15,406 research outputs found
BK 10-15: Research Portfolio TU Delft Faculty of Architecture and the Built Environment
No full textOver the years 2010-2015 TU Delft's Faculty of Architecture and the Built Environment (in Dutch: Bouwkunde or BK) made good progress with its research by:
merging the Architecture faculty and the Built Environment research institute;
streamlining its PhD research by setting-up a graduate school for doctoral education;
co-founding an institute for metropolitan solutions in Amsterdam together with MIT and Wageningen University (targeted yearly budget: 25 M€);
implementing good research management;
increasing the scientific output;
managing a project portfolio with a yearly income of 1.5 M€ in research grants, 5 M€ in contract research and up to 2 M€ in other external funding;
ranking 3rd in the QS World University Rankings by Subject 2015 - Architecture / Built Environment.
Presented in this book is an overview of research data and policies, together with a selection of our finest research results: activities, organisations, facilities/assets, output, including indications of their use and recognition. Now it is not the time to become complacent. Instead, we should look ahead to face new academic and societal challenges and opportunities, knowing we can always do better
Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal transplant patients and increase viral replication and cytopathology
No full textImmunosuppression is required for BK viremia and polyomavirus BK-associated nephropathy (PVAN) in kidney transplants (KTs), but the role of viral determinants is unclear. We examined BKV noncoding control regions (NCCR), which coordinate viral gene expression and replication. In 286 day-matched plasma and urine samples from 129 KT patients with BKV viremia, including 70 with PVAN, the majority of viruses contained archetypal (ww-) NCCRs. However, rearranged (rr-) NCCRs were more frequent in plasma than in urine samples (22 vs. 4%; P > 0.001), and were associated with 20-fold higher plasma BKV loads (2.0 x 10(4)/ml vs. 4.4 x 10(5)/ml; P > 0.001). Emergence of rr-NCCR in plasma correlated with duration and peak BKV load (R(2) = 0.64; P > 0.001). This was confirmed in a prospective cohort of 733 plasma samples from 227 patients. For 39 PVAN patients with available biopsies, rr-NCCRs were associated with more extensive viral replication and inflammation. Cloning of 10 rr-NCCRs revealed diverse duplications or deletions in different NCCR subregions, but all were sufficient to increase early gene expression, replication capacity, and cytopathology of recombinant BKV in vitro. Thus, rr-NCCR BKV emergence in plasma is linked to increased replication capacity and disease in KTs
In vitro and in vivo characterization of the cytomegalovirus and polyomavirus BK specific immune response
No full textDuring my PhD thesis several aspects of the interaction of Cytomegalovirus
and Polyomavirus BK with the host’s immune system were examined (see list
of publications). The overall aim was to compare immune response in healthy
individuals and kidney transplant recipients with or without viral replication.
In healthy individuals, Polyomaviruses BK and JC infect 80% and 60%,
respectively. For CMV seroprevalences may reach up to 80%. Intermittent
virus shedding in urine is observed for BKV in 7%, JCV in 19% and CMV in
0%. However, no virus replication in plasma was detected. Posttransplant,
mainly due to prolonged immune suppression the amount and function of
CMV- and BKV-specific T-cells is impaired. Calcineurin inhibitors lead to a
direct reduction of INFγ production of virus-specific T-cells, whereas antiproliferative
immunosuppressives reduce the expansion capacity in a dosedependent
manner. This may be a major reason for uncontrolled virus
replication.
The humoral response reflects the amount of recent antigen exposure and
does not directly indicate protection from virus replication. Virus-specific
cellular immune responses would probably allow to assessing the risk of
future replication.
Overall the importance of CMV and BKV specific T-cells posttransplant in
controlling virus replication was examined. For both viruses we could
calculate a protective threshold of virus-specific T-cells. CMV-pp65 specific
CD4 T-cells above 0.03% were significantly associated with no CMV
replication during the next eight weeks. Additionally, below this cut-off, CMV
seropositive recipients developed more often GCV-resistant CMV replication.
