiple exposures on active tuberculosis (TB) are largely undetermined. We sought to establish a dose-response relationship for smoking, drinking, and body mass index (BMI) and to investigate the independent and joint effects of these and diabetes on the risk of self-reported symptoms of active TB disease. Methods and Findings We analyzed 14 national studies in 14 high TB-burden countries using self-reports of blood in cough/phlegm and cough lasting > = 3 weeks in the last year as the measures of symptoms of active TB. The random effect estimates of the relative risks (RR) between active TB and smoking, drinking, diabetes, and BMI<18.5 kg/m2 were reported for each gender. Floating absolute risks were used to examine dyads of exposure. Adjusted for age and education, the risks of active TB were significantly associated with diabetes and BMI<18.5 kg/m2 in both sexes, with ever drinking in men and with ever smoking in women. Stronger dose-response relationships were seen in women than in men for smoking amount, smoking duration and drinking amount but BMI<18.5 kg/m2 showed a stronger dose-response relationship in men. In men, the risks from joint exposures were statistically significant for diabetics with BMI<18.5 kg/m2 (RR = 6.4), diabetics who smoked (RR = 3.8), and diabetics who drank alcohol (RR = 3.2). The risks from joint risk factors were generally larger in women than in men, with statistically significant risks for diabetics with BMI<18.5 kg/m2 (RR = 10.0), diabetics who smoked (RR = 5.4) and women with BMI<18.5 kg/m2 who smoked (RR = 5.0). These risk factors account for 61% of male and 34% of female estimated TB incidents in these 14 countries. Conclusions Tobacco, alcohol, diabetes, and low BMI are significant individual risk factors but in combination are associated with triple or quadruple the risk of development of recent active TB. These risk factors might help to explain the wide variation in TB across countries.
Task engagement at work: Characteristics, antecedents and consequences

In this thesis existing theory is extended by combining work engagement and flow research to generate the concept of task engagement, which focuses on episodes of peak performance at work. Using a critical incident methodology in Study 1, task engagement was found to have three key characteristics (i.e., distortion of time; complete absorption in the task; and is a state of high cognitive efficiency). Both situational (i.e., high challenge/high skills, control, and proximal feedback) and psychological antecedents (i.e., safety, availability, meaning and self-efficacy) were also identified. In Study 2, a longitudinal diary study, study 1 findings were replicated and extended by examining duration and frequency of task engagement episodes at work, and their positive impact on employee well-being. Overall, task engagement was found to be a temporal and dynamic construct, involving the interplay of person and situation, which has implications for employee task performance and well-being.
Temporal transcriptomics suggest that twin-peaking genes reset the clock

The mammalian suprachiasmatic nucleus (SCN) drives daily rhythmic behavior and physiology, yet a detailed understanding of its coordinated transcriptional programmes is lacking. To reveal the finer details of circadian variation in the mammalian SCN transcriptome we combined laser-capture microdissection (LCM) and RNA-seq over a 24 hr light / dark cycle. We show that 7-times more genes exhibited a classic sinusoidal expression signature than previously observed in the SCN. Another group of 766 genes unexpectedly peaked twice, near both the start and end of the dark phase; this twin-peaking group is significantly enriched for synaptic transmission genes that are crucial for light-induced phase shifting of the circadian clock. 341 intergenic non-coding RNAs, together with novel exons of annotated protein-coding genes, including Cry1, also show specific circadian expression variation. Overall, our data provide an important chronobiological resource (www.wgpembroke.com/shiny/SCNseq/) and allow us to propose that transcriptional timing in the SCN is gating clock resetting mechanisms. DOI: http://dx.doi. org/10.7554/eLife.10518. 001
Impact of PSA density of transition zone as a potential parameter in reducing the number of unnecessary prostate biopsies in patients with PSA levels between 2.6 and 10.0 ng/mL

ABSTRACT Purpose: To assess the accuracy of prostate-specific antigen (PSA) adjusted for the transition zone volume (PSATZ) in predicting prostate cancer by comparing the ability of several PSA parameters in predicting prostate cancer in men with intermediate PSA levels of 2.6 – 10.0 ng/mL and its ability to reduce unnecessary biopsies. Materials and Methods: This study included 656 patients referred for prostate biopsy who had a serum PSA of 2.6 – 10.0 ng/mL. Total prostate and transition zone volumes were measured by transrectal ultrasound using the prolate ellipsoid method. The clinical values of PSA, free-to-total (F/T) ratio, PSA density (PSAD) and PSATZ for the detection of prostate cancer were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative (benign) were conducted. Results: Cancer was detected in 172 patients (26.2%). Mean PSA, PSATZ, PSAD and F/T ratio were 7.5 ng/mL, 0.68 ng/mL/cc. 0.25 ng/mL/cc and 0.14 in patients with prostate cancer and 6.29 ng/mL, 0.30 ng/mL/cc, 0.16 ng/mL/cc and 0.22 in patients with benign biopsies, respectively. ROC curves analysis demonstrated that PSATZ had a higher area under curve (0,838) than F/T ratio (0.806) (P<0.001) and PSAD (0.806) (P<0.001). With a cut-off value of 0.22 ng/mL/cc, PSATZ had 100% of sensitivity and could have prevented 24% of unnecessary biopsies. Conclusions: PSATZ may be useful in enhancing the specificity of serum PSA. Compared to other PSA related parameters, it was better in differentiating between prostate cancer and benign prostatic enlargement. Also, PSATZ could reduce a significant number of unnecessary biopsies.
Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis

Summary Tick saliva is a rich source of molecules with antiinflammatory, antihemostatic and immunosupressive properties. In this paper, a novel tick salivary gland cDNA with sequence homology to tissue factor pathway inhibitor (TFPI) and coding for a protein called Penthalaris has been characterized from the Lyme disease vector, Ixodes scapularis. Penthalaris is structurally unique and distinct from TFPI or TFPI-like molecules described so far, including Ixolaris, NAPc2, TFPI-1 and TFPI-2. Penthalaris is a 308-amino-acid protein (35 kDa, pI 8.58) with 12 cysteine bridges and 5 tandem Kunitz domains. Recombinant Penthalaris was expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor(TF)-induced factor X (FX) activation with an IC50 of ∼ 100 pM. Penthalaris tightly binds both zymogen FX and enzyme FXa (exosite), but not FVIIa, as demonstrated by column gel-filtration chromatography. At high concentrations, Penthalaris attenuates FVIIa/TF-induced chromogenic substrate (S2288) hydrolysis and FIX activation. In the presence of DEGR-FX or DEGR-FXa, but not des-Gla-DEGR-FXa as scaffolds, tight and stoichiometric inhibition of FVIIa/TF was achieved. In addition, Penthalaris blocks cell surface-mediated FXa generation by monomer (de-encrypted), but not dimer (encrypted) TF in HL-60 cells. Penthalaris may act in concert with Ixolaris and other salivary anti-hemostatics in order to help ticks to successfully feed on blood. Penthalaris is a novel anticoagulant and a tool to study FVIIa/TF-initiated biologic processes.
Biomarkers in adult posthemorrhagic hydrocephalus

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.
A durable and energy efficient main memory using phase change memory technology

Using nonvolatile memories in memory hierarchy has been investigated to reduce its energy consumption because nonvolatile memories consume zero leakage power in memory cells. One of the difficulties is, however, that the endurance of most nonvolatile memory technologies is much shorter than the conventional SRAM and DRAM technology. This has limited its usage to only the low levels of a memory hierarchy, e.g., disks, that is far from the CPU. In this paper, we study the use of a new type of nonvolatile memories -- the Phase Change Memory (PCM) as the main memory for a 3D stacked chip. The main challenges we face are the limited PCM endurance, longer access latencies, and higher dynamic power compared to the conventional DRAM technology. We propose techniques to extend the endurance of the PCM to an average of 13 (for MLC PCM cell) to 22 (for SLC PCM) years. We also study the design choices of implementing PCM to achieve the best tradeoff between energy and performance. Our design reduced the total energy of an already low-power DRAM main memory of the same capacity by 65%, and energy-delay2 product by 60%. These results indicate that it is feasible to use PCM technology in place of DRAM in the main memory for better energy efficiency.
Lymphoid Malignancies in U.S. Asians: Incidence Rate Differences by Birthplace and Acculturation

Background: Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHL), HL, and multiple myeloma, occur at much lower rates in Asians than other racial/ethnic groups in the United States. It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status. Methods: We obtained data about all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from U.S. Census data. Results: Although incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than U.S.-born Asians with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower SES neighborhoods than those living elsewhere. Conclusions: These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL. Impact: Studying specific lymphoid malignancies in U.S. Asians may provide valuable insight toward understanding their environmental causes. Cancer Epidemiol Biomarkers Prev; 20(6); 1064–77. ©2011 AACR.
Spinal Cord Stimulation Electrode Design: Prospective, Randomized, Controlled Trial Comparing Percutaneous and Laminectomy Electrodes—Part I: Technical Outcomes

