The first outbreak of Lumpy Skin Disease in Indonesia.

This study describes the first outbreak of Lumpy Skin Disease (LSD) in cattle in the Bengkalis region, Indonesia, and vaccination to control the epidemic. Data on the outbreak and vaccination was obtained from the local veterinary authority of the Bengkalis region, Indonesia. Climatological data was provided by the Meteorological, Climatological, and Geophysical Agency of Riau Province. Over the 5.5 months, the outbreak caused 10.4% (94/906) morbidity and 0.6% (6/906) mortality of cattle on infected farms. Temporally, three epidemic waves occurred during the outbreak period. Villages with cattle populations of > 150 animals (n = 36) were 5.3 times more likely to be infected with LSD compared to villages with smaller cattle populations (n = 107) (CI: 2.56-10.90, P < 0.01). The vaccination campaign covered 43.8% of cattle in villages within a 10 km radius of the cases. However, vaccination in villages with larger cattle populations (n = 29) was 0.63 less likely to cover 50% of the cattle populations compared to villages with smaller cattle populations (n = 41) (CI: 0.39-1.02, P = 0.05). By the time the first two and the major waves ceased, vaccination had covered only 0.0% (n = 6036), 27.8% (n = 6,036) and 9.7% (n = 5,697) of the cattle in the 10 km radius of the respective spatial clusters. The outbreak was statistically associated with rainfall and its interaction with temperature (F(2, 13) = 5.822, R2 = 0.47, P = 0.016). This study indicates that the LSD outbreak had low morbidity and mortality. Despite the low vaccination rate, the outbreak ceased, possibly due to plummeting of the abundance of insect vectors.

Factors affecting enduring participation in a pig farming program in Southern Papua, Indonesia.

In mid-2016, the local government of Papua, Indonesia, launched a subsidised program to improve pig farming in the area, with 250 participants. This study aimed to investigate factors associated with enduring participation in pig farming among the program participants. Two years after the commencement of the program, one hundred of the 250 participants were recruited into the study and divided into two groups: participants who continued to engage in pig farming ("remain") and those who had quit pig farming ("quit"). Data were collected from interviews, including personal data and events on the farms between April 2017 and March 2018. Multiple correspondence analysis, followed by a two-step cluster analysis and multivariate regression, was used to explore factors associated with the durability of pig farmings. Results indicated that associated factors included feed and water security, the use of concrete material for the pig house floor, the avoidance of swill feeding, reduced pig mortality, and continued pig husbandry training. This study highlights that a good feeding regimen and effective control of pig diseases should be priority pig husbandry techniques to be extended through training and assistance to improve traditional pig farming in Papua.

Activation of a Copper Biscarbene Mechano-Catalyst Using Single-Molecule Force Spectroscopy Supported by Quantum Chemical Calculations.

Single-molecule force spectroscopy allows investigation of the effect of mechanical force on individual bonds. By determining the forces necessary to sufficiently activate bonds to trigger dissociation, it is possible to predict the behavior of mechanophores. The force necessary to activate a copper biscarbene mechano-catalyst intended for self-healing materials was measured. By using a safety line bypassing the mechanophore, it was possible to pinpoint the dissociation of the investigated bond and determine rupture forces to range from 1.6 to 2.6 nN at room temperature in dimethyl sulfoxide. The average length-increase upon rupture of the Cu-C bond, due to the stretching of the safety line, agrees with quantum chemical calculations, but the values exhibit an unusual scattering. This scattering was assigned to the conformational flexibility of the mechanophore, which includes formation of a threaded structure and recoiling of the safety line.

Are infectious reproductive pathogens of large ruminants a threat to improving food security? An investigation from Cambodia.

