Miracle-dz/UniFAR-FTUs huggingface dataset:
Customary International Law: An Instrument Choice Perspective

Contemporary international lawmaking is characterized by a rapid growth of “soft law” instruments. Interdisciplinary studies have followed suit, purporting to frame the key question states face as a choice between soft and “hard” law. But this literature focuses on only one form of hard law — treaties — and cooperation through formal institutions. Customary international law (CIL) is barely mentioned. Other scholars dismiss CIL as increasingly irrelevant or even obsolete. Missing from these debates is any consideration of whether and when states might prefer custom over treaties or soft law. This article applies an instrument choice perspective to demonstrate custom’s continuing relevance to contemporary international lawmaking. First, we use instrument choice to identify the distinctive design features that distinguish CIL from treaties and soft law. As an ideal-type and in comparison to conventions and nonbinding norms, custom is a non-negotiated, unwritten and universal form of cooperation. Second, instrument choice illuminates the constraints that limit custom to particular types of cooperation problems, which we label as custom’s “domains. ” Specifically, CIL’s design features limit custom to situations in which all-states-benefit from a norm, hegemonic custom, and normative custom. Third, an instrument choice approach predicts that states will continue to prefer custom over treaties and soft law when its design features or substantive norms offer advantages over international agreements and nonbinding norms. Custom thus retains contemporary relevance even in an age of soft law and treaties, so long as states act within the constraints imposed by custom’s domains.
Generation and characterization of a tamoxifen inducible Msx1CreERT2 knock‐in allele

Msx1, a member of the Msx gene family, encodes a homeodomain transcription factor and plays critical roles during mouse development in numerous organs. By homologous recombination, we generated a new Msx1 allele (Msx1CreERT2) in which the CreERT2 fusion protein is produced in place of the endogenous Msx1 protein. Using different reporter mouse strains and appropriate tamoxifen treatments, we show that, in mice bearing the Msx1CrERT2 allele, CreERT2 is capable to induce loxP genomic recombination specifically in Msx1‐expressing cells and that this can be obtained during embryonic development as well as after birth. These results show that this new mouse line can be used for lineage tracing of Msx1‐expressing cells and their descendants and, combined with Cre‐inducible Msx null alleles, for the analysis of Msx1 and/or Msx2 functions in the Msx1‐expressing organs, in a time‐dependant manner. genesis 51:110–119, 2013. © 2012 Wiley Periodicals, Inc.
Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis.

BACKGROUND & AIMS Diabetic gastroparesis involves neuropathy, myopathy, and depletion of interstitial cells of Cajal (ICC), which may cause dysrhythmias and impaired neural control. Most murine gastric ICC depend on stem cell factor (SCF) signaling but can also be maintained with insulin or insulin-like growth factor-I (IGF-I). We investigated whether SCF could mediate the actions of insulin and IGF-I. METHODS Expression of insulin receptor, IGF-I receptor, and SCF was studied in gastric muscles and purified ICC by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The effects of insulin/IGF-I deficiency on SCF, ICC, smooth muscle, and neurons were investigated in nonobese diabetic mice and organotypic cultures by immunohistochemistry, microarrays, and/or quantitative RT-PCR. ICC in organotypic cultures were also studied after immunoneutralization of endogenous SCF. RESULTS Insulin and IGF-I receptors were detected in smooth-muscle cells and myenteric neurons but not in ICC. Cell-surface expression of SCF was only found in smooth-muscle cells. ICC depletion in diabetes was accompanied by smooth-muscle atrophy and reduced SCF, whereas neuron-specific gene expression remained unchanged. In organotypic cultures, prevention of ICC loss by insulin or IGF-I was paralleled by rescue of smooth-muscle cells and SCF expression but not of myenteric neurons. Immunoneutralization of endogenous SCF caused ICC depletion closely resembling that elicited by insulin/IGF-I deficiency. CONCLUSIONS Reduced insulin/IGF-I signaling in diabetes may lead to ICC depletion and its consequences by causing smooth-muscle atrophy and reduced SCF production. Thus, myopathy may play a more central role in diabetic gastroenteropathies than previously recognized.
Multiobjective genetic estimation of DC motor parameters and load torque

