Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal Structure and Binding Properties of the Serratia marcescens Chitin-binding Protein CBP21*

Chitin proteins are commonly found in bacteria that utilize chitin as a source of energy. CBP21 is a chitin-binding protein from Serratia marcescens, a Gram-negative soil bacterium capable of efficient chitin degradation. When grown on chitin, S. marcescens secretes large amounts of CBP21, along with chitin-degrading enzymes. In an attempt to understand the molecular mechanism of CBP21 action, we have determined its crystal structure at 1.55 Å resolution. This is the first structure to be solved of a family 33 carbohydrate-binding module. The structure reveals a “budded” fibronectin type III fold consisting of two β-sheets, arranged as a β-sheet sandwich, with a 65-residue “bud” consisting of three short helices, located between β-strands 1 and 2. Remarkably, conserved aromatic residues that have been suggested previously to play a role in chitin binding were mainly found in the interior of the protein, seemingly incapable of interacting with chitin, whereas the structure revealed a surface patch of highly conserved, mainly hydrophilic residues. The roles of six of these conserved surface-exposed residues (Tyr-54, Glu-55, Glu-60, His-114, Asp-182, and Asn-185) were probed by site-directed mutagenesis and subsequent binding studies. All single point mutations lowered the affinity of CBP21 for β-chitin, as shown by 3–8-fold increases in the apparent binding constant. Thus, binding of CBP21 to chitin seems to be mediated primarily by conserved, solvent-exposed, polar side chains.
Why stroke patients don't like Mondays (or Saturdays or Sundays).

judgment needs to be made on an individual basis as it will not be appropriate for all patients. The publication of the guideline is welcome and establishes a benchmark which should encourage the development of improved services for people with PD and their carers. The scope of the guideline is testimony to the complexity of PD and the fact that this is much more than just a disorder of movement: increasing attention is now focused on the ‘non-motor’ and neuropsychiatric aspects of the condition as important determinants of quality of life. In addition, the diagnosis can often be far from straightforward and requires experience and sensitive handling. Because of this a major theme of the guideline is the need for specialist care. A ‘specialist’, however, is not defined beyond someone with expertise in treating the condition. Modernising Medical Careers and the move towards accredited, competency-based training provides an opportunity for the management of movement disorders, including PD, to come of age and develop as a sub-specialty in the same way as has occurred for stroke medicine. There are already many good examples of integrated, multi-disciplinary team-based services managing PD, but this model is still far from universal and thus represents one of the principal challenges to implementation. Geriatricians are particularly well placed in this regard as holistic, team-based working is integral to the ethos of the specialty. Many neurology services are less well served but there may be an opportunity to further foster links between the two disciplines to deliver an integrated service for patients.
Induction of apoptosis in androgen‐independent mouse mammary cell line by 1, 25‐dihydroxyvitamin D3

Androgen‐dependent tumors eventually progress to independent‐tumors after androgen withdrawal. Effective treatment for hormone‐independent tumors is therefore needed. Androgen‐independent CS‐2 cells could grow in serum‐free culture whether androgen is present in the medium or not. In the present study, the mechanism of cell death in CS‐2 cells was examined after 1, 25‐dihydroxyvitamin D3 [1, 25(OH)2D3] treatment. 1, 25(OH)2D3 has been examined as an anti‐tumor agent, but its role in promoting cell death is poorly understood. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, the cells underwent apoptosis with 1, 25(OH)2D3treatment. Northern‐blot analysis was used to identify a series of genes whose expression per cell is enhanced during the apoptotic pathway. In the apoptotic process induced by 1, 25(OH)2D3, mRNA expression of testosterone‐repressed prostatic message 2, transforming growth factor β1, glucose‐regulated 78‐kDa protein and calmodulin increased. Flow‐cytometric analysis showed that 1, 25(OH)2D3 treatment resulted in a block in G0/G1 of the cell cycle. These results demonstrate that androgen‐independent CS‐2 cells retain the ability to undergo apoptosis by 1, 25(OH)2D3. This system appears to be a good model for investigating apoptosis of hormone‐independent cancer. © 1996 Wiley‐Liss, Inc.
Pain, Opioids, and Addiction