In Cambodia, information on common pathogens causing reproductive losses in cattle and buffalo are lacking, despite there being a need to address livestock health to enhance food security. We analysed stored buffalo (n = 29) and cattle (n = 471) serum samples collected in 2016 using commercially available enzyme-linked immunosorbent assay kits. Antibodies to Neospora caninum, bovine viral diarrhoea virus (BVDV), Leptospira interrogans serovar Hardjo and Brucella abortus were detected in buffalo samples at 79.3% (95% CI 64.6-94.0), 3.4% (95% CI 0-10.0), 0% and 0%, respectively, and in cattle at 4.2% (95% CI 2.4-6.0), 6.4% (95% CI 4.2-8.6), 8.1% (95% CI 5.6-10.6) and 0%, respectively. The high N. caninum seroprevalence in buffalo was associated with increasing age, with buffalo having a 13.1% chance of being seropositive at birth, increasing to 99.4% by age 7 (p = 0.045). This suggests a predominance of horizontal transmission, possibly from exposure to faeces from free-roaming village dogs. Cattle L. interrogans serovar Hardjo seroprevalence was highest in Tbong Khmum province (20.4%) compared to other provinces (p < 0.001), and may be compromising bovine fertility and creating a zoonotic risk for smallholders who may contract leptospirosis from farm work. These high infection rates prompt further research to determine: to what extent these pathogens are linked to the low reproductive efficiency observed in large ruminants in Cambodia, the risk factors to pathogen exposure and appropriate strategies to reduce these risks. Low BVDV and B. abortus exposure is an important observation. Increasing large ruminant livestock trade into the country will require improved biosecurity and disease surveillance to prevent their emergence. An enhanced understanding of the status of infectious reproductive livestock pathogens in Cambodia can assist development projects to make evidence-based strategies to enhance cattle and buffalo health and improve food security.

Detection of stress in polymers: mechanochemical activation of CuAAC click reactions in poly(urethane) networks.

We report on copper(i)-bis(N-heterocyclic carbene)s (NHC) for quantitative stress-sensing, embedded within polyurethane networks, triggering a fluorogenic copper(i) azide alkyne cycloaddition (CuAAC) of 8-azido-2-naphtol and 3-hydroxy phenylacetylene. A completely transparent, force responsive poly(urethane) material is generated, allowing a quantification of the applied stress.

CuAAC-Based Click Chemistry in Self-Healing Polymers.

Click chemistry has emerged as a significant tool for materials science, organic chemistry, and bioscience. Based on the initial concept of Barry Sharpless in 2001, the copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC) reaction has triggered a plethora of chemical concepts for linking molecules and building blocks under ambient conditions, forming the basis for applications in autonomous cross-linking materials. Self-healing systems on the other hand are often based on mild cross-linking chemistries that are able to react either autonomously or upon an external trigger. In the ideal case, self-healing takes place efficiently at low temperatures, independent of the substrate(s) used, by forming strong and stable networks, binding to the newly generated (cracked) interfaces to restore the original material properties. The use of the CuAAC in self-healing systems, most of all the careful design of copper-based catalysts linked to additives as well as the chemical diversity of substrates, has led to an enormous potential of applications of this singular reaction. The implementation of click-based strategies in self-healing systems therefore is highly attractive, as here chemical (and physical) concepts of molecular reactivity, molecular design, and even metal catalysis are connected to aspects of materials science. In this Account, we will show how CuAAC reactions of multivalent components can be used as a tool for self-healing materials, achieving cross-linking at low temperatures (exploiting concepts of autocatalysis or internal chelation within the bulk CuAAC and systematic optimization of the efficiency of the used Cu(I) catalysts). Encapsulation strategies to separate the click components by micro- and nanoencapsulation are required in this context. Consequently, the examples reported here describe chemical concepts to realize more efficient and faster click reactions in self-healing polymeric materials. Thus, enhanced chain diffusion in (hyper)branched polymers, autocatalysis, or internal chelation concepts enable efficient click cross-linking already at 5 °C with a simultaneously reduced amount of Cu(I) catalyst and increased reaction rates, culminating in the first reported self-healing system based on click cycloaddition reactions. Via tailor-made nanocarbon/Cu(I) catalysts we can further improve the click cross-linking reaction in view of efficiency and kinetics, leading to the generation of self-healing graphene-based epoxy nanocomposites. Additionally, we have designed special CuAAC click methods for chemical reporting and visualization systems based on the detection of ruptured capsules via a fluorogenic click reaction, which can be combined with CuAAC cross-linking reactions to obtain simultaneous stress detection and self-healing within polymeric materials. In a similar concept, we have prepared polymeric Cu(I)-biscarbene complexes to detect (mechanical) stress within self-healing polymeric materials via a triggered fluorogenic reaction, thus using a destructive force for a constructive chemical response.

