Miracle-dz/UniFAR-FTUs huggingface dataset:
The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D*

Background: Immune activation through a balanced cell surface expression of human NKG2D ligands is crucial for the elimination of diseased cells. Results: Methylselenol induces the expression of the NKG2D ligands MICA/B but specifically inhibits ULBP2 protein expression. Conclusion: Methylselenol regulates NKG2D ligand expression on transcriptional and posttranscriptional levels. Significance: Methylselenol is the first identified metabolite that diversely regulates NKG2D ligands, and, therefore, its implementation could improve NKG2D-based immune therapy. For decades, selenium research has been focused on the identification of active metabolites, which are crucial for selenium chemoprevention of cancer. In this context, the metabolite methylselenol (CH3SeH) is known for its action to selectively kill transformed cells through mechanisms that include increased formation of reactive oxygen species, induction of DNA damage, triggering of apoptosis, and inhibition of angiogenesis. Here we reveal that CH3SeH modulates the cell surface expression of NKG2D ligands. The expression of NKG2D ligands is induced by stress-associated pathways that occur early during malignant transformation and enable the recognition and elimination of tumors by activating the lymphocyte receptor NKG2D. CH3SeH regulated NKG2D ligands both on the transcriptional and the posttranscriptional levels. CH3SeH induced the transcription of MHC class I polypeptide-related sequence MICA/B and ULBP2 mRNA. However, the induction of cell surface expression was restricted to the ligands MICA/B. Remarkably, our studies showed that CH3SeH inhibited ULBP2 surface transport through inhibition of the autophagic transport pathway. Finally, we identified extracellular calcium as being essential for CH3SeH regulation of NKG2D ligands. A balanced cell surface expression of NKG2D ligands is considered to be an innate barrier against tumor development. Therefore, our work indicates that the application of selenium compounds that are metabolized to CH3SeH could improve NKG2D-based immune therapy.
Development of a Fast-Track Protocol for Hydrocele Surgery

Objectives: To describe a multimodal recovery protocol (fast-track surgery) for hydrocele surgery, as developed by our urology department over the course of the last 10 years. Likewise, our aim was to demonstrate the use of this protocol improves the cost effectiveness of the procedure, compared to the classical procedure which requires hospital admission and general or spinal anaesthesia. Material and Methods: We compared two groups of patients. The first group underwent hydrocelectomy under our multimodal recovery protocol in an outpatient setting, with data collected prospectively, while the second group of patients underwent hydrocelectomy before the implementation of the multimodal recovery protocol, with hospital admission and general or spinal anesthesia, with data collected retrospectively. The results obtained were assessed and satisfaction degree ascertained by survey. Results: The results obtained with fast-track protocol were comparable to those of conventional surgery. Only two of the patients needed to be admitted in hospital due to postoperative complications, which it was not related with the outpatient setting treatment. The satisfaction degree with the treatment was found to be over 95%. Conclusions: Virtually all patients affected by hydroceles could be suitable candidates for a fast-track surgery programme, with the consequent improvement in cost-effectiveness of the procedure with no reduction of the quality of care received or patient satisfaction. *Corresponding author: Pedro Navalón Verdejo, Urology Department, University Hospital “Casa de Salud”, Catholic University San Vicente Mártir, Paseo Alameda 38246023, Valencia, Spain, Email: pedronavalon@yahoo.com
Hedgehog signaling.

