Miracle-dz/UniFAR-FTUs huggingface dataset:
Cysteine Cathepsins Trigger Caspase-dependent Cell Death through Cleavage of Bid and Antiapoptotic Bcl-2 Homologues*

As a model for defining the role of lysosomal cathepsins in apoptosis, we characterized the action of the lysosomotropic agent LeuLeuOMe using distinct cellular models. LeuLeuOMe induces lysosomal membrane permeabilization, resulting in release of lysosomal cathepsins that cleave the proapoptotic Bcl-2 family member Bid and degrade the antiapoptotic member Bcl-2, Bcl-xL, or Mcl-1. The papain-like cysteine protease inhibitor E-64d largely prevented apoptosis, Bid cleavage, and Bcl-2/Bcl-xL/Mcl-1 degradation. The pancaspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)fluoromethyl ketone failed to prevent Bid cleavage and degradation of anti-apoptotic Bcl-2 homologues but substantially decreased cell death, suggesting that cathepsin-mediated apoptosis in these cellular models mostly follows a caspase-dependent pathway. Moreover, in vitro experiments showed that one or more of the cysteine cathepsins B, L, S, K, and H could cleave Bcl-2, Bcl-xL, Mcl-1, Bak, and BimEL, whereas no Bax cleavage was observed. On the basis of inhibitor studies, we demonstrate that lysosomal disruption triggered by LeuLeuOMe occurs before mitochondrial damage. We propose that degradation of anti-apoptotic Bcl-2 family members by lysosomal cathepsins synergizes with cathepsin-mediated activation of Bid to trigger a mitochondrial pathway to apoptosis. Moreover, XIAP (X-chromosome-linked inhibitor of apoptosis) was also found to be a target of cysteine cathepsins, suggesting that cathepsins can mediate caspase-dependent apoptosis also downstream of mitochondria.
Effects of low‐dose alfentanil administration on central respiratory drive and respiratory pattern in spontaneously breathing ASA 1 patients

Summary The aim of this study was to assess the short‐term effects of the administration of low doses of alfentanil on respiratory drive and respiratory pattern. We studied 17 ASA I patients scheduled for minor surgery or endoscopic procedures. During spontaneous ventilation, Respiratory Rate, Tidal Volume, Total Respiratory Cycle, Inspiratory and Expiratory Time, Mean Inspiratory Flow, P0.1, Sao2 and Etco2 were all measured. The inspired oxygen concentration was 21% and measurements were made at baseline, 5 min (T1), 10 min (T2) and 15 min (T3) following an intravenous bolus injection 10 µg. kg−1 alfentanil. The administration of alfentanil produced a significant (p < 0.05) reduction in Sao2, minute volume and P0.1. In ASA I spontaneously breathing patients, the pre‐operative administration of low doses of alfentanil can initially reduce the respiratory centre activity leading to a reduction in minute volume and Sao2. We therefore recommend careful monitoring of cardio‐respiratory function in ASA I patients, following the administration of alfentanil.
Is There a Role for Pacing in the Prevention of Paroxysmal Atrial Fibrillation ?

Introduction Atrial fibrillation (AF) is the most common significant cardiac arrhythmia, affecting an estimated four million people worldwide. Its rapid and uncoordinated atrial rhythm significantly compromises hemodynamics, decreases cardiac output, predisposes to ventricular arrhythmias, and sets the stage for thromboembolic complications. Contributing mechanisms are presumed to be the occurrence of long-short cycles, an increased temporal dispersion of refractoriness, and atrial ectopic activity serving as the trigger in the presence of an underlying substrate of progressive myocardial fibrosis, gap junction abnormalities and other changes on a cellular level [1] . The incidence of atrial fibrillation increases with age, affecting 4% of those over 60 and up to 15% of those over 70 [2,3] . Although atrial fibrillation can occur in the absence of other conditions ("lone" AF), it is most often associated with a number of complicating conditions, including hypertension, valvular heart disease, coronary artery disease and others.
[Risk behaviors of intravenous drug users: are females taking more risks of HIV and HCV transmission?].

