Dairy Science & Technology最新文献_第8页

Estimation of Individual Glucose Reserves in High-Yielding Dairy Cows 高产奶牛个体葡萄糖储备的估算

Dairy Science & Technology Pub Date : 2022-06-24 DOI: 10.3390/dairy3030033

Jonas Habel, P. Chapoutot, Christian Koch, A. Sundrum

{"title":"Estimation of Individual Glucose Reserves in High-Yielding Dairy Cows","authors":"Jonas Habel, P. Chapoutot, Christian Koch, A. Sundrum","doi":"10.3390/dairy3030033","DOIUrl":"https://doi.org/10.3390/dairy3030033","url":null,"abstract":"Glucose plays a central role in numerous physiological processes in dairy cows related to immune defence and milk production. A lack of glucose impairs both objectives, although to different degrees. A method for the estimation of glucose balance (GB) in dairy cows was developed to assess glucose reserves in the intermediary metabolism. Digestive fluxes of glucogenic carbon were individually estimated via the Systool Web application based on data on body weight (BW), dry matter intake (DMI), and chemical analyses of feedstuffs. Fluxes of endogenous precursors glycerol, alanine and L-lactate and the glucose demand imposed by major glucose-consuming organs were deduced from BW, lactose yield and lactation stage. GB was calculated for 201 lactations (1 to 105 DIM) of 157 cows fed isoenergetic rations. Individual DMI, BW and milk yield were assessed on a daily basis. The results showed that the GB varied greatly between cows and lactation stages. In the first week of lactation, average daily GB reached levels close to zero (3.2 ± 13.5 mol C) and increased as lactation progressed. Most cows risk substantial shortages of glucose for maintenance during the first weeks of lactation. In face of the specific role of glucose for the functional capability of the immune function, the assessment of glucose reserves is a promising measure for the identification of cows at risk of impaired immunocompetence.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89908990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease 牛奶蛋白衍生阿片肽控制阿尔茨海默病的抗胆碱酯酶抑制、药物相似性评估和分子对接评估

Dairy Science & Technology Pub Date : 2022-06-23 DOI: 10.3390/dairy3030032

Dawei Ji, Jingying Ma, Junyi Dai, MingQiang Xu, P. Harris, M. Brimble, D. Agyei

{"title":"Anticholinesterase Inhibition, Drug-Likeness Assessment, and Molecular Docking Evaluation of Milk Protein-Derived Opioid Peptides for the Control of Alzheimer’s Disease","authors":"Dawei Ji, Jingying Ma, Junyi Dai, MingQiang Xu, P. Harris, M. Brimble, D. Agyei","doi":"10.3390/dairy3030032","DOIUrl":"https://doi.org/10.3390/dairy3030032","url":null,"abstract":"The drug-likeness and pharmacokinetic properties of 23 dairy-protein-derived opioid peptides were studied using SwissADME and ADMETlab in silico tools. All the opioid peptides had poor drug-like properties based on violations of Lipinski’s rule-of-five. Moreover, prediction of their pharmacokinetic properties showed that the peptides had poor intestinal absorption and bioavailability. Following this, two well-known opioid peptides (βb-casomorphin-5, βb-casomorphin-7) from A1 bovine milk and caffeine (positive control) were selected for in silico molecular docking and in vitro inhibition study with two cholinesterase enzyme receptors important for the pathogenesis of Alzheimer’s disease. Both peptides showed higher binding free energies and inhibitory activities to butyrylcholinesterase (BChE) than caffeine, but in vitro binding energy values were lower than those from the docking model. Moreover, the two casomorphins had lower inhibitory properties against acetylcholinesterase (AChE) than caffeine, although the docking model predicted the opposite. At 1 mg/mL concentrations, βb-casomorphin-5 and βb-casomorphin-7 showed promising results in inhibiting both cholinesterases (i.e., respectively 34% and 43% inhibition of AChE, and 67% and 81% inhibition of BChE). These dairy-derived opioid peptides have the potential to treat Alzheimer’s disease via cholinesterase inhibition. However, appropriate derivatization may be required to improve their poor predicted intestinal absorption and bioavailability.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"170 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85081022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Geospatial Fluid Milk Processing Preferences: Is Consumer Taste Perception the Key Factor? 地理空间液态奶加工偏好:消费者味觉感知是关键因素吗?

