Miracle-dz/UniFAR-FTUs huggingface dataset:
A Neuron-Optimized CRISPR/dCas9 Activation System for Robust and Specific Gene Regulation

Abstract CRISPR-based technology has provided new avenues to interrogate gene function, but difficulties in transgene expression in post-mitotic neurons has delayed incorporation of these tools in the central nervous system (CNS). Here, we demonstrate a highly efficient, neuron-optimized dual lentiviral CRISPR-based transcriptional activation (CRISPRa) system capable of robust, modular, and tunable gene induction and multiplexed gene regulation across several primary rodent neuron culture systems. CRISPRa targeting unique promoters in the complex multi-transcript gene brain-derived neurotrophic factor (Bdnf) revealed both transcript- and genome-level selectivity of this approach, in addition to highlighting downstream transcriptional and physiological consequences of Bdnf regulation. Finally, we illustrate that CRISPRa is highly efficient in vivo, resulting in increased protein levels of a target gene in diverse brain structures. Taken together, these results demonstrate that CRISPRa is an efficient and selective method to study gene expression programs in brain health and disease.
Downregulation of SPTAN1 is related to MLH1 deficiency and metastasis in colorectal cancer

Introduction Colorectal cancers (CRCs) deficient in the DNA mismatch repair protein MutL homolog 1 (MLH1) display distinct clinicopathological features and require a different therapeutic approach compared to CRCs with MLH1 proficiency. However, the molecular basis of this fundamental difference remains elusive. Here, we report that MLH1-deficient CRCs exhibit reduced levels of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1), and that tumor progression and metastasis of CRCs correlate with SPTAN1 levels. Methods and results To investigate the link between MLH1 and SPTAN1 in cancer progression, a cohort of 189 patients with CRC was analyzed by immunohistochemistry. Compared with the surrounding normal mucosa, SPTAN1 expression was reduced in MLH1-deficient CRCs, whereas MLH1-proficient CRCs showed a significant upregulation of SPTAN1. Overall, we identified a strong correlation between MLH1 status and SPTAN1 expression. When comparing TNM classification and SPTAN1 levels, we found higher SPTAN1 levels in stage I CRCs, while stages II to IV showed a gradual reduction of SPTAN1 expression. In addition, SPTAN1 expression was lower in metastatic compared with non-metastatic CRCs. Knockdown of SPTAN1 in CRC cell lines demonstrated decreased cell viability, impaired cellular mobility and reduced cell-cell contact formation, indicating that SPTAN1 plays an important role in cell growth and cell attachment. The observed weakened cell-cell contact of SPTAN1 knockdown cells might indicate that tumor cells expressing low levels of SPTAN1 detach from their primary tumor and metastasize more easily. Conclusion Taken together, we demonstrate that MLH1 deficiency, low SPTAN1 expression, and tumor progression and metastasis are in close relation. We conclude that SPTAN1 is a candidate molecule explaining the tumor progression and metastasis of MLH1-deficient CRCs. The detailed analysis of SPTAN1 is now mandatory to substantiate its relevance and its potential value as a candidate protein for targeted therapy, and as a predictive marker of cancer aggressiveness.
MPC for Energy Efficient HVAC Control with Humidity and Latent Heat Considerations

Even though energy efficient climate control of buildings using model predictive control (MPC) has been widely investigated, most MPC formulations ignore humidity and latent heat. The inclusion of moisture makes the problem considerably more challenging, primarily since a cooling and dehumidifying coil model which accounts for both sensible and latent heat transfers is needed. In this work, we propose an MPC controller in which humidity and latent heat are incorporated in a principled manner. We construct low order data-driven models of a cooling and dehumidifying coil that can be used in the MPC formulation. The resulting controller's performance is tested in simulation using a plant that differs significantly from the model used by the optimizer. Additionally, the performance of the proposed controller is compared with that of a naive MPC controller which does not explicitly consider humidity, and also to that of a conventional rule-based controller. Simulations show that the proposed MPC controller outperforms the other two consistently. It is also observed that the naive MPC formulation which does not consider humidity leads to poor humidity control under certain conditions. Such violations in humidity can adversely affect occupant comfort and health.
New Product Developments Post-M&As-Changes in Development Trajectory of Pharmaceutical Firms∗

