This article reviews the background and reemergence of WNF in Israel; the recent

epidemiology of WNF among Israelis; and the disease-control strategies being used to combat the disease. Methods: Employing the comprehensive base of case data that are reported to the Ministry of Health, an epidemiological record was constructed that details the incidence and distribution of WNF cases in Israel in recent years. Results: After decades of small, intermittent outbreaks, nearly 1400 cases of WNF were reported in Israel between 2000 and 2012. Incidence was consistently highest in the coastal cities, among elderly patients, and in the late summer months and early autumn. A broad range of control measures to prevent human infection has been implemented, and attention has been given to issues such as the protection of the national blood bank and the occurrence of long-term sequelae. Conclusions: The reemergence of WNF in Birinapant price Israel is likely the result of a combination of factors including past immunity to the virus among the human population, a marked increase in awareness of WNF among physicians, and more frequent requests for the laboratory testing of suspected cases. In the absence of effective vaccine to protect humans from WNF, the best disease-control strategies include intensive vector-control measures,

the continued development of techniques to forecast outbreaks, and effective public education programs Sapanisertib inhibitor that are targeted toward the high-risk elderly population. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.”
“The generalized entropy theory is applied to assess the joint influence of the microscopic cohesive energy and chain stiffness on glass formation in: polymer melts using a minimal model containing a single bending energy and a single (monomer averaged) nearest neighbor van der Waals energy.

JNK inhibitor The analysis focuses on the combined impact of the microscopic cohesive energy and chain stiffness on the magnitudes of the isobaric fragility parameter m(p) and the glass transition temperature T-g. The computations imply that polymers with rigid structures and weak nearest neighbor interactions are the most fragile, while T-g becomes larger when the chains are stiffer and/or nearest neighbor interactions are stronger. Two simple fitting formulas summarize the computations describing the dependence of M-p and T-g on the microscopic cohesive and bending energies. The consideration of the combined influence of the microscopic cohesive and bending energies leads to the identification of some important design concepts, such as iso-fragility and iso-T-g lines, where, for instance, iso-fragility lines are contours with constant mp but variable T-g. Several thermodynamic properties are found to remain invariant along the iso-fragility lines, while no special characteristics are detected along the iso-T-g lines.

“
“A novel amperometric glucose biosensor based on the nanocomposites of multi-wall carbon nanotubes (CNT) coated with polyaniline (PANI) and dendrimer-encapsulated Pt nanoparticles (Pt-DENs) is prepared. CNT coated

with protonated PANI is in situ synthesized and Pt-DENs is absorbed on PANI/CNT composite surface by self-assembly method. Then Glucose oxidase (GOx) is crosslink-immobilizated onto Pt-DENs/PANI/CNT composite film. The results show that the fabricated GOx/Pt-DENs/PANI/CNT electrode exhibits excellent response performance to glucose, such as low detection limit (0.5 mu M), wide linear Navitoclax range (1 mu M-12 mM), short response time (about 5 s), high sensitivity (42.0 mu A mM(-1) cm(-2)) and stability (83% remains after 3 weeks). (C) 2008 Elsevier B.V. All rights reserved.”
“Objectives: To investigate whether adverse intrauterine and/or childhood exposures, using established anthropometric measures (e.g., components of adult height, including total height, leg length, and trunk length) as a proxy for childhood exposures,

are associated with self-reported Meniere’s disease. Design: Cross-sectional data from the UK Biobank were used to compare 1,327 self-reported Meniere’s cases with 479,500 controls. selleckchem The authors used logistic regression models to investigate the relation of Meniere’s disease with the components of adult height. Models were adjusted for a range of potential confounders including age, sex, body mass index, ethnicity, type 2 diabetes, coronary heart disease, and socioeconomic status. Results: In the UK

