Miracle-dz/UniFAR-FTUs huggingface dataset:
Conditions for helping relations in specialized personal social services – a client perspective on the influence of organizational struc-ture

ABSTRACT This article highlights organizational structure as a factor influencing conditions for helping relations. It is based on a survey study and an interview study, both directed at parents in families that have parallel contacts in different parts of Swedish personal social services (PSS). The aim is to describe and analyse conditions for helping relations when clients with complex needs encounter specialized PSS. Low system trust, people processing dimensions of work, and an organizational and a professional emphasis on formal organizational structures and boundaries were found to constitute unfavourable conditions. Conversely, an occurrence of individual trust, people sustaining and people changing dimensions of work, as well as informal organization and individual social workers’ boundary spanning efforts, constituted favourable conditions. The article concludes that greater understanding of how clients are affected by contextual service conditions can give some pointers towards how to generally improve services for vulnerable and disadvantaged populations.
Mayors and Money: Fiscal Policy in New York and Chicago

Chicago and New York share similar backgrounds but have had strikingly different fates. Tracing their fortunes from the 1930s to the present day, Ester R. Fuchs examines key policy decisions which have influenced the political structures of these cities and guided them into, or clear of, periods of economic crisis.
Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival

ABSTRACT The oncogenic microRNA miR-155 is upregulated by several oncogenic viruses. The precursor of miR-155, termed bic, was first observed to cooperate with myc in chicken B-cell lymphomas induced by avian leukosis proviral integrations. We identified another oncogenic retrovirus, reticuloendotheliosis virus strain T (REV-T), that upregulates miR-155 in chicken embryo fibroblasts. We also observed very high levels of miR-155 in REV-T-induced B-cell lymphomas. To study the role of miR-155 in these tumors, we identified JARID2/Jumonji, a cell cycle regulator and part of a histone methyltransferase complex, as a target of miR-155. The overexpression of miR-155 decreased levels of endogenous JARID2 mRNA. We confirmed that miR-155 directly targets both human and chicken JARID2 by assaying the repression of reporters containing the JARID2 3′-untranslated regions. Further, the overexpression of a sponge complementary to miR-155 in a tumor cell line increased endogenous JARID2 mRNA levels. The overexpression of JARID2 in chicken fibroblasts led to decreased cell numbers and an increase in apoptotic cells. The overexpression of miR-155 rescued cells undergoing cytopathic effect caused by infection with subgroup B avian retroviruses. Therefore, we propose that miR-155 has a prosurvival function that is mediated through the downregulation of targets including JARID2.
PET Imaging of Proliferation with Pyrimidines

Several new tracers are being developed for use with PET to assess pathways that are altered in cancers, including energy use, cellular signaling, transport, and proliferation. Because increased proliferation is a hallmark of many cancers, several tracers have been tested to track the DNA synthesis pathway. Thymidine, which is incorporated into DNA but not RNA, has been used in laboratory studies to measure tumor growth. Because thymidine labeled with 11C undergoes rapid biologic degradation and has a short physical half-life, tracers labeled with 18F have been preferred in PET imaging. One such tracer is 18F-labeled 3′-deoxy-3′-fluorothymidine (18F-FLT). 18F-FLT is trapped after phosphorylation by thymidine kinase 1, whose expression is increased in replicating cells. Several studies on breast, lung, and brain tumors have demonstrated that retention of 18F-FLT correlated with tumor proliferation. Although 18F-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with 18F-FDG. 18F-FLT can be used to image many areas of the body, but background uptake is high in the liver, marrow, and renal system, limiting use in these organs. 18F-FLT PET imaging has primarily been studied in the assessment of treatment response. Rapid declines in 18F-FLT retention within days to weeks have been demonstrated in several tumor types treated with cytotoxic drugs, targeted agents, and radiotherapy. Further work is ongoing to validate this approach and determine its utility in the development of new drugs and in the clinical evaluation of standard treatment approaches.
Improving Industrial Grippers With Adhesion-Controlled Friction

Effective handling of delicate objects remains a challenging problem in manufacturing. Instead of using a specialized gripper or control scheme, we present a solution involving gecko-inspired directional adhesives affixed to an industrial robot gripper and tactile sensor. The adhesives sustain large shear forces with very low pressure. They also release objects without residual adhesion when the grip is relaxed. It is desirable to predict the maximum forces and moments the gripper can exert without slipping. For this purpose the tactile sensor provides an estimate of the area of contact, and a force/torque sensor measures the overall force and moment. To resist forces and moments in multiple directions, it is best if the directional adhesives do not all have a single orientation. A chevron pattern strikes a good balance between performance and ease of fabrication.
From Van Duyn to Mangold via Marshall: Reducing Direct Effect to Absurdity?