Dairy Science & Technology Pub Date : 2022-06-13 DOI: 10.3390/dairy3020031

Kasey M Schalich, P. LaPierre, V. Selvaraj

引用次数: 1

Assessing Compositional and Quality Parameters of Unconcentrated and Refractive Window Concentrated Milk Based on Color Components 基于颜色成分的非浓缩和折光窗浓缩牛奶成分及质量参数评价

Dairy Science & Technology Pub Date : 2022-06-08 DOI: 10.3390/dairy3020030

Asaad R. S. Al-Hilphy, Haider. I. Ali, Sajedah A. Al‐Iessa, Mohsen Gavahian, Amin Mousavi-Khaneghah

{"title":"Assessing Compositional and Quality Parameters of Unconcentrated and Refractive Window Concentrated Milk Based on Color Components","authors":"Asaad R. S. Al-Hilphy, Haider. I. Ali, Sajedah A. Al‐Iessa, Mohsen Gavahian, Amin Mousavi-Khaneghah","doi":"10.3390/dairy3020030","DOIUrl":"https://doi.org/10.3390/dairy3020030","url":null,"abstract":"In this study, a multiple linear regression equation was developed to measure and predict quality parameters of unconcentrated and concentrated milk based on color components. The viscosity, density, pH, moisture, and fat content could be measured using image processing technology. The multiple linear regression model had a good fitting on experimental data considering the limited errors (0.00–1.12%), standard deviation (0.000–0.043), and root mean square error (0.0007–0.3721). Therefore, these models can be used to predict the quality parameters of milk, including fat percentage, pH, viscosity, density, and moisture content, based on color components of unconcentrated and concentrated milk. The maximum and minimum of color change were 12.28 and 5.96, respectively. The values of browning index were also well-predicted and were within the standard limits. The non-destructive and quick procedure that proposed in this study showed a percentage of accuracy in assessing and predicting the quality parameters milk based on color components. Overall, the color correlates with different compositional and physical characteristics, and provide a possible internet of things (IoT)-based approach to accompany the conventional approaches in the future after further evaluation at large scale for various types of milks subjected to various processes.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79470777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Herd Routines and Veterinary Advice Related to Drying-Off and the Dry Period of Dairy Cows 奶牛干乳期和干乳期的放牧习惯和兽医建议

Dairy Science & Technology Pub Date : 2022-06-01 DOI: 10.3390/dairy3020029

K. Persson Waller, H. Landin, A. Nyman

{"title":"Herd Routines and Veterinary Advice Related to Drying-Off and the Dry Period of Dairy Cows","authors":"K. Persson Waller, H. Landin, A. Nyman","doi":"10.3390/dairy3020029","DOIUrl":"https://doi.org/10.3390/dairy3020029","url":null,"abstract":"Bovine mastitis at calving or early lactation is often associated with intra-mammary bacterial infections (IMI) at drying-off (DO) or during the dry period (DP). The IMI risk is associated with management routines at the herd, but knowledge on how farmers and veterinarians comply with national recommendations is scarce, as is their attitudes to the importance of such routines. Therefore, the main aims of this study were to collect information on farmer routines and attitudes, and on veterinary advice and attitudes to DO and DP. Associations between routines and advice, and demographic herd and veterinary variables were also studied. Web-based questionnaires were sent to 2472 dairy farmers and 517 veterinarians. The answers were summarized descriptively, and associations with demographics were evaluated using univariable regression models. The response rate was 14% for farmers and 25% for veterinarians. Routines and advice were in line with recommendations at the time of the study in many, but not all, areas of questioning. Significant associations between herd routines or veterinary advice and demographic variables were also found. Milking system and post-graduate training were the variables associated with the largest number of farmer and veterinary answers, respectively. In conclusion, the results indicate a need for more education on good routines during DO and DP. It was also clear that the national recommendations valid at the time of the study were in need of revision.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78116440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Parmigiano Reggiano Consumption on Blood Pressure of Spontaneous Hypertensive Rats 帕尔马干酪对自发性高血压大鼠血压的影响

