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At least 667 records · Page 37Linked to original sources
PubMed2005

Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid.

OBJECTIVE: To determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro. METHODS: Blocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and (3)H-proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated (3)H-proline. RESULTS: Samples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly. CONCLUSION: These results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.

Animals↗
PubMed1982

Integration of HBV-DNA into liver and hepatocellular carcinoma cells during persistent HBV infection.

The hepatitis B virus carrier state (persistent HBV infection) is characterized by the presence of viral surface antigen (HBsAg) and virion particles (Dane particles) in the blood. From 1% to 10% of carriers develop chronic liver disease and/or hepatocellular carcinoma. Recent studies have demonstrated integrated HBV-DNA in hepatocellular carcinomas and in several human hepatoma cell lines. In hepatoma patients, integrated HBV-DNA has been found in all HBsAg carriers. Nontumorous liver also revealed integrated HBV-DNA with the same or a different hybridization pattern from that observed in the tumor. To explore when integration occurs, carriers of short-term (less than 2 years) or long-term (greater than 8-10 years) were evaluated. DNA extracts from percutaneous (needle) liver biopsies showed free viral DNA with no specific integration bands in short-term carriers. In long-term carriers, HBV-DNA was integrated into the host genome with either a diffuse or a unique hybridization pattern. HBV-DNA integration correlated with the duration of the carrier state and absence of virions in the serum but did not correlate with histologic evidence of chronic hepatitis. These studies suggest that integration of HBV-DNA occurs during persistent HBV infection irrespective of liver disease and precedes development of hepatocellular carcinoma.

Animals↗
PubMed1996

A validatible porosimetric technique for verifying the integrity of virus-retentive membranes.

The verification of membrane integrity for filtration processes specifically designed for the removal of adventitious virus from biotherapeutics is of the utmost importance to both biomanufacturers and regulatory agencies. Although conventional bubble-point and air-diffusion tests are widely accepted for integrity testing of bacteria-retentive membranes, these tests have severe limitations in their ability to assess the integrity of virus-retentive membranes. A novel membrane integrity test based upon liquid-liquid porosimetric principles (CorrTest) has been specifically designed to correlate and predict the virus retention capabilities of Viresolve virus removing membranes. To optimize test sensitivity for both Viresolve/70 and Viresolve/180 membrane types, two distinct porosimetric correlations at different transmembrane pressures have been developed. Based upon an 80% prediction interval, an integrity test performed at either test pressure can reliably predict the ability of Viresolve membranes to remove the bacteriophage phi X174 to within 0.4 log removal value (LRV) units. To maintain test sensitivity and provide greater flexibility for conducting the liquid-liquid intrusion integrity test, appropriate pressure- and temperature-correction equations have been established. The two immiscible fluids employed in the developed technology are easily flushed from the membrane structure and are generally regarded as acceptable, non-toxic reagents for pharmaceutical applications. Consequently, the CorrTest integrity test can reliably and non-destructively measure both pre- and post-use membrane integrity to verify virus removal performance with the Viresolve module.

Bacteriophage phi X 174↗
PubMed1986

IS21 insertion in the trfA replication control gene of chromosomally integrated plasmid RP1: a property of stable Pseudomonas aeruginosa Hfr strains.

Broad host range IncP-1 plasmids are able to integrate into the chromosome of gram-negative bacteria. Strains carrying an integrated plasmid can be obtained when the markers of a temperature-sensitive (ts) plasmid derivative are selected at non-permissive temperature; in this way Hfr (high frequency) donor strains can be formed. The integrated plasmids, however, tend to be unstable in the absence of continuous selective pressure. In order to obtain stable Hfr donor strains of Pseudomonas aeruginosa PAO, we constructed a derivative of an RP1 (ts) plasmid, pME134, which was defective in the resolvase gene (tnpR) of transposon Tn801. Chromosomal integration of pME134 was selected in a recombination-deficient (rec-102) PAO strain at 43 degrees C. Plasmid integration occurred at different sites resulting in a useful set of Hfr strains that transferred chromosomal markers unidirectionally. The tnpR and rec-102 mutations prevented plasmid excision from the chromosome. In several (but not all) Hfr strains that grew well and retained the integrated plasmid at temperatures below 43 degrees C, the insertion element IS21 of RP1 was found to be inserted into the trfA locus (specifying an essential trans-acting replication function) of the integrated plasmid. One such Hfr strain was rendered rec+; from its chromosome the pME134::IS21 plasmid (= pME14) was excised and transferred by conjugation to Escherichia coli where pME14 could replicate autonomously only when a helper plasmid provided the trfA+ function in trans. Thus, it appears that trfA inactivation favours the stability of chromosomally integrated RP1 in P. aeruginosa.

