Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulated Cycling of Mitochondrial Hsp70 at the Protein Import Channel

Hsp70 of the mitochondrial matrix (mtHsp70) provides a critical driving force for the import of proteins into mitochondria. Tim44, a peripheral inner-membrane protein, tethers it to the import channel. Here, regulated interactions were found to maximize occupancy of the active, adenosine 5′-triphosphate (ATP)–bound mtHsp70 at the channel through its intrinsic high affinity for Tim44, as well as through release of adenosine diphosphate (ADP)–bound mtHsp70 from Tim44 by the cofactor Mge1. A model peptide substrate rapidly released mtHsp70 from Tim44, even in the absence of ATP hydrolysis. In vivo, the analogous interaction of translocating polypeptide would release mtHsp70 from the channel. Consistent with the ratchet model of translocation, subsequent hydrolysis of ATP would trap the polypeptide, driving import by preventing its movement back toward the cytosol.
Heartbeat Detection and Rate Estimation from Ballistocardiograms using the Gated Recurrent Unit Network

Inspired by the application of recurrent neural networks (RNNs) to image recognition, in this paper, we propose a heartbeat detection framework based on the Gated Recurrent Unit (GRU) network. In this contribution, the heartbeat detection task from ballistocardiogram (BCG) signals was modeled as a classification problem where the segments of BCG signals were formulated as images fed into the GRU network for feature extraction. The proposed framework has advantages in fusion of multi-channel BCG signals and effective extraction of the temporal and waveform characteristics of the heartbeat signal, thereby enhancing heart rate estimation accuracy. In laboratory collected BCG data, the proposed method achieved the best heart rate estimation results compared to previous algorithms.
Human cell models to study small intestinal functions: Recapitulation of the crypt‐villus axis

The intestinal epithelium is continuously and rapidly renewed by a process involving cell generation, migration, and differentiation, from the stem cell population located at the bottom of the crypt to the extrusion of the terminally differentiated cells at the tip of the villus. Because of the lack of normal human intestinal cell models, most of our knowledge about the regulation of human intestinal cell functions has been derived from studies conducted on cell cultures generated from experimental animals and human colon cancers. However, important advances have been achieved over recent years in the generation of normal human intestinal cell models. These models include (a) intestinal cell lines with typical crypt cell proliferative noncommitted characteristics, (b) conditionally immortalized intestinal cell lines that can be induced to differentiate, and (c) primary cultures of differentiated villuslike cells that can be maintained in culture for up to 10 days. Each of these models should help in the investigation of the specific aspects of human intestinal function and regulation. Furthermore, taken together, these models provide an integrated system that allows an in vitro recapitulation of the entire crypt‐villus axis of the normal human small intestine. Microsc. Res. Tech. 49:394–406, 2000. © 2000 Wiley‐Liss, Inc.
Time-variant Epileptic Brain Functional Connectivity of Focal and Generalized Seizure in Chronic Temporal Lobe Epilepsy Rat*

Seizure types and characteristics may vary with time in a patient with distinct mechanisms underlying the propagation of ictal activity. Similarly, we found that both focal and generalized seizures coexist in some pilocarpine-induced chronic temporal lobe epilepsy (TLE) rats. In different seizure patterns, mapping complex networks and analyzing epileptic characteristics involved in seizure propagation are likely to reflect seizure propagation mechanisms, and indicate the establishment of stimulation strategy for epilepsy treatment, especially on the selection of stimulation targets. In our study, we used Granger causality method to track the time-variant epileptic brain functional connectivity in focal and generalized seizures from multi-site local field potentials (LFPs). Results showed that these two major types of seizures had different propagation patterns during ictal period. When comparing them, generalized seizures involved in a network with more complex relationships and spread to more extensive brain regions than in local seizures at mid-ictal stage. Moreover, we observed that focal seizures had a focused causal hub with strong interactions, while generalized seizures had relative distributed causal hubs to drive the development of seizure during seizure-onset stage. These findings suggest that stimulation strategy might need to be adapted to different seizure types thus allowing for retuning abnormal epileptic brain network and obtaining better treatment effect on seizure suppression.
Tuberculosis in blood and marrow transplant recipients

Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units. Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries. Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 105 inhabitants per year in Spain and about 100 cases per 105 inhabitants per year in Hong Kong respectively. The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7‒57). The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients. Moreover, allogeneic transplantation, graft‒versus‒host disease, and total body irradiation were found to be risk factors associated with TB. Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11). On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100. The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non‒infectious complications after BMT. As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months. In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted. The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored. With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV‒infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of CTLA‐4 chimeric protein on rat autoimmune anti‐glomerular basement membrane glomerulonephritis

