Miracle-dz/UniFAR-FTUs huggingface dataset:
Isolation and Mapping of 62 New RFLP Markers on Human Chromosome I I

Summary To obtain new RFLP markers on human chromosome 11 for a high-resolution map, we constructed a cosmid library from a Chinese hamster x human somatic hybrid cell line that retains only human chromosome 11 in a Chinese hamster genomic background. A total of 3,500 cosmids were isolated by colony hybridization with labeled human genomic DNA. DNA was prepared from 130 of these cosmid clones and examined for RFLP. In 62 of them, polymorphism was detected with one or more enzymes; four RFLPs were VNTR systems. All polymorphic clones were assigned to one of 22 intervals obtained by mapping on a deletion panel of 15 somatic hybrid cell lines containing parts of chromosome 11; 11 clones were finely mapped by in situ hybridization. Although RFLP markers were scattered on the whole chromosome, they were found predominantly in the regions of R-banding. These DNA markers will contribute to fine mapping of genes causing inherited disorders and tumor-suppressor genes that reside on chromosome 11. Furthermore, as one-third of the cosmid clones revealed a band or bands in Chinese hamster DNA, indicating sequence conservation, this subset of clones may be useful for isolating biologically important genes on chromosome 11.
REGIONAL DIFFUSIVITY OF WATER IN MILD COGNITIVE IMPAIRMENT AND ALZHEIMER’S DISEASE

Purpose— To compare the regional diffusivity of water in the brains of normally aging elderly, patients with mild cognitive impairment (MCI), and probable Alzheimer’s Disease (AD). Materials and Methods— We compared the apparent diffusion coefficients (ADC) and the anisotropy indexes (AI) obtained from frontal, parietal, temporal, occipital, anterior and posterior cingulate white matter (WM), thalamic and hippocampal regions of interest (ROI) in 21 probable AD, 19 MCI patients, and 55 normally aging elderly controls without evidence of cognitive impairment. Results— The hippocampal ADC were higher in MCI and AD patients than in controls. ADC of the temporal stem, posterior cingulate, occipital and parietal WM were higher in AD patients than in controls. Except for lower occipital AI in MCI patients than in controls, there were no differences in the AI among the three clinical groups for any of the ROI. Conclusion— Hippocampal ADC were significantly different between controls and MCI: many of whom likely have pre-clinical AD. Elevation in hippocampal ADC may reflect early ultrastructural changes in the progression of Alzheimer’s pathology.
An Underdiscussed Aspect of Chomsky (1959)

Areas of study are sometimes profoundly affected by people outside them. For example, the linguist Noam Chomsky is familiar to many psychologists for his influence in the cognitive revolution, the major shift in the orientation of American psychology from behavioral to cognitive in the 1960s and 1970s (e.g., Auyang, 2000, p. 105; Erneling, 1997; Hunt, 1982, p. 217; Kosslyn & Rosenberg, 2001, p. 238). Some have even suggested that Chomsky’s (1959) review of B. F. Skinner’s (1957) Verbal Behavior, the latter’s theoretical account of how language can be explained in behavioral terms, was responsible for initiating the cognitive revolution (e.g., Bialystock, 1997; Harnish, 2002, p. 44). When Chomsky set out to write his review, he faced a daunting task. While apparently well read in certain areas such as political theory, there is little to indicate he had any previous exposure to psychology except for psychoanalysis (Barsky, 1997) and through linguists who have drawn upon psychology, such as Bloomfield (1933). Psychology in general in the early and mid-20th century was broad and diverse (e.g., Heidbreder, 1933; Hilgard & Bower, 1966), and so too was behavioral psychology. At that time “behaviorism” was used to refer a variety of behavior-oriented work, such as the strict methodological behaviorism of John B. Watson (e.g., Watson, 1913, 1924), the mathematical modeling with intervening variables of Clark L. Hull’s school (e.g., Hull, 1943, 1951, 1952), and the eclectic, molar, purposive behaviorism of Edward C. Tolman (e.g., Tolman, 1922, 1932, 1948), each with its own assumptions and terminologies. Skinner’s approach, radical behaviorism, differed from all of them in that he recognized the fundamental respondent-operant distinction (Skinner, 1935, 1937, 1938, p. 61ff., 1953, pp. 45–90), accepted the reality of private events, and rejected purely hypothetical mental constructs (Skinner, 1945). Verbal Behavior was very specifically based on Skinner’s approach, and any reviewer would have to understand this to do the job properly. Behavior analysts’ responses to Chomsky’s (1959) review of Verbal Behavior have not been positive (e.g., MacCorquodale, 1970; McLeish & Martin, 1975; Richelle, 1976); their counter reviews generally have noted that Chomsky fundamentally misunderstood the 2007, 23, 29–34
Topological frustration in βα -repeat proteins: sequence diversity modulates the conserved folding mechanisms of α / β / α sandwich proteins