Chromosomes, Bacterial↗
PubMed1997

The oculomotor integrator: testing of a neural network model.

An important part of the vestibulo-ocular reflex is a group of cells in the caudal pons, known as the neural integrator, that converts eye-velocity commands, from the semicircular canals for example, to eye-position commands for the motoneurons of the extraocular muscles. Previously, a recurrently connected neural network model was developed by us that learns to simulate the signal processing done by the neural integrator, but it uses an unphysiological learning algorithm. We describe here a new network model that can learn the same task by using a local, Hebbian-like learning algorithm that is physiologically plausible. Through the minimization of a retinal slip error signal the model learns, given randomly selected initial synaptic weights, to both integrate simulated push-pull semicircular canal afferent signals and compensate for orbital mechanics as well. Approximately half of the model's 14 neurons are inhibitory, half excitatory. After learning, inhibitory cells tend to project contralaterally, thus forming an inhibitory commissure. The network can, of course, recover from lesions. The mature network is also able to change its gain by simulating abnormal visual-vestibular interactions. When trained with a sine wave at a single frequency, the network changed its gain at and near the training frequency but not at significantly higher or lower frequencies, in agreement with previous experimental observations. Commissural connections are essential to the functioning of this model, as was the case with our previous model. In order to determine whether a commissure plays a similar role in the real neural integrator, a series of electrical perturbations were performed on the midlines of awake, behaving juvenile rhesus monkeys and the effects on the monkeys' eye movements were examined. Eye movements were recorded using the coil system before, during, and after electrical stimulation in the midline of the pons just caudal to the abducens nuclei, which reversibly made the integrator leaky. Eye movements were also recorded from two of the monkeys before and after a midline electrolytic lesion was made at the location where stimulation produced a leaky integrator. This lesion disabled the integrator irreversibly. The eye movements that were produced by the monkeys as a result of these perturbations were then compared with eye movements produced by the model after analogous perturbations. The results are compatible with the hypothesis that integration comes about by positive feedback through lateral inhibition effected by an inhibitory commissure.

Algorithms↗
PubMed2002

Single-step co-integration of multiple expressible heterologous genes into the ribosomal DNA of the methylotrophic yeast Hansenula polymorpha.

We have investigated the methylotrophic yeast Hansenula polymorpha as a host for the co-integration and expression of multiple heterologous genes using an rDNA integration approach. The ribosomal DNA (rDNA) of H. polymorpha was found to consist of a single rDNA cluster of about 50-60 repeats of an 8-kb unit located on chromosome II. A 2.4-kb segment of H. polymorpha rDNA encompassing parts of the 25S, the complete 5S and the non-transcribed spacer region between 25S and 18S rDNA was isolated and inserted into conventional integrative H. polymorpha plasmids harboring the Saccharomyces- cerevisiae-derived URA3 gene for selection. These rDNA plasmids integrated homologously into the rDNA repeats of a H. polymorpha (odc1) host as several independent clusters. Anticipating that this mode of multiple-cluster integration could be used for the simultaneous integration of several distinct rDNA plasmids, the host strain was co-transformed with a mixture of up to three different plasmids, all bearing the same URA3 selection marker. Transformations indeed resulted in mitotically stable strains harboring one, two, or all three plasmids integrated into the rDNA. The overall copy number of the plasmids integrated did not exceed the number of rDNA repeats present in the untransformed host strain, irrespective of the number of different plasmids involved. Strains harboring different plasmids co-expressed the introduced genes, resulting in functional proteins. Thus, this approach provides a new and attractive tool for the rapid generation of recombinant strains that simultaneously co-produce several proteins in desired stoichiometric ratios.