The interaction of the T cell receptor with the antigen/major histocompatibility class II complex is insufficient to induce optimal T cell activation. Co‐stimulatory signals, including those provided by CD28/CTLA‐4 on T cells and B7 molecules (B7‐1, −2 and −3) on antigen‐presenting cells, are also required. CD28‐B7 interactions can be blocked by a soluble human CTLA‐4 chimeric protein (CTLA4Ig). We tested the effect of administration of CTLA4Ig on experimental anti‐glomerular basement membrane (GBM) autoimmune glomerulonephritis in Wistar‐Kyoto rats induced by immunization with bovine GBM. The disease is characterized by development of antibody to the α3 chain of type IV collagen (Goodpasture's antigen), deposition of rat IgG in GBM, infiltration of the kidney by T cells and macrophages, severe crescent formation and renal failure leading to death in 5–6 weeks. Animals injected with human CTLA4Ig from day 0 to day 14 or to day 35 had reduced disease severity. Beneficial effects were observed even when injections were begun after the onset of glomerulonephritis on day 14. However, the rats developed antibody to the human CTLA4Ig, associated with reduction in levels of circulating CTLA4Ig. The results provide evidence for CD28/CTLA‐4 signaling in rat autoimmune glomerulonephritis, and suggest that more effective inhibition of B7‐dependent T cell activation, such as might be achieved with homologous CTLA4Ig, could be useful in the treatment of autoimmune diseases.
10 KW and up from a helix TWT?

It is well known that wideband helix traveling wave tubes have been limited to peak power levels of several kilowatts, due to the occurrence of backward wave oscillations (BWO). Continuing advancements in TWT technology, however, have made this restriction a thing of the past. Octave bandwidth TWTs have been developed using helix pitch steps, diameter steps, or resonant loss for BWO stability. It would appear that peak power levels in excess of 50 kW are possible by using a combination of these approaches. This paper will first discuss the design and present performance data of a high peak power 10 kw, octave bandwidth, PPM-focused, conduction-cooled, helix TWT, in which "resonant loss" is the only oscillation suppression technique employed. Secondly, by extending this basic tube design, it will be shown that higher peak power levels can easily be achieved.
Population genetic structure and colonisation of the Western Antarctic Peninsula by the seabird tick Ixodes uriae

Recent observations on the western Antarctic Peninsula have suggested that chang- ing climatic conditions may be increasing pressure on breeding seabirds due to higher exploita- tion rates by the tick Ixodes uriae. Using data from 8 microsatellite markers and ticks from 6 Pygoscelis spp. colonies, we employed a population genetics approach to specifically test the hypothesis that I. uriae is expanding south-westward along the peninsula from the Subantarctic region. Contrary to expectations, tick genetic diversity was high within all colonies, and no remaining signal of colonisation events was evident. Although significant geographic genetic structure occurred among ticks from different colonies, these ectoparasites tended to belong to 2 major genetic groups, one found principally in south-western locations (Palmer Station area) and the other in more north-eastern areas (South Shetland Islands). More central colonies showed a mixture of ticks from each genetic group, suggesting that this area represents a hybridisation zone of ticks from 2 distinct origins. A subsequent clustering analysis, including ticks from 2 Subantarc- tic locations, did not reveal the source population for the northern peninsula group. Overall, our data refute the hypothesis of a recent south-westward expansion of I. uriae along the peninsula and suggest that this tick has been present at more southern latitudes for an extended period of time. Further studies on the distribution and genetic characteristics of this ectoparasite around Antarctica are now required to better understand the colonisation process and predict how chang- ing environmental conditions may affect its presence and diversity in seabird colonies.
Comparative analysis of mutations in the p53 and K‐ras genes in pancreatic cancer

Mutations in codon 12 of K‐ras occur in a high proportion of pancreatic cancer cases. Although there is evidence that p53 mutations also occur in this tumor, few studies have been reported to date and no comparison has been made of K‐ras and p53 mutations in the same tissues. Single‐strand conformation polymorphism and sequencing of the PCR products were used to determine mutations in p53 gene; to detect mutations in K‐ras genes, the artificial restriction fragment length polymorphism (RFLP) approach was used. Eight out of 30 tissues from primary pancreas cancer and 3 of 4 samples from metastases showed p53 mutations. Fifteen out of 17 pancreatic cancer cell lines had p53 mutations. In 2 cases, the same p53 mutation was identified in the original tumor and in a tumor‐derived cell line. The majority of p53 mutations were present in exons 5‐9 of the gene. Mutations at codon 12 of the K‐ras gene were identified in 23/32 pancreas cancer tissues and in 14/17 cell lines. There was no relationship between the types of mutation observed in the 2 genes. In conclusion, mutations in K‐ras and p53 genes are common in pancreatic cancer. p53 mutations may occur more frequently in metastatic lesions than in primary tumors, although further work is necessary to investigate this point.
Topographic distribution of sleep spindles in young healthy subjects