The thermodynamic hypothesis of Anfinsen postulates that structures and stabilities of globular proteins are determined by their amino acid sequences. Chain topology, however, is known to influence the folding reaction, in that motifs with a preponderance of local interactions typically fold more rapidly than those with a larger fraction of non-local interactions. Together, the topology and sequence can modulate the energy landscape and influence the rate at which the protein folds to the native conformation. To explore the relationship of sequence and topology in the folding of βα – repeat proteins, which are dominated by local interactions, a combined experimental and simulation analysis was performed on two members of the flavodoxin-like, α / β / α sandwich fold. Spo0F and the N-terminal receiver domain of NtrC (NT-NtrC) have similar topologies but low sequence identity, enabling a test of the effects of sequence on folding. Experimental results demonstrated that both response-regulator proteins fold via parallel channels through highly structured sub-millisecond intermediates before accessing their cis prolyl peptide bond-containing native conformations. Global analysis of the experimental results preferentially places these intermediates off the productive folding pathway. Sequence-sensitive G ō -model simulations conclude that frustration in the folding in Spo0F, corresponding to the appearance of the off-pathway intermediate, reflects competition for intra-subdomain van der Waals contacts between its N- and C-terminal subdomains. these response regulators. Comparison with the results of previous experimental and simulation analyses on the homologous CheY argues that prematurely-folded unproductive intermediates are a common property of the βα -repeat motif. Kathuria thanks Osman Bilsel for guidance in the global analysis, Can Kayatekin and J.A. Zitzewitz for valuable discussions and their help with preparation of the manuscript. This work was supported by NIH grant GM48807 to C.L. Brooks III and NSF grants MCB0327504 & MCB0721312 to C.R. Matthews.
Beamforming Galvanic Coupling Signals for IoMT Implant-to-Relay Communication

Implants are poised to revolutionize personalized healthcare by monitoring and actuating physiological functions. Such implants operate under challenging constraints of the limited battery energy, heterogeneous tissue-dependent channel conditions, and human-safety regulations. To address these issues, we propose a new cross-layer protocol for galvanic coupled implants, wherein the weak electrical currents are used in place of classical radio frequency links. As the first step, we devise a method that allows multiple implants to communicate individual sensed data to each other through code division multiple access, combined with compressive sensing method to lower the transmission time and save energy, as well as delegates the computational burden of dispreading and decoding only to the on-body surface relays. Then, we devise a distributed beamforming approach that allows coordinated transmissions from the implants to the relays by considering the specific tissue path chosen and tissue heating-related safety constraints. We then proceed to implement distributed beamforming on a phantom of human tissue and prove an increase in received signal strength and a decrease in BER due to constructive interference of the signals of each implant. Our contributions are twofold: First, we devise a collision-free protocol that prevents undue interference at neighboring implants, especially for multiple deployments. Second, this is the first application of near-field distributed beamforming in human tissue. Simulation results reveal significant improvement in the network lifetime for implants of up to 79% compared to the galvanic coupled links without beamforming. In addition, the implementation of phantom tissue proves improved communication metrics when beamforming is used.
Acyl-CoA:cholesterol acyltransferase 1 blockage enhances autophagy in the neurons of triple transgenic Alzheimer’s disease mouse and reduces human P301L-tau content at the pre-symptomatic stage