In an article published in 1983, Pierre Pescatore who, as a Member of the Court of Justice, exercised a powerful intellectual influence over the development of European Community law during what might be deemed the Court’s Golden Age, once described direct effect as ‘an infant disease’. What he meant was that, in the early years of the Community, it may have seemed remarkable, even dangerous, that provisions of the EC Treaty or of acts adopted under it could give rise to rights and correlative duties which national courts were called upon to recognise and enforce. But now that Community law had reached maturity, direct effect should be taken for granted, as a normal incident of an advanced constitutional order.
Terminal amino acid sequences and proteolytic cleavage sites of mouse mammary tumor virus env gene products

The mature envelope glycoproteins of mouse mammary tumor virus (gp52 and gp36) were isolated by reversed-phase high-pressure liquid chromatography. The N-terminal amino acid sequence of gp36 was determined for 28 residues. The C-terminal amino acid sequences of gp52 and gp36 were determined by carboxypeptidase digestion. The N-terminal amino acid sequence of gp52 has been reported previously (L. O. Arthur et al., J. Virol. 41:414-422, 1982). These data were aligned with the predicted amino acid sequence of the env gene product obtained by translation of the DNA sequence (S. M. S. Redmond and C. Dickson, Eur. Mol. Biol. Org. J. 2:125-131, 1983). The amino acid sequences of the mature viral proteins were in agreement with the predicted amino acid sequence of the env gene product over the regions of alignment. This alignment showed the sites of proteolytic cleavages of the env gene product leading to the mature viral envelope glycoproteins. The N-terminal amino acid sequence of gp52 starts at residue 99 of the predicted structure indicating proteolytic cleavage of a signal peptide. A dipeptide (Lys-Arg) is excised between the C-terminus of gp52 and the N-terminus of gp36. The C-terminal amino acid sequence of gp36 is identical to the sequence predicted by the codons immediately preceding the termination codon for the env gene product. The data show that there is no proteolytic processing at the C-terminal of the murine mammary tumor virus env gene product and that the env gene coding region extends into the long terminal repeat.
The ubiquitin–proteasome cascade is required for mammalian long‐term memory formation

It has been recently demonstrated that ubiquitin–proteasome‐mediated proteolysis is required for long‐term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long‐term memory in the rat. Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one‐trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training. Proteasome inhibitor I produced similar effects. In addition, inhibitory avoidance training resulted in an increased ubiquitination and 26S proteasome proteolytic activity and a decrease in the levels of IkappaB, a substrate of the ubiquitin–proteasome cascade, in hippocampus 4 h after training. Together, these findings indicate that the ubiquitin–proteasome cascade is crucial for the establishment of LTM in the behaving animal.
Impact of positive fluid balance on mortality and length of stay in septic shock patients

Background: Fluid management is important in critically patients. The aim of this study was to determine the relationship between fluid balance and adverse outcomes of septic shock. Methods: A retrospective study was conducted in the medical Intensive Care Unit (ICU) of a tertiary university hospital in Thailand, over a 7-year period. Results: A total of 1048 patients with an ICU mortality rate of 47% were enrolled. The median cumulative fluid intake at 24, 48, and 72 h from septic shock onset were 4.2, 7.7, and 10.5 L, respectively. Nonsurvivors had a significantly higher median cumulative fluid intake at 24, 48, and 72 h (4.6 vs. 3.9 L, 8.2 vs. 7.1 L, and 11.4 vs. 9.9 L, respectively, P < 0.001 for all). Nonsurvivors also had a significantly higher cumulative and mean fluid balance within 72 h (5.4 vs. 4.4 L and 2.8 vs. 1.6 L, P < 0.001 for both). In multivariate logistic regression analysis, mean fluid balance quartile within 72 h, was independently associated with an increase in ICU and hospital mortality. Quartile 3 and 4 have statistically significant increases in mortality compared with quartile 1 (odds ratio [95% confidence interval] 3.04 [1.9–4.48] and 4.16 [2.49–6.95] for ICU mortality and 2.75 [1.74–4.36] and 3.16 [1.87–5.35] for hospital mortality, respectively, P < 0.001 for all). In addition, the higher amount of mean fluid balance was associated with prolonged ICU stays. Conclusions: Positive fluid balance over 3 days is associated with increased ICU and hospital mortality along with prolonged ICU stays in septic shock patients.
HumanImmunodeficiency Virus Type 1 Fitness Is a Determining Factor in ViralRebound and Set Point in ChronicInfection