Base Sequence↗
PubMed1997

Effect of de-phosphorylation of linearized pAN7-1 and of addition of restriction enzyme on plasmid integration in Penicillium paxilli.

As part of a study to investigate the pathways of plasmid pAN7-1 integration in Penicillium paxilli, a molecular analysis of 90 different integration events was carried out. Twenty out of forty five integration events analyzed from transformants obtained without the addition of restriction enzyme to the transformation reaction mixture were single-copy integrations, whereas the remaining 25 were tandem-repeat integrations. The addition of restriction enzyme resulted in a shift in this ratio in favour of single-copy integration events. Analysis of the 33 tandem-repeat integration events showed that the orientation of the plasmid copies was not random, with 88% organized as tandem head-to-tail arrays. De-phosphorylation of linearized pAN7-1 did not affect the frequency with which multiple copies were integrated. This suggests that the predominant mechanism for the generation of tandem repeats in P. paxilli is by homologous recombination rather than in vivo ligation of linearized plasmids.

Deoxyribonuclease HindIII↗
PubMed2000

How do insects use path integration for their navigation?

We combine experimental findings on ants and bees, and build on earlier models, to give an account of how these insects navigate using path integration, and how path integration interacts with other modes of navigation. At the core of path integration is an accumulator. This is set to an initial state at the nest and is updated as the insect moves so that it always reports the insect's current position relative to the nest. Navigation that uses path integration requires, in addition, a way of storing states of the accumulator at significant places for subsequent recall as goals, and a means of computing the direction to such goals. We discuss three models of how path integration might be used for this process, which we call vector navigation. Vector navigation is the principal means of navigating over unfamiliar terrain, or when landmarks are unavailable. Under other conditions, insects often navigate by landmarks, and ignore the output of the vector navigation system. Landmark navigation does not interfere with the updating of the accumulator. There is an interesting symmetry in the use of landmarks and path integration. In the short term, vector navigation can be independent of landmarks, and landmark navigation needs no assistance from path integration. In the longer term, visual landmarks help keep path vector navigation calibrated, and the learning of visual landmarks is guided by path integration.

Animals↗
PubMed1998

A cross-interval spike train analysis: the correlation between spike generation and temporal integration of doublets.

A stochastic spike train analysis technique is introduced to reveal the correlation between the firing of the next spike and the temporal integration period of two consecutive spikes (i.e., a doublet). Statistics of spike firing times between neurons are established to obtain the conditional probability of spike firing in relation to the integration period. The existence of a temporal integration period is deduced from the time interval between two consecutive spikes fired in a reference neuron as a precondition to the generation of the next spike in a compared neuron. This analysis can show whether the coupled spike firing in the compared neuron is correlated with the last or the second-to-last spike in the reference neuron. Analysis of simulated and experimentally recorded biological spike trains shows that the effects of excitatory and inhibitory temporal integration are extracted by this method without relying on any subthreshold potential recordings. The analysis also shows that, with temporal integration, a neuron driven by random firing patterns can produce fairly regular firing patterns under appropriate conditions. This regularity in firing can be enhanced by temporal integration of spikes in a chain of polysynaptically connected neurons. The bandpass filtering of spike firings by temporal integration is discussed. The results also reveal that signal transmission delays may be attributed not just to conduction and synaptic delays, but also to the delay time needed for temporal integration.

Action Potentials↗
PubMed2003

The years after: a concept of the psychological integration of childhood cancer.