During BKV replication, patients with more than 69 BKV-LT specific T-cells
per 1 Mio PBMCs were significantly more often showing decreasing BKV
loads in plasma. As virus-specific T-cells seem to be crutial in reducing virus replication, and
reduction of immune suppression harbours the risk of acute rejection, a
booster vaccine could be a new therapeutic option. A booster vaccine could
probably elevate the amount of virus-specific T-cells above a critical threshold
of protection from disease, despite effects of immune suppression.
We tried to identify immunodominant regions with the CMV pp65 and BKV LT
proteins. We used a combined approach of computer prediction algorithms
and experimental verification. Epitope mapping of BKV LT with computer
prediction revealed several clusters, which could be immunodominant and
also potentially be processed and recognized in various HLA backgrounds.
The identified cluster regions were synthesised as 15 and 25mers. Expansion
and re-stimulation with predicted epitopes could so far confirm the HLA A and
B-specific prediction of single 9mers covered by the larger 15 and 25mer
sequences. However, other HLA types need to be tested for direct stimulation
and expansion potential of the predicted epitopes. Additionally, tetramer
staining should be performed for verification.
Based on this research, we will be able to improve current immune monitoring
and probably a high-specific peptide-based vaccine against BKV LT could be
developed and be used to increase the amount of BKV-LT specific T-cells.
Another potentially therapeutic agent could be the blockade of PD1 ligand.
PD1 expression in chronic virus infection lead to impaired CD8+ T-cell
function. CMV-specific CD4 T-cells treated with an inhibitory antibody against
PD1 ligand, and thereby activating CD4+ T-cells, lead to a increase of the
expansion capacity. We have shown, that the anti-PD1 ligand antibody
increases various cytokines. This could be also tested for BK virus.
Measurement of virus-specific T-cells may replace serological assays in the
future, due to a better correlation to effective antiviral control, which can be
used as monitoring tool during infection and post-vaccination
Veille BK décembre 2020
No full textCet article du Carnet BK se propose de relayer auprès de nos lecteurs des actualités sur la recherche en art émanant de différents sites en ligne. Appels à publication Les pédagogies féministes dans les domaines artistiques (Date limite 1er mars 2012) Revue Marges n° 39 : éthique et/ou esthétique (date limite : 1er janvier 2021) « Getty Research Journal » appel à publication (date limite : 1er janvier 2021) Opportunités pour chercheurs – bourses et prix Le prix Willibald Sauerländer, M..
Characterizing determinants of BK Polyomavirus-specific immune response
No full textBK polyomavirus (BKPyV) is one of now 13 human polyomavirus (HPyV) species detected in humans. BKPyV is only known to infect humans and seroprevalence rates of more than 90% have been reported in adult populations around the world. Following primary infection, BKPyV persists in the renourinary tract without causing any disease as evidenced by urinary shedding in 5% - 10% of healthy immunocompetent blood donors.
In immunocompromised persons, however, BKPyV can cause significant diseases whereby uncontrolled high-level replication may lead to organ invasive pathologies in kidneys, bladder, lungs, vasculature, and the central nervous system. The most consistently found diseases are BKPyV-associated hemorrhagic cystitis (BKPyVHC) in 5%-20% allogeneic hematopoietic stem cells transplant patients, and BKPyV-associated nephropathy (BKPyVAN) in 1%-15% of kidney transplant patients. BKPyVHC is highly symptomatic with pain, anemic bleeding, and increased mortality. BKPyVAN is asymptomatic except for progressive renal failure and premature return to dialysis. Both entities are characterized by high-level viral replication i.e. with urine BKPyV loads of 8-10 log10 Geq/mL, plasma BKPyV loads often above 4 log10 Geq/mL, and an allogeneic constellation between the virus-infected host cell and the available T-cell effectors. Despite these similarities, the clinical manifestations are strikingly different suggesting relevant, but experimentally undefined differences in pathogenesis. Thus, BKPyVHC typically occurs within 4 weeks after allogeneic HSCT and is confined to the bladder, and typically without kidney involvement. By contrast, BKPyVAN is diagnosed around 3-6 months after kidney transplantation and confined to the kidney allograft without causing cystitis. Although high-level BKPyV replication should be formally amenable to antiviral drug treatment, no effective and BKPyV-specific antiviral therapy is currently available. Therefore, a better understanding of the immune alteration in both diseases has been deemed essential to identify patients at risk and to develop prophylactic, preemptive and therapeutic strategies.