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) isolates from 20 chronically infected patients who participated in a structured treatment interruption (STI) trial were studied to determine whether viral fitness influences reestablishment of viremia. Viruses derived from individuals who spontaneously controlled viremia had significantly lower in vitro replication capacities than viruses derived from individuals that did not control viremia after interruption of antiretroviral therapy (ART), and replication capacities correlated with pre-ART and post-STI viral set points. Of note, no clinically relevant improvement of viral loads upon STI occurred. Virus isolates from controlling and noncontrolling patients were indistinguishable in terms of coreceptor usage, genetic subtype, and sensitivity to neutralizing antibodies. In contrast, viruses from controlling patients exhibited increased sensitivity to inhibition by chemokines. Sensitivity to inhibition by RANTES correlated strongly with slower replication kinetics of the virus isolates, suggesting a marked dependency of these virus isolates on high coreceptor densities on the target cells. In summary, our data indicate that viral fitness is a driving factor in determining the magnitude of viral rebound and viral set point in chronic HIV-1 infection, and thus fitness should be considered as a parameter influencing the outcome of therapeutic intervention in chronic infection.
Increased risk of type 2 diabetes in noncirrhotic patients with chronic hepatitis C virus infection.

OBJECTIVES To investigate whether patients with chronic hepatitis C virus (HCV) infection without evidence of cirrhosis have an increased risk of diabetes mellitus (DM) and to evaluate possible risk factors for diabetes in this group. PATIENTS AND METHODS We conducted a case-control study of 45 consecutive eligible patients with HCV infection and no clinical, scintigraphic, or histological evidence of cirrhosis, and a control group of 90 subjects without liver disease matched by age, sex, and body mass index and similar in their origin distribution. Eighty-eight patients with chronic hepatitis B virus (HBV) infection with no evidence of cirrhosis were also evaluated. The diagnosis of diabetes was based on the 1997 American Diabetes Association criteria. RESULTS Fifteen patients (33%) with HCV infection were found to have type 2 diabetes compared with 5.6% in the control group without liver disease (P < .001) and 12% in the group with HBV infection (P = .004). Comparison of the patients with and without diabetes revealed that positive family history of diabetes, HCV 1b genotype, and a more severe liver histology were significantly associated with DM. CONCLUSIONS Patients with chronic HCV infection have an increased prevalence of type 2 diabetes, and this prevalence is independent of cirrhosis. The pathogenesis is intriguing, appears to be unique to HCV, and requires further study.
At the crossroads: new paradigms of food security, public health nutrition and school food

Abstract Public health nutrition sits at the nexus of a global crisis in food, environmental and health systems that has generated – along with numerous other problems – an urgent and changing problem of food insecurity. The ‘new’ food insecurity, however, is different from the old: it is bimodal, encompassing issues of both under- and over-consumption, hunger and obesity, quantity and quality; it has assumed a decidedly urban dimension; and it implicates rich and poor countries alike. The complexity of the expressions of this challenge requires new approaches to public health nutrition and food policy that privilege systemic, structural and environmental factors over individual and mechanistic ones. In this context, the current paper argues that school food systems rise with buoyant potential as promising intervention sites: they are poised to address both modes of the food security crisis; integrate systemic, structural and environmental with behavioural approaches; and comprise far-reaching, system-wide efforts that influence the wider functioning of the food system. Based on a discussion of Bogotá and other pioneering policies that explicitly aim to create a broader food system with long-term foundations for good public health and food security, the paper suggests a new research and action agenda that gives special attention to school food in urban contexts.
Stress, immunity and illness — a review

Synopsis Psychological factors have long been thought to play a contributing role in either the predisposition, onset or course of various physical illnesses. Recently, rapid advances in immunology have created interest in the interaction between psychosocial factors, behaviour and the immune system. This paper reviews some of the models proposed to explain the relationship between psychological variables and physical illness and presents evidence for a contribution of psychological factors to certain illnesses in which abnormalities in immunologic state are thought to be important. From a somewhat different perspective, animal studies have demonstrated complex effects of stress, on disease susceptibility. Recent human studies have demonstrated consistent immunologic changes in people undergoing acute naturally occurring psychological stress such as bereavement or an important examination. In humans, the effects of chronic stress may be different from acute stress, corresponding to the findings in animals. Abnormalities in immunologic functioning and physical illness are reviewed for different psychiatric disorders — depression, anorexia nervosa and schizophrenia; depression is the only disorder which consistently demonstrated immunologic changes. Possible mechanisms for the stress/immune-change relationship are suggested.
A Simple and Efficient System for Regulating Gene Expression in Human Pluripotent Stem Cells and Derivatives