The Hedgehog (Hh) proteins belong to one of a small number of families of secreted signals that play a central role in the development of most metazoans. hh itself was originally identified as a mutation that causes a “segment polarity” phenotype in Drosophila—as were most of the core components of the Hh signal transduction pathway (Ingham et al. 2011). These components have been highly conserved between flies and vertebrates (Figs. 1 and 2); however, mammals express three related proteins, Sonic hedgehog (Shh), Indian hedgehog, and Desert hedgehog (Dhh), and genetic analysis in mice has uncovered a vertebrate-specific role of the primary cilium in Hh signaling (Goetz et al. 2009). An unusual feature of Hh proteins is their covalent coupling to cholesterol, which occurs during autocleavage of the proprotein to yield the signaling moiety, HhN (Beachy et al. 1997). HhN is also palmitoylated at its amino terminus by an acyl transferase encoded by the Drosophila skinny hedgehog gene (Skn). Secretion of lipidated HhN requires the function of a large multipass transmembrane protein, Dispatched, that is structurally related to the Hh receptor Patched (Ptch1) (Ingham et al. 2011). Binding of HhN to Ptc1 is promoted by two other transmembrane proteins, CDO and BOC (known as IHOG and BOI in Drosophila), which act redundantly to bind HhN via one of several fibronectin III (FnIII) motifs in their extracellular domains (Beachy et al. 2010). In its unbound state, Ptc1 localizes to the primary cilium (Rohatgi and Scott 2007), where it acts via a poorly characterized mechanism, thought to involve the transport of one or more lipids, to suppress the activity of the G-protein-coupled receptor (GPCR)-like protein Smoothened (Smo) (Ayers and Thérond 2010). The principal response of cells to HhN is the activation of target genes by the Gli zinc finger proteins. Gli2 and Gli3 (but not Gli1) are bifunctional transcription factors: their full-length forms function as transcriptional activators, but they can be converted into lower-molecular-weight transcriptional repressors. This is promoted by the phosphorylation of a series of motifs within the carboxy-terminal domain of the protein. These motifs are sequentially phosphorylated by PKA, GSK3, and CKI to generate recognition signals for the F-box protein bTrCP, a component of the SCF complex. This in turn catalyzes the ubiquitylation of the carboxyl terminus, targeting it for degradation by the proteasome to yield the truncated amino-terminal repressor forms, Gli2/3R (Ingham et al. 2011). These bind to Hh target genes to repress their transcription. Gli2/3 proteins appear to shuttle up and down the primary cilium in association with the Cos/Kif7 and SuFu proteins; in the absence of Smo activity, this association seems to promote their processing at the base of the primary cilium. Inactivation of Ptc by HhN results in Smo being transported to the tip of the primary cilium (a process that requires Kif3a and b-arrestin activity), where its activity promotes the dissociation of the Gli2/3-Cos-SuFu complex (Tukachinsky et al. 2010), releasing the full-length highly labile forms
Impedance control of quadruped robot and its impedance characteristic modulation for trotting on irregular terrain

Trotting on irregular terrain is a difficult task as undesirable impulse force by collision between robot foot and an obstacle makes the robot unstable. To cope with the problem, in this paper, variable impedance control algorithm changing leg impedance parameters according to the change of finite trot states is proposed. The state of quadruped trot is divided into five phases and the impedance parameters are changed to generate adequate response to the contact force in each locomotion phase. Simulation of trotting on irregular terrain with half-ellipsoidal trajectory has been performed with the control groups. The simulation has verified that the proposed control method shows outstanding performance and better stability for trotting on the highly irregular terrain.
The pathology of myocardial ischaemia.

To understand the pathology of myocardial ischaemia detailed knowledge of the anatomy and physiology of the coronary arterial tree is required. The anatomy of the major coronary arteries running on the epicardial surface of the heart has been common knowledge for years. The equally important micro-anatomy of vessels within the myocardium has been neglected along with the physiology of intramyocardial blood flow.
Infant and Maternal Risk Factors for Pertussis-Related Infant Mortality in the United States, 1999 to 2004

