Miracle-dz/UniFAR-FTUs huggingface dataset:
The Clp proteins: proteolysis regulators or molecular chaperones?

The Clp proteins constitute a recently discovered family that is represented in every organism examined thus far. (In this review we use the name Clp to mean the family of large homologous proteins, ClpA to -C [756 to 926 amino acids]. This family is distinct from the nonhomologous protease ClpP [207 amino acids].) The family comprises at least three subfamilies, and although they differ somewhat in size and sequence organization, about 420 amino acids in two extensive sequence blocks have been very highly conserved (14). It is probable not only that the family is universal but that several different kinds of Clp proteins (Clp subfamilies) can be made by all cells. For example, Escherichia coli possesses two large Clp proteins, ClpA and ClpB (13, 41), and both human cells and Chinese hamster cells possess multiple proteins that react with antibodies to hspl04, a Clp present in Saccharomyces cerevisiae (37). Investigations with E. coli ClpA suggest that it is involved in the regulation of proteolysis because ClpA strongly activates the nonhomologous ClpP peptidase in the ATP-dependent cleavage of denatured proteins (18, 21). The yeast Clp is the heat shock protein hsplO4 (37), and the E. coli ClpB (23, 37, 41) is the previously identified heat shock protein F84.1 (41). Many heat shock proteins are molecular chaperones (7), and it has been suggested that rather than operating strictly as proteolytic regulators, the heat shock Clp proteins function as chaperones that protect vital cellular components from high-temperature stress (37). This view of Clp protein function is, in fact, not inconsistent with a proteolytic role, since one role of molecular chaperones is to remove denatured proteins which are toxic to the cell. This interpretation does, however, place a different emphasis on the quest for the substrate(s) of the Clp proteins, and it calls for different experimental strategies. The purpose of this review is to summarize what is known about the conservation and structure of Clp proteins and to evaluate the evidence that pertains to their function.
Impact of performance management system on organisational performance of higher education institutions : a case study of Pakistan

Higher education institutions (HEIs) are constantly striving for better quality and effectiveness with a paucity of resources, while simultaneously expected to exhibit greater transparency and accountability in their procedures. Academic institutions are facing challenges of restricted funding and severe competition in the current dynamic environment which is creating the need for more effective and efficient utilization of human capital in possession. This study explores the impact of implementation of Performance Management (PMS) on organisational performance in Higher Education Institutions (HEI) of Pakistan. Several reasons make this sector particularly important for this examination: Firstly, Pakistan is a developing economy and in severe need of highly skilled manpower to develop a strong economy. Higher education institutions play pivotal role in this human development. Thus, effectiveness of performance of faculty members of these institutions is very important. Secondly, the implementation of performance management systems is likely to be one of the revolutionary changes in HEIs. Finally, the uses of PMS in HEIs will provide us with a better understanding of its impact on organisational performance. Therefore, this study aimed to explore the impact of Performance management System in HEIs, and how this use of PMS contributes to the employees’ performance and Organisational Performance. An interpretive approach is used to answer research questions and to explore the implementation of PMS in depth by using qualitative data collection methods. The data subjects were faculty members from business schools of the chosen HEIs. A thematic analysis has been done with the help of NVivo software to analyse the semi-structured interviews. This research contributes to the body of knowledge in relation to the impact of performance management system on the organisational perfroamnce of HEIs in general and more specifically in context of Pakistan. Findings of this research has highlighted the critical issues regarding how performance is managed, evaluated and reported by the HEIs in order to control and organize the dynamics that influence the output of HEIs in Pakistan. Moreover, this study contributed that organisational culture have strong influence on the implementation of PMS in higher education institutions in Pakistan.
TEMPORAL SUCCESSION IN A DESERT STREAM ECOSYSTEM FOLLOWING FLASH FLOODING