Biobank, Meniere’s was inversely associated with overall stature (odds ratio [OR] per standard deviation increase in height, 0.87; 95% confidence interval [CI], 0.80-0.94) and leg length (OR, 0.88; 95% CI, 0.82-0.94) in fully adjusted models. No association was noted in adjusted models with trunk length (OR, 0.94; 95% CI, 0.88-1.01). Conclusions: The specific association between leg length, a potential marker of adverse childhood environments, and Meniere’s may suggest that early-life environmental exposures that influence skeletal growth may also influence the risk INCB028050 order of developing Meniere’s in later life.”
“Background: Physical activity has health benefits across the lifespan, yet only 13 % of Canadian older adults are sufficiently active. Results from a number of observational studies indicate that adults display positive preferences for exercising with others of a similar age and same gender, and that intra-group age- and gender-similarity are associated with elevated exercise adherence. However, research has yet to experimentally examine the extent to which intra-group age- and gender-related similarity affect exercise adherence behaviors.

Measurement of carcass weight and/or lean meat yield may better reflect the true economic effects of parasitism in sheep. (C) 2009 Elsevier B.V. All rights reserved.”
“Purpose of review\n\nThe pathogenesis of systemic lupus erythematosus (SLE) involves aberrancy in multiple components of the immune system including B cells, T cells, cytokines and growth factors. Therapeutic agents targeting these mediators selectively have been tested for the treatment of SLE. This

review summarizes the recent advances in the fast expanding field of these biological therapies.\n\nRecent findings\n\nThe two large phase 2/3 randomized placebo-controlled trials of B-cell depletion, using anti-CD20 antibody, rituximab, in SLE, reported unexpected negative

PXD101 chemical structure results. On the contrary, two large phase 3 trials of belimumab, the monoclonal antibody against B-lymphocyte SBE-β-CD stimulator (BLyS), showed significant clinical benefit. Response rates were 57.6 and 43.2% for 10 mg/kg belimumab, compared with 43.6 and 33.8% for placebo in BLISS-52 and BLISS-76, respectively. Studies of a co-stimulation blocker (abatacept), tumor necrosis factor inhibitor (infliximab), and interleukin-6 inhibitor (tocilizumab) were either negative (abatacept) or were associated with high rates of adverse events. Studies of T cell and interferon inhibition remain in the early development phase.\n\nSummary\n\nDespite the enthusiasm in the field of biologic therapies, the majority of these new modalities have fallen NVP-LDE225 order short of expectations for various reasons. Only belimumab has recently met its primary outcome in two phase 3 trials.”
“Background: Previous schizophrenia research involving the “beads task” has suggested an association between delusions and 2 reasoning biases: (1) “jumping to conclusions” (JTC), whereby early, resolute decisions are formed on the basis of little evidence and (2) over adjustment of probability estimates following a single instance

of disconfirmatory evidence. In the current study, we used a novel JTC-style paradigm to provide new information about a cognitive operation common to these 2 reasoning biases. Methods: Using a task that required participants to rate the likelihood that a fisherman was catching a series of black or white fish from Lake A and not Lake B, and vice versa, we compared the responses of 4 groups (healthy, bipolar, nondelusional schizophrenia and delusional schizophrenia) when we manipulated 2 elements of the Bayesian formula: incoming data and prior odds. Results: Regardless of our manipulations of the Bayesian formula, the delusional schizophrenia group gave significantly higher likelihood ratings for the lake that best matched the colour of the presented fish, but the ratings for the nonmatching lake did not differ from the other groups.

Challenges for learners included perception of decreased access to supervisors, anxiety with peer observation, reduced access to patient presentations and patient reluctance click here to be seen by a learner. Practice challenges were administration requirements, high learner turnover, infrastructure requirements and the requirement for supervisors to cater to a range of learner level needs. Conclusions: The presence of medical students, interns and registrars in general practice has educational benefits to the learners extending to the other stakeholders (staff and patients). Multi-level learners present challenges to the learners and the practice by increasing pressures

on resources, staff (administrative and supervisors) and infrastructure.”
“Background: Atrial fibrillation (AF) is a common arrhythmia showing disease progression. However, learn more echocardiographic prediction of such progression remains incomplete. This study aimed to identify echocardiographic predictors of AF progression in