In order to simplify the offline identification of motor parameters, a new method based on optimization using a multiobjective elitist genetic algorithm is proposed. The non-dominated sorting genetic algorithm (NSGA-II) is used to minimize the error between the current and velocity responses of data and an estimated model. The robustness of the method is shown by estimating parameters of a DC motor in four different cases. Simulation results show that the method successfully estimates the motor parameters and is also capable of identifying a load torque simultaneously.
Determinants of regional and local diversity within the astroglial lineage of the normal central nervous system

Astrocytes are a major component of the resident non‐neuronal glial cell population of the CNS. They are ubiquitously distributed throughout the brain and spinal cord, where they were initially thought to function in both structural and homeostatic capacities, providing the framework and environment in which neurons performed their parenchymal duties. However, this stroma‐like view of astrocytes is no longer satisfactory. Mounting evidence particularly within the last decade indicates that astrocytes do not simply support neuronal activity but directly contribute to it. Congruent with this evolving view of astrocyte function in information processing is the emergent notion that these glial cells are not a homogeneous population of cells. Thus, astrocytes in various anatomically distinct regions of the normal CNS possess unique phenotypic characteristics that may directly influence the particular neuronal activities that define these regions. Remarkably, regional populations of astrocytes appear to exhibit local heterogeneity as well. Many phenotypic traits of the astrocyte lineage are responsive to local environmental cues (i.e., are adaptable), suggesting that plasticity contributes to this diversity. However, compelling evidence suggests that astrocytes arise from multiple distinct progenitor pools in the developing CNS, raising the intriguing possibility that some astrocyte heterogeneity may result from intrinsic differences between these progenitors. The purpose of this review is to explore the evidence for and mechanistic determinants of regional and local astrocyte diversity.
Probability of error analysis of BPSK OFDM systems with random residual frequency offset

In this paper, we derive closed form bit error rate (BER) expressions for orthogonal frequency division multiplexing (OFDM) systems with residual carrier frequency offset (CFO). Most of the published work treats CFO as a nonrandom parameter. But in our study we consider it as a random parameter. The BER performance of binary phase shift keying (BPSK) OFDM system is analyzed in the cases of additive white Gaussian noise (AWGN), frequency-flat and frequency-selective Rayleigh fading channels.We further discuss how these expressions can be related to systems with practical estimators. The simulation results are provided to verify the accuracy of these error rate expressions.
Homonymous and heteronymous monosynaptic reflexes in biceps brachii

Using poststimulus time histograms, it has been reported that stimulation of the median nerve at the elbow produces a monosynaptic EPSP in voluntarily active single motoneurons of the human biceps brachii. The present study was undertaken to: (i) determine whether such stimulation could evoke a reproducible reflex response in biceps brachii; and (ii) establish the optimal conditions for eliciting the reflex under clinical conditions. Twelve normal subjects were studied. No reflex response was recordable when biceps brachii was relaxed. A reflex response with a mean latency of 14.0 ms (±0.96 ms) could be recorded during a background voluntary contraction. The response was small (0.5–4.5% of the maximal M wave) but symmetrical, and could be obtained in all subjects. The responsible afferents appear to be rapidly conducting fibers from forearm flexor muscles and the latencies of the response were consistent with a monosynaptic reflex. Reflex amplitude increased with stimulus intensity and contraction strength. Stimulus rate did not affect amplitude significantly. It is concluded that a reproducible heteronymous monosynaptic reflex can be recorded from the contracting biceps brachii on stimulation of the median nerve at the elbow. Although smaller than the homonymous H reflex evoked by stimulation at Erb's point, it was technically easier to demonstrate that the EMG potential was of reflex origin (rather than part of an M wave). These reflexes should be of value in the assessment of the C‐5/C‐6 segments and the upper trunk of the brachial plexus. © 1995 John Wiley & Sons, Inc.
Practical urinalysis in the cat