IN RESPONSE: I appreciate Dr. Galishoff's comments and for the most part agree. Like other chronic diseases, addiction is not just a problem of biology. A person's environment and his or her behavior also play critical roles in the initiation and perpetuation of the disease of addiction (1). However, for better or worse, as physicians we are primarily trained to diagnose and intervene in biological problems. That is where we excel and where we focus most of our attention. We have a much poorer track record when it comes to intervening in the stickier and more complicated problems of changing unhealthy behaviors and addressing the social determinants that often underlie those behaviors (2, 3). Nevertheless, 1 of the most extraordinary and inspiring aspects of working in the field of addiction is that, unlike other chronic diseases, this condition comes with a built-in community of persons in recovery who are dedicated to changing their own behavior and supporting others in achieving positive behavioral change. This often occurs through 12-stepbased interventions, often buttressed by faith. I agree with Dr. Galishoff: We need to pay close attention to those peer-based, grass-roots interventions, and we need to strongly support attendance among our patients who find them useful. However, I do not believe that this means that secular humanism (or, by extension, atheism) has no role in recovery. Nonfaith-based behavioral interventions have also been shown to increase positive or, as Dr. Galishoff describes them, "moral" behaviors. These should also be encouraged, as should interventions that target such root causes as poverty, trauma, and social isolation (4, 5). I believe that the larger point here is that the field of addiction medicine is now uniquely able to draw upon remarkable scientific advances as well as a robust history of grass-roots commitment to interventions in behavior change. If, as physicians, we are willing to listen to voices of recoveryand if persons in recovery are willing to accept new, scientifically based tools for changewe may be rewarded by an incredibly fruitful and hopeful moment in the history of addiction treatment.
Adoptive Immunotherapy of Experimental Autoimmune Encephalomyelitis Via T Cell Delivery of the IL-12 p40 Subunit1

CD4+ T cells are believed to play a central role in the initiation and perpetuation of autoimmune diseases such as multiple sclerosis. In the murine model for multiple sclerosis, experimental autoimmune encephalomyelitis, pathogenic T cells exhibit a Th1-like phenotype characterized by heightened expression of proinflammatory cytokines. Systemic administration of “regulatory” cytokines, which serve to counter Th1 effects, has been shown to ameliorate autoimmune responses. However, the inherent problems of nonspecific toxicity limit the usefulness of systemic cytokine delivery as a potential therapy. Therefore, we used the site-specific trafficking properties of autoantigen-reactive CD4+ T cells to develop an adoptive immunotherapy protocol that provided local delivery of a Th1 cytokine antagonist, the p40 subunit of IL-12. In vitro analysis demonstrated that IL-12 p40 suppressed IFN-γ production in developing and effector Th1 populations, indicating its potential to modulate Th1-promoted inflammation. We have previously demonstrated that transduction of myelin basic protein-specific CD4+ T cells with pGC retroviral vectors can result in efficient and stable transgene expression. Therefore, we adoptively transferred myelin basic protein-specific CD4+ T cells transduced to express IL-12 p40 into mice immunized to develop experimental autoimmune encephalomyelitis and demonstrated a significant reduction in clinical disease. In vivo tracking of bioluminescent lymphocytes, transduced to express luciferase, using low-light imaging cameras demonstrated that transduced CD4+ T cells trafficked to the central nervous system, where histological analysis confirmed long-term transgene expression. These studies have demonstrated that retrovirally transduced autoantigen-specific CD4+ T cells inhibited inflammation and promoted immunotherapy of autoimmune disorders.
Immune system adaptation in elite athletes

Purpose of reviewTo evaluate the effects of exercise on immune function in relation to infection susceptibility. Recent findingsPostexercise immune function depression is most pronounced when exercise is continuous, prolonged, of moderate to high intensity and performed without food intake. Periods of intensified training that result in overreaching have been shown to chronically depress immune function, with leukocyte functions measured at rest still depressed 24 h after the last exercise bout. Several studies indicate that the incidence of symptoms of upper respiratory tract illness is increased in the days following prolonged strenuous endurance events and it has been generally assumed that this is due to the temporary exercise-induced depression of immune function. More recently it has been proposed that at least some of these symptoms are attributable to inflammation of the upper respiratory tract rather than to infectious episodes. SummaryAlthough elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses. Although it is possible that immune depression linked with prolonged intensive training may determine susceptibility to infection, convincing evidence of a cause and effect relationship remains elusive.
Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells

Abstract A creatinine metabolite, 5-hydroxy-1-methylhydantoin (HMH: NZ-419), a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. In the current study, we demonstrate that HMH modulates the effects of glucose and bradykinin (BK) in vascular smooth muscle cell (VSMC). HMH a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. HMH inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that HMH may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.
Analgesic and sedative effects of caudal epidural tramadol in dromedary camels