GOALS OF WORK: To define and measure the psychological integration of childhood cancer experiences into a personal biography and to explore the association between integration with illness-related factors and psychosocial conditions. PATIENTS AND METHODS: Analysis of cancer survivors' narratives on the course of their illness was used to measure integration. Psychosocial condition, body concepts, health locus of control, and illness-related distress were evaluated by questionnaires. Illness factors were assessed by reviewing hospital case notes and sociodemographic factors by a structured interview. Of 72 eligible subjects contacted, 60 agreed to participate. MAIN RESULTS: High inter-rater correlations established the reliability of the concept of testing integration by narrative analysis. Subjects with good psychological integration of the experience of cancer saw chance as having less to do with illness and health, and perceived illness and therapy retrospectively as more distressing than survivors with poor integration. In contrast, integration did not correlate with distress evoked by present feelings toward illness and therapy or by thoughts of a relapse. CONCLUSIONS: Successful integration of the experience of cancer may be associated with the ability to accept painful feelings and to allow them to emerge, and with a readiness to accept responsibility in relation to health and medical care. Assisting young cancer patients and their families to create and maintain their personal narratives of the experience of illness is an important clinical task for all professionals working in paediatric oncology.

Adaptation, Psychological↗
PubMed1984

An economic volt-hour integrator, compatible with commercial and homemade electrophoresis power supplies.

In isoelectric focusing systems--a technique widely used for separation and characterization of proteins--the value of the volt-hour integral required to achieve steady-state focusing conditions differs markedly for different proteins. A convenient method to measure the correct volt-hour integral for a given protein, thereby assuring intra- and interlaboratory reproducibility of experiments, can be performed with a volt-hour integrator. As commercially available integrators are compatible only with the power supply marketed by the same manufacturer, a volt-hour integrator was designed which can be used in conjunction with any commercial or homemade power supply. This simple, low-cost integrator is expected to be of interest to those researchers who have so far refrained from introducing volt-hour integration, due to incompatibility of commercial volt-hour integrators with their isoelectric focusing system.

Costs and Cost Analysis↗
PubMed1992

Discrimination between myocardial infarct and ventricular tachycardia patients using magnetocardiographic trajectory plots and iso-integral maps.

Magnetocardiograms were recorded from 30 normal (N) subjects, 15 myocardial infarct (MI) patients, and 15 ventricular tachycardia (VT) patients. Discrimination between the groups was affected by iso-integral magnetic field mapping (MFM) and trajectory plotting of MFM extrema. Iso-integral MFM for the QRST, QRS, and ST-T intervals was created for each test group member. A polarity score, based on the number of extrema features present, was assigned to each iso-integral MFM. Differences in group mean integral of QRST map polarity scores were significant (p less than 0.05) between MI and N, between VT and N (p less than 0.005), and between MI and VT (p less than 0.05) subjects. integral of ST-T map polarity scores were significantly (p less than 0.0001) different between VT and N and between MI and VT (p less than 0.001) subjects. Discrimination between MI and VT patients, based on polarity score difference, was 56% accurate using integral of QRS maps and 73% accurate using integral of ST-T maps. For each subject, time-normalized MFM was used to construct trajectory plots of the maxima and minima in the QRS and ST-T intervals. Discrimination between MI and VT patients was based upon intergroup differences in fragmented trajectory plots. When the number of discrete trajectories and/or the total number (F) of trajectory points at which discrete trajectories coexist were considered, QRSmin trajectory plots were significantly (p less than 0.05) different for VT and N, but not for MI and N subjects. The significant (p less than 0.05) difference between MI and VT trajectory plots enabled 76% accuracy for MI and VT identification. ST-Tmax trajectory plots show significantly (p less than 0.0001) higher F values for VT patients facilitating accurate (87%) discrimination between MI and VT patients. These results suggest that the abnormalities of repolarization processes, displayed by MFM as multipolar integral of ST-T maps and/or as fragmented trajectory plots of ST-T extrema, may be useful indicators of the arrhythmia substrate/processes that characterize VT and vulnerable MI patients.

Diagnosis, Differential↗
PubMed1991

A versatile method for integration of genes and gene fusions into the lambda attachment site of Escherichia coli.