hypertensive patients. Methods: Hypertensive patients with paroxysmal AF were divided into two groups: patients with AF which became permanent (group A; n = 13) and those with AF which remained paroxysmal (group B; n = 46) during the same follow-up period (8.0 +/- 2.4 years). Clinical baselines showed no significant differences except for age. Transthoracic echocardiography was recorded 1-2 weeks after termination of the first-detected paroxysms of AF. Results: Echocardiography showed greater left atrial (LA) dimension (p = 0.023) and late diastolic pulmonary vein (PV) backflow velocity (p < 0.001), and a lower LA fractional shortening (p = 0.008) in group A than in group B. Multilogistic regression analysis demonstrated that augmented PV backflow (p = 0.007) and reduced LA fractional shortening (p = 0.032) were independent predictors of the progression of AF. The receiver-operating characteristic curve demonstrated that PV backflow augmentation is the best predictor of future AF perpetuation. Conclusion: PV backflow

leading to cyclic stretching of PV musculature contributes to AF progression. Copyright (C) 2007 S. Karger AG, Basel.”
“Vanadium compounds maintain euglycemic effects in diabetic rats www.selleckchem.com/products/nsc-23766.html long after drug withdrawal and bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV) possesses potent antidiabetic effects in diabetic rats. Here, we investigated the treatment and posttreatment effects of BFOV in diabetic Kuo Kondo [1, 2] with Ay gene (KKAy) mice, and whether these effects were associated with changes in matrix metalloproteinases (MMPs). KKAy mice received normal saline or BFOV initially at 70 mu mol/kg/day for 1 month, which was tapered to 17 mu mol/kg/day in the next 2 months and discontinued thereafter. Compared to diabetic controls, fasting plasma glucose (FPG) was reduced by 46 and 19 % in KKAy mice after 70 mu mol/kg BFOV for 1 month and 3 months after BFOV withdrawal, respectively.

A pooled odds ratio (OR) was calculated using either a random-effect or a fixed-effect model. A total of 16 papers were identified. Among the 11 factors studied, five symptoms demonstrated an increased risk for SDD, including bleeding [OR: 13.617; 95% confidence interval (CI): 3.281, 56.508], vomiting/nausea (OR: 1.692; 95% CI: 1.256, 2.280), abdominal pain (OR: 2.278; 95% CI: 1.631, 3.182), skin rashes (OR: 2.031; 95% CI: 1.269, 3.250), and hepatomegaly (OR: 4.751; 95% CI: 1.769, 12.570). Among the four bleeding-related symptoms including hematemesis, melena,

gum bleeding, and epistaxis, only Selleckchem PHA-739358 hematemesis (OR: 6.174; 95% CI: 2.66, 14.334; P smaller than 0.001) and melena (OR: 10.351; 95% CI: 3.065, Sapitinib 34.956; P smaller than 0.001) were significantly associated with SDD. No significant associations with SDD were found for

gender, lethargy, retroorbital pain, diarrhea, or tourniquet test, whereas headache appeared protective (OR: 0.555; 95% CI: 0.455, 0.676). The meta-analysis suggests that bleeding (hematemesis/melena), vomiting/nausea, abdominal pain, skin rashes, and hepatomegaly may predict the development of SDD in patients with DF, while headache may predict otherwise.”
“It has been suggested that the left pre-supplementary motor area (pre-SMA) could be implicated in facial emotion expression and recognition, especially for laughter/happiness. To test this hypothesis, in a single-blind, randomized crossover study, we investigated the impact of transcranial magnetic stimulation (TMS) on performances of 18 healthy participants during a facial emotion recognition task. Using a neuronavigation system based on T1-weighted magnetic resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over the pre-SMA or the vertex (control condition) in an event-related fashion after the presentation of happy, fear, and