Recovery of a desert stream after an intense flash flooding event is described as a model of temporal succession in lotic ecosystems. A late summer flood in Sycamore Creek, Arizona, virtually eliminated algae and reduced invertebrate standing crop by 98%. Physical and morphometric conditions typical of the preflood period were restored in 2 d and the biota recovered in 2—3 wk. Algal communities responded rapidly and achieved a standing crop of nearly 100 g/m2 in 2 wk. Community composition was dominated by diatoms early in succession and by filamentous greens and blue—greens later. Macroinvertebrates also recolonized denuded substrates rapidly, largely by immigration of aerial adults and subsequent oviposition. Growth and development were rapid and several generations of the dominant mayfly and dipteran taxa were completed during the 1st mo of recovery. Invertebrate dry biomass reached 7.3 g/m2 in 1 mo. Gross primary production (Pg) measured as O2 increased in a similar asymptotic fashion and reached 6.6 g°m—2°d—1 in 30 d. Pg exceeded community respiration (R) after day 5 and Pg/R averaged 1.46 for the remainder of the 2—mo sequence. This ecosystem is thus autotrophic and exports organic matter downstream and by drying, laterally. Uptake of nitrate and phosphorus were proportional to net primary production and exhibited a marked downstream decline in concentration during both light and dark periods. Temporal trajectories of various community and ecosystem attributes are compared with those suggested by Odum (1969) to be diagnostic of successional status. Agreement was poor in attributes which are especially modified in open, frequently disturbed ecosystems such as streams.
The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family*

Zyme/protease M/neurosin/human kallikrein 6 (hK6) is a member of the human kallikrein family of trypsin-like serine proteinases and was originally identified as being down-regulated in metastatic breast and ovarian tumors when compared with corresponding primary tumors. Recent evidence suggests that hK6 may serve as a circulating tumor marker in ovarian cancers. In addition, it was described in the brain of Parkinson's disease and Alzheimer's disease patients, where it is implicated in amyloid precursor protein processing. It is thus a biomarker for these diseases. To examine the mechanism of activation of hK6, we have solved the structure of its proform, the first of a human kallikrein family member. The proenzyme displays a fold that exhibits chimeric features between those of trypsinogen and other family members. It lacks the characteristic “kallikrein loop” and forms the six disulfide bridges of trypsin. Pro-hK6 displays a completely closed specificity pocket and a unique conformation of the regions involved in structural rearrangements upon proteolytic cleavage activation. This points to a novel activation mechanism, which could be extrapolated to other human kallikreins.
A Hands Gesture System Of Control For An Intelligent Wheelchair

When an unfortunate event affects the motor capacity of a person, it is necessary to use devices like wheelchairs that offer a means o displacement for patients with motors problems of the lower limbs. Some patients that cannot manipulate the wheelchair with their arms due to a lack of force or psychomotor problems in the superior members, request electric wheelchairs, frequently manipulated with joysticks; however the joystick manipulation is even not practical and frequently it must be handle with the mouth. The present article presents the partial results in the development of a wheelchair controlled by an intuitive interface, where the instructions are given by hand gesture instructions. The advances are presented in the realization of the control software using a Webcam and some distances and presence sensors controlled by a PIC microcontroller that establishes the communication with a program developed in Labview.
Utilization of Genetically Altered Animals in the Pharmaceutical Industry

The study of transgenic and gene-deleted (knockout) mice provides important insights into the in vivo function and interaction of specific gene products. Within the pharmaceutical industry, genetically altered mice are used predominantly in discovery research to characterize the diverse functions of one or multiple gene products or to establish animal models of human disease for proof-of-concept studies. We recently used genetically altered animals in drug discovery to examine the NF-KB family of transcriptional regulatory genes and to elucidate their essential role in the early onset of immune and inflammatory responses. Transgenic and knockout mice are also useful in drug development, because questions regarding risk assessment and carcinogenesis, xenobiotic metabolism, receptor- and ligand-mediated toxicity, and immunotoxicity can be evaluated using these genetically altered mice. For example, the p53 knockout mouse is one of several genetically altered mice whose use may increase the sensitivity and decrease the time and cost of rodent carcinogenicity bioassays. As with any experimental model system, data obtained from genetically altered mice must be interpreted carefully. The complete inactivation of a gene may result in altered expression of related genes or physiologic compensation for the loss of the gene product. Consideration must also be given to the genetic background of the mouse strain and the impact of strain variability on disease or toxicity models. Despite these potential limitations, knockout mice provide a powerful tool for the advancement of drugs in the pharmaceutical industry.
Twitter in the collaborative classroom: micro-blogging for in-class collaborative discussions