The currently recommended strategy for BKPyVAN is to screen kidney transplant patients for BKPyV replication and to promptly reduce immunosuppressive therapy in those with significant replication to facilitate mounting of BKPyV-specific T cell responses and thereby preventing progression to disease. This manoeuver has been linked to expanding BKPyV-specific T cell responses in the peripheral blood of kidney transplant patients. However, this approach may place patients at risk for acute rejection episodes that predispose equally well to premature kidney transplant failure. Although the clinical feasibility of reducing immunosuppression and curtailing BKPyV replication has been shown to be effective in prospective cohort studies for many, but not all of kidney transplant patients, this approach has not been possible in allogeneic HSCT patients because of concurrent or imminent graft-versus host disease. Thus, there are significant gaps in the current understanding of the BKPyV– host interaction in the normal host and in the allogeneic setting, which need to be investigated for a more effective and safer management of these significant viral complications.
In this thesis, the interaction of BKPyV and the immune response has been approached from two different angles. In the first project, potential mechanisms of BKPyV immune evasion were studied. Here, we focused on a small accessory protein called agnoprotein encoded as a leader protein in the late viral early region (LVGR). Although HPyV genomes overall show a very similar genome organization, agnoproteins are only found in the genomes of BKPyV and JCPyV that have a kidney tropisms, but not in any of the other 11 presumably non-renotropic HPyVs. We hypothesized that agnoprotein could play a role in immune evasion by downregulating HLA expression. The effects of agnoprotein were studied on HLA class I and II expression in vitro by flow cytometry following transfection of primary human renal tubular epithelial cells, which are the viral target of BKPyV-associated nephropathy. In addition, transfected human UTA-6 cells were studied as well as UTA-6 cells bearing a tetracycline-regulated agnoprotein. As control, the effects were compared with the ICP47 protein of Herpes simplex virus-1, which has been previously reported to effectively down-regulate HLA class I. Although both viral proteins share some similarities at the protein level, our results showed that BKPyV agnoprotein did not down-regulate HLA class I or class II molecules. Also, there was not inhibitory effect on the increase of HLA-class I or class-II surface expression following exposure to interferon-. By contrast, ICP47 reduced HLA class I surface expression, but not class II. We also evaluated effects of agnoprotein on virus epitope-specific T-cell killing by 51Chromium release assay, however no interference could be observed. We concluded that agnoprotein did not contribute to these types of HLA-dependent immune evasion processes. However, further investigations are needed to understand if agnoprotein could contribute to viral immune escape by other mechanisms.