Background: Infants aged <12 months have the highest rates of complications and death from pertussis of any age group. Factors that increase the risk of pertussis-related death in infants are not well defined. Methods: The US Multiple Cause-of-Death and Linked Birth/Infant Death databases were used for 1999 to 2004 to examine pertussis-related infant mortality rates and to obtain anonymous records of infants with pertussis listed as a cause of death and of surviving infants. Infant and maternal characteristics present at the time of birth for infants who died with pertussis were compared with those of surviving infants. Results: During 1999 to 2004, 91 infant deaths were reported with pertussis as a cause of death. All infants were 7 months or younger; 58% were age <2 months. The average annual infant mortality rate attributed to pertussis was 3.8 (95% CI: 3.0–4.6) per 1,000,000 live births, and 13.1 (95% CI: 9.8–17.1) per 1,000,000 live births for infants aged <2 months. Infant pertussis deaths showed an independent association with birth weight <2500 g, female sex, Apgar score <8, and mother with <12 years education. The mortality rate among Hispanic infants aged <2 months was 2.6 times greater than among non-Hispanic infants of similar age. Conclusions: Ensuring pertussis booster vaccination of adults and adolescents in close contact with an infant is warranted to prevent transmission of pertussis to vulnerable infants, particularly infants too young to be immunized. Special emphasis should be given to women and infant settings in which the risk of infant pertussis death might be increased.
Long‐term kidney transplant outcome in obese patients in a predominantly African American population

Karabicak I, Aytug S, Lewis S, Shah S, Sumrani N, Hayat A, Distant DA, Salifu MO. Long‐term kidney transplant outcome in obese patients in a predominantly African American population. Clin Transplant 2011: 25: E264–E270. © 2011 John Wiley & Sons A/S.
A 24GHz down-conversion mixer with low noise and high gain

In this paper, a down-converting mixer implemented in the TSMC 0.18-μm CMOS process technology for applications in the 24GHz band is presented. For suppressing the flicker noise generated in the switching stage of the conventional Gilbert cell topology, a current bleeding technique combined with negative resistance is adopted to improve the noise figure (NF) of the mixer. In addition, an inductor is utilized to resonate with the parasitic capacitances at the output of the transconductance (Gm) stage and thus increases the power conversion gain (CG) and the linearity of the proposed mixer. The chip size of the proposed mixer is 1.062 × 0.979 mm2, and the core circuit consumes a dc power of 5.65mW from the 1.8-V voltage supply. The measured CG and NF for the proposed 24GHz mixer are 8.376dB and 11.6dB, respectively. And the measured 1dB compression point (P1dB) is -8.4dBm at the 24GHz operating frequency.
WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity

Significance The anaphase-promoting complex/cyclosome (APC/C) is a large E3 ubiquitin ligase that controls progression through mitosis and entry into G1. Its capacity to recognize and ubiquitinate substrates is dependent on coactivator subunits that interact with substrate degrons and promote a conformational change of the APC/C to increase its affinity for the priming E2 UbcH10. We show that the WD40 domain of anaphase-promoting complex subunit 1 (Apc1) is required for communicating the conformational change initiated by the binding of coactivator to the catalytic module. In contrast to UbcH10, binding of the elongating E2 Ube2S and its APC/C-stimulated activity does not require the active state of the APC/C. The work raises the possibility that conformational changes of the Apc1 WD40 domain may play a role in regulating UbcH10 binding to the APC/C. The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin–RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1WD40). To understand how Apc1WD40 contributes to APC/C activity, a mutant form of the APC/C with Apc1WD40 deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1WD40 abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C–Cdh1 complex with Apc1WD40 deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1WD40 is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.
Increased levels of interferon‐γ primed by culture filtrate proteins antigen and CpG‐ODN immunization do not confer significant protection against Mycobacterium tuberculosis infection