This study aimed to investigate the analgesic efficacy of caudal epidural administration of tramadol in dromedary camels (Camelus dromedarius). A total of 10 dromedary camels of both sexes were selected and randomly assigned to one of two groups to receive epidurally either 1 mg/kg or 2 mg/kg of tramadol hydrochloride. The injections were made into the epidural space at first intercoccygeal junction. Using a pinprick method, analgesia was tested. Duration and onset of complete perineal analgesia were determined. Ataxia and sedation were also assessed and recorded. Clinical parameters including heart rate, respiratory rate and rectal temperature were measured. The lower dose (1 mg/kg) of tramadol induced analgesia only in the tail but the higher dose produced complete antinociception in the tail, anus and perineum. Analgesia of the hind limbs was not achieved after either doses of tramadol. The mean times to onset and duration of complete analgesia in camels receiving epidural tramadol at a dose of 2 mg/kg were 22±2.55 min and 65±8.66 min, respectively. Various degrees of ataxia occurred in all camels. Mild to deep sedation was observed following both doses. Mean heart rate, respiratory rate, and rectal temperature tended to increase for the first 15 or 30 min after injection. Based on the results of this study, analgesic effects of caudal epidural tramadol were dose dependent. Epidural tramadol at a dose of 2 mg/kg would provide suitable postoperative analgesia for various manipulations in the tail, anus and perineum in standing dromedary camels.
Characterization of “Mycobacterium paraffinicum” Associated with a Pseudo-Outbreak

ABSTRACT We describe the first “Mycobacterium paraffinicum” (unofficial taxon) pseudo-outbreak in a tertiary-care medical center. Fifteen clinical nontuberculous mycobacterium isolates from 10 patients were initially identified by biochemical tests and high-performance liquid chromatography as Mycobacterium scrofulaceum. However, further testing by molecular analysis revealed “M. paraffinicum. ” Epidemiological and environmental investigation determined that the ice machine was the source of the pseudo-outbreak.
Colonization vs. demic expansion in the Azapa Valley, Chile: Reply to Rothhammer et al.

we contended that eastern highland populations replaced preexisting Azapa Valley peoples during the Formative surprised us. We have held, ever since the beginning of our craniometric studies, that migration is primarily responsible for the chronological decrease of kinship observed in the Azapa Valley after the Archaic period. This conclusion was again stated in our most recent article on the subject (Rothhammer et al., 2002). It is very different to conclude that gene flow is responsible for microevolutionary change, than to hypothesize that population replacement took place.
The Gatekeeper Program: Proactive Identification and Case Management of At-Risk Older Adults Prevents Nursing Home Placement, Saving Healthcare Dollars Program Evaluation

The Gatekeeper Program is an innovative community and hospital partnership focused on prevention of premature nursing home placement. Utilizing trained volunteers, who come into contact with older adults through their everyday jobs, the program provides assistance to over 1600 older adults. Positive program outcomes include reducing emergency department (ED) and hospital admissions and a 14 million dollar savings in healthcare costs related to nursing home placement.
Instability analysis and robust adaptive control of robotic manipulators

The robustness of adaptive controllers with respect to uncertainty is examined. The uncertainties include bounded input disturbances, unknown and time-varying plant parameters, and unmodeled dynamics. A simple example shows instability of a recent manipulator control scheme in the presence of bounded disturbances. The adaptive laws for updating the controller parameters are modified so that the instabilities are counteracted and robustness is guaranteed. <<ETX>>
Follow the Leader: Simulations on a Dynamic Social Network

This paper introduces a process of individual adjustment based on private local experiences and observation that allows for the emergence of a global social structure that is the equilibrium to the static follow-the-leader game of Goldbaum (2013). The setting rewards agents for being early adopters of popular products or trends. From simple, myopic, self-serving adjustment based on historic evidence by individuals emerges the the equilibrium social structure consisting of a single choice leader and a population of followers, which, in the static setting would require an unlikely degree of coordination to produce. Individual actions take place in a social context with individuals linked via one-way paths of observation. The strategy by which an agent chooses among the available options evolves over time. Different adjustment emergent processes contribute towards the understanding of the unfolding of events that generate the equilibrium structure.
Clarifying inflation models: The precise inflationary potential from effective field theory and the WMAP data