In the second project, we aimed at better characterizing BKPyV-specific CD8 T cell immunity targeting epitopes encoded in the early viral gene region (EVGR). Selected coding sequences of the BKPyV EVGR were submitted to two web-based computer algorithms (SYFPEITHI, IEDB) in order to predict immunodominant 9mer epitopes presented by 14 frequent HLA-class I molecules. For an experimental confirmation, 97 different 9mer epitopes were chemically synthesized and tested in 42 healthy individuals. A total of 39 epitopes could be confirmed by interferon- ELISpot assay in at least 30% of healthy individuals. Interestingly, most of the 9mer epitopes appeared to cluster in short amino acid stretches, and some 9mer could be presented by more than one HLA class I allele as expected for immunodominant domains. HLA-specific presentation was demonstrated by 9mer- MHC-I streptamers for 21/39 (54%) epitopes. The 9mer dependent T-cell killing by 51Chromium release assay and the CD107a surface detection indicated that the 9mer epitopes could be recognized by cytotoxic T-cells. Moving to a clinically relevant situation, 13 9mer epitopes could be validated in 19 kidney transplant patients protected from, or recovering from, BKPyV viremia. The results suggest that, pending further corroboration in larger patient populations, novel 9mer epitopes can be identified, which are associated with CD8 T cell control of BKPyV replication. Thus the identified immunodominant 9mer T-cell epitopes could be further developed for clinical assays to better predict the risk and the recovery of BKPyV diseases, help guiding immunosuppression reduction, and to develop specific adoptive T-cell therapy or vaccine responses to prevent or treat BKPyV-associated disease
BKV Agnoprotein Interacts with α-Soluble N-Ethylmaleimide-Sensitive Fusion Attachment Protein, and Negatively Influences Transport of VSVG-EGFP
No full textBackground: The human polyomavirus BK (BKV) infects humans worldwide and establishes a persistent infection in the kidney. The BK virus genome encodes three regulatory proteins, large and small tumor-antigen and the agnoprotein, as well as the capsid proteins VP1 to VP3. Agnoprotein is conserved among BKV, JC virus (JCV) and SV40, and agnoprotein-deficient mutants reveal reduced viral propagation. Studies with JCV and SV40 indicate that their agnoproteins may be involved in transcription, replication and/or nuclear and cellular release of the virus. However, the exact function(s) of agnoprotein of BK virus remains elusive. Principal Findings: As a strategy of exploring the functions of BKV agnoprotein, we decided to look for cellular interaction partners for the viral protein. Several partners were identified by yeast two-hybrid assay, among them a-SNAP which is involved in disassembly of vesicles during secretion. BKV agnoprotein and a-SNAP were found to partially co-localize in cells, and a complex consisting of agnoprotein and a-SNAP could be co-immunoprecipitated from cells ectopically expressing the proteins as well as from BKV-transfected cells. The N-terminal part of the agnoprotein was sufficient for the interaction with a-SNAP. Finally, we could show that BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter suggesting that agnoprotein may modulate exocytosis. Conclusions: We have identified the first cellular interaction partner for BKV agnoprotein. The most N-terminal part of BKV agnoprotein is involved in the interaction with a-SNAP. Presence of BKV agnoprotein negatively interferes with secretion of VSVG-EGFP reporter
Polyomavirus BK-specific cellular immune response in Kidney transplant recipients
No full textPolyomavirus BK is an emerging pathogen in KT recipients. New potent
immunosuppressive drugs promote reactivation and replication of BKV and progression
towards PVAN. PVAN occurs in up to 10% of the KT recipients with a graft loss in up to
80% of the cases. New potent immunosuppressive drugs, as MMF) and FK506 are risk factors
for developing PVAN. As no proven antiviral drugs are available, the only therapy of choice
is the reduction of immunosuppressiva in order to regain BKV-replication control (H. H.
Hirsch, M. Dickenmann, S. Binggeli, J. Steiger, Schweiz Med Forum 2004; 4:538–541).
BKV-specific cellular and humoral immune response is not well characterized. Recent
findings have shown that BKV-seropositive patients prior to transplantation are not protected
from BKV-replication. In contrast, BKV-specific cellular immune response correlates with
the diagnosis of PVAN (P. Comoli, S. Binggeli, F. Ginevri, H. H. Hirsch, Transplant
Infectious Disease Jun 2006; 8(2):86-94, Review).
The aim of this study was to investigate the interplay of BKV-specific immune response
and BKV-replication in blood samples of KT recipients. We examined the BKV-specific
immune response by ELISpot assay in KT. PBMC of KT recipients were stimulated with
BKV LT-antigen and BKV-VP1 peptide libraries. The BKV-specific immune response was
measured by the detection of IFN-γ by ELISpot assay. From the results of a pilot study with
eight patients we were able to deduce that the dynamics of viral-replication rather than the
viral load correlates with a protective immune response (S. Binggeli, A. Egli, M.