Dairy Science & Technology Pub Date : 2022-05-23 DOI: 10.3390/dairy3020028

L. Basiricò, P. Morera, Chiara Evangelista, G. Galaverna, S. Sforza, B. Prandi, U. Bernabucci, A. Nardone

{"title":"Effect of Parmigiano Reggiano Consumption on Blood Pressure of Spontaneous Hypertensive Rats","authors":"L. Basiricò, P. Morera, Chiara Evangelista, G. Galaverna, S. Sforza, B. Prandi, U. Bernabucci, A. Nardone","doi":"10.3390/dairy3020028","DOIUrl":"https://doi.org/10.3390/dairy3020028","url":null,"abstract":"In recent years, due to the significant increase in hypertension, peptides which are able to reduce blood pressure have gained special interest by scientific research and food industry. Several bioactive peptides with ascertained ACE-inhibitory activity have been found in Parmigiano Reggiano (PR) cheese and/or mixtures deriving from its digestion in vitro, and this may be predictive of its potential antihypertensive effect in vivo. This study investigated the long-term effect of feeding (PR) cheese on blood pressure (BP) of spontaneously hypertensive rats (SHRs). A total of 30 male SHRs, 13 weeks old, were subdivided into 6 groups balanced for body weight and BP, to receive daily dietary supplementation with: 0.1–0.2–0.4–0.6 g PR/rat, captopril, and water. Systolic and diastolic BP were recorded every two weeks, for 10 weeks. Blood samples were collected at the end of the trial. Dietary integration with PR led to a transitory reduction in rats’ pressure in the first 35 days of treatment and pressure decreased in a dose-dependent manner. In the second part of the study, the beneficial effect of PR antihypertensive peptides may have been masked and reduced by the increase in BP of rats linked to the rise in age of animals. No PR derived peptides were detected in rats’ serum. Highlights: Parmigiano Reggiano (PR) cheese led to a transitory reduction in rats’ pressure in the first 35 days of treatment. This effect was PR dose dependent. The highest amounts of PR tested did not increase both systolic and diastolic blood pressures of hypertensive rats.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"289 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73564172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Balancing Trade-Offs in Milk Production by Making Use of Animal Individual Energy Balancing 利用动物个体能量平衡平衡产奶量

Dairy Science & Technology Pub Date : 2022-05-17 DOI: 10.3390/dairy3020027

Theresa Rumphorst, T. Scheu, C. Koch, A. Sundrum

{"title":"Balancing Trade-Offs in Milk Production by Making Use of Animal Individual Energy Balancing","authors":"Theresa Rumphorst, T. Scheu, C. Koch, A. Sundrum","doi":"10.3390/dairy3020027","DOIUrl":"https://doi.org/10.3390/dairy3020027","url":null,"abstract":"Traditionally, the energy supply of dairy cows is based on the average performance of the herd. Because this contradicts the great variation in requirements between individual animals, the objective of the present study was to quantify both the extent and consequences of variation in the relevant sub-variables used to calculate the energy balance (EB) on an individual animal basis. Total energy supply (TES) and requirements (TER) of 28 multiparous German Holstein dairy cows fed TMR with 7.0 MJ NEL were studied between the 2nd and 15th week after calving. TES, mainly influenced by DMI, increased from 100.1 (week 2) to 152.1 MJ NEL/d (week 15; p < 0.01). Weekly coefficients of variation (CV) ranged between 0.10 and 0.16 and were similar to the CV of DMI (0.09 to 0.17). TER, as the sum of energy requirement for maintenance (body weight) and production (milk yield), decreased from 174.8 (week 2) to 164.5 MJ NEL/d (week 15; p < 0.01) and CV varied between 0.16 (week 2) and 0.07 (week 11). EB increased from −74.8 (week 2) to −12.4 MJ NEL/d (week 15; p < 0.01) and CV varied from 0.32 (week 3) to 1.01 (week 10). The results indicate that calculating EB on an individual animal basis is a prerequisite to identify animals with an increased risk of failing to cope with their energy situation, which cause failure costs that drain the profit of affected cows.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78041355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Live Weight and Bone Growth from Birth to 23 Months of Age in Holstein–Friesian, Jersey and Crossbred Heifers 荷斯泰因-弗里西亚、泽西和杂交小母牛出生至23月龄的活重和骨生长

Dairy Science & Technology Pub Date : 2022-05-13 DOI: 10.3390/dairy3020026

M. Gibson, Brooke R. Adams, P. Back, R. Hickson, K. Dittmer, C. Rogers

{"title":"Live Weight and Bone Growth from Birth to 23 Months of Age in Holstein–Friesian, Jersey and Crossbred Heifers","authors":"M. Gibson, Brooke R. Adams, P. Back, R. Hickson, K. Dittmer, C. Rogers","doi":"10.3390/dairy3020026","DOIUrl":"https://doi.org/10.3390/dairy3020026","url":null,"abstract":"Selection pressure for greater milk solid production, calving ease and early puberty attainment has resulted in the alteration of the growth trajectory of New Zealand dairy heifers. Although previous data have looked at stature growth in terms of height and girth, changes in the growth trajectory as a result of seasonal growth has not been examined. In addition, the relative contributions of the appendicular skeleton and thorax in relation to height have not been considered in previous studies. Therefore, the aim of this study was to examine how the proportional contributions of stature change with increases in live weight in Holstein–Friesian, Jersey and Holstein–Friesian–Jersey crossbred heifers from birth to 23 months of age (just prior to calving). Comparisons of height, length, girth and distal and proximal forelimb length (stature) revealed that at the same live weight, measures of girth, length and height did not differ between breeds (p < 0.05). As live weight increases, the relative contribution of the distal limb to increasing height decreases, which is consistent with the cessation of physeal growth occurring earlier in the bones of the distal limb than in the proximal limb. By understanding the timing of proximal and distal growth in dairy heifers, the effect of seasonal growth on longitudinal bone growth can be identified.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73277175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Effects of Yucca schidigera Based Feed Additive on In Vitro Dry Matter Digestibility, Efficiency of Microbial Production, and Greenhouse Gas Emissions of Four Dairy Diets 丝兰基饲料添加剂对4种奶牛日粮干物质体外消化率、微生物生产效率和温室气体排放的影响

