CLUSTERING OF SMALL AGRO-PROCESSING FIRMS IN INDONESIA

Small-scale industries in Indonesia provide more than 65% of total manufacturing employment. Sixty-three percent of small-scale firm employment is in firms that are clustered. A cluster is defined statistically in Indonesia as at least 20 firms in a village. For some agro-processing industries, such as bamboo plaiting, clustering does not involve interaction among firms; for others, notably the furniture industry, clustering firms make joint marketing efforts, subcontract each other, and share large orders. This article uses two recent case studies in the agro-processing sector – the furniture and the palm sugar industries – in Central Java. We argue that the target market of the industry (local or international) influences the nature of the contracts and other forms of interaction in the clusters. Targeting an international market requires formal contracts, more focus on marketing, and separate roles for finishing firms and subcontracting firms. Policy should be directed at enabling clusters to shift to the international market by improving contract enforcement regulations, vocational training, and providing opportunities for group lending.Agribusiness, Industrial Organization,

testosterone and libido in surgically and naturally menopausal women

The assessment and then treatment of a change in libido, or a change in the desire to partake in sexual activity, during the menopausal transition and beyond has been a challenging and elusive area of clinical research. This is partly due to the multidimensional nature of female sexuality, the difficulties of measuring testosterone in women in a reliable and accurate manner, and the complexity of the neurobiology and neurobehavior of female sexual desire. In addition, there is a lack of evidence for diagnostic specificity of low free testosterone levels for the symptom of low libido in women for whom there are no confounding interpersonal or psychological factors; although, in the symptomatic population of surgically or naturally menopausal women, a low level of free testosterone often accompanies a complaint of reduced desire/libido. The randomized clinical trial research on testosterone replacement for naturally and/or surgically menopausal women with sexual dysfunction has been criticized for a high placebo response rate, supraphysiological replacement levels of testosterone, the perception of modest clinical outcome when measuring objective data such as the frequency of sexual intercourse relative to placebo, and the unknown safety of long-term testosterone replacement in the estrogen-replete surgically or naturally menopausal woman. A careful review of current evidence from randomized, controlled trials lends support to the value of the replacement of testosterone in the estrogen-replete menopausal woman for whom libido and desire has declined. The issue of long-term safety remains to be answered. Multifactorial nature of female sexuality The assessment and then treatment of a change in libido, or a change in the desire to partake in sexual activity, during the menopausal transition and beyond has been a challenging and elusive area of clinical research. There is a lack of evidence for the diagnostic specificity of low free testosterone levels for the symptom of low libido in the women for whom there are no confounding interpersonal or psychological factors; although, in the symptomatic population of surgically or naturally menopausal women, a low level of free testosterone often accompanies a complaint of reduced desire/libido [1–6]. Female sexuality is dependent on biological, psychosexual, sociocultural and context-related factors [7–9]. As a consequence, any movement or change in any of these realms may increase or decrease a woman's perception of her drive or motivation to participate in sexual activity. The presence of any chronic medical illness such as diabetes, pulmonary or cardiovascular problems, or depression will in many instances impact a woman's sexuality concurrent with changes related to age [10,11]. The length of the relationship with a partner, as well as aging, has been demonstrated to impact sexual interest and frequency of sexual activity [12,13]. The menopause has been shown to have an incremental effect on a woman's sexuality, separate from the change brought about by aging [14]. The quality of her intimate relationship and the degree to which she feels empowered in it have been demonstrated to affect sexual desire [15]. The culture in which she lives has been shown to affect frequency of sexual intercourse [16]. The degree of stress she is under, as well as her general wellbeing, has also been shown to affect her libido. A recent longitudinal study demonstrated that higher stress lowers wellbeing, resulting in a decrease in sexual arousal, enjoyment, orgasm and desire [17]. In addition, the balance between sexual inhibition and sexual excitement may be unique to each woman and may change according to her circumstances, along with any other change she may have with regard to these opposing forces [18]. Thus, the treatment of any woman distressed by a change in desire at midlife and beyond is driven by many factors. The clinician's task is to elucidate which one or more of these many variables changed in her life, concurrent with her change in sexual desire, and then to determine whether or not these changes are related to her change in sexual desire