Patients with Alzheimer’s disease (AD) display amyloidopathy and tauopathy. In mouse models of AD, pharmacological inhibition using small molecule enzyme inhibitors, or genetic inactivation of Acyl-CoA: cholesterol acyltransferase 1 (ACAT1) diminished amyloidopathy and restored cognitive deficits. In microglia, ACAT1 blockage increases autophagosome formation and stimulates amyloid β peptide1–42 degradation. Here we hypothesize that in neurons ACAT1 blockage augments autophagy and increases autophagy-mediated degradation of P301L-tau protein. We tested this possibility in murine neuroblastoma cells ectopically expressing human tau, and in primary neurons isolated from triple transgenic AD (3XTg-AD) mice that express mutant forms of APP, PS1, and human tau. The results show that ACAT1 blockage increases autophagosome formation and decreases P301L-tau protein content without affecting endogenous mouse tau protein content. In vivo , lacking Acat1 decreases P301L-tau protein content in the brains of young 3XTg-AD mice but not in those of old mice, where extensive hyperphosphorylations and aggregation of P301L-tau take place. These results suggest that, in addition to ameliorating amyloidopathy in both young and old AD mice, ACAT1 blockage may benefit AD by reducing tauopathy
Sleep remains disturbed in obstructive sleep apnea patients treated with positive airway pressure: a three-month cohort study using continuous actigraphy

Objective— Some patients with obstructive sleep apnea (OSA) remain sleepy despite positive airway pressure (PAP) therapy. The mechanisms by which this occurs are unclear but could include persistently disturbed sleep. The goal of this study was to explore the relationships between subjective sleepiness and actigraphic measures of sleep during the first three months of PAP treatment. Methods— We enrolled 80 patients with OSA and 50 comparison subjects prior to treatment and observed them through three months of PAP therapy. PAP adherence and presence of residual respiratory events were determined from PAP machine downloads. Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), and actigraphic data were collected before and at monthly intervals after starting PAP. Results— OSA subjects were sleepier and showed a greater degree of sleep disruption by actigraphy at baseline. After three months of PAP, only ESS and number of awakenings normalized, while wake after sleep onset (WASO) and sleep efficiency (SE) remained worse in OSA subjects. For OSA subjects, FOSQ improved but never reached the same level as comparison subjects. ESS and FOSQ improved slowly over the study period. Conclusions— As a group, OSA patients show actigraphic evidence of persistently disturbed sleep and sleepiness related impairments in day-to-day function after three months of PAP therapy. Improvements in sleepiness evolve over months with more severely affected patients responding quicker. Persistent sleep disruption may partially explain residual sleepiness in some PAP adherent OSA patients.
Organizational Stress Moderates the Relationship between Mental Health Provider Adaptability and Organizational Commitment

Objective— Community mental health providers often operate within stressful work environments and are at high risk for emotional exhaustion, which can negatively affect job performance and client satisfaction with services. This cross-sectional study examines the relationships between organizational stress, provider adaptability, and organizational commitment. Methods— Variables were analyzed using moderated multi-level regression in a sample of 311 mental health providers from 49 community mental health programs. Results— Stressful organizational climate, characterized by high levels of emotional exhaustion, role conflict, and role overload, was negatively related to organizational commitment. Organizational stress moderated the relationship between provider adaptability and organizational commitment, such that those who were more adaptable had greater levels of organizational commitment when organizational stress was low, but were less committed than those who were less adaptable when organizational stress was high. Conclusions— In the current study, providers higher in adaptability may perceive their organization as a greater fit when characterized by lower levels of stressfulness; however, highly adaptable providers may also exercise choice that manifests in lower commitment to staying in an overly stressful work environment. Service systems and organizational contexts are becoming increasingly demanding and stressful for direct mental health service providers. Therefore, community mental health organizations should assess and understand their organizational climate and intervene with empirically based organizational strategies when necessary to reduce stressful climates and maintain desirable employees. manuscript
Experimental and Numerical Analysis of Additively Manufactured Coupons With Parallel Channels and Inline Wall Jets