Dickenmann, I. Binet, J. Steiger, H. H. Hirsch, American Journal of Transplantation, Sep
2006; 6(9):2218-9).
To corroborate this previous observation the BKV-specific cellular immunity in 42 KT
recipients and 10 HB were tested. The KT patients were divided into two groups: patient
group 1 with an increasing or stable viral load (inc/hi)1 and patient group 2 with a decreasing
viral load or after resolved PVAN (dec)2. Indeed patients in group 2 showed a significantly
higher immune response upon stimulation with BKV-LT and BKV-VP1 than patients in
group 1 (P=0.003, P=0.001, respectively, Wilcoxon, two-sided). Detailed analysis revealed a
cut-off of >69 SFU/Mio PBMC for BKV LT-antigen, but not for BKV VP1, with
significantly more KT patients from group 2 (dec) than from group 1 (inc/hi). This cut-off has
to be validated in a prospective study and also analyzed whether such a cut-off can be used for
immunosuppressive reduction guidance.
BKV-specific cell expansion was tested in a short-term culture in the presence of either
BKV-LT or -VP1. After 9-day culture, PBMC were restimulated with BKV-LT or -VP1 and
the responses were then compared with responses to direct stimulation (without prior
cultivation). BKV-LT and -VP1 specific cellular immune responses were significantly higher
after 9-day cultivation than after direct stimulation (P=0.002, P=0.003, respectively,
Wilcoxon, two sided).
Due to high sequence homology between JCV and BKV, JCV-LT and -VP1 overlapping
peptide pools were used to test PBMC-cross recognition. JCV-LT and -VP1 responses were
significantly lower than BKV-mediated response (P=0.008, P<0.001, respectively, Wilcoxon,
two-sided). Comparison of JCV- and BKV-specific responses after 9-day culture revealed that
the BKV-VP1 response was significantly higher than the JCV-VP1 (P=0.016, Wilcoxon, two
sided), but no significant difference was observed for LT-antigen (S. Binggeli, A. Egli, S.
Schaub, I. Binet, M. Mayr, J. Steiger, H. H. Hirsch, American Journal of Transplantation, Mar
2007; 7:1-9).
Agnoprotein, a late viral protein, is highly expressed upon infection. We investigated
whether agnoprotein is able to induce a BKV-specific immune response and whether it may
serve as a diagnostic marker. Immunostaining revealed that agnoprotein was highly expressed
in the cytoplasm of infected cells and was only seen in combination with BKV-LT which is
located in the nucleus. Interestingly, BKV-agnoprotein specific cellular and humoral immune
responses were scarcely detected in HB or KT recipients. There are only few published
studies concerning BKV-agnoprotein, and further investigations are necessary to fully
understand the function of agnoprotein during infection. (D. Leuenberger, P. A. Andresen, R.
Gosert, S. Binggeli, E. H. Ström, S. Bodaghi, C Hanssen Rinaldo, H. H. Hirsch, Clinical and
Vaccine Immunology, Aug 2007; 14(8): 959-968).
As no antiviral treatment is available for BKV, the only therapy is the reduction of
immunosuppressive drugs in order to regain immunological control over BKV-replication and
PVAN. However reduction of immunosuppressants upon PVAN diagnosis bears the risk of
rejection or inflammatory response to BKV. It is difficult to distinguish between these two
outcomes because specific markers are yet lacking. Therefore, it is pivotal to record the
clinico-pathological course of the KT patient in order to correctly diagnose the problem as the
therapies are completely different. Measuring the BKV-specific cellular immune response
may support and complement other markers, such as PCR analysis and biopsies, to better
distinguish between rejection and BKV-specific immune response. (S. Schaub, M. Mayr, A.