The results of various animal model studies of tuberculosis (TB) suggest that culture filtrate proteins (CFPs), which are antigens secreted by Mycobacterium tuberculosis, are largely responsible for improvements in TB vaccines. The great obstacle to developing protein subunit vaccines is that adjuvants are required in order to stimulate relevant protective immune responses. Acting as immune adjuvants, CpG‐oligodeoxynucleotides (CpG‐ODNs) promote the activation of Th1 cells and of pro‐inflammatory cytokines. To evaluate the adjuvant role of CpG‐ODNs in conferring enhanced immunogenic capacity and protection against M. tuberculosis, we immunized mice with CFP antigen combined with synthetic CpG‐ODNs (CFP/CpG) or with incomplete Freund's adjuvant (IFA) (CFP/IFA). Immunization with CFP/CpG induced a T helper 1 (Th1)‐biased response accompanied by a higher immunoglobulin G2a (IgG2a) antibody/IgG1 antibody ratio, elevated production of interferon‐γ (IFN‐γ) by spleen cells and in lungs. However, CFP/IFA‐immunized mice presented higher levels of IgG1 antibodies, as well as increased production of IFN‐γ, interleukin (IL)‐5, and IL‐10 by spleen cells, together with lower levels of IFN‐γ in the lungs. Despite the stronger Th1 response seen in both groups, believed to be necessary for protection against TB, only mice immunized with CFP/IFA were protected after M. tuberculosis infection. Lung histology revealed that lung parenchyma were better preserved in CFP/IFA‐immunized mice, which also presented intense lymphocyte recruitment to the lesion, whereas CFP/CpG‐immunized mice presented severe pulmonary injury accompanied by necrosis. Based on the data presented, we discuss the widely accepted paradigm that high levels of IFN‐γ are directly correlated with protection against experimental TB.
Multi-player Approximate Nash Equilibria

In this paper we study the complexity of finding approximate Nash equilibria in multi-player normal-form games. First, for any constant number m, we present a polynomial-time algorithm for computing a relative (1 - 1(1+(m-1)m))-Nash equilibrium in arbitrary m-player games and a relative (1 - 1(1+(m-1)m))-Nash equilibrium in symmetric m-player games. Next, we show that there is an additive e-well-supported Nash equilibrium, for any e>0, with support equal to O(ln(m n/e)/e2), where n is the number of pure strategies. Finally, we prove that finding additive approximate Nash equilibria is easy in random multi-player games.
(De)Composition of Situation Calculus Theories

We show that designing large situation calculus theories can be simplified by using object-oriented techniques and tools together with established solutions to the frame problem. Situation calculus (McCarthy & Hayes 1969) is one of the leading logical representations for action and change, but large situation calculus theories are not easy to design and maintain, nor are they flexible for extension or reuse. However, we wish to use it to represent large, complex domains. To address this problem, we apply our proposed methodology to situation calculus theories and analyze the composition of theories in this light. The object-oriented tools that we use do not change the semantics of situation calculus, so all the original situation calculus results apply in our setting and vice versa. We get two additional results from this approach. First, we offer a new treatment of loosely interacting agents that uses situation calculus without abandoning the result formalism. This treatment allows a theory-builder to construct a theory without considering its potential inclusion in a multiple-agents setup. Second, theories that we build in this way admit specialized reasoning algorithms.
Impact of Feedback Delay on Rate Adaptation for Multiple Antenna Systems

The design of spectrally efficient and robust schemes is vital to overcome the harsh wireless environment when delivering high data rate services. In the present paper, the performance of a constant power and discrete rate adaptation scheme is evaluated in a multiple antenna scenario. Such a technique has low complexity, and needs a low rate feedback channel to adapt the transmission rate. However, the feedback can become outdated when the channel is rapidly changing. In the light of the feedback delay, the authors propose to analyze the effect of outdated channel information. Closed form expressions are obtained for the bit-error-rate (BER) performance for MIMO diversity, and spatial multiplexing (SM) schemes. Through simulation results, we analyze the impact of feedback delay on the BER. The feedback delay proves to have different impact on each of the MIMO scheme when coupled to a rate adaptive system. We demonstrate that antenna selection suffers more from feedback delay than other diversity schemes. The results can be used to assess the performance of different MIMO techniques, and may be applied to a switching mechanism, where, at each instant, the channel behavior is analyzed and the best fit MIMO mode is selected
Inferring sparsity: Compressed sensing using generalized restricted Boltzmann machines