We investigate the redeployment of resources by the merging firms, relatively to the behaviour of non-merging firms in the pharmaceutical sector. There is the believe that there is something to be strategically gained from purchasing another firm. We question whether and how (i.e. under what circumstances) the novelty of resources (coming from an external target) may provide acquirers an advantage at generating recombinative synergies compared to non-acquirers. We distinguish between different types of overlap of two merging firms: An overlap within a pharmacological sub-field in which both merging firms actively pursuing drug development pre-M&A; overlap within a therapeutic field (in two neighbouring pharmacological sub-fields); and an indirect overlap through joint activities and overlaps in at least one neighbouring field. The results show that merging firms change development trajectory significantly more compared to their non-merging rivals and they have the tendency to invest less in fields in which they overlap and tend to invest more in new but related fields. ∗We thank Otto Toivanen, Frank Verboven and Iain Cockburn, as well as participants at seminars at KU Leuven, Boston University and SMS Conference Berlin for valuable comments. All comments are welcome. Corresponding contact: hendrik.meder@gmail.com †Norteastern Univeristy ‡European Commission, Disclaimer: The views expressed in this paper are purely those of its authors and may not in any circumstances be regarded as stating an official position of the European Commission.
Foreign Competition, Markups and Productivity: The Effect of China on Mexican Firms∗

We investigate the effect of the rise of Chinese exports on Mexican firms using detailed plant-product level production data from Mexico and detailed productlevel trade data. We estimate markups of Mexican exporters at the plant-product level and productivity at the plant level using production data. We find strong evidence that Mexican firms reduce their markups in response to increased competition from Chinese exports, and this effect is more pronounced among lower productivity plants and non-core products within multi-product plants. However, the competitive pressure also increases marginal cost among lower productivity plants and non-core products within multi-product plants, so that the rise in competition doesn’t translate into a more pronounced reduction in prices among these products and plants. Instead, consistent with this rise in marginal cost, we document a fall in measured productivity among lower productivity plants. Within-firm selection mechanisms, by which firms drop their lowest sale products in the face of rising competition, is found to be impaired among lower productivity plants consistent with the decline in their measured productivity.
Almost-orthogonality of restricted Haar functions

We consider the Haar functions $h_I$ on dyadic intervals. We show that if $p>\frac23$ and $E\subset[0,1]$ then the set of all functions $\|h_I1_E\|_2^{-1}h_I1_E$ with $|I\cap E|\geq p|I|$ is a Riesz sequence. For $p\leq\frac23$ we provide a counterexample.
ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNAs

The RNA‐binding protein ALYREF plays key roles in nuclear export and also 3′‐end processing of polyadenylated mRNAs, but whether such regulation also extends to non‐polyadenylated RNAs is unknown. Replication‐dependent (RD)‐histone mRNAs are not polyadenylated, but instead end in a stem‐loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD‐histone mRNAs. SL‐binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre‐mRNA 3′‐end processing by facilitating U7‐snRNP recruitment through physical interaction with the U7‐snRNP‐specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3′‐end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3′‐end processing and nuclear export of non‐polyadenylated mRNAs.
Long-Term Follow-Up Examination of the Internal Jugular Vein After Vessel-Sparing Implantation of a Hickman Catheter or Port Catheter

Introduction: Both a Hickman catheter (HC) and port catheter (Port) can be inserted either percutaneously by the Seldinger technique or by surgical venous cut-down. Catheters are inserted with a vessel-sparing technique when they are placed in the internal jugular vein (IJV) by venous cut-down. Although this technique is common, data are sparse regarding the vessel's state at long-term follow-up. This study was aimed at determining the flow pattern and constitution of the IJV after vessel-sparing implantation of an HC or Port and comparing the outcomes to those of implantation with the Seldinger technique. Methods: One hundred children (58 boys, 42 girls) between 33 days and 18 years of age who underwent a vessel-sparing implantation of an HC or Port in the IJV were prospectively included. All patients underwent surgical venous cut-down at a single institution. Patency and shape of the IJV were determined by ultrasound and categorized according to 2 possible outcomes: relevant alteration (including occlusion of the IJV) and no relevant alteration, with relevant alteration defined as changes that caused an altered flow pattern. Results: Median age was 6 years at the time of operation, and the median indwelling time of catheters was 271 days. Twenty-two of our patients (22%) showed relevant alterations. These changes included high-grade stenosis or lesion in 13 patients (13%) and occlusion in 9 patients (9%). There were no operation-associated complications, such as pneumothorax, hematopericardium, or accidental puncture of the carotid artery. Statistical analysis did not reveal any specific parameter as a risk factor for relevant structural abnormalities. Discussion: In a comparison of our data to the literature, venous cut-down showed an alteration rate of 26% and a patency rate of 85%, whereas the Seldinger technique was found to cause alteration in 15%, with a patency rate of 97% but a successful placement rate of only 90.3–91.6%. Conclusion: The indication for long-term catheter placement may determine which method is preferable. A child who is likely to need more catheters in the future might benefit from the Seldinger technique, since there is a higher chance of long-term patency of the vessel. A patient undergoing chemotherapy might benefit more from the surgical venous cut-down with less placement-associated complications.
Group-based transmission of fatherhood among intergenerational African American fathers: A case study.