Egli, S. Binggeli, B. Descoeudres, J. Steiger, M. J. Mihatsch, H. H. Hirsch, Nephrology
Dialysis Transplantation, Aug 2007; 22(8): 2386-90).
Finding the optimal immunosuppressive drug level is crucial for preventing rejection
(under-immunosuppressed) and viral replication (over-immunosuppressed). Our current study
showed a cut-off level of 6.65 ng/ml FK506 drug level in blood, dividing those KT patients
with and without BKV-replication control (ROC-curve: AUC=0.897, sensitivity=78%,
specificity=86%). If this cut-off is validated by a well designed prospective study, it may
serve as a guideline to administrate the optimal drug level. (S. Binggeli, 2007, current results).
BKV-specific epitopes have received considerable attention in the last five years. We
started with the epitope mapping in a kidney patient with the most common HLA-type: HLAA*
01, HLA-B*08. First screening of BKV-LT revealed ten 15aa long peptides with
immunogenic potential. Three of these ten peptides were further investigated for crossrecognition
with the homologous JCV-peptides. Even though response to the three JCVpeptides
was lower, cellular immune response could be clearly detected. It needs further
investigation to find more BKV-specific epitopes and also to test the ability of CD8+ T-cells
to kill BKV-antigen presenting cells. (S. Binggeli, 2007, current results)
Desenvolvimento e aplicação de um sistema celular repórter para herpes simplex virus e padronização de uma PCR quantitativa para poliomavírus BK
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Biotecnologia e Biociências, Florianópolis, 2014.Pacientes imunodeprimidos podem apresentar infecções virais com evolução rápida, sintomatologias atípicas graves e muitas vezes fatais, sendo fundamental um diagnóstico precoce para estabelecimento do tratamento efetivo, redução da toxicidade e da resistência aos antivirais. HSV-1, HSV-2 e poliomavírus BK são vírus de importância clínica para imunodeprimidos e podem levar a rejeição de órgãos em transplantados. Assim, o objetivo deste trabalho foi desenvolver um sistema celular repórter, utilizando a proteína fluorescente GFP, para HSV-1 e 2 e implantar uma qPCR utilizando amostras clínicas de pacientes transplantados renais para detecção de poliomavírus BK. O sistema celular repórter foi construído através da transfecção de células Vero com o vetor pZsGreen1-1 ligado ao promotor ICP10 (F3R3 e F4R3) da RR1 do HSV-2. A regulação da expressão da GFP via ICP10 é dependente da infecção viral e acontece por meio da proteína viral transativadora VP16 e de fatores celulares Oct-1 e HCF-1. A efetividade do sistema foi avaliada por infecção viral e pela aplicação de antivirais (Aciclovir, ácido gálico, convalotoxina e extrato de Uncaria sp.) e candidatos antivirais inativos (Extrato de Passiflora edulis e derivados de cardenolídeos). O sistema repórter F4R3 ZsGreen1-1 expressou GFP em função da infecção por HSV-1 e 2, a qual foi detectada por microscopia de fluorescência e/ou citometria de fluxo. Em análise por citometria de fluxo, a fluorescência do sistema repórter correlacionou-se diretamente com os títulos virais (MOI de 4,0 x10-3 a 3,3 x10-4, ou seja, 1 partícula viral a cada 250 a 3000 células), o sistema manteve a capacidade de expressão da GFP na presença de agentes sem propriedade antiviral e não expressou fluorescência quando tratado com antivirais. O sistema F4R3 ZsGreen1-1 mostrou-se um sistema funcional com possíveis aplicações para diagnóstico clínico, para elaboração de testes de resistência aos antivirais e para a pesquisa de novos medicamentos. A qPCR para poliomavírus BK foi implantada utilizando amostras de DNA cedidas pelo HEMOSC com iniciadores dirigidos para o antígeno T viral. O limite de detecção foi de 18 cópias genômicas/ reação com quantificações variando entre 9,8 x 105 a 6,7 x 107 cópias genômicas/ mL. A qPCR foi efetiva para