In this work, we consider compressed sensing reconstruction from M measurements of K-sparse structured signals which do not possess a writable correlation model. Assuming that a generative statistical model, such as a Boltzmann machine, can be trained in an unsupervised manner on example signals, we demonstrate how this signal model can be used within a Bayesian framework of signal reconstruction. By deriving a message-passing inference for general distribution restricted Boltzmann machines, we are able to integrate these inferred signal models into approximate message passing for compressed sensing reconstruction. Finally, we show for the MNIST dataset that this approach can be very effective, even for M <; K.
The masking dilemma and its solution. Fusion at the inferred threshold (FIT) and sensorineural acuity level (SAL) tests.

It is difficult or impossible to obtain air or bone conduction threshold levels in some cases of moderately severe conductive involvement because it may be impossible to mask the nontest ear without also masking the test ear. This has been termed the "masking dilemma. " In most of these "masking dilemma" cases the fusion at the inferred threshold (FIT) test can determine the air conduction hearing levels, and in some cases the sensorineural acuity level (SAL) test can help determine the sensorineural function.
Laparoscopic Resection of Colorectal Liver Metastases: Surgical and Long-term Oncologic Outcome

Objective: To analyze the immediate and long-term outcome after laparoscopic resection of colorectal liver metastases and difference between observed and predicted [Fong's and Basingstoke Predictive Index (BPI) scores] survivals. Background: Laparoscopic liver resection has been reported safe and feasible and improves postoperative course. The oncologic outcomes after resection of colorectal metastases are poorly reported. Methods: Between August 1998 and January 2010, 122 patients underwent laparoscopic resection for colorectal liver metastases during 135 procedures at Rikshospitalet. Patients undergoing surgery between August 1998 and June 2009 were included in research analysis. The patients had median Fong's and BPI's scores of 2 (0–5) and 7 (0–23), respectively. Mainstream analysis of hospital data was done on intent-to-treat basis. Intraoperative incidents and postoperative complications were analyzed according to the Satava and Clavien-Dindo classifications. Median follow-up was 24 (0–100) months. Results: One hundred fifty-one liver resections were performed in 107 patients during 118 procedures: 117 nonanatomic and 34 anatomic liver resections. There were 5 conversions to laparotomy (4.2%). The resection margin was free of tumor tissue in 141 (93.4%) of 151 specimens, and the distance between the resection margin and tumor tissue was median 6 (0–40) mm. Intraoperative incidents occurred in 14 cases (11.9%), including 5 (4.2%), 8 (6.8%), and 1 (0.8%) cases of grades I, II, and III, respectively. Postoperative complications were observed in 16 cases (14.3%), including 2, 3, 7, 3, 0, and 1 cases of grades I, II, IIIa, IIIb, IV, and V, respectively. During follow-up, 21 patients received repeat liver resection of recurrences (11 by laparoscopy and 10 by laparotomy). The 5-year overall survival rates were 51% as laparoscopically completed cases and 47% as intent-to-treat. The observed actuarial survival values exceeded the values expected by Fong's and BPI's score, with 10.2% and 6.7% as laparoscopically completed cases and with 3.8% and 2.4% as intent-to-treat, respectively. Conclusions: Laparoscopic resection is a favorable alternative to open liver resection for patients with colorectal liver metastases. The observed actuarial survival values after laparoscopic resection surpass the values expected by major scoring systems.
Belief Propagation Min-Sum Algorithm for Generalized Min-Cost Network Flow

Belief Propagation algorithms are instruments used broadly to solve graphical model optimization and statistical inference problems. In the general case of a loopy Graphical Model, Belief Propagation is a heuristic which is quite successful in practice, even though its empirical success, typically, lacks theoretical guarantees. This paper extends the short list of special cases where correctness and/or convergence of a Belief Propagation algorithm is proven. We generalize the formulation of Min-Sum Network Flow problem by relaxing the flow conservation (balance) constraints and then proving that the Belief Propagation algorithm converges to the exact result.