We have developed a versatile method for integration of modified genes and gene fusions into the bacteriophage lambda attachment site (attB) of the Escherichia coli chromosome. The method relies on two components: (1) a DNA integration cassette, flanked by multiple restriction enzyme sites, which contains the lambda attP site and, as a selectable marker, the Tn5 aphA gene conferring kanamycin resistance (KmR); and (2) a plasmid with the lambda int gene transcribed from the tet promoter. A fragment carrying the gene in question is ligated to the integration cassette, resulting in a circular piece of DNA unable to replicate. The ligation product is then transformed into a strain that contains the int-carrying plasmid. Selection for KmR results in colonies with the cassette integrated into the attB site of the E. coli chromosome. This method was used for integration of several lacZ and phoA promoter fusions. The integration products were analyzed by Southern hybridization. In addition, we found, fortuitously, that the ligated DNA circles could also integrate by homologous recombination, although usually at a much lower frequency than the Int-mediated integration into attB.

Alkaline Phosphatase↗
PubMed1992

Different pathways for chromosomal integration of transfected circular pSVneo plasmids in normal and established rodent cells.

The chromosomal integration of transfected circular plasmid pSV2neo molecules was investigated in normal and established mammalian fibroblasts, including two secondary cultures of normal mouse fibroblast lines, one established mouse-hamster hybrid cell line, R44, and the human fibrosarcoma line, HT1080. The physical organization of the integrated molecules was studied by restriction analysis. The results showed that whereas the normal fibroblasts predominantly integrated one head-to-tail partial dimeric molecule, the established cells predominantly integrated distinctly different molecular forms including deleted monomeres (HT1080) and various complex concatemeric molecules (R44), and frequently at more than one chromosomal site (R44). We also constructed a head-to-tail dimeric version of the plasmid, which in the case of the normal fibroblasts again integrated as a partial dimeric molecule in at least 50% of these cells. This result excluded the possibility that the normal mouse transfectants were selected for the integration of two functional neo genes. Thus, it is concluded that the distinctly different molecular forms integrated in normal and established cells demonstrate the operation of different integration pathways, the possible nature of which is discussed.

Animals↗
PubMed1991

Threshold integration of bi-amplitude signals.

This study examined the pattern of intensity integration at threshold. The stimuli studied are unique in that they have a compound peak-to-peak amplitude envelope. This waveform was partitioned into two segments, each having a different peak-to-peak magnitude (bi-amplitude). All signals in the bi-amplitude series were the same duration (100 ms). Therefore, threshold differences between these signals are due solely to the integration of intensity in the amplitude dimension. A prediction of the pattern of thresholds, based on the diverted-input hypothesis, suggested that little or no integration would occur when the amplitude difference between segments is greater than a specific magnitude. Our results indicate that there are similarities in the integration process found with variable duration signals and with bi-amplitude signals. We conclude that previous estimates of the minimum intensity level based on temporal integration data underestimates the intensity levels that can contribute to threshold. Our results suggest that there are no apparent constraints on the intensity levels that can be integrated near threshold. The auditory system integrates distributed stimulus intensity in both the time and amplitude dimensions. Temporal integration in the auditory system can be viewed as a signal process, where an enhanced internal representation is given low-level stimuli.

Acoustic Stimulation↗
PubMed2006

Exploring ego-integrity in old adults: a Q-methodology study.