Regulatable transgene expression in human pluripotent stem cells (hPSCs) and their progenies is often necessary to dissect gene function in a temporal and spatial manner. However, hPSC lines with inducible transgene expression, especially in differentiated progenies, have not been established due to silencing of randomly inserted genes during stem cell expansion and/or differentiation. Here, we report the use of transcription activator‐like effector nucleases‐mediated targeting to AAVS1 site to generate versatile conditional hPSC lines. Transgene (both green fluorescent protein and a functional gene) expression in hPSCs and their derivatives was not only sustained but also tightly regulated in response to doxycycline both in vitro and in vivo. We modified the donor construct so that any gene of interest can be readily inserted to produce hPSC lines with conditional transgene expression. This technology will substantially improve the way we study human stem cells. Stem Cells 2014;32:1230–1238
Digital rectal examination, serum prostatic specific antigen or transrectal ultrasonography: the best tool to guide the treatment of men with benign prostatic hyperplasia

Purpose of review Benign prostatic hyperplasia can be considered a progressive disease, and identifying men with progressive disease could have a significant impact on the decision to choose the different therapeutic options. Numerous pieces of evidence demonstrate the impact of the prostate volume on the disease progression. It has been accepted that digital rectal examination, serum prostatic specific antigen and transrectal prostate ultrasound are the available tools for the prostate volume estimation. This review examines the updated information on these tools for their guidance in the benign prostatic hyperplasia management. Recent findings Digital rectal examination is unreliable in assessing the prostate volume; however, it is still important to use it to rule out prostate cancer or neurological problems. Prostatic specific antigens should be recommended as a part of patient evaluation because of their impact on the prediction of disease progression. Transrectal prostate ultrasound may be the best tool in the estimation of the exact prostate size. Summary Numerous pieces of evidence have clearly demonstrated the impact of the prostate volume on the disease progression. Digital rectal examination seems to be good at identifying very large prostate. Prostatic specific antigen is the best tool for predicting disease progression and guiding the therapeutic options. For surgical guidance, transrectal prostate ultrasound is the useful tool available for the exact prostate volume estimation.
Potent, specific MEPicides for treatment of zoonotic staphylococci

Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact, zoonoses that cause serious infections in human patients. The global spread of multidrug-resistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius. A series of lipophilic ester prodrugs (termed MEPicides) structurally related to FSM were synthesized, and data indicate that the presence of the prodrug moiety not only substantially increased potency of the inhibitors against staphylococci, but also bypassed the need for GlpT-mediated cellular transport. Collectively, our data indicate that the prodrug MEPicides selectively and robustly inhibit DXR in zoonotic staphylococci, and further, DXR represents a promising, druggable target for future development. Author Summary The proliferation of microbial pathogens resistant to the current pool of antibiotics is a major threat to public health. Drug resistance is pervasive in staphylococci, including several species that can cause serious zoonotic infections in humans. Thus, new antimicrobial agents are urgently need to combat these life-threatening, resistant infections. Here we establish the MEP pathway as a promising new target against zoonotic staphylococci. We determine that fosmidomycin (FSM) selectively targets the isoprenoid biosynthesis pathway in zoonotic staphylococci, and use forward genetics to identify the transporter that facilitates phosphonate antibiotic uptake. Employing this knowledge, we synthesized a series of potent antibacterial prodrugs that circumvent the transporter. Together, these novel prodrug inhibitors represent promising leads for further drug development against zoonotic staphylococci.
Molecular cloning and characterization of a Streptococcus sanguis DNase necessary for repair of DNA damage induced by UV light and methyl methanesulfonate

We developed a method for cloning cellular nucleases from streptococci. Recombinant lambda gt11 bacteriophage containing streptococcal nuclease determinants were identified by the production of pink plaques on toluidine blue O DNase plates. We used this technique to clone a 3.2-kilobase-pair EcoRI fragment with DNase activity from the chromosome of Streptococcus sanguis. The locus was designated don (DNase one) and could be subcloned and stably maintained on plasmid vectors in Escherichia coli. Minicell analyses of various subclones of the don locus allowed us to determine the coding region and size of the Don nuclease in E. coli. The don gene product had an apparent molecular mass of 34 kilodaltons and degraded native DNA most efficiently, with lesser activity against denatured DNA and no detectable activity against RNA. S. sanguis don deletion mutants were constructed by transformation of competent cells with in vitro-prepared plasmid constructs. S. sanguis don deletion mutants retained normal transformation frequencies for exogenously added donor DNA. However, when compared with Don+ wild-type cells, these mutants were hypersensitive to DNA damage induced by UV light and methyl methanesulfonate. An S. sanguis don-specific DNA probe detected homology to chromosomal DNA isolated from Streptococcus pneumoniae and Streptococcus mutans Bratthall serogroups d and g. Our results suggested that the don locus was the S. sanguis allele of the previously described S. pneumoniae major exonuclease and was involved in repair of DNA damage. Furthermore, hybridization studies suggested that the don locus was conserved among species of oral streptococci.