Series outline: This is the first article in a two-part series on urinalysis in the cat. The focus of Part 1 is urine macroscopic examination. Part 2, to appear in the May 2016 issue, discusses urine microscopic examination. Practical relevance: Urinalysis is an essential procedure in feline medicine but often little attention is paid to optimising the data yielded or minimising factors that can affect the results. Clinical challenges: For the best results, appropriately collected urine should be prepared promptly by specialist laboratory personnel for the relevant tests and assessed by a clinical pathologist. This is invariably impractical in clinical settings but careful attention can minimise artefacts and allow maximum useful information to be obtained from this seemingly simple process. Audience: Clinical pathologists would be familiar with the information provided in this article, but it is rarely available to general or specialist practitioners, and both can potentially benefit. Equipment: Most of the required equipment is routinely available to veterinarians. However, instructions have been provided to give practical alternatives for specialist procedures in some instances. Evidence base: Evidence for much of the data on urinalysis in cats is lacking. Validation of the human equipment used routinely, such as dipsticks, is also lacking. As such, the evidence base for feline urinalysis is quite poor and information has largely been extrapolated from the human literature. Information from feline studies has been included where available. In addition, practical clinicopathological and clinical observations are provided.
Immunomodulants for the treatment of HIV infection: the search goes on

The natural history of HIV infection has been greatly modified by the introduction of powerful antiretroviral agents that act on multiple steps of HIV replication. Thus, antiretroviral therapy (ART) has prolonged the life of HIV-infected individuals, significantly impacting on the progression to AIDS. It was assumed that ART-induced suppression of HIV would have resulted in a degree of immune recovery sufficient enough to allow immune control over HIV replication independently of the use of drugs. Unfortunately, interruption of therapy, even after long periods of full suppression of viral replication, is almost inevitably associated with a prompt rebound of HIV viraemia. The outcome of this observation is that ART has to be considered as a lifelong therapy, with the associated resulting problems of the emergence of multi-drug resistant viral strains, toxic effects, costs and compliance. The use of immunomodulants in association with ART could achieve the goal of boosting the immune response to a threshold, permitting the immune response to indefinitely suppress HIV replication.
Modulation of the activities of AMP‐activated protein kinase, protein kinase B, and mammalian target of rapamycin by limiting energy availability with 2‐deoxyglucose

2‐Deoxyglucose (2‐DG), which has been shown to inhibit mammary carcinogenesis, was used as a metabolic probe to investigate effects of limiting energy availability (reduced cellular ATP) on patterns of proteins' phosphorylation that play a role in the development of cancer. Experiments were conducted using a human breast cancer cell line, MDA‐MB‐468, and 1‐methyl‐1‐nitrosourea‐induced rat model for mammary carcinogenesis. Under in vitro conditions in which cellular ATP concentration decreased rapidly with increasing 2‐DG in a dose and time dependent manner, levels of phosphorylated mammalian target of rapamycin (P‐mTOR) decreased in parallel to decreases in ATP concentration. Concomitantly, phosphorylation of two upstream regulators of mTOR, AMP‐activated protein kinase (AMPK) and Akt/protein kinase B were increased and decreased, respectively, with increased levels of phosphorylated acetyl‐CoA carboxylase as an indicator of AMPK activation. Levels of insulin like growth factor 1‐receptor and phosphoinositide‐3 kinase p110α were also reduced. Similar effects were observed in mammary carcinomas in vivo at concentration of 0.03% (w/w) dietary 2‐DG that inhibited carcinogenesis. In vitro, downregulation of mTOR was accompanied by decreases in phosphorylation of two of mTOR's targets, 70‐kDa ribosomal protein S6 kinase and eukaryote initiation factor 4E binding protein 1. Glucose treatment reversed 2‐DG effects. When cells were transfected with dominant‐negative AMPKα2, effects of 2‐DG on mTOR and its downstream effectors were diminished, providing evidence of a link between AMPK and mTOR when energy availability was limited. This work indicates that AMPK, Akt, and mTOR are candidate targets for efforts to inhibit the carcinogenic process by limiting energy availability. © 2008 Wiley‐Liss, Inc.
Closure of unroofed coronary sinus with a covered stent in a symptomatic infant

A covered stent was used for percutaneous closure of an unroofed coronary sinus in an infant with congestive heart failure secondary to increased pulmonary flow. Prior to the stent deployment, the location of the entrance of the coronary vein into the coronary sinus was demonstrated with a selective left coronary artery angiogram to facilitate placement of the stent. The procedure was well tolerated without complications. The infant's symptoms improved significantly after the procedure. © 2007 Wiley‐Liss, Inc.
Diabetes and Poor Disease Control: Is Comorbid Depression Associated With Poor Medication Adherence or Lack of Treatment Intensification?