angry faces. Compared with performances during vertex stimulation, we observed that TMS applied JQ-EZ-05 in vivo over the left pre-SMA specifically disrupted facial happiness recognition (FHR). No difference was observed between the 2 conditions neither for fear and anger recognition nor for reaction times (RI). Thus, interfering with pre-SMA activity with event-related TMS after stimulus presentation produced a selective impairment in the recognition of happy faces. These findings provide new insights into the functional implication of the pre-SMA in FHR, which may rely on the mirror properties of pre-SMA neurons.”
“Chronic kidney disease is often not associated with significant symptoms or abnormalities in common laboratory test results. Diagnosis is supposedly facilitated by calculating the glomerular filtration rate (GFR) from serum creatinine. A reference range GFR. however, does not exclude renal disease, because renal disease causes the subsequent decrease of renal function.

g., special wards for children and their parents, children of mentally ill parents), in medical teaching and postgraduate education as well as representative functions in societal AZD7762 solubility dmso and political issues.”
“Objective. To investigate the effect of differential coping designs on the stress distributions of an all-ceramic crown on, the upper central incisor under varying loads.\n\nMethods. 3D finite element models with three differential coping designs of an all-ceramic crown on, the upper central incisor were constructed using CAD (computer aided design) software. The coping,

designs included: CC (conventional coping), MCL (modified coping without veneer coverage in lingual, surface) and MCM (modified coping without veneer coverage in lingual margin). Loading that, simulated the maximum bite force (200 N) was applied to the crown at differential

locations (incisal, edge, lingual fossa and lingual margin). The first principal stress values for the full crown were, calculated and expressed as stress intensity in MPa.\n\nResults. The simulations showed the stress distribution tendencies of the all-ceramic crown with, differential coping materials were similar. The stress concentration was found in the cervical region, coping/veneer layer interface and the loading area for both the coping layer and the veneer layer. Maximal stress value was observed in the loading area. Stress values varied SB203580 in vitro for the three types of, coping designs; however, compared with CC and MCM, MCL exhibited the lowest stress values.\n\nSigncance. Modified coping without PD-1/PD-L1 Inhibitor 3 research buy veneer coverage in the lingual side (MCL) proved promising in, preventing all-ceramic crown failures that originate from veneering porcelain, especially under, abnormal occlusal force. Crown Copyright (C) 2013 Published by Elsevier Ltd on

behalf of Academy of Dental Materials. All rights reserved.”
“Arginine-vasopressin (AVP), corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) play a role in the stress response. The CRF-producing paraventricular nucleus of the hypothalamus (PVN), oval bed nucleus of the stria terminalis (BSTov) and central amygdala (CeA), and the Ucn1-expressing non-preganglionic Edinger-Westphal nucleus (npEW) all possess AVP receptors. We hypothesized that AVP is involved in the response of these four brain centers to acute physiological (ether) stress. To test this hypothesis, we studied AVP-deficient Brattleboro (BB) rats using quantitative immunocytochemistry. First, we showed that non-stressed wild-type (WT) and BB rats did not differ from each other in Fos contents, indicating similar (immediate early) gene expression activity, but that in BB rats CRF contents were lower in the PVN and higher in the CeA. Second, we found that stress induced Fos response in the PVN, CeA and npEW with strengths different for each center, but similar for BB and WT rats.

Improvements in both CABG (including total arterial revascularization, off-pump CABG and no-touch’ graft harvesting)

and PCI (including newer-generation stents, adjunctive pharmacotherapy and intracoronary imaging) mean that they will continue to challenge each other in the future. A heart team’ approach is strongly recommended to select an evidence-based, yet individualized, revascularization strategy for all patients with complex coronary artery disease. Finally, optimal medical therapy is important for all patients with coronary artery disease, regardless of the mode of revascularization.”
“Objectives: To determine the prevalence of cardiovascular disease, levels of cardiovascular risk factors, and extent of preventive care in Gullah African Americans with a high click here familial risk of type 2 diabetes mellitus. Methods: Between 1995 and 2003, 1321 Gullah African Americans with a high prevalence of diabetes mellitus from the South Carolina Sea Islands