Dairy Science & Technology Pub Date : 2022-05-06 DOI: 10.3390/dairy3020025

U. Anele, Xavier Crumel, Lydia K. Olagunju, D. P. Compart

{"title":"Effects of Yucca schidigera Based Feed Additive on In Vitro Dry Matter Digestibility, Efficiency of Microbial Production, and Greenhouse Gas Emissions of Four Dairy Diets","authors":"U. Anele, Xavier Crumel, Lydia K. Olagunju, D. P. Compart","doi":"10.3390/dairy3020025","DOIUrl":"https://doi.org/10.3390/dairy3020025","url":null,"abstract":"The present study evaluated the effects of a feed additive (synthesized from Yucca schidigera) on some fermentation variables. In the first of two experiments, seven concentrations of the feed additive were evaluated using the in vitro batch culture technique to determine the optimum dose to use in the second experiment. The substrates used were a total mixed ration (TMR) and alfalfa hay. The levels of inclusion were 0 (control), 0.5, 1, 2, 4, 6, and 8 g/head/d. After this initial evaluation, 2 g/head/d was selected for the second experiment. For the second study, four dietary substrates (two corn silages and two TMR; collected from different dairy farms in the Piedmont, North Carolina, area) were used. Incubation times were 3, 6, and 24 h and treatments were 0 (control) and 2 g/head/d of the feed additive. Inclusion of the feed additive did not affect (p > 0.05) in vitro dry matter disappearance. Additionally, the feed additive had no effect (p > 0.05) on short-chain fatty acid concentrations, microbial mass, and efficiency of microbial production. Methane production was reduced by 22.7% with feed additive inclusion. Similarly, lower (p = 0.013; 18%) carbon dioxide concentration was observed in the feed additive treatment. Ammonia and hydrogen sulfite concentrations were similar (p > 0.05) for both treatments. Inclusion of the feed additive at 2 g/head/d decreased methane and carbon dioxide concentrations in most of the diets. The energy saved by reducing the amount of methane produced was not partitioned into valuable products such as short-chain fatty acids and microbial mass.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84508679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Occurrence of Polyphenols, Isoflavonoids, and Their Metabolites in Milk Samples from Different Cow Feeding Regimens 不同奶牛喂养方案牛奶样品中多酚、异黄酮及其代谢物的存在

Dairy Science & Technology Pub Date : 2022-05-06 DOI: 10.3390/dairy3020024

G. Rocchetti, F. Ghilardelli, Martina Mosconi, F. Masoero, A. Gallo

{"title":"Occurrence of Polyphenols, Isoflavonoids, and Their Metabolites in Milk Samples from Different Cow Feeding Regimens","authors":"G. Rocchetti, F. Ghilardelli, Martina Mosconi, F. Masoero, A. Gallo","doi":"10.3390/dairy3020024","DOIUrl":"https://doi.org/10.3390/dairy3020024","url":null,"abstract":"In this work, milk samples collected in a cohort of intensive dairy farms of the Po Valley (Italy) were screened for their (poly)-phenolic profile to check the occurrence of phenolic metabolites of biological interest. The selected dairy farms were previously classified on the basis of their cow feeding system, considering the utilization of corn silage as the main ingredient of the rations. Overall, ultra-high-pressure liquid chromatography coupled with mass spectrometry using an Orbitrap analyzer, followed by unsupervised and supervised statistics, allowed identifying clear different phenolic distributions in the milk samples. Accordingly, a great variability in the phenolic profiles of the different milk samples was observed, with two main phenolic clusters outlined by the unsupervised hierarchical clustering approach and not fully correlated to the nutritional strategy considered. The variables’ importance in the projection approach allowed selecting the most important metabolites, resulting in samples’ discrimination. Among the most discriminative compounds, we found phenolic metabolites (such as hippuric acid and 4-hydroxyhippuric acid), followed by lignans (such as enterolactone) and isoflavonoids (such as equol and O-desmethylangolensin). Taken together, our findings suggested that both the feeding systems and the ability of dairy cows to process parent phenolic compounds were the main factors providing the final (poly)-phenolic profile of the milk samples. Future targeted and ad hoc studies appear of great interest to evaluate the potential biological effects of these compounds on cow health.","PeriodicalId":11001,"journal":{"name":"Dairy Science & Technology","volume":"88 12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83457744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1