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

Supported by the European and Developing Country Clinical Trials Partnership (grant IP.2007.32011.011) and the Global Alliance for TB Drug Development, with support from the Bill & Melinda Gates Foundation, US Agency for International Development, UK Department for International Development, Directorate-General for International Cooperation of the Netherlands, Irish Aid and Australian Department of Foreign Affairs and Trade.Background Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Methods Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Results Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. Conclusions Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.Publisher PDFPeer reviewe

Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials

Supported by the European and Developing Country Clinical Trials Partnership (grant IP.2007.32011.011) and the Global Alliance for TB Drug Development, with support from the Bill & Melinda Gates Foundation, US Agency for International Development, UK Department for International Development, Directorate-General for International Cooperation of the Netherlands, Irish Aid and Australian Department of Foreign Affairs and Trade.Background Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. Methods Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. Results Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c-statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. Conclusions Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383.Publisher PDFPeer reviewe

STREET: A Multi-Task Structured Reasoning and Explanation Benchmark

We introduce STREET, a unified multi-task and multi-domain natural language reasoning and explanation benchmark. Unlike most existing question-answering (QA) datasets, we expect models to not only answer questions, but also produce step-by-step structured explanations describing how premises in the question are used to produce intermediate conclusions that can prove the correctness of a certain answer. We perform extensive evaluation with popular language models such as few-shot prompting GPT-3 and fine-tuned T5. We find that these models still lag behind human performance when producing such structured reasoning steps. We believe this work will provide a way for the community to better train and test systems on multi-step reasoning and explanations in natural language.Comment: Published in ICLR 202

Use of a chimeric Hsp70 to enhance the quality of recombinant Plasmodium falciparum S-adenosylmethionine decarboxylase protein produced in Escherichia coli