We clarify inflaton models by considering them as effective field theories in the Ginzburg-Landau spirit. In this new approach, the precise form of the inflationary potential is constructed from the present WMAP data, and a useful scheme is prepared to confront with the forthcoming data. In this approach, the WMAP statement excluding the pure {phi}{sup 4} potential implies the presence of an inflaton mass term at the scale m{approx}10{sup 13} GeV. Chaotic, new and hybrid inflation models are studied in an unified way. In all cases the inflaton potential takes the form V({phi})=m{sup 2}M{sub Pl}{sup 2}v({phi}/M{sub Pl}), where all coefficients in the polynomial v({phi}) are of order one. If such potential corresponds to supersymmetry breaking, the corresponding susy breaking scale is {radical}(mM{sub Pl}){approx}10{sup 16} GeV which turns to coincide with the grand unification (GUT) scale. The inflaton mass is therefore given by a seesaw formula m{approx}M{sub GUT}{sup 2}/M{sub Pl}. The observables turn to be two-valued functions: one branch corresponds to new inflation and the other to chaotic inflation, the branch point being the pure quadratic potential. For red tilted spectrum, the potential which fits the best the present data (vertical bar 1-n{sub s} vertical bar < or approx. 0.1,r <more » or approx. 0.1) and which best prepares the way for the forthcoming data is a trinomial polynomial with negative quadratic term (new inflation). For blue tilted spectrum, hybrid inflation turns to be the best choice. In both cases we find an analytic formula relating the inflaton mass with the ratio r of tensor to scalar perturbations and the spectral index n{sub s} of scalar perturbations: 10{sup 6}(m/M{sub Pl})=127{radical}(r vertical bar 1-n{sub s} vertical bar) where the numerical coefficient is fixed by the WMAP amplitude of adiabatic perturbations. Implications for string theory are discussed. « less
The effect of anthelmintic treatment on helminth infection and anaemia

A 24-week randomized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections. A total of 553 women were randomly assigned to 1 of 4 intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half way through the trial, group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment. Prevalence and intensity of helminth infections (egg counts/g stool) of Ascaris lumbricoides, Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment. Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group. All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups. Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration.
Genetic Polymorphisms Involved in Carcinogen Metabolism and DNA Repair and Lung Cancer Risk in a Japanese Population

Background: Several components of overall lung carcinogenesis, carcinogen metabolic and DNA repair pathways may be involved in individual genetic susceptibility to lung cancer. Methods: We evaluated the role of cytochrome P450 (CYP) 1A1 rs4646903 and rs104894, glutathione S-transferase (GST) M1 and GSTT1 deletion polymorphisms, GSTP1 rs1695, x-ray repair, excision repair cross-complementing group 2 (ERCC2) rs13181, complementing defective in Chinese hamster 1 rs25487, and XRCC3 rs861539 in a case-control study comprising 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results: CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25–2.38), rs1048943 (OR = 1.40, 95% CI = 1.02–1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01–1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04–2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28–2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12–2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not. A pertinent combination of multiple “at-risk” genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77–12.7) increased risk of lung cancer. Conclusions: A pertinent combination of multiple at-risk genotypes may detect a high-risk group. Further studies are warranted to verify our findings.
Retinal projections to the superior colliculus and dorsal lateral geniculate nucleus in the tammar wallaby (Macropus eugenii): II. Topography after rotation of an eye prior to retinal innervation of the brain

Retinal projections to visual centers in a marsupial mammal, the tammar wallaby (Macropus eugenii), have been investigated after an eye rotation prior to retinal innervation of the brain. Retinal topography to the superior colliculus and dorsal lateral geniculate nucleus was mapped by using laser lesions of the retina and horseradish peroxidase histochemistry. Despite the change in orientation of optic axon outgrowth from the developing eye after rotation, retinal ganglion cells made orderly connections in the colliculus and geniculate according to their original retinal position within the eye and not their rotated position. Axons must have corrected their pathways at some point between the back of the eye and their targets. The optic chiasm was one such site. Optic axons from the rotated eye took an abnormal course at the caudal end of the chiasm.
Geometría del pensamiento

Ha surgido un nuevo modelo formal para la representacion de los aspectos cognitivos en general. Su autor percibe este modelo como una concepcion que amplia los enfoques simbolico y asociativo, tradicionalmente usados para este mismo proposito, permitiendo ademas compatibilizar dichos enfoques tradicionales, a pesar que ambos se presentaban, hasta hace muy poco tiempo, como posiciones fundamentalmente distintas o inclusive antagonicas. Desde el punto de vista practico, el nuevo modelo tiene tambien la ventaja de resultar facilmente susceptible de automatizacion a traves de computadoras electronicas digitales contemporaneas. Las aplicaciones inmediatas se hallan por ejemplo en las areas de aprendizaje automatico (“machine learning”), soporte (automatico) a procesos inductivos, e investigaciones semanticas, percibiendose asi mismo un enorme potencial futuro en areas complementarias.