Objective: To hypothesize that patients with comorbid depression and diabetes and poor disease control will have poorer adherence to disease control medication and less likelihood of physician intensification of treatment. Many patients with diabetes fail to achieve American Diabetes Association Guidelines for glycemic, blood pressure and lipid control. Depression is a common comorbidity and may affect disease control through adverse effects on adherence and physician intensification of treatment. Methods: In a cohort of 4117 patients with diabetes, depression was measured at baseline with the Patient Health Questionnaire-9 (PHQ-9). Patient adherence and physician intensification of treatment were measured in those who had evidence of poor disease control (HbA1c ≥8.0%, LDL ≥130 mg/dL, systolic blood pressure ≥140 mm Hg) over this 5-year period. Poor adherence was defined as having medication refill gaps for ≥20% of days covered for medications prescribed for each of these conditions. Treatment intensification was defined as an increased medication dosage in a class, an increase in the number of medication classes, or a switch to a different class within 3-month periods before and after notation of above target levels. Results: Among patients with diabetes and poor disease control, depression was associated with an increased likelihood of poor adherence to diabetes control medications (odds ratio [OR] = 1.98; 95% Confidence Interval [CI] = 1.31, 2.98), antihypertensives (OR = 2.06; 95% CI = 1.47, 2.88), and LDL control medications (OR = 2.43; 95% CI = 1.19, 4.97). In patients with poor disease control who were adherent to medication or not yet started on a medication, depression was not associated with differences in likelihood of physician intensification of treatment. Conclusions: In patients with diabetes and poor disease control, depression is an important risk factor for poor patient adherence to medications, but not lack of treatment intensification by physicians. ADA = American Diabetes Association; GH = Group Health; LDL = low-density lipoprotein; HbA1c = hemoglobin A1c; CMG = continuous multiple interval measure of gaps; SBP = systolic blood pressure.
Sigma Receptor Binding Assays

Sigma receptors, both Sigma‐1(S1R) and Sigma‐2 (S2R), are small molecule‐regulated, primarily endoplasmic reticulum (ER) membrane‐associated sites. A number of drugs bind to sigma receptors, including the antipsychotic haloperidol and (+)‐pentazocine, an opioid analgesic. Sigma receptors are implicated in many central nervous system disorders, in particular Alzheimer's disease and conditions associated with motor control, such as Amyotrophic Lateral Sclerosis (ALS). Described in this unit are radioligand binding assays used for the pharmacological characterization of S1R and S2R. Methods detailed include a radioligand saturation binding assay for defining receptor densities and a competitive inhibition binding assay employing [3H]‐(+)‐pentazocine for identifying and characterizing novel ligands that interact with S1R. Procedures using [3H]‐1,3‐di(2‐tolyl)guanidine ([3H]‐DTG), a nonselective sigma receptor ligand, are described for conducting a saturation binding and competitive inhibition assays for the S2R site. These protocols are of value in drug discovery in identifying new sigma ligands and in the characterization of these receptors. © 2015 by John Wiley & Sons, Inc.
Quality of clinical practice guidelines for persons who have sustained mild traumatic brain injury

Background: Mild TBI is one of the most common neurological disorders occurring today. For individuals who experience persistent symptoms following mild TBI, consequences can include functional disability, stress and time away from one's occupation. The objective of the study was to evaluate the quality of clinical practice guidelines (CPGs) that include recommendations on the care of persons who have sustained mild TBI and associated persistent symptoms. Methods: A minimum of four appraisers used the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument to evaluate seven CPGs found via a systematic search of bibliographic databases and internet resources. Results: High AGREE scores were obtained for the domains Scope and Purpose and Clarity and Presentation. The CPGs fared less well on Rigour of Development, Stakeholder Involvement, Editorial Independence and Applicability. The number of recommendations addressing the care of persistent symptoms following mild TBI was meager, with the exception of military guidelines. Conclusions: There is considerable variability in the quality of guidelines addressing mild TBI and, overall, the CPGs reviewed score lower on Rigour of Development than CPGs for other medical conditions. There is a clear need for clinical guidance on the management of individuals who experience persistent symptoms following mild TBI.
Cutting Edge: Instructive Role of Peripheral Tissue Cells in the Imprinting of T Cell Homing Receptor Patterns1