While small group discussion during undergraduate classes is an important pedagogic strategy, there are two primary concerns for instructors - how to monitor the conversation that goes on within groups and how to ensure that ideas that emerge within the groups become part of the classroom discourse. In this paper, we describe a design-experiment conducted in two sections of the same undergraduate education class, exploring the use of Twitter and a shared display of the Twitter-chat, to address these issues. We describe three iterations of the use of Twitter in the classes and our reflections on how it influenced the teaching experience. Data from student surveys indicates that students had minimal experience using Twitter for academic activities prior to participation in this class and that they felt Twitter was a valuable tool to support their in-class learning activities. The teaching team found that the use of Twitter kept students on task and focused on the activity, but expressed some concern about the depth of engagement with ideas during the task.
Processing Map and Essential Cleavage Sites of the Nonstructural Polyprotein Encoded by ORF1 of the Feline Calicivirus Genome

ABSTRACT Feline calicivirus (FCV) nonstructural proteins are translated as part of a large polyprotein that undergoes autocatalytic processing by the virus-encoded 3C-like proteinase. In this study, we mapped three new cleavage sites (E46/A47, E331/D332, and E685/N686) recognized by the virus proteinase in the N-terminal part of the open reading frame 1 (ORF1) polyprotein to complete the processing map. Taken together with two sites we identified previously (E960/A961 and E1071/S1072), the FCV ORF1 polyprotein contains five cleavage sites that define the borders of six proteins with calculated molecular masses of 5.6, 32, 38.9, 30.1, 12.7, and 75.7 kDa, which we designated p5.6, p32, p39 (NTPase), p30, p13 (VPg), and p76 (Pro-Pol), respectively. Mutagenesis of the E to A in each of these cleavage sites in an infectious FCV cDNA clone was lethal for the virus, indicating that these cleavages are essential in a productive virus infection. Mutagenesis of two cleavage sites (E1345/T1346 and E1419/G1420) within the 75.7-kDa Pro-Pol protein previously mapped in bacterial expression studies was not lethal.
AIS Electronic Library (AISeL)

In the big data era, analysis with data sets becomes more and more important. How to obtain valuable information from the data records is all we care about. However, most of the time, there are outliers among the data records. Outliers can lead to wrong information extracted from the data sets, detecting them can help us modify these rules or get them easier. In this paper, we combine the distance-based and clustering-based outlier detection methods, use the theory of minimum spanning tree and standard normal distribution to define a new method of outlier detection. At the same time, our algorithm can find the data records which we should pay attention to in the data sets. The algorithm works with two phases. During the first phase, we build a minimum spanning tree by all data records, compute the average weight and the standard deviation of it. In the second phase, we use the distance of each data record with its $K$ nearest neighbours to discover the outliers. Experimental results show our algorithm is more accurate and efficient.
Model predictions for the wide-angle x-ray scatter signals of healthy and malignant breast duct biopsies

Abstract. Wide-angle x-ray scatter (WAXS) could potentially be used to diagnose ductal carcinoma in situ (DCIS) in breast biopsies. The regions of interest were assumed to consist of fibroglandular tissue and epithelial cells and the model assumed that biopsies with DCIS would have a higher concentration of the latter. The scattered number of photons from a 2-mm diameter column of tissue was simulated using a 110-kV beam and selectively added in terms of momentum transfer. For a 1-min exposure, specificities and sensitivities of unity were obtained for biopsies 2- to 20-mm thick. The impact of sample and tumor cell layer thicknesses was studied. For example, a biopsy erroneously estimated to be 8 mm would be correctly diagnosed if its actual thickness was between 7.3 and 8.7 mm. An 8-mm thick malignant biopsy can be correctly diagnosed provided the malignant cell layer thickness is >0.96 mm. WAXS methods could become a diagnostic tool for DCIS within breast biopsies.
Gene variants in the folate‐mediated one‐carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects

We evaluated 35 variants among four folate‐mediated one‐carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects. Cases with a diagnosis of single gene disorders or chromosomal aneusomies were excluded. Controls were randomly selected from area hospitals in proportion to their contribution to the total population of live‐born infants. Odds ratios (OR) and the 95% confidence intervals (CI) were computed for each genotype (homozygous variant or heterozygote, vs. homozygous wildtype) and for increase of each less common allele (log‐additive model). Interactions between each variant and three folate intake variables (maternal multivitamin use, maternal dietary folate intake, and combined maternal folate intake) were also evaluated under the log‐additive model. In general, we did not identify notable associations. The A allele of MTHFD1 rs11627387 was associated with a 1.7‐fold increase in conotruncal defects risk in both Hispanic mothers (OR = 1.7, 95% CI = 1.1–2.5) and Hispanic infants (OR = 1.7, 95% CI = 1.2–2.3). The T allele of MTHFR rs1801133 was associated with a 2.8‐fold increase of risk among Hispanic women whose dietary folate intake was ≤25th centile. The C allele of MTHFR rs1801131 was associated with a two‐fold increase of risk (OR = 2.0, 95% CI = 1.0–3.9) only among those whose dietary folate intake was >25th centile. Our study suggested that MTHFD1 rs11627387 may be associated with risk of conotruncal defects through both maternal and offspring genotype effect among the Hispanics. Maternal functional variants in MTHFR gene may interact with dietary folate intake and modify the conotruncal defects risk in the offspring. © 2012 Wiley Periodicals, Inc.
Editorial: an anniversary and a new member of the family

How rapidly a decade flashes by! Was it really 10 years ago when we heard, bit by bit, about a new disease with frightening, even apocalyptic potential? When tales of heroism were supplanted, temporarily, by fears of bioterrorism as the ominously numbered room 911 of the Metropole Hotel accommodated the first case to come to widespread attention in the West? The true origin turned out to be nature, not man, acting as a malign force to create a novel pathogen. And now, we have another virus from the same family affecting the same body system as the one from a decade ago. Will it stay localised to small pockets of infection or cause another pandemic like its cousin? The story of Severe Acute Respiratory Syndrome (SARS) is given in standard textbooks [1]. The first cases appeared in Guandong, China in November 2002, but were not widely reported. Dr Carlo Urbani identified a case in Hanoi in February 2003 and urged the WHO into action, but soon succumbed to SARS himself. SARS coronavirus (SARS-CoV) was identified as the causative agent [2] and the palm civit the offending mammal vector that facilitated transfer from bats [1]. The cellular receptor was identified as angiotensin converting enzyme 2 [3]. Koch’s postulates were fulfilled when virus derived from cell culture produced pneumonia in macaques from whom SARS-CoV could be reisolated [4]. SARS-CoV was not highly contagious early in the disease course but, once the viral load peaked around day 10 of illness, the scene was set for transmission, especially when respiratory secretions were manipulated during clinical care. Standard precautions for control of infection, coupled with restrictions on international travel, were effective at terminating transmission and ending the pandemic, but left behind a case fatality rate of approximately 10% among the more than 8000 people affected [1]. Many treatments were tried in sick patients but without the controls necessary to determine if any intervention had beneficial or detrimental effects. Indeed, a systematic review,
Detecting Abnormal Trading Activities in Option Markets

We develop an econometric method to detect “abnormal trades” in option markets, i.e., trades which are not driven by liquidity motives. Abnormal trades are characterized by unusually large increments in open interest, trading volume, and option returns, and are not used for option hedging purposes. We use a multiple hypothesis testing technique to control for false discoveries in abnormal trades. We apply the method to 9.6 million of daily option prices.
Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633.