Mechanochemical Activation of Fluorogenic CuAAC "Click" Reactions for Stress-Sensing Applications.

Strategies for visualizing stress within polymeric materials are of growing interest during the past decade. In this paper, stress-sensing materials, triggered by a mechanoresponsive catalytic system based on latent copper(I)bis(N-heterocyclic carbene) mechanophores, are reported, which can be activated by compression force to trigger a fluorogenic copper(I)-catalyzed alkyne/azide "click" cycloaddition reaction, activating a fluorescent dye useful for stress-sensing applications in bulk polymeric materials. The focus is placed on the polymeric architecture, which is responsible for an efficient stress transmission, revealing the greatest activation for network-based mechanocatalysts, observing "click" conversions up to 44%, while chain-extended and linear mechanocatalysts activate either in a less efficient manner or are not completely latent in the initial state. The developed catalysts enable "irreversible" mechanochromic systems for stress-sensing devices.

Investigations of selected pathogens among village pigs in Central Papua, Indonesia.

Village pig husbandry is an important part of livestock production in Papua Province, Eastern Indonesia. However, high level of disease and mortality constrains production. The aim of this study was to investigate the prevalence of the selected pathogens in village pigs in the Jayawijaya Region of Papua Province, Indonesia. Two studies were conducted: Study 1 determined the prevalence of selected pathogens in dead or moribund pigs sent to the main local market for sale. Study 2 recorded the prevalence of the selected pathogens, on pig farms in the Subdistrict of Wamena that had not recorded a case of pig mortality during the duration of Study 1. Blood samples of individuals from both groups were tested for CSF antigen and antibody, as well as antibody against PCV2. Organs with evident pathological changes from Study 1 and tonsilar swabs from Study 2 were subjected to bacteriological culture and identification of Streptococcus suis and Streptococcus zooepidemicus. Faecal samples from both studies were examined for eggs of strongyle parasites, Trichuris suis, Ascaris suum, Strongyloides ransomi and coccidia. The main infections in both studies were CSF, PCV2 and strongyle parasites, but prevalence was higher in Study 1 (P < 0.05). T. suis and S. zooepidemicus were prevalent in pigs in Study 1, but rare in healthy pigs (P < 0.05). Infections with coccidia, A. suum and S. ransomi were common but did not differ between groups (P < 0.05), with S. suis infections uncommon in both studies. This suggests that infections with CSF, PCV2, strongyle and T. suis are important pathogens in village pig farms in Jayawijaya. Local pig husbandry practices, such as confining pigs and heat-treating pig feeds, may be practical solutions to help minimize infection in village pigs in Jayawijaya.

Evaluation of furazolidone, sulfadimidine and amprolium to treat coccidiosis in Beetal goats under field conditions.