PROBLEM Nonresidential fatherhood contributes to the fact that over 70% of African American (AA) children grow up in homes without their biological fathers. In the absence of gender-specific parental guidance, AA young men who become fathers may lack paternal-parenting preparation. METHODS This secondary data analysis describes the verbal exchange of fatherhood perspectives among four experienced fathers and one adolescent father who participated in a pilot of group-based fatherhood intervention. Qualitative descriptive case study methodology guided by Social Learning Theory was used to explore the transmission of fathering perspectives between fathers. FINDINGS Qualitative thematic analysis affirmed that adverse emotional and psychological distress may be avoided with positive parenting preparedness. Culturally-specific group-based bidirectional learning can transmit fatherhood knowledge and skills to adolescent nonresidential fathers and this new perspective can contribute to adolescent wellbeing. CONCLUSIONS There is a need to investigate channels for AA adolescent boys, young men and fathers to engage in cultural-congruent paternal modeling in the event that their biological father or other social father role models are absent from their lives.
Analysis of Profitability and its Determinants in Small Scale Turkey Production in Anambra State, Nigeria

The study analysed the profitability of turkey production and its determinants in Anambra State, Nigeria. This was borne out of the deficit reported on the animal protein supply and consumption of the people in the area.The data used were obtained from a crosssectional survey of turkey farmers in the state. Multi-stage sampling technique which included purposive and simple random techniques were used to select 83 farmers for the study. The data collected were analysed using descriptive statistics, ordinary least square (regression), budgetary tools and profitability ratios. The results showed that majority of the farmers were 43.9 years, attended secondary education, had turkey farming experience of 11.5 years and a household size of 6 persons on the average. The budgetary estimation showed a Net return of ₦1, 498.27,Profitability Index (PI) of 0.57, Return on Investment (RoI) of 56.67%, Capital Turn-Over (CTO)of 1.57 and a Gross ratio of 0.64. These results, with a Z-value of 42.49 (P<0.01) indicated that the enterprise was profitable. Experience, stock size, and cost of medication were the positive determinants of profitabilityof the enterprise in the area,(P<0.05). Hence, farmers are encouraged to invest more in the production of turkey birds.
Evaluation of two bovine SNP genotyping arrays for breed clustering and stratification analysis in well-known taurine and indicine breeds

Abstract The present study aimed to evaluate the efficiency of two Bovine SNP genotyping arrays (i.e., 50 K and HD) for breed clustering and stratification related studies in taurine and indicine breeds. The whole-genome SNP data at two densities were assembled into three datasets (A, B and C). Dataset A (N = 213) included 50 K genotypic data for five taurine (Holstein–Friesian, Guernsey, Brown Swiss, Angus and Jersey) and two indicine (Gir and Nellore) breeds. Dataset B (N = 241) included the same breeds with HD density data. Dataset C (N = 299) included 50 K SNP genotypic data for six taurine (Holstein–Friesian, Jersey, Guernsey, Brown Swiss, Angus and Hereford) and six indicine (Hariana, Kankrej, Brahman, Nellore, Sahiwal and Gir) breeds. The analysis was done using ADMIXTURE program (bioinformatics-based) and cross-validation errors and Principal Component Analysis (statistical analysis). The proportion of polymorphic markers and minor allele frequencies were assessed for each breed. The proportion of markers polymorphic was consistently higher in taurine breeds when compared with breeds from indicine group. Minor allele frequency estimates and ADMIXTURE results showed differential patterns for both the lineages. However, no significant increase in the accuracy of genomic clustering was found on moving from 50 K to HD density data.
Treatment outcomes and associated factors in tuberculosis patients at Jimma University Medical Center: A 5-year retrospective study