Tissue-specific homing of effector and memory T cells to skin and small intestine requires the imprinting of specific combinations of adhesion molecules and chemokine receptors by dendritic cells in the draining lymph nodes. In this study, we demonstrate that CD8+ T cells activated by Ag-pulsed bone marrow-derived dendritic cells were induced to express the small intestine homing receptors α4β7 integrin and chemokine receptor CCR9 in coculture with small intestinal epithelial cells. In contrast, in coculture with dermal fibroblasts the skin-homing receptor E-selectin ligand was induced. Interestingly, the imprinting of gut homing receptors on anti-CD3/anti-CD28 stimulated T cells was induced by soluble factors produced by small intestinal epithelial cells. Retinoic acid was identified as a crucial factor. These findings show that peripheral tissue cells directly produce homing receptor imprinting factors and suggest that dendritic cells can acquire their imprinting potential already in the peripheral tissue of origin.
Loss of primitive hematopoietic progenitors in patients with human immunodeficiency virus infection.

A number of hematologic abnormalities, including cytopenias, have been observed in patients with human immunodeficiency virus (HIV) infection. To elucidate their mechanisms, primitive cells from bone marrow aspirates of 21 patients with HIV-1 infection were quantitated by flow cytometry. The mean percentage of CD34+ cells is not significantly altered in HIV-1-infected patients in comparison with HIV-1-seronegative controls. In contrast, two- and three-color immunofluorescence analysis showed that in all HIV-1 samples, most CD34+ cells coexpressed the CD38 antigen. The proportion of HIV-1-derived CD34+ cells that did not express the CD38 antigen was significantly lower (HIV-1+: mean, 1.73%; controls: mean, 14%; P < .0005) than in controls. Moreover, of Thy-1+ cells, the proportion of CD34+ cells was twofold lower in HIV-1-infected patients (HIV-1+: mean, 12%; controls, 25%, P < .0005), which suggests that phenotypically primitive cells are depleted in HIV-1 infection. In vitro functional analysis in long-term cultures of sorted CD34+ cells from seven HIV-1 patients showed that CD34+ cells from HIV-1 patients generated much fewer colonies both in the nonadherent and adherent layers than CD34+ cells from controls after 5 weeks of culture (10-fold and four-fold less, respectively). Precise long-term culture initiating cell (LTC-IC) frequency in the CD34+ cell population was determined in three patients by limiting dilution and was markedly decreased in comparison to that of normal controls (from twofold to > sevenfold decreased). To determine if primitive cells were infected by HIV-1, both methylcellulose colonies generated from long-term culture of CD34+ cells and various CD34+ cell fractions purified by flow cytometry were evaluated for the presence of HIV-1 by polymerase chain reaction (PCR). Progeny from long-term culture was HIV-1-negative in three samples. In addition, using a sensitive PCR technique, the HIV-1 genome could not be detected in CD34+, CD34+/CD38-, and CD34+/CD4+ cells. These data show that hematologic disorders in HIV disease may be the consequence of a deficit of primitive cells. However, direct infection of these cells by HIV-1 does not seem to be responsible for this defect.
Neutralizing antibody responses of humans and mice to vaccination with Venezuelan encephalitis (TC-83) virus

Laboratory workers were vaccinated with Venezuelan encephalitis virus, strain TC-83. After 2 to 3 years, they were bled, and their sera were tested for neutralizing antibody to all known Venezuelan encephalitis subtypes and varieties. The results indicated higher titers to epizootic than to enzootic Venezuelan encephalitis viruses and suggested that individuals vaccinated with TC-83 do not produce significant neutralizing antibody to heterologous subtypes. Mice vaccinated, bled, and tested in a similar manner produced much the same antibody profiles as did the humans and resisted challenge with all Venezuelan encephalitis viruses tested. In addition, the serum dilution plaque reduction neutralization test used was shown to be highly specific and adequate for diagnosis of infections with Venezuelan encephalitis viruses.