Present paper developed a series of additively manufactured parallel cooling channels with streamwise wall jets inside, which could be suitable for double-wall and near-wall cooling configurations in gas turbine hot section components. The tested coupons consisted of parallel channels, each channel further divided into small chambers using several spanwise separation walls. Height of these walls was kept less than channel height, thus forming a slot with one of the end walls. Coolant entered from one side of channel and formed streamwise wall jet while crossing through the slot over to the downstream chamber. The test coupons were additively manufactured by selective laser sintering (SLS) technique using Inconel 718 alloy. Steady-state heat transfer experiments with constant wall temperature boundary condition were performed to analyze effect of pitch between subsequent slots and blockage ratio (ratio of separation wall height to channel height) on heat transfer. The channel Reynolds number ranged from 1800 to 5000. Numerical simulations were performed using ANSYS cfx solver with SST k–ω turbulence model to obtain detailed understanding of existing flow field. Experimental results showed heat transfer enhancement of up to 6.5 times that of a smooth channel for the highest blockage ratio of 0.75. Numerical results revealed complex flow field which consisted of wall jets along with impingement, separation, and recirculation zones in each chamber. For all configurations, gain in heat transfer was accompanied with high pressure drops. However, coupled with the high heat transfer, this design could lead to potential coolant savings.
Overweight and obesity prevalence among school-aged Nunavik Inuit children according to three BMI classification systems

Purpose— Little is known about the suitability of three commonly-used body mass index (BMI) classification system for Indigenous children. This study aims to estimate overweight and obesity prevalence among school-aged Nunavik Inuit children according to International Obesity Task Force (IOTF), Centers for Disease Control and Prevention (CDC), and World Health Organization (WHO) BMI classification systems, to measure agreement between those classification systems, and to investigate whether BMI status as defined by these classification systems is associated with levels of metabolic and inflammatory biomarkers. Methods— Data were collected on 290 school-aged children (8–14 years; 50.7% girls) from the Nunavik Child Development Study (NCDS) with data collected in 2005–2010. Anthropometric parameters were measured and blood sampled. Participants were classified as normal weight, overweight and obese according to BMI classification systems. Weighted Kappa (kw) statistics assessed agreement between different BMI classification systems and multivariate analysis of variance ascertained their relationship with metabolic and inflammatory biomarkers. Results— The combined prevalence rate of overweight/obesity was 26.9% (with 6.6% obesity) with IOTF, 24.1% (11.0%) with CDC, and 40.4% (12.8%) with WHO classification systems. Agreement was the highest between IOTF and CDC (kw=0.87) classifications, and substantial for IOTF and WHO (kw=0.69), and CDC and WHO (kw=0.73). Insulin and high-sensitivity C-reactive protein plasma levels were significantly higher from normal weight to obesity, regardless of classification system. Among obese subjects, higher insulin level was observed with IOTF. Conclusion— Compared with other systems, IOTF classification appears to be more specific to identify overweight and obesity in Inuit children.
49.1: Invited Paper: Optical Sensitive Organic Memory Transistors

This work discusses the electrical properties of the 2,9‐di‐decyl‐dinaphtho‐[2,3‐b:20,30‐f]‐thieno‐[3,2‐b]‐thiophene (C10‐DNTT) organic field effect transistors under different programming conditions. We noticed that the shifting of threshold voltage (Vth) can last for more than 20000 seconds which allows these devices to store information as a memory buffer. These devices can be further integrated into an array form for large area optical signal sensing.
Calf thymus RE-C as an essential component for DNA polymerase 6 and e holoenzymes function