Background: Monitoring the outcome of tuberculosis (TB) treatment and investigating factors associated with unsuccessful outcome are essential, as unsuccessful treatment fuels resistance to antibiotics. This study aimed to investigate the treatment outcome and associated factors with an unsuccessful outcome at Jimma University Medical Center (JUMC), Southwest Ethiopia. Methods: A 5-year retrospective analytical study, including all types of TB cases who sought care at JUMC between September 1, 2012, and August 31, 2017, was conducted. Treatment outcomes and TB types were categorized according to the National TB Control guideline. Bivariate analysis was used to analyze the association between treatment outcome and potential variables. Results: Overall data from 1249 patients' records were included in the study. The proportion of male patients was higher (815, 65.3%) than that of females. The mean age (± standard deviation, range) of the cases was 26 (±11. 6, 1–71) years. Of the total, 292 (23.3%) were smear-positive pulmonary TB (PTB), 489 (39.2%) smear-negative PTB, and 468 (37.5%) extra-PTB (EPTB) cases. Available treatment outcomes indicate that 253 (20.2%) were cured, 850 (68.0%) completed therapy, 58 (4.8%) died, 83 (6.6%) defaulted, and 5 (0.4%) failed the therapy. About 76 (5.6%) cases were transferred out and 44 (3.2%) cases were lost to follow-up. In total, 146 (11.7%) patients had an unsuccessful outcome. Unsuccessful treatment outcome was associated with smear-negative PTB (odds ratio [OR] =2.0, 95% confidence intervals [CI] =1.1, 3.7), EPTB (OR = 2.1, 95% CI = 1.2, 3.4), and unknown human immunodeficiency virus (HIV) status (OR = 7.9, 95% CI = 2.5, 25.0). Conclusion: The treatment success rate of overall TB patients is lower than end TB Strategy target of ≥90% success rate. Smear-negative PTB, EPTB cases, and those with unknown HIV status tend to have unsuccessful outcome.
Differences in lower quarter Y-balance test with player position and ankle injuries in professional baseball players

Purpose: Although there has been research about the correlation between ankle injury and Y-balance test (YBT) conducted in other sports, there has been a lack of research on the correlation between ankle injury among baseball players and YBT scores or on differences in scores according to baseball positions. This study focused on professional baseball players as its subjects with the aims of analyzing the correlation between YBT and ankle injury and assessing differences in YBT between baseball positions. Methods: Age, height, weight, body mass index, and spine malleolar distance of 42 professional baseball players were measured. YBT measurements were performed using each foot in three distinct directions. YBT normalized reach distances, composite score, and reach asymmetry were analyzed. Results: The mean right posteromedial normalized reach distances for the player positions were significantly different between the pitchers (107.7%) and infielders (113.7%) (p = 0.028). For the composite score, the difference between the pitchers (92.3%) and infielders (95.0%) was statistically significant (p = 0.048). The anterior reach asymmetry was larger in the injured group than in the noninjured group (p = 0.041). Conclusion: This study shows that YBT can be used as a way of evaluating the injury of baseball players. It also shows the reference value of YBT according to position in professional baseball players. This study could be useful for the treatment of ankle injury of baseball players. Level of evidence: Level 3.
Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients

Abstract Background The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma. Patients and methods ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS). Results The detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma. Conclusion Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.
Reprogrammable Electro-Optic Nonlinear Activation Functions for Optical Neural Networks

We introduce an electro-optic hardware platform for nonlinear activation functions in optical neural networks. The optical-to-optical nonlinearity operates by converting a small portion of the input optical signal into an analog electric signal, which is used to intensity -modulate the original optical signal with no reduction in processing speed. Our scheme allows for complete nonlinear on–off contrast in transmission at relatively low optical power thresholds and eliminates the requirement of having additional optical sources between each of the layers of the network Moreover, the activation function is reconfigurable via electrical bias, allowing it to be programmed or trained to synthesize a variety of nonlinear responses. Using numerical simulations, we demonstrate that this activation function significantly improves the expressiveness of optical neural networks, allowing them to perform well on two benchmark machine learning tasks: learning a multi-input exclusive-OR (XOR) logic function and classification of images of handwritten numbers from the MNIST dataset. The addition of the nonlinear activation function improves test accuracy on the MNIST task from 85% to 94%.
THE RELATIONSHIP BETWEEN RACE , ETHNICITY , AND SENTENCING OUTCOME : A META-ANALYSIS OF SENTENCING RESEARCH

The Anti-Drug Abuse Act of 1988 requires us to study capital sentencing procedures to determine if the race of either the victim or the defendant influences the likelihood that defendants will be sentenced to death. We did an evaluation synthesisa review and critique of existing researchon this subject to fulfill the mandate. This report provides a summary of our findings and a discussion of our approach and data limitations.