7007 Background: In 2004, preliminary results of CALGB 9633 demonstrated statistically significant evidence that adjuvant chemotherapy with paclitaxel and carboplatin (PC) improved disease-free (DFS) and overall survival (OS) in resected stage IB NSCLC. Indeed, the study was closed early by the DSMB after a planned interim analysis demonstrated a p value for OS less than a prespecified stopping boundary. However, two larger trials, NCIC-JBR10 and ANITA, have shown significant OS advantages with adjuvant chemo, but failed to demonstrate improved survival in the stage IB subset. This report provides more mature data from CALGB 9633. METHODS InCALGB 9633, stage IB patients (pts) were randomized following resection to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks ×4 cycles or to observation. While initially planned to accrue 500 pts, the accrual rate was <50% of expected. Because slow accrual allowed longer observation times for each pt, the accrual target was reduced to 384 pts. OS is the primary endpoint. The redesigned study had 80% power to detect a hazard ratio (HR) of 0.67 after 150 observed deaths using a 1-tailed logrank test conducted at the 0.05 level of significance. RESULTS Between 9/15/96 and 11/26/03, 344 pts were randomized. Median follow-up is 54 mo. Demographics and toxicity has been previously reported (JCO Sup, 22:621a, 2004). The current intent-to-treat analysis shows a significant improvement in DFS favoring adjuvant chemo (HR=0.74; 90% 2-sided CI: 0.57-0.96; p=0.027). There is a trend toward improvement in OS that is not significant (HR=0.80; 90% CI: 0.60-1.07; p=0.10). There is, however, a significant advantage in 3-yr survival (79% vs. 70%; p=0.045). Five-yr survival is not different (60% vs. 57%; p=0.32), although median follow-up is <5 yrs and CIs are wide. Continued follow-up is planned since only 131 of 150 deaths required for final analysis have been observed. CONCLUSIONS This updated but "preliminary" analysis no longer shows a significant OS advantage for adjuvant chemotherapy in stage IB NSCLC. However, the re-designed study does not have adequate power to detect small differences in OS that may be clinically significant. Advantages in DFS and 3-yr survival support continued consideration of adjuvant PC in stage IB NSCLC. [Table: see text].
Kinetics of MK-801 and its effect on quinolinic acid-induced seizures and neurotoxicity in rats.

MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate], a noncompetitive antagonist of the N-methyl-D-aspartate-type of excitatory aminoacid receptors, was measured in plasma and brain tissues after i.p. administration to rats by using a novel high-performance liquid chromatography assay. The drug reached maximal concentrations in plasma and brain within 10 to 30 min of injection (2 mg/kg) with an elimination half-life of 1.9 and 2.05 hr, respectively. Mean ratio of brain area concentration-time curve to plasma area concentration time curve was 12.5, referring to total plasma concentrations. MK-801 distributed almost equally between plasma and red cells (mean blood-to-plasma ratio averaged 1.2 +/- 0.2 when calculated 30 and 180 min from drug administration). Plasma and brain concentrations of MK-801 rose almost linearly from 0.5 to 4 mg/kg 30 min after injection and the brain-to-plasma ratio (12.9 +/- 2.8) was constant in the dose range studied. The distribution of the drug in various brain regions 30 and 180 min after 2 mg/kg i.p. showed no preferential concentration or retention in any of the areas studied. The anticonvulsant effect of MK-801 was evaluated against limbic seizures (measured by EEG) induced by intrahippocampal injection of 120 nmol of quinolinic acid, an agonist of the N-methyl-D-aspartate-type receptors, in freely moving rats. At 0.25 and 0.5 mg/kg, MK-801 significantly lowered by 71 to 77% the number of seizures and by 80% the total time spent in seizures (P less than .01). (ABSTRACT TRUNCATED AT 250 WORDS)
Four decades of engaging customers in product innovation

Over the past four decades, various attempts to expand the innovation theory have engendered a sea change in this domain of research. With an ongoing focus on co-innovation for value creation, a wide-ranging analysis has been developed to reconceptualize this synchronous and interactive activity (Ramirez, 1999) and highlight the roles of various players in the process. Whilst co-innovation involves a range of actors, much research has emphasized the importance of customers in this collaboration due to their pivotal inputs in the organizations’ innovation process (O’Hern and Rindfleisch, 2010).