By using a complementation assay that enabled DNA polymerase 6 and DNA polymerase to replicate a singly-DNA primed M13 DNA in the presence of proliferating cell nuclear antigen (PCNA) and Escherichia coil single-stranded DNA binding protein (SSB), we have purified from calf thymus in a five step procedure a multipolypeptide complex with molecular masses of polypeptides of 155, 70, 60, 58, 39 (doublet), 38 (doublet) and 36 kDa. The protein is very likely replication factor C (Tsurimoto, T. and Stillman, B. (1989) Mol. Cell. Biol. 9, 609 - 619). This conclusion is based on biochemical and physicochemical data and the finding that it contains a DNA stimulated ATPase which is under certain conditions stimulated by PCNA. Together RF-C, PCNA and ATP convert DNA polymerases 6 and e to holoenzyme forms, which were able to replicate efficiently SSB-covered singly-DNA primed Ml 3 DNA. Calf thymus RF-C could form a primer recognition complex on a 3'-OH primer terminus in the presence of calf thymus PCNA and ATP. Holoenzyme complexes of DNA polymerase 6 and e could be isolated suggesting that these enzymes directly interact with the auxiliary proteins in a similar way. Under optimal replication conditions on singly-DNA primed Ml 3 DNA the DNA synthesis rate of DNA polymerase 6 was higher than of DNA polymerase &. Based on these functional date possible roles of these two DNA polymerases in eukaryotic DNA replication are discussed.
Complex model description and main capacitor sizing for the cross-coupled charge pump synthesis process

Abstract This paper presents a dynamic part of the pump stage model of the cross-coupled charge pump. The complex model has been used for both the estimation of the N-stage pump properties in a wide range of the input parameters and derivation of equations for synthesis process, as the main capacitor sizing, which is also mentioned in the article. Dynamic part of the model (pump stage capacitances) is determined from Ward’s capacitance piece-wise model through the BSIM MOSFET model equations. Main capacitor and load capacitor sizing are based on the time response characteristics fulfilling the system behavior in time. Guideline on the MOS transistor sizing as the nonlinear main pump capacitor and specification of the diode transistor for the design process are also clarified. The characteristics of the proposed circuit have been verified in the professional design environment Mentor graphics and analysis algorithm based on the state-space description of the inner complex model was programmed in Maple SW. The main benefit is to offer the alternative way of the charge pump synthesis by using the complex model and symbolic description of all formulae to find the required pump parameters without long-time simulation process.
Approaches to reporting long-term data

Background— Long-term clinical studies are essential for monitoring the effectiveness and safety of a drug. Information provided by long-term clinical studies complements the results of short-term, randomized, controlled trials, which often form the basis of regulatory approval for a new drug application. However, with increasing study duration, the use of placebo becomes less ethical, forcing an open-label study design where a reference estimate for comparison, a placebo-treated cohort, is no longer available. Moreover, as the duration of a study increases and the number of patients continuing in the study declines, missing data become more of a problem: they may bias the results. Therefore, standard analytical strategies used in short-term randomized, controlled trials (intent-to-treat, per-protocol) may not always be appropriate for data generated in long-term studies. Discussion— We suggest using an intent-to-observe population in long-term studies, applying at least three different methods for handling missing data, testing for bias as a sensitivity analysis and reporting results of more than one method if they differ from one another. The use of multiple analyses is supported by regulatory authority and expert guidelines, although it has not been widely adopted in the medical literature. Summary— Given the inherent limitations of accounting for missing data with each method, the multiple-analysis approach provides more information with which to make better informed decisions, and clearly defined multiple analytical methods may
Molecular Tools for Selective Activation of Astrocytes In Vivo Temporal Control of Astrocyte Activation In Vivo Using Optogenetics

Astrocytes are the predominant glial type in the central nervous system and play important roles in assisting neuronal function and network activity. Astrocytes exhibit complex signaling systems that are essential for their normal function and the homeostasis of the neural network. Altered signaling in astrocytes is closely associated with neurological and psychiatric diseases, suggesting tremendous therapeutic potential of these cells. To further understand astrocyte function in health and disease, it is important to study astrocytic signaling in vivo. In this review, we discuss molecular tools that enable the selective manipulation of astrocytic signaling, including the tools to selectively activate and inactivate astrocyte signaling in vivo. Lastly, we highlight a few tools in development that present strong potential for advancing our understanding of the role of astrocytes in physiology, behavior, and pathology.