BACKGROUND This work was aimed at identifying differences in HIV and HCV risk behaviors among intravenous drug users (IDUs) according to the gender and their determinants. METHODS IDUs over 18 years, having had sexual intercourse and able to answer the questionnaire were interviewed in 10 drug abuse treatment centers or social institutions using a questionnaire adapted from the one used in the survey of sexual lifestyle in France. RESULTS Over 612 eligible IDUs, 595 completed the questionnaire (women: 29%);37% had multiple partners with no difference according to the gender; 14% of the women and 7% of the men reported trading sex. More women reported inconsistent condom use (46% vs. 55%) and inconsistent clean equipment use (65% vs. 73%). A younger age, independently associated to sharing equipment (men: OR = 0.94; 95% CI = 0.90-0.99; women: OR = 0.92; 95% CI = 0.85-0.99) and inconsistent HIV serology testing, independently associated to inconsistent condom use (men: OR = 3.36; 95% CI = 2.02-5.60; women: OR = 10.72; 95% CI = 3.18-36.18), were the only risk markers common to both genders. For women, being HIV negative increased the risk of inconsistent condom use. Low educational level increased the risk of inconsistent clean equipment use. No risk marker among those analyzed was associated to having had multiple partners. For men, low socioeconomic status markers, a steady sexual partner or not living in couple and educational level were associated with sexual risk behaviors (inconsistent condom use and having multiple partners); low socioeconomic status markers were associated with injecting risk behaviors (inconsistent clean equipment use and sharing). CONCLUSIONS Women were more likely to have both sexual and injecting risk behaviors; their significant risk markers are less numerous thus harm reduction could be more difficult than for men.
Probable benefits of green tea with genetic implications

Tea is produced from the Camellia sinensis plant and can generally be divided into categories based on how they are processed. In general, green tea that is unfermented C. sinensis has been considered superior to black tea in health benefits. It contains a unique set of catechins that possess biological activity as antioxidant, anti-inflammatory and antiproliferative, which is potentially significant to the prevention and treatment of various forms of diseases. Oral cavity oxidative stress and inflammation, consequent cigarettes due to nicotine and acrolein, may be reduced in the presence of green tea polyphenols. In addition, green tea polyphenols can close down halitosis through modification of odorant sulfur components. Usually, green tea defends healthy cells from malignant transformation and locally has the ability to induce apoptosis in oral cancer cells. In unison, there is an increasing implication in the health benefits of green tea in the field of oral health. This review will cover recent findings on the therapeutic properties and anticancer health benefits of green tea.
Identification of Multipath Routing Based on End-to-End Packet Order

Multipath routing, which is increasingly common in today's Internet, can lead two end-hosts to own multiple routing paths. This will impose adverse effects on most of the current network measurement methods, as they generally need to assume a single active path between any pair of end-hosts at any given time. In this paper, we attempt to identify whether multipath routing exists between two end-hosts using end-to-end packet order. We show theoretically that the probability of observing no out-of-order delivery among a strip of packets is always lower when the two end-hosts get multiple instead of a single path to forward them. Based on such investigation, we design a probe and use it to propose an end-to-end measurement scheme that can simultaneously identify multipath routing and its type (e.g., flow-based or packet-based). Both experiment and simulation results validate the effectiveness of our proposed scheme.
Resorbable defect analog PLGA scaffolds using CO2 as solvent: structural characterization.

After tooth extraction, the immediate wound treatment by implanting an exact copy of the root could prevent alveolar bone atrophy. The implant should have an interconnected porosity in order to promote tissue in-growth. This communication reports a novel method to realize such net-shaped porous scaffolds fabricated within a few minutes. Porosity and micro-architecture are evaluated by Hg-porosimetry and by image analysis of electron and light microscopy as well as by computed micro-tomography. The total porosity of the scaffold corresponds to (63 +/- 3)%, mainly related to open interconnected porosity. Micro-tomography, as a noninvasive 3D method, is best suited to uncover pores of about 100 microm, a diameter especially important for tissue in-growth. The differentiation between open and closed porosity, however, depends on the method chosen. This effect is attributed to the spherical pores with an orifice only detected in the 3D analysis. Consequently, the closed porosity is overestimated by 8% evaluating 2D images. Finally, the mean pore diameter is found to be 106 and 100 microm for 2D and 3D analysis, respectively. Although the porosity of the scaffold needs to be further optimized for clinical applications, the procedure proposed is a promising route in manufacturing open porous implants without the use of any organic solvent.
Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes

ABSTRACT Aim: To characterise the impact of increasing severity and frequency of hypoglycaemia on utility, quality of life, primary care resource use and productivity (time away from normal activities) in people with both Type 1 and Type 2 diabetes. Methods: A postal survey was sent to 3200 people with diabetes. Self-reported episodes of mild, moderate, severe and nocturnal hypoglycaemia were quantified from a list of signs and symptoms. A number of instruments were used to explore the effect of frequency and severity of hypoglycaemia on quality of life and productivity. Results: There were 861 respondents for whom diabetes type was identifiable. Of these respondents, 629 (73%) experienced some form of hypoglycaemia, 516 (60%) non-exclusively experienced mild or moderate hypoglycaemia, 57 (7%) experienced severe hypoglycaemia and 191 (22%) experienced nocturnal hypoglycaemia. Quality of life and health-related utility decreased as the frequency and severity of hypoglycaemia increased. The use of primary care resources and lost productivity increased as the severity and frequency of hypoglycaemia increased. These associations were independent in multivariate analysis. Conclusions: These findings suggest hypoglycaemia impacts heavily on the well-being, productivity and quality of life of people with diabetes, and that every effort should be made to minimise hypoglycaemia while aiming for good glycaemic control.
Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis

Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch–CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer.
Comparison of binding of mixed ribose-deoxyribose analogues of CUCU to a ribozyme and to GGAGAA by equilibrium dialysis: evidence for ribozyme specific interactions with 2' OH groups.

Dissociation constants at 15 degrees C were measured by equilibrium dialysis for the binding of rCrUrCrU, dCrUrCrU, rCdUrCrU, rCrUdCrU, and rCrUrCdU to the L-21 ScaI form of the self-splicing group I LSU intron from Tetrahymena thermophila. Substitution of deoxyribose for ribose in each of the middle two positions makes the free energy change for binding 1-2 kcal/mol less favorable, compared to about 0.3 kcal/mol less favorable for each of the terminal positions. Dissociation constants for binding of the same oligomers to rGGAGAA were measured by optical melting methods. Substitution of a single deoxyribose for ribose makes the free energy change for binding less favorable by 0.4-0.9 kcal/mol for this simple duplex formation. Comparison of the effects for binding to ribozyme and to rGGAGAA indicate that ribozyme-specific tertiary interactions dependent on the middle two 2' OH groups of rCrUrCrU add about 2 kcal/mol of favorable free energy for binding to L-21 ScaI. Comparisons are made with results from gel retardation studies [Pyle, A. M. , McSwiggen, J. A. , & Cech, T. R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 8187-8191; Pyle, A. M. , & Cech, T. R. (1991) Nature (London) 350, 628-631].
CHAPTER 4 Stress Reactivity and Trauma : Deviant in Holocaust Survivors , but not in their

The long-term effects of the Holocaust trauma in survivors and their offspring might have affected their neurobiological system. Here we explore the influence of childhood exposure to the traumatic stress, at least characterized by loss of both parents during the Holocaust, on cortisol reactivity of the survivors and their daughters more than 60 years later. Holocaust survivors and comparison participants living in Israel were carefully matched to form a case-control study design with two generations, including four groups: 32 elderly female Holocaust survivors and their 47 adult daughters, and 33 elderly women in the comparison group, and their 32 adult daughters (total N = 174). The Trier Social Stress Test was used and saliva samples were taken to measure cortisol levels. Holocaust child survivors showed elevated levels of cortisol secretion immediately before the onset of the stress procedure, followed by a strong decline of cortisol levels. In contrast, comparison participants showed the expected increase of cortisol levels in response to induced stress. Adult offspring of Holocaust survivors, however, did not display different cortisol reactivity compared to that of their matched controls. The Holocaust seems to be imprinted in the neurobiological system of the survivors, but not of their offspring. Chapter 4. Stress Reactivity and Trauma 67
MSK1 and MSK2 Are Required for the Mitogen- and Stress-Induced Phosphorylation of CREB and ATF1 in Fibroblasts