Coccidiosis is a protozoal and occasionally fatal diarrheic disease of goats imposing heavy economic losses to farming community. This study aimed to evaluate the efficacies of Furazolidone, Sulfadimidine and Amprolium against coccidiosis in Beetal goats. Twenty-four (24) Beetal goats naturally infected with coccidiosis were randomly divided into four groups of 6 (A-D). Goats in groups A, B and C were treated orally with Furazolidone (10 mg/Kg), Sulfadimidine (100 mg/Kg) and Amprolium (55 mg/Kg), respectively for 7 days. Goats in-group D served as positive control. Oocysts per gram (OPG) of feces counts of individual goats in each group were performed on Days; 0 (pre-treatment) 7, 14 and 21 (post-treatment). OPG counts amongst goats in all groups at day 0 were not significant (P>0.05). On days 7, 14 and 21, OPG values decreased significantly (P<0.05) in groups A, B and C compared to group D. The efficacy of Furazolidone, Sulfadimidine and Amprolium was 98.6, 98.0 and 99.6 percent, respectively on Day 21 (end of trial). Statistically, the efficacies of three drugs were not significantly different (P>0.05). In conclusion, Furazolidone, Sulfadimidine and Amprolium are well-tolerated and any one of these may be recommended to effectively treat coccidiosis in Beetal goats.

Traditional pig farming practices and productivity in the Jayawijaya region, Papua Province, Indonesia.

The objective of the current survey was to provide an update on pig farming practices in the Jayawijaya region, Papua Province, Indonesia. A structured semi-close-ended questionnaire was used to interview 367 farmers across the Jayawijaya region. Results showed that farms, on average, comprised of 8.8 pigs (CI 8.5-9.1). The average litter size was 6.0 (CI 5.7-6.3) piglets, the farrowing frequency was once a year, and the annual mortality rate was 50.2% (CI 48.4-51.9). On average, 43.4% farms (CI 36.4-50.7) allowed pigs to roam freely during daylight hours. Farmers used pigs for their own consumption (62.4%, CI 57.4-67.4), as a gift (56.6%, CI 51.5-61.7), or for sale (50.7%, CI 45.6-55.8). Veterinary services were used intensively by just 11.7% of farmers (CI 8.2-16.5). Furthermore, 34.2% (CI 29.3-39) of farmers would sell sick pigs, and 63.1% (CI 58.2-68.1) would slaughter and consume them. It was also recorded that 68.6% of farmers (CI 63.7-73.4) would eat sick pigs that had died naturally. These findings suggest that traditional pig farms in Jayawijaya are of low productivity. Moreover, the free roaming of pigs and the sale and consumption of sick pigs have the potential to allow pathogens to circulate between pig and human populations.

A Mechanochemically Triggered "Click" Catalyst.

"Click" chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site- and stress-specific "click" reactions--a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper-catalyzed "click" reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N-heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state.

Self-healing polymers via supramolecular forces.

As polymers and polymeric materials are "the" smart invention and technological driving force of the 20th century, the quest for self-healing or self-repairing polymers is strong. The concept of supramolecular self-healing materials relies on the use of noncovalent, transient bonds to generate networks, which are able to heal the damaged site, putting aspects of reversibility and dynamics of a network as crucial factors for the understanding and design of such self-healing materials. This Review describes recent examples and concepts of supramolecular polymers based on hydrogen bonding, π-π interactions, ionomers, and coordinative bonds, thus convincingly discussing the advantages and versatility of these supramolecular forces for the design and realization of self-healing polymers.

Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy.

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is an emerging cancer therapeutic that just recently gained Food and Drug Administration approval for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor (Her)2-negative breast cancer in combination with the ER degrader fulvestrant. However, CDK4/6 inhibitors are not cancer-specific and may affect also other proliferating cells. Given the importance of T cells in antitumor defense, we studied the influence of palbociclib/fulvestrant on human CD3+ T cells and novel emerging T cell-based cancer immunotherapies. Palbociclib considerably inhibited the proliferation of activated T cells by mediating G0/G1 cell cycle arrest. However, after stopping the drug supply this suppression was fully reversible. In light of combination approaches, we further investigated the effect of palbociclib/fulvestrant on T cell-based immunotherapies by using a CD3-PSCA bispecific antibody or universal chimeric antigen receptor (UniCAR) T cells. Thereby, we observed that palbociclib clearly impaired T cell expansion. This effect resulted in a lower total concentration of interferon-γ and tumor necrosis factor, while palbociclib did not inhibit the average cytokine release per cell. In addition, the cytotoxic potential of the redirected T cells was unaffected by palbociclib and fulvestrant. Overall, these novel findings may have implications for the design of treatment modalities combining CDK4/6 inhibition and T cell-based cancer immunotherapeutic strategies.