BACKGROUND: Achieving ego-integrity involves fully accepting oneself and is important in quality of later life, but the concept of ego-integrity in old adults has not yet been well articulated in nursing practice. OBJECTIVES: This study aimed to elucidate the concept of ego-integrity in late adulthood in terms of the range of meanings this concept embraces within contemporary Korean society. DESIGN: Q-methodology was applied, which represents a method for measuring subjectivity. SETTINGS: The study was performed in a community setting in the Republic of Korea. PARTICIPANTS: The participants were 26 old adults, aged 65-70 years, living in the community in Korea. Two inclusion criteria were applied: (1) the participants had to be literate and competent to ensure that they were able to sort the cards stating the Q-samples in a forced distributive manner, and (2) the participants were regarded by researchers as having achieved ego-integrity in late adulthood as described in the literature. METHODS: Data obtained from June 2004 to December 2004 from a sample of 26 older adults were analyzed by PCQ software (a factor analysis program for the Q-technique) to delineate the factors of ego-integrity in late adulthood. RESULTS: A four-factor solutions for the study subjects indicates that there were differences in the frames of reference in achieving ego-integrity in late adulthood. The frames of reference of the four factors were: (1) a satisfactory connection between the generations, (2) enjoying a peaceful life, (3) peace through acceptance, and (4) achieving a praiseworthy life in spite of adversity. CONCLUSION: The projected property of ego-integrity in late adulthood is closely related to cultural and psycho-social environmental influences throughout the life span. Culturally sensitive life-reviews methods need to be developed to intervene in the specific ways that individual older adults achieve their own ego-integrity throughout their life experiences.

Aged↗
PubMed2026

Integrating Genomic and Nongenomic Data to Stratify the Risk of Contralateral Breast Cancer After Radiation Therapy.

PURPOSE: Women treated with radiation therapy (RT) for breast cancer have an increased risk of developing radiation-associated contralateral breast cancer (CBC). Predicting CBC events is challenging because of the complex interplay of genomic, treatment, personal, and clinical factors. This study investigated computational methods that integrate genome-wide single-nucleotide polymorphisms and nongenomic data to develop a risk stratification model for developing CBC in women treated with RT for their first primary breast cancer. METHODS AND MATERIALS: This study used a subset of the population-based Women's Environmental Cancer and Radiation Epidemiology study that included 633 CBC cases and 1253 individually matched unilateral breast cancer controls who were treated with RT and had single-nucleotide polymorphism data available from a genome-wide association study. The study population was split into training, validation, and test sets for rigorous modeling and validation. Three data integration methods were compared in terms of their ability to stratify CBC risk: (1) naive integration; (2) sequential integration; and (3) sequential iterative integration. A biological analysis of the final model was performed using gene set enrichment analysis and protein-protein interaction analysis with gene annotation information informed by the model. RESULTS: The best-performing integration method was the sequential iterative integration equipped with the mixed-effect random forest algorithm. This approach achieved an area under the curve of 0.64 to stratify CBC risk in the test set, representing moderate predictive power. Calibration analysis showed good agreement between the lowest and highest risk bins stratified using sorted predicted values in the test set, resulting in an odds ratio of 3.27 for both predicted and observed CBC occurrence. Gene set enrichment analysis and protein-protein interaction analysis revealed that genes with high importance scores were associated with pathways relevant to lipid and fatty acid metabolism as well as breast cancer sensitivity to tamoxifen. CONCLUSIONS: The mixed-effect random forest approach demonstrated the potential for integrating high-dimensional genomic and low-dimensional nongenomic data to stratify CBC risk.

Humans↗
PubMed2006

Integrated waste management--looking beyond the solid waste horizon.

Waste as a management issue has been evident for over four millennia. Disposal of waste to the biosphere has given way to thinking about, and trying to implement, an integrated waste management approach. In 1996 the United Nations Environmental Programme (UNEP) defined 'integrated waste management' as 'a framework of reference for designing and implementing new waste management systems and for analysing and optimising existing systems'. In this paper the concept of integrated waste management as defined by UNEP is considered, along with the parameters that constitute integrated waste management. The examples used are put into four categories: (1) integration within a single medium (solid, aqueous or atmospheric wastes) by considering alternative waste management options, (2) multi-media integration (solid, aqueous, atmospheric and energy wastes) by considering waste management options that can be applied to more than one medium, (3) tools (regulatory, economic, voluntary and informational) and (4) agents (governmental bodies (local and national), businesses and the community). This evaluation allows guidelines for enhancing success: (1) as experience increases, it is possible to deal with a greater complexity; and (2) integrated waste management requires a holistic approach, which encompasses a life cycle understanding of products and services. This in turn requires different specialisms to be involved in the instigation and analysis of an integrated waste management system. Taken together these advance the path to sustainability.

Conservation of Natural Resources↗