ABSTRACT Using mouse knockouts for mitogen- and stress-activated protein kinase 1 (MSK1) and MSK2 and a double knockout of both MSK1 and MSK2, we show that these protein kinases are required for the stress-induced phosphorylation of transcription factors CREB and ATF1 in primary embryonic fibroblasts. In contrast mitogen-induced phosphorylation of CREB and ATF1 is greatly reduced but not totally abolished. The mitogen- and stress-induced phosphorylation of CREB at Ser133 has been linked to the transcription of several immediate early genes, including c-fos, junB, and egr1. The knockout of both MSK1 and MSK2 resulted in a 50% reduction in c-fos and junB gene transcription in response to anisomycin or UV-C radiation but only a small reduction in response to tetradecanoyl phorbol acetate or epidermal growth factor in fibroblasts. The transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.
Modular Femoral Offset Stems Facilitate Joint Line Restoration in Revision Knee Arthroplasty

Restoration of proper joint line position in revision total knee arthroplasty is essential in promoting recovery of function. We retrospectively analyzed joint line restoration and clinical outcomes in 22 consecutive femur revision cases using modular offsets of variable length and direction between the intramedullary fixation rod and the femoral component. Flexion and extension gap balancing techniques and medial epicondylar referencing was used to achieve proper position of the joint line. Position of the reconstructed joint line from postoperative radiographs was compared to the baseline position of intended anatomic placement determined from pre-operative planning radiographs. Postoperative joint line height averaged 1.6 mm distal to baseline (range, 5 mm distal to 2.5 proximal). Joint line was restored to within 2 mm of anatomic position in 12 of the 22 knees. Sixteen patients received conventional, minimally constrained tibial inserts, and joint stability was achieved in all cases.Level of Evidence: Therapeutic study, Level IV (case series). See Guidelines for Authors for a complete description of levels of evidence.
[Prognostic factors of prostate cancer: usefulness of Ki-67 expression in preoperative biopsies].

OBJECTIVES To evaluate the usefulness of Ki-67 expression in preoperative diagnostic biopsies to predict prostate cancer biochemical relapse after radical prostatectomy. METHODS We analyze the expression of Ki-67 in ultrasound guided biopsies of 103 patients who underwent radical prostatectomy. Mean follow-up was 3.4 years (1.3-8.8 yr.). We correlated biochemical progression with traditional prognostic factors such as PSA (> 10/< or = 10), Gleason (> or = 7/< 7), pT classification (pT3/pT 0-2), and the immunohistochemical prognostic factor Ki-67 (> 3%/< or = 3%). RESULTS 71/103 (69%) patients did not have progression and 32 (31%) had biochemical progression. Mean preoperative PSA was 10.7 ng/ml in patients without progression and 20.90 ng/ml in patients with biochemical progression (p = 0.0001). Mean Gleason score was 6.03 in patients without progression and 6.75 in patients with biochemical progression (p = 0.0001). Ki-67 expression was 3.95% in patients without progression in comparison to 5.05% of patients with biochemical progression. 12/67 (17.9%) of pT 0-2 tumors and 20/36 (55.6%) pT3 tumors progressed (p = 0.0001). Multivariate analysis indicates that there is not relationship between Ki-67 (> 3% < or = 3%) in preoperative biopsy specimens and prostate cancer biochemical progression after radical prostatectomy (p = 0.204). CONCLUSIONS The immunohistochemical prognostic factor Ki-67 (> 3%/< or = 3%) in preoperative biopsies is less effective than classic factors, PSA (> 10/< or = 10), Gleason score (> or = 7/< 7) and pT classification (pT3/pT 0-2), to predict prostate cancer biochemical progression after radical prostatectomy.
Two-layer coding of video signals for VBR networks