The Epidemiology and Control of Bovine Viral Diarrhoea Virus in Tropical Indonesian Cattle.

This review aims to update the knowledge of the epidemiology of Bovine viral diarrhoea virus (BVDV) in Indonesia and Southeast Asia and provide a perspective on the control options for BVDV in the Indonesian cattle population in the future. Studies on BVDV in Indonesia, since its first report in that country, and the updated beef and dairy cattle industries are reviewed. In ten of 34 provinces, BVDV is endemic. The subgenotypes of BVDV-1a and BVDV-1c are predominant in Indonesian cattle. However, BVDV is currently not a priority disease to control in Indonesia. Cattle imports from Australia appear to be potentially the most significant source of transmission of BVDV into native cattle, but the control of BVDV conducted in the local quarantine facilities is currently not achieving the aim of controlling BVDV; thus, complementary measures are needed. With the small-scale nature of the vast majority of cattle breeding in the country, the control of BVDV in provinces in which cattle breeding is economically essential may need to be organised by regional and provincial governments. Gaps in our knowledge of BVDV are identified in this review, and strategies for the control of BVDV in Indonesia are discussed.

Self-Diagnostic Polymers-Inline Detection of Thermal Degradation of Unsaturated Poly(ester imide)s.

Monitoring polymer degradation is an important quest, particularly relevant for industry. Although many indirect methodologies for assessing polymer degradation exist, only few are applicable for an inline-monitoring via optic detection-systems. An inline-monitoring system is introduced for the thermal degradation of crosslinked poly(ester imide)s (PEIs) by embedding trifluoroacetyl functionalized stilbene molecules, serving as chemosensors to track the release of generated alcoholic byproducts. Nucleophilic addition of an alcohol to the sensors trifluoroacetyl functionality triggers hemiacetal formation which is accompanied by significant changes in optical properties, in turn allowing monitoring of sensor activation by direct spectroscopy. Fluorescence spectroscopy offers an easy detection tool for the inline thermal monitoring of PEI-degradation.

Tunneling Atomic Force Microscopy Analysis of Supramolecular Self-Responsive Nanocomposites.

A big step forward for composite application in the sector of structural materials is given by the use of Multi-Wall Carbon Nanotubes (MWCNTs) functionalized with hydrogen bonding moieties, such as barbiturate and thymine, to activate self-healing mechanisms and integrate additional functionalities. These materials with multiple healing properties at the same damaged site, imparted by hydrogen bonds, will also have the potential to improve material reliability, extend the service life, reduce replacement costs, and improve product safety. This revolutionary approach is obtained by integrating the non-covalent interactions coupled with the conventional covalent approach used to cross-link the polymer. The objective of this work is to characterize rubber-toughened supramolecular self-healing epoxy formulations based on unfunctionalized and functionalized MWCNTs using Tunneling Atomic Force Microscopy (TUNA). This advanced technique clearly shows the effect produced by the hydrogen bonding moieties acting as reversible healing elements by their simultaneous donor and acceptor character, and covalently linked to MWCNTs to originate self-healing nanocomposites. In particular, TUNA proved to be very effective for the morphology study of both the unfunctionalized and functionalized carbon nanotube-based conductive networks, thus providing useful insights aimed at understanding the influence of the intrinsic nature of the nanocharge on the final properties of the multifunctional composites.

Targeting Acute Myeloid Leukemia Using the RevCAR Platform: A Programmable, Switchable and Combinatorial Strategy.