consented to and enrolled in the Sea Islands Genetic African American Registry (Project SuGAR). A cross-sectional analysis of cardiometabolic risk, preventive care, and self-reported LY3023414 in vitro cardiovascular disease was conducted. Results: Cardiometabolic risk factor levels were high and vascular disease was prevalent. Among the subjects with diabetes mellitus, the mean disease duration was 10.5 years; approximately one-third reported reduced vision or blindness; and

bigger than 80% reported numbness, pain, or burning in their feet. Preventive diabetes carewas limited, with smaller than 60%, smaller than 25%, and smaller than 40% seeing an ophthalmologist, podiatrist, and dentist, respectively, within the past year. Only 54.4% of women and 39.3% of men reported daily glucose 17-AAG chemical structure monitoring. Conclusions: As the largest existing study of Gullah individuals, our study offers insight into not only the level of cardiovascular risk in this population but also the pathophysiological mechanisms central to ancestral differences in cardiometabolic risk in the broader African American population.”
“Background The propofol concentration during constant infusion is affected by a change in cardiac output, but the effect of this change on remifentanil, which is frequently used in combination with propofol, is unclear. Methods Ten swine were anaesthetised through inhalation of isoflurane and maintained with 1.5% isoflurane. After infusion of remifentanil (0.5g/kg/min) and propofol (6mg/kg/h after 2mg/kg bolus infusion) for 60min (baseline 1), cardiac output was increased by continuous infusion of dobutamine and termination of isoflurane (high cardiac output state). Dobutamine infusion was then stopped, 1.5% isoflurane was restarted, and cardiac output was allowed to return to baseline (baseline 2). Finally, cardiac output was decreased by administration of 3% isoflurane (low cardiac output state).

Normalizing to M-wave produced the greatest spatial variability (45% greater than unnormalized EMG) and increased inter-participant variability SU5402 by 70%. Unnormalized bipolar LG sEMG may provide misleading results about representative muscle activity in walking due to spatial variability. For the peak value and MVC approaches, different electrode locations likely have minor effects on normalized results, whereas electrode location should be carefully considered when normalizing walking

sEMG data to maximal M-waves. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown(1). Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR 5.3 (95% CI = 2.3-13), P = 2 x 10(-6); replication study OR = 8.59 (3.19-25.05), P = 2 x 10(-8); combined OR = 6.99 (3.68-13.57), P = 4 x 10(-11)) and that disrupts cardiomyocyte structure in vitro.

Its prevalence was found to be high (similar to 4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy JAK inhibitor will help in identifying and counseling individuals predisposed to cardiac diseases in this region.”
“A specific mutation (Delta E302/303) in the torsinA gene underlies most cases of dominantly inherited early-onset torsion dystonia. This mutation causes the protein to aggregate and form intracellular inclusion bodies in cultured cells and animal models. Co-expression of the wildtype and mutant proteins resulted in the redistribution of the wildtype protein from the endoplasmic reticulum to inclusion bodies in cultured HEK293 cells, and this was associated with increased

interaction between the two proteins. Expression of Delta E302/303 but not wildtype torsinA in primary postnatal midbrain neurons resulted in the formation of intracellular inclusion bodies, predominantly in dopaminergic neurons. Tyrosine https://www.selleckchem.com/products/SB-202190.html hydroxylase, was sequestered in these inclusions and this process was mediated by increased protein-protein interaction between mutant torsinA and tyrosine hydroxylase. Analysis in an inducible neuroblastoma cell culture model demonstrated altered tyrosine hydroxylase activity in the presence of the mutant but not wildtype torsinA protein. Our results suggest that the interaction of tyrosine hydroxylase and mutant torsinA may contribute to the phenotype and reported dopaminergic dysfunction in torsinA-mediated dystonia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