The application of an automatic sleep spindle detection procedure allowed the documentation of the topographic distribution of spindle characteristics, such as number, amplitude, frequency and duration, as a function of sleep depth and of recording time. Multichannel all‐night EEG recordings were performed in 10 normal healthy subjects aged 20–35 years. Although the interindividual variability in the number of sleep spindles was very high (2.7±2.1 spindles per minute stage 2 sleep), all but two subjects showed maximal spindle activity in centro‐parietal midline leads. Moreover, this topography was seen in all sleep stages and changed only slightly – to a more central distribution – towards the end of the night. On the other hand, slow (11.5–14 Hz) and fast (14–16 Hz) spindles showed a completely different topography, with slow spindles distributed anteriorly and fast spindles centro‐parietally. The number of sleep spindles per min was significant depending on sleep stages, with the expected highest occurrence in stage 2, and on recording time, with a decrease in spindle density from the beginning towards the end of the night. However, spindle amplitude, frequency and individual duration was not influenced by sleep depth or time of the night.
Nonoperative management of splenic injuries: have we gone too far?

HYPOTHESIS Patients with severe blunt injuries to the spleen have a high likelihood of failing nonoperative management of splenic injuries (NOMSI). DESIGN Review of medical records, helical computed tomographic imaging data, and trauma registry data. SETTING Academic level I trauma center at a large county hospital. PATIENTS A total of 105 patients with blunt trauma to the spleen, admitted between January 1995 and December 1998, who survived more than 48 hours and had complete records. Of these patients, 53 (56%) were selected for NOMSI. The splenic injury was graded by the Organ Injury Scale of the American Association for the Surgery of Trauma (grades I to V, with grade V being the worst possible injury). MAIN OUTCOME MEASURES Failure of NOMSI, defined as the need for operation to the spleen after a period of nonoperative management. RESULTS Compared with patients who had successful NOMSI, the 29 patients (52%) in whom NOMSI failed were older and more severely injured. They also required extra-abdominal operations more frequently, underwent transfusion with more units of blood while being managed nonoperatively, and had higher grades of splenic injury. Splenic injury grade III or higher and transfusion of more than 1 U of blood were identified as independent risk factors for failure of NOMSI. The existence of both risk factors predicted failure in 97% of cases. The grading by computed tomography correlated well with the actual injury to the spleen as seen at operation. CONCLUSIONS In patients with high-grade splenic injuries who require a transfusion of more than 1 U of blood, NOMSI is very likely to fail. Decreasing the threshold for operation or intensifying the monitoring is highly recommended for such patients.
A Bacteriophage Lambda-Based Genetic Screen for Characterization of the Activity and Phenotype of the Human Immunodeficiency Virus Type 1 Protease

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) resistance to antiretroviral drugs is the main cause of patient treatment failure. Despite the problems associated with interpretation of HIV-1 resistance testing, resistance monitoring should help in the rational design of initial or rescue antiretroviral therapies. It has previously been shown that the activity of the HIV-1 protease can be monitored by using a bacteriophage lambda-based genetic assay. This genetic screening system is based on the bacteriophage lambda regulatory circuit in which the viral repressor cI is specifically cleaved to initiate the lysogenic to lytic switch. We have adapted this simple lambda-based genetic assay for the analysis of the activities and phenotypes of different HIV-1 proteases. Lambda phages that encode HIV-1 proteases either from laboratory strains (strain HXB2) or from clinical samples are inhibited in a dose-dependent manner by the HIV-1 protease inhibitors indinavir, ritonavir, saquinavir, and nelfinavir. Distinct susceptibilities to different drugs were also detected among phages that encode HIV-1 proteases carrying different resistance mutations, further demonstrating the specificity of this assay. Differences in proteolytic processing activity can also be directly monitored with this genetic screen system since two phage populations compete in culture with each other until one phage outgrows the other. In summary, we present here a simple, safe, and rapid genetic screening system that may be used to predict the activities and phenotypes of HIV-1 proteases in the course of viral infection and antiretroviral therapy. This assay responds appropriately to well-known HIV-1 protease inhibitors and can be used to search for new protease inhibitors.
Measuring Informal Innovation: From Non-R&D to On-line Knowledge Production