Two-layer conditional-replenishment coding of video signals over a variable-bit-rate (VBR) network is described. A slotted-ring network based on an Orwell protocol is assumed, where transmission of certain packets is guaranteed. The two-layer coder produces two output bit streams: the first bit stream contains all the important structural information in the image and is accommodated in the guaranteed capacity of the network, while the second adds the necessary quality finish. The performance of the coder is tested with CIF standard sequences and broadcast-quality pictures. The portion of the VBR channel allocated to the lower layer as guaranteed bandwidth is examined. Using broadcast-quality pictures, statistics were obtained on the performance of this system for different choices of bit rate in the lower layer. The effect of lost packets is shown on CIF standard picture sequences. It is shown that the coder performs well for a guaranteed channel rate as low as 10-20% of the total bit rate. >
The Research of the Property Service Enterprise's Innovation Based on the Customer Relationship Management Theory

Customer is the basis of the property services enterprise, the competition of property services enterprise is the competition for grabbing customers. It is necessary to achieve the following objectives: to provide the right product or service at the right time, to satisfy the customer needs and desires. But the management of property services enterprise is found many kinds of problems. Though they pay close attention to collecting information on customers, but the actual work is not satisfactory. The paper research innovation based on the customer relationship management in the property service enterprise, through set the goal of implementation of the customer relationship management, positioning on services market, optimizing the service processes, to form all employees "customer-centric" business philosophy. The customer satisfaction and customer loyalty rely on quality of customer complaints handling, The ideas of CRM requires a complete understanding of property services enterprises throughout the customer life cycle, they must provide the platform to communicate with customers. Property services enterprise set up various office of customer service center is in the implementation of CRM strategies. Taking all kinds method to improve service efficiency, and ultimately achieving higher goals of customer satisfaction.
The Use of Carbohydrate Binding Modules (CBMs) to Monitor Changes in Fragmentation and Cellulose Fiber Surface Morphology during Cellulase- and Swollenin-induced Deconstruction of Lignocellulosic Substrates*

Background: Fiber fragmentation is thought to occur at dislocations, which are potential targets for the non-hydrolytic protein, Swollenin. Results: Changes in cellulose morphology within dislocations were assessed using fluorescent CBMs; Swollenin appeared to promote fragmentation at these sites. Conclusion: Swollenin targets and disrupts cellulose at fiber dislocations. Significance: Fragmentation is a key step in cellulose deconstruction and is enhanced by the actions of Swollenin. Although the actions of many of the hydrolytic enzymes involved in cellulose hydrolysis are relatively well understood, the contributions that amorphogenesis-inducing proteins might contribute to cellulose deconstruction are still relatively undefined. Earlier work has shown that disruptive proteins, such as the non-hydrolytic non-oxidative protein Swollenin, can open up and disaggregate the less-ordered regions of lignocellulosic substrates. Within the cellulosic fraction, relatively disordered, amorphous regions known as dislocations are known to occur along the length of the fibers. It was postulated that Swollenin might act synergistically with hydrolytic enzymes to initiate biomass deconstruction within these dislocation regions. Carbohydrate binding modules (CBMs) that preferentially bind to cellulosic substructures were fluorescently labeled. They were imaged, using confocal microscopy, to assess the distribution of crystalline and amorphous cellulose at the fiber surface, as well as to track changes in surface morphology over the course of enzymatic hydrolysis and fiber fragmentation. Swollenin was shown to promote targeted disruption of the cellulosic structure at fiber dislocations.
Evaluation of an Immunochromatographic Assay Kit for Rapid Identification of Mycobacterium tuberculosis Complex in Clinical Isolates

ABSTRACT We evaluated a new immunochromatographic assay (ICA) using mouse monoclonal anti-MPT64 antibody for rapid discrimination between Mycobacterium tuberculosis and nontuberculous mycobacteria in clinical isolates. A study with mycobacteria and other organisms showed excellent sensitivity (≅99%) and specificity (100%) and an appropriate detection limit (105 CFU/ml) when tested with M. tuberculosis H37Rv. This ICA can simplify the identification of M. tuberculosis in clinical laboratories.