V. All rights reserved.”
“Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor-specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy

were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols SB203580 (TGs) in patients’ response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic PD-1/PD-L1 Inhibitor 3 complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease-free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer

patients are associated with their response to chemotherapy. What’s new? Up to 25% of breast tumors show pathologic complete response (pCR) following neoadjuvant chemotherapy. Identifying biomarkers that could predict pCR could help select those patients who would most benefit from therapy. Knowing that blood oleic acid concentration is increased in cancer patients and associated with breast cancer predisposition, here the authors explored how serum lipidomic profiles may be associated with pCR in patients receiving therapy. Lowered concentrations of oleic acid in serum triacylglycerols were found to be associated with pCR in breast cancer patients receiving neoadjuvant chemotherapy. This highlights the importance of systemic lipid metabolism status in response to chemotherapy.”
“Survivin

Rabusertib manufacturer is ubiquitously expressed in patients with head neck squamous cell carcinoma (HNSCC) and is associated with poor survival and chemotherapy resistance. Sepantronium bromide (YM155) is a selective survivin suppressant that exhibits potent antitumor activities by inducing apoptosis and autophagy in various types of cancer. However, the curative effects and underlying mechanisms of YM155 in HNSCC remain unclear. This study showed that survivin overexpression positively correlated with p-S6, p-Rb and LAMP2 but negatively correlated with the autophagic marker LC3 in human HNSCC tissues. In vitro studies revealed that YM155 triggered apoptosis of HNSCC cells in mitochondria and death receptor-dependent manner. The treatment also significantly enhanced autophagy by upregulating Beclin1, which led to cell death.

To achieve the desired structural properties of the graft, most importantly a diametric compliance of 6%/100 mmHg, finite element methods and genetic algorithms were used in an integrated approach to identify the mechanical properties of an adventitial fabric layer that were required to optimally complement an intimal/medial polyurethane layer with interconnected

porosity of three different size classes. The models predicted a compliance of 16.0, 19.2, and 31.5%/100 selleckchem mmHg for the non-reinforced grafts and 5.3, 5.5, and 6.0%/100 mmHg for the fabric-reinforced grafts. The latter, featuring fabrics manufactured according to the required non-linear mechanical characteristics numerically predicted, exhibited an in vitro compliance of 2.1 +/- 0.8, 3.0 +/- 2.4, and 4.0 +/- 0.7%/100 mmHg. The combination

of finite element methods and genetic algorithms was shown to be able to successfully optimize the mechanical design of the composite graft. The method offers potential for the application to alternative concepts of modular vascular grafts and the incorporation of tissue ingrowth and biodegradation.”
“Basement membrane (BM) is a complex network of interacting proteins, including type IV collagen (Col IV) that acts as a scaffold that stabilizes the physical structures of tissues and regulates cellular processes. In the mammary gland, check details BM is a continuous deposit that separates epithelial cells from stroma, and its degradation is related with an increased potential for invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to one mesenchymal state, and is a normal process during embryonic development, tissue remodeling and wound healing, as well as it has been implicated

during cancer progression. In breast cancer cells, native Col IV induces migration and gelatinases secretion. However, the role of native Col IV on MG-132 cost the EMT process in human mammary epithelial cells remains to be investigated. In the present study, we demonstrate that native Col IV induces down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2 and Sip1 transcripts. Native Col IV also induces an increase in N-cadherin and vimentin expression, an increase of MMP-2 secretion, the activation of FAK and NFKB, cell migration and invasion in MCF10A cells. In summary, these findings demonstrate, for the first time, that native Col IV induces an EMT-like process in MCF10A human mammary non-tumorigenic epithelial cells. (C) 2012 Elsevier Ltd. All rights reserved.”
“The present study was designed to evaluate the expression and subcellular distribution of the familial acute myelogenous leukemia-related factor (FAMLF). A 14-amino acid epitope of the predicted open reading frame of the FAMLF gene was identified using bioinformatics. This polypeptide was synthesized, conjugated to keyhole limpet hemocyanin and was subsequently used to produce antibodies.