Clinical translation of novel immunotherapeutic strategies such as chimeric antigen receptor (CAR) T-cells in acute myeloid leukemia (AML) is still at an early stage. Major challenges include immune escape and disease relapse demanding for further improvements in CAR design. To overcome such hurdles, we have invented the switchable, flexible and programmable adaptor Reverse (Rev) CAR platform. This consists of T-cells engineered with RevCARs that are primarily inactive as they express an extracellular short peptide epitope incapable of recognizing surface antigens. RevCAR T-cells can be redirected to tumor antigens and controlled by bispecific antibodies cross-linking RevCAR T- and tumor cells resulting in tumor lysis. Remarkably, the RevCAR platform enables combinatorial tumor targeting following Boolean logic gates. We herein show for the first time the applicability of the RevCAR platform to target myeloid malignancies like AML. Applying in vitro and in vivo models, we have proven that AML cell lines as well as patient-derived AML blasts were efficiently killed by redirected RevCAR T-cells targeting CD33 and CD123 in a flexible manner. Furthermore, by targeting both antigens, a Boolean AND gate logic targeting could be achieved using the RevCAR platform. These accomplishments pave the way towards an improved and personalized immunotherapy for AML patients.

Infection with Bovine Viral Diarrhea Virus in Cattle in Southern Papua, Indonesia.

The aim of this preliminary study was to determine the prevalence of Bovine Viral Diarrhea Virus (BVDV) and its association with reproductive problems in cattle in Timika, Southern Papua, Indonesia, an emerging area for beef production. Serum from 77 beef cattle was collected from four villages and tested, using both antibody and antigen ELISA kits for BVDV. Data of the villages of origin, age, breed, sex and the number of parities of the cattle were collected. The pregnancy status of the cattle was determined by rectal examination. Results showed that the prevalence of BVDV antibody in individual cattle in Timika was 11.7% (CI: 6.1 - 20.0%), while at the farm level the antibody prevalence was 18.4% (CI: 8.9 - 33.7%).). Seropositivity for BVDV increased with age (P=0.02), from 0% (CI: 0 - 37.2%) in less than two-years old to 28.6% (CI: 11.3 - 55.0%) in cattle older than eight years of age. BVDV antibody was 2.9 times more prevalent in non-pregnant cows than in antibody negative cows (CI: 1.02 - 8.14, P=0.04). BVD antigen was not detected in the present study. This study reported for the first time, evidence of infection with BVDV in cattle in Papua and indicated that BVDV infection may be associated with infertility.

Synthesis and Mechanochemical Activity of Peptide-Based Cu(I) Bis(N-heterocyclic carbene) Complexes.

With the class of shock-absorbing proteins, nature created some of the most robust materials combining both mechanical strength and elasticity. Their excellent ability to dissipate energy to prevent surrounding cells from damage is an interesting property that regularly is exploited for applications in biomimetic materials. Similar to biomaterials, where mechanical stimuli are transmitted into a (bio)chemical response, mechanophoric catalysts transform mechanical energy into a chemical reaction. Force transmission is realized commonly by polymeric handles directing the applied force to the mechanophoric bond, which in turn leads to stress-induced activation of the catalyst. Therefore, shock-absorbing proteins able to take up and store mechanical energy elastically for subsequent force transduction to the labile bond seem to be perfect candidates to fulfill this task. Here, we report on the synthesis of two different latent mechanophoric copper(I) bis(N-heterocyclic carbene) complexes bearing either two carboxyl groups or two amino groups which allow conjugation reactions with either the N- or the C-terminus of amino acids or peptides. The chosen catalysts can be activated, for instance, by applying external mechanical force via ultrasound, removing one N-heterocyclic carbene (NHC) ligand. Post-modification of the mechanophoric catalysts via peptide coupling (Gly, Val) and first reactions showed that the mechanoresponsive behavior was still present after the coupling. Subsequent polycondensation of both catalysts lead to a polyamide including the Cu(I) moiety. Mechanochemical activation by ultrasound showed conversions in the copper(I)-catalyzed alkyne-azide "click" reaction (CuAAC) up to 9.9% proving the potential application for the time and spatial controlled CuAAC.