análises de amostras clínicas e apresentou limite de detecção suficiente para avaliação de risco de nefropatia em transplantados renais.Abstract : Immunosuppressed patients can present viral infections with fast evolution, severe atypical symptomatologies and often fatal, being essential the early diagnosis for the establishment of effective treatments, reduction of toxicity and development of resistance to antiviral. HSV-1, HSV-2 and polyomavirus BK are virus of clinical importance for immunosuppresed and can lead to the rejection of transplanted organs. Therefore, the aim of this work was to develop a reporter cellular system, using the fluorescent protein GFP, for HSV-1 and 2, and deploy a qPCR using clinical samples from patients submitted to renal transplant, for the detection of polyomavirus BK. The reporter cellular system was constructed through the transfection of Vero cells with the vector pZsGreen1-1 connected to the promoter ICP10 (F3R3 and F4R3) of the RR1 of the HSV-2. The regulation of the expression of GFP via ICP10 is dependent of the viral infection and happens through the viral transactivating protein VP16, and the cellular factors Oct-1 and HCF-1. The effectivity of the system was evaluated by viral infection and through the application of antiviral (Acyclovir, gallic acid, convalotoxina and extract of Uncaria sp.) and inactive antiviral candidate (Extract of Passiflora edulis and derivatives cardenolide). The reporter system F4R3 ZsGreen1-1 expressed GFP as a function of the infection for HSV-1 and 2, which was detected by fluorescence microscopy and/or flow cytometry. In flow cytometry, the fluorescence of the reporter system was directly correlated with virus titers (MOI 4,0 x10-3 to 3,3 x10-4, that is, 1 viral particle to each 250 to 3000 cells), the system maintained the ability to GFP expression in the presence of agents without antiviral property and no expressed fluorescence when treated with antivirals. The system F4R3 ZsGreen1-1 revealed a functional system with possible applications for clinical diagnosis, elaboration of tests of resistance to the antiviral and for new drugs research. The qPCR to polyomavirus BK was deployed using DNA samples provided by HEMOSC with primers directed to the viral antigen T. The limit of detection was 18 genome copies /reaction with quantification ranging between 9.8 x 105 to 6.7 x 107 genome copies /mL. The qPCR was effective for the analyses of clinical samples and presented enough sensitivity for risk evaluation of nephropathy in renal transplant
Sebuah Review Tentang Referral Pesantren Dan Masalah Adaptabilitas Santri Di Tengah Keterbatasan Kualitas Guru Bimbingan dan Konseling (Guru BK)
No full textKajian ini bertujuan untuk mendeskripsikan kajian implementasi konsep alih kasus (Referral) menghadapi keterbatasan pelaksanaan konseling di pesantren. Metode yang digunakan adalah literatur review dengan sumber primer berupa literatur terkait seputar referral dalam konseling, masalah adaptabilitas santri, dan keterbatasan kualitas Guru BK di Pesantren, mesin pencarian artikel menggunakan Google Cendikia dan Garuda, data awal artikel yang diperoleh berjumlah 40 artikel, setelah dilakukan penyaringan dengan pembatasan kategori dan rentang tahun (minimal 2010), dan kemudian melalui proses analisis isi setiap artikel, didapatkan hasil 21 artikel yang dinilai paling relevan dengan bahasan kajian. Hasil kajian menunjukkan masalah adaptabilitas santri dan kualitas guru bk yang terbatas di Pesantren, sehingga berdampak pada tidak optimalnya layanan bk. Dari hasil kajian diperoleh kesimpulan bahwa referral merupakan opsi solusi dalam mengatasi kendala palaksanaan layanan bk yang optimal dalam jangka waktu pendek sampai menengah.
Kata kunci: referral, adaptabilitas, keterbatasan kualitas guru bimbingan dan konselin
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