In this paper we explore the concept of informal innovation by investigating it both on the input (activities) and output (impact) side of the innovation process. Informal innovation is defined as innovation that is not explicitly planned and budgeted and therefore remains largely hidden in (aggregate) innovation data. We take a statistical approach to reveal the significant potential of informal innovation. We furthermore conceptualize and operationalize informal innovation as an activity taking place without R&D (in non-R&D firms). In general, on the input side, we show that around half of the innovative firms in our sample (of innovative firms in the Swiss Innovation Survey of 2002) develop innovations without any R&D. Moreover, on the output side, over one third of the innovative sales and production cost reductions can be attributed to informal innovation. Although the results appear to be rather pervasive, they are strongest for small firms, low-tech firms and firms in service industries. This leads us to conclude that informal innovation is not just an important complement to formal innovation - as scarcely acknowledged in literature - but that is largely takes place next to and as a substitute for formal innovation as well - which is largely neglected in literature to date. We furthermore explore the possible attributes of the process of informal innovation and develop a preliminary framework that needs to be investigated into further detail by future research. In particular, we argue that 'on-line' activities are a crucial part of the innovation process, although it has been largely neglected to date. It becomes clear that the literature on learning-by-doing and learning-by-using needs to be expanded by more explicitly focusing on the processes that are at the heart of the (informal) innovation process in order to clearly show the sources of innovation. In order to do this, we indicate some possible avenues for future research to improve the measurement of (informal) innovation.
Temperature-Insensitive Micro Fabry–PÉrot Strain Sensor Fabricated by Chemically Etching Er-Doped Fiber

Micro extrinsic Fabry-Perot interferometric (MEFPI) sensors are fabricated by chemically etching Er-doped fibers with mixed hydrochloric (HCl) and hydrofluoric (HF) acid and fusion splicing. Compared with MEFPI sensors fabricated by etched single-mode fibers, the sensor performance is greatly improved by the chemical reaction between HCl acid and doped Er2O3. A maximum visibility of ~24 dB is obtained, comparable to that of MEFPI sensors fabricated by excimer lasers. Our MEFPI sensor has high mechanical strength as the etching rate difference between fiber core and cladding is enlarged. Preliminary results indicate that this kind of sensor is insensitive to temperature while highly sensitive to strain, with sensitivities of ~0.65 pm/degC and ~3.15 pm/muepsiv, respectively.
The Brassica napus blackleg resistance gene LepR3 encodes a receptor-like protein triggered by the Leptosphaeria maculans effector AVRLM1.

LepR3, found in the Brassica napus cv 'Surpass 400', provides race-specific resistance to the fungal pathogen Leptosphaeria maculans, which was overcome after great devastation in Australia in 2004. We investigated the LepR3 locus to identify the genetic basis of this resistance interaction. We employed a map-based cloning strategy, exploiting collinearity with the Arabidopsis thaliana and Brassica rapa genomes to enrich the map and locate a candidate gene. We also investigated the interaction of LepR3 with the L. maculans avirulence gene AvrLm1 using transgenics. LepR3 was found to encode a receptor-like protein (RLP). We also demonstrated that avirulence towards LepR3 is conferred by AvrLm1, which is responsible for both the Rlm1 and LepR3-dependent resistance responses in B. napus. LepR3 is the first functional B. napus disease resistance gene to be cloned. AvrLm1's interaction with two independent resistance loci, Rlm1 and LepR3, highlights the need to consider redundant phenotypes in 'gene-for-gene' interactions and offers an explanation as to why LepR3 was overcome so rapidly in parts of Australia.
Response of broiler chicks to dietary Rhazya stricta and Nigella sativa

1. Rhazya stricta leaves and Nigella sativa seeds were fed to 7-d-old Hibro broiler chicks at 20 and 100 g/kg of the diet for 7 weeks. Although 20 and 100 g/kg N. sativa seed diets did not adversely affect growth, a decrease in body weight and feed efficiency and hepatonephropathy were observed in the chicks fed on the 100 g/kg R. stricta diet. 2. These changes, associated with macrocytic hypochromic anaemia, were correlated with alterations in serum aspartate transaminase' (AST) and alanine transaminase (ALT) activities and concentrations of total protein, albumin, globulin, cholesterol, calcium and other serum constituents. 3. The effect of 20 g/kg R. stricta diet on chicks was not associated with development of biliary hyperplasia or catarrhal enteritis after 7 weeks of treatment.