S-adenosylmethionine decarboxylase (PfAdoMetDC) from Plasmodium falciparum is a prospective antimalarial drug target. The production of recombinant PfAdoMetDC for biochemical validation as a drug target is important. The production of PfAdoMetDC in Escherichia coli has been reported to result in unsatisfactory yields and poor quality product. The coexpression of recombinant proteins with molecular chaperones has been proposed as one way to improve the production of the former in E. coli. E. coli heat shock proteins DnaK, GroEL-GroES and DnaJ have previously been used to enhance production of some recombinant proteins. However, the outcomes were inconsistent. An Hsp70 chimeric protein, KPf, which is made up of the ATPase domain of E. coli DnaK and the substrate binding domain of P. falciparum Hsp70 (PfHsp70) has been previously shown to exhibit chaperone function when it was expressed in E. coli cells whose resident Hsp70 (DnaK) function was impaired. We proposed that because of its domain constitution, KPf would most likely be recognised by E. coli Hsp70 co-chaperones. Furthermore, because it possesses a substrate binding domain of plasmodial origin, KPf would be primed to recognise recombinant PfAdoMetDC expressed in E. coli. First, using site-directed mutagenesis, followed by complementation assays, we established that KPf with a mutation in the hydrophobic residue located in its substrate binding cavity was functionally compromised. We further co-expressed PfAdo- MetDC with KPf, PfHsp70 and DnaK in E. coli cells either in the absence or presence of over-expressed GroEL-GroES chaperonin. The folded and functional status of the produced PfAdoMetDC was assessed using limited proteolysis and enzyme assays. PfAdo- MetDC co-expressed with KPf and PfHsp70 exhibited improved activity compared to protein co-expressed with over-expressed DnaK. Our findings suggest that chimeric KPf may be an ideal Hsp70 co-expression partner for the production of recombinant plasmodial proteins in E. coli.S1 Fig. KPf and PfHsp70 do not co-purify with PfAdoMetDC. Western blot representing the purification of PfAdoMetDC expressed in E. coli BL21 (DE3) Star cells rehosted with various chaperone combinations. Lanes: U–PfAdoMetDC expressed in the absence of supplemented chaperones; K–PfAdoMetDC co-expressed with supplemented DnaK; KPf–PfAdoMetDC expressed in cells supplemented with KPf; Pf70 –PfAdoMetDC expressed in cells supplemented with PfHsp70; K-EL–PfAdoMetDC expressed in cells supplemented with DnaK and GroEL-GroES; KP-EL–PfAdoMetDC expressed in cells supplemented with KPf and GroEL-GroES; Pf70-EL–PfAdoMetDC expressed in cells supplemented with PfHsp70 and GroEL-GroES; +C–positive consisting of purified PfHsp70 protein.Western blot analysis of PfHsp70 (70 kDa) detected using α-PfHsp70 antibody. Numbers to the left represent protein markers (Fermentas) in kDa.S2 Fig. Sequence alignment of PfHsp70 and E. coli DnaK. Sequence alignment of E. coli DnaK (accession number: BAA01595.1) and PfHsp70 (accession number: PF08_0054) were conducted using ClustalW and Boxshade. The following structural features are highlighted: the highly conserved linker segment (black horizontal line) which separates the ATPase domain from the peptide binding domain. Residues Y145, N147, D148, N170 and T173 in the ATPase domain that interact with DnaJ as reviewed by Shonhai et al (8) are shown with black arrows. Residues G400, D526 and G539 in the peptide binding domain of DnaK that are important for interaction with DnaJ, and the aligned residues in PfHsp70 are shown as black arrows. Identical residues are presented in white against a black background and similar residues are shown in black against a grey background).S1 Table. E. coli strains and plasmids used in this study.S2 Table. Description of primers used towards generation of destination plasmids.The National Research Foundation for an equipment grant (UID, 75464) awarded to AS. AS is a recipient of a Georg Foster research fellowship awarded by the Alexander von Humboldt Foundation of Germany. XHM is a recipient of a National Research Foundation (South Africa) scarce skills scholarship and also received a grant from the University of Zululand Research Committee. AB is a recipient of a postdoctoral fellowship awarded by the NRF.http://www.plosone.orgam2016BiochemistryUP Centre for Sustainable Malaria Control (UP CSMC

The Atacama Cosmology Telescope: Cosmology from Galaxy Clusters Detected via the Sunyaev-Zel'dovich Effect

We present constraints on cosmological parameters based on a sample of Sunyaev-Zel'dovich-selected galaxy clusters detected in a millimeter-wave survey by the Atacama Cosmology Telescope. The cluster sample used in this analysis consists of 9 optically-confirmed high-mass clusters comprising the high-significance end of the total cluster sample identified in 455 square degrees of sky surveyed during 2008 at 148 GHz. We focus on the most massive systems to reduce the degeneracy between unknown cluster astrophysics and cosmology derived from SZ surveys. We describe the scaling relation between cluster mass and SZ signal with a 4-parameter fit. Marginalizing over the values of the parameters in this fit with conservative priors gives sigma_8 = 0.851 +/- 0.115 and w = -1.14 +/- 0.35 for a spatially-flat wCDM cosmological model with WMAP 7-year priors on cosmological parameters. This gives a modest improvement in statistical uncertainty over WMAP 7-year constraints alone. Fixing the scaling relation between cluster mass and SZ signal to a fiducial relation obtained from numerical simulations and calibrated by X-ray observations, we find sigma_8 = 0.821 +/- 0.044 and w = -1.05 +/- 0.20. These results are consistent with constraints from WMAP 7 plus baryon acoustic oscillations plus type Ia supernoava which give sigma_8 = 0.802 +/- 0.038 and w = -0.98 +/- 0.053. A stacking analysis of the clusters in this sample compared to clusters simulated assuming the fiducial model also shows good agreement. These results suggest that, given the sample of clusters used here, both the astrophysics of massive clusters and the cosmological parameters derived from them are broadly consistent with current models.Comment: 12 pages, 7 figures. Submitted to Ap