OBJECTIVE The clinical use of spinal cord stimulation for treatment of chronic intractable pain has been increasingly successful because of recent technical improvements, particularly the development of multiple-contact electrodes supported by programmable implanted pulse generators. Contemporary electrodes can be placed percutaneously in some cases and require a limited laminectomy in other cases. METHODS We performed a prospective, randomized, controlled trial comparing two prototypical electrode designs, using a computerized system that allows direct patient interaction and quantitative measurements. A series of 24 patients with chronic lumbosacral pain syndromes first underwent testing with percutaneous four-contact electrodes and then underwent implantation, at the same spinal level, of one of two different electrode configurations; 12 patients received a new percutaneous four-contact electrode of the same design and 12 received an insulated four-contact array, which was implanted via laminectomy. RESULTS The insulated array performed significantly (P = 0.0005–0.0047) better than the temporary percutaneous electrode for the same patients, according to all three measures tested (ratings of paresthesia coverage of pain, coverage calculated from patient drawings, and amplitudes), at the “usage” amplitude for the three standard bipoles examined. The insulated array also performed significantly (P = 0.0000–0.026) better than the permanent percutaneous electrode in terms of coverage ratings and amplitude requirements. Low back coverage ratings were significantly better for the insulated array than for the temporary percutaneous electrode, and scaled amplitudes necessary for low back coverage were significantly better for the permanent percutaneous electrode than for the temporary electrode. In comparison with the percutaneous temporary electrode, at subjectively identical stimulation intensities, the permanent insulated array required significantly lower amplitude. CONCLUSION We can immediately infer from these technical data that the use of an insulated array, in comparison with a percutaneous electrode, would double battery life. Extended follow-up monitoring will be required to assess the extent to which the technical advantages we observed for the insulated array might be associated with improved clinical outcomes.
Cancer anorexia: hypothalamic activity and its association with inflammation and appetite‐regulating peptides in lung cancer

Energy homeostasis is mediated by the hypothalamus, whose inflammation‐induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non‐anorexic (NA) cancer patients, and in controls (C).
Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development

NK cell maturation depends on transcription factor ID2 blocking acquisition of a naïve T cell gene program. Establishing NK cell IDentity The transcription factor ID2 is required for normal differentiation of all innate lymphoid cells, including natural killer (NK) cells. Zook et al. have characterized ID2-deficient NK cells and investigated how ID2 supports full maturation of NK cells into cytotoxic effectors. They found that ID2 limited chromatin accessibility at multiple lymphocyte-associated genes correlated with a naïve gene program, thereby enabling an effector gene program to take hold. This study provides insight into the series of transcriptional programming steps that underpin normal NK cell differentiation. All innate lymphoid cells (ILCs) require the small helix-loop-helix transcription factor ID2, but the functions of ID2 are not well understood in these cells. We show that mature natural killer (NK) cells, the prototypic ILCs, developed in mice lacking ID2 but remained as precursor CD27+CD11b− cells that failed to differentiate into CD27−CD11b+ cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naïve T lymphocyte–associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules and altered the NK cell response to inflammatory cytokines. In the absence of ID2, CD27+CD11b− NK cells expressed ID3, a helix-loop-helix protein associated with naïve T cells, and they transitioned from a CD8 memory precursor–like to a naïve-like chromatin accessibility state. We demonstrate that ID3 was required for the development of ID2-deficient NK cells, indicating that completely unfettered E protein function is incompatible with NK cell development. These data solidify the roles of ID2 and ID3 as mediators of effector and naïve gene programs, respectively, and revealed a critical role for ID2 in promoting a chromatin state and transcriptional program in CD27+CD11b− NK cells that supports cytotoxic effector differentiation and cytokine responses.
EVALUATION OF NEXRAD STAGE III PRECIPITATION DATA OVER A SEMIARID REGION 1

This study examines NEXRAD Stage III product (hourly, cell size 4 km by 4 km) for its ability in estimating precipitation in central New Mexico, a semiarid area. A comparison between Stage III and a network of gauge precipitation estimates during 1995 to 2001 indicates that Stage III (1) overestimates the hourly conditional mean (CM) precipitation by 33 percent in the monsoon season and 55 percent in the nonmonsoon season; (2) overestimates the hourly CM precipitation for concurrent radar‐gauge pairs (nonzero value) by 13 percent in the monsoon season and 6 percent in the nonmonsoon season; (3) overestimates the seasonal precipitation accumulation by 11 to 88 percent in monsoon season and underestimates by 18 to 89 percent in the nonmonsoon season; and (4) either overestimates annual precipitation accumulation up to 28.2 percent or underestimates it up to 11.9 percent. A truncation of 57 to 72 percent of the total rainfall hours is observed in the Stage III data in the nonmonsoon season, which may be the main cause for both the underestimation of the radar rainfall accumulation and the lower conditional probability of radar rainfall detection in the nonmonsoon season. The study results indicate that the truncation caused loss of small rainfall amounts (events) is not effectively corrected by the real‐time rain gauge calibration that can adjust the rainfall rates but cannot recover the truncated small rainfall events. However, the truncation error in the monsoon season may be suppressed due to the larger rainfall rate and/or combined effect of overestimates by bright band and hail contaminations, virga, advection, etc. In general, improvement in NEXRAD performance since the monsoon season in 1998 is observed, which is consistent with the systematic improvement in the NEXRAD network.